HBV Surface Antigen Positivity Research Articles

Comparison of prognosis by viral etiology in patients with hepatocellular carcinoma after radiofrequency ablation

Background. Radiofrequency ablation (RFA) has been performed as a first line curative treatment modality for patients with hepatocellular carcinoma (HCC) within the Milan criteria currently. However, prognosis of hepatitis B- and hepatitis C-related HCC after RFA remains debatable. This study aimed to assess the impact of viral etiology on the prognosis of HCC patients undergoing RFA.Material and methods. One hundred and ninety-two patients with positive serum HBV surface antigen (HBsAg) and negative serum antibody against HCV (anti-HCV) were enrolled as the B-HCC group and 165 patients with negative serum HBsAg and positive anti-HCV as the C-HCC group. Post-RFA prognoses were compared between the two groups using multivariate and propensity score matching analyses.Results. The B-HCC group had higher male-to-female ratio and better liver functional reserve than the C-HCC group. After a median follow-up of 23.0 ± 22.7 months, 55 patients died and 189 patients had tumor recurrence after RFA. The cumulative five-year survival rate was 75.9% and 69.5% in the B-HCC and C-HCC groups, respectively (p = 0.312), while the five-year recurrence-free survival rate was 19.0% and 26.6%, respectively (p = 0.490). After propensity-score matching, the B-HCC group still had comparable overall survival rate (p = 0.679) and recurrence-free survival rate (p = 0.689) to the C-HCC group. For 132 patients with Barcelona-Clinic Liver Cancer stage 0, the five-year overall survival and recurrence-free survival rates were also comparable between the two groups (p = 0.559 and p = 0.872, respectively).Conclusion. Viral etiology is not essential for determining outcome in HCC patients undergoing RFA.

Prevalence of Hepatitis B in Insular Regions of Southeast China: A Community-Based Study

ObjectiveHepatitis B virus (HBV) infection remains a significant public health problem. The purpose of this study was to investigate the seroepidemiology of HBV in people living in the insular regions, and to provide the most recent baseline data for planning and monitoring of health.MethodsA cross-sectional, community-based survey was conducted without age restriction, on two isolated islands, Zhoushan and Yuhuan, China. The study sample was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 15878 participants.ResultsThe prevalences of anti-HBV core antibody (anti-HBc), hepatitis B virus surface antigen (HBsAg), and anti-HBV surface antibody (anti-HBs) were 33.1, 10.4, and 56.1%, respectively. We found statistically significant differences of HBV markers in men versus women (P<0.01). The prevalence of HBV infection increased with age. There were significant differences in the rates of HBsAg and anti-HBc positivity between the two islands (P<0.01). Alanine aminotransferase (ALT) levels were elevated (>38 IU/L) in 15.6% and 7.2% of the HBsAg-positive and negative groups, respectively. Elevated ALT levels were significantly higher in males (12.0%) compared with females (5.8%) (P<0.01). The α-fetoprotein (AFP) positivity rate was 0.6% in HBsAg-positive participants over the age of 30.ConclusionDue to the geographic location, we found that the HBV prevalence and potential for the development of hepatocellular carcinoma remained high in insular regions of southeast China, and are far above the national figures. Although a vaccination program has been in effect over the last 20 years, several additional measures should be adopted by the government to limit the spread of hepatitis B. These include the management of high risk persons and the floating population living on the islands, expansion of the immune population, and increased health education for fisherman.

The association between hepatitis B virus infection and disease activity, synovitis, or joint destruction in rheumatoid arthritis

The prevalence of chronic hepatitis B virus (HBV) infection in China is high. Four percent of patients with HBV infection can present with polyarthritis and positive rheumatic factor similar to rheumatoid arthritis (RA). Here, we investigated the association between HBV infection and serological, radiological, or histological disease status in RA. According to HBV infection status, 223 consecutive hospitalized Chinese patients with RA were divided into the groups of chronic HBV infection, past HBV infection, and no HBV infection. Clinical data and hand radiographs were collected. Synovium was obtained by closed-needle biopsy, and serial tissue sections were stained immunohistochemically for HBV surface antigen (HBsAg) and cluster of differentiation (CD) markers. (1) The prevalence of HBsAg positivity and chronic hepatitis B in RA was consistent with the age-matched general Chinese population (11.2 vs. 8.7 %, 1.7 vs. 1.0 %, respectively, P > 0.05). (2) Clinical parameters, disease activity score in 28 joints, or Sharp scores showed no significant difference among the three groups in 206 RA or 140 treatment-naïve patients, both with active disease (all P > 0.05). (3) Synovial immunohistochemical staining showed negative HBsAg in ten RA patients with HBV carrier status and ten RA patients with past HBV infection. Except for higher subintimal CD3+ cell density in the past HBV infection group, Krenn's synovitis score, mean densities of subintima positive-staining cells (CD20, CD38, CD79a, and CD68), and CD34+ microvessel counts showed no significant difference among RA patients with HBV carrier status, past HBV infection, or no HBV infection (all P > 0.05). Chronic HBV infection may have no significant effect on disease activity, synovitis, or joint destruction in RA.

Effectiveness of HBV Vaccination in Infants and Prediction of HBV Prevalence Trend under New Vaccination Plan: Findings of a Large-Scale Investigation

BackgroundHepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention.MethodsTo evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined.ResultsOf the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%.ConclusionsThe national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.

Serological survey of viral hepatitis markers among newly diagnosed patients with HIV/AIDS in China

The aim of the study was to determine the seroprevalence and epidemiological features of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among patients newly diagnosed with HIV/AIDS in China. Two thousand and forty patients newly diagnosed with HIV/AIDS from 10 provinces in China were selected during 2009 to 2010. Serum samples obtained from each individual were screened for HBV and HCV serum markers [HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), HBV envelope antigen (HBeAg), HBV envelope antibody (HBeAb), HBV core antibody (HBcAb) and HCV antibody (HCVAb)]; liver function tests were also performed. Demographics and medical histories were collected. Of the 2040 patients, 741 (36.3%) were positive for at least one HBV and HCV serum marker; 300 (14.71%) were HCVAb positive, and 248 (12.16%) were isolated HCVAb positive; 222 (10.9%) were positive for HBsAg; 19 (0.93%) were positive for both HBsAg and HCVAb. The highest prevalence of HBsAg positivity was found in Guangxi (15.31%), followed by Guangdong (15.19%) and Shanghai (14.36%). The highest prevalence of HCVAb positivity was found in Xinjiang (43.18%), followed by Henan (39.06%) and Yunnan (27.36%). The proportion of patients with abnormal liver function in patients positive for HCVAb and/or HBsAg was significantly higher than that in those who were negative for both HCVAb and HBsAg (P < 0.001). The seroprevalence of HBV and HCV among patients newly diagnosed with HIV/AIDS in China is high. HBsAg and HCVAb positivity prevalences were found to vary significantly in different provinces in China. Patients newly diagnosed with HIV/AIDS and coinfected with HBV and HCV are at higher risk of abnormal liver function. It is necessary to routinely screen for HBV and HCV infection among patients newly diagnosed with HIV/AIDS.

HIV and Hepatitis B coinfection among perinatally HIV-infected Thai adolescents.

This study aimed to determine the prevalence of hepatitis B virus (HBV) coinfection and HBV seropositivity in perinatally HIV-infected adolescents. A secondary objective was to describe the clinical characteristics of adolescents with chronic HBV/HIV coinfection. Multicenter cross-sectional study of perinatally HIV-infected adolescents aged 12-25 years. HBV surface antigen, surface antibody (anti-HBs) and core antibody (anti-HBc) were measured. Coinfection was defined as having persistently positive HBV surface antigen. Seroprotective antibody from immunization was defined as having anti-HBs ≥10 mIU/mL with negative anti-HBc. HBV DNA quantitation and rtM204V/I mutation analysis (lamivudine resistance-associated mutation) were performed in adolescents with chronic HBV infection. From November 2010 to March 2011, 521 patients were enrolled. Mean (SD) of CD4 lymphocyte count was 685 (324) cells/μL. The prevalence of HBV/HIV coinfection was 3.3% (95% confidence interval: 1.9-5.2%). Protective antibody against HBV was found in 18% of population, and this was significantly higher among adolescents who received than those who did not receive HBV revaccination after receiving antiretroviral therapy (93% versus 6%, P < 0.01). Among adolescents with chronic HBV infection, 88% have received lamivudine; however, 69% have HBV DNA >10 copies/mL and 75% had the rtM204V/I mutation. The prevalence of HBV coinfection in HIV-infected Thai adolescents was 3.3%. Most HIV-infected adolescents had no HBV protective antibody; therefore, revaccination with HBV vaccine is encouraged. The high prevalence of HBV-lamivudine resistance underscores the importance of HBV screening prior to antiretroviral therapy initiation to guide the selection of optimal regimen for coinfected children.

Prevalence and risk factors for HIV, hepatitis B virus, and syphilis among pregnant women in Mayotte, Indian Ocean, 2008–2009

ObjectiveTo assess the prevalence and risk factors for HIV, hepatitis B virus (HBV), and syphilis among pregnant women living on the Indian Ocean island of Mayotte. MethodsA cross-sectional survey was conducted among 671 pregnant women at 11 prenatal clinics on Mayotte between September 15, 2008, and September 27, 2009. Sociodemographic and behavioral characteristics were collected by interviewer-administered questionnaire. Blood samples were obtained for HIV, HBV, and syphilis testing. Risk factors were analyzed by exact logistic regression. ResultsNo prevalent case of HIV infection was detected among the study population. The prevalence of HBV surface antigen and active syphilis (defined as a positive test result by both rapid plasma reagin and Treponema pallidum hemagglutination assays) was 3.4% and 2.1%, respectively. A positive HBV surface antigen test was associated with being born in Comoros and having sex with a casual partner during the previous year. Lack of education and a history of sexually transmitted infections in the past 5years were associated with active syphilis. ConclusionThe continuing low prevalence of HIV and high prevalence of sexually transmitted infections among pregnant women on Mayotte confirmed the so-called “Indian Ocean paradox.”

Transient elastography and simple blood markers in the diagnosis of esophageal varices for compensated patients with hepatitis B virus‐related cirrhosis

Transient elastography (TE) has been useful in esophageal varices (EV) diagnosis for chronic hepatitis C patients. In the present study, we evaluate the usefulness of TE and simple blood markers in the EV diagnosis of patients with hepatitis B virus (HBV)-related cirrhosis, prospectively. Consecutive patients with compensated cirrhosis and positive HBV surface antigen were enrolled, prospectively. At enrollment, the aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR) and the AST to platelet ratio index (APRI) were recorded, and TE was performed. Two experienced endoscopists assessed EV independently. High-risk EV was defined as small size with a red color sign, and medium or large in size. The diagnostic performances, optimal cut-offs, and the validities of TE, APRI, platelet count (PLT), and AAR in EV diagnosis were assessed. A total of 126 patients (male/female: 93/33; mean age: 54.5 years) with reliable TE results were analyzed. There was good agreement between two endoscopists in assessing the presence of EV and high-risk EV (kappa value: 0.82 and 0.96). Forty-eight (38.1%) patients had EV (small: 35; high risk: 13). There was correlation between TE result and EV size (r = 0.515, P < 0.001). TE, APRI, and PLT were similar; however, superior to AAR in the diagnostic accuracies for EV and high-risk EV. In high-risk EV prediction, the negative predictive value (NPV) was 97%, 98%, and 98%, with cut-offs of 21 kPa, 1.24, and 110 (× 10(9) /L) for TE, APRI, and PLT, respectively. For compensated patients with HBV-related cirrhosis, TE, APRI, and PLT are useful in excluding high-risk EV with high NPV.

Seroconversion of hepatitis B virus surface antigen in chronic hepatitis B child treated with entecavir

Sir, Hepatitis B virus (HBV) infection in children possesses a higher rate of progression to chronic hepatitis, however, a consensus guideline for treatment has not been established so far.[1,2] Entecavir as carbocyclic analog with inhibition of HBV replication[3] is shown encouraging effects in control of chronic HBV infection.[3] In the present article, we present seroconversion of hepatitis B virus surface antigen (HBsAg) by entecavir administrated in a young child with chronic hepatitis B. A 4-year-old girl was presented in a history of chronic HBV infection for 2 years. The perinatal history indicated that her mother was a HBV carrier, and grandmother died of cirrhosis due to chronic hepatitis B. The patient was vaginally born, and was immunized with hepatitis B vaccine and high-titter immunoglobulin against HBV at birth. During past 2 years, the patient had been administrated with Chinese herbal medicines. Because of unsatisfying theroputic effect, the patient was then transferred to our department. On admission, abdominal computed tomography (CT) scan demonstrated a normal size of the liver, but the spleen was enlarged in size. The laboratory tests showed that alanine aminotransferase (ALT) 92 U/L, aspartate transaminase (AST) 96 U/L, γ-glutamyl transpeptadase (GGT) 8 U/L, HBsAg positive, HBeAg positive, anti-HBV core antibody positive, and HBV DNA level 2.703 × 107 copies/mL. The autoimmune antibodies were absent, and serum markers for hepatitis A virus, hepatitis C virus, hepatitis E virus, cytomegalovirus, and Epstein Bar virus were negative. The patient was diagnosed with chronic hepatitis B with positive HBsAg. After informed consent was obtained from her parents, the patient was started with oral administration of entecavir at dose of 0.16 mg once a day. During administration of entecavir, the patient was regularly monitored by tests of liver function, HBsAg and HBV DNA level, and hematologic system. Tests showed that ALT was declined 2 weeks after entecavir administrator, and was normalized 4 weeks after treatment. The level of HBV DNA decreased in 2 weeks, and negative 24 weeks after entecavir administration. Interestingly, we noticed that HBeAg seroconversion was started 12 weeks after the treatment, and HBsAg became negative 48 weeks after treatment, followed by HBsAg seroconversion 72 weeks after treatment. Entecavir was terminated at 192nd week when liver function and HBV DNA were back to normal. Entecavir was tolerated well in this little patient, and nephrotoxicity or myopathy were not noticed during the treatment. The patient has so far been followed-up for a period of 96 weeks since the termination of entecavir. The patient has positive anti-HBs, anti-HBe, anti-HBc, and normal liver function [Table 1]. The girl is well and in healthy condition now. Table 1 Variations of laboratory tests before and after treatment of entecavir The ultimate goal of antiviral treatment in chronic HBV infection is to eradicate replicating HBV. HBV requires HBsAg to propagate infection and cause disease. Entecavir is a nucleoside analog with therapeutic effect on chronic HBV,[4–7] and has been shown to decrease HBsAg in animal research.[8] Although potential effects of entecavir on chronic HBV infection were reported in some other studies,[3,4–6] those studies had no involved lowering of HBsAg or HBsAg seroconversion. The satisfied outcome observed in our little girl patient using entecavir might be the first case, specifically lowering HBsAg or HBsAg seroconversion, in the reported literatures. Large sample are, however, needed to evaluate entecavir in term of clinical efficacy in children with chronic HBV.

Prevalence of hepatitis B in the southeast of China

Hepatitis B is a major public health problem in China. However, in the past 10 years, estimates of the prevalence of hepatitis B virus (HBV) have been sparse, with results that do not always agree. The purpose of this study was to investigate the epidemiology of HBV in adults and to provide the most recent baseline data for planning and monitoring of health. The prevalence of HBV was determined in a community-based, cross-sectional, age-stratified sample of adults (aged 20 years or older). The study population was selected using random multistage cluster sampling. Demographic information and serological samples were obtained from 19 933 participants. The prevalence of anti-HBV core antibody, HBV surface antigen (HBsAg), and anti-HBV surface antibody was 38.6, 7.9, and 44.9%, respectively. We found statistically significant differences in hepatitis B infection between men and women (P<0.001). The prevalence of HBV infection increased with age. The rates of HBsAg positivity and HBV infection in individuals living on an island were higher than those of individuals living in plains. The alanine aminotransferase level was elevated (≥38 IU/l) in 15.7 and 7.2% of HBsAg-positive and HBsAg-negative patients; the proportion of elevated alanine aminotransferase was markedly higher in men (12.7%) than in women (4.7%) (P<0.001). The α-fetoprotein-positive rate was 2% in HBsAg-positive individuals who were aged 30 years or older. Borderline intermediate/high endemicity was found among adults in the northern region of Zhejiang Province. The vaccination program has contributed to a reduction in infection over the last 20 years, although further efforts are required to turn the region into a 'low-endemicity' area.

Immunogenicity of two different hepatitis B vaccine schedules

Dear Sir, A letter by Rashmi Ranjan Das et al. was recently published in Infection in which the authors commented on our article entitled “Immunogenicity of recombinant hepatitis B vaccine: comparison of two different vaccination schedules” [1]. We would like to take the opportunity provided by this letter to discuss our findings in particular and hepatitis B epidemiology in Turkey in general. The study performed by Das et al. [2] is one of the few published to date that compares different vaccination schedules of hepatitis B immunization in children [2–4]. These authors performed a randomized clinical trial on the immunogenicity of two different hepatitis B vaccine schedules, i.e., birth, 6 weeks, and 14 weeks (Group A) or 6, 10, and 14 weeks (Group B), and found that seroconversion rates for hepatitis B vaccine were comparable in the two groups. In contrast, two other studies [3, 4], similar to our study, revealed lesser seroconversion in infants whose vaccination started immediately after birth. Such data will contribute to the generation of recommendations on the optimal timing of the initial dose of hepatitis B immunization in infants. In addition to seroprotection, other factors, such as the feasibility of screening for hepatitis B virus surface antigen (HBsAg) in pregnancy and changing epidemiology of the disease in vaccinated populations will also have an effect on these recommendations. With respect to hepatitis B epidemiology in Turkey, we agree with the conclusions of Das et al. [2]. It is likely that vaccinated children born to HBsAg-positive mothers or living in areas where hepatitis B infection is endemic are exposed to hepatitis B throughout childhood. Such children can obtain natural booster doses, which is also an approach to be considered in countries with moderate endemicity. Turkey is known to have moderate hepatitis B endemicity, but in the previous decade the prevalence of HBsAg positivity declined from 4.19 to 2.10 [5–8]. Although hepatitis B infection seroprevalances are accepted to have increased in the more eastern regions in Turkey relative to the western ones, a recent study found that the incidence of hepatitis B carriers in pregnancy was 2.1% in southeastern regions of Turkey [9]. This decrease is the result of the implementation of hepatitis B vaccination programs for infants in 1998 and catch-up vaccination programs for school-age children. According to Turkish Ministry of Health data, the hepatitis B coverage rate for infants <1 year of age in 2010 was 95%, and incidences of HBsAg positivity for children <5 years of age were 3/100,000 and 0.5/100,000 in 2005 and 2010, respectively [10]. Turkey is shifting from moderate to low endemicity and, consequently, the possibility of repeated sub-clinical exposure and natural boosters is also decreasing. These facts support the comment made in our study “as children need long-term protectivity and if immunological memory may later decline or become undetectable, the risk of breakthrough infection may occur”. Infants born to HBsAg-positive mothers should receive the first dose of hepatitis B vaccine at birth, but the first dose may be given at a later age for other children. However, screening is costly and not usually feasible in Turkey. In countries where screening programs for pregnancy are not available, vaccination at birth for hepatitis B perinatal infections is still a necessity. We agree with Das et al. [2] on the necessity of post-vaccination follow-up of different schedules, including birth dose of vaccination with sero-epidemiological studies. As we emphasized previously, our study is a preliminary report and we plan to follow up these infants until puberty and evaluate their immunological status.

Safety and efficacy of raltegravir in patients with HIV‐1 and hepatitis B and/or C virus coinfection

The aim was to examine the long-term safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B virus (HBV) and/or hepatitis C virus (HCV) coinfection in three double-blind, randomized, controlled Phase III studies. In STARTMRK, treatment-naïve patients received raltegravir 400 mg twice a day (bid) or efavirenz 600 mg at bedtime, both with tenofovir/emtricitabine. In BENCHMRK-1 and -2, highly treatment-experienced patients with multi-drug resistant virus and prior treatment failure received raltegravir 400 mg bid or placebo, both with optimized background therapy. Patients with chronic HBV and/or HCV coinfection were enrolled if baseline liver function tests were ≤5 times the upper limit of normal. HBV infection was defined as HBV surface antigen positivity for all studies; HCV infection was defined as HCV RNA positivity for STARTMRK and HCV antibody positivity for BENCHMRK. Hepatitis coinfection was present in 6% (34 of 563) of treatment-naïve patients (4% HBV only, 2% HCV only and 0.2% HBV+HCV) and 16% (114 of 699) of treatment-experienced patients (6% HBV only, 9% HCV only and 1% HBV+HCV). The incidence of drug-related adverse events was similar in raltegravir recipients with and without hepatitis coinfection in both STARTMRK (50 vs. 47%) and BENCHMRK (34 vs. 38.5%). Grade 2-4 liver enzyme elevations were more frequent in coinfected vs. monoinfected patients, but were not different between the raltegravir and control groups. At week 96, the proportion of raltegravir recipients with HIV RNA <50 HIV-1 RNA copies/mL was similar between coinfected and monoinfected patients (93 vs. 90% in STARTMRK; 63 vs. 61% in BENCHMRK). Raltegravir was generally well tolerated and efficacious up to 96 weeks in HIV-infected patients with HBV/HCV coinfection.

Hepatitis B virus and sexual behavior in Rakai, Uganda

HIV and hepatitis B virus (HBV) co-infection poses important public health considerations in resource-limited settings. Demographic data and sera from adult participants of the Rakai Health Sciences Program Cohort in Southwestern Uganda were examined to determine HBV seroprevalence patterns in this area of high HIV endemicity prior to the introduction of anti-retroviral therapy. Commercially available EIAs were used to detect prevalent HBV infection (positive for HBV core antibody [anti-HBc] and/or positive HBV surface antigen [HBsAg]), and chronic infection (positive for HBsAg). Of 438 participants, 181 (41%) had prevalent HBV infection while 21 (5%) were infected chronically. Fourteen percent of participants were infected with HIV. Fifty three percent showed evidence of prevalent HBV infection compared to 40% among participants infected with HIV (P = 0.067). Seven percent of participants infected with HIV were HBsAg positive compared to 4% among participants not infected with HIV (P = 0.403). The prevalence of prevalent HBV infection was 55% in adults aged >50 years old, and 11% in persons under 20 years. In multivariable analysis, older age, HIV status, and serologic syphilis were significantly associated with prevalent HBV infection. Transfusion status and receipt of injections were not significantly associated with HBV infection. Contrary to expectations that HBV exposure in Uganda occurred chiefly during childhood, prevalent HBV infection was found to increase with age and was associated sexually transmitted diseases (HIV and syphilis.) Therefore vaccination against HBV, particularly susceptible adults with HIV or at risk of HIV/STDs should be a priority.

Hepatitis B reactivation induced by Rituximab maintenance therapy for lymphoma

Dear Editor, Hepatitis B virus (HBV) reactivation is a serious problem for patients with malignancy when receiving cytotoxic chemotherapy, especially for lymphoma patients [1]. Pei et al. [2] demonstrate that Rituximab-based chemotherapy regimen increases risk of HBV reactivation. For patients with positive HBV surface antigen (HBsAg), the consensus in Taiwan is prophylaxis with anti-HBV drugs during and 3 to 6 months after chemotherapy. With more evidence for use of Rituximab in 2-year maintenance therapy for follicular lymphoma [3] and for further treatment of diffused large B cell lymphoma, it remains unclear whether HBV prophylaxis during Rituximab maintenance therapy is indicated. Here, we present a 41-year-old woman with nonHodgkin's lymphoma (NHL) who died of HBV reactivation during Rituximab maintenance therapy. This patient was diagnosed as NHL, diffused large B cell stage IV, with initial presentation of abdominal fullness. Because of positive HBsAg, she received Lamivudine 100 mg per day during her six cycles of R-CHOP regimen (375 mg/M Rituximab, 750 mg/M cyclophosphamide, 50 mg/M Adriamycin, 1.4 mg/M vincristine, and 40 mg/ M prednisolone for 5 days). She achieved complete remission after this full course of chemotherapy, as shown by negative image findings of computer tomography and positron emission tomography. This patient received lamivudine daily for another 6 months after chemotherapy. She then entered a clinical trial of Rituximab maintenance therapy with schedule of 375 mg/M every 2 months for 2 years. Unfortunately, she suffered from reactivation of HBV, and fulminant hepatitis about 30 days after the ninth treatment with Rituximab. Her liver function is shown in Fig. 1. The patient's HBV DNA was 8.87×10 IU. There were no detectable mutations. We shifted her anti-HBV drug to Entecavir 1 mg per day, but she was not responsive. This patient eventually died of fulminant hepatitis. Rituximab-induced profound hypogammaglobulinemia and impaired humoral immune response have been demonstrated and might be responsible for HBV reactivation [4,5]. There is no consensus of HBV prophylaxis during Rituximab single therapy because only a few cases of HBV reactivation are reported [6,7]. Even if it is highly effective [8], one of the serious problems of HBV prophylaxis with lamivudine comes from its high resistance, which is about 25% annually [9]. For those receiving long-term Rituximab therapy, Entecavir may be a better option because it has minimal resistance rate after 5-years of use in patients with chronic hepatitis B [10]. C.-H. Cho :W.-L. Hwang :C.-L. Teng (*) Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, 160, Section 3, Chungkang Road, Taichung 407, Taiwan e-mail: drteng@vghtc.gov.tw

Resolved Hepatitis B Virus Infection Is Not Associated with Worse Outcome after Allogeneic Hematopoietic Stem Cell Transplantation

Serologic evidence of resolved hepatitis B virus (HBV) infection has been associated with reactivation of hepatitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the true impact of this finding is unknown. We conducted a retrospective matched-control analysis of the outcomes of 76 patients with positive HBV core antibody (HBcAb) and negative HBV surface antigen (HBsAg) at the time of allo-HSCT for hematologic or solid malignancies. Control patients (matched controls), with negative serology for HBV and other viral hepatitides, were matched by age, diagnosis, disease risk, intensity of conditioning regimen, and donor type. In addition, the HBcAb-positive patients and all seronegative patients (all controls, n = 1858) undergoing transplantation during the same period were compared to adjust for other confounding effects. Patient characteristics and baseline hepatic function studies were similar in the HBcAb-positive and matched control groups. The cumulative incidence of hepatitis B reactivation (defined as the emergence of HBsAg in serum) was 11.6% at 3 years. There were no significant differences in overall survival, relapse, nonrelapse mortality, and incidence of acute graft-versus-host disease between the HBcAb-positive and control groups. Our data suggest that seropositivity for HBcAb and seronegativity for HBsAg at the time of transplantation does not seem to adversely affect outcome after allo-HSCT.

Hepatitis B or hepatitis C coinfection in HIV‐infected pregnant women in Europe

The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV-infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use. Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti-HCV) was collected retrospectively from the antenatal records of HIV-infected women enrolled in the European Collaborative Study and linked to prospectively collected data. Of 1050 women, 4.9% [95% confidence interval (CI) 3.6-6.3] were HBsAg positive and 12.3% (95% CI 10.4-14.4) had anti-HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV-seropositivity prevalence (28%; 95% CI 22.8-35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86-4.58], age (for > or =35 years vs. <25 years, AOR 3.45; 95% CI 1.66-7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78-12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20-6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08-13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV-seropositive than in HIV-monoinfected women (AOR 0.34; 95% CI 0.20-0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28 log(10) HIV-1 RNA copies/mL vs. HIV-monoinfected women; P=0.03). HIV/HCV-seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV-monoinfected women (AOR 1.95; P=0.049). Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART.

Integration of hepatitis B virus DNA into the myeloid/lymphoid or mixed-lineage leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular carcinoma

Integration of hepatitis B virus (HBV) DNA into host DNA is detected in about 90% of HBV-related hepatocellular carcinoma (HCC), but the preferential sites of the viral integration etiologically relevant to oncogenesis have been controversial. By using an adaptor-ligation/suppression-PCR, we identified four integrations into the myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4) gene from 10 HCC patients with positive HBV surface antigen (HBsAg). Determination of the cellular-virus DNA junction demonstrated that various lengths of the virus were integrated within 300 bp of intron 3 flanked by the Alu element of MLL4. Chimeric hepatitis B virus X gene (HBx)/MLL4 transcripts and the HBx fusion proteins were detected. DNA microarray revealed that HBx/MLL4 fusion proteins suppressed unique genes in HepG2 cells. Finally, chromosomal translocations of intron 3 of MLL4 to the specific region of chromosome 17p11.2 in 22 out of 32 HCC patients were observed, showing that the intron 3 region of MLL4 gene would be a target of translocation breakpoint. In conclusion, the present data suggest that the translocation breakpoint of MLL4 gene is one of the preferential targets for HBV DNA integration into the MLL4 gene and the HBV DNA integration may be involved in liver oncogenesis.

Infliximab in Ankylosing Spondylitis Associated With Chronic Hepatitis B Infection. Role of Lamivudine Therapy

Anti-tumor necrosis factor-a (TNF) therapy has been associated with reactivation of hepatitis B virus infection. Case reports have suggested the concomitant need of lamivudine treatment in patients with HBV infection treated with antiTNFa agents. We describe a case of ankylosing spondylitis with positive HBV surface antigen (HBsAg) treated with infliximab and lamivudine. Clinical response was excellent but when lamivudine therapy was stopped, reactivation of replication viral occurred. After the reintroduction of lamivudine, viral replication was controlled and liver function tests were normalized. Preventive long-term lamivudine therapy is mandatory when anti-TNFa therapy is maintained in patients with chronic HBV infection.

Highly endemic hepatitis B infection in rural Vietnam

Hepatitis B is a major public health problem in Vietnam; however, estimates of the prevalence of hepatitis B virus (HBV) and hepatitis delta virus (HDV), and risk factors in rural Vietnam are limited. The aim of this study was to determine HBV and HDV prevalence, and identify risk factors for HBV infection. A cross-sectional seroprevalence study was undertaken in two rural districts in Thai Binh province. The study population was randomly selected using multistage sampling. Demographic and behavioral risk information and serological samples were obtained from 837 participants. Mean age was 42.3 years +/- 15.8 (range, 16-82 years), and 50.8% were female. Prevalence of anti-HBV core antibody (anti-HBc) and hepatitis B virus surface antigen (HBsAg) was 68.2% and 19.0%, respectively, and hepatitis B e antigen HBeAg was detected in 16.4% of the HBsAg-positive group. Prevalence of HDV was 1.3% in the HBsAg-positive group. Factors associated with HBV infection (anti-HBc or HBsAg positive) were age 60 years or older (OR, 3.82; 95% CI, 1.35-10.80; P = 0.01), residence in Vu Thu district (OR, 3.00; 95% CI, 2.16-4.17; P < 0.0001), hospital admission (OR, 2.34; 95% CI, 1.33-4.13; P = 0.003) and history of acupuncture (OR, 2.01; 95% CI, 1.29-3.13; P = 0.002). Household contact with a person with liver disease (OR, 2.13; 95% CI, 1.29-3.52; P = 0.003), reuse of syringes (OR, 1.81; 95% CI, 1.25-2.62; P = 0.002) and sharing of razors (OR, 1.69; 95% CI, 1.03-2.79; P = 0.04) were independent predictors of HBsAg positivity. Alanine aminotransferase (ALT) level was elevated (>40 IU/L) in 43% of the HBsAg-positive group; proportion elevated was higher in HBeAg-positive (65%) compared with HBeAg-negative (39%) individuals in this group (P = 0.02). Hepatitis B virus infection is highly endemic in rural Vietnam. Poor infection control activities in health-care settings contribute to high HBV prevalence in this region. Universal HBV infant vaccination and improved infection control procedures are required for improved HBV control in Vietnam.

Is the increased risk of liver enzyme elevation in patients co-infected with HIV and hepatitis virus greater in those taking antiretroviral therapy?

To investigate if the risk of liver enzyme elevation (LEE) in HIV/hepatitis B or C (HBV, HCV) co-infection is altered by HAART (two or more drugs). Analysis comprised HIV-positive patients in the ICoNA study without acute hepatitis who had >or= 1 positive HCV antibody test and > 1 positive HBV surface antigen test. LEE was defined as > 5x baseline alanine aminotransferase (ALT) or > 3.5x baseline if the baseline was > 40 IU/l. Analysis used Poisson regression with generalized estimating equation correction to examine HBV or HCV co-infection, use of HAART, baseline ALT and demographics as LEE predictors. Of the 5272 patients, 47.6% were co-infected with HCV/HBV; 29.9% were female and 39% were intravenous drug users. There were 275 episodes of LEE during 18 259 person-years follow up. Taking HAART did not significantly increase risk of LEE [adjusted relative risk (RR), 1.19; 95% confidence interval (CI), 0.81-1.75; P = 0.37]. Co-infection increased the risk of LEE (adjusted RR, 5.07; 95% CI, 3.47-7.48; P < 0.001), with no significant differences if taking HAART (adjusted RR, 4.99; 95% CI, 3.38-7.37) or not (adjusted RR, 6.02; 95% CI, 2.02-17.98) (P = 0.74 for interaction). Females were at lower risk of LEE than males (adjusted RR, 0.59; 95% CI, 0.42-0.83; P = 0.02). HIV and HBV/HCV co-infection per se is associated with increased risk of LEE that is not modified by HAART. The recommendation for caution in HAART use in co-infected patients, simply based on a high rate of LEE in people on therapy, may be questionable.