Hepatitis delta virus infection: a recently imported disease in New Zealand

In a study of 565 hepatitis B antigen (HBsAg) positive persons from the Auckland region, antibody to the hepatitis delta virus was detected in 38. The largest number were in Samoans (61%) although the infection was present in some other Pacific Islanders. Among HBsAg positive healthy blood donors, antenatal patients and acute hepatitis patients between 3.8 and 4.8% were anti-delta positive; while 28% of chronic hepatitis patients were positive suggesting an association between this disease and delta infection. Some positive results were also found in sera from intravenous drug addicts. By contrast, anti-delta was uncommon in New Zealand born Maoris or Europeans. Delta infection can be detected in some Pacific Islanders, some European immigrants as well as intravenous drug addicts and has the potential to spread in an epidemic form to HBsAg carriers in the general community. Widespread vaccination against hepatitis B is recommended to eventually reduce the number of HBsAg carriers in New Zealand.     

Passive immunoprophylaxis of hepatitis B virus infections in newborn infants

Newborn infants of mothers who were chronic carriers of hepatitis Bs antigen (HBsAg) were randomly allocated to be treated or not treated with hyperimmune hepatitis B immunoglobulin (HBIg) at birth and six weeks and were then followed up to one year with sequential blood tests. Ninety percent of all untreated infants born of mothers positive for both HBsAg and hepatitis Be antigen became chronic carriers of HBsAg at one year. In contrast only 9% of infants treated with HBIg became HBsAg positive. Mothers who were HBsAg positive but hepatitis Be antigen negative only uncommonly infected their infants, with 6% being HBsAg positive at one year. Nearly all infections were in Pacific Islanders, Maoris or Asians. It is recommended that antenatal testing of these groups most at risk for hepatitis B virus spread, be initiated, followed by passive immunoprophylaxis with HBIg of infants born of HBsAg, HBeAg positive mothers.     

Serological markers of hepatitis B infection in Niue children

Hepatitis B infection is hyperendemic in the adult population of Niue. In order to determine the age at which infection is acquired and the contribution of vertical and horizontal transmission, the sera from 1055 children were tested for markers of hepatitis B infection. Eleven percent (11.0%) were found to be carriers of hepatitis B surface antigen (HBsAg) and a further 33.6% had antibody to hepatitis B surface antigen (anti-HBs). While less than 15% of the population were infected before the age of two years, these children had the greatest risk of becoming chronic carriers. The simplest method of controlling hepatitis B infection in Niue would be to immunise all newborn babies.     

e Antigen-antibody system as indicator of liver damage in patients with hepatitis-B antigen.

The clinical relevance of the e antigen-antibody system was investigated in 61 people persistently positive for hepatitis-B surface antigen, including 22 healthy carriers. The e antigen was not detectable in any of the healthy carriers, whereas it was found in 15 out of 28 patients with chronic aggressive hepatitis and two out of 11 with chronic persistent hepatitis. Its presence therefore indicates chronic liver disease but its absence does not exclude it. It may prove to be a particularly useful prognostic aid in chronic persistent hepatitis, since one of the two patients in whom it was found later developed aggressive hepatitis. In contrast, e antibody is of little diagnostic help, for, though it was found mostly in healthy carriers (18;82%), it was also detectable in 9 (23%) of the patients with chronic hepatitis. In 13 (76%) of the patients positive for e antigen Dane particles were seen on electron microscopy, but these were also present in 5 (19%) of the patients positive for e antibody. These findings are consistent with other evidence suggesting that e antigen is not a surface component of the Dane particle, but rather an independent soluble protein manufactured by the host in response to infection with the hepatitis-B virus.     

Serum hepatitis B surface antigen levels in the natural history of chronic hepatitis B infection

BACKGROUND The production of hepatitis B surface antigen (HBsAg) may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The impact of age on HBsAg production remains unclear. AIM To determine the age-specific distribution patterns of HBsAg and related factors during the natural course of CHB infection. METHODS Seven hundred and sixty-eight untreated HBsAg carriers were enrolled in the study. The parameters and distribution patterns of HBsAg were evaluated in relation to age and immune phases. RESULTS The HBsAg levels were significantly lower in the HBeAg-negative stage, with the lowest levels in inactive carriers. The HBsAg tended to decrease from hepatitis to cirrhosis and to hepatocellular carcinoma, and from Child-Pugh class A to B and to C. Age and HBV DNA were independently associated with HBsAg levels. In HBeAg-positive patients, the HBsAg levels were distributed in a triphasic-like decline pattern by 2 logs across age strata. For HBeAg-negative patients, the titres in inactive carriers exhibited a 2-log reduction, but remained unchanged over age strata in patients with HBeAg-negative hepatitis. The ratios of HBsAg/HBV-DNA were highest, but steadily decreased with age in inactive carriers, whereas the levels remained largely unchanged over the entire age strata in patients with HBeAg-negative hepatitis. CONCLUSIONS Age and HBV DNA levels are independent parameters of HBsAg levels. During the natural course of CHB infection, HBsAg levels decrease with age and disease progression, but the patterns are significantly different between the immune phases of CHB. This information may contribute to our understanding of the immunopathogenesis of chronic hepatitis B and management involving HBsAg quantification.     

血清HBsAg与HBVDNA定量关系分析

目的定量检测血清乙型肝炎病毒表面抗原（HBsAg）浓度与乙型肝炎病毒DNA（HBVDNA）,并探讨两者的相关关系及临床应用价值。方法随机选取HBsAg阳性的患者135例,采用化学发光法（CLIA）定量检测其血清中HBsAg、乙型肝炎病毒e抗原（HBeAg）,同时采用实时荧光定量聚合酶链反应（FQ-PCR）检测其血清中HBVDNA载量。结果 135例患者中HBeAg阳性的61例,HBVDNA阳性的87例,其HBsAg和HBeAg浓度值与HBVDNA载量的相关系数（r）分别为：0.583（P〈0.01）、0.550（P〈0.01）,HBsAg与HBeAg的r值为：0.699（P〈0.01）。结论血清HBsAg浓度与HBVDNA载量及HBeAg浓度均成高度正相关,可较好的反应HBV的复制水平,便于临床开展应用。     

聚合酶链反应在慢性乙型肝炎病毒感染者中的实用意义

应用聚合酶链反应检测51例慢性肝炎,19例慢性HBsAg携带者(ASC)和26例HBV感染后的健康者血清中的HBV DNA。结果14例HBeAg阳性患者HBV DNA全部阳性,37例HBeAg阴性者中24例阳性(64.9％)。其中HBV·M阴性9例,有6例阳性。5例抗-HBs阳性者3例阳性。ASC和健康者PCR-HBV DNA检出率分别为36.8％和26.9％,明显低于慢性肝炎的74.5％。结果提示,慢性肝炎患者HBeAg阴性甚至HBV·M阴性时,往往大部分仍有HBV复制,且可能与病变活动有关。ASC和健康者总体病毒复制水平较低,可能与无明显的肝脏病表现有关。     

Liver disease and hepatitis B infection in a large New Zealand family

This study illustrates the relationship between the hepatitis B virus (HBV) carrier state and primary hepatocellular carcinoma in a large family of Maori (173 members) amongst whom four brothers have died of primary hepatocellular carcinoma. The brothers were from a generation of fourteen siblings, eleven of whom were tested for hepatitis B surface antigen (HBsAg) and all found to be positive. Amongst the offspring of this generation there were 13 HBsAg positives from 28 children (46%) born to female carriers but no HBsAg positives amongst the 28 offspring of male carriers. The study provides further evidence that the morbidity which often follows HBsAg carriage, may be associated with early (perinatal) infection. There was a marked decrease in HBV serologic markers in succeeding generations, from 100% in generation two, to 55% in generation three and 14% in generation four, unrelated to the use of hepatitis B vaccine.     

Liver function and hepatitis markers in carriers of hepatitis B virus in New Zealand

AIMS: The Hepatitis Foundation has identified many chronic carriers of hepatitis B virus (HBV) in community surveys of schools and family contacts. This study reports the characteristics of carriers and the relationship between hepatitis markers and liver function. METHODS: Demographic data from confirmed chronic carriers of HBV in the North Island were correlated with liver function and hepatitis markers. Longitudinal data were obtained by following a cohort for two years with regular blood tests. RESULTS: Of 2778 confirmed carriers of HBV most were children or young adults and 56% were male. Sixty percent were Maori and 26% Pacific Island people. Loss of HBsAg occurred at less than 1% per year compared to 9% for HBeAg. Mean ages for 50% loss of HBeAg were 14 years for children of HBV negative mothers and 19 years for those of HBV carrier mothers. Fewer adult males than females were HBeAg positive. Alanine aminotransferase levels above 50 IU/L were found in 16% of HBeAg positive and 6% HBeAg negative cases. Other factors significantly associated with raised alanine aminotransferase were male gender (OR 1.8) and age more than 15 years (OR 2.0). Thirty five percent of HBeAg positive carriers with raised alanine aminotransferase levels spontaneously seroconverted to HBeAg negative in two years. However, raised alanine aminotransferase in HBeAg negative carriers was persistent in most cases and 38% had HBV-DNA detectable in serum. CONCLUSIONS: HBV carriage is less benign in adults than children, even after loss of HBeAg. It is recommended that all HBV carriers have regular checks of liver function. Those with persistent abnormality should be strongly advised to restrict alcohol and be assessed for possible antiviral treatment.     

A controlled study of treatment with recombinant interferon alpha in chronic hepatitis B virus infection: induction and maintenance schedules

To determine the antiviral effect of recombinant-interferon (rIFN)-alpha in hepatitis B virus (HBV) chronic infection, a controlled study was carried out. A total of 20 HBsAg chronic carriers (18 chronic active hepatitis and 2 chronic persistent hepatitis) were included. All of them had remained HBeAg, HBV-DNA and HBV-DNA polymerase (HBV-DNAp) positive at least six months before treatment. The patients were randomly assigned to two groups: control (n = 10), and treatment (n = 10). A dose of 5.5 megaunits of rIFN-alpha/m2 body surface was administered every day for 21 days (induction) and twice a week for six months thereafter (maintenance). No basal differences were observed between the two groups. No case of intolerable toxicity was observed. One treated patient died in a car crash in the second month. At the end of the first week of therapy, 7/10 (70%) of the treated patients became HBV-DNAp negative. However, in the fifth month only 2 patients remained HBV-DNAp negative and also became HBV-DNA and HBeAg negative. In contrast, no changes in viral markers among control cases were observed. In conclusion, rIFN-alpha has an antiviral effect on chronic HBV infection; however, the induction plus maintenance schedule is not useful to obtain a permanent effect.     

Prevalence of hepatitis B infections in a multiracial New Zealand community

Plans to control hepatitis B virus (HBV) infections in a high risk mixed race community, included the need for prevalence studies of HBV markers. Accordingly 7901 subjects, 93% of the population of Kawerau, where European and non-European children are present in almost equal numbers, were tested for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Positive HBsAg sera were titred and tested for hepatitis B e antigen (HBeAg). Highest rates for HBsAg and anti-HBs combined, were found in the 15-19 year old age groups; 61.6% in Europeans and 74.5% in non-Europeans. HBsAg prevalence was 4.2% and 18.2% respectively in the same groups. Ninety-six point four percent of 503 HBsAg positives followed up were confirmed as carriers. Infectivity as shown by HBeAg prevalence and HBsAg titre was highest in 0-10 year olds and declined with age. Prevalences were low in children aged less than one year old, suggesting that perinatal transmission was not a major factor in childhood carriage. Therefore attempts to control acquisition of carriage by vaccinating only those children of HBeAg positive mothers are unlikely to be successful.     

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.     

Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood-acquired chronic hepatitis B virus infection

Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2-week gap, by thrice weekly lymphoblastoid a-interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg),‘e’ antigen (HBeAg) and HBV-DNA positive] became HBeAg and HBV-DNA negative during therapy and remained so after 12 months post-therapy follow-up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV-DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV-DNA negative but HBeAg positive at the end of follow-up. None of the eight untreated control patients seroconverted during an identical follow-up period. Two further patients were HBsAg and HBeAg positive but HBV-DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2–6 weeks after prednisolone withdrawal, loss of HBV-DNA 0–8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated.     

Serum HBsAg changes in HBeAg positive chronic hepatitis B patients with continuous viral load reductions during treatment with adefovir or peg-interferon-alpha-2a

Hepatitis B surface antigen (HBsAg) loss under antiviral therapy is rare in chronic hepatitis B patients and the dynamics of serum HBsAg in these patients are not available. The changes in serum HBsAg following treatment with adefovir (n=31) or peg-interferon-alpha-2a (n=23) were studied in hepatitis B e-antigen (HBeAg) positive chronic hepatitis B patients. Abbott Architect HBsAg assay was used to quantify serum HBsAg. HBsAg levels were significantly decreased during the first 12 weeks of treatment with median change of -397.0 IU/ml and -555.4 IU/ml, respectively for adefovir and peg-interferon-alpha-2a (p=0.005 and 0.001, respectively). Beyond 12 weeks, no further significant HBsAg reductions were found even in patients with sustained viral replication inhibition in either group. Three distinct patterns of HBsAg changes were observed in most patients in both treatment groups: biphasic pattern (rapid HBsAg reduction from baseline to week 12); assurgent pattern (higher HBsAg level at week 12 than at baseline); and wavy pattern (HBsAg reduction from baseline to week 12, followed by relapse at week 24 or week 28). These results might offer insights into the possible mechanism(s) underlying the unusual occurrences of HBsAg loss under antiviral therapy.     

2002～2007年安康市大学新生乙型肝炎病毒感染状况调查

目的:了解安康市大学新生中乙肝病毒感染现状与发展趋势。方法:对2002～2007年安康市两所大学的入学新生采用酶联免疫吸附试验(ELISA)进行乙肝标志物检测,并对检测结果进行统计分析。结果:共调查10 115人,HBsAg总阳性率为5.07%,其中2002～2004年HBsAg阳性率为5.98%,2005～2007年HBsAg阳性率为4.40%,差异有显著性(P<0.001)。男、女生HBsAg总阳性率分别为5.39%、4.74%,差异无显著性。结论:安康市大学新生乙型肝炎病毒检出率呈逐年下降,男生人数多于女生。     

Hepatitis B immune globulin

Hepatitis B immune globulin (HBIG) is a purified solution of human immunoglobulin that has high titers of antibody to hepatitis B surface antigen (anti-HBs). It is derived from plasma donated by individuals immune to hepatitis B viral infection. HBIG is widely administered to confer passive prophylactic immunity against the hepatitis B virus because of the ability of anti-HBs to neutralize hepatitis B virions. However, it is not indicated for the treatment of acute or chronic hepatitis B. The use of HBIG is recommended in the following clinical situations: i) Acute exposure to blood and secretions containing hepatitis B surface antigen (HBsAg); ii) sexual contact with HBsAg-positive persons; iii) household exposure to persons with acute hepatitis B; iv) perinatal exposure of infants born to HBsAg-positive mothers; v) liver transplantation.     

聚乙二醇干扰素α-2a治疗e抗原阳性慢性乙型肝炎疗效的影响因素

目的探讨聚乙二醇干扰素α-2a治疗e抗原阳性慢性乙型肝炎疗效的影响因素。方法评价性别、丙氨酸氨基转移酶、HBVDNA定量和乙肝病毒基因型对疗效的影响。结果HBV基因型为疗效影响因素,性别、丙氨酸氨基转移酶、HBVDNA定量对疗效无影响。结论基因型是聚乙二醇干扰素α-2a治疗慢性乙型肝炎疗效的影响因素。     

A study of street heroin lots for the presence of the hepatitis B surface antigen

Hepatitis B surface antigen (HBsAg) of subtype ay predominates among narcotic addicts infected with hepatitis B virus (HBV) in Europe, Australia and the United States. However, the ad subtype predominates among the non-addict carriers of HBsAg. We investigated the possibility that heroin lots were contaminated with HBV at a source of opium production, the Middle East, a geographical region where HBsAg/ay predominates in the general population. One hundred and nine lots of street heroin were assayed for HBsAg by radioimmunoassay. None of the lots tested was reproduceably HBsAg positive. These results suggest that the heroin itself is not responsible for the high incidence of HBV infection or for the predominance of HBsAg/ ay in the addict population. The predominance of HBsAg/ay among addicts in Europe and Australia as well as the United States might be due to extensive needle sharing among a mobile population of drug abusers, although such worldwide dissemination of one subtype by these means is unlikely.     

Rapid procedure for the detection of hepatitis delta virus RNA in sera of HBsAg-positive and anti-delta-positive patients

A synthetic oligonucleotide duplex of 78 bp corresponding to part of the recently published RNA sequence of hepatitis Delta virus (HDV) was cloned into the plasmid pSBO1 and used for the detection of HDV RNA in sera of patients with chronic HDV infection by molecular hybridization. RNA containing the 78 bp sequence was synthesized in vitro and used as a positive control. For this purpose, a fragment containing the cloned oligonucleotide was transferred into the plasmid pSPT 18. HDV RNA was present in 5 out of 32 hepatitis B surface antigen (HBsAg)- and anti-HD-positive patients. It was neither found in the sera of 19 HBsAg-positive, anti-HD-negative patients, nor in the sera of 26 patients with chronic liver disease negative for both HBsAg and anti-HD. The method appears to be suitable for the detection of viruses of which either only parts of the genome or the entire sequence is known.