Drug Induced Liver Disease (Hepatotoxicity)-Chapter 11-HISTOLOGICAL PATTERN IN DRUG-INDUCED LIVER DISEASE Part-1

Acute hepatitis

     DILI accounts for ~10% of acute hepatitis and is perhaps the most common cause of cholestatic hepatitis. A wide variety of drugs can cause acute hepatocellular injury.

Herbal and botanical drugs are an important but often overlooked cause of hepatotoxicity.

Certain commonly consumed herbal agents now being investigated for their hepatoprotective effects, such as turmeric (Curcuma longa) and mate tea (Ilex paraguariensis), are listed as potentially hepatotoxic in various patient literature. Finally, contaminants of herbal supplements should be considered, including heavy metals such as arsenic, cadmium, lead or mercury.

The following morphological patterns can be observed in acute hepatocellular injury.

·         Acute hepatitis. The hallmarks of acute hepatocellular injury are portal and parenchymal inflammation, hepatocellular injury, and/or necrosis (fig 1). By definition, fibrosis is absent. Regenerative features such as binucleate hepatocytes and thick cell plates are common. Prominent Kupffer cells often are present in the sinusoids. The term “cholestatic hepatitis” is used when these changes are accompanied by cholestasis.

·         Necrosis. Acute hepatocellular injury can result in necrosis affecting single (spotty necrosis) or groups of hepatocytes (confluent necrosis). In some cases, confluent necrosis can be zonal and may be helpful in diagnosis. Centrizonal (zone 3) necrosis is characteristic of acetaminophen and halothane, and toxins such as carbon tetrachloride. Isolated necrosis affecting zones 1 and 2 is rare; toxins such as cocaine and ferrous sulfate typically affect zone 1, while beryllium has been implicated in zone 2 necrosis. When extensive, confluent necrosis can lead to acute hepatic failure.

·         Resolving hepatitis. If biopsy is performed later in the disease course, hepatocellular injury and inflammation may be minimal (fig 2). The presence of numerous macrophages in the sinusoids is a helpful clue for the diagnosis of resolving hepatitis. The stain periodic acid–Schiff with diastase can be used to highlight the macrophages (fig 3).

 

Figure.11.1:-Atorvastatin-induced acute hepatitis. Mixed parenchymal inflammation is present, consisting of lymphocytes, plasmahistiocytic cells, and neutrophils. There is no bile duct damage or fibrosis.

Figure.11.2:- Resolving hepatitis. Parenchymal infiltrate is diminished in comparison to acute hepatitis. Hepatocellular injury is minimal. Pigment accumulation in sinusoidal macrophages is prominent.

 

Figure.11.3:- Resolving hepatitis. Sinusoidal macrophages are evident with periodic acid–Schiff (PAS)-positive diastase-resistant cytoplasmic contents.

Figure.11.4:- Acetaminophen toxicity. Marked hepatocellular necrosis is present in a zonal, centrilobular pattern, while the inflammatory infiltrate is minimal. Residual viable hepatocytes show some steatosis.