Hepatic impairment as a risk factor of adverse drug reactions

Abstract

There are a lot of clinical variants of hepatic impairment ranging from asymptomatic increase in transaminases to acute liver failure and fulminant hepatitis. Hepatic impairment is a polietiologic syndrome. According to the epidemiological study conducted in the United States (19982008), the main causes of hepatic impairment were paracetamol overdose (46%), idiopathic liver dysfunction (14%), other drugs (excluding paracetamol, 11%), viral hepatitis B (7%), other infectious and non-infectious diseases with liver damage (except for viral hepatitis) 7%, autoimmune hepatitis (5%), ischemic hepatitis (syn. hypoxic hepatitis, liver infarction) 4%, viral hepatitis A (3%) and Wilson's disease (2%). Hepatic impairment have a direct impact on the pharmacokinetics and pharmacodynamics of drugs decreasing clearance, elimination and excretion of drugs. Also Transjugular intrahepatic porto-systemic shunts, which are often used to treat portal hypertension in patients with liver cirrhosis, can significantly reduce the presystemic elimination of drugs, thereby increasing their absorption. Moreover, in patients with liver cirrhosis, concomitant renal dysfunction also requires an adjustment of the dose of drugs. Correction of pharmacotherapy in accordance to pharmacokinetic and pharmacodynamic changes of drugs ingested by patients with impaired liver function will improve the quality of medical care and reduce the risks of adverse drug reactions.