The remnant liver dysfunction after 84% hepatectomy in dogs

Background/Aims: We have been investigating the mechanism of remnant liver dysfunction after extensive hepatectomy in a canine model since 1990. This study focused on the role of heat shock protein and hepatocyte apoptosis. Methodology: Adult mongrel dogs were randomly divided into 3 groups: Group 1, sham operation; Group 2, 70% hepatectomy; and Group 3, 84% hepatectomy. Heat shock protein and hepatocyte apoptosis after hepatectomy were examined by using isolated hepatocytes and Kupffer cells. Results: Heat shock protein significantly increased in Groups 2 and 3, but rose much higher in Group 3. Examination of pure hepatocyte culture showed no apoptosis in Group 2, but significant apoptosis occurred in Group 3. In co-cultures of hepatocytes and Kupffer cells, induction of apoptosis in Gro up 2 was mild, but it increased earlier and reached very high levels in Gro up 3. The TNF-alpha level in co-culture supernatant was significantly highe r in Group 3 than Group 2. Conclusions: After extensive (84%) hepatectomy, apoptosis signal transducti on predominates over anti-apoptosis signal transduction, despite high expre ssion of heat shock protein in the remnant liver. Accordingly, the cytotoxi c mechanism overcomes the cytoprotective mechanism, leading to significant induction of hepatocyte apoptosis and severe liver damage.