Statins Are Associated With a Decreased Risk of Decompensation and Death in Veterans With Hepatitis C–Related Compensated Cirrhosis.
Mohanty A, Tate JP, Garcia-Tsao G.
Gastroenterology 2016 ; 150:430-40.

Statins increase nitric oxide availability at the intrahepatic level and decrease portal pressure both in experimental animals and in patients with cirrhosis. Their beneficial effect may go beyond reducing portal pressure by increasing flow into the liver, thereby potentially improving liver function. However, statins also can be hepatotoxic.
The objective of this study was to determine whether long-term statin use will be beneficial or detrimental for patients with compensated cirrhosis, in terms of decompensation and survival times. Patients with more severe liver disease are less likely to be prescribed a statin but more likely to decompensate and die. Patients with more severe cardiovascular risks are more likely to receive a statin but may be at higher risk of death. To account for this confounding, a propensity score matching was used.

METHODS: Retrospective cohort using the Veteran Affairs Clinical Case Registry, with nationwide data from veterans infected with the hepatitis C virus. Patients with compensated cirrhosis from January 1996 through December 2009 were identified. Statin use was according to filled prescriptions. Cirrhosis and decompensation were determined from International Classification of Diseases, 9th revision codes, using a validated algorithm.
Cirrhosis decompensation was defined by the presence of 1 of the following : esophageal varices with bleeding, ascites or spontaneous bacterial peritonitis. Patients with HIV and/or HBV co-infection were excluded.

RESULTS: Among 40,512 patients with HCV compensated cirrhosis (98% male; median age, 56 years), 2802 statin users were identified. A propensity score model was developed, using variables associated with statin prescription, and new statin users were matched with up to 5 nonusers; 685 statin users were matched with 2062 nonusers. Discrimination of the propensity score model was 0.92. Statin users had a lower risk of decompensation of cirrhosis (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.39–0.77) and death (HR, 0.56; 95% CI, 0.46–0.69), compared with nonusers. Findings persisted after adjustment for age, FIB-4 index score, serum level of albumin, model for end-stage liver disease and Child-Turcotte-Pugh scores (HR for decompensation, 0.55; 95% CI, 0.39–0.78), and death (HR, 0.55; 95% CI, 0.45–0.68).

CONCLUSIONS: Based on data from the Veteran Affairs Clinical Case Registry, statin use among patients with HCV and compensated cirrhosis is associated with a more than 40% lower risk of cirrhosis decompensation and death. Although statins cannot yet be recommended widely for these patients, their use should not be avoided.

Expert's Commentary

« Previous studies have indicated that statins can prevent the progression of hepatic fibrosis in patients with hepatitis C virus (HCV) infection, improve virological response (VR) rates to antiviral therapy and decrease incidence of hepatocellular carcinoma (HCC) ⁽¹⁾. At the end of 2015 a Taiwanese cohort study demonstrated in the largest study population of HCV patients to date that statin use was also associated with a reduced risk of cirrhosis development in a dose-dependent manner ⁽²⁾. Now the study by Mohanty et al. takes this even a step further by demonstrating that in patients with HCV infection who already have developed compensated cirrhosis statin use is associated with a significant lower risk of developing hard clinical endpoints namely hepatic decompensation or death. This is of great clinical importance in a patient population with limited treatment options beyond liver transplantation and high mortality rates. Interestingly, cardiovascular risk has been shown to be greater in liver disease (20% in liver cirrhosis vs. 12% in the general population), where statins can play an important role as a primary and secondary prevention for coronary artery disease. Unfortunately the cause of death was not obtainable from this database making it unclear whether the decrease in mortality could be owing to a reduction in cardiovascular-related deaths or really just reflects the improvement in liver disease and potentially the lower risk for HCC development. The authors argue that the fact that patients with a high propensity for statin use (ie, patients with a high risk of dying from a cardiovascular-related death) were excluded reduces this possibility. But given the overall higher cardiovascular risk in this particular patient population more data on death causes will be needed to better explain which factors contribute to improved survival. Also these results would be needed for other cirrhosis causes beyond chronic HCV infection. Finally, given that patients with liver cirrhosis are at risk of decreased hepatic clearance, there is concern that this patient population may be at higher risk for complications from statin therapy. Several retrospective studies have showed that statin use in chronic liver disease and cirrhosis in general is safe but clearly close monitoring and continued surveillance is necessary. Overall, in view of the emerging data guideline committees will have to answer the question in how far statin use should receive a stronger recommendation in patients with HCV and compensated cirrhosis. »

Pr Jürgen Rockstroh, University of Bonn

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