Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus.

BACKGROUND & AIMS: There are uncertainties regarding the burden of liver disease in patients with type 2 diabetes (T2D). Thus, we aimed to quantify the burden of liver disease, identify risk factors, and estimate attributable risks in patients with T2D. METHODS: We measured adjusted hazard ratios of liver disease progression to hepatocellular carcinoma and/or decompensated cirrhosis in a 2010-2020 retrospective, bicentric, longitudinal, cohort of 52,066 hospitalized patients with T2D. RESULTS: Mean age was 64±14 years and 58% were men. Alcohol use disorders accounted for 57% of liver-related complications and were associated with all liver-related risk factors. Non-metabolic liver-related risk factors accounted for 37% of the liver burden. T2D control was not associated with liver disease progression. The incidence (95% CI) of liver-related complications and of competing mortality were 3.9 (3.5-4.3) and 27.8 (26.7-28.9) per 1,000 person-years at risk, respectively. The cumulative incidence of liver disease progression exceeded the cumulative incidence of competing mortality only in the presence of well-identified risk factors of liver disease progression, including alcohol use. The incidence of hepatocellular carcinoma was 0.3 (95% CI 0.1-0.5) per 1,000 person-years in patients with obesity and it increased with age. The adjusted hazard ratios of liver disease progression were 55.7 (40.5-76.6), 3.5 (2.3-5.2), 8.9 (6.9-11.5), and 1.5 (1.1-2.1), for alcohol-related liver disease, alcohol use disorders without alcohol-related liver disease, non-metabolic liver-related risk factors, and obesity, respectively. The attributable fractions of alcohol use disorders, non-metabolic liver-related risk factors, and obesity to the liver burden were 55%, 14%, and 7%, respectively. CONCLUSIONS: In this analysis of data from 2 hospital-based cohorts of patients with T2D, alcohol use disorders, rather than obesity, contributed to most of the liver burden. These results suggest that patients with T2D should be advised to drink minimal amounts of alcohol. LAY SUMMARY: There is uncertainty on the burden of liver-related complications in patients with type 2 diabetes. We studied the risks of liver cancer and complications of liver disease in over 50,000 patients with type 2 diabetes. We found that alcohol was the main factor associated with complications of liver disease. This finding has major implications on the alcohol advice given to patients with type 2 diabetes.

[FIB-4 index to rule-out advanced liver fibrosis in NAFLD patients]. / L'index FIB-4 pour faire le diagnostic de fibrose hépatique avancée au cours de la stéatose hépatique.

The FIB-4 index is a biomarker of advanced hepatic fibrosis in a context of fatty liver disease. The calculation of the FIB-4 index requires of age, serum ALT and AST transaminase levels and platelet count. A FIB-4 index<1.45 in a context of fatty liver disease excludes clinically significant hepatic fibrosis. Additional explorations are mandatory to excluded hepatic fibrosis for a a FIB-4 index>1.45 in a context of fatty liver disease. A complete hepatological workup is mandatory for a FIB-4 index>3.25 in a context of fatty liver disease.

Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141).

BACKGROUND & AIMS: In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015). METHODS: A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3-4/F0-2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0-0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1-10% with TVR/BOC-based triple therapy. Costs were €60,000 for 12weeks of IFN-based new DAAs and two times higher for IFN-free regimens. RESULTS: Treatment with IFN-based new DAAs when fibrosis stage ⩾F2 is cost-effective compared to TVR/BOC-based triple therapy (€37,900/QALY gained), but not at F0-1 (€103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective. CONCLUSIONS: Treatment with IFN-based new DAAs at stage ⩾F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.

Management of hepatitis C virus infection in heavy drinkers.

AIM: Optimal management of hepatitis C virus (HCV) infection is controversial in heavy drinkers. We compared the management of HCV infection of heavy drinkers with that of patients without a history of alcohol abuse. METHODS: In a retrospective case-control study, 69 HCV-infected heavy drinkers [daily alcohol consumption at referral above 60 g/day, hereafter 'alcohol group'] were compared with matched HCV-infected patients with low alcohol consumption (<40 g/day, 'control group'). RESULTS: Patients of the 'alcohol group' were younger (42 vs. 45 years, P = 0.05), more often male (69.6 vs. 56.5%, P = 0.11) and had been infected by intravenous drug use (85.5 vs. 45.0%, P < 0.0001). The percentage of patients with a recommendation for treatment according to the French 2002 consensus (bridging fibrosis or genotype 2 or 3) was 52 of 69 (75.4%) in both groups, while the proportion of patients treated was higher in the control group (71.0 vs. 44.9%, P = 0.002). In the 'alcohol group', patients had better access to treatment if they were employed or consumed 170 g/day or less at first referral. Sustained virological response (SVR) was obtained in 10 of 31 patients (32.3%) of the 'alcohol group' vs. 8 of 31 patients (25.8%) of the control group matched for genotype and type of treatment (P = 0.58). CONCLUSION: Heavy drinkers are less often considered for antiviral therapy compared with patients without a history of alcohol abuse. However, once treatment is actually initiated, SVR rates are comparable with those achieved in non-drinkers despite the continuation of alcohol consumption during therapy in some patients.

[Assessment and reversibility of liver fibrosis in viral hepatitis]. / Evaluation et réversibilité de la fibrose hépatique au cours des hépatites virales.

The evaluation of liver fibrosis in chronic viral hepatitis is of paramount importance since secondary complications, including hepatocellular carcinoma, occur in patients with extensive fibrosis and cirrhosis. Clinical examination and some simple biological and morphological tests represent the first step to appraise liver fibrosis in viral hepatitis. Biochemical (Fibrotest, Hepascore, Fibrometre) or morphological (Fibroscan) methods have emerged over the past ten years to avoid--in more than half of patients--the systematic use of the liver biopsy to appraise liver fibrosis in chronic hepatitis C virus infection. The liver biopsy remains however essential in many situations--especially for demonstrating regression of cirrhosis after viral inactivation. Regression of cirrhosis is now a recognized concept, thanks to the next generation of antiviral treatments. Today, the inactivation of viral hepatitis is an achievable primary goal and regression of cirrhosis becomes a reasonable secondary goal.