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Bilan initial: L’infection par le VHC peut évoluer vers une maladie hépatique sévère avec risque de cirrhose et de ses complications : hypertension portale, carcinome hépatocellulaire. Trois méthodes non-invasives permettent d’évaluer la sévérité de la maladie hépatique : élasticité hépatique (Fibroscan®), et tests sanguins (Fibrotest® et Fibromètre®). Recommandations: 3. Pour écarter le diagnostic de maladie hépatique sévère, le résultat d’une des méthodes suivantes doit être utilisé : • FibroScan® < 10 kPa • Fibrotest® ≤ 0,58 • Fibromètre® ≤ 0,786

BACKGROUND AND AIM: HIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools. METHODS: HIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE) with controlled attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP >/=248 dB/m) and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis. RESULTS: 202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%), insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR) (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01-1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50-3.79; p

OBJECTIVE: The controlled attenuation parameter (CAP) measured by transient elastography allows for the noninvasive assessment of hepatic steatosis. However, discrepant results between CAP values and histological evaluation have been reported in particular with high CAP values. We therefore investigated the diagnostic validity of high CAP measurements. METHODS: Forty patients with liver disease and CAP measurements > 300 dB/m that underwent ultrasound-guided or minilaparoscopic liver biopsy were retrospectively enrolled. CAP values were compared with the respective histological and macroscopic evaluation and correlated with clinical parameters. RESULTS: CAP values > 300 dB/m had an 87.5 % specificity for detection of hepatic steatosis but failed to discriminate between steatosis grade S1 - S3. Discordant results, defined as a discrepancy of at least 2 steatosis grades between transient elastography and liver biopsy, were observed in 40 % of cases. The interquartile range (IQR) of CAP was confirmed as a predictor of discrepant findings. Macroscopic evaluation as part of minilaparoscopy detected hepatic steatosis in 74 % of patients with histological grade S2 - S3 in contrast to only 10 % classified as histological grade S0 - S1. CONCLUSION: High CAP measurements need to be interpreted with care and with regard to clinical parameters, in particular when high IQR values are registered.

BACKGROUND: Controlled attenuation parameter (CAP) is a novel, noninvasive technique for assessing hepatic steatosis. However, its role in morbidly obese individuals is unclear. The effect of bariatric surgery on inflammation and fibrosis needs to be explored. OBJECTIVES: To assess the utility of CAP for assessment of hepatic steatosis in morbidly obese individuals and evaluate the effect of bariatric surgery on hepatic steatosis and fibrosis. SETTING: A tertiary care academic hospital. METHODS: Baseline details of anthropometric data, laboratory parameters, FibroScan (XL probe), and liver biopsy were collected. Follow-up liver biopsy was done at 1 year. RESULTS: Of the 124 patients screened, 76 patients were included; mean body mass index was 45.2 +/- 7.1 kg/m(2). FibroScan success rate was 87.9%. The median liver stiffness measurement (LSM) and CAP were 7.0 (5.0-9.5) kPa and 326.5 (301-360.5) dB/m, respectively. On liver histopathology, severe steatosis and nonalcoholic steatohepatitis were present in 5.3% and 15.8%; significant fibrosis (>/=stage 2) and cirrhosis in 39.5% and 2.6%, respectively. Area under receiver operator characteristic curve of LSM for prediction of significant fibrosis (F2-4 versus F0-1) and advanced fibrosis (F3-4 versus F0-2) was .65 (95% confidence interval [CI]: .52-.77) and .83 (95% CI: .72-.94), respectively. The area under receiver operator characteristic curve of CAP for differentiating moderate hepatic steatosis (S2-3 versus S0-1) and severe hepatic steatosis (S3 versus S0-2) was .74 (95% CI: .62-.86) and .82 (95% CI: .73-.91), respectively. At 1-year follow-up, 32 patients underwent liver biopsy. In these patients, there was significant improvement in hepatic steatosis (P = .001), lobular inflammation (P = .033), ballooning (P<.001 and fibrosis .003 nonalcoholic steatohepatitis was resolved in of patients. lsm cap significantly declined. conclusions: are feasible accurate at diagnosing advanced severe hepatic steatosis morbidly obese individuals. bariatric surgery is associated with significant improvement fibrosis. class="article_links">

The potential interaction between chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD), two of the most prevalent liver diseases worldwide, has not been well defined. We performed liver stiffness (LS) and controlled attenuation parameter (CAP) measurements using transient elastography in 1202 CHB patients. Of these, 601 steatotic patients were matched with nonsteatotic controls in a 1:1 ratio by age, gender, nucleoside analogue treatment status, and treatment duration. Severe fibrosis was defined according to EASL-ALEH criteria, and steatosis was defined as CAP >/=222 dB m(-1) . Anthropometric measurements and metabolic-related parameters were recorded. The mean age of the 1202 patients (51.4% male) was 51.8 years. 696 patients (57.9%) were on nucleoside analogues for a median duration of 76.2 months. Among treatment-naive patients, median serum HBV DNA was lower in steatotic individuals than in controls (3.0 vs 3.4 log IU mL(-1) , P

Little information is available on the impact of direct-acting antiviral (DAA) therapy on changes in liver fibrosis and steatosis. Liver stiffness (LS) and controlled attenuation parameter (CAP) values were evaluated using transient elastography. The study subjects were 214 elderly patients infected with HCV genotype 1b who received 24-week daclatasvir and asunaprevir dual therapy. All patients of this retrospective study had no hepatocellular carcinoma before and during DAA therapy. LS and CAP were assessed before treatment (baseline), at end of treatment (EOT), and at 24, 48, 72 weeks (W) after EOT. The rate of sustained viral response (SVR) by daclatasvir and asunaprevir therapy was 91%. LS values for the entire group correlated with Fib-4 index at baseline (r = 0.565, P /=3.25) decreased significantly at each time point compared with baseline (P

INTRODUCTION: In obese individuals, nonalcoholic fatty liver disease (NAFLD) is common but often goes undiagnosed, and therefore untreated. The presence of significant fibrosis is a key determinant of NAFLD progression, and liver steatosis has substantial cardiovascular implications. We aimed to determine the diagnostic accuracy of common noninvasive diagnostic tests for steatosis and fibrosis in the obese. METHODS: We recruited 182 severely and morbidly obese individuals undergoing bariatric surgery (age 44 +/- 12 years, body mass index 45.1 +/- 8.3 kg/m(2)). Medical history, blood tests and liver biopsy were taken on the day of surgery. Serum steatosis and fibrosis scores were calculated. In a subgroup of patients, transient elastography with controlled attenuation parameter (TE/CAP) (n = 82) and proton magnetic resonance spectroscopy ((1)H-MRS) (n = 49) were performed. RESULTS: (1)H-MRS had excellent diagnostic accuracy for steatosis, with strong correlation to steatosis (r = 0.647, p

BACKGROUND: Direct Acting Agents (DAAs) have high cure rate but still lack the knowledge of their effect on hepatic steatosis in chronic hepatitis C (CHC). Controlled Attenuation Parameter (CAP), evaluated with transient elastography, could help in assessment of steatosis grades. We aim to evaluate the effect of DAAs on BMI and steatosis in CHC using CAP. PATIENTS AND METHODS: This cohort study included 155 CHC Egyptian patients divided into three groups according to the DAAs regimens. All patients were subjected to pre-treatment and 3-months post-treatment evaluation including BMI, laboratory workup and liver stiffness measurement with simultaneous CAP determination using the FibroScan((R)) M probe. RESULTS: Patients mean age was 45.78 +/- 11.6 years, 60.6% were females, mean BMI 26.63 +/- 2.75 and 18.1% were cirrhotic. Baseline assessment revealed no steatosis in 43.9%, 32.9% had mild-moderate steatosis and 23.2% had severe steatosis. The overall sustained virological response 12 was 93.6%. Follow-up revealed stationary steatosis in 56.7% of patients and regression in 21.3%. Mean pre-treatment CAP were significantly lower in responders 244.9 +/- 62.4dB/m vs non-responders; 300 +/- 28.4dB/m (p = 0.04). ROC curve delineated 273dB/m as best cutoff for detection of responders with an AUC of 0.801, sensitivity 68.2%, and specificity 100%. BMI significantly increased after treatment (p= 0.004) particularly in patients with worsened steatosis (p = 0.001). Steatosis significantly correlated with BMI (r = 0.3, p value =

BACKGROUND AND AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but has not been evaluated in alcoholic liver disease. We therefore aimed to validate CAP for assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP. METHODS: Cross-sectional, biopsy-controlled, diagnostic study in four European liver centers. Consecutive alcohol-overusing patients underwent concomitant CAP, regular ultrasound and liver biopsy. In addition, we measured CAP before and after admission for detoxification in a separate, single center cohort. RESULTS: A total of 562 patients were included in the study, 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, S3 = 77 (28%), 94 (35%), 64 (24%) and 34 (13%). CAP diagnosed any steatosis and moderate steatosis with fair accuracy (AUC >/=S1 = 0.77; 0.71-0.83; AUC >/=S2 = 0.78; 0.72-0.83) and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75-0.88). CAP was superior to bright liver echo pattern by regular ultrasound. CAP above 290 dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3 days (IQR 4-6) for detoxification, CAP decreased by 32+/-47 dB/m (P/=30 kg/m(2) had a significantly higher CAP, which did not decrease significantly during detoxification. CONCLUSIONS: CAP has a good diagnostic accuracy for diagnosing severe alcoholic liver steatosis and can be used to rule in any steatosis. In non-obese but not in obese patients, CAP rapidly declines after alcohol withdrawal. LAY SUMMARY: Controlled attenuation parameter (CAP) is a new ultrasound based technique for measuring fat content in the liver, but has never been tested for fatty liver due to alcohol. We here examine 562 patients in a multicenter setting. We show that CAP highly correlates with liver fat and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound to determine the severity of alcoholic fatty liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusing patients were more likely to have higher CAP values than lean patients, irrespective of drinking.

The incidence and prevalence of nonalcoholic fatty liver disease (NAFLD) are increasing and identification of people at risk of disease progression is extremely important. The current gold standard for diagnosing NAFLD/nonalcoholic steatohepatitis (NASH) is by liver biopsy, but it has several limitations. Noninvasive tests via biomarkers and transient elastography to assess NAFLD/NASH are being used in clinical practice. The most validated diagnostic panels include the NAFLD fibrosis score, FIB-4 (Fibrosis-4), and FibroMeter. Transient elastography is very useful in evaluating advanced fibrosis and cirrhosis.

Vibration-controlled transient elastography estimates liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), which are noninvasive assessments of hepatic fibrosis and steatosis, respectively. However, prior vibration-controlled transient elastography studies reported high failure rates in patients with nonalcoholic fatty liver disease. We examined the performance characteristics of the FibroScan 502 Touch with two probes, medium (M+) and extra large (XL+), in patients with nonalcoholic fatty liver disease in a multicenter setting. A total of 1,696 exams were attempted in 992 patients (body mass index, 33.6 +/- 6.5 kg/m(2) ) with histologically confirmed nonalcoholic fatty liver disease. Simultaneous assessment of LSM and CAP was performed using the FibroScan 502 Touch with an automatic probe selection tool. Testing was conducted twice in patients by either a single operator (87%) or two operators (13%). Failure was defined as the inability to obtain a valid examination. An examination was considered unreliable if LSM interquartile range/median was >30%. Significant disagreement between two readings was defined as >95% limits of agreement between two readings. A total of 1,641 examinations yielded valid results with a failure rate of 3.2% (55/1,696). The proportion of unreliable scans for LSM was 3.9%. The proportion of unreliable scans with operator experience in the top quartile (>/=59 procedures) was significantly lower than that in the lower three quarters combined (1.6% versus 4.7%, P = 0.02 by Fisher's exact test). The significant disagreement between first and second readings for LSM and CAP when obtained back to back was 18% and 11%, respectively. CONCLUSION: Vibration-controlled transient elastography for estimation of LSM and CAP can be successfully deployed in a multicenter setting with low failure (3.2%) and high reliability (>95%) rates and high reproducibility. (Hepatology 2018;67:134-144).

BACKGROUND: Hepatitis C virus (HCV) is a global health problem that is complicated by liver fibrosis and insulin resistance (IR). AIM: The aim of this study was to validate neutrophils-to-lymphocytes ratio (NLR) and platelets-to-lymphocytes ratio (PLR) as indirect biomarkers of liver fibrosis and IR in HCV patients. PATIENTS AND METHODS: One hundred and fifty patients were enrolled. Physical examination, BMI, liver function tests, serum creatinine, complete blood count, serum HCV RNA count by PCR, and abdominal ultrasonography were performed. Transient elastography measurement using FibroScan was performed. Patients were classified into those with mild fibrosis (F1-F3) and significant fibrosis (F4). IR was defined as homeostasis model assessment of IR more than 2. NLR and PLR were calculated. RESULTS: The average age of the patients was 47.21+/-10.51 years, mainly men (n=119; 79.3%), and 87.3% (n=131) had IR and 44.7% (n=67) had significant fibrosis. PLR was lower in patients with IR (74.95+/-37.90 vs. 94.71+/-31.45; P=0.032) unlike the NLR, which was comparable (P>0.05). Patients with significant fibrosis had lower PLR (66.43+/-39.38 vs. 86.35+/-33.85; P=0.001) unlike NLR (P>0.05). PLR (cutoff>/=77.47) had 78.9% sensitivity, 60.3% specificity, 22.4% positive predictive value, and 95.2% negative predictive value for non-IR (P=0.008). At a cutoff of at least 63.71, PLR had 73.5% sensitivity, 61.2% specificity, 70.1% positive predictive value, and 65.1% negative predictive value for nonsignificant fibrosis (P=0.001). Age and PLR (odds ratio=0.99; 95% confidence interval=0.976-0.999) were predictors of IR, whereas age, total bilirubin, serum albumin, liver stiffness, and PLR (odds ratio=0.98; 95% confidence interval=0.974-0.994) were predictors of significant fibrosis. CONCLUSION: PLR is useful in distinguishing the patients with significant fibrosis or IR unlike NLR.

INTRODUCTION: Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients. METHODS: This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE). RESULTS: 83% were male with a median age of 45, while 131 were co-infected with viral hepatitis. Overall, 18% had significant fibrosis and 7.5% had cirrhosis. 11% of HIV mono-infected patients had significant fibrosis and 2% had cirrhosis. HCV infection (OR:5.3), history of exposure to didanosine (OR:2.7) and HIV load below 40copies/mL (OR:0.5) were independently associated with significant fibrosis, while HCV (OR:5.8), exposure to didanosine (OR:2.9) and azidothymidine (OR:2.8) were independently associated with cirrhosis. Interestingly, in HIV mono-infected patients, a HIV-load below 40copies/mL (OR:0.4) was independently associated with significant fibrosis, and didanosine (OR:20.8) with cirrhosis. CONCLUSION: In conclusion, history of exposure to didanosine and azidothymidine continues to have an impact on the presence of liver cirrhosis in HIV patients. However, HCV co-infection and ongoing HIV-replication have the strongest effect on development of significant fibrosis in these patients.

BACKGROUND: The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete. AIMS OF THE STUDY: We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC. METHODS: We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis. RESULTS: Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92-96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94-98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87-100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87-97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76-94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan(R) in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naive and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations. CONCLUSION: In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients.

AIM: Plasma Gas6 was tested as an alternative to Baveno VI criteria (liver stiffness 150 x 10(9)/l) in an endoscopy-sparing strategy. METHODS: A total of 160 patients with chronic hepatitis C and advanced fibrosis/cirrhosis underwent, on the same occasion, liver elastography, upper endoscopy, a platelet count and serum Gas6 measurement. RESULTS: A total of 74/160 (46%) patients had esophageal varices, that were small (diameter

BACKGROUND AND AIM: HIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools. METHODS: HIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE) with controlled attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP >/=248 dB/m) and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis. RESULTS: 202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%), insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR) (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01-1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50-3.79; p

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is indicated in patients with decompensated portal hypertension (PH). Hepatic venous pressure gradient (HVPG) is considered gold standard for assessment of PH. Because HVPG measurement is invasive, non-invasive methods for evaluating severity of PH are warranted. PATIENTS AND METHODS: We retrospectively correlated spleen stiffness as measured by FibroScan with HVPG in patients who underwent TIPS. Twenty-four patients with spleen stiffness measurement (SSM) one day before (D-1), one day after (D+1) and 28 days after TIPS (D+28) were included. RESULTS: SSM was positively correlated with pre-TIPS HVPG (HVPG <13mmHg, median SSM: 19.7+/-8.6kPa; HVPG 13-24mmHg, median SSM: 45.0+/-15.7kPa; HVPG >24mmHg, median SSM: 75.0+/-6.2kPa; p<0.05]; r(2)=0.72; p<0.001) and decreased significantly after TIPS implantation (D-1, median SSM: 67.1+/-17.3kPa; D+1, median SSM: 44.7+/-18.5kPa; D+28, median SSM: 35.6+/-17.0kPa; p<0.05), while liver stiffness measurement decrease was not statistically significant. CONCLUSIONS: Our study highlights the utility of SSM as non-invasive tool in patients with chronic liver disease in evaluating degree of PH potentially offering a confirmable additional parameter in surveillance of patients undergoing TIPS procedure.

BACKGROUND AND AIMS: Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about prevalence of liver fibrosis in general population. Aim of the study was to investigate the prevalence of liver fibrosis in general adult population with unknown liver disease. METHODS: Population-based, cross-sectional study, performed in Barcelona metropolitan area. Subjects aged 18-75yr were identified randomly from citizens included in primary health care registry. Out of 4,866 subjects invited, 3,076 accepted to participate (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS. RESULTS: Prevalence estimates of increased LS (>/=6.8, >/=8.0, and >/=9.0kPa) were 9.0%, 5.8%, and 3.6%, respectively. Etiology of liver disease was mainly NAFLD, followed by alcohol risk consumption. Factors independently associated with increased LS were male gender, abdominal obesity, type-2 diabetes, serum glucose, HDL, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had very low prevalence of increased LS. The best cutoff of LS for significant liver fibrosis (F2-F4) was 9.2kPa, with high sensitivity and specificity. TE was more accurate than ALT, NAFLD fibrosis score or FIB-4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed. CONCLUSIONS: These findings demonstrate a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. A value of LS

PURPOSE: Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years. PARTICIPANTS: A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits. FINDINGS TO DATE: Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA

BACKGROUND AND AIM: Fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width-platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB-4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis. METHODS: A total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut-offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB-4, and APRI were statistically analyzed. RESULTS: The Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB-4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume-platelet ratio, respectively. The proportion of patient determined as cirrhosis or non-cirrhosis was 65.9% by transient elastography, 36.9% by FIB-4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB-4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively. CONCLUSIONS: In source-limited settings without transient elastography, stepwise applying FIB-4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.

Background: Elevated liver enzymes are frequently observed in renal transplant recipients and warrant further exploration. In immunosuppressed patients, hepatitis E virus (HEV) infection may cause chronic hepatitis, cirrhosis, and extrahepatic manifestations such as renal injury. Methods: We performed a retrospective cross-sectional study investigating the prevalence, clinical correlates, and outcome of chronic HEV infection in a cohort of renal transplant recipients with elevated liver enzymes. Results: Over a period of 30 months, 140 of 1469 renal transplant recipients had elevated liver enzymes, of which serum samples from 98 patients were available to determine HEV status. Seventeen patients were detected with HEV infection, of which 16 developed chronic HEV infection, while 1 patient controlled viremia (prevalence of chronic infection of 16.3%, with a minimum prevalence of 1.1% in the whole cohort). Increased liver stiffness was indicated by an average FibroScan result of 11.2 kPa in these patients. All 16 patients with chronic HEV infection were treated with ribavirin for a mean duration of 3 months. Five patients developed a viral rebound and received a second treatment course, of which 2 controlled HEV replication. Six months after the end of therapy, HEV clearance was achieved in 81.3% of the patients. One patient developed ribavirin resistance. Hemolytic anemia after ribavirin treatment was frequent, requiring blood transfusion in 3 patients. Four patients developed de novo glomerulonephritis, of which 2 were possibly associated with HEV infection. Conclusions: This retrospective study showed that prevalence of chronic HEV infection was high in our renal transplant patient cohort and was associated with significant liver impairment and the occurrence of renal injury. Ribavirin treatment was effective and should be initiated early to avoid complications, but the risk of severe hemolytic anemia makes strict monitoring essential.

BACKGROUND AND AIM: In patients with HCV-related cirrhosis, a SVR may lead to cirrhosis regression. Whether histological changes translate into prevention of long-term complications, particularly hepatocellular carcinoma (HCC) is still unknown. This was investigated in a cohort of histological cirrhotics who had been prospectively followed-up for 10 years after the achievement of a SVR to IFN. METHODS: 38 SVR cirrhotics who underwent a liver biopsy (LB) 5 years post-SVR were prospectively followed to assess the impact of cirrhosis regression on clinical endpoints. RESULTS: During a follow-up of 86 (30-96) months from LB, no patients developed clinical decompensation, whilst 5 (13%) developed HCC after 79 (7-88) months. The 8-year cumulative probability of HCC was 17%, without differences between patients with or without cirrhosis regression [19% (95% CI 6-50%) vs. 14% (95% CI 4-44%), p=0.88]. Patients who developed or did not an HCC had similar rates of residual cirrhosis (p=1.0), collagen content (p=0.48), METAVIR activity (p=0.34), portal inflammation (p=0.06) and steatosis (p=0.17). At baseline, patients who developed an HCC had higher gammaGT (HR 1.03, 95% CI 1.00-1.06; p=0.014) and glucose (HR 1.02, 95% CI 1.00-1.02; p=0.012) values; moreover, they had increased Forns Score (HR 12.8, 95% CI 1.14-143.9; p=0.039), Lok Index (HR 6.24, 95% CI 1.03-37.6; p=0.046) and PLF (HR 19.3, 95% CI 1.72-217.6; p=0.016) values. One regressor died of lung cancer. The 8-year cumulative survival probability was 97%, independently on cirrhosis regression (96% vs. 100%, p=1.0) or HCC (100% vs. 97%, p=1.0). CONCLUSIONS: Post-SVR cirrhosis regression does not prevent HCC occurrence. This article is protected by copyright. All rights reserved.

Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P

BACKGROUND: Serum levels of alpha-fetoprotein (AFP) were reported to increase in patients with significant or advanced hepatic fibrosis. Combination of non-invasive tests decreases the use of liver biopsy in large proportion of chronic HCV patients. AIM: To compare and combine AFP with commonly used non-invasive fibrosis tests in novel scores for prediction of different stages of hepatic fibrosis. PATIENTS AND METHODS: Six hundred and fifty two treatment naive chronic hepatitis C patients were enrolled. Demographic data, basic pre-treatment laboratory tests (complete blood count (CBC), liver biochemical profile and renal functions test, international normalized ratio (INR) in addition to AFP, liver stiffness measurement (LSM) by Fibroscan and liver biopsies were retrospectively analyzed. AST to Platelet Ratio Index (APRI) and FIB-4 scores were calculated. Different predictive models using multivariate logistic regression analysis were generated and presented in equations (scores) composed of a combination of AFP, LSM plus FIB-4/APRI scores. RESULTS: AFP was correlating significantly with LSM, FIB-4 and APRI scores. Areas under receiver operating characteristic curves (AUROCs) for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.931 and 0.955 respectively for equations (scores) containing AFP, LSM and FIB-4. AUROCs for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.929 and 0.959 respectively for equations (scores) containing AFP, LSM and APRI. CONCLUSION: Combining AFP to serum biomarkers and LSM increases their diagnostic performance for prediction of different stages of liver fibrosis. This article is protected by copyright. All rights reserved.

BACKGROUND: Controlled attenuation parameter (CAP) is a novel, noninvasive technique for assessing hepatic steatosis. However, its role in morbidly obese individuals is unclear. The effect of bariatric surgery on inflammation and fibrosis needs to be explored. OBJECTIVES: To assess the utility of CAP for assessment of hepatic steatosis in morbidly obese individuals and evaluate the effect of bariatric surgery on hepatic steatosis and fibrosis. SETTING: A tertiary care academic hospital. METHODS: Baseline details of anthropometric data, laboratory parameters, FibroScan (XL probe), and liver biopsy were collected. Follow-up liver biopsy was done at 1 year. RESULTS: Of the 124 patients screened, 76 patients were included; mean body mass index was 45.2 +/- 7.1 kg/m(2). FibroScan success rate was 87.9%. The median liver stiffness measurement (LSM) and CAP were 7.0 (5.0-9.5) kPa and 326.5 (301-360.5) dB/m, respectively. On liver histopathology, severe steatosis and nonalcoholic steatohepatitis were present in 5.3% and 15.8%; significant fibrosis (>/=stage 2) and cirrhosis in 39.5% and 2.6%, respectively. Area under receiver operator characteristic curve of LSM for prediction of significant fibrosis (F2-4 versus F0-1) and advanced fibrosis (F3-4 versus F0-2) was .65 (95% confidence interval [CI]: .52-.77) and .83 (95% CI: .72-.94), respectively. The area under receiver operator characteristic curve of CAP for differentiating moderate hepatic steatosis (S2-3 versus S0-1) and severe hepatic steatosis (S3 versus S0-2) was .74 (95% CI: .62-.86) and .82 (95% CI: .73-.91), respectively. At 1-year follow-up, 32 patients underwent liver biopsy. In these patients, there was significant improvement in hepatic steatosis (P = .001), lobular inflammation (P = .033), ballooning (P<.001 and fibrosis .003 nonalcoholic steatohepatitis was resolved in of patients. lsm cap significantly declined. conclusions: are feasible accurate at diagnosing advanced severe hepatic steatosis morbidly obese individuals. bariatric surgery is associated with significant improvement fibrosis. class="article_links">

We aimed to assess fibrosis with liver stiffness measurement long-term after sustained virologic response of chronic hepatitis C, and to identify risk factors associated with persisting fibrosis. In this cross-sectional study, patients with chronic hepatitis C and pre-treatment advanced fibrosis or cirrhosis treated successfully at Karolinska University Hospital with an interferon-containing regimen, underwent liver stiffness measurement with FibroScan. The impact of potential risk factors for persisting fibrosis was estimated. We included 269 patients with a median follow-up time of 7.7 years (range 0-20), 84 with a follow-up time of >/= 10 years. Patients with pre-treatment cirrhosis had a significantly higher median liver stiffness level (8.5 kPa 95% CI 7-9.1) at follow-up, than patients with advanced fibrosis (6 kPa 95% CI 5.5-6.4). A majority improved their fibrosis stage after sustained virologic response, but 24% had persisting advanced fibrosis with a liver stiffness level of >/= 9.5 kPa. Among patients with pre-treatment cirrhosis the proportion with persisting advanced fibrosis diminished with longer follow-up time, from 48% after 10 years. The main risk factors for persisting advanced fibrosis were pre-treatment cirrhosis, high age and body mass index. In conclusion, fibrosis improves substantially during long-term follow-up after sustained virologic response in hepatitis C patients with pre-treatment advanced liver fibrosis. Life-style intervention to decrease weight in obese persons and treatment before establishment of cirrhosis should therefore be recommended to avoid persistence of advanced fibrosis after virologic cure. This article is protected by copyright. All rights reserved.

The potential interaction between chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD), two of the most prevalent liver diseases worldwide, has not been well defined. We performed liver stiffness (LS) and controlled attenuation parameter (CAP) measurements using transient elastography in 1202 CHB patients. Of these, 601 steatotic patients were matched with nonsteatotic controls in a 1:1 ratio by age, gender, nucleoside analogue treatment status, and treatment duration. Severe fibrosis was defined according to EASL-ALEH criteria, and steatosis was defined as CAP >/=222 dB m(-1) . Anthropometric measurements and metabolic-related parameters were recorded. The mean age of the 1202 patients (51.4% male) was 51.8 years. 696 patients (57.9%) were on nucleoside analogues for a median duration of 76.2 months. Among treatment-naive patients, median serum HBV DNA was lower in steatotic individuals than in controls (3.0 vs 3.4 log IU mL(-1) , P

INTRODUCTION: The value of repeated liver stiffness measurement (LSM) in non-alcoholic fatty liver disease (NAFLD) has not been shown before. METHODS: A longitudinal study of biopsy-proven NAFLD patients was conducted at the Asian tertiary hospital from November 2012 to January 2017. Patients with paired liver biopsies and LSM were followed prospectively for liver-related and non-liver related complications, and survival. RESULTS: The data for 113 biopsy-proven NAFLD patients (mean age 51.3 +/- 10.6 years, male 50%) were analyzed. At baseline, advanced fibrosis based on histology and LSM was observed in 22 and 46%, respectively. Paired liver biopsy and LSM at 1-year interval was available in 71 and 80% of patients, respectively. High-risk cases (defined as patients with advanced fibrosis at baseline who had no fibrosis improvement, and patients who developed advanced fibrosis on repeat assessment) were seen in 23 and 53% of patients, based on paired liver biopsy and LSM, respectively. Type 2 diabetes mellitus was independently associated with high-risk cases. The median follow-up was 37 months with a total follow-up of 328 person-years. High-risk cases based on paired liver biopsy had significantly higher rates of liver-related complications (p = 0.002) but no difference in other outcomes. High-risk patients based on paired LSM had a significantly higher rate of liver-related complications (p = 0.046), cardiovascular events (p = 0.025) and composite outcomes (p = 0.006). CONCLUSION: Repeat LSM can predict liver-related complications, similar to paired liver biopsy, and may be useful in identifying patients who may be at an increased risk of cardiovascular events. Further studies in a larger cohort and with a longer follow-up should be carried out to confirm these observations.

INTRODUCTION: Achievement of the 2030 World Health Organisation (WHO) global hepatitis C virus (HCV) elimination targets will be underpinned by scale-up of testing and use of direct-acting antiviral treatments. In Australia, despite publically-funded testing and treatment, less than 15% of patients were treated in the first year of treatment access, highlighting the need for greater efficiency of health service delivery. To this end, non-invasive fibrosis algorithms were examined to reduce reliance on transient elastography (TE) which is currently utilised for the assessment of cirrhosis in most Australian clinical settings. MATERIALS AND METHODS: This retrospective and prospective study, with derivation and validation cohorts, examined consecutive patients in a tertiary referral centre, a sexual health clinic, and a prison-based hepatitis program. The negative predictive value (NPV) of seven non-invasive algorithms were measured using published and newly derived cut-offs. The number of TEs avoided for each algorithm, or combination of algorithms, was determined. RESULTS: The 850 patients included 780 (92%) with HCV mono-infection, and 70 (8%) co-infected with HIV or hepatitis B. The mono-infected cohort included 612 men (79%), with an overall prevalence of cirrhosis of 16% (125/780). An 'APRI' algorithm cut-off of 1.0 had a 94% NPV (95%CI: 91-96%). Newly derived cut-offs of 'APRI' (0.49), 'FIB-4' (0.93) and 'GUCI' (0.5) algorithms each had NPVs of 99% (95%CI: 97-100%), allowing avoidance of TE in 40% (315/780), 40% (310/780) and 40% (298/749) respectively. When used in combination, NPV was retained and TE avoidance reached 54% (405/749), regardless of gender or co-infection. CONCLUSIONS: Non-invasive algorithms can reliably exclude cirrhosis in many patients, allowing improved efficiency of HCV assessment services in Australia and worldwide.

FIBROSIS STAGING IN CHRONIC HEPATITIS C
Recommendation 15: TE can be used as the first-line assessment for the severity of liver fibrosis in patients with chronic viral hepatitis C. It performs best with regard to the ruling out of cirrhosis (LoE 1b, GoR A) [4] [98] [100]. Broad consensus (17/0/1, 94 %) RECOMMENDATION 19 LSM changes after successful anti-HCV treatment should not affect the management strategy (e. g. surveillance for HCC occurrence in patients at risk) (LoE 3, GOR D) [52]. Broad con- sensus (16/0/1, 94% FIBROSIS STAGING IN CHRONIC HEPATITIS B Recommendation 20 TE is useful in patients with CHB to identify those with cirrhosis. Concomitant assessment of transaminases is required to exclude flare up (elevation > 5 times upper limit of normal). (LoE 1b, GoR A) [128] [129] [130]. Broad consensus (17/1/0, 94 %) Recommendation 21 TE is useful in inactive HBV carriers to rule out fibrosis (LoE 2, GOR B) [138] [139]. Strong consensus (18/0/0, 100 %) Recommendation 24 LSM changes under HBV treatment should not affect the management strategy (e. g. surveillance for HCC occurrence in patients at risk) (LoE 2b, GOR B) [148] [149]. Strong consensus (16/0/0, 100 %) FIBROSIS STAGING IN NAFLD Recommendation 25 TE can be used to exclude cirrhosis in NAFLD patients (LoE 2a, GoR B) [52] [160]. Broad consensus (13/0/3, 81 %) FIBROSIS STAGING IN ALD TE can be used to exclude cirrhosis in patients with alcoholic liver disease, provided that acute alcoholic hepatitis is not present (LoE 2b, GoR B) [30] [164] [169] [170]. Strong consensus (15/0/0, 100 %) PORTAL HYPERTENSION Recommendation 27 LSM with TE is useful to identify patients with a high likelihood of having clinically significant portal hypertension (HVPG ≥ 10 mmHg) (LoE 2b, GoR B) [188] [189]. Strong consensus (15/0/0, 100 %) Recommendation 28 Liver stiffness using TE combined with platelet count is useful to rule out varices requiring treatment (LoE 2b, GoR B) [194]. Although preliminary results are encouraging, there is insufficient evidence to recommend pSWE and 2D-SWE in this setting. Broad consensus (13/0/1, 93 %)

Management of patients with Chronic Viral Hepatitis C
Recommendation: In patients with chronic hepatitis C, the AGA recommends VCTE, if available, rather than other nonproprietary, noninvasive serum tests (APRI, FIB-4) to detect cirrhosis.
Recommendation: In patients with chronic hepatitis C, the AGA suggests a VCTE cutoff of 12.5 kPa to detect cirrhosis
Recommendation: In noncirrhotic patients with HCV who have achieved SVR after antiviral therapy, the AGA suggests a post-treatment vibration controlled transient elastography cutoff of 9.5 kPa to rule out advanced liver fibrosis.
Recommendation: In adult patients with chronic hepatitis C, the AGA suggests using VCTE rather than MRE for detection of cirrhosis. Management of patients with chronic hepatitis B:
Recommendation: In patients with chronic hepatitis B, the AGA suggests VCTE rather than other nonproprietary noninvasive serum tests (ie, APRI and FIB-4) to detect cirrhosis.
Recommendation: In patients with chronic hepatitis B, the AGA suggests a VCTE cutoff of 11.0 kPa to detect cirrhosis.

Management of patients with Alcoholic Liver Disease
Recommendation: In patients with chronic alcoholic liver disease, the AGA suggests a VCTE cutoff of 12.5 kPa to detect cirrhosis. Prediction of oseophageal varices:
Recommendation: In patients with suspected compensated cirrhosis, the AGA suggests a vibration controlled transient elastography cutoff of 19.5 kPa to assess the need for esophagogastroduodenoscopy to identify high risk esophageal varices.

Management of patients with portal hypertension
Recommendation: In patients with suspected chronic liver disease undergoing elective nonhepatic surgery, the AGA suggests a VCTE cutoff of 17.0 kPa to detect clinically significant portal hypertension to inform preoperative care.

OBJECTIVE: The study aimed to evaluate the prevalence and predictor factors for compensated advanced chronic liver disease (c-ACLD) in patients with hepatitis Delta virus (HDV) infection. METHODS: This cross-sectional study included consecutive HDV-infected patients defined by positive anti-HDV. Patients with hepatitis C coinfection, liver transplantation or presence of conditions that limit liver (LSM) or spleen stiffness measurement (SSM) were excluded. Blood tests, abdominal ultrasound, SSM and LSM by transient elastography (FibroScan(R)) were performed at the same day. Alcohol consumption was quantified using the AUDIT score and c-ACLD was defined by LSM >/= 15 kPa performed by an experimented operator blinded for clinical and laboratory data. RESULTS: 101 patients were eligible and few patients were excluded due to negative anti-HDV (n = 7), hepatitis C coinfection (n = 2), liver transplantation (n = 10) and limitation for LSM or SSM (n = 5). Therefore, 77 patients [61% male, age = 43 (IQR,36-52) years] were included. The prevalence of c-ACLD was 57% (n = 44/77). Patients with c-ACLD had a higher rate of detectable HBV viral load (p = 0.039), higher levels of transaminases, GGT, alkaline phosphatases, total bilirubin and INR (p<0.001 for="" all="" as="" well="" lower="" platelet="" count="" and="" albumin="" levels="" p="">0.001 for both) compared to those without c-ACLD. Patients with c-ACLD had higher SSM [65.2 (IQR,33.8-75.0) vs 21.8 (16.5-32.0) kPa; p<0.001] and higher splenic volume [475 (IQR,311-746) vs 154 (112-283) cm3; p<0.001] compared to those without. Detectable HBV viral load (>10 UI/ml), alkaline phosphatase (per IU/L) and GGT levels (per IU/L) were independently associated with c-ACLD in all multivariate models. Splenic volume [per cm3,OR = 1.01 (95%CI,1.01-1.02);p = 0.002], SSM [per kPa, OR = 1.04 (1.01-1.07);p = 0.012] and splenomegaly [yes vs no,OR = 28.45 (4.42-182.95);p<0.001] were independently associated with c-ACLD. CONCLUSIONS: The prevalence of c-ACLD was high in patients with chronic HDV infection in western Amazon basin. HBV viral load, liver enzymes and splenic features can be used to predict severe liver disease in HDV-infected patients.

Portal hypertension (PHT) is a key event in the evolution of different chronic liver diseases and leads to the morbidity and mortality of patients. The traditional reliable PHT evaluation method is a hepatic venous pressure gradient (HVPG) measurement, which is invasive and not always available or acceptable to patients. The HVPG measurement is relatively expensive and depends on the experience of the physician. There are many potential noninvasive methods to predict PHT, of which liver transient elastography is determined to be the most accurate; however, even transient elastography lacks the accuracy to be a perfect noninvasive diagnostic method of PHT. In this research, we are focusing on noninvasive PHT assessment methods that rely on selected best-supervised learning algorithms which use a wide set of noninvasively obtained data, including demographical, clinical, laboratory, instrumental, and transient elastography measurements. In order to build the best performing classification meta-algorithm, a set of 21 classification algorithms have been tested. The problem was expanded by selecting the best performing clinical attributes using algorithm-specific filtering methods that give the lowest error rate to predict clinically significant PHT. The suggested meta-algorithm objectively outperforms other methods found in literature and can be a good substitute for invasive PHT evaluation methods.

BACKGROUND: We aimed to investigate the early changes in liver and spleen stiffness measurement (LSM, SSM) in hepatitis C virus (HCV) patients with compensated advanced chronic liver disease (cACLD) treated with new antivirals (DAA) to elucidate factors determining the initial change in stiffness and its implications for the long-term follow up of HCV-cured patients. METHODS: A total of 41 patients with cACLD who started DAA therapy underwent LSM and SSM at baseline, week 4, end of treatment (EOT), 24 and 48 weeks of follow up using transient elastography. RESULTS: LSM improved rapidly during the first 4 weeks of treatment (baseline: 20.8kPa; week 4: 17.5kPa, p = 0.002), with no significant changes between week 4 and EOT (18.3kPa, p = 0.444) and between EOT and 48-week follow up (14.3kPa, p = 0.148). Likewise, SSM improved rapidly (baseline: 45.7kPa; week 4: 33.8kPa, p = 0.047), with no significant changes between week 4 and EOT (30.8kPa, p = 0.153) and between EOT and 48-week follow up (31.2kPa, p = 0.317). A higher decrease in LSM was observed in patients with baseline ALT twofold upper limit normal (2 x ULN) than in those with ALT < 2 x ULN (-5.7kPa versus -1.6kPa). Patients who presented a decrease in LSM 10% during treatment compared with those with LSM < 10% decrease, showed lower SSM values, higher platelet counts and lower bilirubin levels at 24-week follow up. Those with decrease in SSM 10%, presented a higher increase in platelets than those with SSM < 10% change (p = 0.015). CONCLUSIONS: LSM and SSM decrease very rapidly during DAA treatment in cACLD patients suggesting that it most probably reflects a reduction in inflammation rather than in fibrosis. cACLD patients should be maintained under surveillance independently of stiffness changes, because advanced fibrosis can still be present.

BACKGROUND: Hepatosplenic schistosomiasis (HES) has not been evaluated by transient elastography so far and its correlation with ultrasound variables remains to be defined. AIMS: The aim of this study was to describe the parameters of liver and spleen stiffness in HES assessed by transient elastography in comparison with cirrhotics and controls evaluating its correlation with ultrasonographic data. PATIENTS AND METHODS: HES, hepatitis C virus-cirrhotic, and control patients were included in this sectional study. Liver and spleen stiffness were compared among the three groups. The ultrasonographic parameters were compared with transient elastography in HES patients. RESULTS: Thirty HES, 30 hepatitis C virus-cirrhotic patients, and 17 controls were included. Those with HES presented liver stiffness that was significantly higher than the controls and lower than the cirrhotics: 9.7 (3.6-75.0) versus 3.7 (2.8-5.4) versus 27.0 (14.7-61.5) kPa (P<0.001). Spleen stiffness values were comparable between hepatosplenic and cirrhotics: 66.4 (25.7-75.0) versus 69.1 (18.0-75.0) kPa (P=0.78) and were significantly higher than the controls 16.5 kPa (6.3-34.3) (P<0.001). In patients with HES, high spleen stiffness was associated with right liver lobe diameter (P=0.015), splenic artery resistance index (P=0.002), portal vein diameter (P=0.021), portal vein area (P=0.008), portal vein congestion index (P=0.035), splenic vein diameter (P=0.013), and spleen diameter (P=0.021). CONCLUSION: Liver stiffness may be a useful tool to differentiate portal hypertension related to cirrhosis from that of HES. High spleen stiffness is a potential surrogate marker of portal hypertension in this population.

BACKGROUND: Variceal bleeding is a common and life-threatening complication in patients with cirrhosis. Screening with upper endoscopy is recommended but is uncomfortable to patients. Non-invasive assessment with transient elastography for liver/spleen stiffness measurement (LSM and SSM) is accurate in detecting varices. AIMS: To test the hypothesis that a new screening strategy for varices guided by LSM/SSM results (LSSM-guided) is non-inferior to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. METHODS: This was a non-inferiority, open-label, randomized controlled trial. Adult patients with known chronic liver diseases, radiological evidence of cirrhosis and compensated liver function. The primary outcome was clinically significant varix diagnosed with upper endoscopy. RESULTS: Between October 2013 and June 2016, 548 patients were randomized to LSSM arm (n = 274) and conventional arm (n = 274) which formed the intention-to-test (ITT) population. Patients in both study arms were predominantly middle-aged men with viral hepatitis-related cirrhosis in 85% of the cases. In the ITT analysis, 11/274 participants in the LSSM arm (4.0%) and 16/274 in the conventional arm (5.8%) were found to have clinically significant varices. The difference between two groups was -1.8% (90% CI, -4.9% to -1.2%, P < .001). The absolute difference in the number of patients with clinically significant varices detected was 5/16 (31.3%) fewer in the LSSM arm. CONCLUSIONS: Non-inferiority of the LSSM-guided screening strategy to the convention approach cannot be excluded by this RCT. This approach should be further evaluated in a cohort of larger sample size with more clinically significant varices.

Postoperative liver failure (PLF) is the primary cause of morbidity and mortality after hepatic resection for hepatocellular carcinoma (HCC). In this study, we evaluated the efficacy of liver stiffness (LS) and spleen stiffness (SS), as measured by transient elastography (TE), for predicting the risk of PLF and overall survival (OS) in these patients.This prospective cohort study included 54 patients diagnosed with HCC who underwent hepatic resection between March 2013 and March 2014. Preoperative measurement of LS and SS using TE was performed on all patients underwent. The predictivity of LS and SS for PLF was assessed by receiver operating characteristic curve analysis. OS according to LS and SS was analyzed using the Kaplan-Meier method and compared using the log-rank test.PLF developed in seven (12.96%) patients. LS was significantly higher in patients with than in those without PLF (P = .03). The area under the curve of LS for predicting PLF was 0.76 (95% confidence interval, 0.62-0.86; P = .02). However, there was no significant difference in SS between patients with and without PLF (P = .36). Moreover, patients with an LS <16.2 kpa="" had="" significantly="" better="" os="" than="" those="" with="" an="" ls="">/=16.2 kPa (P = .028). No significant difference in OS was observed between patients with an SS of <22.3 and="">/=22.3 kPa (P = .378).LS measured by TE can be used to predict the risk of PLF as well as OS in patients with HCC who have undergone hepatic resection. However, SS obtained using TE was not found to be a significant predictor for PLF and OS in our patients.

BACKGROUND & AIMS: NAFLD is highly prevalent but only a small subset of patients develop advanced liver fibrosis with impaired liver-related prognosis. We aimed to compare blood fibrosis tests and liver stiffness measurement (LSM) by Fibroscan for the diagnosis of liver fibrosis and the evaluation of prognosis in NAFLD. METHODS: Diagnostic accuracy was evaluated in a cross-sectional study including 452 NAFLD patients with liver biopsy (NASH-CRN fibrosis stage), LSM, and eight blood fibrosis tests (BARD, NAFLD Fibrosis Score, FibroMeterNAFLD, APRI, FIB4, Fibrotest, Hepascore, FibroMeterV2G). Prognostic accuracy was evaluated in a longitudinal study including 360 NAFLD patients. RESULTS: LSM and FibroMeterV2G were the two best-performing tests in the cross-sectional study: AUROCs for advanced fibrosis (F3/4) were, respectively, 0.831+/-0.019 and 0.817+/-0.020 (p0.041 vs other tests); rates of patients with 90% negative/positive predictive values for F3/4 were 56.4% and 46.7% (p

OBJECTIVES: The aim of the study was to establish the risk of liver toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving etravirine, according to the degree of liver fibrosis. METHODS: A prospective cohort study of 211 HIV-infected patients initiating an etravirine-containing regimen was carried out. HCV coinfection was defined as a positive HCV RNA test, and baseline liver fibrosis was assessed by transient elastography. Hepatotoxicity was defined as clinical symptoms, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value > 5-fold higher than the upper limit of normal if baseline values were normal, or 3.5-fold higher if values were altered at baseline. RESULTS: Overall, 145 patients (69%) were HCV coinfected, with a lower nadir (165 versus 220 cells/muL, respectively; p = 0.03) and baseline (374 versus 498 cells/muL, respectively; p = 0.04) CD4 count than monoinfected patients. Etravirine was mainly used with two nucleoside reverse transcriptase inhibitors (129; 61%) or with a boosted protease inhibitor (PI) (28%), with no significant differences according to HCV serostatus. Transient elastography in 117 patients (81%) showed a median (range) stiffness value of 8.25 (3.5-69) kPa, with fibrosis stage 1 in 43 patients (37%) and fibrosis stage 4 in 28 patients (24%). During an accumulated follow-up time of 449.3 patient-years (median 548 days), only one patient with advanced fibrosis (50.8 kPa) had grade 3-4 liver toxicity (0.7%). Transaminases changed slightly, with no significant differences compared with baseline fibrosis, and nine and six patients had grade 1 and 2 transaminase increases, respectively. Also, HCV coinfection was not associated with a higher risk of discontinuation (25% discontinued versus 21% of monoinfected patients; p = 0.39, log-rank test) or virological failure (8% versus 12%, respectively; p = 0.4). CONCLUSIONS: Our data suggest that etravirine is a safe option for HIV/HCV-coinfected patients, including those with significant liver fibrosis.

Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue. The goal of this study was to assess the clinical use of liver stiffness measurement (LSM) evaluated by supersonic shear imaging (SSI), FibroScan, and acoustic radiation force impulse (ARFI) in a cohort of NAFLD patients who underwent liver biopsy. A total of 291 NAFLD patients were prospectively enrolled from November 2011 to February 2015 at 2 French university hospitals. LSM was assessed by SSI, FibroScan (M probe), and ARFI within two weeks prior to liver biopsy. Calculations of the area under the receiver operating curve (AUROC) were performed and compared for the staging of liver fibrosis. AUROC for SSI, FibroScan, and ARFI were 0.86, 0.82, and 0.77 for diagnoses of >/=F2; 0.89, 0.86, and 0.84 for >/=F3; and 0.88, 0.87, and 0.84 for F4, respectively. SSI had a higher accuracy than ARFI for diagnoses of significant fibrosis (>/=F2) (P = 0.004). Clinical factors related to obesity such as body mass index >/= 30 kg/m(2) , waist circumference >/=102 cm or increased parietal wall thickness were associated with LSM failures when using SSI or FibroScan and with unreliable results when using ARFI. In univariate analysis, FibroScan values were slightly correlated with NAFLD activity score and steatosis (R = 0.28 and 0.22, respectively), whereas SSI and ARFI were not; however, these components of NAFLD did not affect LSM results in multivariate analysis. The cutoff values for SSI and FibroScan for staging fibrosis with a sensitivity >/=90% were very close: 6.3/6.2 kPa for >/=F2, 8.3/8.2 kPa for >/=F3, and 10.5/9.5 kPa for F4. CONCLUSION: Although obesity is associated with an increase in LSM failure, the studied techniques and especially SSI provide high value for the diagnosis of liver fibrosis in NAFLD patients. (Hepatology 2016;63:1817-1827).

Staging of liver fibrosis and diagnosis, or exclusion, of early compensated liver cirrhosis are important in the treatment decisions and surveillance of patients with chronic liver disease. Good diagnostic accuracy, increased availability and the possibility to perform follow-up examinations led to the implementation of noninvasive methods into clinical practice. Noninvasive tests are increasingly included in national and international guidelines, leaving liver biopsy reserved for patients with unexplained discordance or suspected additional aetiologies of liver disease. In addition to staging of liver fibrosis, data on the prognostic value of these methods have increased in the past few years and are of great importance for patient care. This Review focuses on elastography methods for noninvasive assessment of liver fibrosis, disease severity and prognosis. Although liver elastography started with transient elastography, at present all large ultrasonography companies offer an elastography technique integrated in their machines. The goal of this Review is to summarize the methodological problems of noninvasive tests in general, in addition to providing an overview on currently available techniques and latest developments in liver elastography.

AIM: Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this study was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. METHODS: Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan(R) just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. RESULTS: CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m2 (r = 0.579, P

AIM: Transient elastography is a noninvasive and reliable method for the assessment of liver stiffness. This study aimed to assess liver stiffness of asymptomatic liver fluke disease patients by FibroScan and evaluate the factors influencing liver stiffness. METHODS: Overall, 65 patients were prospectively recruited from The First People's Hospital of Foshan, Guangdong, China. All patients were diagnosed with liver fluke disease; their durations of ingested freshwater raw fish or shrimp were more than 10 years, and none of them had abnormal liver function and hepatitis B virus or hepatitis C virus infection, or clinical symptoms. All patients underwent FibroScan, blood biochemical examination, and BMI measurement on the same day. Liver stiffness measurement (LSM) values, sex, age, durations of ingested freshwater raw fish or shrimp, and BMI were recorded. LSM value greater than 7.4 kPa was defined as abnormal. RESULTS: A total of 27 patients (41.5%) had abnormal LSM values. On partial correlation analysis, duration of ingested freshwater raw fish or shrimp was the independent factor that showed a positive correlation with abnormal LSM values (r=0.502, P=0.012). An independent-samples t-test showed that the durations of patients with abnormal LSM values were significantly longer than the durations of patients with normal LSM values (P0.05). CONCLUSION: A high proportion of asymptomatic liver fluke disease patients had abnormal LSM values. The durations of patients with abnormal LSM values were significantly longer than the durations of patients with normal LSM values and the durations of patients with abnormal LSM values were an independent factor that showed a positive correlation with abnormal LSM values.

Prognosis and treatment of liver diseases mainly depend on the precise evaluation of the fibrosis. Comparisons were made between the results of Metavir fibrosis scores and digital morphometric analyses (DMA), liver stiffness (LS) values and aminotransferase-platelet ratio (APRI) scores, respectively. Liver biopsy specimens stained with Sirius red and analysed by morphometry, LS and APRI measurements were taken from 96 patients with chronic liver diseases (56 cases of viral hepatitis, 22 cases of autoimmune- and 18 of mixed origin). The strongest correlation was observed between Metavir score and DMA (r = 0.75 p

BACKGROUND: Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) >/=10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio) instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients. AIM: This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement. METHODS: All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D'Amico stage, VITRO score, APRI and transient elastography (TE). RESULTS: The analysis included 236 patients; 170 (72%) were male, and the median age was 57.9 (35.2-76.3; 95% CI). Disease aetiology included ALD (39.4%), HCV (23.4%), NASH (12.3%), other (8.1%) and unknown (11.9%). The CPS showed 140 patients (59.3%) with CPS A; 56 (23.7%) with CPS B; and 18 (7.6%) with CPS C. 136 patients (57.6%) had compensated and 100 (42.4%) had decompensated cirrhosis; 83.9% had HVPG >/=10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P

Nonalcoholic fatty liver disease (NAFLD) is now the most common form of liver disease in developed countries with an estimated prevalence of 20 - 30% and increasing to as high as 90% in diabetics. As the rates of NAFLD continue to rise in parallel with those of the obesity pandemic, it is increasingly important to differentiate those patients with the highest risk of progression to fibrosis and cirrhosis. In fact, those patients with nonalcoholic steatohepatitis (NASH) and fibrosis are at the greatest risk of progression to advanced disease, cirrhosis, and hepatocellular cancer and are more likely to develop liver related mortality. Thus, it is critically important to distinguish between NASH and non-NASH NAFLD. While liver biopsy remains the gold standard for staging of disease, complications of this procedure and other well recognized limitations make it impractical for widespread use given the overall NAFLD disease burden. Non-invasive imaging modalities are increasingly being utilized to evaluate and stage NAFLD in patients with such a wide spectrum of disease. In this article, the role of these new and promising non-invasive imaging modalities to assess disease severity in NAFLD are reviewed. This article is protected by copyright. All rights reserved.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.

The extent of fibrosis is a major determinant of the clinical outcome in patients with chronic liver diseases. We undertook this study to explore the degree of fibrosis in baseline liver biopsies to predict clinical outcomes in chronic hepatitis B (CHB) patients. Fibrosis quantification was done by image analysis on Masson's trichrome stained sections and correlated with clinical and biochemical parameters, liver stiffness and hepatic vein pressure gradient (HVPG, n=96). Follow-up information collected related to clinical outcome. A total 964 cases analyzed. Median quantitative fibrosis (QF) was 3.7% {interquartile range (IQR): 1.6-9.7%} with substantial variation in various stages. Median QF was F0, 1% (0.7% -1.65%); F1, 3.03% (2.07-4.0%); F2, 7.1% (5.6-8.7%); F3, 12.7% (10.15-16.7%); F4, 26.9% (20.3-36.4%). QF positively correlated with METAVIR staging, liver stiffness measurement, and HVPG. Eighty-nine cases developed liver-related events: decompensation, hepatocellular carcinoma (HCC), liver transplantation and death. Cox-regression analysis after adjusting for METAVIR staging- QF, albumin and AST for composite events; QF and albumin for decompensation and only QF for HCC, were found significant predictors of clinical outcomes. QF categorized into five stages: QF1, 0-5%; QF2, 5.1-10%; QF3, 10.1-15%; QF4, 15.1-20%; QF5, > 20.1%. In patients with advanced stages of QF, a probability of event-free survival found to be low. Quantitative fibrosis in baseline liver biopsy predicts progression of the disease and disease outcome in CHB patients. QF defines the probability of event-free survival in CHB cases.

BACKGROUND & AIMS: We performed a propensity-score matched analysis to investigate whether entecavir, compared with lamivudine, can reduce risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B after adjusting for level of fibrosis. METHODS: We performed a retrospective study of 1079 patients with chronic hepatitis B who received first-line therapy with lamivudine (n=435) or entecavir (n=644) from 2006 through 2013 at Yonsei University College of Medicine in South Korea. Only patients with available liver stiffness value measured by transient elastography were recruited. Liver cirrhosis was diagnosed by ultrasonography. To adjust for the imbalance of patients treated with lamivudine vs entecavir, we performed propensity-score matching (PSM), at a ratio of 1:1, using 7 factors (age, sex, hepatitis B e antigen, alanine aminotransferase, serum albumin, platelet count, and liver stiffness; PSM1) or 8 factors (variables of PSM1 plus ultrasonography measurements of cirrhosis; PSM2). Patients with virologic breakthrough or resistance mutations received rescue therapy. RESULTS: Over the 7 year period, 91 patients developed HCC and 104 had liver-related events in the entire cohort. In multivariate analyses, level of fibrosis, but not antiviral regimen, was independently associated with risk of HCC (P<.05 the psm1 group included pairs of patients and psm2 pairs. similar proportions given lamivudine vs entecavir developed hcc in each model all p>.05). When PSM was applied to patients with liver stiffness measurements =13kPa or >13kPa, patients given lamivudine vs entecavir still had similar cumulative rates of HCC development (all P>.05). CONCLUSION: In a PSM analysis, we associated level of fibrosis, rather than antiviral therapy, with risk of HCC, when patients received appropriate rescue therapy in case of virologic breakthrough or resistance mutations.

Hepatic steatosis assessment is of paramount importance for living liver donor selection because significant hepatic steatosis can affect the postoperative outcome of recipients and the safety of the donor. The validity of various noninvasive imaging methods to assess hepatic steatosis remains controversial. The purpose of our study is to investigate the association between noninvasive imaging methods and pathology to detect steatosis in living liver donors and to propose a prediction model for hepatic steatosis.Liver stiffness measurements (LSMs) and controlled attenuation parameter values in vibration controlled transient elastography, ultrasonography, computed tomography (CT), and magnetic resonance imaging were used as pretransplant screening methods to evaluate living liver donors between 2012 and 2014. Only 1 pathologist assessed tissue sample for hepatic steatosis.The median age of the 79 living donors (53 men and 26 women) was 32 years (16-68 years). The CT liver-spleen attenuation (L-S) difference and the controlled attenuation parameter values were well correlated with the level of hepatic steatosis on liver pathology. Multivariate analysis showed that liver stiffness measurement (LSM) (beta = 0.903; 95% CI, 0.105-1.702; P = 0.027) and the CT L to S attenuation difference (beta = -3.322; 95% CI, -0.502 to -0.142; P = 0.001) were closely associated with hepatic steatosis. We generated the following equation to predict total hepatic steatosis: Hepatic steatosis = 0.903 x LSM - 0.322 x CT L to S attenuation difference (AUC = 86.6% and P = 0.001). The values predicted by the equation correlated well with the presence of hepatic steatosis (r = 0.509 and P

A 60-year-old woman without a history of liver diseases, but with a history of regular alcohol consumption, presented with a right-sided transudative pleural effusion. Neither parenchymal lung lesion nor pleural thickening was seen on a chest computed tomography. On abdominal ultrasonography, the liver size and contour were normal, and ascites was not noted. Despite performing imaging and laboratory studies, we could not find a cause of the pleural effusion. Thus, due to her history of regular alcohol consumption, we decided to measure liver stiffness using a transient elastography (Fibroscan((R)), Echosens(TM), Paris, France), which showed a value of 35.3 kPa suggestive of liver cirrhosis. An intraperitoneal injection of a radioisotope demonstrated the transdiaphragmatic flow of fluid from peritoneal cavity to pleural cavity. The diagnosis was confirmed as hepatic hydrothorax. Management consisting of restricted salt and water intake with diuretics resulted in resolution of the hepatic hydrothorax.

Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB).Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan-Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves.The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791-0.807 vs 0.691-0.725; all P 0.05).LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies.

Non-selective beta-blockers and handling of esophageal varices has been key elements in the treatment of portal hypertension in recent decades. Liver vein catheterization has been essential in diagnosis and monitoring of portal hypertension, but ongoing needs for noninvasive tools has led to research in areas of both biomarkers, and transient elastography, which displays promising results in discerning clinically significant portal hypertension. Novel research into the areas of hepatic stellate cell function and the dynamic components of portal hypertension has revealed promising areas of treatment modalities, targeting intestinal decontamination, angiogenesis, inflammation and oxidative stress. Future studies may reveal if these initiatives lead to developments of new drugs for treatment of portal hypertension.

BACKGROUND AND AIMS: HBsAg seroclearance is the most desired endpoint in chronic hepatitis B (CHB) but occurs uncommonly. Recent studies have shown baseline HBsAg levels to be predictive of HBsAg loss up to 10 years. We report the 28-year rates of HBsAg loss and outcomes in the Kawerau study cohort from New Zealand, and assess the predictive value of baseline HBsAg levels to predict long-term HBsAg loss. METHODS: The 1984 Kawerau community study identified 572 CHB patients, followed up for 28 years (41 % HBeAg-positive, median age 17 years, range 1-71 years). In 2012, surviving individuals attended a local clinic for an interview, blood tests and transient elastography. RESULTS: 384/218 (74 %) surviving individuals attended the clinic in 2012. Spontaneous HBsAg loss occurred in 145 (33 %) after 12,702 person-years of follow-up (1.14 per 100 person-years). Liver stiffness measurements were significantly lower if HBsAg loss occurred 50 years (mean 11.6 kPa), p = 0.0002. No HCC occurred following HBsAg loss (median follow-up 72 months). Predictors of HBsAg loss were older age and lower baseline HBsAg level (HR for HBsAg loss at 28 years 2.7 (95 % CI 1.7-4.2), 6.7 (95 % CI 3.9-11.4) and 9.4 (95 % CI 5.2-16.9), respectively, for HBsAg 1000-9999, 100-999 and 10,000 IU/mL at baseline, (p

BACKGROUND/AIMS: Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). METHODS: From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0+/-12.9 months for decompensation and mortality. RESULTS: A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p

The aim of the present study was to investigate the usefulness of combined detection of liver stiffness (LS) and serum C-reactive protein (CRP) level in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). A total of 156 cases of previously untreated patients with HBV-related LC were classified into the LC group [LC without hepatocellular carcinoma (HCC)] and the HCC group (LC with HCC). Comparative analyses of LS and serum CRP level were conducted between these two groups. LS values and serum CRP levels were found to be significantly higher in the HCC group compared with those in the LC group (P

BACKGROUND: Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. AIM: To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. METHODS: Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy ((1) H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). RESULTS: All HIV-infected individuals (mean +/- s.d. age 54 +/- 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4-13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1-6.2) kPa vs. 4.2 (IQR 3.6-5.0) kPa, P

PURPOSE: The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP). MATERIALS AND METHODS: Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan(R) during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA-IR). RESULTS: Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21-6.64), and positive correlations between the CAP value and HOMA-IR (rho0.407) or fasting C-peptide (rho0.402) were demonstrated. CONCLUSION: Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection.

BACKGROUND AND AIMS: A thick layer of subcutaneous adipose tissue may lead to an overestimation of liver stiffness by transient elastography. The aim of this study was to assess whether liver stiffness measurement (LSM) was overestimated using an XL probe in patients with severe obesity and, if so, to reprocess the data to the adapted depth to obtain the appropriate LSM (LSMa). METHODS: A total of 152 obese patients prospectively underwent bariatric surgery and needle liver biopsy. Liver stiffness was measured by transient elastography 15 days before. To determine whether the LSM was overestimated, an expert operator retrospectively determined whether the skin-to-capsula distance was greater than 35 mm by analyzing the hyperechogenicity of ultrasound signals and the measured slope between 35 and 75 mm. In the case of an overestimation, a deeper measurement depth was selected to calculate the LSMa. RESULTS: There was an overestimation of the LSM obtained between 35 and 75 mm in 76 patients (50%). Among these patients, the LSMa was obtained between 40 and 75 mm in 49 patients and between 45 and 80 mm in 27 patients. Only the percentage of steatosis was independently and positively correlated with LSM overestimation. The areas under receiver operating characteristic of LSMa was 0.82+/-0.04 for predicting fibrosis stage F3. The Obuchowski measure was 0.85+/-0.02. CONCLUSION: The LSM was overestimated in severely obese patients obtained between 35 and 75 mm using an XL probe in 76 patients (50%), but LSM can be performed correctly in these patients after adapting the measurement depth to deeper beneath the patients' skin.

OBJECTIVES: There are scant data on the progression of hepatic steatosis (HS) in HIV infection. We therefore evaluated changes in HS over time in HIV-infected patients using the controlled attenuation parameter (CAP). METHODS: A prospective cohort of 326 HIV-infected patients was included in this study. All patients underwent a CAP measurement. Changes in steatosis were evaluated by calculating the median (Q1-Q3) difference between baseline and 12-month CAP values. RESULTS: The median (Q1-Q3) CAP was 221 (196-252) dB/m at baseline and 224 (198-257) dB/m at the 12-month visit (P = 0.617). Significant steatosis, that is, CAP >/= 238 dB/m, was observed in 76 individuals (37%) at baseline and in 80 (39%) at the 12-month visit (P = 0.683). The following variables were associated with DeltaCAP: plasma HIV RNA [/= 50 HIV-1 RNA copies/mL: median (Q1-Q3) DeltaCAP, 4 (-21, 27) vs. -21 (-49, 4) dB/m, respectively; P = 0.024]; body mass index (BMI) [no increase vs. increase: -13 (-40, 4) vs. 14 (-6, 32) dB/m, respectively; P

OBJECTIVES: The aim of the study was to study the factors associated with immunological recovery in HIV-infected patients with suppressed viral load. METHODS: Nadir and current CD4 cell counts were recorded in 821 patients, as well as many demographic, epidemiological, lifestyle, clinical, therapeutic, genetic, laboratory, liver fibrosis and viral hepatitis parameters. RESULTS: The median age of the patients was 44.4 years [interquartile range (IQR) 40.3-48.0 years], the median time since HIV diagnosis was 15.3 years (IQR 10.5-18.9 years), the median time of suppressed viral load was 7.0 years (IQR 4.0-10.0 years) and the median time on the current antiretroviral regimen was 2.8 years (IQR 1.4-4.7 years). The median nadir and current CD4 counts were 193.0 (IQR 84.0-301.0) and 522.0 (IQR 361.0-760) cells/muL, respectively, separated by a median period of 10.2 years (IQR 5.9-12.9 years). The median CD4 count gain during follow-up was 317.0 (IQR 173.0-508.0) cells/muL. Many variables were associated with CD4 cell gains in univariate analyses, including age, gender, epidemiology, prior clinical conditions, fibrosis stage, transient elastometry, aspartate aminotransferase (AST), nadir CD4 count and hepatitis B and C virus infections and genotypes, as well as the durations of follow-up since nadir CD4 count, overall antiretroviral treatment, current antiretroviral regimen, protease inhibitor therapy and suppression of viral load. Multivariate analysis revealed that longer duration of HIV suppression (P

RATIONALE AND AIMS: Screening and treatment for chronic hepatitis C are very limited in Vietnam and clinical data on HCV-related liver disease in HIV-coinfected people are almost inexistent. This study aimed to assess the severity of liver fibrosis and its risk factors in HIV-HCV coinfected patients in Haiphong, Northern Vietnam. METHODS: A cross-sectional study was conducted at a HIV outpatient clinic. Consecutive HIV treated adults with positive HCV serology completed a standardised epidemiological questionnaire and had a comprehensive liver assessment including hepatic elastography (Fibroscan(R), Echosens). RESULTS: From February to March 2014, 104 HIV-HCV coinfected patients receiving antiretroviral therapy (ART) were prospectively enrolled (99 males, median age: 35.8 (32.7-39.6) years, median CD4 count: 504 (361-624) /mm3. Of them, 93 (89.4%) had detectable HCV RNA (median 6.19 (4.95-6.83 Log10 IU/mL). Patients were mainly infected with genotypes 1a/1b (69%) and genotypes 6a/6e (26%). Forty-three patients (41.3%) had fibrosis >/=F2 including 24 patients (23.1%) with extensive fibrosis (F3) and/or cirrhosis (F4). In univariate analysis, excessive alcohol consumption, estimated time duration from HCV infection, nevirapine and lopinavir-based ARV regimen and CD4 nadir were associated factors of extensive fibrosis/cirrhosis. Alcohol abuse was the only independent factor of extensive fibrosis in multivariate analysis. Using Fibroscan(R) as a gold standard, the high thresholds of AST-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4) had very good performances for the diagnosis of extensive fibrosis/cirrhosis (Se: 90 and 100%, Sp:84 and 81%, AUROCs = 0.93, 95%CI: 0.86-0.99 and 0.96 (0.92-0.99), respectively). CONCLUSION: In this study, nearly 25% of HIV-HCV coinfected patients successfully treated with ART have extensive fibrosis or cirrhosis, and therefore require urgently HCV treatment.

Aims of the study are to investigate, in a cohort of patients affected by HCV chronic hepatitis with genotypes 1 and 4, the prevalence of interleukin 28B (IL28B) genotypes, the possible association between IL28B polymorphism and severity of liver damage, the role of IL28B CC as a predictor of outcome. 365 patients with HCV infection were observed between 2013 and 2014. Demographic, virological, biochemical, and genetic characteristics of each patient were investigated. Liver fibrosis was assessed by transient elastometry. Mean age of the patients (72.9 % males, 27.1 % females) is 50 years. 91.5 % % of patients are Caucasian, 8.5 % African. In the patients with HCV1 and HCV4 a higher frequency of IL28B CT is observed with a prevalence of 52.1 and 61.8 % respectively. As regards ethnic group, African people have a prevalence of 35.5 % for CC, while Caucasians have a prevalence of 23.8 % for CC. In our cohort, IL28B polymorphism does not show significant differences among ethnic groups and in HCV1 and HCV4 genotypes. As described in literature, IL28B CC genotype is confirmed as predictor of sustained virological response in both Caucasians and Africans. A significant correlation between liver fibrosis and IL28B polymorphism emerges.

AIM: Liver volumetric analysis has not been used to detect hepatic remodelling during antiviral therapy before. We measured liver volume (LV) changes on volumetric magnetic resonance imaging during hepatitis C antiviral therapy. METHODS: 22 biopsy-staged patients (median [range] age 45(19-65) years; 9F, 13M) with chronic hepatitis C virus infection were studied. LV was measured at the beginning, end of treatment and 6 months post-treatment using 3D T1-weighted acquisition, normalised to patient weight. Liver outlines were drawn manually on 4 mm thick image slices and LV calculated. Inter-observer agreement was analysed. Patients were also assessed longitudinally using biochemical parameters and liver stiffness using Fibroscan. RESULTS: Sustained viral response (SVR) was achieved in 13 patients with a mean baseline LV/kg of 0.022 (SD 0.004) L/kg. At the end of treatment, the mean LV/kg was 0.025 (SD 0.004, P = 0.024 cf baseline LV/kg) and 0.026 (SD 0.004, P = 0.008 cf baseline LV/kg) 6 months post-treatment (P = 0.030 cf baseline, P = 0.004). Body weight-corrected end of treatment LV change was significantly higher in patients with SVR compared to patients not attaining SVR (P = 0.050). End of treatment LV change was correlated to initial ALT (R (2) = 0.479, P = 0.037), but not APRI, AST, viral load or liver stiffness measurements. There was a correlation of 0.89 between observers for measured slice thickness. CONCLUSIONS: LV increased during anti-viral treatment, while the body weight-corrected LV increase persisted post-antiviral therapy and was larger in patients with SVR.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. A meta-analysis has confirmed decreased serum 25-hydroxyvitamin D levels in NAFLD patients. This intervention study investigates whether vitamin D correction ameliorates hepatic steatosis. METHODS: We prospectively recruited 40 patients from an outpatient liver clinic with vitamin D deficiency (serum 25-hydroxyvitamin D /= 280 dB/m. Patients received 20,000 IU vitamin D/week for six months, while vitamin D status, liver function tests (LFTs), CAP and body composition were monitored. RESULTS: The cohort comprised 47.5% women (age 54.9 +/- 12.1 years; BMI 29.5 +/- 3.0 kg/m2). Mean serum vitamin D level was 11.8 +/- 4.8 ng/ml. CAP decreased significantly from baseline (330 +/- 32 vs. 307 +/- 41 dB/m) during supplementation (P = 0.007). A mean CAP reduction relative to baseline was demonstrated at four weeks and three and six months: -5.3 +/- 13.8%; -6.0 +/- 14.6% and -6.4 +/- 13.0%, respectively. During these time points, restoration of serum vitamin D levels was observed (34.6 +/- 12.9, 36.3 +/- 10.2, 34.8 +/- 9.8 ng/ml; P

AIM: Few studies have investigated the course of liver stiffness after treatment with protease inhibitors. We evaluated the impact of this therapy on liver fibrosis measured by transient elastography. METHODS: This multicenter observational, cohort, prospective study included 90 patients with hepatitis C genotype 1 treated with telaprevir or boceprevir who had advanced fibrosis evidenced by liver stiffness (>/=9.5 kPa). Liver stiffness was measured at baseline and 24 weeks after treatment ended, and was compared with virological responses at week 12. RESULTS: Liver stiffness decreased in 89% of patients who achieved sustained virological response. The median intrapatient liver stiffness value at the end of follow-up decreased by 5.1 kPa (35%) from baseline compared with 0.1 kPa (0.5%) in those who did not achieve a sustained virological response (P

HIV-associated obstructive portopathy (HIVOP) is an obstruction of the hepatic microvasculature of unknown origin. The purpose of this study was to describe the clinical and paraclinical presentation of the disease and its impact in terms of morbidity.Twenty-nine HIV1-infected patients (average 12 years of infection, nadir of CD4 210/mm, including 7 patients with a history of opportunistic infection) with a biopsy-proven or likely HIVOP have been followed up for an average of 6.1 years.Modes of revelation of the HIVOP were: cytolysis and/or cholestasis (60%), occult (14%) or symptomatic (37%) portal hypertension (esophageal varices 17%, ascites 10%, cytopenia 10%), or fortuitous (8%). Hypoalbuminemia (=35 g/L) was present in (31%), thrombocytopenia (

The aim of the present study was to investigate the diagnostic accuracy of Fibroscan for liver fibrosis in patients with chronic hepatitis B (CHB) with alanine aminotransferase (ALT) levels

BACKGROUND & AIMS: Noninvasive methods have been evaluated for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the ability of transient elastography (TE) with the M-probe, and magnetic resonance elastography (MRE) to assess liver fibrosis. Findings from magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) measurements were compared with those from TE-based controlled attenuation parameter (CAP) measurements to assess steatosis. METHODS: We performed a cross-sectional study of 142 patients with NAFLD (identified by liver biopsy; mean body mass index, 28.1 kg/m(2)) in Japan from July 2013 through April 2015. Our study also included 10 comparable subjects without NAFLD (controls). All study subjects were evaluated by TE (including CAP measurements), MRI using the MRE and PDFF techniques. RESULTS: TE identified patients with fibrosis stage >/=2 with an area under the receiver operating characteristic (AUROC) curve value of 0.82 (95% confidence interval [CI]: 0.74-0.89), whereas MRE identified these patients with an AUROC curve value of 0.91 (95% CI: 0.86-0.96; P = .001). TE-based CAP measurements identified patients with hepatic steatosis grade >/=2 with an AUROC curve value of 0.73 (95% CI: 0.64-0.81) and PDFF methods identified them with an AUROC curve value of 0.90 (95% CI: 0.82-0.97; P

Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB).Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan-Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves.The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791-0.807 vs 0.691-0.725; all P 0.05).LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies.

BACKGROUND: There is growing evidence that human genetic variants contribute to liver fibrosis in subjects with hepatitis C virus (HCV) mono-infection, but this aspect has been little investigated in patients co-infected with HCV and human immunodeficiency virus (HIV). We performed the first genome-wide association study (GWAS) of liver fibrosis progression in patients co-infected with HCV and HIV, using the well-characterized French ANRS CO13 HEPAVIH cohort. Liver fibrosis was assessed by elastography (FibroScan(R)) providing a quantitative fibrosis score. After quality control, GWAS was conducted on 289 Caucasian patients, for a total of 8,426,597 genotyped (Illumina Omni2.5 BeadChip) or reliably imputed SNPs. SNPs with p-values

OBJECTIVE: Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis. BACKGROUND: Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation. DESIGN/METHODS: A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303). RESULTS: We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI =0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and =1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency. CONCLUSIONS: Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.

Prevalence of non-alcoholic fatty liver disease is increased in patients with psoriasis. However, it is not known how liver fibrosis correlates with psoriasis. This study investigated the association between psoriasis and liver fibrosis compared with participants without psoriasis within the population-based Rotterdam Study. All participants were screened for liver fibrosis using transient elastography. Liver stiffness > 9.5 kPa suggested advanced liver fibrosis. Psoriasis was identified using a validated algorithm. A total of 1,535 participants were included (mean age +/- standard deviation 70.5 +/- 7.9 years; 50.8% female; median body mass index 26.4 kg/m2 (interquartile range 24.2-28.9)) of whom 74 (4.7%) had psoriasis. Prevalence of advanced liver fibrosis was 8.1% in psoriasis patients compared with 3.6% in the reference group (p = 0.05). The risk of advanced liver fibrosis in psoriasis patients remained comparable after adjustment for demographics, lifestyle characteristics and laboratory findings (odds ratio 2.57 (95% confidence interval 1.00-6.63). This study suggests that elderly people with psoriasis are twice as likely to have advanced liver fibrosis irrespective of common risk factors.

BACKGROUND AND PURPOSE: Transient elastography (TE) has been shown to be a valuable tool for the prediction of large esophageal varices. However, the conclusions have not been always consistent throughout the different studies. Therefore, we performed a further meta-analysis in order to evaluate the diagnostic accuracy of transient elastography for the prediction of large esophageal varices. METHODS: We performed a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL in The Cochrane Library without time restriction. The strategy we used was "(fibroscan OR transient elastography OR stiffness) AND esophageal varices". Accuracy measures such as pooled sensitivity, specificity, among others, were calculated using Meta-DiSc statistical software. RESULTS: Twenty studies (2,994 patients) were included in our meta-analysis. The values of pooled sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio were as follows: 0.81 (95% CI, 0.79-0.84), 0.71 (95% CI, 0.69-0.73), 2.63 (95% CI, 2.15-3.23), 0.27 (95% CI, 0.22-0.34) and 10.30 (95% CI, 7.33-14.47). The area under the receiver operating characteristics curve was 0.83. The Spearman correlation coefficient was 0.246 with a p-value of 0.296, indicating the absence of any significant threshold effects. In our subgroup analysis, the heterogeneity could be partially explained by the geographical origin of the study or etiology; or it could be partially explained blindingly, through the appropriate interval and cut-off value of the liver stiffness (LS). CONCLUSIONS: Transient elastography could be used as a valuable non-invasive screening tool for the prediction of large esophageal varices. However, since LS cut-off values vary throughout the different studies and significant heterogeneity also exists among them, we need more reasonable approaches or flow diagram in order to improve the operability of this technology.