The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient

Abstract

Transmission of hepatitis B infection from hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core (anti-HBc)-positive liver donors has been previously described. The long-term outcome of these transplant-associated de novo hepatitis B patients has not been well described and may affect future use of donor organs that are anti-HBc-positive. We describe the experience in our first 332 transplants, performed before exclusion of anti-HBc-positive liver donors. Nine of these 332 (3%) donors were anti-HBc positive. Three of these 9 (33%) recipients developed transplant-associated de novo hepatitis B infections compared with only 2 of 323 (0.5%) recipients who received anti-HBc-negative donor livers (P = .00014). Of our 9 recipients of anti-HBc-positive livers, 6 (67%) are alive, and no deaths or allograft failures have been related to complications of hepatitis B. Only 1 of 5 patients (20%) with de novo hepatitis B has developed significant graft dysfunction with an average follow-up of more than 7 years (range 63-124 months). The 1 recipient with allograft dysfunction related to de novo hepatitis B has significantly elevated viremia levels (average HBV DNA 460 pg/mL) compared with the other de novo hepatitis B recipients (average HBV DNA 23-58 pg/mL). In summary, anti-HBc-positive donors are more likely to transmit hepatitis B infections to recipients, but these de novo infections usually have a mild clinical course and do not seem to adversely affect long-term patient survival. Hepatitis B-related allograft dysfunction, when it occurs, is associated with higher levels of viral replication. With our current donor shortage, perhaps anti-HBc-positive donors could be used in very selected recipient populations.

Severe clinical course of de novo hepatitis B infection after liver transplantation

“…Dickson et al 4 showed that 50% of infected patients had normal serum aminotransferase activities, and 85% had no or only mild inflammatory activity on liver biopsy. A relatively mild course was also noted in a series reported by Chazoulliéres et al, 6 Roche et al, 5 Douglas et al, 8 Liu et al, 13 Cavallari et al, 12 and Fabia et al 7 These data are in contrast to our experience. In this series, two clinical profiles were identified: (1) 4 patients developed de novo severe chronic hepatitis B, and histological follow-up suggests an accelerated natural history; and (2) 2 patients developed a fulminant hepatitis caused by de novo HBV infection.…”

“…[4][5][6][7][8][9][10][11][12][13][14]19 In our study, 6 HBsAg-negative patients of 136 liver transplant recipients (4.4%) who survived more than 3 months developed posttransplantation hepatitis B. The potential sources of HBV infection after OLT include liver and blood donors and hospital personnel; also, after OLT, intravenous drug abuse or sexual transmission can 6 With PCR technology, a possible source of viral infection was identified in another 2 patients.…”

“…[4][5][6][7][8][9][10][11][12][13][14] Most of the reports of de novo HBV hepatitis showed a picture of mild chronic hepatitis, with only mild inflammatory activity on liver biopsy. Dickson et al 4 showed that 50% of infected patients had normal serum aminotransferase activities, and 85% had no or only mild inflammatory activity on liver biopsy.…”

“…4,6 The outcome of patients with de novo or occult HBV infection is generally better than that of patients with HBV reinfection; however, a wide spectrum of HBV liver diseases is possible, ranging from asymptomatic chronic carriers to severe chronic active hepatitis or cirrhosis. [4][5][6][7][8][9][10][11][12][13][14] To our knowledge, acute liver failure related to de novo HBV infection has not been described.…”

Successful pregnancy in a liver transplant recipient treated with lamivudine for de novo hepatitis B in the graft

“…The potential sources of the infection include transfused blood products, occult donor-organ infection and occult pretransplant infection in the recipient. Blood products are occasionally able to transmit HBV despite negative serological testing [14] or past HBV infection [15,161, with an estimated risk for the latter of 33%-78% [17,18,19,201. In the present case two possible sources of HBV infection were identified: sexual transmission from the HBsAg-positive partner or occult transmission from the HBcAb-positive liver donor.…”