Hepatitis B virus DNA in asymptomatic HBsAg carriers: comparison with HBeAg/anti-HBe status

Sera of 17 HBeAg positive and 104 anti-HBe positive asymptomatic HBsAg carriers from two cohorts were tested for HBV DNA. HBV DNA was found in 13 of 17 HBeAg positive carriers (76.5%) and in only 7 of 104 of anti-HBe positive carriers (6.7%). Eleven of the 17 HBeAg positive carriers were retested for HBV DNA over a period of 7 to 36 months after the initial test. HBV DNA disappeared from the serum in 2 patients in spite of persistence of the HBe antigen. Of the 104 anti-HBe carriers, 89 were retested for HBV DNA over a period of 6 to 52 months after the initial test. HBV DNA disappeared from the serum in 5 of the 7 who were previously positive for HBV DNA, and persisted in 2. These findings indicate that there is an inconstant relationship between the time of seroconversion of HBeAg to anti-HBe and the disappearance of HBV DNA. In one HBeAg positive patient, HBV DNA, which was absent in the serum on first testing, was present on retesting. This suggests that the presence of HBV DNA in the serum of some patients may be intermittent. The presence of HBV DNA in the serum of some anti-HBe positive carriers accounts for the finding that they may be infective. All but one of the HBV DNA positive anti-HBe carriers were born outside North America, most in Asia. HBV DNA were found more frequently in the serum of anti-HBe positive carriers who had biochemical and histological evidence of liver disease than in carriers without such evidence.     

Hepatitis B virus infection among asymptomatic residents of low income community in Ibadan,Southwest, Nigeria

Introduction: Hepatitis B Virus (HBV) infection is one of the most infectious diseases worldwide and a major public health concern. In spite of efforts at controlling the scourge globally, HBV continues to thrive in developing countries, such as Nigeria due to ignorance on its mode of transmission and its asymptomatic nature in the populace. Therefore, this community-based study was carried out in Yemetu community in Ibadan, Nigeria to determine the burden of HBV infection among asymptomatic residents of this community.

Methodology: Blood samples were aseptically collected from consenting 150 participants, male (m = 49) and female (f = 101), age ranged 15–>55 years (Median age = 27.3 years). Astructured questionnaire was used to capture demographic data and other relevant information from these participants. Sera from these samples were tested for HBsAg using a 3rd generation Enzyme-Linked Immunosorbent-Assay (ELISA) Wantai HBV Diagnostics kit. Data were analyzed using Chi-square and ANOVA at 95% CI with P < 0.05 considered as significant.

Results: An overall seroprevalence rate for HBV in this study was 7.3%. HBV infection was higher among male (8.2%) than in female (6.7%), 1.4 times higher in male compared to their female counterparts (OR = 1.37, 95%CI 1.01–2.06) and also statistically significant (P = 0.043). Participants in the age groups 25–34 (10.3%) and >55 (4.2%) years had highest and lowest rates of HBV infection, respectively. Further analysis of the results by occupation shows that HBV infection was highest among Artisans (10.7%), followed by Students (6.9%) and Traders (6.9%) and lowest (5.6%) among Civil servants who are sexually active, married and unmarried. However, these differences were not statistically significant (P = 0.081).

Conclusion: This study reported relatively high prevalence for HBV infection among asymptomatic population, which is of public health importance and this calls for urgent attention. Therefore, public sensitization on HBV transmission and control for all through voluntary counseling and testing is advocated.     

High rate of Hepatitis B virus infection among hairdressers in Ibadan,Nigeria

Hepatitis B virus (HBV) infection is a major public health problem for over two billion people infected globally. Occupationally exposed persons are at high risk of HBV infection and, apart from medical personnel, there is dearth of information concerning the prevalence and awareness of HBV among this population in Nigeria. This study was designed to determine the levels of HBV awareness and prevalence of HBV infection among hairdressers in Ibadan, Nigeria. Hairdressers and teachers (unmatched controls) in four local government areas in Ibadan were tested for HBV infection using ELISA technique. Dried blood spot (DBS) samples were collected from 171 participants. DBS elutes from the samples were tested for HBV surface antigen (HBsAg). The rate of HBV infection was higher (p = 0.005) among the hairdressers (13.0%) than teachers (4.8%). However, teachers were better informed about HBV (38%) compared to hairdressers (13%; p = 0.0001). Differences in HBV awareness and occupation type were found to be significant (P = 0.001). Hairdressers are at high risk of HBV infection and may constitute a major source of HBV spread among urban dwellers, especially in areas where awareness is low. Routine HBV screening and appropriate interventions for hairdressers are recommended to interrupt HBV transmission.     

乙型肝炎病毒感染者血清抗-HBC/IgA检测及其临床意义

以抗人IgA包被反应板,建立血清抗-HBc/IgA ELISA方法,应用此方法对154例HBsAg阳性的HBV感染者进行检测,并对抗-HBc/IgA检测与患者肝组织损伤程度及与血清和组织内HBV标志之间的关系进行了探讨。     

Circulation of hepatitis B virus genotype-E among outpatients in tertiary hospitals in the Niger-Delta region of Nigeria

IntroductionHepatitis B virus (HBV) infection continues to be a significant public health challenge globally, with higher disease burden in developing countries. HBV genotypes are associated with different geographical regions and clinical outcomes. Limited information exists on epidemiology of HBV in the Niger-Delta region (South-South) of Nigeria. Consequently, this study was designed to characterise hepatitis B virus infection among outpatients in selected tertiary hospitals in the region.MethodologyBetween June and August 2017, consenting nine hundred asymptomatic out-patients were enrolled and initially screened for HBV infection using one step Hepatitis B surface antigen (HBsAg) strip and subsequently re-tested using HBsAg and Hepatitis B core total antibody (anti-HBc) specific Enzyme-Linked Immunosorbent Assay (ELISA). Blood serum with detectable HBsAg were subsequently subjected to DNA extraction, S-gene amplification using a nested polymerase chain reaction (PCR) protocol, gel electrophoresis, sequencing and phylogenetic analysis.ResultsSeroprevalence of HBsAg was 4.6% (95% CI 2.5–7.1) and anti-HBc was 10.1% (95% confidence interval (CI) 6.1–15.3). Of the 41 HBsAg positive samples subjected to DNA extraction and HBV S-gene specific PCR, only 6 (14.6%) yielded the expected ∼408bp band. Phylogenetic analysis based on HBV pre-S/S sequences identified all six typable samples as genotype E, subtype ayw4 of the West African clade.ConclusionResults of the study confirm the presence and circulation of HBV genotype-E in the Niger-Delta region of Nigeria, thus corroborating the inclusion of the country in the Genotype E crescent. The authors advocate value-added HBV intervention in the region and the country at large.     

Hepatitis B virus clearance from serum and liver after acute hepatitis delta virus superinfection in chronic HBsAg carriers

Clinical, virological, and histological findings in four HBsAg chronic carriers who cleared HBV markers from both serum and liver following HDV superinfection are described. The patients were long-term HBsAg carriers and all were HBV-DNA/HBeAg positive. Liver biopsy, obtained from three of the patients between 5 and 15 months prior to HDV superinfection, showed chronic persistent hepatitis in two and chronic active hepatitis in one. During the follow-up of 9-19 months, the patients completely recovered from acute delta hepatitis with termination of HBsAg carriage and regression of the histological feature of chronic liver damage. These data demonstrate that sometimes HDV is able to induce a permanent inhibition of its helper virus. HDV superinfection probably enhances the immune clearance of infected cells during the replicative phase of chronic HBV infection.     

A precore-defective mutant of hepatitis B virus associated with e antigen-negative chronic liver disease

The pathogenesis of chronic liver disease (CLD) due to persistent hepatitis B virus (HBV) infection has not been defined, but the disease activity is believed to correlate with the presence of hepatitis B e-antigen (HBeAg) antigenemia and high viremia. The molecular characterization of an HBV mutant isolated from an HBeAg-negative patient with severe CLD required amplification of the circulating HBV DNA (2 pg/ml) by the polymerase chain reaction (PCR). Direct sequencing of the nucleotides from five independent amplifications of the conserved precore region consistently revealed a G to A mutation in each of the two terminal codons of the precore region. Codon 28 was mutated from tryptophan-encoding TGG to a translational stop codon, TAG; codon 29 preceding the core initiation codon was changed from GGC to GAC. For biologic evaluation of these mutations on HBV replication and expression of HBeAg in vitro, HepG2 cells were transfected with cloned, recircularized mutant HBV DNA. The transfected cells contained subviral core particles in the cytoplasm and secreted mature HBV, without HBeAg, into the medium. The findings present the first evidence that complete HBV genomes can be amplified by PCR and are replication-competent in vitro. The data also indicate that HBeAg is not necessary for replication of HBV and furthermore suggest that HBeAg is not required for the progression of HBV-induced CLD.     

Hepatitis B virus DNA in sera of virus carriers positive exclusively for antibodies to the hepatitis B core antigen

The prevalence of serum HBV DNA in individuals positive for anti-HBc alone was determined by the polymerase chain reaction in two groups with endemic HBV infection from Canton (group A) and Hainan (group B), provinces of China. Twenty-one out of 294 individuals in group A (7.2%) and 193 out of 1995 in group B (9.7%) were positive for anti-HBc but negative for other markers of ongoing or past HBV infection (HBsAg and anti-HBs). HBV DNA was detected in 6/21 sera in group A (28.6%) and 68/193 in group B (35.2%) in their initial serum specimen. One of the six HBV-DNA-positive individuals in group A became negative after 6 months and four of the 58 positive in group B became negative at 4 years of follow-up. All of the individuals remained positive for anti-HBc and negative for anti-HBs, but one of them became positive for HBsAg on follow-up. None of the anti-HBc- and HBV-DNA-positive subjects had symptoms of liver diseases. They were, therefore, defined as chronic asymptomatic HBV carriers with undetectable HBsAg. This type of carrier should be added to the typical HBsAg-positive carrier, who constitutes about 10-15% of the general Chinese population, to give a more complete estimate of asymptomatic HBV carriers in China.     

Precision and stability of hepatitis B virus DNA levels in chronic surface antigen carriers

Quantitative determination of hepatitis B virus (HBV) DNA concentration is the most important measure for an estimation of the infectivity of an HBV positive health care worker and the basis for the decision whether he or she is allowed to perform exposure prone procedures. Thus questions are raised on how reliable quantitative HBV DNA assays are, and how stable is the HBV DNA concentration is in a healthy chronic HBV carrier. Therefore, in the present study two commercially available quantitative HBV DNA assays, the Amplicor HBV Monitor and the HBV Test Hybrid Capture II, and an "in house" quantitative HBV TaqMan PCR, analysing 101 sera of HBsAg positive patients for HBV DNA were compared. In addition, HBV DNA concentrations were followed in 14 healthy chronic carriers for up to 6 years. Despite a good overall correlation between the three tests considerable differences were found for the results of individual sera. Fifty-one percent of sera showed differences within one order of magnitude, 45% differed by a factor above 10 and 4% even by a factor of 100 and higher. The follow-up of the HBV DNA concentrations in 14 carriers showed in 7 carriers a rather stable course with variations within one order of magnitude, whereas in the other half the DNA concentrations fluctuated by factors between 10(2) and 10(6) over the observation period. Thus, viral load determinations in health care workers have to be interpreted with some caution, especially when they are the basis of far-reaching decisions.     

Patterns of serologic markers of hepatitis B virus infection and the risk of transmission among pregnant women in southwestern Nigeria

Hepatitis B virus (HBV) infection is a major health concern in developing countries that has a high morbidity and mortality rate. Vertical transmission of HBV from mother to child has been identified as a major factor leading to chronicity with attendant liver conditions, especially in poor socioeconomic settings. This study aims to evaluate the prevalence of serological HBV markers among pregnant women in Ibadan southwestern Nigeria and to determine the implications for perinatal HBV transmission. This study revealed the presence of varied HBV serological patterns of infection or immunity among pregnant women in Ibadan, Nigeria, and thus the risk of mother to child transmission.     

The effect of Hepatitis D co-infection on the immunologic and molecular profile of Hepatitis B in asymptomatic Chronic Hepatitis B patients in southwest Nigeria

ABSTRACT

Introduction: Hepatitis D infection causes severe form of viral hepatitis in humans and only affects those with hepatitis B either as a co-infection or superinfection. The aim of this study was to determine the prevalence of Hepatitis D and its effect on the immunologic and molecular profile of Hepatitis B among asymptomatic Chronic Hepatitis B patients in Abeokuta.

Methodology: A cross-sectional study of 99 chronic HBV patient who met the inclusion criteria. All the patients were tested for HBsAg, anti HCV, HDV antigen, anti HDV, HBsAg quantification, and HBV DNA quantification. Associations were tested for and P value less than 0.05 was considered significant.

Results: The participants included 53 (58%) male and 38 (42%) females with ages ranging from 18 to 69 (means 39 ± 11) years. Ten (11%) participants were positive for HDV-Ag while 1 (1.1%) was positive for anti-HDV. Five (5.5%) were positive for HIV 1 &2 while 1 (1.1%) was positive for anti HCV. HBV DNA quantification ranged from 15 to 17,000,000 IU/ml while HBsAg quantification ranged from 0.25 to45,520 IU/ml. There was no statistically significant relationship between HDV-Ag and age (p = .51), sex (p = .73), HBV DNA (p = .8) and HBsAg quantification (p = 1).

Conclusion: The prevalence of HDV-Ag among asymptomatic treatment naïve chronic hepatitis B patients in Abeokuta was 11% and there was no significant difference in the levels of HBV DNA and HBsAg among those with or without hepatitis D.     

Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients

Human hepatitis B virus (HBV) and hepatitis C virus (HCV) are two major etiologic agents of chronic hepatitis, which is closely related to the development of hepatocellular carcinoma (HCC). A possible involvement of HBV co-infection was investigated in ongoing HCV-related liver diseases in HCV-infected patients. A prevalence of anti-HBc in anti-HCV–positive/HBsAg-negative chronic hepatitis patients and a low copy number of HBV DNA were found in most of the liver biopsy samples of anti-HCV–positive/HBsAg-negative patients. The present data suggest that HBV co-infects frequently with HCV and may play an important role in the development of HCC in the anti-HCV–positive/HBsAg-negative patients with chronic hepatitis. J. Med. Virol. 54:249–255, 1998. © 1998 Wiley-Liss, Inc.     

Seroprevalence of hepatitis B surface antigenemia and viral infectivity among liver cancer patients accessing care at a tertiary health facility in Southwest Nigeria

Introduction: Hepatitis B virus (HBV) infection is a public health challenge globally, associated with hepatocellular carcinoma and known to be highly endemic in developing countries. Its comorbidity with cancer in infected patients poses greater challenge in their management. This study was therefore designed to determine the burden of HBV infection and its correlation among cancer patients assessing care in a tertiary health facility in southwest Nigeria.Methodology: A total of 122 plasma samples from consenting cancer patients were tested for Hepatitis B surface Antigen (HBsAg) using a commercial enzyme-linked immunosorbent (ELISA) assay and their plasma HBV DNA quantified by COBAS Amplicor HBV Monitor assay. Data were analyzed using SPSS version 21 and chi-square (χ2) test was used to determine association while p < 0.05 considered statistically significant. Results: An overall HBsAg rate of 13.9% was found among the study population. The distribution of HBsAg positivity among the subjects with condition of cancer showed 9(23.7%) with chronic liver disease (CLD), 4(10.8%) in primary liver carcinoma (PLCC) and 4(8.5%) with pyrexia of unknown origin (PUO). The CLD group had highest viral infectivity (Mean=8324.3 Copies/Ml) and lowest among those with PLCC (468.4 Copies/Ml). The rate for HBsAg was higher in male (14.7%) than in their female (13.0%) counterparts with significant statistical association by gender (p>0.0314) and peaked (23.5%) among age group 20-29 years.Conclusion: This study identified high rate of HBV infection among the population and could be investigated as a predictor for cancer. This finding is vital in the management of cancer patients coinfected with HBV.     

Evaluation of performance testing of different rapid diagnostic kits in comparison with EIAs to validate detection of hepatitis B virus among high risk group in Nigeria

Background: Hepatitis B virus (HBV) causes chronic liver-associated diseases and its early detection is of high public health importance. Its diagnosis is mainly based on immunological assays among which Enzyme-Linked Immunosorbent Assay (ELISA) and rapid tests are the most common and widespread methods. However, a major challenge is the discordance of results of any two laboratory assays which cannot be easily resolved. Therefore, this study was designed to evaluate the validity and reliability of commercially available five rapid test kits in comparison with two Enzyme Immunoassays (EIAs) in Nigeria using hepatitis B surface antigen as a reference marker.

Methods: A total of 100 sera of previously diagnosed consenting HBV-positive patients from private diagnostic laboratories in Ibadan between March and August, 2011 were tested using two EIA and five rapid commercially available HBV test kits in Nigeria. Data were analyzed by SPSS version 15, while bivariate and multivariate analyses were carried out to identify associations at P < 0.05 considered significant.

Results: Overall, the sensitivity rates of the two EIA kits were 100% and 99.9% (95% confidence interval [CI] = 98.9–99.7) with specificity of 100% and 99.9% (95% CI = 98.9–99.7), respectively. The sensitivity of the five rapid test kits ranged from 97.5% (95% CI = 96.4–97.6) to 98.9% (95% CI = 97.9–99.9) with specificity of 80% (95% CI = 79.3–80.9) to 90% (95% CI = 89.2–91.0). Also, the positive predictive value ranged from 88% (95% CI = 88.2–89.9) to 89% (95% CI = 88.2–89.9), while the negative predictive value ranged from 80% (95% CI = 79.3–80.9) to 90% (95% CI = 89.2–91.0) for the five rapid kits. However, that of the two EIAs ranged from 99.9% (98.9–99.7) to 100%. Further analysis showed significant (P = 0.033) variations in the sensitivity and specificity of the EIAs and rapid test kits.

Conclusions: The results from this study have clearly revealed the challenges of diagnosis of HBV infections in Nigeria. This study has also demonstrated that the sensitivity of most of the rapid test kits may not be adequate when compared with EIA for early detection of HBV infections. The implications of possible misdiagnosis on the various intervention strategies that rely predominantly on correct HBV status of an individual are enormous. Therefore, there is the need to further compliment the use of rapid test kits with EIAs for HBV control in Nigeria.     

血清HBV标志物阴性肝炎肝组织中HBV DNA表达的研究

目的 :研究HBVDNA在血清HBV标志阴性肝炎肝组织中的表达。方法 :对 4 5例HBV血清标志阴性肝炎患者 ,进行肝组织HBVDNA的原位杂交检测。结果 :原位杂交表明 ,HBVDNA阳性 7例 (阳性率 15 5 6 % ) ,阳性信号主要存在于肝细胞的胞核中 ,少数位于胞浆内 ;结论 :血清HBV标志阴性肝炎肝组织中可检出HBVDNA ,有利于提高对HBV感染的诊断     

Performance of HBsAg quantification assays for detection of Hepatitis B virus genotypes and diagnostic escape-variants in clinical samples

BackgroundThe impact of hepatitis B virus (HBV) genomic variability on the measurement of HBsAg level has been poorly evaluated.ObjectiveThis study was designed to compare the performance of all the available assays measuring HBsAg level in this setting.Study designA large selection of wild type HBV genotypes (n = 184) and HBsAg strains harboring mutations in the S gene (n = 81) from clinical samples was studied with three HBsAg quantification assays: Architect HBsAg (Abbott), LiaisonXL Murex HBsAg Quant (DiaSorin) and the Elecsys HBsAgII (Roche).ResultsThe overall percentage of positive results was 99.2% for Abbott, 98.9% for DiaSorin and 98.1% for Roche. Abbott and Roche assays provided an excellent concordance in HBsAg quantification (global mean bias of −0.006 logIU/mL). By contrast, DiaSorin underestimated HBsAg level with values 0.112 logIU/ml and 0.103 logIU/ml lower than Abbott and Roche, respectively. By contrast, DiaSorin slightly over quantified gtC (2.5% over the expected value) while Abbott provided values 6.2% lower than expected and 16.2% lower than what observed for the other genotypes. HBsAg quantitative assays were influenced by HBs protein substitutions irrespective to the genotype but no specific protein pattern that would particularly impair the quantification by one technique has been identified. However, Roche seemed to be particularly impacted by substitutions at 145 residue: 75% of under quantified samples carried a substituted 145 residue.ConclusionThis head-to-head comparison indicates a good correlation between all current systems used to quantify HBsAg but clearly shows an influence of both the genotype and the presence of “a” determinant variants in the absolute quantification of HBsAg. While these discrepancies may not translate into major clinical consequence, they may explain an absence of detection of weak concentration of HBsAg on some systems.     

Hepatitis B virus genotype G: prevalence and impact in patients co-infected with human immunodeficiency virus

Relatively little is known about the role of hepatitis B virus (HBV) genotype G (HBV/G) in patients co‐infected with human immunodeficiency virus (HIV) and HBV. This study examined the prevalence and association of HBV/G to liver fibrosis in co‐infected patients. HBV genotypes were determined by direct sequencing of the HBV surface gene or Trugene® HBV 1.0 assay in 133 patients infected with HIV/HBV. Quantitative testing of HBV‐DNA, HBeAg, and anti‐HBe were performed using the Versant® HBV 3.0 (for DNA) and the ADVIA®Centaur assay. The non‐invasive biomarkers Fib‐4 and APRI were used to assess fibrosis stage. Genotype A was present in 103/133 (77%) of the cohort, genotype G in 18/133 (14%) with genotypes D in 8/133, (6%), F 2/133 (1.5%), and H 2/133 (1.5%). Genotype G was associated with hepatitis B e antigen‐positivity and high HBV‐DNA levels. Additionally, HBV/G (OR 8.25, 95% CI 2.3–29.6, P = 0.0012) was associated with advanced fibrosis score using Fib‐4, whereas, being black was not (OR 0.19, 95% CI 0.05–0.07, P = 0.01). HBV/G in this population exhibited a different phenotype than expected for pure G genotypes raising the question of recombination or mixed infections. The frequent finding of HBV/G in co‐infected patients and its association with more advanced fibrosis, suggests that this genotype leads to more rapid liver disease progression. Further studies are needed to understand why this genotype occurs more frequently and what impact it has on liver disease progression in patients with HBV/HIV. J. Med. Virol. 83:1551–1558, 2011. © 2011 Wiley‐Liss, Inc.     

A review of the management of perforated duodenal ulcers at a tertiary hospital in south western Nigeria

Background

Gastro-duodenal perforations are common and may complicate peptic ulcer disease. Management is often by surgical closure.

Objective

To determine the patterns of presentation and mode of management of duodenal ulcer perforations.

Methods

Retrospective review of patients with duodenal ulcer perforations seen at the Obafemi Awolowo University Teaching Hospital between June 2001 and July 2011. Patients'' records were reviewed for demography, duration of disease, probable risk factors, type of surgery and complications. Data obtained was analyzed using SPSS 15.0.

Result

Forty- five patients were reviewed. There were 37 males (82.2%). Mean age was 39.7years (range 15–78years). There were 10 (22.6%) students and 8(17.8%) farmers. NSAIDs abuse (11), previous peptic ulcer disease (2), and no prior dyspeptic symptoms (20) constituted 24.4%, 4.4% and 44.4% respectively of cases. Seven (16%) patients presented less than 24 hours of onset of illness. Forty one perforations (91.1%) involved the first part of duodenum. Twenty two (49%) patients had Graham''s omental patch. We had one (2.2%) failed repair and six (13.3%) mortalities.

Conclusion

Late presentation of duodenal ulcer perforation is common with high mortality. Pragmatic surgical intervention with Graham''s omentopexy with broad spectrum antibiotics is still commonly practiced.     

Hepatitis B virus DNA in liver, serum, and peripheral blood mononuclear cells after the clearance of serum hepatitis B virus surface antigen

The integration of hepatitis B virus (HBV) DNA in the liver of chronic HBV carriers has been documented extensively. However, the status of the viral genome during acute infection has not been assessed conclusively. While HBV DNA sequences are detected often in serum, liver, and peripheral blood mononuclear cells (PBMCs) after the clearance of serum the hepatitis B virus surface antigen (HBsAg), the precise status of the viral genome, and in particular the possible persistence of integrated genomes in PBMCs, has not been established. A highly sensitive PCR-derived assay (Alu-PCR) was employed to re-examine liver and PBMC specimens obtained from patients with acute (n = 19) and chronic (n = 22) hepatitis in whom serum HBsAg was present (n = 12) (HBV-related chronic active hepatitis) or absent with anti-HCV (n = 10) (HCV-related chronic active hepatitis). Viral integration was demonstrated in 3 out of 19 liver specimens from patients with acute hepatitis and 12 out of 12 specimens from patients with chronic hepatitis. Viral integration was also observed in 4 out of 7 PBMC samples from HBV-related chronic active hepatitis patients and 2 out of 10 liver and PBMC samples from HCV-related chronic active hepatitis patients. In one liver specimen from an acute hepatitis patient, HBV DNA was found integrated in the intronic sequence of the tumour necrosis factor (TNF)-induced protein gene; viral integration into cellular sequences was also found in the PBMCs of four HBV-related chronic active hepatitis and two HCV-related chronic active hepatitis. The results demonstrate the early integration of HBV genome during acute viral infections and the persistence of the viral genome in an integrated form in PBMCs.