Disease burden of chronic hepatitis C among immigrants in Canada

Immigrants with chronic hepatitis C (CHC) in Canada have doubled risk of hepatocellular carcinoma. To measure the burden of CHC among immigrants in Canada. A decision analytic model was developed to compare immigrants with CHC and age‐matched immigrants without CHC for survival years, quality‐adjusted life‐years (QALYs) and medical costs per life year. Hepatitis C epidemiology among immigrants was based on hepatitis C prevalence in their home countries. A cohort of immigrant patients was retrospectively followed up to estimate fibrosis stage distribution, treatment patterns and prognosis of compensated cirrhosis. Other model variables were based on published sources. Base case analysis, one‐way sensitivity analysis and probabilistic sensitivity analysis were performed to measure the burden of CHC and assess the impact of uncertainty associated with model variables on the burden of CHC. CHC could reduce survival by 9.6 years [95% credible interval (CI): 8.0–10.9 years], reduce QALYs by 9.5 years (95% CI: 6.0–13.8 years) and increase medical costs per life year by $1950 (95% CI: $1518 to $2486, 2006 Canadian dollars). Because nearly half of immigrants with CHC were not diagnosed until the development of cirrhosis, the burden of CHC was highly sensitive to the risks of liver‐related complications and mortality but insensitive to pegylated interferon plus ribavirin. The burden of CHC among immigrants in Canada is substantial mainly due to liver‐related complications and mortality. The delay in diagnosis was another important contributor to the burden of CHC among immigrants.     

HBsAg疫苗冲击树突状细胞联合乙肝免疫球蛋白对慢性乙型肝炎及HBV携带者的疗效

目的:观察HBsAg疫苗冲击的树突状细胞与乙肝免疫球蛋白联合应用对慢性乙型肝炎的疗效．方法:慢乙肝患者66例每月1次注射HBsAg疫苗(106／次)冲击的树突状细胞,乙肝免疫球蛋白200 U／次,6次为1疗程,共2疗程,治疗结束后检查肝功能,HBV DNA定量及乙肝标志．结果:HBeAg阳性慢乙肝27例治疗后有7例显示完全应答,14例显示部分应答．HBeAg阴性的慢乙肝15例中有4例出现完全应答,8例显示部分应答．慢性HBV携带者13例中5例显示完全应答,2例表现为部分应答．11例非活动性 HBsAg携带者中2例出现完全应答．结论:HBsAg疫苗冲击的树突状细胞与乙肝免疫球蛋白联合可试用于慢乙肝的治疗．     

Long-term outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B

Purpose

The aim of this study was to elucidate the long-term outcome after hepatitis B surface antigen (HBsAg) seroclearance in a large number of Japanese patients.

Methods

We studied the biochemical, virologic, histologic, and prolonged prognoses of 231 Japanese patients with HBsAg seroclearance (median follow-up, 6.5 years). Serum alanine aminotransferase, serum hepatitis B virus (HBV) markers, liver histology, and clinical aspects were monitored. HBV-DNA levels were measured with the qualitative polymerase chain reaction assay. The mean age of patients with HBsAg seroclearance was 52 years.

Results

After HBsAg seroclearance, 203 patients (87.9%) had normal alanine aminotransferase levels 1 year after HBsAg seroclearance. HBV-DNA showed positive results in 4 patients (1.7%) 1 year after HBsAg seroclearance. Thirteen patients were examined for histologic changes of the liver after HBsAg seroclearance. All patients showed marked improvement of necroinflammation of the liver, but only 2 of the 13 patients showed no liver fibrosis. Liver cirrhosis and hepatocellular carcinoma did not develop in any of the 164 patients without evidence of liver cirrhosis at the time of HBsAg seroclearance. Hepatocellular carcinoma developed in 2 of the 67 patients with liver cirrhosis at the time of HBsAg seroclearance. During the observation period, 15 patients died. However, the cause of death of these 15 patients was not related to liver disease, such as hepatocellular carcinoma, decompensated liver cirrhosis, and rupture of esophageal varices.

Conclusion

Our results suggest that HBsAg seroclearance confers favorable long-term outcomes in patients without hepatocellular carcinoma or decompensated liver cirrhosis at the time of HBsAg seroclearance     

Characterizing hepatitis B stigma in Chinese immigrants

Health-related stigma is a cause of stress, alienation and discrimination that can serve as a barrier to prevention and care for infectious diseases such as HIV. Hepatitis B virus (HBV)-related stigma is common in Asian immigrants, but has not been formally evaluated. The aim of this study was to develop and validate the first HBV stigma instrument and to begin to evaluate HBV stigma in Chinese immigrants. The HBV stigma instrument was developed based on constructs from validated HIV stigma scales and organized into five domains. A written survey was compiled to include demographic data, HBV knowledge questions and stigma items. The survey was pilot tested in English and Chinese and then finalized. Data were obtained from 201 patients seen in an urban Chinatown Internal Medicine practice. The stigma items showed a high degree of reliability when assessed in aggregate (α = 0.85) as well as within individual domains. Stigma was greatest in the Fear of Contagion domain. Knowledge questions showed a corresponding deficit in understanding of modes of HBV transmission. An inverse relationship between stigma scores and familiarity with HBV provided evidence of construct validity. In multivariable analysis, having a family member with HBV and higher HBV knowledge subset scores were associated with lower degrees of stigma. In conclusion, the hepatitis B stigma instrument showed reliability and construct validity. The relationship identified between familiarity and knowledge regarding HBV with lower stigma scores provides the basis for the development of interventions to reduce HBV stigma.     

Dynamics of hepatitis B e antigen index ratio correlate with treatment response in chronic hepatitis B patients.

BACKGROUND/AIM: Hepatitis B e antigen (HBeAg) seroconversion is an important event in the natural history of chronic hepatitis B virus (HBV) infection. Whether early dynamics of HBeAg index ratio could predict therapeutic endpoint of HBeAg seroconversion in patients receiving lamivudine remains unclear and thus deserves investigation. METHODS: A total of 52 patients (males/females, 40/12; mean age, 31.1+/-7.5 years) with HBeAg-positive chronic hepatitis B and serum alanine aminotransferase (ALT) level > or = 5 x upper limit of normal were enrolled. They received daily 100 mg lamivudine for at least 1 year. Pretreatment HBeAg index ratio and the dynamics during treatment [early serologic response (ESR) and serologic breakthrough (SB)] between responders and non-responders were compared. RESULTS: Of these 52 patients, mean pretreatment serum ALT level was 580 IU/l and baseline HBeAg index ratio (S/N) was 37.9. The overall 1-year on-treatment combined response rate was 50%. By using linear regression analysis, HBeAg index ratio was positively correlated with serum HBV DNA level (Pearson's correlation coefficient: 0.62, P<0.0001). By using multivariate logistic regression analysis, ESR could predict the success of treatment response (P=0.0302), and SB had a 90% positive predictive value of treatment failure. CONCLUSIONS: HBeAg index ratio is closely correlated with serum HBV DNA level, and the dynamics of HBeAg index ratio may predict 1-year on-treatment combined response to lamivudine in HBeAg-positive chronic hepatitis B patients.     

对现行慢性乙型肝炎治疗的评价

最近来自澳大利亚、希腊、意大利、西班牙、中国台湾、英国和美国等7个国家和地区的14名专家对现行慢性乙型肝炎治疗中的16个问题进行了讨论。1名荷兰专家提供了基础资料，但未参加会议。每名专家在治疗慢性乙型肝炎方面均有丰富的经验和临床背景，其主要研究领域包括免疫病理学、分子病毒学和抗病毒治疗等。会议分3个阶段进行：第一阶段，先由3个小组讨论会的主席向与会代表作专题报告和介绍研讨会的讨论框架；第二阶段，3个小组讨论会同时举行，由1名主席和4名专家参加，专家们在提供资料时报告方法学、病例数及预后，确定证据级别等；第三阶段，召开全体大会，所有14名专家一起审核小组讨论会的纪要，并对每一个问题逐一进行了讨论，然后无记名投票。     

Hepatic steatosis in chronic hepatitis B develops due to host metabolic factors: A comparative approach with genotype 1 chronic hepatitis C

BACKGROUND/AIMS: Hepatic steatosis has not been adequately studied in chronic hepatitis B, while it is considered to be a cardinal feature in chronic hepatitis C and to be mainly metabolically induced in patients infected with genotype 1. We investigated the prevalence of and the parameters associated with steatosis in HBeAg-negative chronic hepatitis B. METHODS: We studied 213 patients with HBeAg-negative chronic hepatitis B and compared them with 163 patients with genotype-1 chronic hepatitis C. Steatosis was semi-quantitatively graded. RESULTS: Steatosis was significantly less frequent in chronic hepatitis B than chronic hepatitis C (60% versus 72%, P=0.016), but there was no difference in the prevalence of moderate/severe steatosis. In chronic hepatitis B, steatosis was associated only with higher body mass index (P=0.002), while moderate/severe steatosis was associated only with higher body mass index (P=0.043) and diabetes (P=0.031). Steatosis was relatively less frequent in chronic hepatitis B than chronic hepatitis C non-diabetic, normal-weight patients (45.6% versus 62.5%, P=0.063), but it did not differ in diabetic and/or overweight/obese patients with chronic hepatitis B or chronic hepatitis C. CONCLUSIONS: Hepatic steatosis in HBeAg-negative chronic hepatitis B (a) is less frequent than in genotype-1 chronic hepatitis C, (b) is mainly associated with presence of host metabolic factors, such as high body mass index and diabetes and (c) does not seem to be associated with the severity of liver histological lesions.     

慢性乙型重型肝炎患者血清乙型肝炎病毒基因型分析

目的探讨慢性重型肝炎患者血清乙型肝炎病毒基因型特点及其与病毒复制水平的关系。方法选择慢性肝炎、肝硬化和重型肝炎各40例，用PE-R微板核酸-ELISA杂交技术进行HBVDNA基因分型，并同时进行HBVDNA定量检测。结果慢性重型肝炎组与肝硬化组D基因型和与D型相关的混合型所占百分率分别为50．0％和25．0％，两者有显著差异(X^2=4．3，P=0、0377)；56．5％的D基因型是慢性重型肝炎，而C基因型患者只有28．3％，差异显著(X^2=4．34，P=0、037)。结论乙型肝炎病毒基因型是否与慢性重型肝炎的发病有关，需进一步研究。     

hepatitis B virus burden in developing countries

Hepatitis B virus(HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.     

Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients

BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance.     

慢性乙型肝炎的免疫治疗研究进展*

临床上应用的抗乙型肝炎病毒（HBV）药物主要有干扰素和核苷（酸）类似物两类,在大多数慢性HBV感染者即使经过长期的抗病毒治疗仍不能彻底清除病毒。感染的控制和病毒的清除有赖于机体的免疫系统。感染慢性化与机体特异性免疫功能,尤其是细胞免疫功能低下密切相关。通过增强抗HBV感染的免疫治疗是被人们寄予厚望的一种治疗策略。目前研究的热点主要包括免疫激动剂、特异性细胞毒性T淋巴细胞（CTL）负调节分子阻断剂、特异性CTL调节分子激动剂或佐剂、治疗性疫苗、特异性T细胞受体（TCR）转基因技术、携带嵌合抗原受体的T细胞和多糖类物质等,本文对近年来这方面的研究进展进行了综述。     

Influence of occult hepatitis B virus infection in chronic hepatitis C outcomes

Persistence of hepatitis B virus-DNA in the sera,peripheral blood mononuclear cells or in the liver of hepatitis B surface antigen(HBsAg) -negative patients with or without serological markers of previous exposure(antibodies to HBsAg and/or to HB-core antigen) defines the entity called occult hepatitis B infection(OBI).Co-infection with hepatitis B and hepatitis C viruses is frequent in highly endemic areas.While this co-infection increases the risk of liver disease progression,development of cirrhosis and ...     

膦甲酸钠治疗慢性乙型重型肝炎临床疗效观察

目的　探讨膦甲酸钠 (PFA)治疗慢性重型肝炎 (CSH)的临床效果。方法　选择CSH患者 42例 ,随机分为治疗组 ( 2 1例 )及对照组 ( 2 1例 ) ,两组均给予综合基础保肝、支持疗法及防治有关并发症等治疗 ,治疗组另加用PFA注射液 2 .4g静脉滴注 ,每日 2次 ,应用 4周～ 8周。结果　治疗组无论从症状及肝功能恢复、HbeAg阴转、HBVDNA水平下降程度及治愈率等方面均明显优于对照组 (P <0 .0 1)。结论　PFA对于重型肝炎治疗 ,具有改善症状 ,抑制HBV复制 ,促进肝功能恢复 ,提高治愈率等优点     

Viral and host causes of fatty liver in chronic hepatitis B

AIM: To investigate the viral and host causes of fatty liver in chronic hepatitis B patients and the role of fat deposits in liver damage. METHODS: A total of 164 patients (113 males and 51 females, average age 35±11.3 years, and range 10-62 years) with previously untreated chronic hepatitis B were included in the study. The patients were divided into two groups depending on the result of liver biopsy: group without steatosis (100 patients with <5% hepatosteatosis) and group with steatosis (64 patients with >5% hepatosteatosis). The groups were compared in terms of gender, body mass index (BMI), liver enzymes (ALT, AST, ALP, GGT), cholesterol, triglyceride, HBeAg, viral load, and histological findings. In the group with steatosis, the patients were subdivided depending on the degree of steatosis into mild group (45 patients with 5-24% steatosis), and severe group (19 patients with >25% steatosis). RESULTS: In the group of chronic hepatitis B with steatosis, the mean age, BMI, cholesterol, and triglyceride levels were significantly higher than those in the group without steatosis (P<0.05). Steatosis was found in 53 (46.9%) of male patients and 11 (22%) of female patients (P<0.05). No significant difference was found in the positivity of ALT, AST, ALP, GGT, HBeAg, viral load, histological activity index (HAI) and stage between the two groups (P>0.05). In the group with severe steatosis, the BMI was significantly higher than that in the group with mild steatosis (P<0.05). No significant difference was found in the other parameters between the groups (P>0.05). CONCLUSION: Steatosis in chronic hepatitis B appears to be a result of metabolic factors of the host rather than the effect of viruses. Steatosis is unrelated to the HAI and degree of fibrosis, which are considered as the histological indicators of liver damage.     

Distribution of hepatitis B virus genotypes in patients with chronic hepatitis B in Turkey

AIM: Hepatitis B virus (HBV) strains isolated worldwide has been classified into eight genomic groups deduced from genome comparisons and designated as genotypes A to H. We aimed to investigate prevalence of HBV genotypes and subtypes in Turkey. METHODS: A total of 88 chronic hepatitis B (CHB) patients from 15 hospitals throughout the country were included. Patients who were HBsAg positive in serum at least for 6 mo, who had HBV-DNA in serum and elevation of ALT levels more than two times upper limit of normal, and who had percutaneous liver biopsy within 6 mo were included. Genotyping of HBV was done by restriction fragment length polymorphism (RFLP). The patients received subcutaneous 9 MU interferon-α 2a thrice a week for a period of 6 mo. RESULTS: Genotype D was detected in 78 of 88 (88.7%) patients, however, genotyping failed in two patients (2.3%), while no product was obtained in eight (9.0%) patients. Regarding subtypes, D2 was more prevalent (67 patients between 78% and 85.9%) followed by subtype D2+deletion (seven patients of 78 or 8.9%), subtype D1(three patients of 78% or 3.9%) and subtype D3 (one patient of 78% or 1.3%). Thirty-three patients (37.5%) were HBeAg positive compared to 55 (62.5%) anti-HBe positive patients. The endpoint for the viral response of HBeAg positive patients was 27.2%, while it was found 52.7% in HBeAg negative patients (P<0.05). Long-term persistent viral response was 29.5% for all patients. CONCLUSION: This multi-center study indicates that the predominant genotype with CHB patients in Turkey like in other Mediterranean countries is genotype D.     

Lamivudine therapy for children with chronic hepatitis B

AIM: To assess the effectiveness and side-effects of lamivudine therapy for children with chronic hepatitis B (CHB) who fail to respond to or have contraindications to interferon-α(IFN-α) therapy. METHODS: Fifty-nine children with CHB were treated with 100 mg lamivudine tablets given orally once daily for 12 mo. Alanine aminotransferase (ALT) activity was evaluated monthly during the therapy and every 3 months after its discontinuation. HBe antigen, anti-HBe antibodies, HBV DNA level in serum were evaluated at baseline and every six months during and after the lamivudine therapy. Sustained viral response (SVR) to lamivudine therapy was defined as permanent (not shorter than 6 mo after the end of the therapy), namely ALT activity normalization, seroconversion of HBeAg to anti-HBe antibodies, and undetectable viral HBV-DNA in serum (lower than 200 copies per mL). The analysis of the side-effects of the lamivudine treatment was based upon interviews with the patients and their parents using a questionnaire concerning subjective and objective symptoms, clinical examinations, and laboratory tests performed during clinical visits monthly during the therapy, and every 3 mo after the therapy. RESULTS: ALT normalisation occurred in 47 (79.7%) patients between the first and 11th mo of treatment (mean 4.4±2.95 mo, median 4.0 mo), and in 18 (30.5%) of them after 2 mo of the therapy. There was no correlation between the time of ALT normalization and the children's age, the age of HBV infection, the duration of HBV infection, inflammation activity score (grading), staging, ALT activity before treatment, serum HBV DNA level, and lamivudnie dose per kg of body weight. HBeAg/anti HBe seroconversion was achieved in 27.1% of cases. The higher rate of seroconversion was connected with lower serum HBV DNA level and longer duration of HBV infection. There was no connection between HBeAg/ anti HBeAb seroconversion and the children's age, age of HBV infection, grading, staging, ALT activity before treatment, and lamivudnie dose per kg of body weight. No complaints or clinical symptoms were observed during lamivudine therapy. Impairment of renal function or myelotoxic effect was noted in none of the patients. CONCLUSION: One year lamivudine therapy for children with chronic hepatitis B is effective and well tolerated. Seroconversion of HBeAg/HBeAb and SVR are connected with lower pre-treatment serum HBV DNA level.     

慢性乙型肝炎抗病毒治疗新进展

慢性乙型肝炎是由乙型肝炎病毒感染引起的、以肝脏炎症和坏死病变为主的一种全身性感染病。目前,治疗乙型肝炎的抗病毒药物主要包括干扰素和核苷酸类似物两类。现在正在探索开发新药及优化联合、免疫疗法或凋亡疗法（促进感染细胞凋亡）来彻底根除慢性HBV 感染。     

拉米夫定治疗对慢性乙型肝炎患者血清IL-18的影响

目的观察拉米夫定对慢性乙型肝炎患者血清IL-18的影响。方法将32例慢性乙型肝炎患者随机分为对照组(15例)和治疗组(17例)。两组治疗前和疗程结束后,采用双抗体夹心ELISA法检测不同时期血清IL-18水平。结果治疗组血清IL-18水平在治疗后1月、6月较对照组明显下降,与对照组相比有统计学差异(P<0.01~0.05)。结论拉米夫定治疗后IL-18水平下降,提示拉米夫定可调节免疫功能,减轻肝脏炎症细胞浸润。     

华东某农村地区戊型肝炎负担的调查

目的分析戊型肝炎的疾病负担,为卫生决策提供科学依据。方法采用问卷调查方式,对江苏省东台市农村人群戊型肝炎主动监测网络收集的病例进行调查,获得戊型肝炎的疾病负担情况。结果戊型肝炎的总经济负担为2 910 362.60元,人均经济负担为11 641.45元,是东台市农村居民人均纯收入的1.26倍;失能调整生命年为28.94人年,患者的负担强度为115.78人年/千人。结论戊型肝炎的疾病负担较重,应加大防制力度。