Increased severity and morbidity of acute hepatitis in drug abusers with simultaneously acquired hepatitis B and hepatitis D virus infections.

Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.     

应用血清学方法鉴别急性和慢性病毒性乙型肝炎

本文用ELISA间接法检测急性和慢性乙型肝炎病人血清特异性抗HBcIgG,用ELISA捕捉法检测特异性抗HBcIgM。11例急性乙肝病人急性期抗HBcIgM100％阳性,抗HBcIgG全部阴性;恢复期抗HBcIgM 81.8％阴转,抗HBcIgG则100％阳转。17例慢性乙肝病人抗HBcIgM82.35％阳性,抗HBcIgG 100％阳性。被检血清经密度梯度超速离心,证实抗HBcIgM和抗HBcIgG两类抗体反应在急性和慢性乙肝病人血清中具有不同的动态规律。     

Seroepidemiologic study of adult T-cell leukemia virus (ATLV) and hepatitis B virus infection in Okinawa, Japan

A total of 2,283 serum samples were collected from healthy subjects in three islands of the Yaeyama district of Okinawa, Japan. These sera were tested for the presence of hepatitis B surface antigen (HBsAg), for antibody to hepatitis B core antigen (anti-HBc), and for antibody to adult T-cell leukemia-associated antigen (anti-ATLA). Correlation between hepatitis B virus infection and adult T-cell leukemia virus (ATLV) infection was determined by using the prevalence rates for three virus markers. Overall prevalence of HBsAg, anti-HBc and anti-ATLA was 6.5%, 57.4%, and 17.9%, respectively. Age-specific prevalence of anti-HBc and anti-ATLA increased with age, but that of HBsAg did not. Sex-specific prevalence of HBsAg was significantly higher in males than in females, but that of anti-ATLA was significantly higher in females than in males. Statistical analysis revealed that prevalence of anti-ATLA was significantly higher in HBsAg-positive persons and HBsAg-negative/anti-HBc-positive persons than in those negative for HBsAg and anti-HBc. These data suggest that hepatitis B virus-infected persons have a significantly higher chance of adult T-cell leukemia virus infection than those without hepatitis B virus infection in the area studied.     

Immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) as a marker of interferon therapy in patients with persistent hepatitis B virus infection

Immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) was measured by radioimmunoassay in the sera of 96 HBV carriers. IgM anti-HBc was detected in 17 of 66 patients with chronic active hepatitis and in 4 of 11 with liver cirrhosis. This antibody was not present in asymptomatic carriers or in patients with chronic persistent hepatitis. Testing of sequential samples revealed that the presence of IgM anti-HBc indicated active replication of HBV and at the same time an immune response to the virus. The relationship between IgM anti-HBc and the response to interferon (IFN) therapy was also studied. Results showed that IgM anti-HBc is a useful marker of the efficacy of interferon therapy.     

Antinuclear antibody (anti-HBc) and liver pathology in acute and chronic virus B hepatitis]

HBsAg and anti-HBc, the antibody to core antigen of hepatitis B virion, were titrated by solid phase radioimmunoassay in 40 sera of HBsAg carriers with acute and chronic hepatitis and in 20 healthy subjects carrying anti-HBc alone or associated with anti-HBs. No correlation was found between HBsAg and anti-HBc titers in the single category of patients. In contrast, geometric mean titer of anti-HBc (ranging from 2(14) to 2(15)) of patients with chronic active hepatitis was significantly higher ( p = < 0.01) than that of patients with acute or chronic persistent hepatitis and healthy HBsAg carriers (ranging from 2(9) to 2(14)). Anti-HBc titer of 20 subjects without detectable HBsAg was less than 2(7). These data suggest that in subjects with persistent B virus infection, anti-HBc response is correlated with synthesis of viral genome rather than of surface antigens, so that a much higher titer of anti-HBc was detected only in patients with a more active liver disease.     

Detection of core antibody in hepatitis B infection.

Hepatitis B core antigen (HBcAg) is found on the decoated Dane particle and on a morphologically similar particle detected mainly in the nucleus of hepatocytes of patients with hepatitis B. HBcAg prepared from the liver of a chimpanzee infected with hepatitis B virus was used to test human serum for core antibody (anti-HBc) by complement fixation. Anti-HBc was found in serum collected from patients with hepatitis B in both the acute and convalescent stages, from carriers of hepatitis B surface antigen (HBsAg) and from patients with chronic liver or renal disease who were carriers of HBsAg. It was not found in patients with hepatitis A or infectious mononucleosis, or in healthy persons who were not carriers of HBsAg.     

A seroepidemiologic study of hepatitis B virus infection among barbers in Huangshi City, Hubei, China

Between March and August 1986 in Huangshi City, serum samples were collected from 316 apparently healthy barbers as a study group, as well as from 361 healthy employees of department stores as a control group. They were tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) by enzyme-linked immunoadsorbent assays. Barbers showed a prevalence higher than that in controls for HBsAg (16.8 vs. 9.2%, P less than 0.01), anti-HBs (67.1 vs. 45.9%, P less than 0.001), and anti-HBc (39.2 vs. 21.2%, P less than 0.001). The prevalence of at least one marker of hepatitis B virus (HBV) infection was significantly higher in barbers than in controls (86.1 vs. 61.7%, P less than 0.001). Although the socioeconomic status and education level did not correlate with the frequency of HBV markers, the prevalence of HBsAg increased in parallel with the duration of practice. Because of their high risk for HBV infection, barbers need to be screened for markers of HBV infection on a routine basis, and are prime candidates for immunoprophylaxis with hepatitis B vaccine.     

Prevalence of hepatitis B viral markers in Vietnamese blood donors

Serum samples were assayed using radioimmunoassay in 573 Vietnamese blood donors living in Hano? (North Viet Nam). 66 (11.5%) subjects were HBsAg-positive. Of these 66 HBsAg carriers, 17 (25,8%) were positive for hepatitis B e antigen (HBeAg) and 43 (65.1%) for antibody to HBeAg (anti-HBe). 22 (3.8%) subjects were positive for antibody to hepatitis B core antigen (anti-HBc) alone. 402 (70.2%) subjects were positive for antibody to HBsAg (anti-HBs). This anti-HBs percentage increased with age. Only 83 (14.5%) subjects were negative for all hepatitis B viral (HBV) markers. This no HBV markers percentage decreased with age. The chi 2 test showed a non significant difference for frequencies of HBsAg, anti-HBc alone, anti-HBs but a significant one for frequencies of no HBV markers in men and women.     

Importance of markers of hepatitis B virus in alcoholic liver disease.

To determine the importance of the presence of serological markers of hepatitis B virus infection in patients with alcohol related liver disease we compared cumulative alcohol intake and clinical and histological features in patients with markers of hepatitis B virus infection and in those without. Hepatitis B surface antigen (HBsAg) was detected in five (2%) out of 285 patients studied and antibody to HBsAg (anti-HBs) in 41 (14%); one patient had antibody to hepatitis B core antigen alone. The combined prevalence of markers of hepatitis B virus infection was similar in patients with alcoholic cirrhosis (18%) and precirrhotic liver disease (13%). Two patients positive for HBsAg had histological features of both alcoholic liver disease and chronic active hepatitis, with stainable HBsAg. Patients with anti-HBs were, however, histologically indistinguishable from patients without markers, and the mean cumulative alcohol intake of patients with anti-HBs was similar to or even higher than that of patients with liver disease of comparable severity who had no evidence of previous infection. The presence of markers of hepatitis B virus infection was related to former residence in countries with a high prevalence of the infection and to previous parenteral treatment and blood transfusions. Infection with hepatitis B virus does not enhance the development of chronic liver disease in heavy drinkers, except in the small number who remain positive for HBsAg.     

Epidemiologic features of hepatitis B virus infection in northern Labrador.

We studied the epidemiologic features of hepatitis B virus (HBV) infection in northern Labrador to determine the prevalence of the infection and to obtain a database to develop a vaccination strategy. The study population included seven communities in which five ethnic groups were represented: Inuit, Innu, mixed Inuit and European ancestry ("settler"), nonnative/nonsettler transient population ("white") and people of Innu-white or Innu-Inuit origin ("mixed"). Blood samples from 2156 people (62% of the area residents) were tested for antibody to HBV core antigen (anti-HBc), HBV surface antigen (HBsAg), HBV e antigen (HBeAg), anti-HBc IgM and antibody to the surface antigen (anti-HBs). The overall crude prevalence rate of HBV seromarkers was 14.7% and the HBsAg carrier rate at least 3.2%; the rates were highest for Inuit (26.4% and 6.9% respectively), followed by settler (10.0% and 1.9% respectively) and Innu (7.6% and 0.4% respectively); the white and mixed groups had the lowest overall rates (2.5% and 3.3% respectively). Although the overall prevalence rates were about the same for the two sexes, the HBsAg carrier rate was higher in males (male:female ratio 1.6:1.0). No HBV carriers were positive for HBeAg or anti-HBc IgM antibody. The rate of exposure to HBV was 4% for those below the age of 20 years and reached a peak for those aged 45 to 54 years (85% for Inuit, 40% for settlers and 37% for Innu). There was also a wide variation in the age-standardized prevalence rates (0% to 27.9%) among the ethnic groups in the seven communities surveyed.     

Antibody to hepatitis B core antigen in chronic active hepatitis.

Antibody to hepatitis B core antigen (anti-HBc), which has been assumed to be a more sensitive indicator of hepatitis B virus replication than hepatitis B surface antigen (HBsAg), was detected in the sera of 26 of our 65 patients with HBsAg-negative chronic active hepatitis. Thus despite the absence of HBsAg the liver disease could be the consequence of chronic infection with hepatitis B virus in these patients. They differed, however, from a group of 35 patients with HBsAg-positive hepatitis in being older on average and having less active liver lesions. The two groups could represent either two stages of chronic infection with hepatitis B virus or two types of response to it.     

Seroepidemiology of hepatitis B virus infection and high rate of response to hepatitis B virus Butang vaccine in adolescents from low income families in Central Brazil

In order to evaluate the seroepidemiology and response to Butang vaccine in adolescents from low income families in Central Brazil, blood samples of 664 adolescents were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) markers, and multiple logistical regression analysis was carried out to determine variables associated with hepatitis B virus (HBV) infection markers. further, three 20 microg Butang vaccine doses were offered to all susceptible individuals (n = 304). Among those who accepted them (n = 182), the seroresponse was evaluated in 170 individuals by quantitative anti-HBs. an overall hbv prevalence of 5.9% was found: four adolescents were HBsAg positive, 24 were anti-HBc, anti-HBs-reactive, and 11 were anti-HBc only. The analyse of risk factors showed that age 16-19 years, place of birth outside Goiás, school B and body piercing were statistically associated with HBV infection markers (p < 0.05). All 170 adolescents responded to Butang, and a geometric mean titer (gmt) of 4344 mUI/ml was obtained. these results reinforce the importance of hepatitis b vaccine in adolescents despite of the hbv regional endemicity, and suggest that three doses of 20 microg of the Butang should guarantee protective anti-hbs levels to individuals at a critical time for hepatitis b acquiring such as latter adolescence and adulthood.     

A case of hepatitis B reactivation due to the hepatitis B virus escape mutant in a patient undergoing chemotherapy

A 62-year-old man had chronic hepatitis B virus (HBV) infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient’s virologic markers were positive for hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc), while antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine (LMV) therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin (TB) were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C (HBsAg subtype adw) with immune escape mutations, F8L, S34L, F41S, G44V, F93C, V96G, L110I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.     

Modulation of hepatitis B infection by intravenous application of an immunoglobulin preparation that contains antibodies to hepatitis B e and core antigens but not to hepatitis B surface antigen.

Repeated administration of an intravenous immunoglobulin containing antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc) but free of antibody to hepatitis B surface antigen (anti-HBs) before and after the inoculation of 10(4.9) 50% chimpanzee infective doses of hepatitis B virus (HBV) markedly prolonged the incubation period of HBV in experimentally infected chimpanzees. Similar administration of an immunoglobulin preparation containing anti-HBc but free of anti-HBe and anti-HBs or intramuscular administration of a single dose of immunoglobulin containing anti-HBe and anti-HBc 3 days before or after inoculation with HBV did not appear to modulate HBV infection. These observations suggested that anti-HBe, or an unidentified antibody associated with it, may have biological activity in the modulation of HBV replication.     

Detection of hepatitis B virus infection markers at a collective

The occurrence of serological markers of hepatitis B virus infection among the members of a newly formed community (370 persons) was determined. The markers were detected with the use of highly sensitive methods for the detection of HBsAg, anti-HBs, HBeAg, anti-HBc, IgM anti-HBc. At the time of the formation of this community HBsAg, anti-HBs and anti-HBc were detected, respectively, in 4%, 11% and 31.3% and 6 months later, in 8.4%, 9.5% and 46.4% of persons. The presence of a considerable number of inapparent forms of hepatitis B and differences in the degree of the involvement of individual groups in this community into the epidemic process have been shown.     

Antibodies against HBV, HCV and HAV detected by using microparticle enzyme immunoassay in hepatitis outpatients

The presence of the hepatitis B surface antigen (HBsAg), of the antibodies against HBc, HCV and HAV was determined in outpatients in the period September 2005 - December 2006. The serum samples were analyzed by using Enzyme Immunoassay microparticles (Abbott AxSYM System). At least one test was positive in 238 patients (15.4%) of the total of 1547 patients. Of the 238 positive subjects, in 130 positive subjects (54.6%) the existence of HBV infection could be ascertained based on the presence of HBsAg or of the antibodies against HBc or of their association; 83 patients (34.9%) presented antibodies against HCV and in other 12 patients the antibodies against HCV were associated with HBsAg or with antibodies against HBc, suggesting the coexistence of HCV and HBV infection. The antibodies against HCV and the associations between HCV and HBV were mostly detected in subjects with the diagnosis of cirrhosis, liver failure or chronic hepatitis. Of the 13 (5.46%) patients with antibodies against HAV, 6 patients presented the associations: in 2 cases antibodies anti-HAV with positive HBsAg, in 1 case antibodies anti-HAV and anti-HBc with positive HBsAg, in 2 cases antibodies anti-HAV and anti-HBc and in 1 case antibodies anti-HAV and anti-HCV.     

The frequency of detection of markers of hepatitis virus B infection among the inhabitants of Rustavi, the Georgian SSR

Blood serum samples from 1,087 patients with acute viral hepatitis were studied. HBsAg was detected in 36.6% of cases. The study of anti-HBc IgM made it possible to diagnose hepatitis B in 6.6% of cases. The study of blood serum samples from 362 donors, 2,356 pregnant women and 163 medical workers in Rustavi for the presence of the markers of hepatitis B infection revealed a wide spread of hepatitis B in Rustavi.     

Hepatitis B infection among patients attending a sexually transmitted diseases clinic in Rio de Janeiro, Brazil

Hepatitis B virus (HBV) has a low endemicity in Rio de Janeiro, Brazil. Sexual transmission must play an important role in this virus, but the prevalence and risk factors have never been properly investigated. The aim of this paper is to determine the prevalence and risk factors for HBV infection in patients attending a Sexually Transmitted Diseases Clinic of the Universidade Federal Fluminense, from the State of Rio de Janeiro, Brazil. In a retrospective study, HBV seroprevalence was investigated in 440 patients. Serum of each patient was assayed for antibodies against hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg) and antibodies against hepatitis B surface antigen (anti-HBs). Demographic and risk factor data were extracted from clinic notes. The overall seroprevalence of exposure markers for HBV (anti-HBc, HBsAg and anti-HBs) were 13%, 3.4% and 8.5% respectively. Homo/bisexual behaviour, anal intercourse, HIV infection, positive serology for syphilis and blood transfusion were predictors of the HBV exposure. Among demographic data, age and place of birth were associated with the anti-HBc seropositivity.     

Suitability of yeast- and Escherichia coli-expressed hepatitis B virus core antigen derivatives for detection of anti-HBc antibodies in human sera

Antibody to hepatitis B virus core antigen (anti-HBc) is one of the most important serological markers during hepatitis B virus (HBV) infection. The quality of the hepatitis B virus core antigen (HBcAg; diagnostic antigen) is crucial to the accuracy of anti-HBc detection. In an attempt to explore the suitability of recombinant HBcAg (rHBcAg) for diagnostic purposes, HBcAg was expressed in Escherichia coli (E. coli) and Pichia pastoris (P. pastoris) and evaluated for the detection of anti-HBc. The expression level of the recombinant protein satisfied the criteria for large-scale biologic production. P. pastoris- and E. coli-derived rHBcAg were purified with gel filtration followed by sucrose gradient (reagents A and C) or with a monoclonal anti-HBc antibody binding (reagents B and D) and were utilized to detect anti-HBc in competitive inhibition enzyme-linked immunosorbent assay (ELISA) format. The ELISA using P. pastoris-derived rHBcAg had a higher specificity and sensitivity than that using E.coli-derived rHBcAg to detect the anti-HBc standard panel. Serum specimens were collected from HBV-infected patients and healthy individuals (voluntary blood donors). Anti-HBc was detected in those specimens using P. pastoris- and E. coli-derived rHBcAg. The positive rate of anti-HBc detection in HBV-infected patients' sera was 100% with reagents A and B, 96.4% with reagent C, and 93.6% with reagent D. The negative rate in healthy control sera was 100% with reagents A and B, 97.0% with reagent C, and 99.7% with reagent D. These data indicate that P. pastoris-derived rHBcAg is superior to E.coli-derived rHBcAg for the detection of anti-HBc using the diagnostic ELISA.