Orthotopic liver transplantation for patients with hepatitis B virus-related liver disease

Abstract

Fifty-nine patients with prior hepatitis B virus infection underwent orthotopic liver transplantation. During the first 2 mo, mortality was not significantly different in the hepatitis B virus-infected group (25.5%) vs. a hepatitis B virus-immune control group (21%). Beyond 2 mo, the mortality, rate of graft loss, need for retransplantation and incidence of abnormal liver function were significantly higher in the hepatitis B virus-infected group. Treatment of the hepatitis B virus infection was attempted with passive immunization, combined active and passive immunization, alpha-interferon or nothing. The clinical outcome was not significantly influenced by any of these therapies. However, of the patients who lived more than 60 days, 6 of 22 treated with active plus passive immunization were cleared of HBsAg, something achieved once in 16 patients treated with alpha-interferon, never in 3 patients with passive immunization only and once in 4 patients with no therapy. In patients with recurrent hepatitis B virus infection, the pace of hepatitis development in the graft appeared to be accelerated, and this was particularly striking in patients who underwent multiple retransplantations at progressively shorter intervals. None of the patients who became HBsAg-negative had HBeAg preoperatively.

Fig. 1

Percentage of patients who survived more than 60 days who became positive as time passed for the serological or clinical parameters shown. Once a change to positive occurred, this was permanent and contributory to subsequent cumulative scores with the exception of the anti-HBs antibodies. The rise in anti-HBs antibodies in the first 100 days and subsequent decline reflected HBIG administration and later discontinuance.

Fig. 2

Summary of histopathological structure in allografts of 35 patients who developed recurrent HBV infection after liver transplantation. Note the changes in histopathological classification that occurred in many of the recipients who had serial biopsies.

Fig. 3

Evolution of histopathological changes in serial liver biopsies of patient OT #810 with recurrent HBV-induced cirrhosis. (a) At 71 days, mild spotty hepatocyte necrosis was seen. PT = portal tract. (H & E, original magnification × 300). (b) At 147 days, features of acute hepatitis were evident, superimposed on bridging and piecemeal necrosis (arrow), that were suggestive of a transition to chronic hepatitis with progression (H & E, original magnification × 300). (c) At 187 days, early regenerative nodule formation was already present (H & E, original magnification × 300). (d) At 203 days, failed graft removed at retransplantation that showed well-developed cirrhosis (H & E, original magnification × 100).

Fig. 4

Failed allograft removed at 378 days in a patient who had subacute hepatic failure. (a) Very little inflammation but marked hepatocellular swelling and degeneration in the centrilobular regions. Bridging (arrow) between central veins and between portal and central veins was seen. PT = portal tract, CV = central vein. (H & E, original magnification × 300). (b) Tissue expression of HBcAg. This was most intense and largely restricted to the degenerating hepatocytes, where both nuclear and cytoplasmic core antigen were detected (immuno-peroxidase stain for HBcAg, original magnification × 120).