Clinical library

Assessment of Liver Fibrosis with Elastography Point Quantification vs Other Non-Invasive Methods

BACKGROUND & AIMS: Elastography point quantification (ElastPQ) is a non-invasive method for assessing liver fibrosis based on liver stiffness. We evaluated the accuracy of ElastPQ for the staging of liver fibrosis in patients with chronic liver disease (CLD) compared with aspartate transaminase to platelet ratio index, fibrosis-4 index, and transient elastography (TE), using liver biopsy as reference standard. METHODS: We performed a retrospective study of 406 patients with CLD of any etiology who underwent liver biopsy analysis from September 2012 through June 2017 at a clinic in Bologna, Italy. We obtained liver stiffness measurements, made by ElastPQ and TE, for 361 patients. Liver fibrosis stage was assessed by the METAVIR scoring system. Areas under the receiver operating characteristic curve (AUROC) were used to assess the diagnostic performance of ElastPQ. RESULTS: ElastPQ values correlated with histologic detection of fibrosis (r=0.718; P<.001). The AUROC values were 0.856 for detection of significant fibrosis (F>/=2), 0.951 for advanced fibrosis (F>/=3), and 0.965 for cirrhosis. The best cut-off values identified for classifying patients with F>/=2, F>/=3, or cirrhosis were 6.0 kPa, 6.2 kPa, and 9.5 kPa, respectively: these were lower than those for TE. Comparison of ElastPQ with TE data resulted in superimposable diagnostic accuracy of both methods for each stage of liver fibrosis. Both elastography techniques performed better than aspartate transaminase to platelet ratio index or fibrosis-4 index scores (P<.05 for all AUROC comparisons). CONCLUSION: ElastPQ has good to excellent performance for the non-invasive staging of liver fibrosis in patients with CLD. ElastPQ identified patients with fibrosis or cirrhosis with levels of accuracy that were not inferior to those of TE, and outperformed serum fibrosis indexes in identifying each stage of liver fibrosis.

Vukotic, R. | 2018 | Italy | Clin Gastroenterol Hepatol (Clinical Gastroenterology and Hepatology)

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LSM by VCTE™ | Original contribution | Mixed etiologies of CLD

24.04.2024

Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP. METHODS: This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres. 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-centre cohort. RESULTS: A total of 562 patients were included in the study: 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, and S3=77 (28%), 94 (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and moderate steatosis with fair accuracy (area under the receiver operating characteristic curve [AUC] >/=S1=0.77; 0.71-0.83 and 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 290dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3days (interquartile range 4-6) for detoxification, CAP decreased by 32+/-47dB/m (p<0.001). Body mass index predicted higher CAP in both cohorts, irrespective of drinking pattern. Obese patients with body mass index >/=30kg/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: CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining 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.

Thiele, M. | 2018 | Denmark | Journal of Hepatology

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CAP™ | Original contribution | Alcoholic Liver Disease

24.04.2024

Liver stiffness measurement in the primary care setting detects high rates of advanced fibrosis and predicts liver-related events in hepatitis C

BACKGROUND & AIMS: As many as 70% of individuals with chronic hepatitis C (CHC) are managed solely in primary care. The aims of this study were to determine the prevalence of elevated liver stiffness measurement (LSM) in a cohort of community managed patients with CHC and to evaluate predictors of advanced liver disease and liver-related events. METHODS: A prospective cohort of adult patients with CHC were recruited from 21 primary care practices throughout Victoria, Australia. Inclusion criteria included the presence of CHC for >6months, no recent (<18months) specialist input and no history of hepatocellular carcinoma. Clinical assessment, LSM and phlebotomy were carried out in primary care. A hospital cohort was recruited for comparison. Participants were followed longitudinally and monitored for liver-related events. RESULTS: Over 26months, 780 community patients were recruited and included in the analysis. The median LSM was 6.9kPa in the community, with 16.5% of patients at risk of advanced fibrosis (LSM >/=12.5kPa); of these 8.5% had no laboratory features of advanced liver disease. The proportion at risk of cirrhosis was no different between the community and hospital cohorts (p=0.169). At-risk alcohol consumption, advancing age, elevated body mass index and alanine aminotransferase were independent predictors of elevated LSM. Over a median follow-up of 15.2months, liver-related events occurred in 9.3% of those with an LSM >/=12.5kPa. An LSM of 24kPa had the highest predictive power for liver-related events (hazard ratio152; p<0.001). CONCLUSION: The prevalence of advanced fibrosis, as determined by LSM, in primary care managed CHC is significant and comparable to a hospital cohort. Furthermore, this study supports the use of LSM as a community screening tool in a CHC population and indicates a possible role in predicting liver-related events. LAY SUMMARY: The prevalence of advanced liver disease in primary care managed hepatitis C is unknown. Our data suggests that rates of advanced fibrosis in the community are significant (16.5%), often underdiagnosed and comparable to rates seen in specialist referral centres. Liver stiffness measurement is a feasible community screening tool prior to hepatitis C therapy and can predict liver-related adverse events.

Sood, S. | 2018 | Australia | Journal of Hepatology

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LSM by VCTE™ | Original contribution | Healthy subjects

24.04.2024

Beneficial Effects of Lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease

BACKGROUND & AIMS: Around 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese NAFLD patients and identify predicting factors for treatment response. METHODS: 154 community NAFLD patients were randomized to participate in a 12-month lifestyle intervention programme and regular exercise or receive usual care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed till Year 6. The Asian body mass index (BMI) cutoff of 25 kg/m(2) was used to define non-obese NAFLD. RESULTS: 77 patients each were assigned to the intervention and control groups (39 and 38 in each group had baseline BMI <25 and >/=25 kg/m(2), respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs 18%, P<0.001; obese: 61% vs 21%, P<0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3-5% weight reduction; the same could only be achieved in obese patients with 7-10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalization than the control group. CONCLUSIONS: Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population. LAY SUMMARY: Some NAFLD patients are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3-10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run.

Woo, J. | 2018 | Hong Kong | Journal of Hepatology

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LSM by VCTE™ | Original contribution | NAFLD/NASH

24.04.2024

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease

BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage >/=F3). METHODS: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. RESULTS: The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. CONCLUSION: In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58.

Thiele, M. | 2018 | Denmark | Gastroenterology

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LSM by VCTE™ | Original contribution | Alcoholic Liver Disease

24.04.2024

Meta-analysis of the accuracy of transient elastography in measuring liver stiffness to diagnose esophageal varices in cirrhosis

BACKGROUD: To assess the diagnostic performance of transient elastography (TE) in detecting the presence and size of esophageal varices (EV) in cirrhotic patients. METHODS: We searched PubMed, Web of Science, Wiley Online Library, Science Direct, China National Knowledge Infrastructure, WeiPu, WanFang database, and Baidu Scholar to identify studies that evaluated the diagnostic accuracy of TE in liver stiffness measurement, compared with esophagogastroduodenoscopy (EGD), for the detection of the presence and degree of EV in cirrhosis. RESULTS: We included 32 studies in the presence of any EV (grade 1-3; n = 4082), 27 studies on substantial EV (grade 2-3; n = 5221) and 5 studies on large EV (grade 3). The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were 0.8 (95% CI, 0.78-0.86), 0.68 (95% CI, 0.62-0.74), and 10 (95% CI, 7-14) for any EV; 0.81 (95% CI, 0.77-0.85), 0.72 (95% CI, 0.66-0.77), and 11 (95% CI, 8-15) for substantial EV; and 0.92 (95% CI, 0.83-0.96), 0.78 (95% CI, 0.70-0.85), and 40 (95% CI, 15-107) for large EV. Subgroup analysis revealed that the heterogeneity among studies on any EV could potentially be explained by study location, proportion of Child A, and time interval between TE and EGD; for substantial EV, the proportion of Child A, etiology of cirrhosis, and the time interval between TE and EGD were important heterogeneity factors. Publication bias was found among studies evaluating diagnostic performance of TE for any EV. CONCLUSION: TE is a good tool for detecting the presence and degree of EV; however, in determination of the liver stiffness cutoff values means that TE is only cautiously used in clinical practice.

Zhang, Y. | 2018 | China | Medicine (Baltimore)

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LSM by VCTE™ | Meta-analysis | Mixed etiologies of CLD

24.04.2024