liver-damage image




Liver Injury: 


Liver injury is defined as rise in either


(a) ALT level more than three times of upper limit of normal (ULN)
(b) ALP level more than twice ULN (upper limit normal)
(c) total bilirubin level more than twice ULN when associated with increased ALT or ALP.

Liver damage is further characterized into
  • hepatocellular (predominantly initial Alanine transferase elevation) 
  • cholestatic (initial alkaline phosphatase rise) types.

Specific histo-pathological patterns of liver injury from drug induced damage are discussed below.

Zonal Necrosis: This is the most common type of drug induced liver cell necrosis where the injury is largely confined to a particular zone of the liver lobule. It may manifest as very high level of ALT and severe disturbance of liver function leading to acute liver failure.
Drugs include:
Paracetamol, carbon tetrachloride

Hepatitis: In this pattern hepatocellular necrosis is associated with infiltration of inflammatory cells. There can be three types of drug induced hepatitis.
(A) viral hepatitis type picture is the commonest, where histological features are similar to acute viral hepatitis.
(B) in the focal or non specific hepatitis scattered foci of cell necrosis may accompany lymphocytic infiltrate.
(C) chronic hepatitis type is very similar to autoimmune hepatitis clinically, serologically as well as histologically.

Causes:
(a) Viral hepatitis like: Halothane, isoniazid, phenytoin
(b) Focal hepatitis: Aspirin
(c) Chronic hepatitis: Methyldopa, diclofenac
Cholestasis: Liver injury leads to impairment of bile flow and clinical picture is predominated by itching and jaundice. Histology may show inflammation (cholestatic hepatitis) or it can be bland without any parenchymal inflammation. In rare occasions it can produce features similar to primary biliary cirrhosis due to progressive destruction of small bile ducts (Vanishing duct syndrome).
Causes:
(a) Bland: Oral contraceptive pills, anabolic steroid, androgens
(b) Inflammatory: Allopurinol, co-amoxiclav, carbamazepine
(c) Ductal: Chlorpromazine, flucloxacillin

Steatosis : Hepatotoxicity may manifest as triglyceride accumulation which leads to either small droplet (microvesicular) or large droplet (macrovesicular) fatty liver. There is a separate type of steatosis where phospholipid accumulation leads to a pattern similar to the diseases with inherited phospholipid metabolism defects (e.g. Tay-Sachs disease)
Causes:
(a) Microvesicular: Aspirin (Reye's syndrome), ketoprofen, tetracycline
(b) Macrovesicular: Acetamenophen, methotrexate
(c) Phospholipidosis: Amiodarone, total parenteral nutrition

Granuloma: Drug induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. More than 50 drugs have been implicated.
Causes:
Allopurinol, phenytoin, isoniazid, quinine, penicillin, quinidine

Vascular Lesions : They result from injury to the vascular endothelium.
Causes:
Venoocclusive disease: Chemotherapeutic agents, bush tea
Peliosis hepatis: anabolic steroid
Hepatic vein thrombosis: Oral contraceptives

Neoplasm :Neoplasms have been described with prolonged exposure to some medications or toxins. Hepatocellular carcinoma, angiosarcoma and liver adenomas are the ones usually reported.
Causes:
Vinyl chloride, combined oral contraceptive pill, anabolic steroid, arsenic, thorotrast
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