IRON AND COPPER DEPOSITION IN CHRONIC ACTIVE HEPATITIS AND LIVER-CIRRHOSIS - PATHOGENETIC ROLE IN PROGRESSIVE LIVER CELL-DAMAGE

Iron and copper deposition were examined in patients with chronic acti ve viral hepatitis (CAH) and posthepatitic liver cirrhosis (LC) by Ber lin blue, rhodanine, or Victoria blue staining and X-ray microanalysis . Considerable iron or copper deposition was demonstrated in the perip heral zones of hepatic lobules in both CAH (53% of specimens) and LC ( 63% of specimens). Frozen sections taken from the 2 CAH surgical secti ons with iron depositions were examined by photoncounting image analys is, and superoxide liberation from the metal granules were demonstrate d. In areas of metal deposition, vacuolation of liver cell nuclei, acc umulation of lipofuscin, and induction of metallothionein (69% of rhod anine- or Victoria blue-positive specimens) were often demonstrated, w hereas induction of ferritin was found only in 14% of Berlin blue-posi tive specimens. The PCNA index was significantly lower in areas of met al deposition than in the adjacent areas without metal deposition, ind icating 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 o f hepatic lobules may be involved in the progression of viral hepatiti s from its acute phase to CAH and finally to LC phase, resulting in pi ecemeal necrosis. However, cholangitis could not be demonstrated in th e present study.