Hepatitis B virus DNA in serum and liver is commonly found in chinese patients with chronic liver disease despite the presence of antibodies to HBsAg

Zhang, Yongyuan; Hansson, Bengt; Kuo, Lin Sheng; Widell, Anders; Nordenfelt, Erik

doi:10.1002/hep.1840170403

Cited by 104 publications

(75 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…16 In the human disease situation, circulating and integrated HBV-DNA sequences have been found in patients with serologically unidentified pathogenesis of HCC 13,15 and in the presence of hepatitis B surface antigen antibodies. 14,31 Low-level viremia persisted in all woodchucks investigated despite that 7 of them developed detectable anti-WHs, indicating that virus propagation progressed in the context of antivirus-specific humoral immunity. This observation is comparable with recent findings showing long-term persistence of HBV DNA in serum, and viral DNA and RNA sequences in PBMC of immune patients with a history of SLAH type B.…”

Section: Discussionmentioning

confidence: 99%

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

Michalak

Pardoe²,

Coffin³

et al. 1999

Hepatology

131

322

View full text Add to dashboard Cite

Traces of hepatitis B virus (HBV) genome can persist for years following recovery from hepatitis B. To determine overall duration, molecular characteristics, and pathological implications of this serologically undetectable form of hepadnaviral carriage, we have analyzed the expression of transcriptionally active virus genomes, their infectivity, and examined liver alterations during the natural lifespan of woodchucks convalescent from acute infection with HBVrelated woodchuck hepatitis virus (WHV). In this study, we document lifelong persistence of scanty amounts of replicating virus both in the liver and lymphatic system after spontaneous resolution of an episode of experimental hepadnaviral hepatitis. Antibodies to virus nucleocapsid (core) were found to be the most reliable immunovirological marker coexisting with occult infection. In the majority of convalescent woodchucks, serial liver biopsies showed protracted minimal to mild necroinflammation with periods of normal morphology; however, hepatocellular carcinoma (HCC) ultimately developed in 2 of 9 animals studied. Inocula derived from lymphoid cells of convalescent animals induced classical acute hepatitis in virus-naive woodchucks that progressed to chronic hepatitis and HCC in 1 of the animals, demonstrating infectivity and pathogenic competence of the carried virus. Our results reveal that low levels of infectious WHV and residual hepatic inflammation usually continue for life after resolution of hepatitis and that this recovery does not avert HCC development. They also demonstrate that, in addition to the liver, the lymphatic system is the site of the occult lifelong maintenance of replicating hepadnavirus. (HEPATOLOGY 1999;29:928-938.)Current evidence indicates that carriage of minute quantities of hepatitis B virus (HBV) genome can continue for years following complete clinical and serological recovery from acute hepatitis B. 1-5 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. 2 These findings imply that HBV eradication does not coincide with the rise of antivirusspecific humoral and cellular immune responses and with clinical resolution of acute hepatitis.It is expected that this serologically undetectable persistence of HBV may have important epidemiological and pathogenic implications, whose range has yet to be established. This assumption is based on a growing number of observations indicating that HBV infection can appear in recipients of organs from HBV serologically negative donors, [7][8][9][10][11][12] and that hepatocellular carcinoma (HCC) with integrated HBV genomic sequences can arise in ...

show abstract

Section: Discussionmentioning

confidence: 99%

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

Michalak

Pardoe²,

Coffin³

et al. 1999

Hepatology

131

322

View full text Add to dashboard Cite

show abstract

“…Indeed, HBV DNA may be found in 5% to 30% of the subjects with acute or chronic non-A, non-B hepatitis, [33][34][35][36] or in HBsAg carriers undergoing HBsAg clearance. 16 There could be various explanations of HBV DNA findings in HBsAg-negative sera.…”

Section: Discussionmentioning

confidence: 99%

Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis

et al. 1998

View full text Add to dashboard Cite

The incidence of delayed hepatitis B surface antigen (HBsAg) clearance in the natural history of chronic hepatitis B virus (HBV)-infected patients was low. Previous studies regarding the prognosis in such patients were controversial. Among 1,355 chronic carriers from 1985 to 1997, spontaneous HBsAg clearance was observed in 55 patients. During a mean follow-up period of 23 months, 18 (32.7%; all were male subjects) developed serious complications, including 11 with hepatocellular carcinoma (HCC) (9 of them underwent surgical resection), 6 with cirrhosis, and 1 with subfulminant liver failure. The overall cumulative probability of complications was 29.8% at 4 years, and it was higher in males (P ‫؍‬ .044) and patients aged 45 years or more (P ‫؍‬ .006); the latter carried an 8.6-fold increased risk (95% CI: 1.2-64.6; P ‫؍‬ .037) of adverse events. Histories of acute or chronic infection by hepatitis

show abstract

“…The diagnosis of HBV infection is usually based on the detection of hepatitis B surface antigen (HBsAg), and the disappearance of this antigen indicates the clearance of HBV (6). However, previous studies have shown that HBV DNA can be detected in patients with chronic liver disease who are negative for HBsAg but positive for antibodies to hepatitis B core antigen (anti-HBc) (1,12,21). More recently, this so-called occult HBV infection has frequently been identified in patients with chronic HCV infection (5,10,19), and in such patients this occult infection may be associated with more severe liver damage and even the development of hepatocellular carcinoma (HCC) (3,18,20).…”

mentioning

confidence: 99%

Occult Hepatitis B Virus Infection and Clinical Outcomes of Patients with Chronic Hepatitis C

et al. 2002

View full text Add to dashboard Cite

Although occult hepatitis B virus (HBV) infections in individuals without detectable hepatitis B surfaceantigen (HBsAg) may occur and have been reported to be common in patients with chronic hepatitis C, the clinical relevance remains controversial. We searched for serum HBV DNA in 210 HBsAg-negative patients with hepatitis C virus (HCV)-related liver disease (110 patients with chronic hepatitis, 50 patients with cirrhosis, and 50 patients with hepatocellular carcinoma) by PCR. Most of the patients had detectable antibodies to HBsAg or HBV core antigen. All of the 110 chronic hepatitis C patients were treated with a combination therapy consisting of interferon plus ribavirin. In addition, 100 HBsAg-negative healthy adults served as controls. Thirty-one of the 210 patients (14.8%) had HBV DNA in their sera, as did 15 of the 100 healthy controls (15%). HBV DNA was not detected in the sera of those negative for serological markers of HBV infection. In patients with chronic HCV infection, the prevalence of occult HBV infection did not parallel the severity of liver disease (14.5% in patients with chronic hepatitis, 8% in patients with liver cirrhosis, and 22% in patients with hepatocellular carcinoma). In addition, the sustained response to combination therapy against hepatitis C was comparable between patients with and without occult HBV infection (38 versus 39%). In conclusion, these data suggest that occult HBV infection does not have clinical significance in chronic hepatitis C patients residing in areas where HBV infection is endemic.Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for a substantial proportion of cases of chronic liver disease including chronic hepatitis, cirrhosis, and liver cancer. It is estimated that there are 350 million HBV carriers and 170 million HCV carriers worldwide (6). HBV and HCV are transmitted parenterally and share common routes of infection; thus, infection with both viruses may occur, particularly in areas where the two viruses are endemic and among people at high risk for parenteral infections (4, 15). The diagnosis of HBV infection is usually based on the detection of hepatitis B surface antigen (HBsAg), and the disappearance of this antigen indicates the clearance of HBV (6). However, previous studies have shown that HBV DNA can be detected in patients with chronic liver disease who are negative for HBsAg but positive for antibodies to hepatitis B core antigen (anti-HBc) (1, 12, 21). More recently, this so-called occult HBV infection has frequently been identified in patients with chronic HCV infection (5,10,19), and in such patients this occult infection may be associated with more severe liver damage and even the development of hepatocellular carcinoma (HCC) (3,18,20). In addition, several studies have suggested that occult HBV infection may correlate with a lack of response to interferon treatment in patients with chronic hepatitis C (3, 5, 22). Taken together, a low-level HBV infection not only may contribute to the severity of HCV-related liver d...

show abstract

Hepatitis B virus DNA in serum and liver is commonly found in chinese patients with chronic liver disease despite the presence of antibodies to HBsAg

Cited by 104 publications

References 38 publications

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

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

Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis

Occult Hepatitis B Virus Infection and Clinical Outcomes of Patients with Chronic Hepatitis C

Contact Info

Product

Resources

About