Statin use and risk of progression to liver cirrhosis in chronic hepatitis B independent of conventional risk factors: A nationwide study

Abstract

Many studies have elucidated the protective associations of statin use with liver cancer or mortality, but studies examining statin's effect on the risk of progression to liver cirrhosis considering medical/metabolic conditions or lifestyle factors are lacking. We aimed to assess statin's benefit independent of conventional risk factors. We identified 25,033 pairs of statin users (using statins for ≥90 days) and nonusers among patients with chronic hepatitis B (CHB) in the Republic of Korea's National Health Insurance Service database from 2010 to 2018. The primary endpoint was progression to cirrhosis from an inactive carrier or simple CHB. The cumulative probability was plotted using the Kaplan‐Meier method. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using the multivariable Cox proportional hazard model. During a 218,472 person‐year follow‐up, 2210 incident cases of progression to cirrhosis occurred. The 5‐year cumulative risks were 4.0% and 6.3% in statin users and nonusers, respectively ( p < 0.001). Statin use was significantly associated with a decreased risk of progression to cirrhosis (aHR, 0.59; 95% CI, 0.55–0.65; p < 0.001), after adjusting for age, sex, hypertension, diabetes, dyslipidemia, antiviral therapy, aspirin use, metformin use, nonstatin medication for dyslipidemia, smoking, drinking, obesity, exercise, and liver dysfunction. This protective association was still significant in a dose–response manner and with different time lags for outcomes. Conclusion : Statin use is associated with a decreased risk of progression to cirrhosis among patients with CHB, independent of metabolic and lifestyle factors. Future studies are required to validate this observation.

Review of the role of statins in cirrhosis and portal hypertension

“…Notably, statins decreased portal pressure independently of the use in combination with propranolol. Only 1 trial failed to show a significant reduction in portal pressure; in this trial simvastatin was Yun, Hepatol Commun, 2022 [22] Republic Pose, Lancet Gastroenterol Hepatol, 2020 [20] 9 prescribed in combination with carvedilol instead of propranolol. [15] The use of carvedilol as bleeding prophylaxis in this trial could have affected the negative results, but further controlled studies are needed to assess the potential effect of this combination.…”

From liver to hormones: The endocrine consequences of cirrhosis

“…Atorvastatin, simvastatin, rosuvastatin, fluvastatin, and lovastatin have demonstrated benefits in reducing the risk of hepatic decompensation, variceal bleeding, and mortality, especially in compensated cirrhotic patients[ 136 , 137 ]. Statin use is associated with a lower risk of LC progression in chronic hepatitis B patients[ 138 ]. Nationwide studies revealed statin use’s correlation with reduced HCC development, regardless of DM or LC presence[ 139 ].…”

Statins in Chronic Liver Disease: Review of the Literature and Future Role

“…Two large nationwide cohort studies showed that statin use in patients with HBV reduced risk of cirrhosis by ∼36% and >49% cumulatively over a 5- and 12-year follow-up period, respectively ( p < 0.001). 67 68 Statin use lowered the risk of overall hepatic decompensations in patients with HBV after >144 months of follow-up, compared with non-users (adjusted hazard ratio [aHR] = 0.39, 95% CI: 0.26–0.62). 69 Of all decompensating events, ascites and hepatic encephalopathy (HE) were most frequently prevented.…”