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.     

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.     

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。     

IgM antibody against hepatitis B core antigen (IgM anti-HBc): diagnostic and prognostic significance in acute HBsAg positive hepatitis.

IgM antibody against hepatitis B core antigen (IgM anti-HBc), a marker of recent hepatitis B virus infection, was sought by radioimmunoassay in sera diluted 1/4000 from 376 patients presenting to four centres in Italy with acute, apparently type B hepatitis (hepatitis B surface antigen (HBsAg) positive). In 320 patients (85%) a positive IgM anti-HBc test result confirmed that hepatitis was due to primary infection with hepatitis B virus. In the remaining 56 patients absence of the IgM marker indicated that they were previously unrecognised long term carriers of HBsAg. Further serum analysis often showed delta infection and occasionally hepatitis A or cytomegalovirus infection as the true cause of their illness. After six to eight months circulating HBsAg persisted in 38 of 45 patients (84%) without IgM anti-HBc but in only six of 150 patients (4%) with the IgM antibody (p less than 0.0001). A negative IgM anti-HBc test result in patients with acute HBsAg positive hepatitis points to a factor other than hepatitis B virus as the cause of the liver damage and predicts the carriage of HBsAg.     

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.     

In vitro production of antibody to hepatitis B core and E antigens by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection

To evaluate the relative immunogenicity of and the mechanism for production of antibody to hepatitis B core (HBc) and hepatitis B e (HBe) Ag, we investigated the in vitro anti-HBc and anti-HBe production by PBMC from 25 patients with chronic active hepatitis (CAH) (15 with HBeAg and 10 with anti-HBe) and 12 ASC (5 with HBeAg and 7 with anti-HBe) in the presence of PWM, rHBcAg, or purified HBeAg. PWM-stimulated culture produced higher titer anti-HBc (mean % inhibition +/- SD = 73 +/- 23%, p less than 0.001) than anti-HBe (34 +/- 17%). HBcAg stimulation elicited greater anti-HBc response (43 +/- 26%, p less than 0.001) than did HBeAg for anti-HBe (26 +/- 12%). Both HBcAg and HBeAg induced equivalent anti-HBe response. Anti-HBc production in response to HBcAg was higher in CAH patients (51 to 55%) than in asymptomatic carriers of hepatitis B surface Ag (22 to 28%) irrespective of their HBeAg/anti-HBe status, but reflecting serum anti-HBc value. Similar findings were noted in HBeAg-stimulated anti-HBe production for the two patient groups. In HBeAg- and anti-HBe-positive CAH, HBcAG-stimulated anti-HBc production was similar in T (1.4 x 10(6)) and B (0.6 x 10(6)) cells coculture, and B cells (2 x 10(6)) alone culture. However, in the HBeAg-stimulated culture, T plus B cells produced significantly higher titer anti-HBe than B cells alone did. These results indicate that HBcAg has a relatively higher immunogenicity in terms of antibody production as compared to HBeAg. Furthermore, HBcAg was shown to function as a T cell-dependent and -independent Ag, whereas HBeAg is T cell-dependent during chronic hepatitis virus B infection in man.     

Tendency and analysis of the epidemic situation in parenteral virus hepatitis B and C in the Russian Federation and a number of its regions

As revealed in the present survey, during the last 3 years, against a background of decreased number of registered cases of acute hepatitis B (HB) and acute hepatitis C (HC), an increase in the proportion of patients with the chronic forms of these diseases was observed. The incidence rate of carriership of hepatitis B (HBV) and hepatitis C viruses (HCV) is many times greater than morbidity rates in acute and chronic forms of the disease. Such differences could be due to imperfect laboratory and clinical diagnosis. The registered statistics on HBV and HCV carriership included newly detected HBsAg and anti-HCV in the absence of clinical manifestations, which did not reflect the true spread of HBV and HCV in a given territory. The group of HBV and HCV carriers was found to include a considerable proportion of patients with asymptomatic form of HB and HC. It was testing for HBsAg, anti-HCV only without determination of virus replication markers (anti-HBc IgM, HBV DNA, anti-HCV IgM, HCV RNA) that seemingly determined the category of carriers greatly exceeding the true incidence. To obtain reliable epidemiological information, the complex detection of HB and HC infection markers is necessary.     

Epidemiological characteristics and the importance of carriers of the surface antigen of the hepatitis B virus (HBsAg)

The occurrence of HBsAg carriership in Leningrad has been found to be 1.4% according to the results of countercurrent immunoelectroosmophoresis (CIEO) and 2.1% according to the results of the passive hemagglutination (PHA) test. In children HBsAg occurs with higher frequency: 1.9% according to the results of CIEO and 3.4% according to the results of the PHA test. The latter test reveals HBsAg carriers more completely, especially in women who have usually less pronounced antigenemia than men. Most of chronic HBsAg carriers are patients with chronic forms of hepatitis B (chronic active hepatitis and chronic persistent hepatitis); frequently they become the source of infection among their relatives under the conditions of family contacts. A complex of antiepidemic measures is necessary in the foci of chronic HBsAg carriership.     

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.     

Evaluation of an immunoenzyme test (ELISA) for the determination of an Ag/Ab system correlated to non-A, non-B post-transfusion hepatitis

An ELISA for the detection of a Ag/Ab system related to non-A, non-B post-transfusion hepatitis (NANB-PTH) has been developed. A convalescent serum from a patient suffering, 14 month before, of NANB-PTH was used both as capture and detector antibody in a "sandwich" type immunoassay to detect an Ag (Ag-NANB). A "blocking" immunoassay was used, in the same test, to detect the corresponding antibody (Ab-NANB). All patients with NANB-PTH were positive, alternately, for Ag-NANB or Ab-NANB. The Ag was found in the acute phase sera of 3 out of 22 cases of NANB-PTH (13,6%), but in none of 29 acute hepatitis type B,26 acute hepatitis type A,14 NANB sporadic hepatitis, 5 infectious mononucleosis and 8 healthy subjects. 2/3 Ag-NANB positive subjects became chronic carriers of this Ag, whereas the third seroconverted for Ab-NANB after the first two months of their disease. Furthermore, a significant increase of the Ab-NANB titer was observed in the convalescent phase of the disease in 18/20 NANB-PTH. As expected, a relatively high prevalence for Ab-NANB was found in the other groups of patients, suggesting the high diffusion of the agent, but none of these subjects showed a progressive increase of the antibody titer during the course of their disease.     

Screening of Danish blood donors for hepatitis B surface antigen using a third generation technique.

The profit to be gained by testing Danish blood donors for hepatitis B surface antigen (HBsAg) with a third generation technique instead of the currently used immunoelectrophoresis was investigated by additional screening of 48 750 blood units by radioimmunoassay three weeks after donation. Twenty nine units were positive for HBsAg on radioimmunoassay (0.059%). Only six of these were found by immunoelectrophoresis (0.012%). Most of the 23 donors positive on radioimmunoassay and negative on immunoelectrophoresis were healthy carriers of HBsAg (20) or had asymptomatic chronic liver disease (two). One donor had acute hepatitis B. Fifteen of the 23 blood units were transfused. The 15 recipients were monitored biochemically and serologically for up to nine months. One recipient developed fulminant hepatitis B, three developed acute hepatitis B, and one became a healthy carrier of HBsAg. All these patients had received blood from healthy carriers of HBsAg. Two recipients were immunised against HBsAg, and in one patient no seroconversion was observed. The remaining recipients died soon after transfusion or were protected by antibodies to HBsAg that had been present before the transfusion. Testing of Danish blood donors using a third generation technique identified a substantial number of donors positive for HBsAg overlooked by immunoelectrophoresis. Most of these donors were healthy carriers of HBsAg. Blood taken from such carriers is highly infectious when transfused, probably because of the large amount of material transmitted.     

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.     

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.     

应用酶联免疫吸附试验检测不同类型乙型肝炎中激活补体类HBsAg循环免疫复合物

本文以抗人C_(?)的羊IgG为包被抗体,以HRP-HBs抗体为指示抗体,建立了可检测激活补体类HBsAg循环免疫复合物(HBsAg/C3-CIC)的C_3捕捉法酶联免疫吸附试验。检测了236例六种类型临床诊断为乙型肝炎的病人血清标本,其阳性率分别为:无症状携带者(ASC)12.9％(4/31),急性肝炎(AH)36.7％(22/60),慢性迁延性肝炎(CPH)33.3％(7/21),慢性活动性肝炎(CAH)59.6％(34/57),重型肝炎(SH)77.8％(14/18),肝炎后肝硬化(PLC)67.3％(33/49),阳性率与肝损严重程度明显相关(P<0.01)。认为HBs-Ag/C3-CIC可能在乙型肝炎病毒引起的慢性活动性肝炎、重型肝炎和肝炎后肝硬化的发病过程中起重要作用,并可作为乙型肝炎的诊断、临床分型和预后判断的指标之一。     

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.     

Frequency of detecting viral hepatitis B markers in the patients of a hemodialysis ward

The data, obtained as the result of the examination of 22 patients with chronic renal insufficiency and analysis of 105 samples of transfusion blood at the department of chronic hemodialysis, are presented. To detect the markers of hepatitis B (HBsAg, anti-HBs, anti-HBc), a complex of biochemical investigations was carried out with the use of counter-current immunoelectrophoresis, the passive hemagglutination test, enzyme immunoassay, and solid-phase radioimmunoassay. The markers of hepatitis B were detected in 72.6% of patients with chronic renal insufficiency and in 21% of healthy persons. Changes in the activity of biochemical characteristics of hepatic samples were detected only in one patient. In no case clinical symptoms of the disease were observed. Out of 105 samples of transfusion blood, 9.5% contained HBsAg. The results of our investigations indicate that the markers of hepatitis B are widely spread among patients with chronic renal insufficiency, which makes it possible to consider them as a "high risk group" with respect to hepatitis B infection. To decrease the risk of hepatitis B among patients with chronic renal insufficiency, it is very important that highly sensitive tests be introduced into practice for the selection of donors and the detection of patients with the asymptomatic forms of hepatitis B and carriers at the department of chronic hemodialysis.     

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.     

Detection of a new antibody system reacting with Dane particles in hepatitis B virus infection.

Antibodies in the serum reacting with antigens on the surface of radiolabelled Dane particles distinct from hepatitis B surface and core antigens (HBsAg and HBcAg) were detected, using a double antibody precipitation assay, in 12 out of 15 patients early in the course of acute type B hepatitis and at the time of disappearance of circulating Dane particles. No such antibody activity was found in 15 of the 16 patients with HBsAg-positive chronic active hepatitis, 13 of whom had complete Dane particles in the serum. In a group of 16 asymptomatic HBsAg carriers (without Dane particles in serum) antibody activity was shown in nine. This demonstration of antibodies precipitating Dane particles may be relevant to the clearance of circulating hepatitis B virions and the termination of infection in acute type B hepatitis. Their absence in all but one of the cases of chronic active hepatitis might explain why the virus infection persists in this group of patients.     

Seroprevalence of Hepatitis B virus infection among an Afro-descendant community in Brazil

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.     

Prognosis for the patients with chronic hepatitis B

The purpose of the research was to determine the influence of the hepatitis B virus on the progression of the chronic liver disease. In the present paper, 127 patients who were followed up for five years and who had histologically verified chronic liver disease, are described. Fifty two of them were carriers of HBsAg, 75 patients were HBsAg negative, but had other markers typical for a previous infection of HBV in the sera. All the patients were nonalcoholics and no drug addicts. In the sera of these 127 patients markers of HBV were prospectively followed up: HBsAg, HBeAg, anti-HBs, anti-HBc, anti-HBe, HBVDNA, antiHCV for C virus and anti-D for D virus. It was proved by these investigations that HBV provokes very severe chronic hepatitis: CAH (chronic active hepatitis) and CH (cirrhosis hepatis). It was also proved that HBV replicated in 44.20% patients, namely, HBVDNA was positive in the sera of those patients. In 26.08% of such patients the mutant form of HBV was present. In spite of progressive liver disease and without any antiviral therapy all the patients with chronic HBV cirrhosis hepatis were, after five year-follow-up, in Child-Pugh A grade. It was found that the patients who were HBsAg negative, but had one or more markers of HBV positive in the sera, had also a severe chronic hepatitis. That group of patients remains our object of further research. The five-years follow-up of all these patients demonstrates that it is necessary to find out an efficient medicament against HBV chronic hepatitis. Obligatory vaccination of the risk population against virus B remains the only prevention against this severe disease.