Despite advances in treatment of chronic hepatitis B virus (HBV) infection, liver transplantation remains the only hope for many patients with end-stage liver disease due to HBV. In a study of the natural history of HBV-related cirrhosis in the pre-nucleos(t)ide analogue era, the five-year survival was 71 percent for the entire group of patients, but only 14 percent for those with decompensated disease (figure 1) .
The initial results with liver transplantation for chronic hepatitis B in the 1980s were disappointing, with graft reinfection rates approaching 80 to 100 percent [2-4]. In many patients, reinfection was associated with severe and rapidly progressive liver disease, resulting in two-year graft and patient survival of 50 percent compared to 80 percent in those transplanted for other types of chronic liver disease . With these poor results and limited supply of donor organs, many centers and third party payers abandoned liver transplantation for patients with chronic hepatitis B .
Since the late 1980s, the introduction of effective measures to prevent and treat reinfection using strategies involving hepatitis B immune globulin (HBIG) and subsequently nucleos(t)ide analogues have significantly improved the outcome of liver transplantation [7-10]. The overall survival of patients transplanted for HBV-related cirrhosis now exceeds 85 percent at one year and 75 percent at five years [7,10-13]. Furthermore, rates of transplantation for HBV-related end-stage liver disease have dropped substantially, with a 47 percent decrease in liver transplantation waiting list registrations between 1999 and 2006 .
HBV REINFECTION AFTER LIVER TRANSPLANTATION
The high rate of HBV reinfection after liver transplantation is probably due to enhanced virus replication resulting from immunosuppression and direct stimulatory effects of steroid therapy on the glucocorticoid-responsive enhancer region of the HBV genome [15,16]. Extra-hepatic reservoirs of HBV, such as peripheral blood mononuclear cells, spleen, and other organs, may also contribute to graft reinfection .
Risk factors for reinfection — Patients with HBV-related cirrhosis who are eligible for transplantation can be conceptually divided into those with high versus low risk of reinfection.