[Analysis of HBsAg screening among rural childbearing age people in Yunnan province during 2013-2017].

Objective: To explore the current status of HBV infection before pregnancy among rural childbearing age people in Yunnan province, find out the population at high risk and areas with high incidence and provide evidence for promoting pre-pregnancy aristogenesis and medical interventions for prevention of HBV infection. Methods: The subjects in the study were rural childbearing age people aged 18-49 who received the national free pre pregnancy eugenic health examination in Yunnan province during 2013-2017. Descriptive analysis was conducted for HBsAg positive rate and its difference among various characteristics. The SPSS 22.0 software was used for statistical analysis. Results: A total of 2 180 841 rural childbearing age people were surveyed, the HBsAg positive rate before pregnancy was 3.13%(68 314/2 180 841) in Yunnan. And the HBsAg positive rate was 3.56% (37 694/1 057 376) in men, higher than that in women (2.73%, 30 620/1 123 465). The HBsAg positive rate was highest in age group 41-49 years (3.77%, 3 126/82 931). The HBsAg positive rate was higher in minority ethnic group (3.77%, 27 974/742 518) than in Han ethnicity group (2.81%, 40 024/1 425 870). Moreover, the highest HBsAg positive rate of was 8.20%(851/10 378) in Yao ethnic group. The people with education level of primary education had the highest HBsAg positive rate (3.97%, 17 294/435 219). The HBsAg positive rate was highest in Xishuangbanna Dai autonomous prefecture (6.65%, 3 875/58 232) in Yunnan. Moreover, the HBsAg positive population in severe poor area (3.32%, 19 755/595 665) was higher than those in less poor area (3.17%, 29 750/939 101) or normal areas (2.91%, 18 809/646 075). There was significant difference in HBsAg positive rate among populations in different age groups, ethnic groups, education level groups, areas and economic level groups (P<0.001). Conclusions: The HBsAg positive rate in rural childbearing age people in Yunnan was related to multi factors, including sex, age, ethnic group, education level, area and economic development level. The HBsAg positive rate was higher in men, older age and lower education level, minority ethnic group (especially in Yao ethnic group), from Xishuangbanna prefecture and the poor living conditions in childbearing age population.

Tenofovir prophylaxis for preventing mother-to-child hepatitis B virus transmission in China: A cost-effectiveness analysis.

OBJECTIVES: This study aimed to evaluate whether tenofovir prophylaxis for mothers with high viral loads in late pregnancy is a cost-effective way to prevent mother-to-child hepatitis B virus (HBV) transmission in China. METHODS: A decision tree Markov model was constructed for a cohort of infants born to HBV surface antigen-positive mothers in China, 2016. The expected cost and effectiveness were compared between the current active-passive immunoprophylaxis strategy and the tenofovir prophylaxis strategy, and the incremental cost-effectiveness ratio was calculated. One-way and multi-way probabilistic sensitivity analyses were performed. RESULTS: For 100,000 babies born to mothers positive for hepatitis B surface antigen, tenofovir prophylaxis strategy will prevent 2213 perinatal HBV infections and will gain 931 quality-adjusted life years when compared with the current active-passive immunoprophylaxis strategy. The incremental cost-effectiveness ratio was ï¿¥59,973 ($9087) per quality-adjusted life years gained. This result was robust over a wide range of assumptions. CONCLUSIONS: Tenofovir prophylaxis for mothers with high viral loads in late pregnancy was found to be more cost-effective than the current active-passive immunoprophylaxis alone. Embedding tenofovir prophylaxis for mothers with high virus loads into the present hepatitis B prevention strategies should be considered to further prevent mother-to-child hepatitis B transmission in China.

Self-motivated medical care-seeking behaviors and disease progression in a community-based cohort of chronic hepatitis B virus-infected patients in China.

BACKGROUND: To determine the treatment behaviors among a community-based cohort of chronic hepatitis B virus (HBV)-infected persons and to examine the disease progression among non-antiviral-treated HBV-infected cases after 5 years of follow-up. METHODS: We conducted a community-based prospective study on people with chronic HBV infection in mainland China from 2009 to 2014. In 2009, we recruited participants who were identified as HBV infected in 2006 in a national sero-survey. A face-to-face follow-up investigation was completed in 2014, and the personal information, the clinical diagnosis provided at the last hospital visit, the HBV antiviral treatment history, and the insurance type was collected for each patient for analysis. Multivariable logistic regression was used to identify factors that are associated with active medical care- seeking and antiviral treatments. RESULTS: Among the 2422 chronic HBV-infected patients recruited in 2009, 1784 (73.7%) were followed-up to 2014, and 638 (35.8%) had sought medical care in hospitals; among them, 140 (21.9%) received antiviral treatments. The lowest medical care-seeking rate (26%) was in participants over 50-year old. We determined that the frequency of medical care-seeking was higher among those participants living in urban areas (aRR = 1.3, 95% CI:1.0-1.6), those in 0-19-year old (aRR = 1.5, 95% CI:1.1-2.1), 20-39-year old (aRR = 2.2, 95% CI:1.7-3.0) and 40-49-year old (aRR = 1.5, 95% CI:1.1-2.0), and persons with insurance of the type Urban residents' basic medical insurance (URBMI) or Commercial health insurance (CHI) (aRR = 2.5, 95% CI:1.7-3.6) and New Rural Cooperative Medical System (NRCMS) (aRR = 1.9, 95% CI:1.4-2.6). Patients were more likely to receive antiviral treatment if they were 20-39-year old (aRR = 0.4, 95% CI:0.3-0.7), had insurance of the type URBMI or CHI (aRR = 2.6, 95% CI:1.1-6.3) or NRCMS (aRR = 3.0, 95% CI:1.3-6.9) and were treated at prefecture and above-level hospitals (aRR = 2.0, 95% CI:1.4-3.0). Among non-antiviral-treated HBV-infected cases, we found the annual rates for HBsAg sero-clearance, progress to cirrhosis and HCC were 1.0, 0.6 and 0.2%, respectively. CONCLUSION: The rates of medical care-seeking and antiviral treatment were low among community-based chronic HBV-infected persons, thus we recommend improving the insurance policies for HBV-infected persons to increase the antiviral treatment rate, and conducting extensive education to promote HBV-infected patients actively seeking medical care from hospitals.

Cost-effectiveness analysis of hepatitis B vaccine booster in children born to HBsAg-positive mothers in rural China.

OBJECTIVE: In rural areas of China with highly endemic for hepatitis B virus (HBV) infection, protective efficacy was observed in adulthood when a one-dose HBV vaccine booster was administered to high-risk children born to mothers who were positive for hepatitis B surface antigen (HBsAg). The aim of this study was to estimate the cost-effectiveness of an HBV vaccine booster in this specific group of children when given at 10 years of age. METHODS: Two potential strategies were considered: strategy 1 was a one-dose booster given if the child was negative on HBsAg screening; strategy 2 was a one-dose booster given if the child was negative on both HBsAg plus anti-HBs screening. A decision tree combined with a Markov model was developed to simulate the booster intervention process and to simulate the natural history of HBV infection in a cohort of 10-year-old children who were born to HBsAg-positive mothers. The model was calibrated based on multiple selected outcomes. Costs and quality-adjusted life years (QALYs) were measured from a societal perspective. Cost-effectiveness ratios (CERs) of the different strategies were compared in both base-case and one-way sensitivity analyses. RESULTS: Compared to the current practice of 'no screening and no booster', both strategy 1 and strategy 2 were cost-saving, with CERs estimated at US$ -6961 and US$ -6872 per QALY gained, respectively. In the one-way sensitivity analysis for strategy 1, all the CERs were found to be less than US$ -5000 per QALY gained after considering the uncertainty of all the variables, including vaccination protective efficacy, natural history, behavior, and various costs and utility weights. In a 'worst case' scenario (all parameter values simultaneously being at the worst), the CER of strategy 1 increased to US$ 3263 per QALY gained, which was still less than the GDP per capita of China in 2016 (US$ 8126). CONCLUSIONS: A hepatitis B vaccine booster given to children born to HBsAg-positive mothers in rural China would be cost-effective and could be considered in HBV endemic areas.

Epidemiology and clinical management of HIV-HBV coinfected patients in a large AIDS Reference Center in Belgium.

Objectives: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are both worldwide health concerns with similar routes of transmission and no curative treatment to date. Coinfection is associated with increased morbidity and mortality. We aim to provide epidemiological data about HIV-HBV coinfected patients and asses if management of patients following European recommendation (EACS) was achieved in a large AIDS Reference Center in Belgium. Methods: Retrospective review of the HIV database of Saint-Pierre University Hospital in Brussels (Belgium) focusing on HIV-HBV coinfected patients in active follow-up. We classified patients in six serological profiles: (A) patients with active chronic HBV infection (HBsAg positive and HBeAg positive), (B) patients with persistent chronic HBV infection (HBsAg positive and HBeAg negative), (C) patients with isolated core antibody (isolated anti-HBc positive), (D) patients with resolved HBV infection (anti-HBc positive and anti-HBs positive), (E) vaccinated patients (anti-HBs positive), and (F) patients with all above markers negative. Chronic HBV infection (cHBV) was defined by two positive hepatitis B surface antigens (AgHBs positive) with at least 6-month intervals and chronic HBeAg positive group by a positive AgHBe (Ag HBe positive). We reviewed individual files of HIV-HBV chronically coinfected patients to assess if European recommendations in terms of HBV coinfection management were adequately followed in our center. Results: Among 2601 HIV-infected patients in active follow-up, 98 (3.8%) were chronically infected with HBV. Median age of chronically coinfected patients was 46 years with male predominance and heterosexual Africans representing the majority. Among the chronically coinfected patients, 33.7% were HBeAg positive carriers. Mean HBV DNA and ALT/AST were significantly higher in the chronic HBeAg positive (cHBeAg positive) patients compared to chronic HBeAg negative patients (cHBeAg negative). Nearly 95% of the cHBV patients were treated with two anti-HBV drugs (99% for the cHBeAg positive group), with 79% having Tenofovir (TDF) in their antiretroviral treatment history. 8% were screened for hepatitis D virus (HDV) antibodies. Liver fibrosis, upper endoscopy and alpha-foetoprotein were assessed at least once in the last 5 years in 32%, 31% and 32% of cHBV patients respectively. cHBeAg positive patients were not significantly monitored closer except for liver fibrosis assessment in 52% (p < 0.0017). Conclusion: The prevalence of cHBV coinfection in the Saint-Pierre HIV cohort is lower than in neighboring European countries. Hepatic monitoring should be reinforced in our cHBV and cHBeAg positive patients because of higher risk of progression to cirrhosis progression and hepatocellular carcinoma.

Prevention of Perinatal Transmission of Hepatitis B Virus: Assessment Among Wisconsin Maternity Hospitals.

PURPOSE: To evaluate the completeness of identification of pregnant women testing positive for hepatitis B surface antigen (HBsAg) and birth dose hepatitis B vaccine administration, and the extent of appropriate prophylaxis of infants born to women with and without maternal HBsAg status documented in the infant medical record. METHODS: We conducted medical record reviews of 3058 maternal and infant pairs at 58 Wisconsin maternity hospitals that cumulatively delivered 90% of Wisconsin's 2010 birth cohort. RESULTS: A documented HBsAg test result for the current pregnancy was included in 2928 (95.7%) of maternal records, and in 2676 (87.5%) infant records. Four infants (15%) were born to HBsAg-positive women; all 4 infants received appropriate prophylaxis: hepatitis B immunoglobulin (HBIG) and a dose of hepatitis B vaccine within 12 hours of birth. However, among 382 infants without a documented maternal HBsAg test result in the infant medical record, only 135 (35%) received appropriate prophylaxis: a dose of hepatitis B vaccine within 12 hours of birth or a dose of hepatitis B vaccine and HBIG within 12 hours of birth for infants weighing < 2000 g. Among all infants, 81.6% received hepatitis B vaccine prior to hospital discharge. CONCLUSIONS: Hospitals must ensure that infants without a documented maternal HBsAg test result receive appropriate prophylaxis to prevent hepatitis B vaccine infection. All infants, regardless of maternal HBsAg test result, should receive a dose of hepatitis B vaccine before hospital discharge to serve as a "safety net" to prevent infection among infants born to HBsAg-positive women who are not identified prenatally. A written hospital policy for universal hepatitis B vaccine birth dose administration should be developed to reinforce admission orders.

Assessment of Long-Term Outcomes in Hbs Ag-Negative Renal Transplant Recipients Transplanted from Hbs Ag-Positive Donors.

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of renal transplantation from Hbs Ag-positive donors to Hbs Ag-negative recipients. MATERIAL AND METHODS: A total of 78 patients who underwent renal transplantation in our clinic between January 2006 and May 2014 were included in the study. Patients were divided into 2 groups: Group 1: Donor Hbs Ag (+) (n=26, Hbs Ab (-), Hbe Ag (-), Hbe Ab (+), Hbc Ig total (+) and HBV DNA (+), male/female (M/F): 16 (61.5%)/10 (38.5%), and Group 2: Donor Hbs Ag (-) (n=52, M/F: 41 (78.8%)/11 (21.2%). Hbs Ab levels were similar in recipients in both groups. Data were collected retrospectively. Analyses were performed by using SPSS 20.0 software, and patient and graft survival were measured by using Kaplan-Meier survival curve and compared by using the log-rank test. RESULTS: Demographic data were similar in the 2 groups. The rate of acute Hepatitis B infection was significantly higher in Group 1 than in Group 2 [n=3 (11.5%) vs. n=0 (0%), respectively, p=0.012]. Acute hepatitis B attacks were detected in vaccinated patients. Graft survival rates (groups 1 and 2, respectively; at 1st, 3rd, 5th and 8th years: 95% vs. 96%, 95% vs. 94%, 85% vs. 88%, 85% vs. 82%, p=0.970) and patient survival rates (p=0.098), acute rejection rates (p=0.725), delayed graft function, chronic allograft dysfunction, new-onset diabetes after transplantation (NODAT), cytomegalovirus infection, and the need for postoperative dialysis and plasmapheresis were similar between groups. CONCLUSIONS: Our study revealed that the risk of developing acute hepatitis B was higher in patients renally transplanted from Hbs Ag (+) donors, but the other clinical outcomes were similar between groups.

Flow-through, viral co-infection assay for resource-limited settings.

Here we present a new and rapid immunofiltration assay for simultaneous detection of HIV p24 and hepatitis B virus antigens. The assay platform is composed of a 13 mm nitrocellulose filter spotted with capturing bioprobes and inserted in a Swinnex(®) syringe filter holder. Samples and reagents are flown through the nitrocellulose filter by manual pressure on the syringe. A colorimetric detection allows for naked eye results interpretation. The assay provides sensitivity in the picomolar range in just 5 min, even using low volumes of sample in complex matrix. Probe deposition by spotting allows for flexible combinations of different capturing agents and multiple diagnoses; furthermore, the very simple and inexpensive set-up makes the syringe-based immunoassay on paper microarray a suitable diagnostic system for resource-limited settings.

OPTN/SRTR 2012 Annual Data Report: liver.

Liver transplant in the us remains a successful life-saving procedure for patients with irreversible liver disease. In 2012, 6256 adult liver transplants were performed, and more than 65,000 people were living with a transplanted liver. The number of adults who registered on the liver transplant waiting list decreased for the first time since 2002; 10,143 candidates were added, compared with 10,359 in 2011. However, the median waiting time for active wait-listed adult candidates increased, as did the number of candidates removed from the list because they were too sick to undergo transplant. The overall deceased donor transplant rate decreased to 42.3 per 100 patient-years, and varied geographically from 18.9 to 228.0 per 100 patient-years. Graft survival continues to improve, especially for donation after circulatory death livers. The number of new active pediatric candidates added to the waiting list also decreased. Almost 75% of pediatric candidates listed in 2009 underwent transplant within 3 years; the 2012 rate of deceased donor transplants among active pediatric wait-listed candidates was 136 per 100 patient-years. Graft survival for deceased donor pediatric transplants was 92.8% at 30 days. Medicare paid for some or all of the care for more than 30% of liver transplants in 2010.

Management of hepatitis C virus infection in heavy drinkers.

AIM: Optimal management of hepatitis C virus (HCV) infection is controversial in heavy drinkers. We compared the management of HCV infection of heavy drinkers with that of patients without a history of alcohol abuse. METHODS: In a retrospective case-control study, 69 HCV-infected heavy drinkers [daily alcohol consumption at referral above 60 g/day, hereafter 'alcohol group'] were compared with matched HCV-infected patients with low alcohol consumption (<40 g/day, 'control group'). RESULTS: Patients of the 'alcohol group' were younger (42 vs. 45 years, P = 0.05), more often male (69.6 vs. 56.5%, P = 0.11) and had been infected by intravenous drug use (85.5 vs. 45.0%, P < 0.0001). The percentage of patients with a recommendation for treatment according to the French 2002 consensus (bridging fibrosis or genotype 2 or 3) was 52 of 69 (75.4%) in both groups, while the proportion of patients treated was higher in the control group (71.0 vs. 44.9%, P = 0.002). In the 'alcohol group', patients had better access to treatment if they were employed or consumed 170 g/day or less at first referral. Sustained virological response (SVR) was obtained in 10 of 31 patients (32.3%) of the 'alcohol group' vs. 8 of 31 patients (25.8%) of the control group matched for genotype and type of treatment (P = 0.58). CONCLUSION: Heavy drinkers are less often considered for antiviral therapy compared with patients without a history of alcohol abuse. However, once treatment is actually initiated, SVR rates are comparable with those achieved in non-drinkers despite the continuation of alcohol consumption during therapy in some patients.

Electronic messages increase hepatitis B screening in at-risk Asian American patients: a randomized, controlled trial.

BACKGROUND: Hepatitis B (HBV) induced hepatocellular carcinoma is the greatest cancer health disparity affecting Asian Americans, but the prevalence of screening to detect HBV is suboptimal. AIMS: Our aims were to determine the effectiveness of electronic health record (EHR) prompts to increase ordering of HBV tests among primary care providers (PCPs) within an academic health system. METHODS: We conducted a randomized, controlled trial between April and June 2011 among 76 PCPs caring for 175 outpatient adults with Chinese or Vietnamese surnames, with appointments with providers and no history of HBV testing. Providers were randomized to either receive an EHR prompt for HBV testing prior to patients' appointments or usual care. Primary outcomes were the proportion of patients (1) whose physician ordered a HBsAg test and (2) who completed testing. Secondary outcomes were (A) test results and (B) whether the physicians followed-up on the results. RESULTS: HBsAg tests were ordered for 36/88 (40.9 %) of the intervention patients and 1/87 (1.1 %) of the control patients [χ (2) (df = 1) = 41.48, p < 0.001]. Thirty intervention patients (34.1 %) and no control patients completed the HBsAg test [χ (2) (df = 1) = 35.80, p < 0.001]. Four (13.3 %) of the completed tests were HBsAg-positive, 14 (46.7 %) were immune, and 12 (40 %) were unprotected from HBV. Two HBsAg-positive patients were referred to specialists, and 3 unprotected patients were vaccinated for HBV. CONCLUSIONS: EHR-based provider prompts significantly increased HBV testing in Chinese and Vietnamese patients when compared to "usual care." EHR prompts are a promising intervention that could significantly increase screening for HBV.

Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectiveness analysis.

PURPOSE: Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy that can be largely prevented with antiviral prophylaxis. It remains unclear whether HBV screening is cost effective. METHODS: A decision model was developed to compare the clinical outcomes, costs, and cost effectiveness of three HBV screening strategies for patients with lymphoma before R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy: screen all patients for hepatitis B surface antigen (HBsAg; Screen-All), screen patients identified as being at high risk for HBV infection (Screen-HR), and screen no one (Screen-None). Patients testing positive were administered antiviral therapy until 6 months after completion of chemotherapy. Those not screened were initiated on antiviral therapy only if HBV hepatitis occurred. Probabilities of HBV and lymphoma outcomes were derived from systematic literature review. A third-party payer perspective was adopted, costs were expressed in 2011 Canadian dollars, and a 1-year time horizon was used. RESULTS: Screen-All was the dominant strategy. It was least costly at $32,589, compared with $32,598 for Screen-HR and $32,657 for Screen-None. It was also associated with the highest 1-year survival rate at 84.99%, compared with 84.96% for Screen-HR and 84.86% for Screen-None. The analysis was sensitive to the prevalence of HBsAg positivity in the low-risk population, with Screen-HR becoming least costly when this value was ≤ 0.20%. CONCLUSION: In patients receiving R-CHOP for lymphoma, screening all patients for HBV reduces the rate of HBV reactivation (10-fold) and is less costly than screening only high-risk patients or screening no patients.

Models of community-based hepatitis B surface antigen screening programs in the U.S. and their estimated outcomes and costs.

OBJECTIVES: Information on the process and method of service delivery is sparse for hepatitis B surface antigen (HBsAg) testing, and no systematic study has evaluated the relative effectiveness or cost-effectiveness of different HBsAg screening models. To address this need, we compared five specific community-based screening programs. METHODS: We funded five HBsAg screening programs to collect information on their design, costs, and outcomes of participants during a six-month observation period. We categorized programs into four types of models. For each model, we calculated the number screened, the number screened as per Centers for Disease Control and Prevention (CDC) recommendations, and the cost per screening. RESULTS: The models varied by cost per person screened and total number of people screened, but they did not differ meaningfully in the proportion of people screened following CDC recommendations, the proportion of those screened who tested positive, or the proportion of those who newly tested positive. CONCLUSIONS: Integrating screening into outpatient service settings is the most cost-effective method but may not reach all people needing to be screened. Future research should examine cost-effective methods that expand the reach of screening into communities in outpatient settings.

Immunocapture enzyme-linked immunosorbent assay for assessment of in vitro potency of recombinant hepatitis B vaccines.

Quantification of hepatitis B surface antigen (HBsAg) or relative in vitro potency in the final vaccines is a prerequisite for hepatitis B vaccine batch release. The commercial kit for automated analysis (AxSYM) is expensive, and an alternative is required for the estimation of HBsAg in hepatitis B vaccines. Mouse monoclonal antibodies (MAbs) specific for HBsAg were developed and characterized. One of the monoclonal antibodies (HBs06) was used in development of an immunocapture ELISA (IC-ELISA) as an unlabeled capture antibody and biotin-labeled detection antibody. The IC-ELISA was standardized and validated using experimental hepatitis B vaccine batches with various HBsAg concentrations per dose and commercial vaccines. The vaccine was treated with an alkaline solubilizer to desorb the HBsAg from Algel-adjuvanted vaccines before testing, and the sensitivity of the test was 5 ng/ml. A good correlation could be observed between the HBsAg estimates derived by both formats, except for the higher HBsAg concentration range, where the IC-ELISA format could estimate closer to the actual values than AxSYM. There was a significant correlation between the estimated relative potencies of the two methods. There was lack of correlation between the in vivo potency and the relative in vitro potency. However, the estimates of IC-ELISA were comparable to the in vivo values when compared with the estimates of AxSYM. The IC-ELISA can therefore be considered to be a reliable test for deriving in vitro relative potency and antigen concentration in vaccine batches for batch control and release.

Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion-transmitted hepatitis B virus infection in Switzerland, a low-endemic region.

BACKGROUND: The risk of transfusion-transmitted hepatitis B virus (HBV) in Switzerland by testing blood donors for hepatitis B surface antigen (HBsAg) alone has been historically estimated at 1:160,000 transfusions. The Swiss health authorities decided not to introduce mandatory antibody to hepatitis B core antigen (anti-HBc) testing but to evaluate the investigation of HBV nucleic acid testing (NAT). STUDY DESIGN AND METHODS: Between June 2007 and February 2009, a total of 306,000 donations were screened routinely for HBsAg and HBV DNA by triplex individual-donation (ID)-NAT (Ultrio assay on Tigris system, Gen-Probe/Novartis Diagnostics). ID-NAT repeatedly reactive donors were further characterized for HBV serologic markers and viral load by quantitative polymerase chain reaction. The relative sensitivity of screening for HBsAg, anti-HBc, and HBV DNA was assessed. The residual HBV transmission risk of NAT with or without anti-HBc and HBsAg was retrospectively estimated in a mathematical model. RESULTS: From the 306,000 blood donations, 31 were repeatedly Ultrio test reactive and confirmed HBV infected, of which 24 (77%) and 27 (87%) were HBsAg and anti-HBc positive, respectively. Seven HBV-NAT yields were identified (1:44,000), two pre-HBsAg window period (WP) donations (1:153,000) and five occult HBV infections (1:61,000). Introduction of ID-NAT reduced the risk of HBV WP transmission in repeat donors from 1:95,000 to 1:296,000. CONCLUSIONS: Triplex NAT screening reduced the HBV WP transmission risk approximately threefold. NAT alone was more efficacious than the combined use of HBsAg and anti-HBc. The data from this study led to the decision to introduce sensitive HBV-NAT screening in Switzerland. Our findings may be useful in designing more efficient and cost-effective HBV screening strategies in low-prevalence countries.

Impact of immunosuppressive medication on the risk of renal allograft failure due to recurrent glomerulonephritis.

Recurrent glomerulonephritis is a major problem in kidney transplantation but the role of immunosuppression in preventing this complication is not known. We used data from the United States Renal Data System to examine the effect of immunosuppressive medication on allograft failure due to recurrent glomerulonephritis for 41,272 patients undergoing kidney transplantation from 1990 to 2003. Ten-year incidence of graft loss due to recurrent glomerulonephritis was 2.6% (95% confidence interval [CI]: 2.3-2.8%). After adjusting for important covariates, the use of cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, sirolimus or prednisone was not associated with graft failure due to recurrent glomerulonephritis. There was no difference between cyclosporine and tacrolimus or between azathioprine and mycophenolate mofetil in the risk of graft failure due to recurrent glomerulonephritis. However, any change in immunosuppression during follow-up was independently associated with graft loss due to recurrence (adjusted hazard ratio 1.30, 95% CI: 1.06-1.58, p = 0.01). In patients with a pretransplant diagnosis of glomerulonephritis, the risk of graft loss due to recurrence was not associated with any specific immunosuppressive medication. The selection of immunosuppression for kidney transplant recipients should not be made with the goal of reducing graft failure due to recurrent glomerulonephritis.

Cost-effectiveness of peginterferon alpha-2a compared to lamivudine treatment in patients with hepatitis B e antigen positive chronic hepatitis B in Taiwan.

BACKGROUND: Peginterferon alpha-2a (40KD), a new treatment option for patients with chronic hepatitis B (CHB), offers improved efficacy with a defined treatment duration compared with lamivudine, but at a higher cost. We undertook an economic evaluation of peginterferon alpha-2a from the perspective of the Taiwan Bureau of National Health Insurance to assess the clinical outcomes and costs of 48 weeks of peginterferon alpha-2a for the treatment of patients with hepatitis B e antigen (HBeAg)-positive CHB, compared to lamivudine treatment for 48 weeks. METHODS: We performed a cost-effectiveness analysis using a state-transition Markov model simulating the natural history of HBeAg-positive CHB. Efficacy data were obtained from a randomized clinical trial of 820 patients (87% were Asian) comparing peginterferon alpha-2a to lamivudine. We modeled a hypothetical cohort of 32-year-old patients with HBeAg-positive CHB. Life expectancy, quality-adjusted life expectancy, lifetime costs ($NTD) and incremental cost-effectiveness ratios (ICER) were estimated. One-way sensitivity analyses were performed on all parameters in the model to evaluate uncertainty. RESULTS: Treatment with peginterferon alpha-2a compared to lamivudine resulted in higher total costs, but longer quality-adjusted life expectancy, yielding an ICER of $NTD 381 000 ($US 12,000) per quality-adjusted life year (QALY) gained. Although there is uncertainty associated with the prognosis of HBeAg-positive CHB, the ICER did not exceed $NTD 485,000 ($US 15,000) per QALY gained despite variation in the parameters used in the analysis. CONCLUSIONS: Our analysis suggests that 48-week treatment with peginterferon alpha-2a compared to 48-week treatment with lamivudine in HBeAg-positive patients offers life expectancy and quality of life benefits at a favorable cost-effectiveness ratio.

Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection.

Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects. Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV-specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

Therapy of hepatitis B -- viral suppression or eradication?

The practicing clinician is currently faced with a number of treatment options for chronic hepatitis B. Beginning in 1998 with the licensing of lamivudine and subsequently adefovir, the treatment paradigm shifted from 4 to 6 months of conventional alfa interferon to a year of nucleoside analog therapy. However, prolonged treatment with nucleoside analogs is often needed to optimize virological response. Recently, a 48-week regimen of pegylated interferon for hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B has been shown to be effective, and long-term nucleoside analog therapy has been demonstrated to maintain viral suppression. These findings have added to the complexity of decision-making and have raised questions about whether a finite course of pegylated interferon or nucleoside analog therapy, with possible long-term maintenance, is better as first-line therapy. Each of these fundamentally different approaches has advantages and limitations, and both have a place in the therapeutic armamentarium against chronic hepatitis B. Long-term therapy with nucleoside analogs, however, raises a number of practical concerns that have not been fully addressed as of yet. I will present evidence in support of the recommendation that antiviral therapy should ideally be directed toward achieving the highest rate of viral clearance with the shortest interval of treatment.