Metformin and liver cirrhosis
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Metformin and Liver Cirrhosis: A Comprehensive Review
Introduction to Metformin and Liver Cirrhosis
Metformin, a widely used medication for type 2 diabetes mellitus (T2DM), has been the subject of extensive research regarding its effects on liver cirrhosis. Liver cirrhosis, often resulting from chronic liver diseases such as hepatitis C and non-alcoholic steatohepatitis (NASH), poses significant health risks, including hepatocellular carcinoma (HCC) and liver-related mortality. This article synthesizes current research on the impact of metformin on patients with liver cirrhosis.
Metformin and Mortality in Cirrhotic Patients
Reduced Overall Mortality
Several studies have demonstrated that metformin use in patients with cirrhosis and diabetes is associated with reduced overall mortality. A large cohort study involving 74,984 patients with cirrhosis found that metformin use was independently associated with a significant reduction in mortality (HR 0.68, 95% CI 0.61-0.75). Another study confirmed these findings, showing that continuation of metformin after a cirrhosis diagnosis significantly improved survival rates (HR 0.43, 95% CI 0.24-0.78).
Liver-Related Mortality and Complications
While metformin reduces overall mortality, its impact on liver-related mortality and complications such as hepatic decompensation and HCC is less clear. The same cohort study noted that metformin did not significantly reduce the incidence of HCC or hepatic decompensation after adjusting for concomitant statin exposure. However, other research indicates that metformin use is associated with a lower risk of liver-related death and transplantation in patients with hepatitis C virus (HCV) cirrhosis.
Metformin and Hepatocellular Carcinoma (HCC)
Preventive Effects on HCC
Metformin has shown promise in reducing the risk of HCC in patients with cirrhosis. A study on patients with NASH-related cirrhosis found that metformin use was associated with a significant reduction in the risk of HCC (aHR 0.78, 95% CI 0.69-0.96). Additionally, metformin was found to prevent liver tumorigenesis by attenuating fibrosis in a transgenic mouse model of HCC.
Mechanisms of Action
The protective effects of metformin against HCC may be attributed to its ability to improve liver function, inhibit hepatic stellate cell activation, and reduce liver fibrosis. Furthermore, metformin has been shown to suppress hepatic progenitor cell activation, which is crucial in preventing the development of HCC in cirrhotic livers.
Metformin and Liver Function
Safety in Liver Disease
Despite concerns about metformin's safety in patients with liver disease, evidence suggests that it does not exacerbate liver injury. A review of the literature found no substantial evidence that metformin causes or worsens liver injury, even in patients with elevated transaminases. Moreover, metformin has been shown to improve liver function and histological alterations in insulin-resistant rat models of NASH and cirrhosis.
Monitoring and Contraindications
Routine monitoring of liver transaminases before and during metformin therapy is not substantiated, as metformin is not considered intrinsically hepatotoxic. However, caution is advised in patients with advanced cirrhosis, particularly those with arterial hypoxemia, due to the increased risk of lactic acidosis.
Conclusion
Metformin appears to be a safe and beneficial treatment for patients with diabetes and liver cirrhosis. It is associated with reduced overall mortality and may lower the risk of HCC and liver-related complications in certain populations. While routine liver function monitoring is not necessary, careful patient selection and monitoring are essential to mitigate risks. Further research is needed to fully understand the long-term benefits and safety of metformin in cirrhotic patients.
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