HBc Ab Research Articles

Impact of past HBV exposure on virological response to combined interferon ribavirin therapy in patients with chronic HCV genotype 4

Aim: is to investigate if past exposure to HBV in chronic HCV infection promotes the progression of liver disease and influences Interferon (INF) response or not. Methods: 185 patients with chronic HCV were recruited and randomized into 2 groups, group I was treated with PEG-IFN alfa-2b plus ribavirin and group II with 3 MU/TIW IFN alfa-2b plus ribavirin. All patients had HBsAg negative & patients had HBc Ab positive tested for HBsAb. Patients with HBc Ab (n = 37) were tested for serum HBV DNA. Pretreatment liver biopsy and Immunohistochemistry was performed for detection of HBsAg and HBcAg using monoclonal antibodies. Demographic and laboratory data were collected. Results: 70/185 (38%) patients had Anti-HBc, 37 (20%) had isolated anti-HBc and none of the 37 subjects with isolated anti-HBc had serum HBV DNA. Sustained Viral Response (SVR) was achieved in 32/70 (46%) and 46/115 (40%) in anti-HBc seropositive and seronegative patients respectively, in conventional IFN group SVR was 37% and 39% in past HBV exposed patients and unexposed respectively, in PEG IFN group SVR was 59% and 41% in past HBV exposed patients and unexposed respectively. Among anti-HBc and anti-HBs seropositive patients SVR was 10/12 [83%] and 4/21 [19%] p = 0.004 in PEG and conventional IFN respectively. Marked fibrosis was diagnosed in 20% past HBV exposed patients versus 10% in unexposed patients (p = 0.01). Conclusion: past HBV exposure promotes the progression of liver disease but has no effect on the SVR to antiviral therapy in chronic HCV genotype 4 patients.

Effect of etanercept and entecavil in a patient with rheumatoid arthritis who is a hepatitis B carrier: a review of the literature

In this report, we describe a case of a 48-year-old Japanese woman who is a hepatitis B (HB) carrier with rheumatoid arthritis (RA). She had the following antibody profile: HBs Ag(+), HBs Ab(-), HBe Ag(-), HBe Ab (+), HBc Ab(-) and undetectable HBV-DNA level. She was treated with auranofin, salazosulfapyridine, and bucillamine. Finally, she was treated with D: -penicillamine, but her disease activity remained elevated. Prophylactic treatment of entecavir 0.5 mg daily was started in March 2008 and all disease-modifying anti-rheumatic drugs were stopped. After 2 weeks, etanercept monotherapy was started at 25 mg subcutaneously once a week. Significant improvement in clinical parameters of disease activity and well being was observed. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and HB virus viral load did not change significantly. Serum ALT, AST, and HB virus viral load were followed-up at every 3-month intervals, from initiation of therapy up to 24 months after the start of treatment with etanercept. We have also summarized the course of nine RA patients who received etanercept and were HB carriers or had chronic HB according to our literature search. Based on the results of our study, treatment of these patients with etanercept co-administered with lamivudine or entecavir appears to be safe.

Hepatitis B core antibody in blood donor in sistan-balutuestan province of Iran

Safety of blood donor is an important issue for a recipient of blood so all blood donors are to screened for viral such as HBV, HCV, and HIV. Nevertheless, infections sometime occur by blood and its products. Because we haven't got any awareness about isolated Hbc Ab from a blood donor who presented of occults B hepatitis which can transmit infection to blood recipient, we decided to evaluate HbcAb in a blood donor in this province. This is a cross-sectional study on a blood donor in Sistan-Balutuestan province in southeast of Iran in 2010. All individuals referred for blood donation recruited to this. After consent demographic data was recorded from each case, 5 ml blood sample was drawn and centrifuged to separate out the serum and then HbsAb, HbcAb was assayed. Data analyzed by SPSS 16 and frequency, chi- square test, and Fisher exact test was used and if P > 0.05 it was accented as significant association. All individuals were men with age 55 10.5 years. The number of people who had free job was 149 (34.6%) and the number of people whose education level was diploma was 159 (36.9%). About 423 (98.1%) lived in urban areas. The mean weight of men was 76.6 13.7; about 259 (60.1%) men were married. A total of 22 (5.1%) had a positive smoking history. HBc Ab was positive in 87 (20.2%). Nearly all people had HBsAb titer more than 10 IU/L. This study showed that some of the blood donors had isolated HbcAb positive therefore we recommend HbcAb screening for blood donation.

Estimation of T-helper 1 Cytokines (IFN-y and TL-2) in HBV Infected patients and Individuals vaccinated with Recombinant HB Vaccine

Background and objective: The specific cellular immune responses play a main role in the hepatic necrosis that occurs with hepatitis B virus (HBV) infection. Interferon-g (IFN-g) and interleukin-2 (IL-2) are considered examples on T helper 1(Th1) cytokines which required for host antiviral immune response and involved in cell-mediate immunity against HBV infection. This study was designed to estimation T-helper 1 cytokines (IFN-g and IL-2) in HBV infected patients and individuals vaccinated with recombinant HB vaccine. Methods: The study groups were classified into patient group 35 (15 acute hepatitis (AH) and 20 chronic hepatitis(CH)) and 35 vaccinated group (20 responder (RD) and 15 Nonresponder (NRD)) and 18 control group, during May to November 2007. Blood samples were taken from patients and hospitals staffs in Nanakaly, Erbil and Rizgary Teaching Hospital to detect hepatitis B surface antigen (HBsAg), anti hepatitis core antibody IgM (Anti- HBc Ab(IgM)), Anti-HBs Ab, IFN-g level and IL-2 level in serum by enzyme linked immunosorbent assay (ELISA). Results: The concentration of IFN-g and IL-2 levels in the AH group differed significantly compared with healthy control and CH patients (p<0.01) by F-test. LSD-analysis for IFN-g also revealed same result while IL-2 level significantly increased in healthy control only. Ftest for IFN-g revealed (p<0.05) among RD group, NRD group and healthy non vaccinated (HN) control in ≥30 and <30 years old respectively but inverse result was observed in IL-2 levels (p>0.05).

ANTIBODY TITRATION AND IMMUNE RESPONSE OF IRANIAN β-THALASSEMIC PATIENTS TO HEPATITIS B VIRUSE VACCINE (BOOSTER EFFECT)

Background: Thalassemia is hereditary anemia with lifelong transfusion as treatment and hepatitis B virus (HBV) infection is one of the transfusion transmitted infections (TTI). HBV vaccinination is obligatory for these patients by 3 double-dose injections. The authors studied the HBV status and immune response to vaccination by hepatitis B surface antibody (HBsAb) titration in their thalassemic patients. They also compared these results with their previous study to find out the effectiveness of a booster dose in the immunity of patients against HBV. Materials and Methods: Hepatitis B surface antigen (HBsAg), HBsAb, and hepatitis B core antibody (HBcAb) were detected in sera of 416 patients at the Tehran Adult Thalassemia Clinic. The immune status was classified into 4 categories: (1) immune to HBV via the vaccination (positive vaccinal)—if HBs Ag: negative, HBsAb: positive, HBcAb: negative; (2) immune to HBV via the natural disease (past infection)—if HBs: negative, HBsAb and HBcAb: both positive; (3) nonimmune to HBV (negative)—if all three parameters were negative; (4) carrier of HBV (carrier state)—if HBs Ag was positive and HBsAb and HBc Ab: both negative. Also grading of immunity done by HBsAb titration as positive if HBsAb titer was more than 100 IU/mL, negative if HBsAb titer was less than 10 IU/mL, and weakly positive if antibody level was 10–100 IU/mL. Results: There were 416 patients: 302 (72.5%) with thalassemia major (TM), 104 (25%) thalssemia intermedia (TI), 7 (1.6%) sickle thalassemia (ST), and 3(0.7%) α-thalassemia (HbH disease). The mean age was 25.6 ± 8.3 yr and median age was 24 yr; there were 247 (59.4%) males and 169 (40.6%) females. A total of 257 patients (61.7%) were splenectomized. According to our classification 289 (69.4%) were immunized by vaccination; 80 (19.2%) were immunuzed by past infection; 44 (10.5%) were negative, and 3 (0.7%) were in carrier state of HBV. In grading of immunity to HBV vaccination, 319 (76.6%) patients had HBsAb > 100 IU/mL (positive), 77 (18.5%) between 10 and 100 IU/mL (weakly positive), and 20 (4.8%) less than 10 IU/mL (negative). There was no significant correlation between the level of HBsAb and spelenectomy or type of thalassemia. Conclusion: Response rate to vaccination is more than 95% after complete course (3 doses) in healthy individuals but failure to fulfill vaccination seems a problem in chronic transfused patients. These results reflect advantages of a booster dose of vaccine, which increased the protection level among these high-risk patients from 46.9% (in the authors’ previous data) up to 69.4% in this study.

Long Term Effects of One or Two Doses of Hepatitis B Vaccine in Adults After Five Years

The aim of this study is to evaluate hepatitis B vaccine protection in those adults who have taken one or two does of vaccine before. It was a retrospective cross sectional study was conducted on fifty-six military personnel in Tehran, Iran in the spring 2007. Demographic data such as age, marital status, education level, number of vaccine doses injected and, type of vaccine and date of last vaccination was collected. Their serum was tested for HBs Ab, HBc Ab and HBs Ag and finally the results were analyzed by SPSS software. All individuals were male with the mean age of 33.9+/-8.9 years. Twelve individuals who had only received one dose of injected vaccine had no antibody against HBsAg and no protection against hepatitis B virus. Of forty-four individuals that had received two doses of injected vaccine, 27 persons (61.4%) were protected and had serum HBsAb more than 10 MIU mL(-1). In conclusion one dose of HBV vaccine cannot produce immunity for five years but two doses of HBV vaccine can produce immunity for five years. However, HBsAb should be tested to make sure of immunity.

Transplantation of livers from HBc Ab positive donors into HBc Ab negative recipients: a strategy and preliminary results

Here we describe a strategy for using livers from hepatitis B core antibody (anti-HBc) positive donors in anti-HBc negative recipients and report our preliminary results. Adult anti-HBc negative recipients were immunized against hepatitis B virus (HBV) prior to transplantation. Liver biopsies from anti-HBc positive, HBs Ag negative donors were performed at the time of procurement to rule out acute hepatitis or chronic liver disease. Donor serum and liver samples were collected for HBV DNA analysis by PCR. Recipients were given HBIG (10000 units, i.v.) during the anhepatic phase of transplantation. Patients were treated with lamivudine (150 mg) beginning on postoperative day (POD) 1. If HBV DNA was not detected in either donor liver or serum by PCR, recipient antiviral therapy was stopped. If donor liver and serum were positive for HBV DNA by PCR, the recipient was maintained on combination lamivudine and HBIG therapy. If HBV DNA was detected in donor liver but not in donor serum, the patient was managed on lamivudine therapy alone. Between February 1999 and June 2000, six anti-HBc negative recipients received liver transplants from anti-HBc positive donors. PCR analysis of serum from the six donors was negative for HBV DNA in each, while donor liver PCR analysis was positive in five of six for HBV DNA. Accordingly, all patients were given HBIG in the anhepatic phase of transplantation and five of six were maintained on daily lamivudine therapy. Follow-up periods have ranged from 2 to 18 months. There has been no emergence of de novo hepatitis B. Serial serum HBs Ag and HBV DNA assays have all proven negative. Moreover, while on lamivudine therapy, 2 patients now have undetectable HBV DNA in hepatic allograft biopsies by PCR analysis. Our strategy for using livers from anti-HBc donors has yielded promising initial results. De novo hepatitis B has not occurred and our data suggest residual hepatitis B virus may be eradicated in recipients maintained on lamivudine therapy.

Effects of interferon-γ and-β in treatment of chronic hepatitis B

After pretreatment with interferon (IFN)-γ in order to increase the expression of HLA class I antigens, IFN-β was administered to 16 patients with chronic hepatitis B for the purpose of evaluating efficacy of IFN-γ plus IFN-β treatment. The patients were divided into two groups. Group I patients ( n = 6) received IFN-γ at a dosage of 0.5 ∼ 2.0 M JRU/day for 8 weeks. Group II patients ( n = 10) received IFN-γ at the same dosage and then, after a 4 ∼ 8 week interval, received IFN-β 3 ∼ 6 MU/day for 7 weeks. Serum β 2 MG levels increased more during the IFN-γ administration period than in the IFN-β period, while the increases of serum 2–5 AS activity and the decrease of DNA-P were observed more markedly during the IFN-β period. Increases in ALT level, which is considered to reflect the enhanced immune response level, were observed 4 ∼ 8 weeks after completing IFN-γ administration. After completion of each regimen, two of the six group I patients and four of the ten group II patients were evaluated as responders; one in group I, and two in group II were transient responders; and three in group I, and four in group II were non-responders. In the responders, pretreatment IgM HBc Ab levels were significantly lower than those of non-responders, and they increased more during IFN administration as compared to non-responders ( P < 0.05). Seven of eight patients (one in group I, and seven in group II), who were non-responders to previous IFN therapy, became responders in this IFN-γ plus IFN-β treatment. Results suggest that IFN-γ alone is lacking in effectiveness for treatment of chronic hepatitis B, whereas the combination of IFN-γ and subsequent IFN-β administration can improve the clinical outcome of intractable chronic hepatitis B.

Specific detection of anti-HBc antibodies with an enzyme immunoassay using recombinant HBcAg and monoclonal antibodies

An enzyme immunoassay for the detection of total anti-HBc antibodies in undiluted serum samples was developed. This assay utilizes an anti-HBc monoclonal antibody and a recombinant HBc antigen. The results of the clinical validation are now reported. A total of 1,301 sera were tested using both the Recombinant TOTAL HBc Ab EIA and a reference assay. The specificity was evaluated on a panel of 573 normal human sera and human sera from subjects with pathological findings unrelated to a hepatitis B virus infection. The sensitivity was studied on a total of 455 sera from HBV infected patients at different stages of infection. The final results indicate 99.8% sensitivity and 99.8% specificity. In addition, 273 sera with either isolated anti-HBc antibodies or with anti-HCV antibodies were tested. The agreement between the Recombinant and the reference assay for these two populations, 96.6 and 90.1%, respectively, is discussed.

Viral risks associated with blood transfusion

The presence of viruses in blood cells or plasma from asymptomatic donors is the major risk of transmitting an infectious agent through blood transfusion. The main viruses involved are hepatitis viruses and retroviruses. The risk of transmitting hepatitis B virus (HBV) and hepatitis C virus (HCV) has been progressively and efficiently reduced in the last years by the successive introduction of hepatitis B surface antigen (HBsAg) screening, elevated serum alanine aminotransferase (ALT), antibody to hepatitis B core (HBc Ab), and more recently antibody to hepatitis C virus (HCV Ab). The risk of transmitting human retroviruses like human immunodeficiency virus (HIV) and human T-cell leukemia/lymphoma virus (HTLV) has also been reduced drastically thanks to screening for corresponding antibodies. However, except for HBs Ag screening, the immunoassays used for HCV, HIV, or HTLV only detect antibodies. Therefore, although they are infectious, a few blood units may be not discarded. The efficacy of preventive measures depends on the incubation time, the infectivity during this silent phase, and the sensitivity of screening procedures. Human cytomegalovirus (HCMV) and parvovirus B 19 are responsible for common infections. Consequently, 30% to more than 50% adults have serologic evidence of past infection. However, both viruses may cause severe primo-infections in some circumstances, especially in pregnant women or immunodeficient individuals.

166 THE RELATIONSHIP BETWEEN DISTURBED LIVER FUNCTION, IRON AND MARKERS OF HEPATITIS B UIRUS INFECTION IN BRITISH CHILDREN WITH BETA THALASSAEPIIA

Although chronic liver dysfunction in β Thalassaemia major has been associated with transfusion induced iron overload. Chronic Hepatitis B virus (HBV) infection has also recently been implicated. We, therefore, studied 16 children (8 male, 8 female) aged 1-14 years, to assess the influence of iron overload measured by serum ferritin and the volume of transfused blood, and the presence of markers of HBV infection (HBs Ag, HBc Ab, HBs Ab) on liver dysfunction. Thirteen children had elevated serum transaminases; 6 of these had received > 10D units of blood and had had serum ferritin levels of > 6,000mcg/L. All 16 received chelation therapy with a fall in serum ferritin levels from a maximum of 1280-13, 900mcg/L to a minimum of 370-5, 450mcg/L. Concommitant improvement in liver function occured in 10. Although 11 patients had visited HBV endemic areas and 6 had been transfused there, only 2 developed markers of HBV infection. Both had clinical, biochemical and serological evidence of acute HBV infection; they had abnormal liver function prior to the HBV infection, and transaminases returned to these levels after the acute HBV infection. Thus in children, iron overload rather than HBV infection is the major cause of chronic liver dysfunction. However, active immunisation against HBV is necessary to protect these children who commonly receive transfusion whilst in endemic areas.

Clinical and chemotherapeutic study of hepatocellular carcinoma in Malaysia. A comparison with African and American patients

Twenty Malaysian patients with unresectable primary liver cell cancer were prospectively studied at the General Hospital, Kuala Lampur, and were compared for clinical features with an equal number each of African and American patients being studied by the Eastern Cooperative Oncology Group. The patients received intravenous 5-FU and oral MeCCNU which was used for the first time in an Asian country. Most of the Malaysian patients were Chinese, belonged to younger age groups, and presented with massive hepatomegaly, jaundice, and fever. Toxicity to MeCCNU invariably occurred in the form of leukopenia or thrombocytopenia, but none life threatening. Partial response was seen in 20% of Malaysians as compared to 16% in Americans and none in Africans. Malaysians achieved a median survival of 16 weeks compared to 28 weeks in Americans and only eight weeks in Africans. Malaysian Chinese patients were all HBc Ab + ve. Other factors which may have played an etiologic role in the induction of primary liver cancer included alcohol, Chinese herbal medicines, aflatoxin and habitual use of medicated rubbing oils.