Statins decrease the risk of decompensation in HBV- and HCV-related cirrhosis: a population-based study.
Chang FM et al.
Hepatology 2017 Sept; 66:896-907

Background & Aim: Statin decreased the risk of decompensation and mortality in veteran patients with cirrhosis due to hepatitis C virus (HCV). Whether this beneficial effect can be extended to cirrhosis in general population or cirrhosis with other causes, such as hepatitis B virus (HBV) infection and alcohol, remains unknown. Statin also decreased the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV and HCV infection. It is unclear whether the effect can be observed in patients already with cirrhosis. We aimed to determine the statin effect on decreasing decompensation, mortality and HCC in HBV-, HCV and alcohol-related cirrhosis.

Methods: Cirrhotic patients were identified from a representative cohort of Taiwan National Health Insurance beneficiaries from 2000-2013. Statin users, defined as having a cumulative defined daily dose (cDDD) ≥ 28, were selected and served as the case cohort. Statin non-users (< 28 cDDD) were matched through propensity scores. The association between statin use and the risk of decompensation, mortality, and HCC were estimated.

Results: A total of 1,350 cirrhotic patients were enrolled. Among patients with cirrhosis, statin use had decreased the risk of decompensation, mortality and HCC in a dose dependent manner (p for trend: < .0001, < .0001, and 0.009). Regression analysis showed a lower risk of decompensation among statin users with cirrhosis due to chronic HBV (adjusted hazard ratio [95% confidence interval], 0.39 [0.25–0.62]) or HCV infection (0.51 [0.29–0.93]). The lowered risk of decompensation was of borderline significance among statin users with alcohol-related cirrhosis (0.69 [0.45-1.07]).

Conclusions: Statin use decreases the decompensation rate in both HBV- and HCV-related cirrhosis. Of borderline significance is a decreased decompensation rate in alcohol-related cirrhosis.

Expert's Commentary

The potential impact of HMG-CoA reductase inhibitors, aka “statins”, on HCV infection and the end organ effects of HCV infection have gained increasing attention. The interaction of the HCV virus with the host lipid metabolism pathway in the hepatocyte is well recognized, thus it is not surprising that statins were investigated initially for their antiviral potential and later for their impact on end organ disease, likely to be driven by more pleotropic effects. Statins have been shown to suppress replication of genomic and subgenomic HCV in the replicon system [Amemiya JID 2008:197] and in the interferon-era appeared to improve virologic response to therapy [Bader et al J Viral Hep 2013]. More recently, statins have been associated with a decreased risk of progression to cirrhosis, decompensation, HCC, and death in patients with HCV infection. While the direct mechanism(s) of this reported benefit is unknown, it is likely multifactorial given the metabolic complications related to HCV infection and the known pleotropic effects of statins. However, HBV is not known to have the same metabolic effects as HCV infection, thus it is of interest to investigate the impact of statins on other liver diseases. Using the same large database as one of the first reports of statin association with HCC in HCV infection, this group wanted to expand an investigation of the association of statins and liver disease outcomes in patients with other liver diseases and in those who already have cirrhosis. The study initially identified over 15,000 patients with cirrhosis and used propensity score matching to identify a well-characterized and matched cohort of statin-user and non-users. Overall, statin-users had a significantly lower risk of decompensation (adjusted HR [95% CI]: 0.39 [0.30–0.50]), mortality (adjusted HR [95% CI]: 0.46 [0.34–0.63]), and HCC development (adjusted HR [95% CI]: 0.52 [0.35–0.76]) than non-users. When the authors stratified the analysis by type of liver disease there were notable differences: (1) statins had less impact on alcohol-related liver disease, (2) while statins resulted in a decrease in decompensation with HCV-associated liver disease, this was not true for HCC or mortality, (3) for HBV-related liver disease statins decreased the risk of decompensation and mortality, but not HCC. The vast amount of data published in the last 3-5 years of statins in liver disease has been observational, thus lacking in mechanistic exploration. Therefore, while these data are quite intriguing, the reason for the improved outcomes in patients with liver disease who are on statins remains unclear. To date there is not enough evidence to start patients with liver disease on statins unless otherwise indicted for primary or secondary cardiovascular risk. However, these data and others overwhelming suggest that statins are safe in patients with hepatitis C and B, including those with concomitant liver disease. Meanwhile, we and others have shown that patients with HCV infection are less likely to receive statins when indicated for prevention – and this is something that needs to change.

Pr Susanna Naggie