Conference Coverage

Statins Appear Safe, Even Beneficial, in Cirrhosis



SAN DIEGO – Statin therapy is not only safe for patients with cirrhosis, it may slow the progression of their liver disease to hepatic decompensation and help them live longer, a study has shown.

The findings, reported at the annual Digestive Disease Week, should help allay fears that decreased hepatic clearance of statins could lead to complications in patients with advanced liver disease, as was previously hypothesized, said lead investigator Dr. Sonal Kumar.

"In fact, it seems the opposite may be true," said Dr. Kumar of Brigham and Women’s Hospital, Boston, referring to the results of her retrospective study in which statin therapy in cirrhosis patients was associated with a decreased risk of hepatic decompensation, a delay in the time to decompensation, and reduced all-cause mortality, compared with cirrhosis patients not taking statins.

The investigators were aware that some clinicians either do not initiate statin therapy or discontinue statins in patients with advanced liver disease because of perceived safety concerns. Dr. Kumar and her colleagues sought to determine the actual effect of statin therapy on the risk of hepatic decomposition in cirrhosis.

They identified all patients with biopsy-proven cirrhosis who had taken statins for a minimum of 3 months for treatment of dyslipidemia. A control population of cirrhosis patients not on statins was matched 2:1 for age, gender, and Child-Pugh class from the Partners HealthCare System Research Patient Data Registry, which includes demographic and diagnostic information on patients treated at Massachusetts General Hospital and Brigham and Women’s Hospital.

The primary outcomes of the study were hepatic decompensation, defined as the development of ascites, jaundice (bilirubin greater than 2.5 mg/dL), hepatic encephalopathy, or variceal hemorrhage, and time to decompensation. Mortality was a secondary outcome, Dr. Kumar explained.

The investigators created a Cox proportional hazards model for decompensation to control for age, Child-Pugh class, diabetes, coronary artery disease, and hepatocellular carcinoma, and they used conditional logistic regression to assess mortality, she said.

Of 243 cirrhosis patients included in the analysis, 81 were statin users and 162 were matched controls. "In each group, approximately 70% of patients were Child-Pugh A and 30% were Child-Pugh B/C, and the MELD [Model for End-Stage Liver Disease] score, albumin, presence of varices, and beta-blocker use were similar between groups," Dr. Kumar noted. In the statin group, which was followed for a mean of 1,756 days, decompensation was reported in 31 patients (38.2%), compared with 80 patients (50.62%) in the control group.

The control patients were followed for a mean of 1,503 days, and on Cox analysis, "statin therapy was the only factor significantly associated with lower decompensation risk, with a hazard ratio of 0.46." Additionally, Kaplan-Meier curves showed a significantly longer time to decompensation in patients receiving statin therapy, she said. In subgroup analyses, significantly longer time to decompensation was observed in Child-Pugh A and Child-Pugh B/C patients.

Overall mortality was significantly lower in the statin group, at 37.0%, than in the control group, at 50.6%, said Dr. Kumar. Statin use remained significantly associated with decreased mortality in multivariate analysis, with an odds ratio of 0.36, while coronary artery disease and hepatocellular carcinoma were associated with increased mortality, with respective odds ratios of 3.6 and 4.9.

There were no statistically significant differences in cause of death between the two groups, "however it is important to note that cause of death was not documented for approximately one-third of the study patients, so we cannot make definitive statements about whether patients on statins were less likely to die of liver-related or cardiovascular causes than patients in the control group," said Dr. Kumar.

The apparent hepatoprotective effect of statin therapy in cirrhosis patients may be a function of previously observed hemodynamic and molecular effects of statins, Dr. Kumar hypothesized. Sinusoidal endothelial dysfunction with decreased nitric oxide production contributes to increased hepatic resistance in cirrhosis, she explained. Just as statins improve endothelial dysfunction in the peripheral vasculature, they may also improve the vascular disturbances that contribute to portal hypertension in cirrhosis by selectively increasing nitric oxide availability in the liver, thus reducing pressures, she said.

The retrospective design of the study limits the conclusions that can be taken from it. Specifically, "we can’t say that all patients with liver disease should be prescribed statins," Dr. Kumar said. "What we can say is that statin therapy is safe in this population, it may be beneficial for its effects on the liver as well as the cardiovascular system, and clinicians should not hesitate to prescribe it for appropriate cardiovascular indications in cirrhosis patients." The findings also indicate that prospective studies are warranted to clarify the role of statins in advanced liver disease, she stressed.

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