Long-term efficacy of hepatitis B vaccination in healthcare workers of Oil Company Hospital, Tehran, Iran (1989-2005)

OBJECTIVE: This study was conducted to evaluate the 16-year efficacy of hepatitis B virus (HBV) vaccine in healthcare workers of Oil Company Hospital, Tehran, Iran. METHODS: Two hundred healthcare workers were enrolled in the study in 1989. All HBV markers were tested and those with positive HBV markers, positive antihepatitis C virus or anti-HIV were excluded from the study. The remaining participants received three doses of HBV vaccine and again all of our participants were reevaluated in 2005. Hepatitis B surface antigen (HBsAg), antihepatitis B surface antibody (anti-HBsAb), and antihepatitis B core antibody (anti-HBcAb) were checked in all participants and those with anti-HBcAb above 10 IU/l were excluded from the final evaluation. RESULTS: No participant was positive for HBsAg in either 1989 or 2005. Protective levels of anti-HBsAb were absent in all participants in 1989, but present in 67 (80.7%) participants in 2005 (P<0.001). Anti-HBsAb titer after vaccination was significantly higher in female participants than in male participants (P=0.01). Mean anti-HBsAb titer was 640+/-411.7 IU/l (range: 2-1000 IU/l) and the lowest protective titer was 12 IU/l. CONCLUSION: According to our results, 80.7% of our participants had a protective titer of anti-HBsAb 16 years after vaccination. Although all anti-HBc positive participants were free of clinical hepatitis and were negative for HBsAg, hepatitis B vaccination was proved to be highly effective in preventing clinically significant infection and chronic carrier status up to 16 years after the primary vaccination. Hence, HBV revaccination may not be mandatory in healthcare workers, according to their sufficient long-term level of anti-HBsAb.     

Prevalence of occult hepatitis B & C in HIV patients infected through sexual transmission.

BACKGROUND: Prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) markers including active and occult infection has not been described in diverse cohorts among HIV-infected patients in India. Earlier studies have explained the role of HBV/HCV co-infection in cohorts of injection drug users (IDUs) but the sexual co-transmission of HBV/ HCV is not completely understood. OBJECTIVE: The objective of this study was to assess the prevalence of occult HBV & HCV infection in HIV positive sexually acquired transmission risk group. MATERIALS AND METHODS: 58 sexually acquired HIV positive patients were taken up for the study of occult HBV/HCV co-infection. Data on demographics, sexual behaviour, sexually transmitted diseases (STD), medical history, laboratory tests viz., serum ALT and CD4 count were recorded. HBV serology included HBsAg, anti HBs, IgG anti HBc and HBV DNA (PCR). HCV serology included anti HCV & HCV RNA (RT-PCR). RESULTS: Occult HBV infection (HBV DNA) was observed in 12.2% (7/58 with HBsAg -ve and IgG anti HBc +ve subjects) while an overall prevalence of HBV DNA was 13.7% (12% occult & 1.7% in HBsAg+ve patients). Out of 58 HIV positive patients 29.3% demonstrated reactivity for any marker of past or current HBV infection. (HBsAg 1.7%, anti HBs 10.3% anti HBc IgG 17.2%). 4/58 (6.8%) revealed anti HCV positivity along with HCV RNA positivity by RT-PCR while 6/58 (10.3%) individuals revealed an occult HCV infection (anti HCV negative). The overall HCV RNA prevalence was 17.2%. 2 out of 58 (3.4%) individuals were positive for occult infection of both HBV DNA & HCV RNA (Triple infection HIV/HBV/ HCV). The HBV/HCV co-infected group (n = 18) showed a significantly high ALT (114.3 + 12.3 U/I) & low CD4 count (202.5 + 33.7 cells/mm3). The percent prevalence of HBV/ HCV co-infection was higher in the illiterate group, in men less than 30 years of age, and in those who were married and exhibited polygamous activity. CONCLUSIONS: The study demonstrated that in HIV infected patients testing only serological viral markers like HBsAg, antiHBcIgG & anti HCV, fails to identify the true prevalence of co-infection with HBV & HCV. Qualitative PCR for HBV DNA & HCV RNA detects co-infection in patients who are negative for serological markers. Also, in subjects who had only a sexual risk factor for parenterally transmitted infections, HIV may enhance the sexual transmission of HBV and HCV.     

Impact of occult HBV infection in HIV/HCV co-infected patients: HBV-DNA detection in liver specimens and in serum samples

Prevalence and impact of occult HBV infection in HIV positive patients is controversial. The aims of this study were to determine the prevalence of occult HBV infection and its impact on histological and virological parameters. 52 HIV/HCV (but HBsAg-negative) co-infected patients, 29 HBsAg and anti-HCV negative chronic hepatitis, and 20 HBsAg positive chronic hepatitis controls were studied. DNA was extracted from frozen biopsies and amplified with primers for S, C and X regions, and for (ccc) HBV-DNA. Sera were tested for HBV-DNA with two quantitative assays (Cobas Amplicor HBV Monitor, and the real-time COBAS (r) Taqman HBV Test, Roche Diagnostics, UK). Occult HBV infection was detected in 7 (13.4%) liver biopsies of the study group, and in none case of the non viral chronic hepatitis group (p=0.04). All serum samples were HBV-DNA negative with Cobas Amplicor HBV monitor assay, while 3 cases were found positive with real time PCR. Statistical analysis didn't show any impact of occult HBV infection on liver histology, CD4+ cells count, HIV and HCV load, and ALT levels. Occult B infection is relatively frequent in HIV/HCV co-infected patients, and is underestimated by common HBV-DNA serological assays. However, it doesn't seem to exert a relevant impact.     

人类免疫缺陷病毒感染者合并隐匿性乙型肝炎病毒感染的现状调查

目的 调查分析上海地区HIV感染者中隐匿性HBV感染的流行现状.方法 对上海市公共卫生临床中心就诊的HIV感染者在尚未接受抗病毒治疗前采集血标本,检测HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc,抗-HCV,CD4+T细胞计数,使用巢式PCR法检测HBV S区.结果 105例(男92例,女13例)HBsAg阴性的HIV感染者中32例(男27例,女5例)HBV DNA阳性;16～30岁年龄组22例,其中5例HBV DNA阳性,31～49岁年龄组44例,其中15例HBV DNA阳性,50～75岁年龄组39例,其中12例HBV DNA阳性;32例中有27例至少一项HBV血清学标志物阳性,5例均阴性.47例合并HCV感染者中有14例HBV DNA阳性,阳性率29.8%;58例未合并HCV感染的HIV感染者中18例HBV DNA阳性,阳性率为31.0%.CD4+T细胞计数平均值145.1个/μ(4～623个/μ1),75例CD4+T细胞<200个/μ1的患者中有26例HBV DNA阳性,约占34.7%,30例CD4+T细胞>200/μ1患者中有6例HBV DNA阳性,阳性率为20.0%.以上各项之间两两相比差异均无统计学意义.结论 HIV感染者中存在隐匿性HBV感染,且与HIV感染者性别、年龄、HBV标志物、是否合并HCV感染及CD4+T细胞计数无明显相关.     

经血液(非静脉吸毒者)和性途径传播的HIV感染者合并HBV和HCV感染的现状

目的 探讨我国经血液(非静脉吸毒者)和性途径传播的HIV感染者合并乙型肝炎和丙型肝炎的状况.方法 回顾性分析2005年1至9月在全国13个研究中心就诊的362例HIV/AIDS患者(静脉吸毒者除外),应用酶联免疫试剂盒分别测定其HBsAg、抗-HBs,HBeAg、抗-Hbe、抗-HBc和抗-HCV.采用t检验和X2检验分别对计量和计数结果进行统计学分析.结果 315例检测血HBV和HCV的患者中,HBsAg阳性14例,占4.4%;抗-HCV阳性158例,占50.2%,抗-HCV阴性157例,占49.8%;HIV、HBV、HCV共感染2例,占0.6%.抗-HCV阳性组中经血液和性传播的比例分别占92%和4%,以血液传播为主;抗-HCV阴性组中经血液和性传播的比例分别占11%和66%,以性传播为主.抗-HCV阳性组的HIV确诊时间、CD4+T淋巴细胞绝对计数、ALT和AST均高于抗-HCV阴性组.两组患者的HBV标志物表达也存在差异,其中抗-HCV阳性组中HBsAg阳性2例,占1.3%,抗-HCV阴性组中HBsAg阳性12例,占7.6%,两组比较差异有统计学意义(X2=7.542,P<0.01).10例HBsAg阳性者进行HBV DNA检测,其中4例阳性,抗-HCV均为阴性.57例抗-HCV阳性患者进行HCV RNA检测,阳性者占63.2%.结论 我国输血和性传播途径的HIV感染合并HBV或HCV感染,以合并HCV感染为主,并多见于经输血感染者.合并HCV感染可加重HIV患者的肝脏损伤,同时也可能存在干扰HBV复制的情况.     

Assessment of chronic hepatitis B: the importance of hepatitis B virus DNA testing

Background: Chronic hepatitis B (CHB) has an estimated prevalence of 90 000 to 160 000 in Australia. Cirrhosis and hepatocellular carcinoma are important complications of CHB and appropriate evaluation of hepatitis B surface antigen (HBsAg)‐positive individuals is vital to identify treatment candidates. Methods: A review of the database of a tertiary hospital was performed and 348 HBsAg‐positive individuals with baseline demographic, virological, serological and biochemical variables were identified and evaluated cross‐sectionally. A small subgroup of hepatitis B e antigen (HBeAg)‐negative patients with normal alanine aminotransferase (ALT) at baseline were identified and followed longitudinally. Results: 175/348 (50%) of patients were in the HBeAg‐negative, chronic hepatitis phase of disease, 22% in the HBeAg‐positive immune clearance and 6% in the immune tolerant phases. HBeAg‐negative patients were older and more likely to be male than HBeAg‐positive patients. The correlation between hepatitis B virus (HBV) DNA and ALT levels was examined. ALT and HBV DNA levels showed no correlation in HBeAg‐positive CHB and only a weak correlation in HBeAg‐negative patients. Furthermore, 35% of HBeAg‐negative patients with detectable HBV DNA had a normal ALT. Conversely 38% of HBeAg‐negative patients with no detectable HBV DNA had an elevated ALT. A persistently normal ALT over 24 months was seen in five of nine HBeAg‐negative patients with normal initial ALT and detectable HBV DNA. Conclusion: Appropriate evaluation of HBeAg‐negative CHB must include HBV DNA because the ALT is not a reliable guide to underlying viral replication.     

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

AIM: To study the intrahepatic expression of hepatitis B surface antigen(HBs Ag) and hepatitis B core antigen(HBc Ag) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients(mean age of 40.3 ± 2.5 years), comprising of 14 HBe Ag positive and 19 HBe Ag negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma(mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBc Ag and HBs Ag was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBc Agand HBs Ag staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBe Ag negative patients, the HBe Ag positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBe Ag positive patients had intrahepatic HBc Ag staining; predominantly with "diffuse" distribution(79%) and "mixed cytoplasmic/nuclear " pattern(79%). In comparison, only 5% of the HBe Ag-negative patients had intrahepatic HBc Ag staining. However, the intrahepatic HBs Ag staining has wider distribution among the HBe Ag negative patients, namely; majority of the HBe Ag negative cases had "patchy" HBs Ag distribution compared to "rare" distribution among the HBe Ag positive cases. All but one patient with HCC were HBe Ag negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBc Ag and HBs Ag were seen in 13(100%) and 10(77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBc Ag and HBs Ag were detected in tumor tissues but not the adjacent liver in 4(44%) and 1(11%) patient respectively. CONCLUSION: Isolated intrahepatic HBc Ag and HBs Ag can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.     

The incidence and predictors of HBV relapse after cessation of tenofovir therapy in chronic hepatitis B patients

This study investigates the incidences and predictors of hepatitis B virus (HBV) relapse after tenofovir disoproxil fumarate (TDF) therapy in hepatitis B e antigen (HBeAg)‐positive and ‐negative patients. We retrospectively recruited 143 chronic hepatitis B (CHB) patients without cirrhosis (39 HBeAg‐positive and 104 HBeAg‐negative patients) who were previously treated with TDF and had post‐treatment follow‐up for at least 6 months (median: 55, IQR 36‐85 weeks). All the patients fulfilled the stopping criteria of APASL 2012. The virological and clinical relapse rates at 104 weeks in HBeAg‐positive patients were 66.6% and 59.1%, while they were 72.3% and 55.9%, respectively, in HBeAg‐negative patients. Cox regression analysis revealed that the higher end‐of‐treatment HBsAg levels were an independent factor of virological relapse in HBeAg‐positive and HBeAg‐negative patients. The end‐of‐treatment HBsAg levels of 200 (area under the receiver operating characteristic (AUROC): 0.624) and 80 IU/mL (AUROC: 0.959) were the optimal values for predicting HBV relapse in HBeAg‐positive and HBeAg‐negative patients, respectively. The virological relapse rate at 78 weeks was 14.3% and 19.6% in HBeAg‐positive and HBeAg‐negative patients who achieved HBsAg ≤200 IU/mL and HBsAg ≤80 IU/mL, respectively. Two patients experienced hepatic decompensation upon hepatitis flares, and no patient died after timely retreatment. Seven patients experienced off‐therapy HBsAg loss. The cumulative rates of HBsAg loss at 104 weeks were 45.5% and 59.3% in patients with end‐of‐treatment HBsAg ≤80 IU/mL and ≤50 IU/mL, respectively. In conclusions, the end‐of‐treatment HBsAg levels were a useful marker for predicting HBV relapse in HBeAg‐positive and HBeAg‐negative CHB patients.     

Hepatitis B Surface Antigen Declines and Clearance During Long-Term Tenofovir Therapy in Patients Coinfected With HBV and HIV

Background.?The kinetics of hepatitis B surface antigen (HBsAg) are predictive in HBV-infected patients treated with pegylated interferon. Knowledge about the value of HBsAg levels in patients coinfected with HBV and human immunodeficiency virus (HIV) is lacking. Methods.?We quantified serum HBsAg in a Dutch multicenter cohort of 104 patients coinfected with HIV and HBV who were treated with tenofovir disoproxil fumarate (TDF) as part of highly active antiretroviral therapy. The median duration of therapy was 57 months (interquartile range, 34-72 months). Results.?Hepatitis B e antigen (HBeAg)-positive patients achieved a decline of 2.2?log IU/mL in HBsAg, whereas HBeAg-negative patients only achieved a decline of 0.6?log IU/mL during 6 years of TDF therapy. Declines in HBsAg at months 6 and 12 correlated with CD4 cell count for HBeAg-positive patients. Five HBeAg-positive patients (8%) and 3 HBeAg-negative patients (8%) cleared HBsAg. HBeAg-negative patients who cleared HBsAg had lower baseline HBsAg as compared to patients who remained HBsAg positive. The majority of patients who cleared HBsAg achieved this end point within the first year. In HBeAg-positive patients, decline in HBsAg at month 6 was predictive of achieving HBsAg seroclearance. Conclusions.?Receipt of TDF therapy by HIV/HBV-coinfected patients for up to 6 years led to a significant decrease in HBsAg in the HBeAg-positive population. HBsAg kinetics early during treatment were predictive of HBsAg seroclearance and correlated with an increased CD4 cell count, underlining the importance of immune restoration in HBV clearance.     

Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain

INTRODUCTION: There are very limited data about the prevalence of multiple hepatitis virus infections in HIV infected individuals. In HIV uninfected individuals with triple BCD hepatitis, hepatitis D virus (HDV) appears to be the dominant virus. However, in HIV infected patients with triple hepatitis it is not known if HDV replication inhibits hepatitis B virus (HBV) and/or hepatitis C virus (HCV) replication. METHODS: We calculated the prevalence of single (B or C), dual (BC) and triple (BCD) hepatitis in 423 HIV-infected patients with positive HCV serum antibodies and/or positive serum HBsAg. In patients with multiple infections we performed an evaluation of serum markers of HBV, HCV and HDV replication. RESULTS: The prevalence of multiple hepatitis was 4.7% (95% confidence interval, 2.7-6.7%). Multiple hepatitis occurred only among patients who acquired HIV through injection drug use. The most common multiple hepatitis was triple BCD. Patients with hepatitis BC and past or chronic hepatitis D were significantly more likely to have cirrhosis and a negative serum HBeAg and HCV PCR than patients with single hepatitis B or hepatitis C. Patients with chronic hepatitis D showed uniform suppression of HBV and HCV replication markers. CONCLUSIONS: In our geographic area approximately 5% of HIV infected patients with hepatitis suffer multiple hepatitis virus infection. In patients with triple hepatitis BCD virus infection, HDV appears to be the dominant virus causing inhibition of both HBV and HCV replication.     

Hepatitis B virus reactivation during belatacept treatment after kidney transplantation

We report a case of HBV reactivation following belatacept treatment in a patient who underwent kidney transplantation in 2015 for HIV‐associated nephropathy (HIVAN). Human immunodeficiency virus viral load was undetectable prior to transplantation, and CD4+ lymphocyte count was greater than 300/mL. Baseline HBV serology at transplantation was HBsAg negative, anti‐HBcAb positive, anti‐HBsAb 312 UI/L, and HBeAg negative/anti‐HBeAb positive. Liver function tests were normal, and viral DNA was undetectable. Two years later, the patient presented with severe acute hepatitis after a progressive disappearance of anti‐HbsAb, quickly followed by HBV reactivation. Immunosuppressive treatment was drastically reduced, and treatment with entecavir was started. The outcome was favorable, and HBV DNA became undetectable after 9 weeks of treatment. This is the first report of acute hepatitis related to HBV reactivation in a kidney transplant recipient treated with belatacept. The risk for HBV reactivation in patients treated with belatacept should not be underestimated, especially in those with resolved HBV infection.     

Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV‐/HBV‐coinfected patients

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV‐/HIV)‐coinfected patients receiving HBV‐active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV‐active cART in a cohort of 59 HIV‐/HBV‐coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan–Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg‐positive [HBeAg(+); n = 36] and HBeAg‐negative [HBeAg(−);n = 23] patients. HBeAg(+) patients with an HBsAg on‐treatment decline ≥1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(−) patients, a pretreatment baseline cut‐off level of HBsAg ≤100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(−) HIV‐/HBV‐coinfected patients receiving HBV‐active cART.     

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large‐sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)‐positive chronic HBV infection (n = 588), HBeAg‐positive chronic hepatitis B (n = 596), and HBeAg‐negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%‐90% confidence interval: 3.52 log10 IU/mL‐4.99 log10 IU/mL]) in patients with HBeAg‐positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg‐positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg‐negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg‐positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg‐negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.     

Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir

Background and Aim: We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg‐interferon and adefovir for 48 weeks. Methods: Intrahepatic covalently closed circular DNA (cccDNA), total intrahepatic HBV DNA and the proportion of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) positive hepatocytes in 16 hepatitis B e antigen (HBeAg) positive and 24 HBeAg negative patients were measured at baseline and at end of treatment. Results: Baseline intrahepatic markers were not associated with sustained virological response (SVR) defined as HBV DNA < 2000 IU/mL and persistent normal alanine aminotransferase levels at the end of follow‐up (week 72). At end of treatment, intrahepatic cccDNA and total intrahepatic HBV DNA in HBeAg positive patients were significantly lower in patients with HBeAg seroconversion (P = 0.016 and P = 0.010) with positive predictive values (PPV) for SVR of 80% and 80%, respectively. In HBeAg negative patients, intrahepatic cccDNA and total intrahepatic HBV DNA had declined significantly at end of treatment (P = 0.035 and P = 0.041) and corresponding PPV for SVR was 73% and 82%. In HBeAg positive patients, median proportion of HBcAg positive hepatocytes declined significantly (P = 0.002) at end of treatment. In HBeAg negative patients, the proportion of HBsAg positive hepatocytes had declined significantly at end of treatment (P = 0.0009). Using HBsAg ≤ 7.5% as a limit, PPV for SVR in HBeAg negative patients was 83%. Conclusions: At end of treatment in HBeAg positive patients, intrahepatic cccDNA and total intrahepatic HBV DNA were predictive for SVR. In HBeAg negative patients a proportion of < 7.5% HBsAg positive hepatocytes at end of treatment was a strong predictor for SVR.     

乙肝病毒父婴垂直传播感染率的临床调查

目的 调查研究乙型肝炎病毒(hepatitis B virus,HBV)父婴垂直传播感染率的情况.方法 以56对感染HBV的父亲而母亲无HBV标志物的夫妇新生儿脐血做研究组,以10对均不携带HBV的夫妇新生儿脐血做为对照组,分别做HBV PCR检测.结果 在研究组的脐血标本中检出2例HBV DNA阳性标本,而这2例新生...     

慢性HBV感染者外周血CXCR5~+CD4~+Tfh细胞的测定及其与FoxP3~+Treg细胞的相关性

目的:探讨慢性乙型肝炎病毒(hepatitis Bvirus,HBV)感染不同阶段患者外周血CD4+T淋巴细胞中CD4+CXCR5+Tfh细胞及CD4+CD25+FoxP3+Treg细胞的百分比及其意义.方法:应用流式细胞术检测15例慢性无症状HBV携带者(chronic asymptomatic HBV carriers,AsC)、42例慢性乙型肝炎(chronic hepatitisB,CHB)患者(HBeAg阳性25例、HBeAg阴性17例)、11例非活动性HBsAg携带者(inactive HBsAg carriers,InC)外周血CD4+CXCR5+Tfh细胞及CD4+CD25+FoxP3+Treg细胞占CD4+T淋巴细胞的百分比,并与15例健康对照(healthycontrol,HC)进行比较.结果:AsC、HBeAg(+)CHB、HBeAg(-)CHB组外周血CD4+CXCR5+Tfh细胞占CD4+T淋巴细胞的比例分别为17.66(15.34%-20.56%),21.95(19.60%-26.32%),22.33(17.58%-24.85%),显著高于HC组的13.67(9.80%-15.32%),差异具有统计学意义(P<0.001).与AsC及InC组的16.11(12.33%-19.73%)相比,HBeAg(+)、HBeAg(-)CHB组外周血CD4+CXCR5+Tfh细胞占CD4+T淋巴细胞的比例显著升高(P<0.05).此外,AsC组外周血CD4+CD25+FoxP3+Treg细胞占CD4+T淋巴细胞的比例为7.70(6.35%-9.13%),显著高于HC组的6.53(5.54%-7.35%),P<0.05.HBeAg(+)CHB组外周血CD4+T淋巴细胞中CD4+CD25+FoxP3+Treg细胞的频率为7.52(6.09%-8.49%),与AsC组相比呈降低的趋势.外周血CD4+CXCR5+Tfh细胞占CD4+T淋巴细胞的比例与HBVDNA载量呈负性相关(r=-0.275,P<0.05);而与血清ALT水平、HBsAg滴度无相关性.结论:CD4+CXCR5+Tfh细胞可能参与了慢性HBV感染所介导的免疫反应,外周血CD4+CD25+FoxP3+Treg细胞及CD4+CXCR5+Tfh细胞的消长可能与疾病的活动性相关.     

Five‐year on‐treatment efficacy of lamivudine‐, tenofovir‐ and tenofovir + emtricitabine‐based HAART in HBV–HIV‐coinfected patients

Summary. Data on the efficacy of lamivudine (LAM)‐, tenofovir (TDF)‐ and emtricitabine (FTC)‐based antiretroviral therapy (HAART) in HBV–HIV coinfection are limited. We completed a retrospective analysis of HBV–HIV‐coinfected patients treated at the Medical University of Vienna. One‐hundred and ten coinfected patients were included, with 57% being initially HBV e‐Antigen (HBeAg) positive. Baseline HBV load was significantly higher in HBeAg+ than in HBeAg? patients (5962 ± 3663 vs 20 ± 19 × 10⁶ IU/mL; P < 0.0001). Over a median observation period of 83 month (range: 26–183), 87% received HAART and 91% showed a suppression of HBV replication. After 5 years of continuous treatment, HBeAg seroconversion was achieved in 21% of LAM‐, 50% of TDF‐ (P = 0.042 vs LAM) and in 57% of TDF + FTC (P = 0.008 vs LAM)‐treated patients, respectively. HBsAg loss after 5 years was found in 8% (LAM), 25% (TDF; P = 0.085 vs LAM) and 29% (TDF + FTC; P = 0.037 vs LAM) of HBeAg+ patients. In HBeAg? patients, HBsAg loss was achieved in 11% (LAM), 27% (TDF; P = 0.263 vs LAM) and 36% (TDF + FTC; P = 0.05 vs LAM), respectively. Pretreatment CD4+ counts did not influence rates of HBeAg seroconversion and of HBsAg loss. Patients with HBsAg loss had lower baseline HBV‐DNA levels and higher AST/ALT levels than patients without HBsAg loss. Transient HAART‐related hepatotoxicity was found in 32% (Grade I: 21%; II:7%; III:2%; IV:0%). Most HBV–HIV‐coinfected patients achieve complete suppression of HBV replication despite high baseline viremia. TDF‐based HAART leads to high rates of HBeAg seroconversion and HBsAg loss after 5 years of continuous exposure. One‐third of HBV–HIV‐coinfected patients may experience transient HAART‐related hepatotoxicity.     

Cellular immune responses in hepatitis B virus e antigen negative chronic hepatitis B

The immunopathogenesis of hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) virus (HBV) infection has not been adequately investigated. We studied the cellular immune responses of peripheral lymphocytes using proliferating assays, intracellular cytokine staining (ICS) and ELISPOT interferon-gamma (IFN-gamma) assays after non-specific and specific stimulation with whole HBV proteins and synthetic peptides. Thirty patients with HBeAg negative CHB, eleven HBsAg inactive carriers, nine patients with acute hepatitis B and 22 healthy controls were included in the study. Patients with HBeAg negative CHB demonstrated an increased number of peripheral CD8+ T cells while their peripheral blood mononuclear cells showed increased proliferation after in vitro stimulation with overlapping hepatitis B core derived peptides and an envelope derived epitope (HBs 182-191 aa), similar to those observed in acute hepatitis B. Using ICS, we found an expanded population of IFN-gamma producing T lymphocytes, CD4+ and CD8+, after non-specific stimulation, in HBeAg negative CHB compared to all other groups. HBeAg negative CHB and acute hepatitis B patients had a similarly increased number of core specific T cells measured by the IFN-gamma assays. Inactive HBsAg carriers showed minimal proliferative responses overall while they exhibited an increased number of envelope specific effector T cells (measured by ICS). In conclusion, we showed that overall CD4+ T cell responses from patients with HBeAg negative CHB were comparable to those of acute hepatitis B, while inactive HBsAg carriers despite their limited proliferative capacity the effector activity of their peripheral T cells was maintained.     

Treatment of polyarteritis nodosa related to hepatitis B virus with interferon-alpha and plasma exchanges.

OBJECTIVES--To test the effectiveness of and tolerance to interferon-alpha 2b (INFa2b) in association with plasma exchanges for the treatment of polyarteritis nodosa (PAN) related to hepatitis B virus (HBV). METHODS--A prospective, non blinded, multicentre trial was carried out in which patients with multisystemic HBV-related PAN were included. Each patient received the association of INFa2b and plasma exchanges. The end point of the study was control of the disease (recovery or remission) or death. RESULTS--Six patients were included in the study. Each patient had histopathological or arteriographic evidence of vasculitis and was infected with actively replicating HBV. All patients were alive at the end of the study and no longer presented clinical or laboratory evidence of systemic vasculitis. HBeAg/anti-HBeAb seroconversion was observed in four patients (66.6%) and HBsAg/anti-HBsAb in 3/6 (50%). Two patients are still being treated with INFa2b because of chronic active hepatitis. CONCLUSIONS--It is considered that this new therapeutic approach to HBV-related PAN effectively cured systemic vasculitis and was associated with control of HBV infections. Antiviral therapy may have a role to play as the first line treatment regime of virus-induced vasculitis.     

Excellent outcome of Lamivudine treatment in patients with chronic renal failure and hepatitis B virus infection

Chronic hepatitis B virus (HBV) is associated with increased morbidity and mortality in patients with chronic renal failure (CRF) and renal transplant recipients. Lamivudine (3TC) has been shown to be a potent inhibitor of HBV replication. It appears to be safe and effective in patients with CRF, though experience is still limited. We describe 4 patients with CRF on hemodialysis who showed a rapid and full response to 3TC, administered for a median of 10 months. All patients had serum alanine transferase (ALT) levels 3 to 6 times the upper limit of normal prior to treatment, and different degrees of histologic inflammatory activity (Knodell score 4 to 8, median 6). All were serum HBsAg- and HBeAg-positive, with serum HBV DNA 1-3.9 x 107 copies/mL (median 1 x 107 copies/mL). Within 4 to 8 weeks of initiation of therapy, HBV DNA became undetectable and serum ALT normalized. Serum HBeAg disappeared in all 4 patients, with the emergence of anti-HBeAb in 3 of them. Three patients also lost HBsAg with the evolution of a protective anti-HBsAb titer. One patient has already undergone successful kidney transplantation with no evidence of HBV recurrence (serum HBV DNA negative) 16 months postoperatively.Although our study sample is small, these data suggest that 3TC can induce a complete biochemical, virological and serological response in patients with CRF and HBV infection. Its use may enable safe kidney transplantation in selected patients.