George Cholankeril

Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis

Objectives:Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD.Methods:We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies.Results:We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39–0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51–0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29–0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37–0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46–0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46–0.98); in the randomized controlled trial, HR was 0.39 (0.15–0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding.Conclusions:Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.

Treatment of patients waitlisted for liver transplant with all‐oral direct‐acting antivirals is a cost‐effective treatment strategy in the United States

All‐oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre‐LT versus post‐LT. The objective of this study was to analyze the cost‐effectiveness of pre‐LT versus post‐LT treatment with an all‐oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision‐analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30‐year time horizon from a third‐party US payer perspective and estimated their health and cost outcomes based on pre‐LT versus post‐LT treatment with an all‐oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL‐4, SOLAR‐1, and SOLAR‐2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre‐LT treatment strategy resulted in 11.48 per‐patient quality‐adjusted life years and

Hepatocellular carcinoma in non-alcoholic steatohepatitis: Current knowledge and implications for management

365,948 per patient lifetime costs versus 10.39 and

Nonalcoholic Fatty Liver Disease: Epidemiology, Natural History, and Diagnostic Challenges.

283,696, respectively, in the post‐LT arm. In the DCC analysis, the pre‐LT treatment strategy resulted in 9.27 per‐patient quality‐adjusted life years and

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

304,800 per patient lifetime costs versus 8.7 and

Improved Outcomes in HCV Patients Following Liver Transplantation During the Era of Direct-Acting Antiviral Agents

283,789, respectively, in the post‐LT arm. As such, the pre‐LT treatment strategy was found to be the most cost‐effective in both populations with an incremental cost‐effectiveness ratio of

Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents

74,255 (HCC) and

Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease

36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post‐LT, treatment sustained virological response rates, LT costs, and baseline Model for End‐Stage Liver Disease score (DCC analysis only). Conclusion: The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre‐LT treatment with a highly effective, all‐oral DAA regimen provides the best health outcomes and is the most cost‐effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46–56).

Alcoholic Liver Disease replaces Hepatitis C Virus Infection as the Leading Indication for Liver Transplantation in the United States

With the prevalence of hepatitis C virus expected to decline, the proportion of hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is anticipated to increase exponentially due to the growing epidemic of obesity and diabetes. The annual incidence rate of developing HCC in patients with NASH-related cirrhosis is not clearly understood with rates ranging from 2.6%-12.8%. While multiple new mechanisms have been implicated in the development of HCC in NASH; further prospective long-term studies are needed to validate these findings. Recent evidence has shown a significant proportion of patients with non-alcoholic fatty liver disease and NASH progress to HCC in the absence of cirrhosis. Liver resection and transplantation represent curative therapeutic options in select NASH-related HCC patients but have placed a significant burden to our healthcare resources and utilization. Currently NASH-related HCC is the fastest growing indication for liver transplant in HCC candidates. Increased efforts to implement effective screening and preventative strategies, particularly in non-cirrhotic NASH patients, are needed to reduce the future impact imposed by NASH-related HCC.

Underutilization of Living Donor Liver Transplantation in the United States: Bias against MELD 20 and Higher.

4. F incane M M , S teens G A , C ow an M J, D aaei G , in JK , P aorek C J, et l. N atnal, reonal, nd gbal trnds in bdy-m ss index snce 180: sstem tic anlysis of halth exam intion suveys nd eidem iogical stdies w ith 60 couy-years nd ·1 m ilion paripants. Lncet 2011;:557-567. 5. W ng R J, A gilar M , C hung R , P erum pail R B , H aison S A , Y ouossi Z M , et l. N onaoholic steahepatitis is he second leding etlogy of ler diease am ng aults aw ating ler tranlantation in he