Isolated serum hepatitis B core antibody seropositivity: A diagnostic risk factor for occult hepatitis B infection

Anti‐HBc screening and nucleic acid testing for hepatitis B viral DNA (HBV DNA) detection in blood donors are not routinely performed in clinical settings in Nigeria. This raises serious concerns for safety of blood at a time that global health standards advocate for transfusion safety. The aim of this research is to investigate if presence of anti‐HBc in blood donors is actually associated with occult hepatitis B infection through basic and advanced procedures. Prospective blood donors who were seronegative for HBsAg but sero‐positive for anti‐HBc (with or without other markers) among the four hundred and seventy enrolled in a cross‐sectional study were selected for this study. Samples were further screened for hepatitis B core immunoglobulin M by enzyme‐linked immunosorbent assay. Nucleic acid testing was performed for confirmation of occult hepatitis B infection. Anti‐HBc was detected in 20 (32.8%) of the sixty‐one HBsAg antigen‐negative blood donors which constituted 13.0% of the total number of enrolled blood donors. Anti‐HBc total‐positive differentiation showed eighteen (90.0%) anti‐HBc (IgG) and two (10%) anti‐HBc (IgM) were detected. Nucleic acid testing showed 5.0% prevalence of occult hepatitis B infection among the anti‐HBc‐positive blood donors with estimated HBV DNA viral load of 58 IU/ml. Demonstration of 5.0% occult hepatitis B prevalence showed the possibility of post‐transfusion hepatitis B infection in transfusion recipients with consequent possible liver damage should hepatitis B surface antigen alone be the continued practice in clinical settings. The inclusion of antibody to hepatitis B core antigen screening in addition to hepatitis B surface antigen marker is an essential step to ensuring optimal blood safety and prevent post‐transfusion hepatitis.     

Molecular characterization of occult hepatitis B cases in Greek blood donors

The use of sensitive nucleic acid testing for hepatitis B virus in blood donors revealed a number of HBV DNA(+) cases among HBsAg(?) donors, a status known as occult HBV infection. The purpose of this study was the serological and molecular characterization of occult HBV infection in Greek blood donors. A prospective study was undertaken in order to identify occult HBV infection cases in blood donors. As part of the routine screening of blood donations in Greece, blood units were screened individually by a multiplex HIV‐1/HCV/HBV nucleic acid assay. Initially reactive samples were retested with discriminatory assays. HBV DNA(+)/HBsAg(?) samples were tested further for HBV serological markers and HBV DNA was quantified by real‐time PCR. Molecular characterization was performed by sequencing the envelope and polymerase genes of HBV. Preliminary screening revealed 21 occult cases with the following patterns: anti‐HBc only: 7 donors, anti‐HBc/anti‐HBs: 7 donors, anti‐HBc/anti‐HBe: 5 donors, anti‐HBc/anti‐HBs/anti‐HBe: 2 donors. In all cases, the HBV DNA load was <351 IU/ml. Sequencing was successful in 10 donors (classified within genotype D) revealing several amino acid substitutions related to diagnostic escape and antiviral resistance. HBsAg diagnostic failure and low viral replication in occult HBV infection carriers could possibly be attributed to multiple changes in envelope and polymerase regions, respectively. J. Med. Virol. 81:815–825, 2009. © 2009 Wiley‐Liss, Inc.     

Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin

The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real‐time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg‐IFNα and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti‐HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non‐responder. Furthermore, in this cohort composed of 12% anti‐HBs negative/anti‐HBc positive and 20% anti‐HBs positive/anti‐HBc positive patients, anti‐HBc was not associated with pre‐therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real‐time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti‐HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment. J. Med. Virol. 82: 000–000, 2010. © 2010 Wiley‐Liss, Inc. J. Med. Virol. 82: 747–754, 2010. © 2010 Wiley‐Liss, Inc.     

奉贤地区HBsAg阴性的HBV自然感染母亲对新生儿影响的研究

目的　为揭示HBsAg阴性的乙型肝炎病毒 (HBV)自然感染孕妇的宫内感染及其危险因素。方法　采用多聚酶链反应 (PCR)技术结合酶联免疫吸附法 (ELISA) ,对奉贤地区 131例HBsAg阴性的HBV自然感染孕妇外周血 ,及其分娩后的脐带血进行HBV血清学标志物 (HBVM)和HBVDNA检测。结果　HBsAg阴性的HBV自然感染孕妇宫内的感染率 (除外单一抗 -HBs阳性 )为 5 2 6 7% ;脐血中不同HBVM组合的HBVDNA检出率依次为 :抗 -HBe( )、抗 -HBc( ) >抗 -HBs( )、抗 -HBe( )、抗 -HBc( ) >抗 -HBs( )、抗 -HBe( ) >抗 -HBs( )、抗 -HBc( ) >抗 -HBs( ) ;脐血HBVDNA总检出率为 16 79%。结论　HBsAg阴性的HBV自然感染孕妇也可能发生宫内感染。提议HBsAg阴性的HBV自然感染孕妇和新生儿有进行自动和被动免疫接种的必要性     

Occult hepatitis B in persons infected with HIV is associated with low CD4 counts and resolves during antiretroviral therapy

Occult hepatitis B virus (HBV) is defined by the presence of plasma HBV DNA in individuals with HBV core antibodies (anti‐HBc), but without HBV surface antigen (HBsAg). The prevalence of occult HBV in HIV‐infected patients remains controversial, and the risk factors, clinical significance and effect of highly active antiretroviral therapy (HAART) are unknown. The aim of this study was to determine prevalence, risk factors, and clinical significance of occult HBV in HIV‐infected patients and to evaluate the effect of HAART. Plasma HBV DNA levels were determined in 191 HIV positive, antiretroviral naïve patients, who were anti‐HBc positive and HBsAg negative. Quantitative HBV DNA was determined using a Taqman real‐time nested PCR. Additionally, plasma HIV RNA levels, CD4 cell counts, anti‐HBs‐antibodies, anti‐HCV‐antibodies, ALT, AST, and γGT were determined. Occult HBV (a plasma HBV DNA level >50 copies/ml) was detected in 9/191 (4.7%) of the patients. Among 45 anti‐HBs‐negative patients (isolated anti‐HBc positive), the prevalence was 11.1%. Patients with occult HBV had significantly lower CD4 count compared to anti‐HBc‐positive/HBsAg negative/HBV DNA‐negative patients (105 ± 157 (median ± SD) vs. 323 ± 299 cells/mm³, P = 0.019). When HAART (including lamivudine) was initiated in the patients with occult HBV, HBV DNA was no longer detectable in any of the patients during 3 years of follow‐up. In conclusion, occult HBV was associated with low CD4 counts and may be viewed as opportunistic reactivation of HBV that resolves as a consequence of HAART induced immune reconstitution and/or the effect of lamivudine. J. Med. Virol. 81:441–445, 2009. © 2009 Wiley‐Liss, Inc.     

Increased detection of HBV DNA in HBsAg‐positive and HBsAg‐negative South African HIV/AIDS patients enrolling for highly active antiretroviral therapy at a Tertiary Hospital

This retrospective study investigated the prevalence of hepatitis B virus (HBV) in 192 stored sera from human immunodeficiency virus (HIV) positive South African patients initiating antiretroviral therapy (ART), and explored the implications of HBV–HIV co‐infection on laboratory diagnosis of HBV. HBV serology (HBsAg, anti‐HBs and anti‐HBc) and nested HBV PCR assays targeting the HBV polymerase gene were performed, with HBV DNA positive samples being quantified with Cobas Taqman HBV test 48 assay (Roche Diagnostics). The study found that 63% (121/192) of patients had past or present HBV infection, and 40.6% (78/192) had detectable HBV DNA. Also, 22.9% (44/192) of patients were HBsAg positive and HBV DNA positive, while 23% (34/148) of HBsAG negatives had occult HBV infections. Of the 78 HBV DNA positive samples, 62.8% had viral loads ranging from 10² to ≥10⁸ IU/ml, and 37.2% had HBV viral loads <200 IU/ml. There was a statistically significant positive association between HBsAg‐positivity and high viral loads, with 27% (12/44) of HBsAg positives having HBV viral loads between 10⁴ and ≥10⁸ IU/ml, compared to only 5.9% (2/34) of HBsAg negatives (relative risk: 4.64; 95% confidence interval: 1.11, 19.35; chi‐square P‐value = 0.015). The study shows that the majority of HIV/AIDS patients initiating ART have either acute or chronic HBV infections, and further confirms that HIV remains a risk factor for occult HBV infections in South African patients as previously shown. The findings strongly support HBV screening in all HIV‐positive patients initiating ART in South Africa, considering that current ART regimens include drugs with anti‐HBV activity (e.g., lamivudine). J. Med. Virol. 81:406–412, 2009. © 2009 Wiley‐Liss, Inc.     

Prevalence of hepatitis B virus and risk factors in Brazilian non‐injecting drug users

Non‐injecting drug users are at high‐risk for acquiring hepatitis B virus (HBV), although the factors contributing to this increased risk are not known. In the present study, the overall and occult HBV infection prevalence rates were determined in a large population of non‐injecting drug users in the Central‐West region of Brazil. HBV genotypes and predictors of infection were also identified. A total of 852 individuals in 34 drug treatment centers were interviewed, and their serum samples were tested for the presence of HBV markers by ELISA. HBsAg and anti‐HBc‐positive samples were tested for HBV DNA by PCR. Samples with HBV DNA were genotyped by restriction fragment length polymorphism (RFLP). The overall prevalence of HBV infection was 14% (95% CI: 11.7–16.5). A multivariate analysis of risk factors showed that age >30 years, non‐white race/ethnicity, duration of drug use >10 years, lifetime number of sexual partners >10, non‐use of condoms, and HCV and HIV status were associated significantly with HBV infection. Of the 9 (1%) HBsAg‐reactive samples, HBV DNA was present in 2/2 of HBeAg‐positive and in 5/7 anti‐HBe‐positive samples. An occult HBV infection rate of 2.7% (3/110) was found among anti‐HBc‐positive individuals. All HBV DNA‐positive samples were genotyped: seven were genotype A, two were genotype D, and one was genotype F. Finally, few individuals (8%) had serological evidence of a previous HBV vaccination. These findings indicate that preventive interventions are needed for both sexual and drug‐related high‐risk behavior. Additionally, non‐injecting drug users should be targeted for HBV vaccination. J. Med. Virol. 81:602–609, 2009 © 2009 Wiley‐Liss, Inc.     

Occult hepatitis B in the genotype H‐infected Nahuas and Huichol native Mexican population

Mexico is considered to be a low endemic country for HBV infection. However, a high anti‐HBc against a low hepatitis B surface antigen (HBsAg) seroprevalence is the reported characteristic of native Mexicans. HBV diagnosis and genotype distribution was examined in native populations (Nahuas and Huichol, n = 306), and compared to a non‐native population (Mestizos, n = 17). Overall, 6% of the natives were positive for HBsAg and 33% had detectable anti‐HBc. HBsAg prevalence was lower in Nahuas compared to Huichols (1.4% vs. 9.4%, P < 0.002). Occult hepatitis B was detected in 14.2% (41/289) of natives, who either tested positive (5.88%, 17/289 HBsAg‐negative) or negative for anti‐HBc marker (8%, 24/289 HBsAg‐negative). Age‐adjusted anti‐HBc seroprevalence and HBsAg quantitation revealed a sub‐optimal sensitivity of conventional immunoassays. Nahuas had HBV/H and Huichol had HBV/A as the predominant genotypes followed by genotypes D, C, B, A, and D, G and H, respectively. A less variable HBV/H was characteristic in Mestizos, compared to a much variable HBV/H identified among the Nahuas. In conclusion, these findings indicate a high HBV endemicity among native Mexican groups where occult B infection is common. The different distribution of HBV genotypes among natives suggests multiple reservoirs of HBV from which these genotypes spread into the local communities. High anti‐HBc seroprevalence against a low HBsAg prevalence rate may be due to the limited sensitivity of the immunoassays for the detection of HBsAg that are available in Mexico and/or unknown immunogenetic characteristics of native Mexicans. J. Med. Virol. 82:1527–1536, 2010. © 2010 Wiley‐Liss, Inc.     

The prevalence and long term outcome of occult hepatitis B virus infections in community based populations

Features of occult hepatitis B infection in community‐based populations have yet to be described. In this study we documented: (1) the prevalence and demographics, (2) associated serology and viral loads, and (3) clinical outcomes of occult hepatitis B infection in community‐based populations. Hepatitis B surface antigen (HBsAg)‐negative sera collected from three Northern Canadian communities (HBsAg prevalences: 11–12%) in 1983–1985 were tested for HBV‐DNA by nested stage polymerase chain reaction. Of 706 HBsAg negative sera, 9 (1.3%) were HBV‐DNA positive. The median age of occult hepatitis B infected patients at the time of sampling was 9.8 years (range 3.1–50.4 years) and six (67%) were female. Two (22%) individuals were anti‐HBs positive (in the absence of prior vaccination). Viral loads were undetectable in all but two samples (2.40 and 2.86 log₁₀ IU/ml). Only one of the five (20%) patients who were assessed clinically, remained HBV‐DNA positive at 25–30 year follow‐up. There was no clinical, biochemical or radiologic evidence of chronic hepatitis, cirrhosis or hepatocellular carcinoma in these individuals or on review of the charts from the remaining four infected patients. The results of this study suggest that in community‐based populations: (1) occult hepatitis B infection is not as common as HBsAg positive infection, (2) the majority of infected subjects are young females, (3) a minority are anti‐HBs positive, (4) viral loads are either undetectable or low, and (5) in the absence of concurrent liver disease, occult hepatitis B infection does not appear to be associated with long term adverse clinical outcomes. J. Med. Virol. 84:1369–1375, 2012. © 2012 Wiley Periodicals, Inc.     

Presence of occult HBV, but near absence of active HBV and HCV infections in people infected with HIV in rural South Africa

Human immunodeficiency (HIV), hepatitis B (HBV), and hepatitis C (HCV) viruses are endemic in Sub‐Saharan Africa, but data regarding the prevalence of hepatitis co‐infections in HIV‐positive individuals residing there are limited. The aim of the study was to determine the prevalence of HBV, HCV, and occult HBV (presence of HBV‐DNA in the absence of HBsAg) in a rural, South African cohort. The results were compared to various ethnic groups in a Dutch cohort of people infected with HIV. Antiretroviral‐naïve individuals with HIV from both a rural South African clinic (n = 258), and a Dutch University hospital (n = 782), were included. Both serological (HBV and HCV) and molecular (occult HBV) assays were performed. Logistic regression analysis was used to define independent predictors of a hepatitis co‐infection. HBV and HCV prevalence rates in the South African cohort were exceptionally low (0.4%, 1/242 and 0.8%, 2/242, respectively), compared to those observed in Caucasians (HBV 4.4% and HCV 10.9%) and African immigrants (HBV 8.9% and HCV 4.8%). Conversely, occult HBV was observed in a considerable proportion (10%, 6/60) of South African patients who were anti‐HBc‐positive but HBsAg‐negative. Occult infections were less frequent in Caucasians and Africans in the Dutch cohort (3.2% and 1.4%, respectively). Independent predictors for occult HBV were not identified, but a trend towards more occult HBV at lower CD4 counts was observed. Local HBV/HCV prevalence data are needed to optimize vaccination and antiretroviral treatment strategies. Occult HBV in patients with HIV may be missed regularly when molecular analyses are not available. J. Med. Virol. 83:929–934, 2011. © 2011 Wiley‐Liss, Inc.     

Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus

Hepatocellular carcinoma (HCC) develops several years after the eradication of hepatitis C virus (HCV) by interferon therapy. Risk factors for the development of HCC are only partly understood. To elucidate the role of occult hepatitis B virus (HBV) infection in hepatocarcinogenesis in patients with sustained virologic response, the prevalences of HBV‐related makers were examined. Study group comprised 16 patients with sustained virologic response (group A) and 50 with HCV (group B). Anti‐HBc and anti‐HBs in serum were examined by enzyme‐linked immunoassay. HBV DNA in liver was examined by nested polymerase chain reaction, using primers specific for genes encoding for HBx, HBsAg, HBcAg, and HBV cccDNA. Sequence of the amplified HBV DNA for ‘a’ determinant of HBsAg was determined in HCC. Anti‐HBc was positive in 10 of 16 in group A and 25 of 50 in group B. HBV DNA in liver was detected in 12 of 16 in group A and 21 of 50 in group B (P = 0.044). In group A, HBV DNA in liver was detected frequently in patients without cirrhosis and in those with a longer period from the time of HCV eradication to the development of HCC. Mutation in ‘a’ determinant of HBsAg was found in three HCC of group A. Occult HBV infection may be one of the most important risk factors in hepatocarcinogenesis of Japanese patients with sustained virologic response. J. Med. Virol. 81:1009–1014, 2009. © 2009 Wiley‐Liss, Inc.     

The prevalence of antibodies to human herpesvirus 8 and hepatitis B virus in patients in two hospitals in Tanzania

The aim of this study was to determine the seroprevalence of human herpesvirus 8 (HHV‐8) and the immunization status for hepatitis B virus (HBV) infection in febrile patients in two districts of the United Republic of Tanzania. Between February and March 2007, blood samples were collected in Pemba Island and Tosamaganga from 336 outpatients and sent to the Virology Laboratory in Rome (Italy) for testing. HHV‐8 DNA and HBV‐DNA were amplified by two in‐house molecular methods, anti‐HHV‐8 antibody titers were determined by an immunofluorescence assay (IFA), and anti‐HCV, HBsAg, anti‐HBs, and anti‐HBc were evaluated by microplate enzyme immunoassay (MEIA). The seroprevalence of HHV‐8 was 30.7% (96/313). In Pemba Island, the prevalence was lower than in Tosamaganga (14.4% vs. 46.3%). A higher prevalence of low titers of HHV‐8 IgG (<1:80, 81%) was found among those under 5 years of age. HHV‐8 DNA was detected in six seropositive patients (6.7%). The prevalence of HBsAg, anti‐HBs, and anti‐HBc was 4.3%, 37.6%, and 29.3%, respectively. Out of 277 patients, 70 had had a previous infection (25.3%). One case of occult hepatitis was found. The cover of hepatitis B vaccination was higher among children born after 2002 (66.7%) than in patients born before 2002. HHV‐8 infection is endemic in Tanzania and the seroprevalence rate was higher in the mainland than on Pemba Island. The 3.9% percentage of HBsAg in children younger than 4 years of age suggests that increased efforts are required in order to achieve universal and compulsory immunization of children against HBV. J. Med. Virol. 82:1569–1575, 2010. © 2010 Wiley‐Liss, Inc.     

Detection of hepatitis B virus in serum using amplification of viral DNA by means of the polymerase chain reaction

A new assay was developed for the detection of hepatitis B virus (HBV) in human serum using amplification of a short viral DNA sequence by means of the polymerase chain reaction. As little as 0.4 fg viral DNA, corresponding to about 130 genome equivalents, per ml serum could be detected after the amplification procedure. This assay detected viral DNA in a number of patients with proven or suspected chronic HBV infection who were all negative for HBV DNA in the conventional hybridisation assay. We found HBV DNA in all of six HBeAg-positive and in three of eight HBeAg-negative HBsAg carriers, as well as in all of 11 patients with chronic liver disease with antibodies against the HBV core antigen (anti-HBc) as the sole marker for HBV infection, and in three of five apparently healthy individuals showing only anti HBc. Thus, this method is an important improvement for the diagnosis of persistent HBV infections, especially in patients where a definitive serological diagnosis is not possible.     

Case report: Detection of a hepatitis B surface antigen variant emerging in an elderly patient after an ischemic cerebral vascular accident

HBV reactivations are observed frequently in patients with past hepatitis B infection receiving cytotoxic and/or immunosuppressive chemotherapy for hemato‐oncological malignancies or autoimmune diseases. Recent ischemic stroke was shown to induce immunodepression by misunderstood mechanisms. To our knowledge, the association between HBV reactivation and ischemic stroke has not been reported before. This study reports the case of an anti‐HBs‐ and anti‐HBc‐positive patient who presented HBV reactivation in a context of recent ischemic stroke, with no other intercurrent iatrogenic phenomenon or usual immunosuppressive pathology. J. Med. Virol. 84:1897–1900, 2012. © 2012 Wiley Periodicals, Inc.     

Significance of liver histology in HBsAg‐positive,IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis

Delladetsima I, Papatheodoridis G V, Tiniakos D G, Hatzakis A & Tassopoulos N C
(2012) Histopathology  61, 881–888 Significance of liver histology in HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis Aims: The natural course of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus (HBV)‐related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients. Methods and results: Fifty patients with HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty‐six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre‐existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P = 0.034). Conclusions: Histological information is very important for the prognosis of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.     

Molecular analysis of the hepatitis B virus presurface and surface gene in patients from eastern China with occult hepatitis B

This study was designed to detect and analyze mutations that occur within the presurface and surface (pre‐S/S) gene of HBV in patients with occult hepatitis B, and determine their relationship to that disorder. Among 254 HBsAg negative samples of blood collected in eastern China, 183 were positive for anti‐HBc alone, 61 were positive for anti‐HBe alone, and 10 samples were positive for HBeAg. Within this group, 15 samples were found to be HBV DNA positive by real‐time PCR and were designated Group I. A control group of 28 HBsAg positive samples were chosen at random from patients with chronic hepatitis B and designated Group II. The HBV pre‐S/S gene was amplified by PCR and subjected to sequencing analysis. Occult hepatitis B was found in 1.6% of the patients with anti‐HBc alone and in 3.3% of those with anti‐HBe alone. Occult hepatitis B also was found in all HBsAg negative but HBeAg positive samples. Sequencing analysis showed a significant correlation between point mutations within the “a” determinant and occult hepatitis B (P < 0.0001), and a close relationship between pre‐S deletion mutations and occult hepatitis B (P = 0.06). There were unique amino acid mutations at the G145 position other than G145R. The HBV DNA levels in patients with occult hepatitis B were significantly lower than those found in the control group. The “a” determinant mutations and pre‐S deletions may play important roles in occult hepatitis B by affecting the expression, synthesis and secretion of the S protein and by impeding viral release and replication. J. Med. Virol. 85: 979–986, 2013. © 2013 Wiley Periodicals, Inc.     

Acute hepatitis: significance of antibody to hepatitis B core antigen.

The value of testing for core antibody (anti HBc) in acute hepatitis was assessed in 503 patients. All hepatitis B surface antigen (HBsAg) positive patients tested were also anti HBc positive. Of the 110 HBsAg negative, anti HBc positive patients, 32 were found to have surface antibody, indicating previous infection with hepatitis B virus (HBV). Of the remaining 78 patients in whom anti HBc alone was detectable, follow-up specimens were received from 28 and, of these, 21 were then found to be anti HBc negative. Thus in acute hepatitis non-specific transient reactions to core antigen may appear, and the presence of anti HBc alone cannot be considered adequate evidence for a diagnosis of HBV infection.     

Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the serum in absence of hepatitis B surface antigen (HBsAg). Studies were conducted to screen for occult HBV infection among family members of HBV carriers, incidentally detected positive for HBV infection with a view to assess the pattern of virus transmission among them. Nested PCR assay, employing independent sets of primers to surface and core genes, was used for detection of HBV DNA in serum samples from 28 index cases with asymptomatic HBV infection, and in serum samples from 72 HBsAg negative/anti-HBc positive family members. HBV DNA was detected in 15 HBsAg negative family members of 10 HBsAg positive index patients and was studied in detail. Direct sequencing of S gene region of 25 isolates (10 index cases and 15 contacts) and phylogenetic analysis with data base sequences revealed that genotypes A, C, and D and subtype adw2, adr, and ayw3 were present among them. Evidence of transmission from outside family sources was found in addition to intrafamilial transmission among individuals with occult infection. Mutations in the major hydrophilic loop (MHL) of the S gene region were also detected, including the 'vaccine escape' mutation G145R in three cases. Although majority of the occult infection was associated with low viral load, 3/15 (20%) cases were with higher viral load and potential infectivity. These cases are especially notable in diagnostic, blood banking, and transplantation services.     

The prevalence of “anti‐HBc alone” and HBV DNA detection among anti‐HBc alone in Korea

The “anti‐HBc alone” is a frequent serological finding in clinical laboratories, making it difficult to determine whether the HBV infection has resolved. The objectives of this study were to investigate the prevalence of anti‐HBc alone and HBV DNA detection (occult HBV infection) among anti‐HBc alone, and to describe the demographic and clinical characteristics of anti‐HBc alone. A total of 17,677 sera referred from the Health Promotion Center (HPC group, 4,014 sera) as well as all the hospital clinical departments (Patient group, 13,663 sera) were tested for HBs Ag, anti‐HBc, and anti‐HBs. HBV DNA test using real‐time PCR was performed on 230 anti‐HBc alone. The prevalence of anti‐HBc alone was 8.9%, significantly higher in the Patient group than in the HPC group. The prevalence of anti‐HBc was higher in men than women and was increased with age. Very low levels of HBV DNA were found in only 4 (1.7%) out of 230 subjects with anti‐HBc alone. They were patients with conditions unrelated to chronic liver disease. Considering the high prevalence of anti‐HBc alone, the frequency of occult HBV infection among anti‐HBc alone was unexpectedly low. In addition, HBV viral load was low in these patients. Further studies are required to determine the clinical significance and infectivity of anti‐HBc alone, in conjunction with very low levels of HBV DNA and to standardize the detection methodology for both anti‐HBc alone and HBV DNA. J. Med. Virol. 82:1508–1514, 2010. © 2010 Wiley‐Liss, Inc.