Drugs and the Liver

Introduction

The liver is the primary site of drug metabolism. The liver converts drugs from fat-soluble to water-soluble substances that can be excreted in urine or bile

Drugs to avoid in cirrhosis

The following drugs should be avoided as they may exacerbate the complications of cirrhosis:

• NSAIDs: can reduce renal blood flow to precipitate hepatorenal failure. May also promote mucosal ulceration, leading to variceal haemorrhage
• ACE inhibitors: can reduce renal blood flow to precipitate hepatorenal failure
• Codeine: leads to hepatic encephalopathy
• Narcotics: leads to hepatic encephalopathy
• Anxiolytics: leads to hepatic encephalopathy

Drug-induced liver injury

Many drugs impair liver function. Most drug reactions are self-limiting and chronic liver damage is rare, although acute liver failure can occur. Jaundice indicates more severe damage.

Cholestasis e.g. antibiotics, oestrogens

Chlorpromazine and antibiotics such as flucloxacillin can cause cholestatic hepatitis. This is characterised by inflammation and canalicular injury. Co-amoxiclav is the most common antibiotic to cause abnormal LFTs, although these changes take 10-40 days to develop.

Oestrogens can cause pure cholestasis (reduced bile flow with no liver injury). However, modern contraceptives are safe from this adverse effect.

Hepatocyte necrosis e.g. paracetamol, isoniazid

The commonest cause of drug-induced hepatocyte damage is paracetamol. This leads to high ALT.

Vascular/sinusoidal lesions e.g. cancer drugs, vitamin A

Alkylating agents used in chemotherapy (e.g. busulfan, azathioprine) can damage the vascular endothelium and lead to venous outflow obstruction.

Chronic overdose of vitamin A can damage the sinusoids and trigger local fibrosis, resulting in portal hypertension.

Hepatic fibrosis e.g. methotrexate

Most injuries cause by drugs are reversible, so fibrosis is rare. However, methotrexate can cause acute liver damage when started and leads to cirrhosis at chronic high doses. Risk factors include pre-existing liver disease and high alcohol intake.