Iron and
copper deposition were examined in patients with chronic active viral
hepatitis (CAH) and posthepatitic
liver cirrhosis (LC) by
Berlin blue,
rhodanine, or
Victoria blue staining and X-ray microanalysis. Considerable
iron or
copper deposition was demonstrated in the peripheral zones of hepatic lobules in both CAH (53% of specimens) and LC (63% of specimens). Frozen sections taken from the 2 CAH surgical sections with
iron depositions were examined by photoncounting image analysis, and
superoxide liberation from the
metal granules were demonstrated. In areas of
metal deposition, vacuolation of liver cell nuclei, accumulation of
lipofuscin, and induction of
metallothionein (69% of
rhodanine- or
Victoria blue-positive specimens) were often demonstrated, whereas induction of
ferritin was found only in 14% of
Berlin blue-positive specimens. The
PCNA index was significantly lower in areas of
metal deposition than in the adjacent areas without
metal deposition, indicating lowered proliferative capability in the former. These results indicate that cell-mediated immune mechanisms causing the disturbance of bile secretion and
heavy metal deposition in the peripheral zones of hepatic lobules may be involved in the progression of viral
hepatitis from its acute phase to CAH and finally to LC phase, resulting in piecemeal
necrosis. However,
cholangitis could not be demonstrated in the present study.