Persistent viremia after recovery from self-limited acute hepatitis B

Abstract

To define the duration of viremia in the course of acute hepatitis B, we semiquantitatively determined the levels of hepatitis B virus (HBV) DNA in the sera, using polymerase chain reaction (PCR) coupled with Southern blotting, of non-immunocompromised patients with self-limited acute hepatitis B. In the sera of 10 of 11 patients, HBV DNA, which was presumably coated with viral proteins, was detected for a long period after recovery, even at the final observation times, which ranged from 6 to 19 months after disease onset. To characterize the mode of HBV that was present in serum, we immunoprecipitated immune complexes in sera by the addition of anti-human immunoglobulin G (IgG) and determined the levels of HBV DNA separately in the supernatants and pellets. In the acute phase of hepatitis B, high levels of HBV DNA were detected both in the supernatants and pellets at comparative levels. After the convalescent phase, the amount of HBV DNA in the supernatant decreased with respect to that in the pellets. It is notable that, in most cases, serum HBV persisted as a form of immune complex even after the seroconversion to antibody to hepatitis B surface antigen (anti-HBs). These data suggest that the replication of HBV may persist in some organs, most likely in the liver or peripheral blood cells, for a long period after recovery from acute hepatitis B, and the data indicate the possible transmission of HBV from organ transplantation donors who exhibit serological markers of past infection only. (HEPATOLOGY 1998;27:1377-1382.)The duration of viremia in acute hepatitis B has been considered to cease with the clearance of the hepatitis B surface antigen (HBsAg) from serum. 1,2 However, in view of the fact that viremia in chronic hepatitis B persists after the disappearance from serum of HBsAg and the appearance of an antibody to HBsAg (anti-HBs), both of which occur in the natural course of the disease and during interferon therapy, [3][4][5][6][7][8][9] the duration of viremia in acute hepatitis B must be determined using sensitive methods to prevent the transmission of hepatitis B upon transfusion of HBsAg-negative blood [10][11][12] from patients who are recovering from acute hepatitis. Indeed, a recent study using polymerase chain reaction (PCR) has shown that hepatitis B virus (HBV) persists even in serological recovery from acute hepatitis B. 13 It is also important to determine whether HBV exists in a free or immunoglobulin (Ig)-bound form if HBV persists in serum. The extent of viremia and the modality of the virus during and after the course of acute hepatitis B, however, have not been well described. In the present study, we semiquantitatively measured the level of HBV DNA in the sera of patients in Japan, where acute hepatitis B rarely evolves into chronic infection. 14,15 PATIENTS AND METHODSPatients. We studied 11 consecutive Japanese patients (male: female ϭ 10:1) with self-limited acute hepatitis B who were admitted to our hospitals from 1991 to 1995 (Table 1). All 11 patients exhibited single-peaked ele...

Molecular characterization of occult hepatitis B virus in genotype E-infected subjects

“…The presence of anti-HBs suggests recovery from an acute infection, although the simultaneous presence of HBV DNA suggests persistence of the virus, as described previously (Rehermann et al, 1996;Yotsuyanagi et al, 1998). In contrast, individuals carrying anti-HBc only can be either chronic carriers at the tail end of carriage, where HBsAg levels are below the limit of sensitivity of screening assays, or individuals who have recovered from the infection, but no longer carry detectable anti-HBs, an antibody with considerable shorter longevity than antiHBc (Allain, 2004).…”

Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus

“…Recently, it has been shown that in persons who recover from acute hepatitis B and do not become chronically infected, HBV DNA can be found in as many as 50% years after resolution of the infection, suggesting that HBV, like other DNA viruses, may persist at low levels indefinitely. 25,26 The clinical outcome after clearance of HBsAg is generally much better than in persons who continue to be HBsAg-positive. Liver inflammation and fibrosis has been found to improve over time.…”

Occult lifelong persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis

“…[1][2][3][4][5] In these convalescent patients, HBV DNA have been detected both in serum and in circulating lymphomononuclear cells, often despite the presence of neutralizing antibodies to virus envelope (hepatitis B surface antigen) 2,3,5 and a vigorous polyclonal HBV-specific cytotoxic T-cell response. 3,4,6 In addition, traces of hepatitis B surface antigen and HBV-DNA-reactive particles with physicochemical properties of intact virions have been detected in the circulation of some of the recovered individuals.…”