Statins confer decompensation, survival effects in chronic viral hepatitis
Use of statins may cut the risk of new-onset liver decompensation and death in patients with chronic viral hepatitis, as shown in a recent study.
“Statins represent a potential prognosis modifying agent in patients with chronic liver disease, an important contribution given the limited treatments currently available,” according to a team of investigators from Hong Kong.
Conducting a propensity score–matched landmark analysis including 69,184 chronic viral hepatitis patients, the investigators found that the primary outcome of a composite of portal hypertension-related liver decompensation events occurred less frequently with statin use vs nonuse (hazard ratio [HR], 0.55; 95 percent CI, 0.36 to 0.83; p=0.005). [Aliment Pharmacol Ther 2017;doi:10.1111/apt.14341]
The protective association between the lipid-lowering drug and the primary outcome was largely attributed to a reduced risk of ascites in patients taking statins (HR, 0.57; 0.36 to 0.92; p=0.02).
Statins also reduced the risk of overall death by 13 percent (HR, 0.87; 0.76 to 0.99; p=0.035), which increased to 23 percent with drug exposure of >385 cumulative Defined Daily Dose (HR, 0.77; 0.60 to 1.00; p=0.046). No effect was observed for variceal bleeding (HR, 0.43; 0.13 to 1.37; p=0.152).
The cohort consisted of 2,053 statin users and 67,131 nonusers. Patients were 60 years of age on average, with majority being male and predominantly infected with hepatitis B virus. The mean follow-up period was 2.7 years among statin users vs 2.8 years among nonusers.
“Our findings are likely explained by the pleiotropic effects of statins on portal hypertension,” the investigators said.
Previous reports have identified hepatic endothelial dysfunction and the subsequent impairment in nitric oxide synthase as important contributors to intrahepatic vascular resistance, in addition to architectural distortions due to cirrhosis. [J Hepatol 2010;53:558-567]
Statins then improve endothelial nitric oxide synthase expression and activity, with the resulting increase in hepatic nitric oxide reducing hepatic resistance, ameliorating vasorelaxation and potentially improving liver function, as shown in animal and human mechanistic studies. [J Hepatol 2007;46:1040-1046; Hepatology 2007;46:242-253]
Despite the presence of several limitations, including the inability to determine the severity of underlying liver disease, “our results contribute to the growing evidence that the benefits and safety of statins likely outweigh their potential hepatotoxic effects, and their use in chronic liver disease should not be reflexively avoided,” the investigators said.