Acute and chronic drug-induced hepatitis

Area of Science:

• Hepatology
• Toxicology
• Pharmacology

Background:

• Adverse drug reactions (ADRs) can manifest as diverse liver diseases, often mimicking naturally occurring hepatic conditions.
• Drug-induced liver injury (DILI) is frequently mediated by reactive metabolites formed within hepatocytes.
• Protective mechanisms like epoxide hydrolases and glutathione conjugation can be overwhelmed, leading to liver damage.

Purpose of the Study:

• To elucidate the mechanisms underlying drug-induced liver diseases, including toxic and allergic hepatitis.
• To identify factors contributing to individual patient susceptibility to DILI.
• To describe the pathogenesis of drug-induced phospholipidosis and its potential progression to liver disease.

Main Methods:

• Review of existing literature on drug metabolism and hepatotoxicity.
• Analysis of clinical presentations and pathological findings in DILI cases.
• Discussion of genetic and acquired factors influencing drug metabolism and immune responses.

Main Results:

• Acute hepatitis can result from predictable toxic hepatitis (e.g., paracetamol overdose) or idiosyncratic toxic hepatitis (e.g., isoniazid).
• Allergic hepatitis arises from reactive metabolites modifying proteins, triggering immune responses, and is associated with hypersensitivity symptoms.
• Lysosomal phospholipidosis, caused by cationic amphiphilic drugs, can lead to liver lesions and cirrhosis in susceptible individuals, particularly those with cytochrome P-450 isoenzyme deficiencies.

Conclusions:

• DILI encompasses a spectrum of liver conditions, including toxic hepatitis, allergic hepatitis, and phospholipidosis.
• Patient susceptibility to DILI is influenced by genetic polymorphisms and acquired factors affecting drug metabolism and immune responses.
• Early recognition and discontinuation of the offending drug are crucial to prevent progression to chronic liver disease or cirrhosis.