FREQUENCY AND DISTRIBUTION OF DNA FRAGMENTATION AS A MARKER OF CELL-DEATH IN CHRONIC LIVER-DISEASES

To study the early stages of cell death in various types of chronic li ver injury, liver biopsies from a total of 26 patients, including 7 wi th chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with a lcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis(AI/D H), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragment ation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibro sis, using a computer with Sigmascan software. The number of positive hepatocytes/mm(2) was similar in the biopsies of patients with CHC, CH B, ALD and AI/DH, but significantly lower in PBC. The number of positi ve sinusoidal lining cells/mm(2) was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining reveale d that the ISNTA-positive sinusoidal lining cells were also CD68 posit ive, indicating that they were Kupffer cells. The frequency of ISNTA p ositivity did not correlate with serum AT or ALT levels, steatosis, ce ll swelling or cirrhosis. ISNTA-positive hepatocytes were more frequen t than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver dis eases, that the high frequency of DNA fragmentation in Kupffer cells i n CHC suggests that during chronic hepatitis C infection activated Kup ffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degre e of cell injury in the liver.