Drug-induced liver disease

Drug-induced liver disease

Hepatic injury caused by drugs accounts for 2–5% of hospital admissions for jaundice. Drugs that cause hepatotoxicity may be subdivided into predictable (dose-dependent) and idiosyncratic, although more than one mechanism may occur with a single drug (see Fig. 5.11).

·        Direct hepatotoxins have a direct physico-chemical effect on the cells, e.g. membrane disruption which leads to metabolic defects.

·        Cytotoxic indirect hepatotoxins interfere with the hepatocytes’ integrity, most commonly this manifests as fatty change and necrosis due to decreased removal of lipid from the cell.

·        Cholestatic drugs interfere with the uptake or excretion of bile by hepatocytes, which manifests as cholestasis in the upper biliary tree.

·        Idiosyncratic hepatotoxins appear to cause a chronic active hepatitis similar to autoimmune chronic hepatitis and there may be antinuclear and anti smooth muscle antibodies present in serum. Though rare, they are important because the disease is reversible on with drawal.

The pathophysiology of drug hepatotoxicity may also be divided into the liver pathology caused (see Table 5.6).