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Statin use associated with dose-dependent reduction in cirrhosis, HCC in patients with HCV

In patients with hepatitis C, both atorvastatin and fluvastatin use were associated with a dose-dependent reduction in both cirrhosis and hepatocellular carcinoma, according to recent findings published in Hepatology.

“This was the first study of patients with chronic HCV to be associated with a clear, dose-dependent reduction in rates of both incident cirrhosis and HCC with statins, independent of fibrosis stage or attainment of sustained viral response,” Raymond T. Chung, PhD, director of Hepatology and Liver Center at Massachusetts General Hospital, told Healio.com/Hepatology. “We also observed a difference in effect according to statin type, with the greatest antifibrotic benefits seen in users of atorvastatin and fluvastatin, a finding we hope to validate in future studies.”

Raymond T. Chung

Previously, researchers associated statin use with a reduction in both cirrhosis and HCC in patients with HCV. In 2015, Yang et al. observed that statin use was associated with a dose-dependent reduction in cirrhosis. However, the patients in this population-based cohort did not have laboratory-confirmed diagnoses of HCV. Further, the study did not adjust for statin type, baseline disease activity or fibrosis severity.

To provide a more conclusive answer to Yang et al.’s study, Chung and colleagues assessed a well-established cohort of U.S. veterans. They aimed to determine the impact of statin type and dose on fibrosis progression and HCC in patients with HCV. The researchers identified 9,135 patients in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database who were initiated on HCV antibody therapy between 2001 and 2014, 1,649 of whom developed cirrhosis and 239 of whom developed HCC. The researchers measured statin use with cumulative defined daily dose, which is the assumed average maintenance dose per day for a drug when used in its main indication as defined by the WHO.

They found that statin use was associated with a 44% reduction in cirrhosis (adjusted HR [aHR] = 0.6; 95% CI, 0.53-0.68) and a 49% reduction in HCC (aHR = 0.51; 95% CI, 0.36-0.72). For cirrhosis, the aHR was 0.74 (95% CI, 0.59-0.93) for a cumulative defined daily dose between 28 mg and 89 mg, 0.71 (95% CI, 0.59-0.88) for a daily dose between 89 mg and 180 mg, and 0.6 (95% CI, 0.53-0.68) for a dose greater than 180 mg. For HCC, the researchers observed a similar dose-dependent relationship. The average change in FIB-4 score was –0.17 for atorvastatin (n = 944) and –0.13 for fluvastatin (n =34), after adjusting for baseline score and cirrhosis predictors (P = .04).

Tracey G. Simon

“Whether statins can be recommended as antifibrotic or chemopreventive agents to reduce liver disease progression remains to be seen,” Tracey G. Simon, MD, fellow of gastroenterology at Massachusetts General Hospital told Healio.com/Hepatology.

The findings of statins in reducing HCC and cirrhosis is not new, but there are three other novel findings, according to an editorial by Juan G. Abraldes, MD, in the division of gastroenterology at the University of Alberta, and Kelly W. Burak, MD, FRCPC, BSc, MSc (Epid) of Calgary Liver Unit, division of gastroenterology and hepatology at University of Calgary, Canada, and colleagues.

Juan G. Abraldes

“First, although statins improved rates of sustained viral response, the preventive effect of statins was equally strong in patients not achieving sustained viral response,” Abraldes and colleagues wrote. “Second, the chemopreventive effect against development of HCC was independent of the effect of fibrosis progression. Third, the beneficial effects of statins were dose dependent, and statin specific, mainly with atorvastatin and fluvastatin.”

Abraldes and colleagues wrote that patients with chronic liver disease and cardiovascular indications should be treated with a statin. However, more randomized controlled trials need to be conducted to recommend statins in patients without cardiovascular indications.

“On the choice of statin, and the potential relevance of dosing, the current study provides some hints,” Abraldes and colleagues wrote. “But not definitive answers.” – by Will Offit

Disclosure: One researcher reports receiving investigator initiated grants to the institution from Gilead and AbbVie. Please see the full study for a list of all other researchers’ relevant financial disclosures. Abraldes reports consulting for Promethera, receiving grants from Gilead and receiving speaker fees from Janssen. Burak reports consulting for and being on the speakers bureau of Gilead and Astellas. She consults for and received grants from Lupin. She is on the speakers bureau of and received grants from Bayer. She consults for Janssesn, BTG, AbbVie and Merck. She received grants from Verlyx.