Statin drugs decrease progression to cirrhosis in HIV/hepatitis C virus coinfected individuals

Abstract

Introduction Chronic HIV/HCV co-infection carries increased risk of cirrhosis, hepatocellular carcinoma, and death. Due to anti-inflammatory properties, HMG co-A inhibitors (statins) may be useful adjunctive therapy to reduce liver disease progression. Methods Clinical information was extracted from the Veterans Affairs HIV and HCV Clinical Case Registries (1999–2010). HIV-related variables included combination anti-retroviral therapy (cART) era of diagnosis, CD4 cell count, and percent time with undetectable HIV viral load. Metabolic variables included diabetes, low-HDL, and hypertension. Statin use was measured as percent time with active prescription (time-updated throughout the follow-up period). Cox proportional hazards analysis was used to determine risk factors for cirrhosis (ICD-9 or APRI>2) overall and in groups stratified by alanine aminotransferase (ALT) level above and below 40 IU/L. Results The cohort included 5985 HIV/HCV co-infected veterans. The majority was black race, and the mean age at index date was 45 years. Statin use was significantly protective of cirrhosis for patients with ALT ≤40 IU/L; for every 30% increase in time on statin, there was a 32% decreased risk of developing cirrhosis (HR 0.68, 95% CI 0.47 −0.98). Diabetes and low-HDL were significantly associated with cirrhosis in patients with ALT > 40 IU/L (HR 1.15, p <0.04 and HR 1.3, p <0.0001). Conclusions Statin drug use is beneficial in mitigating the risk of liver disease progression for HIV/HCV co-infected patients without advanced liver disease. Low-HDL and diabetes in co-infected patients with abnormal ALT have greater risk of cirrhosis development.

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).…”

“…Epidemiological studies have observed a protective association between statin use and hepatocellular cancer 30–32 . Recent studies have also suggested an association between statin use and risk of fibrosis progression and hepatic decompensation in patients with CLDs, although the effects have been variable 33–43 .…”

Update in HIV–hepatitis C virus coinfection in the direct acting antiviral era

“…With respect to medications and fibrosis progression, a retrospective study of 5,985 HIV/HCV co-infected veterans suggested statin use may be associated with slower fibrosis progression, although this finding was only significant in a sub-cohort of patients with low ALT [67]. An exploratory study in co-infected patients with concomitant non-alcoholic steatohepatitis showed 48 weeks of pioglitazone therapy resulted in reduced hepatic fat measured by magnetic resonance spectroscopy [68].…”