Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV.

OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers and antibodies against hepatitis C virus by enzyme linked immunosorbent assay (ELISA) and for HIV antibody by enzyme immune analysis and western blotting. SETTING--Large referral university hospital with an external AIDS clinic in the metropolitan area of Barcelona, Spain. SUBJECTS--243 Intravenous drug misusers, 143 of their regular heterosexual partners, and 105 homosexual men. MAIN OUTCOME MEASURES--Prevalences of hepatitis C virus, hepatitis B virus, and HIV infections. RESULTS--In all, 178 of the 243 (73%) intravenous drug misusers, 16 out of 143 (11%) of their partners, and 17 of the 105 (16%) homosexual men had antibodies against hepatitis C virus. The presence of hepatitis C virus infection was unrelated to sex, age, the presence of HIV or hepatitis B virus infections, or the Centers for Disease Control stage of HIV. In sexual partners of intravenous drug misusers there were strong correlations between the presence of hepatitis C virus infection and that of HIV (p = 0.001) and hepatitis B virus (p = 0.013) infections. CONCLUSIONS--Intravenous drug misusers have a high risk of acquiring hepatitis C virus, hepatitis B virus, and HIV infections, but the presence of hepatitis C virus infection seems to be unrelated to the presence of the other two viruses. Homosexual men have a high prevalence of HIV and hepatitis B virus infections with a low prevalence of hepatitis C virus infection, the presence of which is not related to that of the other two infections. Conversely, heterosexual partners of intravenous drug misusers have low prevalences of the three virus infections, but the presence of hepatitis C virus infection correlates significantly with the presence of HIV and hepatitis B infections. The rate of sexual transmission of hepatitis C virus seems to be low, even in partners of people known to be seropositive for this virus.     

Clinical and epidemiologic characteristics of hepatitis C in a gastroenterology/hepatology practice in Ottawa.

OBJECTIVE: To examine the clinical and epidemiologic features of hepatitis C virus (HCV) infection in a gastroenterology/hepatology practice in Ottawa. DESIGN: Retrospective chart review. PATIENTS: Sixty-three consecutive patients found to be anti-HCV positive. Their charts were analysed with respect to risk factors, history of hepatitis, serum aspartate aminotransferase (AST) levels and the presence of hepatitis B markers. The long-term sexual partners of 29 patients agreed to undergo HCV antibody testing. RESULTS: Of the patients 48 (76%) had been exposed to HCV parenterally: 27 used intravenous drugs, and 21 had received blood or blood products. Eleven patients did not have any known risk factor (sporadic infection), but eight of them had lived in countries where hepatitis C may be more prevalent; the other three had locally acquired infection. The mean serum AST level at the first visit was 140 (normally less than 40) IU/L. At least one hepatitis B marker was identified in 33% of the patients. None of the sexual partners who were tested were anti-HCV positive. CONCLUSION: Most cases of hepatitis C in Ottawa are acquired through parenteral exposure; sexual transmission is rare. Sporadic infection in the Ottawa region is rare but may be more common in people from countries with a higher prevalence rate of hepatitis C. Most cases of hepatitis C are asymptomatic.     

Science commentary: Behaviour of hepatitis C virus

Objective: To determine the risk factors for and timing of vertical transmission of hepatitis C virus in women who are not infected with HIV-1. Design: Follow up for a median of 28 (range 24-38) months of babies born to women with antibodies to hepatitis C virus but not HIV-1. Subjects: 442 mothers and babies, of whom 403 completed the study. Main outcome measures: Presence of antibodies to hepatitis C virus and viral RNA and alanine aminotransferase activity in babies. Presence of viral RNA, method of infection with hepatitis C, method of delivery, and type of infant feeding in mothers.Results: 13 of the 403 children had acquired hepatitis C virus infection at the end of follow up. All these children were born to women positive for hepatitis C virus RNA; none of the 128 RNA negative mothers passed on the infection (difference 5%, 95% confidence interval 2% to 7%). 6 children had viral RNA immediately after birth. 111 women had used intravenous drugs and 20 had received blood transfusions. 11 of the infected children were born to these women compared with 2 to the 144 with no known risk factor (difference 7%, 2% to 12%).Conclusions: This study suggests that in women not infected with HIV only those with hepatitis C virus RNA are at risk of infecting their babies. Transmission does seem to occur in utero, and the rate of transmission is higher in women who have had blood transfusions or used intravenous drugs than in women with no known risk factor for infection.

Key messages

• Little information exists on vertical transmission of hepatitis C virus in women not infected with HIV
• This study in a large unselected population of infants born to HIV-1 negative mothers suggests that intravenous drug use itself is an important risk factor for transmission of hepatitis C virus
• Maternal post-transfusional hepatitis is also an important risk factor for infection of infants
• Viral genotype, maternal viraemia, type of delivery (vaginal delivery or caesarean section) and breast feeding do not seem to be risk factors
• In utero transmission of hepatitis C virus has been suggested by RNA positivity on day of birth in some infected children

     

Hepatitis B Virus Infection—Current Concepts of Chronicity and Immunity

Among the three types of viral hepatitis agents—A, B and non-A, non-B—the hepatitis B virus (HBV) has been best characterized by immunologic and recombinant DNA technologies. The indefinite persistence of hepatitis B virus infection in 85% to 90% of perinatally infected infants and in about 10% of those infected later in life accounts for a worldwide epidemiologic reservoir of more than 200 million carriers who are at a high risk for the development of δ-infection, chronic liver disease and hepatocellular carcinoma. Active immunization with a safe and effective vaccine, derived from the plasma of carriers of hepatitis B surface antigen (HBsAg), is envisaged to avoid viral hepatitis type B and its chronic sequelae. In addition to serologic and immunohistochemical markers of hepatitis B virus infection, hybridization assays using cloned HBV DNA have provided new insight into the biology of this virus, its persistence and its oncogenic potential in humans and in animal models. Genetic similarities have been recognized between HBV and the antigenically distinct non-A, non-B agents implicated in some cases of transfusion-associated chronic hepatitis. Structurally this unique group of HBV and HBV-like agents are DNA viruses with functional attributes of integration and replication analogous to the retroviruses.     

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study

Objectives

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants.

Background

Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood.

Methods

Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection.

Results

34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding.

Conclusions

Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.     

Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection.

OBJECTIVE--To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN--Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING--Four major medical centres in the United States. PATIENTS--12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES--In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS--Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS--Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.     

Hepatitis B viral factors and clinical outcomes of chronic hepatitis B

Hepatitis B virus (HBV) infection is an important health problem and the major cause of chronic hepatitis, cirrhosis as well as hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can be divided into 4 dynamic phases in HBV carriers who acquire the virus early in life. In general, the frequency and severity of hepatitis flares in the immune clearance or reactivation phase predict disease progression in HBV carriers, and early HBeAg seroconversion typically confers a favorable outcome. In contrast, late or absent HBeAg seroconversion after multiple hepatitis flares accelerates the progression of chronic hepatitis to cirrhosis. Recently, several hepatitis B viral factors predictive of clinical outcomes have been identified. For example, serum HBV DNA level at enrollment is the best predictor of adverse outcomes (cirrhosis, HCC and death from liver disease) in adults with chronic HBV infection. In addition, HBV genotype C, basal core promoter (BCP) mutant and pre-S deletion mutant are associated with increased risk of HCC development. In conclusion, hepatitis B viral factors such as serum HBV DNA level, genotype and mutants have already been clarified to influence disease progression of chronic hepatitis B. Further studies are needed to investigate the pathogenic mechanism of each viral factor.     

Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study

Objectives: To estimate the incidence of HIV and hepatitis C virus and risk factors for seroconversion among a cohort of injecting drug users. Design: Retrospective cohort study. Setting: Primary healthcare facility in central Sydney. Subjects: Injecting drug users tested for HIV-1 antibody (n=1179) and antibodies to hepatitis C virus (n=1078) from February 1992 to October 1995. Main outcome measures: Incidence of HIV-1 and hepatitis C virus among seronegative subjects who injected drugs and underwent repeat testing. Demographic and behavioural risk factors for hepatitis seroconversion. Results: Incidence of HIV-1 among 426 initially seronegative injecting drug users was 0.17/100 person years (two seroconversions) compared with an incidence of hepatitis C virus of 20.9/100 person years (31 seroconversions) among 152 injecting drug users initially negative for hepatitis C virus. Incidence of hepatitis C virus among injecting drug users aged less than 20 years was 75.6/100 person years. Independent risk factors for hepatitis C virus seroconversion were age less than 20 years and a history of imprisonment. Conclusions: In a setting where prevention measures have contributed to the maintenance of low prevalence and incidence of HIV-1, transmission of hepatitis C virus continues at extremely high levels, particularly among young injecting drug users.

Key messages

• The prevalence and incidence of hepatitis C virus is high, while the prevalence and incidence of HIV remains low among injecting drug users
• Young age and history of imprisonment are risk factors for acquisition of hepatitis C virus infection
• HIV prevention strategies have been relatively ineffective in preventing hepatitis C virus infection in this population
• The role of imprisonment in the acquisition of hepatitis C infection should be further investigated

     

Seroprevalence of viral hepatitis in riverine communities from the Western Region of the Brazilian Amazon Basin.

The western region of the Brazilian Amazon Basin has long been shown to be a highly endemic area for hepatitis B and hepatitis D viruses. Data concerning the prevalence of hepatitis C and E viruses in this region are still scarce. In this study we investigated the presence of hepatitis A, B, C, D and E viruses infection in communities that live along the Purus and Acre rivers in the states of Acre and Amazonas within the Amazon Basin. A total of 349 blood samples were collected and tested for hepatitis A-E serological markers (antibodies and/or antigens) using commercial enzyme linked immunosorbent assays. Anti-HCV positive sera were further assayed by an immunoblot. HBsAg positive sera were subtyped by immunodifusion. The overall prevalence for hepatitis A, B, C, and E were 93.7%, 66.1%, 1.7%, and 4%, respectively. A very high prevalence of delta hepatitis (66.6%) was found among HBsAg positive subjects. Hepatitis A, B and D viruses were shown to be largely disseminated in this population, while hepatitis C and E viruses infection presented low prevalence rates in this region. The analysis of risk factors for HBV infection demonstrated that transmission was closely associated with sexual activity.     

The occurrence rate of HGV/GBV-C RNA and risk factors in patients of narcological dispensary in Novosibirsk

The occurrence rate of HGV/GBV-C RNA, genotypic variety of isolates and various risk factors of infection with HGV/GBV-C were evaluated in 500 patients of the narcological dispensary of Novosibirsk. The occurrence rate of HGV/GBV-C RNA among all examined blood sera was 33.6%. At the same time in blood sera with HCV markers the occurrence rate of HGV/ GBV-C was 42.9% and in sera with negative results for markers HCV--25%. For gene typing of obtained isolates the direct sequencing of the amplification products of fragment NS3B and the phylogenetic analysis of the sequences thus obtained were used. Almost all isolates subjected to gene typing belonged to genotype 2, widespread in Europe, and only 1 isolate was classified with genotype 4. Statistically significant (p<0.05) risk of HGV/GBV-C infection among the examined subjects was linked with the intravenous use of drugs (OR 2.15), risky sexual behavior (OR 1.8) and the presence of virus hepatitis C (OR 2.26).     

Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is not uncommon as a result of similar routes of infection. Patients who are coinfected represent a unique group with diverse serologic profiles. Combined chronic hepatitis B and C leads to more severe liver disease and an increased risk of hepatocellular carcinoma. Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized based on patient variables such as serologic and virologic profiles, patient's prior exposure to antiviral treatment, and the presence of other parenterally transmitted viruses such as hepatitis D virus and human immunodeficiency virus. The natural history and treatment of patients with HBV and HCV coinfection is reviewed.     

No Evidence of Presence of Parvovirus 4 in a Swedish Cohort of Severely Immunocompromised Children and Adults

The recently discovered human parvovirus 4 (PARV4) has been associated with seropositivity for human immunodeficiency virus, hepatitis B virus and hepatitis C virus. High prevalence is seen especially in intravenous drug users. The virus has been detected in blood products and persons who have been repeatedly transfused have shown to be a risk-group. Furthermore, reports from different parts of the world suggesting a prevalence ranging from zero to one third of the healthy population and the virus is thought to cause a latent or persistent infection. We investigated the presence of PARV4 DNA and parvovirus B19 (B19) DNA in serum from 231 severely immunocompromised cancer patients that have been exposed for blood products. Compared to B19, which was found in 3.9% of the patients, we found no evidence of PARV4. Our results may indicate a very low prevalence of the virus in Sweden, and it would be useful to measure the real PARV4 exposure of the healthy population as well as individuals with known risk factors by serology.     

In vitro investigation of HBV clinical isolates from Chinese patients reveals that genotype C isolates possess higher infectivity than genotype B isolates

Hepatitis B virus (HBV) genotype B and C are two major genotypes that are prevalent in Asia and differ in natural history and disease progression. The impact of HBV genotypes on viral replication and protein expression has been explored by the transfection of hepatoma cells with replication-competent HBV DNA, which mimics the later stages of the viral life cycle. However, the influence of HBV genotypes on the early events of viral infection remains undetermined, mainly due to the difficulties in obtaining sufficient infectious viral particles for infection assays. Here, we report that a high-titer HBV inoculum can be generated from the transient transfection-based cell model after optimizing transfection conditions and modifying the HBV-expressing construct. By performing in vitro infection assays using transiently transfected derived viruses, we found that clinical genotype C isolates possessed higher infectivity than genotype B isolates. Moreover, we identified a naturally occurring mutation sL21S in small hepatitis B surface protein, which markedly decreased the infectivity of HBV genotype C isolates, but not that of genotype B isolates. In summary, using infectious viral particles provided by the optimized transient transfection-based cell model, we have been able to investigate a wide range of HBV variants on viral infectivity, which may contribute to our understanding of the reasons for different clinical outcomes in HBV infections and the development of therapeutic drugs targeting the early stages of HBV life cycle.     

Hepatitis B virus infection among street youths in Montreal

BACKGROUND: Street youths are at high risk for many health problems, including sexually transmitted diseases and bloodborne infections. The authors conducted a cross-sectional anonymous study from December 1995 to September 1996 involving street youths in Montreal to estimate the prevalence of risk behaviours for hepatitis B virus (HBV) infection and of markers of past and present HBV infection. METHODS: Participants were 437 youths aged 14 to 25 meeting specific criteria for itinerancy who were recruited in collaboration with the 20 major street youth agencies in Montreal. Sociodemographic and lifetime risk factor data were obtained during a structured interview, and a blood sample was taken to test for HBV markers (hepatitis B surface antigen and antibodies to the hepatitis B core antigen). Univariate analyses and multivariate logistic regressions were conducted. RESULTS: The mean age of the subjects was 19.5 years; 69.3% (303/437) were males. Many subjects had high-risk behaviours: 45.8% (200/437) had injected drugs, 24.5% (107/436) had engaged in prostitution, and 8.7% (38/437) reported having a sexual partner with a history of unspecified hepatitis. The prevalence rate for one or both HBV markers was 9.2% (40/434) (95% confidence interval [CI] 6.7%-12.3%). Multivariate logistic regression analysis showed that being over 18 years of age (adjusted odds ratio [OR] 4.5, 95% CI 1.8-11.7), having injected drugs (adjusted OR 3.5, 95% CI 1.5-8.3) and having had a sexual partner who had unspecified hepatitis (adjusted OR 3.2, 95% CI 1.3-7.5) were all associated with HBV infection. INTERPRETATION: Street youths are at high risk for HBV infection. Early and complete HBV vaccination among this vulnerable population is urgently needed.     

Risk of hepatitis B infection among young injection drug users in San Francisco: opportunities for intervention

Objective To compare the demographic characteristics and risk behaviors for hepatitis B infection among injection drug users younger than 30 years with those aged 30 or older and to evaluate participants'' knowledge, attitudes, and experiences of infection, screening, and vaccination against hepatitis B virus. Design A systematic sample of injection drug users not currently in a treatment program were recruited and interviewed at needle exchange programs and community sites. Participants 135 injection drug users younger than 30 years and 96 injection drug users aged 30 or older. Results Injection drug users younger than 30 were twice as likely as drug users aged 30 or older to report having shared needles in the past 30 days (36/135 [27%] vs 12/96 [13%]). Injection drug users younger than 30 were also twice as likely to report having had more than two sexual partners in the past 6 months (80/135 [59%] vs 29/96 [30%]). Although 88 of 135 (68%) young injection drug users reported having had contact with medical providers within the past 6 months only 13 of 135 (10%) had completed the hepatitis B vaccine series and only 16 of (13%) perceived themselves as being at high risk of becoming infected with the virus. Conclusion Few young injection drug users have been immunized even though they have more frequent contact with medical providers and are at a higher risk for new hepatitis B infection than older drug users. Clinicians caring for young injection drug users and others at high risk of infection should provide education, screening, and vaccination to reduce an important source of hepatitis B infection.     

慢性病毒性肝炎研究进展

近年,慢性病毒性肝炎研究领域有较大进展,慢性乙型肝炎病毒（HBV）感染,虽然有了应用广泛、历史较久、且效果较好的疫苗,但迄今仍是世界范围肝硬化和肝癌的主要诱因。传染途径可经产道、性接触和非肠道途径（包括静脉吸毒、血制品等）。成年病人有少有变慢性,但一岁以下患儿90％变成慢性肝炎。慢性肝损伤的临床表现可以是轻微的炎症重到晚期肝硬化,程度不等。α干扰素（IFNα）是治疗活动性肝炎的产宰药物,单核苷酸类药物（lamivudine和adefovir）也具有同样的疗效。晚期肝病和肝癌患者可进行移植,但异常伴发移植物的感染。乙型肝炎免疫球蛋白和新型抗病毒药物联合应用,可降低移植物感染的严重性。丙型肝炎病毒（HCV）在20世纪后期感染了大约1％的世界人口。这中RNA病毒非经口传播,绝大多数病人变成慢性肝炎,约20％逐渐演变成肝硬化或肝癌。用IFNα和病毒唑（Ribavirin）联合治疗,约40％病人的病理表现有所改善。肝移植对某些病例是适宜的,但移植物感染仍是悬而未决的问题,新发现的庚型肝炎病毒（HGV）和TT病毒目前认为并不引起严重的肝损害。     

The rate of detection of hepatitis B markers in persons with chronic alcoholism

A total of 707 males suffering from chronic alcoholism and 447 male donors not abusing alcohol have been surveyed in different regions of the USSR. The presence of HBsAg, as well as anti-HBs and anti-HBc antibodies, has been determined by the enzyme immunoassay. The survey has revealed a high rate of hepatitis B virus infection in chronic alcoholics in comparison with the control group, which gives grounds for including such persons into a high risk group with respect to viral hepatitis B infection.     

The prevalence of hepatitis B and C markers among narcotic users

611 patients with acute parenteral virus hepatitis (VH) were studied with a view to find out markers indicating the presence of hepatitis B and hepatitis C virus infection (HB, HC, HB + C, HC + HBsAg). Of these, 166 patients (27.2%) systematically used narcotic drugs intravenously. Essential differences between drug users and VH patients without drug addiction were established regarding the distribution of patients by age and sex, the etiological structure and severity of the disease. Thus, in the group of drug users the prevalence of males, young people (15-29 years of age) and the mixed form of hepatitis B + C was noted. In VH patients using drug the disease took a more severe course than in such patients without drug addiction. The highest proportion of intravenously drug users with a severe and moderate course of the disease was found among patients with HB + C and HB.     

从动物模型看乙型病毒性肝炎致病机制的研究进展

乙型肝炎病毒(Hepatitis B virus,HBV)是通过血液和体液传播的嗜肝DNA病毒,尽管有有效的预防疫苗,乙型病毒性肝炎仍是我国乃至全球人类健康的重大威胁。HBV的易感宿主只局限于人以及黑猩猩等灵长类动物,HBV感染性疾病的研究遇到很大困难。多种小动物研究模型的建立,使我们对HBV感染致病机制的认识有了很大进步,包括:分子病毒学特征、在感染细胞中生命周期、机体的抗病毒免疫反应、肝脏病变的免疫病理机制等。但是,由于已有动物模型的种种限制,我们对HBV感染及乙型肝炎发生和发展的认识还远远不够,目前除了抗病毒治疗外,还没有有效地治疗慢性乙肝的方法。建立能够真实反映临床HBV感染、乙肝发生和进展过程的纯系小鼠模型,对于我们全面深入地理解HBV感染的侵入机制、宿主和病毒之间相互作用,以及发展预防和治疗HBV感染的新方法都具有非常重要的意义。     

Hepatitis B virus and the development of human embryonal tumors

Sera from children bearing embryonal tumors and from their parents were screened for the presence of hepatitis B virus (HBV) and its DNA by means of serology and molecular hybridization, respectively. Sera from tumor-bearing children and their parents both contain HBV or its DNA at average 5 times more frequently than the healthy donors or patients with non-oncological diseases. It is suggested that the presence of HBV or its DNA is caused not solely by infection during cure but also by vertical transmission from parents. The presence of HBV or its DNA might be treated as a risk factor increasing the development of embryonal tumors.