The threat of hepatitis B virus recurrence: A sword of damocles to the liver transplant recipient

Abstract

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanined by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in the native liver increased the risk of HBV induced tissue damage in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function. Four patients who underwent transplantation for hepatitis B virus-related liver disease developed rapidly progressive liver failure attributable to recurrent hepatitis B disease typified by hyperbilirubinemia and distinctive hepatocyte ballooning and progressive fibrosis consistent with recently reported fibrosing cholestatic hepatitis. Among these four patients, the mean interval from transplantation to redocumentation of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) was 5 months, to development of malaise and jaundice 6 months, to histological diagnosis 7 months, and to graft failure 8 months. the only patient who underwent retransplantation had accelerated recurrence of the same syndrome with biopsy documentation 1 month later and graft failure 2 months. Distinctive histological features included confluent hepatocelular balloning and progressive periportal fibrosis followed by lobular collapse over 4-6 weeks without significant inflammation. Immunohistochemical staining showed marked HBsAg and hepatitis B core antigen (HBcAg) immunoreactivity. The rapid development of cytolytic hepatocellular necrosis and lobular collapse with promient HBcAg immunoreactivity without significant inflammation suggests a cytolytic rather than immune pathogenesis for this unique and devastating form of recurrent hepatitis B that might better be termed “fibrosing cytolytic hepatitis”.