Hepatitis B Surface Antigen Antibodies Research Articles

Successful interferon treatment in a patient chronically infected with hepatitis B virus carrying unusual S‐ (and P‐) mutants in the presence of anti‐HBs antibodies

Hepatitis B virus (HBV) immune escape mutants with point mutations within the S gene may arise during the natural course of HBV infection, due to a positive selection pressure exerted by the host immune response. Mutations within the immunodominant B and T cell epitopes of hepatitis B surface antigen (HBsAg) allow the resulting S-mutants to propagate even in the presence of neutralizing anti-HBs antibodies and the HBV-specific T-cell immune response. To study the antiviral effect of Pegylated-interferon (Peg-IFN) in a patient with chronic hepatitis B carrying unusual S-(and P-) mutants in the presence of anti-HBs antibodies. We report on a 43-year-old male chronically infected with a genotype A HBV strain, with cocirculation of both HBsAg and anti-HBs antibodies, who received treatment with 120 mug of Peg-IFN for 24 weeks. HBeAg seroconversion and clearance of both HBV DNA by polymerase chain reaction and HBsAg were successfully achieved. Improved histology was observed in a biopsy performed 44 weeks after Peg-IFN therapy was completed. It seems plausible that the ascribed genotype A could have contributed to the effective response to Peg-IFN, even though the treatment was provided only throughout a 24-week period. To our knowledge, this is the first report regarding the successful result obtained by using Peg-IFN as a treatment for a chronically HBV-infected patient carrying HBsAg immune escape mutants.

High prevalence of occult hepatitis B in Baltimore injection drug users

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in a serum or liver in the absence of hepatitis B surface antigen (HBsAg). The prevalence and clinical correlates of occult hepatitis B remain incompletely defined. A cross-sectional study was performed to determine the prevalence of occult hepatitis B in a high-risk cohort composed of 188 injection drug users in Baltimore, Maryland. All individuals had chronic hepatitis C viral infections confirmed by RNA detection and liver biopsy. Serologic assays for HBsAg and core antibody (HBcAb) were performed. Serum HBV DNA was detected using the COBAS HBV AMPLICOR monitor assay (lower limit of detection, 200 HBV copies per milliliter) and a semi-nested polymerase chain reaction (PCR) assay (lower limit of detection, 15 HBV copies per milliliter). Although almost all individuals (96%) were anti-HBC positive, only 8 of 188 (4%) were HBsAg positive. Occult hepatitis B was not identified using the COBAS assay, but was found in 81 of 180 (45%) of individuals using semi-nested PCR. Of the 8 HBsAg positive individuals, HBV DNA was found in 1/8 using the COBAS assay and 6/8 using the nested PCR assay. Overall, liver disease was mild, with a median serum alanine aminotransferase (ALT) of 38 IU/L, median activity grade of 3/18, and median fibrosis stage of 1/6. No association was found between the serum AST (aspartate aminotransferase), activity grade, or stage of liver disease and the presence of occult hepatitis B. Serum ALT levels were slightly higher in patients without occult hepatitis B (46 vs. 35 IU/L), and the median years since first injection drug use was somewhat longer in those without occult hepatitis B (24 vs. 20 years). In conclusion, although further research is needed to assess its clinical significance, there is a high prevalence of occult HBV infection in this cohort of HCV-infected injection drug users.

Waning Immunity To Plasma–Derived Hepatitis B Vaccine and the Need for Boosters 15 Years After Neonatal Vaccination

Neonatal immunization with hepatitis B (HB) vaccine is highly effective; however, more needs to be learned about the duration of protection and indications for boosters. We measured antibody to HB core antigen (anti-HBc), HB surface antigen (HBsAg), and pre- and postbooster titers of HBsAg antibody (anti-HBs) 15 years after primary neonatal immunization with plasma-derived HB vaccines in 2 cohorts of 15-year-old children. Group A consisted of 78 children who were born to HB e antigen-positive HBsAg carrier mothers and had developed protective levels of anti-HBs antibodies (> or =10 mIU/mL) following HB immunization. Group B consisted of 113 apparently healthy children whose anti-HBs titers after vaccination were unknown. Anti-HBs was undetectable (antibody titer <10 mIU/mL) in 29.9% in group A and 62.4% in group B (P < .001). Anti-HBc was detected in 33.3 % in group A and 4.4 % in group B (P < .001). After a single booster dose of HB vaccine, 2.7% in group A and 3.3% in group B remained anti-HBs-negative. A blunted serological response was noted in approximately 20% in both groups. One HBsAg carrier was detected in group A (1.3%) and 4 in group B (3.5%). Fifteen years after neonatal immunization with plasma-derived HB vaccine, a large proportion of children exhibited waning immunity. This poses the risk of breakthrough infection. A single booster augmented the serological response to the vaccine in most but not all subjects. In conclusion, our findings suggest that one or more booster immunizations are needed in seronegative subjects by at least 15 years following neonatal immunization with plasma-derived HB vaccine.

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.

High prevalence of transfusion-transmitted virus among patients with non-B, non-C hepatocellular carcinoma

Many patients with hepatocellular carcinoma are positive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus (anti-HCV). Recently, transfusion-transmitted virus (TTV) DNA was identified in the serum of patients with non-B, non-C posttransfusion hepatitis. In this study, the prevalence of TTV DNA in the serum of patients with non-B, non-C hepatitis-associated hepatocellular carcinoma was evaluated. Fifteen patients with hepatocellular carcinoma negative for HBsAg, antibodies to hepatitis B core antigen (anti-HBc), and anti-HCV antibodies were enrolled in this study (non-B, non-C group). Fifteen patients positive for HBsAg and negative for anti-HCV antibody (HBV group) and another group of patients negative for HBsAg but positive for anti-HCV antibody (HCV group) were also enrolled in this study. Data obtained from 27 healthy subjects negative for both HBsAg and anti-HCV antibody and normal levels of serum alanine aminotransferase represented controls. The healthy control group, the non-B, non-C group, and the HCV group were age-matched. TTV DNA was detected by heminested polymerase chain reaction in which specific primers were used. TTV DNA was detected in 10 of 15 patients (67%) in the non-B, non-C group. This prevalence rate in the non-B, non-C group was significantly higher than that in the HBV group (3 of 15 patients, 20%) and the control group (9 of 27 patients, 33%), but it was not significantly different from that in the HCV group (7 of 15 patients, 47%). The noncancerous hepatic tissue samples of 10 TTV-DNA positive patients in the non-B, non-C group included 2 with chronic hepatitis and 8 with cirrhosis. This study showed that TTV DNA is frequently detected in the serum of patients with non-B, non-C hepatocellular carcinoma. This result suggests a potential pathogenetic association between hepatocellular carcinoma and TTV infection.

Prevalence of anti-hepatitis A antibodies, hepatitis B viral markers, and anti-hepatitis C antibodies among immigrants from the former USSR who arrived in Israel during 1990-1991.

The goal of this study was to assess the susceptibility of the sub-population of over 500,000 immigrants from the former USSR who came to Israel during 1989-94 to HAV infection, and to provide military physicians with estimates of the prevalence of HBV and HCV carriage in this sub-population. 987 males aged 17-49 and 195 females aged 17-19, reporting to military recruitment offices between December 1991 and March 1992 were tested. Anti-HAV, anti-HBV antibodies and hepatitis B surface antigen (HBsAg) were detected by using standard enzyme immunoassay (EIA) tests, and anti-HCV antibodies by a second-generation EIA and confirmed by a third-generation INNO-LIA test. It was found that in the 17-19-year age-group the prevalence of anti-HAV antibodies was 37%, anti-HBV was 12.8%, HBsAg was 3.0% and anti-HCV 1.3%. All markers were higher among males. The prevalence of anti-HAV and anti-HBs antibodies increased with age among males. That of HBsAg and anti-HCV antibodies increased with age overall. In the multiple logistic regression analysis, HAV and HBV seropositivity were significantly associated with the mother's education and republic of origin. It was concluded that the prevalence of anti-HAV antibodies is similar to that among the local population, which should not be considered at a higher risk of infection during military service. On the other hand, the higher prevalence of HBsAg and anti-HCV antibodies in this sub-population should heighten the awareness of the possibility of chronic liver pathology.

Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study.

The objectives of this study were to investigate the prevalence of infections with hepatotrophic viruses in an anti-human immunodeficiency virus (HIV)-positive population from Buenos Aires and to compare it among the main risk groups for HIV infection. Four hundred and eighty-four consecutive patients attending the HIV outpatients clinic were studied: 359 men and 125 women, median age 29 years (range 16-67 years); 35.5% had presented acquired immune deficiency syndrome (AIDS)-defining conditions. Two hundred and thirty-four patients were intravenous drug users (IVDU), 99 had homosexual and 142 heterosexual preference, seven had received blood transfusions and two had no risk factors. Hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (HBcAb) and to hepatitis C virus (anti-HCV) were investigated in all patients; antibodies to HBsAg (HBsAb) and IgG antibodies to hepatitis D virus (anti-HDV) in all HBcAb-positive patients; hepatitis B e antigen and antibodies to HBeAg (HBeAg) in all HBsAg-positive patients; IgG antibodies to hepatitis A virus (anti-HAV) in the first 307 patients; and IgG antibodies to hepatitis E virus (anti-HEV) in the first 91 patients. As control groups, contemporary voluntary blood donors were studied for prevalence of HAV, HBV, HCV and HEV. The percentages of HBcAb, HBsAg, anti-HCV and anti-HEV (58.5, 14.5, 58.5 and 6.6%, respectively) were significantly higher in anti-HIV-positive patients than in control groups (3.2, 0.5, 1.0 and 1.8%, respectively) (P = 0.000). The prevalence of HBcAb was significantly higher in IVDU (72.6%) than in heterosexuals (33.8%) (P = 0.0001) and in homosexuals (59.6%) (P = 0.0189). The percentage of HBsAg was significantly higher in IVDU (19.2%) than in heterosexuals (6.3%) (P = 0.0004). Anti-HCV was significantly higher in IVDU (92.3%) than in homosexuals (14.1%) and in heterosexuals (33.1%) (P = 0.000 in both cases). The prevalence of anti-HDV was relatively low (1.9%). There was no difference in the percentage of anti-HAV between HIV-positive and negative subjects. In conclusion, there is a high prevalence of HBV and HCV infections in HIV-positive patients from our area. Drug use is the main route of transmission, but prevalence of HCV in patients with, probably, sexually acquired HIV infection is also higher than in the control group. The increased prevalence of HEV infection in HIV-positive individuals is another provocative finding that warrants further study.

IMMUNIZATION OF ADOLESCENTS FOR HEPATITIS B USING A 0,2,4 MONTH DOSING SCHEDULE. † 36

Universal Hepatitis B vaccination of adolescents has been recommended by the American College of Physicians. Logically, efforts to mass immunize adolescents have been implemented in the school systems. A shorter dosing schedule of the hepatitis B vaccine has been initiated in order to accommodate the academic year, although the efficacy is undocumented.Objectives: 1) To verify the immunity induced by a 0,2,4 month dosing schedule of the hepatitis B vaccine for adolescents and 2) to identify rates of hepatitis B infection in an adolescent population considered eligible for hepatitis B vaccination. Method: Adolescents from two general teen clinics in urban settings were randomly recruited to participate in receiving the hepatitis B vaccine series on a 0,2,4 month dosing schedule. Serologies for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb), and hepatitis B surface antigen antibody (HBsAb) were obtained at time 0 and at least 4 weeks after the third vaccination. Participants completed a one page risk behavior and demographic questionnaire.Results: 160 adolescents enrolled in the study. Of this group no known prior exposure or infection with hepatitis B was reported. Two subjects showed evidence of chronic hepatitis B infection, (HBcAb positive (+), IgM HBcAb negative (-) HBsAg +, HBsAb -) and one subject had evidence of past hepatitis B infection, (HBcAb +, HBsAb +, and HBsAg -). All three subjects were immigrants from the East Asia. Two had reported having sexual intercourse. Currently, 35 subjects have completed the study. 100% of the susceptible participants developed protective levels of antibodies against hepatitis B surface antigen with a geometric mean antibody titer of 1235 mIU. One subject with chronic hepatitis B showed no response to the hepatitis B vaccine. Conclusion: Our preliminary data shows that the 0,2,4 month vaccination schedule of hepatitis B is adequate to produce an appropriate immune response for hepatitis B in an adolescent population. However, the identification of chronic hepatitis B in this population raises the concern of inadequate detection of'at risk' groups. More evaluation of hepatitis B screening in adolescents may be necessary.

Treatment of chronic hepatitis B and C with interferon-alpha in renal allograft recipients: preliminary results

We evaluated the effects of treatment with interferon (IFN) on liver disease and renal allograft function in ten immunosuppressed cadaver kidney recipients. Two females and eight males (mean age 39 years) with biopsy-proven chronic active hepatitis (n = 8) or persistent hepatitis (n = 2) and serum positive for hepatitis B surface antigen (HBsAg) and HBe antigen (n = 5) or serum positive for anti-HCV antibodies (n = 3) or serum positive for HBsAg, anti-HCV and anti-HDV antibodies (n = 2) received 3 million units IFN thrice weekly of 6 months. All patients responded with a reduction in serum aminotransferase activity and in five of them liver function completely normalized. Three patients among five infected with HBV cleared HBeAg. During the follow-up period liver function remained stable in 9 patients after discontinuation of IFN therapy. Three patients lost their grafts due to rejection 1, 2, and 4 months after IFN therapy, respectively. In six patients renal function remained stable during and after IFN therapy. We conclude that in selected groups of renal allograft recipients IFN can be used safely and effectively for the treatment of chronic viral hepatitis.

Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. A prospective study

Patients with cirrhosis have a high risk of hepatocellular carcinoma (HCC) but it is unclear how the etiology of liver disease influences tumor development. The authors evaluated hepatitis B and C virus (HBV, HCV) infection in cirrhosis in relation to the risk of HCC. Two hundred and ninety consecutive cirrhotic patients were followed prospectively with periodic ultrasound examination. At entry, patients were tested for markers of HBV and HCV to assess relation to tumor development during follow-up. Twenty and five-tenths percent of patients were hepatitis B surface antigen (HBsAg) positive and 68.9% were positive for HCV antibodies. Previous alcohol abuse was present in 26.2%. During follow-up (46.3 +/- 21.4 months), HCC developed in 32 patients (11.0%) (annual incidence approximately 3%) including 19.6% of HBsAg-positive patients, 12.2% of HCV antibody positive patients and 14.4% of patients with a history of alcohol abuse. The highest rate of HCC was in patients with dual HBsAg and anti-HCV positivity with or without previous alcohol abuse, whereas the lowest incidence (0%) was in cases without risk factors. By univariate analysis, age older than 59 years (P < 0.005), longer duration of cirrhosis (P < 0.005), serum alpha-fetoprotein levels higher than 20 ng/ml (P < 0.05), and dual HBsAg and HCV positivity (P < 0.02) appeared to be associated with HCC. By multivariate analysis, age (P < 0.01), positivity for HBsAg and HCV antibodies (P < 0.05), male sex (P < 0.05), and previous alcohol abuse (P < 0.08) were independently related to tumor appearance. These results, although confirming that male sex and previous alcohol abuse are risk factors for hepatocellular carcinoma in cirrhosis, indicate that concurrent hepatitis B and C virus infection determines the highest risk of developing hepatocellular carcinoma.

Hepatitis B core antibody screening of voluntary blood donors: an extended pilot study using a modified passive haemagglutination assay

Summary. Screening for hepatitis B surface antigen (HBsAg), even by the most sensitive techniques, fails to detect all carriers of the hepatitis B virus (HBV). The presence of hepatitis B core antibody (anti‐HBc) in the absence of HBsAg is a common finding in donors implicated in cases of post‐transfusion hepatitis B (PTHB), and viral DNA may also be demonstrated in many of these individuals. An extended pilot study of routine screening of all donations for anti‐HBc in addition to HBsAg was introduced into the Mersey and North Wales Regional Transfusion Service in November 1991 to improve surveillance for carriers of HBV. In order to reduce costs a modified passive haemagglutination assay was evaluated and found to have a sensitivity of 99% and specificity of 98% compared with a conventional assay. In the first 6 months 60 530 donations were tested and 12 (0–02%) were found to have anti‐HBc in the absence of HBsAg or adequate antibodies to HBsAg (anti‐HBs). These sera will later be submitted for polymerase chain reaction (PCR) testing in order to determine their infectivity or otherwise by the detection HBV DNA sequences.

Immunization of SCID-Hu mice and generation of anti–hepatitis B surface antigen–specific hybridomas by electrofusion

Human hybridomas with specificity for recombinant hepatitis B surface antigen (HBSAg) were produced by adoptive transfer of human peripheral blood mononuclear cells prepared from HBSAg-immune donors to CB.17 mice bearing the severe combined immunodeficiency (SCID) phenotype. A total of ten SCID-Hu mice were immunized with recombinant HBSAg. Eight SCID-Hu mice found to have human HBSAg antibody in their serum were sacrificed, and single-cell suspensions were made from their spleens. The SCID-Hu spleen cells were electrofused to the mouse-human fusion partner H7. HBSAg-specific hybridomas were recovered from all fusions. This method may provide the means for the production of other human hybridomas and may, in some cases, circumvent the need for in vitro immunization or Epstein-Barr virus transformation of human B lymphocytes.

The risk for hepatitis A, B, and C at two institutions for children in Somalia with different socioeconomic conditions.

The prevalence of serologic markers for hepatitis A, B, and C was investigated in children from two residential institutions in Somalia. Among 596 individuals at one residence (Shebeli), the prevalences were 96% for antibody to hepatitis A virus (anti-HAV), 75% for total hepatitis B virus (HBV) markers, 16% for hepatitis B surface antigen (HBsAg), and 1.5% for antibody to hepatitis C virus (anti-HCV). Corresponding figures for the 76 individuals at a smaller residence (Societe Organisation Sociale, SOS) were 59%, 20%, 3.9%, and 0%, respectively. At Shebeli, the HBsAg carrier rates in the 1-10-year-old age group was 28% for boys and 16% for girls. These rates were significantly higher than in the older children (16% and 7.4% for boys and girls, respectively). Fifty-eight percent of the HBsAg carriers were positive for hepatitis B e antigen. Total HBV markers were significantly more frequent in girls from Shebeli, when their duration of residence was longer than five years (89% versus 63%). The duration of stay did not influence the prevalences of HBsAg, HAV, or HCV antibodies. A followup study of children initially seronegative for HBV markers was carried out after two years. For children at Shebeli 1-10 years old, the annual seroconversion rates to HBV markers (95% confidence interval) was 60.5% (42.7-77.0%). The corresponding rate for children at SOS was 10.2% (5.2-17.5%). The differences between the two institutions in the prevalence of serologic markers for hepatitis A and B, and in the annual seroconversion rate to HBV markers reflected different rates of horizontal transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

A high proportion of sera of heroin addicts possesses anti-HLA class I and class II reactivity

The anti-HLA reactivity of sera from 210 heroin addicts was tested by the direct binding with 125I-labeled preparations of HLA class I and class II molecules purified from human B-cell lines of various HLA haplotypes. A high proportion (81.7%) of the sera tested possessed anti-HLA class I and II reactivity. The reactivity did not show any allospecificity and was apparently mediated by antibodies. The control included 100 healthy blood donors, 25 male homosexuals positive for anti-HIV (human immunodeficiency virus) antibodies, and 25 patients positive for HBsAg (hepatitis B surface antigen). Of these controls, only one of the healthy blood donors was positive for anti-HLA reactivity ( P ⪡ 0.001). Among heroin addicts, the reactivity was independent of the presence of either HBsAg or anti-HIV antibodies in the serum.

Occurrence and distribution of hepatitis B infection in the aboriginal population of Western Australia.

In 1986, the prevalences of hepatitis B surface antigen (HBsAg), and other serological markers of infection with hepatitis B virus in the Western Australian adult Aboriginal population, were estimated using a stratified random sample of 1,150 subjects. When the estimates were standardised to the age and sex distribution of the total population of aborigines aged 12 years or over, the prevalence of HBsAg was 7% (95% confidence interval 6-9%). The prevalence of any marker, that is HBsAg and/or hepatitis surface antibody (anti-HBs), was 49% (44-54%). The follow-up blood specimens obtained from three-fifths of the antigenemic subjects indicated that 96% (88-99%) were hepatitis B carriers. Male subjects had twice the prevalence of HBsAg (10%; 7-13%) when compared with females (4%; 3-6%). However, there was only a modest elevation of the prevalence of any marker in men (53%) compared with women (46%). There was evidence that the prevalence of HBsAg increased with age, but this was not the case with any marker. Geographically, there was substantial variation in hepatitis B infection rates. The Eastern Goldfields region had the highest prevalence (HBsAg 12%; any marker 66%), followed by the Kimberley, Pilbara and Central regions (HBsAg 7-9%; any marker 56-59%). The lowest rates were evident in Perth and the South West (HBsAg 3-5%; any marker 23-25%). The highest prevalence of markers in any discrete community was observed in the desert people of Warburton (HBsAg 22%; any marker 85%). These data indicate that, according to World Health Organisation criteria, the aboriginal population of Western Australia has an intermediate to high risk of infection with hepatitis B.

The prevalence of serological markers for hepatitis B virus infection amongst anaesthetists in the Oxford region.

A total of 125 anaesthetists from nine hospitals within the Oxford region were surveyed to study the prevalence of serological markers for hepatitis B virus (HBV) infection. No anaesthetists were positive for Hepatitis B Surface Antigen (HBsAg) and only four (3.2%) were positive for HBsAg antibody (anti-HBsAg). This result is in marked contrast to other studies and suggests that anaesthetists in the United Kingdom do not constitute a high risk population. The reasons for this are discussed.

A STUDY ON SO‐CALLED NOVEL INCLUSION BODY IN HUMAN HEPATOCYTE

The so-called novel inclusion body (NIB) is an intrahepatocytic structure which is frequently observed in human cirrhotic liver. It resembles very much to, but definitely differs from Hepatitis B surface antigen (HBsAg) morphologically. The age distribution of liver cirrhosis cases positive for NIB is similar to that positive for HBsAg, except for an existence of a time lag in mean age. One of the best staining methods to demonstrate NIB, for example, is to exhibit it as a reddish body stained by Luna, with a contrast of HBsAg counterstained purple in color by aldehyde fuchsin after thiosulfation. Electron microscopy of the liver obtained from a patient, negative for both HBsAg and Hepatitis B e antigen (HBeAg) but positive for Hepatitis B core antibody (HBcAb) and Hepatitis B surface antigen antibody (HBsAb) clinically, revealed some unfamiliar, tubular and cisternal arrays showing a network pattern and ring-shaped structure at the site exactly corresponding to NIB localization. These are considered to have been induced from the endoplasmic reticulum by an unknown agent, for which non A non B hepatitis virus (NANBV) is rationally postulated as one of the possibilities. A close relation between NIB and NANBV is highly suspected because of much similarities in histology, histochemistry, age distribution, and electron microscopy. The true nature of NANBV should be rescrutinized, especially in relation with Hepatitis B virus infection, since NIB is quite often observed also in cirrhotic liver positive for HBsAg.