Prevalence of Hepatitis δ (Delta) Virus Infection A Seroepidemiologic Study

In assessing the prevalence of hepatitis δ (delta) virus (HDV) infection in 358 patients with acute hepatitis B seen in Los Angeles between 1983 and 1985 and in 196 patients with chronic hepatitis B followed between 1980 and 1985, we found that 23% of patients with chronic and 5% of patients with acute hepatitis B were infected with HDV. Among patients with chronic hepatitis B, the prevalence of HDV infection was 73% in intravenous drug users and 14% in homosexual men. Acute coinfection with the hepatitis B virus was also more frequent in drug users (8%) than in other groups. δ-Hepatitis is a common infection in hepatitis B virus carriers in Los Angeles, particularly in drug addicts, but also in homosexual men who do not abuse drugs intravenously.     

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.     

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.     

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。     

Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada

Objective

The prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk.

Methods

HBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV.

Results

Nine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections.

Conclusion

Chronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection.     

重庆地区乙肝血清特殊模式患者HBV基因分型及临床自然病程分析

目的了解重庆地区乙肝病毒（HBV）血清学标志物为特殊模式的HBV感染患者病毒基因型的分布情况,分析其临床特征及自然病程。方法从1000例HBV感染者中检测到48例乙肝病毒血清学标志物为特殊模式的患者（HBsAg与抗一HBs同时阳性,HBeAg与抗一HBe同时阳性）。采用巢式聚合酶链式反应（nPCR）对特殊模式患者的HBV进行基因分型,同时对两组特殊模式患者的临床资料和HBV感染的自然史进行分析。结果48例乙肝病毒血清学标志物为特殊模式的HBV感染者中,36例患者HBsAg与抗-HBs同时阳性,12例患者HBeAg与抗-HBe同时阳性。HBeAg＋／抗-HBe＋患者组的年龄较HBsAg＋／抗-HBs＋患者组的小（P〈0．05）。HBsAg＋／抗-HBs＋患者中,3例（8．3％）为B2亚型,12例（33．3％）为c2亚型,21例（58．4％）未分型;HBeAg＋／抗-HBe＋患者中,8例（66．7％）为B2亚型,1例（8．3％）为c2亚型,3例（25．0％）未分型,两组在HBV基因型的分布上差异具有统计学意义（Y2=17．44,P〈0．05）。在HBsAg＋／抗-HBs＋患者中,2例（4．2％）处于免疫清除期,14例（29．2％）处于低复制期,7例（14．6％）处于再活动期。HBeAg＋／抗-HBe＋患者中,5例（10．4％）处于免疫清除期。两组在HBV感染的自然病程中的分布差异具有统计学意义（X2=18．26,P〈0．05）。结论重庆地区乙肝病毒血清学标志物为特殊模式的慢性HBV感染者中,HBeAg与抗-HBe同时阳性的HBV感染者中B2亚型为优势基因型;HBsAg与抗-HBs同时阳性的HBV感染者中,HBV基因型以C2亚型为主。     

Practical guidelines for assessing patients positive for hepatitis B surface antigen.

In assessing the patient the hepatitis B surface antigen (HBsAg) the physician must decide on the basis of physical findings, results of laboratory tests and biopsy, when indicated, whether the patient is an asymptomatic carrier or has acute or chronic hepatitis. Asymptomatic carriers of HBsAg must be educated in personal hygiene and the possibility of transmission, should not be allowed to donate blood or breast-feed and should not work with blood products for human use or pharmaceutical products designated for intravenous use. However, it is otherwise not necessary to advise these individuals to change their profession.     

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.     

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.     

激活补体类乙型肝炎病毒表面抗原(HBsAg)循环免疫复合物在急慢性乙型肝炎中的意义

激活补体类HBsAg循环免疫复合物(HBsAg/C3-CIC )的检出率,与HBV复制标志的关系,在急慢性乙型肝炎病毒感染中表现不同。在慢性肝病(包括慢性迁延性乙型肝炎、慢性活动性乙型肝炎、乙型肝炎后肝硬化和HBV感染指标阳性的原发性肝癌)患者中,HBeAg阳性者,其HBsAg/C3-CIC的检出率显著高于HBeAg阴性者,且随HBeAgS/N值的升高而增加。在由HBV e系统组合成的四种模式中,单纯HBeAg阳性模式的检出率显著高于其它三种模式;在多聚白蛋白受体(PHSAr)阳性者中检出率显著高于PHSAr阴性者。而急性乙型肝炎(AH)的HBsAg/C3-CIC检出率无类似差异。这些结果提示,HBsAg/C3-CIC在HBV感染的急慢性肝病中具有不同的病理生理意义。     

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。     

Chronic Hepatitis Associated with Drug Abuse: Significance of Hepatitis B Virus

One hundred and seventy-seven former heroin addicts, consisting of 85 who were newly admitted to a methadone maintenance program and 92 who had received methadone for a mean period of 30 months, were prospectively studied for up to 2 years in order to determine: (1) the effect of heroin withdrawal on the hepatic abnormalities, and (2) the incidence of HBsAg, anti-HBs, and anti-HCc as indices of the frequency of hepatitis B virus infection. Our study indicates that (1) hepatic abnormalities persist when heroin is discontinued and are not temporally related to drug and/or needle usage, and (2) that 71% of subjects had either HBsAg or anti-HBs; anti-HBc was tested for in 16 patients and was present in 100%, although 9 of the 16 were both HBsAg- and anti-HBs-negative. This study suggests that hepatitis B is largely responsible for the liver dysfunction. It is proposed that an abnormality in immune function, induced by heroin, is responsible for the high incidence of chronic hepatitis. Attention is drawn to the similarity between former drug addicts and hemophiliacs, since both develop chronic hepatitis in spite of anti-HBs in the serum.     

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.     

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.     

Hepatitis B core and surface antigens and delta agent in chronic liver disease in Kuwait

Hepatitis B surface antigen was detected immunohistochemically in 25 out of 85 liver biopsies (29.4%) of chronic liver disease. Core antigen was also demonstrated in 9 of the 25 Hepatitis HBs Ag positive biopsies (36%). Delta agent however, was found in only one case of HBs positive chronic active hepatitis. The number of hepatocytes staining positively for HBc antigen was greater in those biopsies with the strongest staining for HBs antigen. The only case of chronic active hepatitis positive for delta agent showed that the positive staining was confined to the nuclei of few hepatocytes. The routine histology showed chronic active hepatitis with a moderate degree of inflammation. The present results confirm our previous reports that almost one third of chronic liver disease in Kuwait is associated with hepatitis B infection. Previous serological studies suggest that delta agent infection is also common; however, the present study suggest that delta agent may be a transient, and not a major, contributing factor in the progression of liver disease.     

Hepatitis B among drug addicts]

In the years 1980-1988 twenty five drug addicts were identified among 1841 patients hospitalized for acute hepatitis in the Dep. of Hepatology at the Institute of Infectious and Parasitic Diseases in Warsaw. 15 drug addicts had hepatitis B and 10 had hepatitis A. It was found, that the course of acute type B hepatitis was milder in drug addicts, than among control group consisting of non-addicts.     

Hepatitis B virus surface and core antigens in the liver of primary hepatocellular carcinoma cases in Virginia

Zenker-fixed paraffin-embedded sections of biopsy liver tissue from 64 cases of primary hepatocellular carcinoma (PHC) were stained for hepatitis B surface antigen (HBsAg) and for hepatitis B core antigen (HBcAg) by histochemical and/or immunohistochemical techniques in a retrospective study. PHC arose in livers with postnecrotic cirrhosis in 30 (46.9%) cases. Controls included liver biopsy sections from 123 miscellaneous liver disorders and from 67 randomly selected autopsy specimens, none of which were known to be associated with hepatitis B virus (HBV) infection. HBsAg was detected in tumorous hepatocytes in only one of the 64 cases of PHC. HBsAg was identified in nontumorous hepatocytes of 8 (20%) of 40 specimens that contained adequate nontumorous liver tissue. All of these HBsAg positive cases of PHC were associated with cirrhosis. Thus HBsAg was detected in 8 (33.3%) of 24 cases of PHC with cirrhosis, but in none of the remaining 16 cases without cirrhosis. HBcAg was not detected in the hepatocytes of those HBsAg positive PHC cases tested. Our results suggest that HBV infection may successively lead to chronic hepatitis, cirrhosis and ultimately PHC.     

The epidemiological aspects of viral hepatitides in Estonia]

The etiological structure of viral hepatitides among the adult population of Tallinn and the occurrence of markers of hepatitis B and hepatitis C virus infections in medical workers, addict introducing drugs intravenously and hemodialysis patients were studied. Changes in the etiological structure of viral hepatitides were established: they took the form of a decrease in the level of hepatitis A morbidity and the considerable growth of the role of hepatitides B and C, as well as the newly detected circulation hepatitis D virus. About one-third in the structure of morbidity in viral hepatitides were hepatitis cases without markers of hepatitis A, B or C viruses (non-A, non-B, non-C). The highest rates of hepatitis B virus infection (78.9%) and hepatitis C virus infection (82.5%) were detected among drug addicts. Their level of HBsAg was 8.8%. In the group of medical workers, 25% of the examinees, i.e. every fourth person, had markers of hepatitis B virus, while antibodies to hepatitis C virus were detected in 5% of cases. Among hemodialysis patients these rates were 21.4% and 10.7% respectively.     

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.     

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.