Significance of IgM antibody to hepatitis B core antigen in a Greek population with chronic hepatitis B virus infection

IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to persistent infection with hepatitis B virus (HBV). We studied 186 Greek HBsAg carriers for IgM anti-HBc and attempted to correlate it with other HBV and hepatitis delta virus (HDV) markers. Overall, IgM anti-HBc was detected more frequently than HBV DNA in this population (50% vs 34, p less than 0.001); this was also true for the 149 of the 186 HBsAg carriers with antibody to hepatitis B e antigen (anti-HBe) (48% vs 22%, p less than 0.001). The opposite was found in the carriers positive for hepatitis B e antigen (HBeAg): HBV DNA was observed in 93% and IgM anti-HBc in 64% of the cases (p less than 0.05). The detection of these markers was independent of sex. Serum alanine aminotransferase (ALT) levels were significantly more elevated in patients with positive tests for IgM anti-HBc and HBV DNA than in patients positive only for HBV DNA (p less than 0.001) irrespective of their HBeAg or anti-HBe status. Moreover, the detection of elevated ALT was independent of the intensity of the HBV DNA hybridization signal. Antibodies to hepatitis delta antigen (HDAg) were only found in 4 (2.4%) of 167 patients tested.     

Serologic markers of hepatitis B virus (HBV) and hepatitis D virus infection in carriers of hepatitis B surface antigen who are frequently exposed to HBV

Serum hepatitis B e antigen (HBeAg) and HBV DNA are indicators of active replication of HBV, whereas IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to chronic HBV infection. Fifty-eight carriers of hepatitis B surface antigen (HBsAg) who had frequent parenteral exposures were studied for the presence of HBeAg, HBV DNA, IgM anti-HBc and hepatitis delta virus (HDV) serologic markers. Active replication of HBV was detected in 36.2% (25% of drug addicts, 16.7% of thalassemia patients, and 46.9% of hemodialysis patients) and seropositivity for IgM anti-HBc in 55.2% of the HBsAg carriers. Among the 39 HBsAg carriers who were negative for HBeAg, IgM anti-HBc was detected significantly more frequently than HBV DNA (46.1% vs. 5.1%, p less than 0.001). Serologic evidence of HDV infection was detected in 35% of drug addicts, 50% of thalassemia patients and in 9.4% of hemodialysis patients. These data revealed that continued replication of HBV was more frequent in hemodialysis patients than in drug addicts and thalassemia patients who are HBsAg carriers and the opposite was true for the prevalence of HDV infection.     

Hepatitis B virus infection and hepatocellular carcinoma: correlation between IgM antibody to hepatitis B core antigen, hepatitis B e antigen, and hepatitis B DNA

Sera from 102 black patients with primary hepatocellular carcinoma (PHC) and hepatitis B surface antigenemia were tested for immunoglobulin M antibody against hepatitis B core (IgM anti-HBc), hepatitis B e antigen (HBeAg), and hepatitis B viral (HBV) DNA. Their prevalences were compared to those of a control group of 124 age and sex matched black HBV carriers without tumor. IgM anti-HBc was present in 68.6%, HBeAg in 32.3%, and HBV-DNA in 26.7% of the patients. In the control population, IgM anti-HBc was present in 45%, HBeAg was detected in 3.2%, and HBV-DNA in 25.8%. We conclude that IgM anti-HBc is present appreciably more often than either HBeAg or HBV-DNA in patients with PHC. HBeAg or IgM anti-HBc in serum of HBsAg positive carriers may predict an added risk of PHC development in South African blacks.     

Determination of hepatitis B virus DNA incidence, viral load, and mutations in blood donors with HBsAg and anti-HBs-negative serology and antibodies to hepatitis B core antigen

BACKGROUND: The aim of the present study was to determine hepatitis B virus DNA incidence, viral load, and mutations in blood donors with HBsAG and anti-HBs negative serology and antibodies to hepatitis B core antigen. METHODS: Blood samples were collected from 1000 blood donors with HBsAg-negative test results. Anti-HBc total screening was performed using the ELISA method. HBsAg-negative/anti-HBc total-positive samples were tested for anti-HBs, anti-HBc IgM, HBeAg, and anti-HBe. Samples with isolated anti-HBc were determined for viral load of HBV DNA using real-time PCR. RESULTS: Anti-HBc total was established as positive in 200 (20%) of the 1000 blood donors. While anti-HBs was negative in 59 (29.5%) of the 200 anti-HBc-positive samples, it was found to be positive in 141 (70.5%) of them. All of the other hepatitis B markers were negative in all of the anti-HBs-negative samples. HBV DNA was not detected in the sera of the isolated anti-HBc-positive blood donors with real-time PCR. CONCLUSION: Although we could not detect HBV DNA in the sera of the isolated anti-HBc-positive blood donors, findings in the literature suggest that anti-HBc testing should be used in combination with HBsAg for the screening of blood donors to reduce risk. After that, the most appropriate algorithm to follow can be HBV DNA screening of donors.     

Hepatitis B virus markers in the population of Dar es Salaam, Tanzania

A total of 542 serum samples from healthy adults (medical students and medical staff, blood donors and pregnant women) residing in or near the city of Dar es Salaam, Tanzania were examined for markers of hepatitis B virus (HBV) infection. Of these samples, 95 (17.5%) were not found to contain any HBV marker when examined by enzyme-linked immunoassay for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). HBsAg was demonstrated in 52 (9.6%) samples of which 7 (13.5%) were positive for hepatitis Be antigen (HBeAg) and 17 (32.7%) were positive for anti-HBc IgM. None of 9 HBsAg positive pregnant women were carriers of HBeAg. These results show that hepatitis B infection is very common in this country. The relatively low prevalence of HBeAg among HBsAg carriers may indicate that transmission of hepatitis B at birth is not of major importance.     

Occult hepatitis B virus infection as a cause of posttransfusion hepatitis in patients with cancers

Background

Prevalence of hepatitis B virus (HBV) infection is increased in patients of cancer with increased mortality. Multiple transfusions of blood and blood-related products are a potential source.

Aims

This study aims to assess the incidence of hepatitis B surface antigen (HBsAg) seroconversion in cancer patients receiving transfusion of blood or blood-related products and identify possible reasons for infection in these patients.

Material and Methods

Patients of cancer receiving blood products, who were HBsAg-, anti-hepatitis B core (HBc)-, and HBV DNA-negative prior to transfusion, were tested for HBsAg by ELISA at 6, 12, and 24 weeks after the last transfusion. Blood donors were screened for HBsAg by ELISA.

Results

Twenty of 3,600 (0.56 %) blood donors tested positive for HBsAg and were rejected. Nine of 150 (6 %) cancer patients became HBsAg-positive posttransfusion which included seven patients who presented with acute hepatitis B and other two patients who remained HBsAg-positive without hepatitis. In 6/9 (66.6 %) patients, HBsAg positivity was related to blood transfusion as their corresponding blood donors on retesting the stored samples were positive for anti-HBc antibody and HBV DNA. In other three patients, the cause of their HBsAg positivity could not be ascertained.

Conclusion

Occult HBV infection in blood donors is a potential source of posttransfusion HBV infection in recipients. Anti-HBc antibody and HBV DNA should be tested in blood donors especially when blood is given to cancer patients receiving chemotherapy.     

Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen

Several recent reports have shown that hepatitis B virus (HBV) could be frequently transmitted to the recipients from donors who have antibodies to hepatitis B core antigen (anti-HBc) through liver transplantation. We provide here the molecular evidence of latent HBV infection accompanied with ongoing viral replication in the liver tissue of anti-HBc-positive healthy individuals. HBV DNA was detectable in 13 of 14 healthy donors who were positive for both anti-HBc and antibodies to hepatitis B surface antigen (anti-HBs), but in none of 3 who were positive for anti-HBs alone. The detected HBV genomes from these subjects included covalently closed circular DNA and pregenomic RNA, the replication intermediate of HBV. Notably, 5 of 7 cases tested were predominantly infected with wild type HBV strains without any mutations in the precore and core promoter regions under the presence of circulating antibody to hepatitis B e antigen. Interestingly, a predominant clone detected in one donor showed a 63-nucleotide deletion in the precore region including an encapsidation signal sequence. Our findings indicate that the majority of healthy individuals positive for anti-HBc, which had been assumed to denote a past history of transient HBV infection, were latently infected with the episomal form of HBV accompanied by ongoing viral replication and few nucleotide mutations in the precore and core regions.     

Anti-HBc of IgM-class,HBeAg and anti-HBe in acute and chronic hepatitis B

ABSTRACT— The presence and persistence of IgM antibody against hepatitis B core antigen (anti-HBc IgM) and the correlation with other HBV markers were studied in 42 patients, all of whom had acute HBsAg-positive hepatitis but whose subsequent diseases differed. All patients initially had anti-HBc IgM. In 13 out of 15 patients with uncomplicated acute hepatitis, anti-HBc IgM disappeared within 6 months after onset of the disease. In five out of 12 patients, who in spite of transient HBsAg developed chronic liver disease, the anti-HBc IgM persisted for more than 2 years. Among 15 patients with persistent HBsAg, anti-HBc IgM was present from 7 months to more than 8 years. Seroconversion from HBeAg to anti-HBe was observed in seven patients and in five of these anti-HBc IgM disappeared during the follow-up period. These results indicate that anti-HBc IgM can be used as a serological marker of recent or ongoing HBV infection.     

Antibody to hepatitis B core antigen as a paradoxical marker for non-A, non-B hepatitis agents in donated blood

The relationship between the presence of antibody to hepatitis B core antigen (anti-HBc) in donor blood and the development of hepatitis in recipients of that blood was studied in 6293 blood donors and 481 recipients who were followed for 6 to 9 months after transfusion. Of 193 recipients of at least 1 unit of blood positive for anti-HBc, 23 (11.9%) developed non-A, non-B hepatitis compared with 12 (4.2%) of 288 recipients of only anti-HBc-negative blood (p less than 0.001). Donor anti-HBc status was not significantly associated with the development of hepatitis B in the recipient and was negatively associated with the development of cytomegalovirus hepatitis. The relationship of donor anti-HBc status and the development of non-A, non-B hepatitis in the recipient was independent of transfusion volume and elevated donor transaminase level. Although 88% of anti-HBc-positive blood units were not associated with recipient non-A, non-B hepatitis, calculation of maximal corrected efficacy predicted that exclusion of anti-HBc-positive donors might have prevented 43% of the cases of non-A, non-B hepatitis with a donor loss of 4%. Because of the serious chronic consequences of non-A, non-B hepatitis, surrogate tests for non-A, non-B virus carriers must be seriously considered.     

Update on occult hepatitis B virus infection

The event of mutations in the surface antigen gene of hepatitis B virus(HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core(anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection(OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction(PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for:(1) patients with a previous history of chronic or acute HBV infection;(2) patients co-infected with hepatitis C virus/human immunodeficiency virus;(3) patients undergoing chemotherapy or anti-CD20 therapy;(4) recipients of organ transplant;(5) blood donors;(6) organ transplant donors;(7) thalassemia and hemophilia patients;(8) health care workers;(9) patients with liver related disease(cryptogenic);(10) hemodialysis patients;(11) patients undergoing lamivudine or interferon therapy; and(12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.     

Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection

OBJECTIVES: In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, the clinical relevance of low viremia levels remains unclear. We evaluated the clinical significance of a single baseline serum HBV DNA measurement by a quantitative polymerase chain reaction (PCR) assay in this setting. METHODS: In total, 196 patients with HBeAg-negative chronic HBV infection (62 inactive carriers, 134 with chronic hepatitis B) were studied. ALT activity was normal at baseline in 25/134 HBeAg-negative chronic hepatitis B patients (18.7%), whereas it remained normal throughout follow-up in all inactive carriers. RESULTS: HBV DNA was <30,000 copies/ml in 14 (10.5%) and <100,000 copies/ml in 17 (12.9%) HBeAg-negative chronic hepatitis B patients, whereas it was <30,000 copies/ml in all inactive carriers (undetectable in 14). In particular, HBV DNA levels were <100,000 copies/ml in eight (32%) and <30,000 copies/ml in five (20%) of the 25 patients with HBeAg-negative chronic hepatitis B and normal baseline ALT values. HBV DNA levels with a cut-off at 30,000 or 100,000 copies/ml could correctly classify 92.9% or 91.3% of patients with HBeAg-negative chronic HBV infection, whereas ALT or IgM anti-HBc (IgM class antibody to HBV core antigen) index > 0.200 could correctly classify only 87.2% and 82.1% of patients, respectively. A combined HBV DNA and IgM anti-HBc index performed better by correctly classifying 94.4% of cases. CONCLUSIONS: Serum HBV DNA levels evaluated by sensitive quantitative PCR assays can be used for differentiation between HBeAg-negative chronic hepatitis B and inactive hepatitis B surface antigen carrier state, but the cut-off level should be set at approximately 30,000 copies/ml and certainly lower than the recently suggested level of 100,000 copies/ml.     

Changes in levels of hepatitis B virus markers in patients positive for low-titer hepatitis B surface antigen

Aim: Recently, patients positive for the low-titer hepatitis B surface antigen (HBsAg) have been found occasionally owing to the increase in the accuracy of detection methods. The aim of this study is to clarify the clinical status of acute hepatitis B virus (HBV) infection in patients positive for low-titer HBsAg. Method: Eight patients, who were positive for HBsAg at low titers and diagnosed as having acute HBV infection, were enrolled in this study. Assays of HBsAg, hepatitis B core antibody (anti-HBc), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), hepatitis B surface antibody (anti-HBs) and HBV DNA, and biochemical tests were basically conducted every 4 weeks for at least 24 weeks. Result: The average cut-off index of HBsAg was 8.7 ± 9.6 (range, 1.0–25.7). All the patients were negative for anti-HBc, HBeAg, anti-HBe and HBV DNA on their initial visit. The genotype of HBV could be determined in four patients: two were infected with genotype B/HBV, one was infected with genotype A/HBV, and the remaining patient was infected with genotype C/HBV. Although HBsAg clearance was observed within 4 months in all the patients, none of the other HBV markers seroconverted during the observation period. Conclusion: HBV infection terminating with seronegativity for HBV markers may occur in transient HBV infection.     

Lack of occult hepatitis B virus infection among blood donors with isolated hepatitis B core antibody living in an HBV low prevalence region of Iran

BackgroundOccult hepatitis B virus (HBV) infection in blood donors is considered a potential threat for the safety of the blood supply, however conclusive studies on this issue are lacking. The aim of this study was to assess the occult HBV infection in blood donors with isolated hepatitis B core antibody (anti-HBc) living in the city of Arak, in the Central Province of Iran, as a low prevalence region for HBV.MethodsA total of 531 voluntary blood donors in Arak, Iran were included in this study. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), anti-HBc, and hepatitis C antibody (anti-HCV) were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of cases with isolated anti-HBc (HBsAg-negative, anti-HBs-negative, and anti-HBc-positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler.ResultsOf 531 subjects enrolled in this study, 11 (2.1%, 95% confidence interval 0.8–3.2%) had isolated anti-HBc. HBV-DNA was not detected in any of the cases with isolated anti-HBc.ConclusionsOur study showed that all the blood donors with isolated anti-HBc were negative for HBV-DNA, and occult HBV infection did not occur in the blood donors of this low prevalence region for HBV infection.     

Evidence that anti-HBc but not HBV DNA testing may prevent some HBV transmission by transfusion

Blood donor screening for antibody to hepatitis B core antigen (anti-HBc) implemented in some countries as a surrogate marker for non-A, non-B hepatitis has been superseded by anti-HCV screening. To assess the value of anti-HBc screening for the detection of hepatitis B surface antigen-negative blood donations that might contain infectious HBV, HBV genomic detection and recipient testing were used. Blood donations were screened and confirmed by multiple anti-HBc assays. Donations containing isolated anti-HBc and those with anti-hepatitis B surface antigen (anti-HBs) level < 0.1 IU/ml were tested for the presence of HBV DNA. Recipients of previous donations from the corresponding donors during the previous 5 years were traced and tested for markers of HBV infection. Of 103 869 donations screened, 586 (0.56%) were anti-HBc positive, two of which contained HBsAg, and 413 (0.4%) had protective (>/= 0.1 IU/ml) levels of anti-HBs. Anti-HBs < 0.1 IU/ml was found in 102 of these donations (0.1%) and isolated anti-HBc in 69 (0.07%). No donations with isolated anti-HBc were HBV DNA confirmed positive. Of 278 recipients of previous donations from 171 donors at risk of HBV carriage, 12 had markers of HBV infection. Six recipients had other identified risk factors. An association with blood transfusion was considered probable in two and possible in four recipients. None of the six corresponding donors had detectable HBV DNA 6-40 months after the implicated donation. The frequency of HBV transmission by chronic carriers negative for hepatitis B surface antigen was estimated in this study to be 1 in 52,000 donations (CI 0.3-7.8/100,000) from HBsAg-negative donors. Such HBV infectious donations may not be detected by DNA amplification.     

Reactivation of hepatitis B virus in anti-HBe-positive chronic active type B hepatitis: molecular and immunohistochemical studies

The causes of acute clinical exacerbations, and the role of reactivation of hepatitis B virus (HBV) in 16 non-cirrhotic patients with chronic active type B hepatitis (CAH-B) negative for serum hepatitis B e antigen (HBeAg) but positive for anti-HBE, were studied by molecular hybridization and immunohistochemical methods. IgM antibody to hepatitis A virus (anti-HAV IgM) and antibody to delta agent (anti-delta) were negative in all. HBeAg reappeared transiently in only two patients. Serum hepatitis B virus (HBV) DNA levels increased during acute exacerbations in 14 patients (88%), and decreased after the episode. Cytoplasmic hepatitis B core antigen (HBcAg) expression was found in 9 out of 13 patients (69%) during acute exacerbation. By Southern blot hybridization, 5 of 6 (83%) liver tissues obtained during clinical exacerbations had free replicative forms of HBV DNA. In 20 control patients with no exacerbation, serum HBV DNA, HBcAg expression in hepatocytes and free replicative forms of HBV DNA were positive in 15% (3/20), 10% (2/20) and 25% (2/8), respectively--figures significantly lower than those of the group studied. We conclude that acute exacerbations sometimes seen in patients with anti-HBe-positive CAH-B in Taiwan are caused mainly by reactivation of HBV.     

Low rate of occult hepatitis B virus infection among anti-HBc positive blood donors living in a low prevalence region in Brazil

OBJECTIVE: The aim of this study was to determine the rate of occult hepatitis B virus (HBV) infection among blood donors living in a geographic region of low (5.6%) anti-HBc prevalence. SUBJECTS AND METHODS: Sera from 150 candidate blood donors whose blood was rejected due to total anti-HBc reactivity (despite absence of HBsAg) were tested for anti-HBs and IgM anti-HBc antibodies, as well as for HBeAg/anti-HBe. Serum HBV DNA was sought by using a PCR assay able to amplify part of the surface gene. Viral load was measured in the PCR positive samples. RESULTS: The pattern 'anti-HBc alone' (without HBsAg and anti-HBs antibodies) was found in 64 (42.7%) subjects. IgM anti-HBc and anti-HBe antibodies were detected in 2 (1.3%) and 80 (53.3%) samples, respectively. No sample was HBeAg-reactive. HBV DNA was repeatedly found in five (3.3%) samples, three of which were anti-HBs positive and two anti-HBs negative. All five HBV DNA positive samples showed a low viral load (<1000copies/ml). CONCLUSIONS: The data indicated a low rate of occult infection among anti-HBc positive, HBsAg negative blood donors living in a region of low prevalence of infection. Viral load was very low in all HBV infected subjects.     

Replication of hepatitis B virus in adult carriers in an endemic area

We have examined serological markers of replicative and nonreplicative infection in 124 adult, black South African carriers of hepatitis B virus (HBV), in whom this infection is predominantly acquired in early childhood. The mean age of the group was 36 years. Antibody to hepatitis B e antigen (anti-HBe) was present in the serum of 93.5% of these carriers. Only 25.8% of the carriers were positive for HBV DNA in serum, and in the majority of these only trace amounts were detectable. IgM antibody to hepatitis B core antigen (IgM anti-HBc) was negative in 54% of the carriers, and only 26% had IgM anti-HBc in high titer. A significantly greater proportion of carriers who were positive for anti-HBe were positive for IgM anti-HBc (43.1%) than were positive for HBV DNA (24.5%). Serum aminotransferases were less than twofold elevated in 90.3% of the carriers. Only one carrier has thus far developed hepatocellular carcinoma. These results suggest that there is an inexorable progression to predominantly nonreplicative infection in the majority of southern African adult, black carriers, an occurrence that may take several decades. In areas endemic for HBV infection, antiviral agents effective against replicative HBV will have to be administered in childhood.     

Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core antibody and HBV DNA in monitoring the response to treatment in patients with chronic hepatitis B

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-α (IFN-α). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-α2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.     

A case of HBs antigen negative fulminant hepatitis with IgM antibody to hepatitis B core antigen persisting more than seven years

A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver.