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 hepatitis B virus (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.