When rheumatology meets hepatology: are anti-TNFs safe in hepatitis B virus carriers?

Over the past decades, more effective and less toxic biologicals have revolutionized rheumatology therapy in our battle against the autoimmune chronic inflammation of rheumatoid arthritis and spondyloarthropathy. But what about for patients who have previously had an infection of the liver? Prior hepatitis B virus infection clearly presents a challenge for clinicians. In a study by Charpin and colleagues of 21 patients whose hepatitis B virus serology suggested carrier status, anti-TNF treatment appeared to be safe during a limited follow-up period of 3 years. Studies are needed with longer follow-up, particularly in patients with low antibody titres (antiHBc). In the 3-year period, however, about 30% of the patients developed significant lowering of antibody titres, which may become relevant during long-term follow-up. Charpin and colleagues are the first to reveal promising data on the relative safety of anti-TNFs in a small series of hepatitis B carriers for up to 3 years.In the previous issue of Arthritis Research & Therapy Charpin and colleagues present French results from an interesting cohort of 21 hepatitis B virus (HBV) carriers with active rheumatoid arthritis or spondyloarthropathy being treated with antibodies to TNF [1]. What do we know about anti-TNF therapy in patients who have recovered from HBV infection? Hepatology has provided knowledge on HBV infection and antivirals have made hepatitis a potentially well-treatable disease since three decades ago [2]. For the past couple of decades, mono-clonal antibodies against TNF have been available, revolutionizing antirheumatic therapy [3]. Together with immunological progress, however, has come clinical complexity. For a rheumatologist encountering a patient with severe and active rheumatoid arthritis or spondyloarthropathy who is also an HBV carrier, hepatitis is regarded as a significant comorbidity. The rheumatologist is trained not to rest until the inflammatory disease has gone into remission; to achieve this target, he will prescribe all disease-modifying antirheumatic drugs (DMARDs), including anti-TNFs. Now a difficult question arises: how to safely achieve complete remission. Methotrexate, the cornerstone of our best disease modifying regimens, is contraindicated in liver disease.HBV, a DNA virus transmitted percutaneously, sexually, and perinatally, affects up to 400 million people worldwide. HBV infection accounts for up to 5,000 deaths in the United States each year and 1 million deaths worldwide from cirrhosis, liver failure, and hepatocellular carcinoma. Important viral proteins include an envelope protein, hepatitis B surface antigen (HBsAg), a structural nucleocapsid core protein, hepatitis B core antigen (HBcAg), and a soluble nucleocapsid protein, hepatitis B e antigen (HBeAg). Serum HBsAg is a marker of HBV infection, and antibodies against HBsAg signify recovery. Serum HBeAg is a marker of active viral replication and may be accompanied by serum levels of HBV DNA that are 100,000 to 1,000,000 IU per milliliter or higher. Eradication of HBV infection is difficult as long-enduring, covalently closed circular DNA (cccDNA) becomes established in hepatocytic nuclei from where HBV DNA becomes integrated into the host genome. The study by Charpin and colleagues included 58 patients with serologically cured HBV infection - that is, HBsAg-negative plus anti-HBc-positive patients - and of these, 24 had been treated with anti-TNFs for rheumatoid arthritis or spondylitis. Additionally, three were lost due to withdrawn consent (n = 1), HBV-unrelated death (n = 1) and being lost from follow-up (n = 1). Finally, 21 HBV carriers being treated with anti-TNFs were included: 3 being treated with adalimumab, 14 with etanercept, and 4 with infliximab.In the United States and Western Europe, most acute HBV infections occur during adolescence and early adulthood due to sexual activity, intravenous drug use, and occupational exposure. In immunocompetent adolescents and adults, a strong cellular immune response to ''foreign'' HBV proteins expressed by hepatocytes results in clinically apparent acute hepatitis, which in 99% of infected people affects clearance of the infection [4,5]. The progression of liver disease after HBV infection is fostered by active virus replication, indicated by a serum HBV DNA level of 1,000 to 10,000 IU per milliliter. In such cases anti-TNFs are contraindicated but antiviral regimens should be considered. A serum HBV DNA level <1,000 IU per milliliter and normal alanine amino-transferase (ALT) levels are considered to be indicators of inactive carriers with only a low risk of clinical progression [6]; rarely, reactivation can occur spontaneously or with immunosuppression [7-9]. As clinical and histological improvement accompanies reductions in HBV replication, interventions reducing HBV replication are indicated in such cases to limit progressive liver disease. When virus infection has been overcome, immunosuppression is relatively contraindicated. Practically, outcomes of HBV infection evolve only over decades. Clinical trials, as well as Charpin and colleagues'' study, are limited to only several years, rarely up to 5 years. Surrogate, achievable endpoints are therefore used, including serologic (HBsAg recurrence, representing recurrent hepatitis versus adequate antiHBc levels, suggesting carrier state), virologic (log₁₀ reduction versus increase in the HBV DNA level, or suppression versus expression of HBV DNA to an (un)detectable level (<10 to 100 IU per millilitre)), as well as a commonly used biochemical parameter (normalization versus increase above the upper normal limit of the serum ALT level).Over the past decades, more effective and less toxic biologicals have revolutionized rheumatology therapy in our battle against the chronic autoimmune inflammation of rheumatoid arthritis and spondyloarthropathy. Unmet needs are adequate access and long-term safety issues regarding tumor and infection risk. What if one has previously had an infection of the liver? Patients who have had a prior HBV infection clearly present a challenge for clinicians. If HBV serology suggests a carrier state, then anti-TNF appears to be safe during a limited follow-up period of 3 years. Studies are needed with longer follow-up, particularly in patients with low antibody titres (anti-HBc). In a 3-year period, however, about 30% of the French patients in the study by Charpin and colleagues developed significant lowering of antibody titres, which may become relevant during long-term follow-up. Charpin and colleagues are the first to reveal promising data on the relative safety of anti-TNFs in a small series of HBV carriers over a period of 3 years.     

High Risk of Hepatitis B Reactivation among Patients with Acute Myeloid Leukemia

BackgroundHepatitis B virus (HBV) infections are common and associated with significant morbidity and mortality in cancer patients. However, the incidence and risk factors of HBV reactivation in patients with acute myeloid leukemia (AML) are rarely investigated.MethodsAML patients followed-up at the National Taiwan University Hospital between 2006 and 2012 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed.ResultsFour hundred and ninety patients comprising 265 men and 225 women were studied. The median age was 52 years (range, 18 - 94). Chronic HBV carriage was documented at the time of leukemia diagnosis in 57 (11.6%) patients. Forty-six (80.7%) of the 57 HBV carriers received prophylaxis with anti-HBV agents. Sixteen HBV carriers (28.1%) developed hepatitis B reactivation during or after chemotherapy, including 7 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among AML patients with HBV carriage was 9.5 per 100 person-years. Prophylaxis with anti-HBV agents significantly decreased the risk of hepatitis B reactivation among HBV carriers (13% vs. 61%, p<0.001). Four (2.8%) of 142 patients with initial positive anti-HBsAb and anti-HBcAb experienced hepatitis B reactivation and lost their protective anti-HBsAb. Multivariate analysis revealed that diabetes mellitus (p=0.008, odds ratio (OR) = 2.841, 95% confident interval (CI): 0.985-8.193) and carriage of HBsAg (p<0.001, OR=36.878, 95% CI: 11.770-115.547) were independent risk factors for hepatitis B reactivation in AML patients.ConclusionsHepatitis B reactivation is not uncommon in the HBsAg positive AML patients. Prophylaxis with anti-HBV agent significantly decreased the risk of hepatitis B reactivation.     

Occult hepatitis B virus infection among injecting drug users in the Central-West Region of Brazil

The prevalence of occult hepatitis B virus (HBV) infection was investigated in 149 hepatitis B surface antigen (HBsAg) negative injecting drug users (IDUs) in the Central-West Region of Brazil. Of these individuals, 19 were positive for HBV DNA, resulting in an occult HBV infection prevalence of 12.7% (19/149); six of these 19 individuals had anti-HBV core and/or anti-HBV surface antibodies and 13 were negative for HBV markers. All IDUs with occult hepatitis B reported sexual and/or parenteral risk behaviours. All HBV DNA-positive samples were successfully genotyped. Genotype D was the most common (17/19), followed by genotype A (2/19). These findings reveal a high prevalence of occult HBV infection and the predominance of genotype D among IDUs in Brazil''s Central-West Region.     

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

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

Reactivation of Hepatitis B Virus in HBsAg-Negative Patients with Hepatocellular Carcinoma

Background & Aims

Despite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE).

Methods

A total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2–3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46).

Results

During the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216–116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation.

Conclusions

TACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.     

Risk of vertical transmission of hepatitis B virus in Tunisia

The risk of vertical transmission of hepatitis B virus (HBV) varies with type of viral endemicity, degree of maternal infection and genomic characteristics of the virus. The aim of this study is to estimate this risk in Tunisia using serological and molecular methods to evaluate HBV replication, to determine viral genotypes and to detect presence of occult hepatitis in 2709 pregnant women. Serological markers were detected by ELISA methods, Genotype was determined by PCR-RFLP and occult hepatitis by nested-PCR. Four percent of women were positive for HBsAg; only 3% of them were also positive for HBeAg. Viral replication, over than 10(3) copies/ml, was detected in 61% of positive HBsAg patients. Three viral genotypes were detected: D (95%), B (3%) and A (3%). Occult hepatitis was detected in 4% of sera with "anti-HBc isolated" profile. In conclusion, the risk of vertical transmission of HBV exists in Tunisia. It increases by frequency of precore mutants, predominance of the genotype previously associated with high levels of replication and possibility of occult hepatitis B. These results show the importance of screening by serological HBV markers systematically during pregnancy with evaluation of viral replication in order to prevent vertical risk by efficient tools.     

A case of hepatitis B reactivation in an anti-HBs positive, anti-HBc positive non-Hodgkin’s lymphoma patient

Dear Editor, We report a case of HBV reactivation in an anti-HBs positive,anti-HBc positive non-Hodgkin's lymphoma patient.Hepatitis B virus (HBV) reactivation is a well-recognized complication of patients undergoing chemotherapy or immunosuppressive therapy for lymphomas.The presence of antibodies to the hepatitis B surface antigen (anti-HBs) has been identified to be a factor preventing HBV reactivation in patients with occult HBV infection receiving chemotherapy.In this paper,we present a non-Hodgkin Lymphoma patient who,before immunosuppressive therapy,displayed positive anti-HBs and positive antibodies to hepatitis B core antigens (anti-HBc),as markers of resolved HBV infection,and developed hepatitis B surface antigen (HBsAg) and high viraemia with an HBV escape mutant after rituximabbased administration.The sequencing data revealed HBV genotype D with two known escape mutations,P120S.     

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.     

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.     

乙型肝炎病人尿细胞中HBV的实验研究

本文采用间接免疫荧光法（ＩＦ）,ＲＰＨＡ法,ＥＬＩＳＡ法及斑点杂交技术检测１０例无症状ＨＢ－ｓＡｇ携带者及８９例乙肝病人尿细胞中的ＨＢｓＡｇ、ＨＢｅＡｇ及ＨＢＶＤＮＡ,发现尿细胞中有ＨＢｓＡｇ、ＨＢｅＡｇ、ＨＢＶＤＮＡ存在。结果提示：乙肝无症状携带者及乙肝病人尿细胞中具有ＨＢｓＡｇ、ＨＢｅＡｇ、ＨＢＶＤＮＡ,因此更进一步证实尿液具有传染性。     

Success of a program of routine prenatal screening for hepatitis B surface antigen: the first 2 years.

Prenatal screening for hepatitis B surface antigen (HBsAg) restricted to women with defined risk factors for chronic hepatitis B virus (HBV) infection fails to identify many carriers. A centralized program of routine HBsAg screening for all pregnant women in Alberta was introduced in 1985. We collected and analysed data for the first 2 years of the program in Edmonton to determine the frequency of risk factors for HBsAg positivity, the proportion of multiparous HBsAg-positive women not identified in previous pregnancies, the efficiency and cost-effectiveness of providing immunoprophylaxis to infants at risk of HBV infection and the degree of success in inducing adequate protection. A total of 149 women (158 pregnancies) were found to be HBsAg positive. Risk factors were readily ascertainable for 85% of the women; the remaining 15% would not have been identified through risk-selective screening. The most common risk factors were Oriental ethnic origin, history of hepatitis, jaundice or multiple transfusions of blood or blood products, and occupational exposure to blood. Although 86% of the multiparous HBsAg-positive women had risk factors, only 7% had been identified in previous pregnancies. The Alberta program appears to be cost-effective. We conclude that only routine prenatal screening will identify all infants at risk of perinatal HBV infection and that a comprehensive public health program involving central laboratories, private physicians and public health staff can be highly effective and efficient in protecting infants against hepatitis B.     

Cytokine expression during chronic versus occult hepatitis B virus infection in HIV co-infected individuals

Chronic hepatitis B virus infection is characterized by persistent detectable levels of hepatitis B surface antigen (HBsAg) and HBV DNA in the serum. In contrast, HBsAg is not detectable during occult HBV infection, despite the presence of HBV DNA. An altered host immune response could play a role in the development of occult HBV infection; however, potential differences in immune responses among chronic and occult HBV-infected patients have not been evaluated in vivo. In the current study, we evaluated serum levels of regulatory, apoptotic, and fibrotic/anti-fibrotic cytokines/markers as indicators of immune responses in 25 chronic and 12 occult HBV-infected patients. More than half of the patients in both chronic and occult HBV infection groups had IL-2, IL-4, IL-13, and IFN-γ levels below detectable limits. In contrast, most patients had detectable levels of IL-8, IL-10, IP-10, sFas, sFasL, and TGF-β1. Of these, only sFas was significantly different between the two groups, with lower levels observed during occult compared to chronic HBV infection (p = 0.01). As a surrogate marker of apoptotic inhibition, decreased sFas during occult HBV infection suggests that apoptosis occurs at different rates in occult compared to chronic HBV infection and therefore, may contribute to persistence of occult HBV infection.     

Hepatitis B virus surface antigen can activate human monocyte-derived dendritic cells by nuclear factor kappa B and p38 mitogen-activated protein kinase mediated signaling

Hepatitis B virus Ag (HBsAg), a major antigen of hepatitis B virus (HBV), is also a vaccine component for prevention of HBV infection. Dendritic cells (DCs) of HBV carriers reportedly exhibit functional impairment. In this study, the aim was to investigate the effect of HBsAg on activation of human monocyte-derived dendritic cells (MD-DCs), and the subsequent signal transduction pathway. Treatment of MD-DCs with HBsAg resulted in enhanced cell surface expression of cluster of differentiation 80, CD83, CD86 and major histocompatibility complex class II, and increased interleukin (IL)-12 p40, IL-12p70, and IL-10 production. Furthermore, HBsAg treatment of MD-DCs with HBsAg resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon and IL-10. The pathway of MD-DCs activation by HBsAg was further investigated in the present study. Inhibition of nuclear factor (NF)-kappa B (κB) by helenalin and p38 mitogen-activated protein kinase (MAPK) by SB203580 prevented production of IL-12 p40, IL-12 p70, and IL-10. HBsAg also augmented MAPK phosphorylation. Thus, cytokine secretion of human MD-DCs by HBsAg is blocked by inhibition of the NF-κB and p38 MAPK pathways. Likewise, decreased inhibition of kappa B alpha concentrations and MAPK phosphorylation are critical for MD-DC maturation by HBsAg. These findings may provide a strategy for improving the prophylactic and therapeutic efficacy of vaccines and tumor therapies that utilize these pathways.     

Patterns of hepatitis B virus infection in Brazilian human immunodeficiency virus infected patients: high prevalence of occult infection and low frequency of lamivudine resistant mutations

Hepatitis B virus (HBV) molecular profiles were determined for 44 patients who were infected with human immunodeficiency virus (HIV) type 1 and had antibodies to the hepatitis B core antigen (anti-HBc), with and without other HBV serological markers. In this population, 70% of the patients were under lamivudine treatment as a component of antiretroviral therapy. HBV DNA was detected in 14 (32%) patients. Eight out of 12 (67%) HBsAg positive samples, 3/10 (30%) anti-HBc only samples, and 3/22 (14%) anti-HBs positive samples were HBV DNA positive. HBV DNA loads, measured by real time polymerase chain reaction, were much higher in the HBsAg positive patients (mean, 2.5 x 10(9) copies/ml) than in the negative ones (HBV occult infection; mean, 2.7 x 10(5) copies/ml). Nine out of the 14 HBV DNA positive patients were under lamivudine treatment. Lamivudine resistant mutations in the polymerase gene were detected in only three patients, all of them belonging to the subgroup of five HBsAg positive, HBV DNA positive patients. A low mean HBV load (2.7 x 10(5) copies/ml) and an absence of lamivudine resistant mutations were observed among the cases of HBV occult infection.     

Prevalence of occult hepatitis B virus infection in kidney transplant recipients

In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.     

Rare Detection of Occult Hepatitis B Virus Infection in Children of Mothers with Positive Hepatitis B Surface Antigen

The prevalence of occult Hepatitis B virus (HBV) infection in children was considerably varied from 0.1–64% in different reports. In this study we aimed to investigate the prevalence of occult HBV infection among the children born to mothers with positive hepatitis B surface antigen (HBsAg) in Jiangsu, China. Serum samples were collected from 210 children of 207 mothers with positive HBsAg. HBV serological markers were detected by ELISA and HBV DNA was detected by nested PCR. Homology comparison of HBV sequences recovered from the child and mother was used to define the infection. Three children (1.43%) were positive for HBsAg, in whom the HBV pre S and S gene sequence in each child was identical to that in her mother. Of the 207 HBsAg-negative children, nine displayed HBV DNA positive by two nested PCR assays using primers derived from S and C genes. However, the sequence alignment showed that the sequences in each child were considerably different from those in his/her mother. Therefore, the sequences amplified from the children were very likely resultant from the cross-contaminations. Furthermore, the nine children with ‘positive HBV DNA’ were all negative for anti-HBc, and one had anti-HBs 3.42 mIU/ml and eight others had anti-HBs from 72 to >1000 mIU/ml, indicating that the nine children were less likely infected with HBV. Therefore, none of the 207 HBsAg-negative children of HBV-infected mothers was found to have occult HBV infection. We conclude that the prevalence of occult HBV infection in vaccinated children born to HBsAg positive mothers should be extremely low. We recommend that homology comparison of sequences recovered from the child and mother be used to define the occult HBV infection in children born to HBV infected mothers.     

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.     

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.     

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

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

乙型肝炎病人重叠感染丙型肝炎的评价

应用ＥＬＩＳＡ和ＰＣＲ法检测５０２例乙肝病人血清,４０１例ＨＢｓＡｇ阳性血清中,有１１４例（２８．４％）抗－ＨＣＶ和ＨＣＶＲＮＡ双项阳性,２５例（６．２％）ＨＣＶＲＮＡ单项阳性;２１例（５．２％）抗－ＨＣＶ单项阳性。将ＨＢｓＡｇ乙肝病人分成ＨＢＶＤＮＡ,ＨＢｅＡｇ阳性组和ＨＢＶＤＮＡ,ＨＢｅＡｇ阴性组。前者抗－ＨＣＶ阳性率为１１．６％～２０．５％,ＨＣＶＲＮＡ阳性率为１６．２％～２０．５％。后者抗－ＨＣＶ阳性率为２０．２％～５５．６％,ＨＣＶＲＮＡ阳性率为２３％～６０．３％。结果说明长期携带ＨＢＶ者和慢性乙肝病人均可重叠ＨＣＶ感染。ＨＢＶＤＮＡ阳性组抗－ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于ＨＢＶＤＮＡ阳性组