Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology. Two hundred forty-six consecutive patients from two ethnic groups had successful liver stiffness measurement and satisfactory liver biopsy specimens. The area under the receiver-operating characteristics curve (AUROC) of transient elastography for F3 or higher and F4 disease was 0.93 and 0.95, respectively, and was significantly higher than that of the aspartate aminotransferase-to-alanine aminotransferase ratio, aspartate aminotransferase-to-platelet ratio index, FIB-4, BARD, and NAFLD fibrosis scores (AUROC ranged from 0.62 to 0.81, P < 0.05 for all comparisons). At a cutoff value of 7.9 kPa, the sensitivity, specificity, and positive and negative predictive values for F3 or greater disease were 91%, 75%, 52%, and 97%, respectively. Liver stiffness was not affected by hepatic steatosis, necroinflammation, or body mass index. Discordance of at least two stages between transient elastography and histology was observed in 33 (13.4%) patients. By multivariate analysis, liver biopsy length less than 20 mm and F0-2 disease were associated with discordance. Conclusion: Transient elastography is accurate in most NAFLD patients. Unsatisfactory liver biopsy specimens rather than transient elastography technique account for most cases of discordance. With high negative predictive value and modest positive predictive value, transient elastography is useful as a screening test to exclude advanced fibrosis. Liver biopsy may be considered in NAFLD patients with liver stiffness of at least 7.9 kPa. (HEPATOLOGY 2010;51:454-462.)See Editorial on page 370.
Patients with simple steatosis may still develop NASH and fibrosis progression. Weight reduction is associated with non-progressive disease. All patients with NAFLD should undergo periodic assessment and lifestyle modification.
Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population and is the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of NAFLD, with hepatic necroinflammation and faster fibrosis progression. With an increasing number of patients developing NASH-related end-stage liver disease and pharmacological treatments on the horizon, there is a pressing need to develop NAFLD and NASH biomarkers for prognostication, selection of patients for treatment and monitoring. This requirement is particularly true as liver biopsy utility is limited by its invasive nature, poor patient acceptability and sampling variability. This article reviews current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis. For each biomarker, we evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. We cover biochemical, imaging and genetic biomarkers and discuss biomarker discovery in the omics era.
Entecavir is a potent antiviral agent with high genetic barrier to resistance, hence it is currently recommended as first-line antiviral therapy for chronic hepatitis B (CHB). The aim of this study was to investigate the efficacy of entecavir on clinical outcomes and deaths. It was a retrospective-prospective cohort study based on two cohorts of patients. The entecavir cohort included consecutive CHB patients who had received entecavir 0.5 mg/day for at least 12 months. The historical control cohort included untreated patients recruited since 1997 who underwent routine clinical care. The primary outcome was the 5-year cumulative probability of hepatic events, defined as any cirrhotic complications, hepatocellular carcinoma (HCC), and/or liver-related mortality. A total of 1,446 entecavir-treated patients (72% men; age, 51 6 12 years; follow-up, 36 6 13 months) and 424 treatment-naïve patients (65% men; age, 41 6 13 years; follow-up, 114 6 31 months) were studied. Overall, there was no difference in hepatic events between the entecavir and control cohorts. Among patients with liver cirrhosis (482 entecavir-treated, 69 treatment-naïve), entecavir-treated patients had reduced risks of all clinical outcomes when compared with treatment-naïve patients with cirrhosis after adjusted for model for end-stage liver disease score: hepatic events (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.34-0.78; P 5 0.002), HCC (HR, 0.55; 95% CI, 0.31-0.99; P 5 0.049), liver-related mortality (HR, 0.26; 95% CI, 0.13-0.55; P < 0.001), and all-cause mortality (HR, 0.34; 95% CI, 0.18-0.62; P < 0.001). Entecavir-treated patients with cirrhosis who failed to achieve undetectable hepatitis B virus DNA (105/482 [22%]) had comparable risk of hepatic events as the untreated patients. Conclusion: Entecavir therapy reduces the risks of hepatic events, HCC, liver-related and all-cause mortality of CHB patients with liver cirrhosis in 5 years, particularly among those who had maintained viral suppression. (HEPATOLOGY 2013;58:1537-1547 C hronic hepatitis B (CHB) is the leading cause of liver cirrhosis and hepatic events, including various cirrhotic complications and hepatocellular carcinoma (HCC) in Asia. 1 A high level of hepatitis B virus (HBV) DNA has been consistently shown to be an independent risk factor for the development of cirrhosis and HCC. 2,3 Antiviral therapy is effective in suppressing HBV DNA and reducing the risk of hepatic events and HCC. 4,5 Lamivudine, the first generation oral nucleoside analogue was shown to reduce the incidence of hepatic events in patients with advanced fibrosis or compensated cirrhosis by 50%. 6 However, the clinical benefit may be negated by lamivudine resistance and virologic relapse after cessation of treatment. 6,7 Therefore, lamivudine is no longer the firstline antiviral therapy for CHB. Instead, nucleos(t)ide analogues with high genetic barrier to resistancenamely, entecavir and tenofovir disoproxil fumarateare recommended by international guidelines. [8][9][10] Entecavir is a more potent ...
NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.
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