Evaluation of paracetamol-induced damage in liver biopsies. Acute changes and follow-up findings

In 100 patients who had taken an acute overdose of paracetamol the liver was biopsied percutaneously on the 4th day or as soon thereafter as recovery of the clotting mechanism allowed. A system for grading the histological changes in the liver is described. The hallmark of severe (grade III) damage is centrizonal necrosis, for which there is probably a dosage threshold. Consequent changes include phagocytosis of cell debris, reticulin collapse, and an inflammatory infiltration; acidophil degeneration of hepatocytes is sometimes prominent; regenerative growth is already evident after 4 days. Mild (grade I) damage is characterized by excess of lipofuscin pigment in centrizonal hepatocytes, sparse focal necrosis of liver cells, and some phagocytosis of lipofuscin. The findings in moderate (grade II) damage are similar but more pronounced. Five patients died in acute hepatic failure, and 22/100 showed severe (grade III) changes but survived. Forty-nine patients representing all three grades of liver damage were rebiopsied after 3 months. Central necrotic zones were found to have been completely reconstituted leaving only minor abnormalities except for one patient who showed mild centrilobular fibrosis and scarring of a nonprogressive nature.