Resolution of acute hepatitis B virus (HBV) infection re-Adoptive immunity transfer has been reported to be quires adequate B-and T-cell responses, which lead to the effective in clearing chronic hepatitis B virus (HBV) inproduction of protective antibodies, as well as a broad-based fection. Two hundred twenty-six patients who received T-cell response against multiple HBV antigenic determinants allogeneic bone marrow transplantation (BMT) between located on the viral envelope, nucleocapsid, and polymerase May 1990 and September 1995 were screened for hepatigene products. 6 Similar responses have been found in chronitis B markers. Twenty-one patients were hepatitis B surcally infected patients during spontaneous or interferon-inface antigen (HBsAg) positive before BMT. The median duced HBeAg seroconversion, but the cytotoxic T lymphocyte follow-up period was 20 months (range, 2-59 months). response is absent or weak in other chronically infected pa-Two of these patients had sustained clearance of HBV tients. 7 infection after transplantation. Both patients were hep-Recently, it has been shown that adoptive transfer of imatitis B e antigen (HBeAg)-negative, hepatitis B e antimunity to HBV can be accomplished by bone marrow transbody (anti-HBe)-positive, and serum HBV DNA-negaplantation (BMT) from donors who are immune because of tive (by dot-blot hybridization) before BMT. Both had past infection or active immunization. 8-11 Furthermore, cleara flare in the serum alanine transaminase (ALT) level
ance of chronic HBV infection has been reported after BMT around the time of HBsAg clearance. Sustained clearfrom immune donors, possibly through the transfer of both ance of HBsAg was observed in 2 of the 5 patients who humoral and cellular immunity. 12,13 This has led to the sugreceived hepatitis B surface antibody (anti-HBs)-posigestion that adoptive immunity transfer may be employed to tive marrow but in none of the 16 patients who received treat chronic HBV infection. However, it is not clear how anti-HBs-negative marrow (P Γ΅ .05). One additional pafrequent clearance of chronic HBV infection occurs after BMT tient who received anti-HBs-positive marrow had tranfrom immune donors. In addition, there is concern that sucsient HBsAg seroconversion. Among the 18 patients who cessful transfer of the cytotoxic T lymphocyte response may remained persistently HBsAg-positive after BMT, 3 had lead to massive lysis of infected hepatocytes, resulting in HBeAg seroconversion and 3 had reversion to HBeAg acute liver failure. 8 Clearly, the major obstacle to the use of positivity. In this study, we found a significant associaadoptive immunity transfer as a treatment for chronic HBV tion between clearance of HBV infection and anti-HBsinfection is the high morbidity and mortality associated with positive bone marrow donors. Adoptive immunity trans-BMT. The aim of this study was to determine the serological fer is effective in clearing HBV from patients with and clinical outcome of HBsAg-positive BMT recipients in chronic HBV infection. (HEPATOLOGY 1997;25:1497-1501.) relation to the HBV status (carrier/immune/seronegative) of the donors. Chronic hepatitis B infection is a serious global health problem affecting approximately 300 million individuals. Of
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these, many will die of cirrhosis or hepatocellular carcinoma.