Atorvastatin and fluvastatin are associated with dose‐dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES

Abstract

Background Statins are associated with delayed fibrosis progression and a reduced risk of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV). Limited data exist regarding the most effective type and dose of statin in this population. We sought to determine the impact of statin type and dose upon fibrosis progression and HCC, in patients with HCV. Methods Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified all subjects initiated on anti-HCV therapy from 2001 to 2014, and all incident cases of cirrhosis and HCC. Statin use was measured using cumulative defined daily dose (cDDD). Multivariable Cox proportional hazard regression models were used to examine the relationship between statin use and the development of cirrhosis and HCC. Results Among 9,135 eligible subjects, 1,649 developed cirrhosis, and 239 developed incident HCC. Statin use was associated with a 44% reduction in development of cirrhosis (adjusted HR 0.6, 95% CI 0.53, 0.68). The adjusted HRs (95% CI) of fibrosis progression with statin cDDD 28–89, 89–180, and >180, were 0.74 (0.59,0.93), 0.71 (0.59,0.88), and 0.6 (0.53,0.68), respectively. Mean change in FIB-4 score with atorvastatin (n=944) and fluvastatin (n=34) was −0.17 and −0.13 respectively (p=0.04) after adjustment for baseline FIB-4 score and established predictors of cirrhosis. Statin use was also associated with a 49% reduction in incident HCC (adjusted HR 0.51, 95% CI 0.36, 0.72). A similar dose-response relationship was observed. Conclusion In patients with chronic HCV, statin use was associated with a dose-dependent reduction in incident cirrhosis and HCC. Atorvastatin and fluvastatin were associated with the most significant anti-fibrotic effects, compared to other statins.

Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis

“…Of the 1706 unique studies identified using our search criteria, 13 studies met our inclusion criteria and were included in our meta-analysis (3 RCTs and 10 observational studies) 33–43, 50, 51 Six studies included participants with non-cirrhotic CLDs 35, 39–43 , six studies included participants with compensated cirrhosis 36, 37, 42, 43, 50, 51 , and three studies included individuals with decompensated cirrhosis 33, 34, 38 . One study was excluded as it represented a population already included in another, more recent study; 52 one small RCT of statins in NASH was excluded due to insufficient information 53 .…”

“…Five studies reported risk of development of cirrhosis (or progression of fibrosis) in patients with baseline non-cirrhotic CLDs 35, 39–41, 43 . In three studies, diagnosis of cirrhosis (or fibrosis progression) was ascertained based on a combination of administrative claims codes and calculated serum fibrosis markers (FIB-4 or APRI); one study was a post-hoc analysis of the HALT-C trial included patients with paired liver biopsies, with fibrosis progression defined based on increase in Ishak fibrosis stage by ≥ 2.…”

“…On exclusion of one study, which relied exclusively on administrative claims codes with very large protective effect size, a 35% lower risk of development of cirrhosis (or progression of fibrosis) in statin-exposed patients was a more conservative estimate (RR, 0.65; 95% CI, 0.48–0.87), with considerable heterogeneity (I 2 =89%). Three studies specifically reported the outcome of fibrosis progression (based on either paired liver biopsies or serum fibrosis markers) 39, 40, 43 . On meta-analysis of these studies, statin exposure was associated with a 27% lower risk of fibrosis progression (RR, 0.73; 95% CI, 0.54–1.00, p=0.049).…”

The Relationship between Serum Bilirubin and Elevated Fibrotic Indices among HBV Carriers: A Cross-Sectional Study of a Chinese Population

“…Noninvasive methods had overcome the limitations of liver biopsy and were also used as prognostic indices for subjects with hepatitis B-associated HCC [39]. Furthermore, the accuracy of FIB-4 and APRI were 78% and 76% [40], suggesting they were suitable for regular monitoring of disease progression [41,42]. Thus, using APRI and FIB-4 to assess liver fibrosis was acceptable in the circumstances of the study.…”

Association of a 3′ untranslated region polymorphism in proprotein convertase subtilisin/kexin type 9 with HIV viral load and CD4+ levels in HIV/hepatitis C virus coinfected women

“…Use of lipid lowering medications was inversely associated with LDL-C levels in both HCV/HIV co-infected and HIV monoinfected women, highlighting the effectiveness of these medications despite dysregulated lipid homeostasis. Furthermore, a recent study observed that statin use was associated with lower incidence of liver cirrhosis and hepatocellular carcinoma in HCV + veterans [47] . A future research priority will therefore be to define effects of recently-approved PCSK9 inhibitors – which have favorable toxicity and drug-drug interaction profiles as compared to statins - in HIV monoinfected and HCV/HIV co-infected women.…”