Serum Hepatitis B Surface Antigen Research Articles

Seroprevalence of Hepatitis‐B infection amongst Taiwanese university students 18 years following the commencement of a national Hepatitis‐B vaccination program

In Taiwan, the nation-wide Hepatitis-B virus (HB) vaccination program was first launched in July 1984 and was directed to those infants born to hepatitis B surface antigen (HBsAg) carrier mothers in Taiwan. From July 1986 onwards, all infants born in Taiwan were immunized against HB. This study examined the HB-infection status amongst students at a Taiwanese university 18 years subsequent to the implementation of universal HB vaccination. A total of 1,969 new university entrants in 2005 were grouped into 1 of 3 distinct birth cohorts according to their HB-vaccination schedule (cohort-1 students born prior to July 1, 1984; cohort-3 students born subsequent to June 30, 1986) and were examined for their serum HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) status. Immunity arising from vaccination was defined as an anti-HBs level 10 mIU/ml. We observed a trend toward a decreasing anti-HBc-positive rate and a decreasing HBsAg carrier rate from, respectively, 26.5 and 8.7% for cohort-1 to 4.7 and 1.7% for cohort-3 students. The prevalence of students featuring seronegativity for all three HB markers increased from 12.3% for cohort-1 to 48.8% for cohort-3 individuals. Amongst the 1,695 subjects revealing seronegativity for HBsAg and anti-HBc, their anti-HBs level was analyzed according to their birth year. The prevalence of students featuring a non-protective anti-HBs level increased from 11.9% for birth-year 1984 individuals to 48.2% for birth-year 1987 students. The introduction of HB vaccine has effectively reduced the transmission of HBV infection in Taiwan, 18 years subsequent to the commencement of the universal HB-vaccination program. A "waning-off" effect of anti-HBs seropositivity acquired from the HB vaccination program has also been observed.

Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy

Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy

Five-year follow-up of a hepatitis B virus-positive recipient of hepatitis B surface antigen-positive living donor liver graft

The shortage of cadaveric donor organs has led to the use of living donors and marginal cadaveric donors. To date, there have been only 2 reports on the use of hepatitis B surface antigen (HBsAg)-positive liver grafts. Here we describe the 5-yr posttransplantation sequence of a hepatitis B virus (HBV)-positive recipient who received an HBsAg-positive living donor liver graft. A 43-yr-old HBV-positive patient with hepatorenal syndrome received a living donor liver graft in October 2000 from a 27-yr-old HBsAg-positive carrier with no clinical evidence of HBV infection other than the serologic markers. The recipient recovered slowly after liver transplantation (LT). Recipient serum HBsAg was continuously positive despite anti-HBV therapy with high-dose hepatitis B immunoglobulin (HBIG) and lamivudine. The patient was also treated with famciclovir and interferon; to date, a final regimen of lamivudine and adefovir has kept liver function stable for 20 months. The recipient has lived for 64 months after transplantation. The donor has not revealed any clinical evidence of active hepatitis during follow-up. In conclusion, our result implicates that a recipient of liver graft from an HBsAg-positive carrier may survive for a long period following antiviral therapy with lamivudine and adefovir. Considering this living donor case and previously reported cases, the use of an HBsAg-positive cadaveric liver graft may deserve attention when no other donor is available.

RNA interference-mediated control of hepatitis B virus and emergence of resistant mutant

Background & Aims Present therapy for chronic hepatitis B attains control only in limited proportions. Small interfering RNA (siRNA) offers a new tool with potential therapeutic applications for hepatitis B virus (HBV). Given the importance of sequence identity in the effectiveness of siRNA and the heterogeneity of HBV sequences among different isolates, a short hairpin RNA (shRNA)-expressing plasmid, pSuper/HBVS1, was developed to target a region conserved among major HBV genotypes and assess its effectiveness control of HBV. Methods HBV replication-competent plasmid was cotransfected with pSuper/HBVS1 to HuH-7 cells or to mice. The levels of viral proteins, RNA, and DNA were examined in transfected cells and animals. The effects of pSuper/HBVS1 on clinical isolates with genotypes B and C were also determined. Results pSuper/HBVS1 significantly decreased levels of viral proteins, RNA, and DNA for HBV genotype A in cell culture and in mice. Comparable suppressive effects were observed on clinical isolates of genotypes B and C. A clone with a silent mutation in the target region was identified from a patient with genotype C. This mutant revealed diminished sensitivity to pSuper/HBVS1 and could be selected out in the presence of pSuper/HBVS1 in cell culture. Conclusions These findings indicated that shRNA could suppress HBV expression and replication for genotypes A, B, and C, promising an advance in treatment of HBV. However, the emergence of resistant mutants in HBV quasispecies should be considered.

Hepatitis B infection among Asian American Pacific Islanders in the Rocky Mountain area

To detect the rate of hepatitis B virus (HBV) infection among Asian American Pacific Islanders (AAPIs), data on hepatitis B antigens and antibodies were collected as part of a community health fair. Two hundred seventy adults received free hepatitis B screening. The serological results of 82 Whites showed that 1.2% were positive for serum hepatitis B surface antigen (HBsAg) and 21% were positive for serum hepatitis B antibody (HBAb). Of 161 AAPIs, 4.3% were positive for serum HBsAg and 60% were positive for HBAb. Despite the limitation of design, these data provide some insight on the rate of HBV infection in AAPIs because there are no data on prevalence of HBV infection of AAPIs in the Rocky Mountain Area.

A novel amperometric immunosensor based on three-dimensional sol–gel network and nanoparticle self-assemble technique

A novel hepatitis B surface antigen (HBsAg) immunosensor has been developed by self-assembling gold nanoparticles to a thiol-containing sol–gel network. A cleaned gold electrode was first immersed in a hydrolyzed mercaptopropyltrimethoxysilane (MPS) sol–gel solution to assemble three-dimensional silica gel, and then gold nanoparticles were chemisorbed onto the thiol groups of the sol–gel network. Finally, hepatitis B surface antibody (HBsAb) was adsorbed onto the surface of the gold nanoparticles. Thus, an interfacial design of bare gold electrode (BGE)/MPS/Au/HBsAb was prepared to detect HBsAg in human serum based on the specific reaction of HBsAb and HBsAg. The electrochemistry of ferricyanide redox reaction was used as a marker to probe the interface and as a redox probe to determinate HBsAg. The main conditions of the assembly of MPS sol–gel, gold nanoparticles, the immobilization of HBsAb, and incubation time were investigated in detail. Compared with the glutaraldehyde binding approach, the antibodies immobilized by this method present larger amount and higher immunoactivity. The linearity of HBsAg in the range of 2–360 ng/mL with the correlation coefficient of 0.998 was obtained. This immunosensor system was evaluated on several clinical sample, the analytical results obtained by this method were in agreement with those detected by the enzyme-linked immunosorbent assay (ELISA) method, indicating a promising alternative tool for clinical diagnosis. Moreover, the studied immunosensor exhibited good reproducibility, long-term stability, high sensitivity and specificity.

Quantitative detection of hepatitis B surface antigen by chemiluminescent microparticle immunoassay during lamivudine treatment of chronic hepatitis B virus carriers

The usefulness of fully automated chemiluminescent microparticle immunoassay (Architect HBsAg QT) for monitoring serum levels of hepatitis B virus (HBV) during antiviral therapy remains unclear. Using this assay, hepatitis B surface antigen (HBsAg) was measured in 20 patients with chronic hepatitis B before and during lamivudine treatment. At the start of therapy, 12 patients had detectable hepatitis B e antigen (HBeAg) and 8 did not. The median serum HBV DNA level and HBsAg concentration (25th-75th centile) were 7.2 (6.1-7.8) log genome equivalents/ml and 3,932 (1,585-12,330) IU/ml, respectively. The HBsAg concentration was significantly higher in HBeAg positive than in HBeAg negative patients (P=0.031). There was a significant correlation between the HBsAg concentration and HBV DNA level (r=0.490, P=0.027). The HBsAg concentration negatively correlated with patient age (r=-0.395, P=0.085). After the start of lamivudine therapy, HBV DNA levels fell rapidly in all patients. Serum HBsAg concentrations also fell in most patients, but to a lesser extent. When drug-resistant variants emerged, serum HBsAg usually increased before biochemical breakthrough. Although HBV DNA was elevated persistently after the emergence of drug-resistant variants, the increase in HBsAg was transient. In some patients, the increase in HBsAg preceded the increase in HBV DNA. Monitoring of serum HBsAg concentrations with the use of Architect HBsAg QT, in addition to measurement of HBV DNA levels, is helpful for evaluating the response to lamivudine treatment and for the early detection of drug-resistant strains.

Reductions in Serum Hepatitis B Surface Antigen (HBsAg) Occur in Parallel with Reductions in Intrahepatic HBV Covalently Closed Circular (ccc) DNA in Chronic Hepatitis B (CH-B) Patients Receiving Adefovir Dipivoxil (ADV)

Introduction: We previously demonstrated that 48 weeks of ADV therapy reduced intrahepatic HBV cccDNA by a median of 86% (p=0.002 vs. placebo) in CH-B patients and was correlated with significant reductions in serum and intracellular HBV DNA (HEPATOLOGY 2002;36: 296A). Since HBV cccDNA is the transcriptional template for HBsAg, we investigated whether reductions in cccDNA translated into significant reductions in serum HBsAg titer.

Overview of commercial HBV assays systems.

Measurement of viral nucleic acid in serum is often a valuable adjunct to the management of viral infections (). In hepatitis B, tests for hepatitis B virus (HBV) DNA have been used widely (Table 1), but their interpretation and significance have yet to be defined. HBV DNA assays are limited by lack of standardization and variable sensitivity. Because HBV may circulate in serum at high levels (as high as 1010 virions/mL), direct molecular hybridization assays are capable of detecting HBV DNA in a high proportion of patients, particularly those with active disease and both HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) in serum. Commercial assays comprise the liquid hybridization assay (Genostics™, Abbott Laboratories, Chicago, IL), the hybridization capture assay (Digene, HC II), and branched DNA (bDNA) signal amplification assay (Versant, Bayer Diagnostics). Furthermore, a quantitative polymerase chain reaction (PCR) assay for HBV DNA has been developed (Amplicor Monitor HBV, Roche Diagnostics); it detects HBV DNA in a higher proportion of patients with chronic hepatitis B and often yields positive results, even in HBsAg carriers without apparent disease. Table 1 Different Principles of HBV DNA Quantification Signal amplification assays Liquid hybridization DNA-RNA hybridization Branched DNA technology, bDNA Target amplification assays Polymerase chain reaction (PCR) Transcription-mediated amplification (TMA) Nucleic acid based amplification (NASBA) Ligase chain reaction (LCR)

Occult HBV infection—both hidden and mysterious

Occult HBV infection—both hidden and mysterious

Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?

Transplantation of livers from anti-hepatitis B core antibody (anti-HBc)-positive donors into anti-HBc-negative recipients is associated with a high rate of viral transmission. We report a prophylaxis regimen based on virologic evaluation of the donor. Liver and serum from hepatitis B surface antigen (HBsAg)-negative, anti-HBc-positive donors were evaluated by polymerase chain reaction (PCR) for hepatitis B virus (HBV) DNA. All anti-HBc-negative recipients were given a single dose of hepatitis B immunoglobulin (HBIG) during the anhepatic phase of transplantation and were placed on maintenance lamivudine monotherapy. Recipients were followed up longitudinally monitoring intrahepatic HBV DNA as well as serologic HBsAg and HBV DNA by PCR. Between January 1999 and August 2001, 14 anti-HBc-negative recipients received liver transplants from anti-HBc-positive donors. All donor serum was negative for HBV DNA. In total, nine of 14 (64%) livers had detectable HBV DNA; 1 patient was initially PCR-negative and low levels of HBV DNA were detected in a posttransplantation liver biopsy. Mean follow-up was 33 months (range, 22 to 51), and patient and graft survival were each 93%. One case of de novo hepatitis B occurred in a patient noncompliant with lamivudine, although all other serial serum HBsAg assay results were negative. Single-dose HBIG followed by maintenance lamivudine monotherapy prevented de novo hepatitis B in compliant patients. For the cohort of compliant patients that were initially HBV DNA-positive, 7 of 8 (88%) now have undetectable virus in the hepatic allograft by PCR analysis. Nevertheless, there is no evidence to suggest that viral eradication occurs. Accordingly, all patients are maintained on continued lamivudine prophylaxis.

Quantitation of hepatitis B surface antigen by an automated chemiluminescent microparticle immunoassay

A fully automated chemiluminescent microparticle immunoassay (Architect HBsAg QT) was used for the detection and quantitation of hepatitis B surface antigen (HBsAg). The assay is capable of processing up to 800 HBsAg tests per hour. The concentration of HBsAg is determined by utilizing a previously generated Architect HBsAg calibration curve. Architect HBsAg QT sensitivity was found to be around 0.2 ng/ml which is equivalent or superior to other known and commercially available enzyme immunoassays and/or chemiluminescent immunoassays. We performed a quantitative study of HBsAg, HBeAg, HBV-DNA and HBV-DNA polymerase in over 733 sera obtained from 43 chronic hepatitis B carriers. Serum HBsAg levels detected by Architect HBsAg QT were found to be higher in HBeAg-positive than in anti-HBe-positive HBV chronic carriers and correlated with the level of serum HBV-DNA and HBV-DNA polymerase.

Different expression of hepatitis B surface antigen between hepatocellular carcinoma and its surrounding liver tissue, studied using a tissue microarray.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is highly associated with chronic liver disease, including hepatitis B viral infection. In order to study the association between hepatitis B virus (HBV) infection and HCC development, tissue microarrays were used to detect the expression of hepatitis B surface antigen (HBsAg) in 194 HCCs and their surrounding liver tissues, using anti-HBsAg monoclonal antibody. The results showed that the expression of HBsAg is significantly lower in tumour tissue than in non-tumour tissue. Among the 138 cases with positive serum HBsAg, expression of HBsAg was more frequently detected in non-tumour tissue (103 cases, 75%) than in tumour tissue (11 cases, 8%). RT-PCR and Southern blot analysis were performed to explore the mechanism of the decreased expression of HBsAg in tumour cells. The RT-PCR results showed that absence or decreased expression of the HBV S gene was detected in 3/15 (20%) and 6/15 (40%) HCCs, respectively. Integration of HBV in 23 pairs of HCCs and their matched non-tumour liver tissues was studied by Southern blot. The results showed that the integrated HBV S gene sequence was detected in 19/23 tumours (83%) and 1/23 non-tumour tissues (4%), whereas the free replicative virus form was observed in 3/23 tumours (13%) and 14/23 non-tumour tissues (61%). These findings suggest that HBsAg-negative results in tumour tissues were directly related to HBV DNA insertion and provide new insights into the involvement of HBsAg in hepatocarcinogenesis.

Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties

Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-ABXTL. A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-ABXTL and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-ABXTL induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-ABXTL binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-ABXTL could be combined with other monotherapies that are currently used to treat HBV carriers. (HEPATOLOGY 2002;35:673-679.)

Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination.

Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. Before universal HBV immunization was started in Taiwan in 1984, the carrier rate for hepatitis B surface antigen (HBsAg) was 15% to 20% in the general population. To quantify the population impact of a mass vaccination program for HBV 15 years after its implementation. Descriptive analysis of serologic markers of HBV in healthy children and adolescents. Chung-Cheng District, Taipei City, Taiwan, in 1999. 1357 persons younger than 15 years of age, who were born after the implementation of universal HBV vaccination, and 559 persons 15 to 20 years of age, who were born before the program began. Repeated serologic surveys similar to those done before and 5 and 10 years after the national vaccination program was implemented. All participants were tested for serum HBsAg, its antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). During the 15 years since the vaccination program was implemented, the prevalence of HBsAg among persons younger than 15 years of age decreased from 9.8% in 1984 to 0.7% in 1999; among persons 15 to 20 years of age, the 1999 prevalence of HBsAg was 7% (P < 0.001). Hepatitis B core antibody seropositivity, which represents HBV infection, was found in 2.9% of persons younger than 15 years of age and in 20.6% of persons 15 to 20 years of age (P < 0.001); in the same age groups, the rate of anti-HBs seropositivity was 75.8% and 70.7%, respectively (P = 0.02). Universal vaccination significantly decreased the HBV carrier rate and infection rate among children and adolescents born since the program began. By decreasing the carrier pool, continuation of the national HBV immunization program should prevent HBV infection in the children of Taiwan, and, subsequently, adults as well.

Determination of hepatitis B virus subtypes by an enzyme immunoassay method using monoclonal antibodies to type-specific epitopes of HBsAg.

We described a Hepatitis B surface antigen (HBsAg) subtyping method based on a commercial enzyme immunoassay (EIA) for detection of HBsAg in which the procedure was modified to include the use of monoclonal antibodies with restricted anti-HBs specificities. This method, which was able to classify HBsAg as: ayw1, ayw2, ayw3, ayw3* (intermediate between ayw3 and ayw4), ayw4, ayr, adw2, adw4 and adr, was compared to counter electrophoresis procedure (CEP) by testing HBsAg positive sera from blood donors included in a prospective national epidemiological survey. Among the 256 HBsAg positive samples tested with both techniques, 111 (43.3%) could not be subtyped with CEP vs 10 (3.9%) with our modified EIA. This difference was related to the serum HBsAg concentration which must be greater than 3000 ng/mL and 100 ng/mL for CEP and EIA, respectively. The results obtained from 145 sera with both methods were concordant. Seventeen out of 18 samples partially classified as ay with CEP were completely determined with EIA. This reliable procedure, derived from commercially available reagents, can be easily used in several applications such as large epidemiologic studies and as a substitute for nucleotide sequencing genotyping which is not adapted for large-scale screening and not applicable on samples from nonviremic hepatitis B virus (HBV) carriers.

Long-term experience with lamivudine therapy for hepatitis B virus infection after liver transplantation

Hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is associated with a high recurrence rate and poor prognosis. This is the first study of the efficacy of long-term lamivudine therapy for patients with HBV infection after OLT. Eight patients (5 men, 3 women) aged 35 to 63 years (mean, 50 years) with HBV infection after OLT (6 patients, recurrent infection; 2 patients, de novo infection) were treated with lamivudine, 100 mg/d, on a compassionate-use basis. Before treatment, all had detectable HBV DNA in serum, and 5 patients (62.5%) had detectable serum hepatitis Be antigen (HBeAg). Duration of treatment was 24 to 50 months (mean, 36 months). Patients were monitored for serum alanine aminotransferase level (ALT), HBV DNA (by hybridization), hepatitis B surface antigen (HBsAg), and HBeAg before and after therapy, and liver histological findings were scored for inflammation and fibrosis. After treatment, 3 patients (32.5%) had undetectable HBV DNA by hybridization assay. None of the patients lost serum HBeAg and HBsAg, except for 1 patient who lost serum HBeAg and became serum antibody to HBeAg-positive. Serum ALT levels normalized in 5 patients (62.5%). Blinded histological assessment showed improvement in 1 patient, no change in 2 patients, and worsening in 5 patients. YMDD variants of HBV were detected in 5 patients (62.5%) within 9 to 20 months (mean, 13 months) of lamivudine therapy. Of these, 2 patients (40%) had hepatic failure (1 patient died of massive variceal bleed) and 3 patients remain clinically stable. Lamivudine therapy was continued in the latter patients. Although lamivudine is a potentially effective therapy for HBV infection after OLT, emergence of high mutation rates with long-term therapy, histological progression, and the possibility of hepatic failure point to the need to investigative combinations of antiviral therapy.

Long-term experience with lamivudine therapy for hepatitis B virus infection after liver transplantation.

Hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is associated with a high recurrence rate and poor prognosis. This is the first study of the efficacy of long-term lamivudine therapy for patients with HBV infection after OLT. Eight patients (5 men, 3 women) aged 35 to 63 years (mean, 50 years) with HBV infection after OLT (6 patients, recurrent infection; 2 patients, de novo infection) were treated with lamivudine, 100 mg/d, on a compassionate-use basis. Before treatment, all had detectable HBV DNA in serum, and 5 patients (62.5%) had detectable serum hepatitis Be antigen (HBeAg). Duration of treatment was 24 to 50 months (mean, 36 months). Patients were monitored for serum alanine aminotransferase level (ALT), HBV DNA (by hybridization), hepatitis B surface antigen (HBsAg), and HBeAg before and after therapy, and liver histological findings were scored for inflammation and fibrosis. After treatment, 3 patients (32.5%) had undetectable HBV DNA by hybridization assay. None of the patients lost serum HBeAg and HBsAg, except for 1 patient who lost serum HBeAg and became serum antibody to HBeAg-positive. Serum ALT levels normalized in 5 patients (62.5%). Blinded histological assessment showed improvement in 1 patient, no change in 2 patients, and worsening in 5 patients. YMDD variants of HBV were detected in 5 patients (62.5%) within 9 to 20 months (mean, 13 months) of lamivudine therapy. Of these, 2 patients (40%) had hepatic failure (1 patient died of massive variceal bleed) and 3 patients remain clinically stable. Lamivudine therapy was continued in the latter patients. Although lamivudine is a potentially effective therapy for HBV infection after OLT, emergence of high mutation rates with long-term therapy, histological progression, and the possibility of hepatic failure point to the need to investigative combinations of antiviral therapy.

A novel mimetic enzymatic fluorescence immunoassay for hepatitis B surface antigen by using a thermal phase separating polymer.

Iron tetrasulfonatophthalocyanine (FeTSPc), a peroxidase mimic, was used as a labeling reagent and poly(N-isopropylacrylamide) (PNIP) as the separation support of the immune complex for the mimetic-enzymatic immunoassay of hepatitis B surface antigen (HBsAg). PNIP was precipitated from aqueous solution when the ambient temperature was higher than its lower critical solution temperature of 31 degrees C. In a sandwich immunoassay, the antigen (HBsAg) first reacted with mouse anti-human HBsAg antibody immobilized on PNIP (PNIP-antibody) and then further reacted with FeTSPc-labeled mouse anti-HBsAg antibody (antibody-FeTSPc) at room temperature in a homogeneous format. After changing the temperature to separate the PNIP-antibody-HBsAg-antibody-FeTSPc conjugate moiety, it was re-dissolved and determined by coupling with the fluorogenic reaction of hydrogen peroxide and p-hydroxyphenylpropionic acid. The sensitivity of this method (3 ng mL-1) was close to that of the traditional ELISA using the same reactants. However, the assay was much faster (the assay time decreased from 100-120 to 45 min). This method was applied to determine HBsAg in human serum with satisfactory results.

The Clinical Features of Chronic Hepatitis C Are Not Affected by the Coexistence of Hepatitis B Virus DNA in Patients Negative for Hepatitis B Surface Antigen

Hepatitis B virus (HBV) DNA has been detected in the sera of hepatitis patients who are negative for hepatitis B surface antigen (HBsAg) by polymerase chain reaction (PCR). The purpose of the present study was to clarify the clinical characteristics of patients with chronic hepatitis C who are negative for serum HBsAg and positive for HBV DNA. The subjects included 49 patients with chronic hepatitis C who were negative for serum HBsAg and 119 blood donors who served as healthy controls. Serum samples were tested for the presence of HBV DNA by the nested PCR method. Serum HBV DNA was detected in 18 (37.7%) of the 49 chronic hepatitis C patients and in none (0%) of the 119 blood donors. Among the hepatitis C patients, HBV DNA was detected in 20.7% of those who were negative for all HBV-associated markers and in 57.1% of those who were positive for one or more HBV-associated marker. The HBV DNA-positive rate among those in each F stage did not significantly differ. The liver function parameters of the HBV DNA-positive and the HBV DNA-negative chronic hepatitis C patients did not significantly differ. These results suggest that hepatitis C virus is frequently coinfected with serum HBsAg-negative HBV, and that the incidence of HBV infection in blood donors is low. However, it is considered that HBsAg-negative HBV infection does not modify the blood biochemical features of chronic hepatitis C.