Nationwide cohort study suggests that nucleos(t)ide analogue therapy decreases dialysis risk in Taiwan Residents chronic kidney disease patients acquiring hepatitis B virus infection

AIM To investigate the risk of end-stage renal disease(ESRD) in hepatitis B virus(HBV)-infected patients with chronic kidney disease(CKD) with and without nucleos(t)ide analogue(NA) therapy.METHODS This nationwide cohort study included 103444 Taiwan Residents CKD adults without hepatitis C virus infection from the Taiwan Longitudinal Health Insurance Database 2005 between 1997 and 2012. We identified 2916 CKD patients who acquired HBV infection and did not receive NAs(untreated cohort), and they were propensitymatched 1:4 with 11664 uninfected counterparts. We also identified 442 CKD patients who acquired HBV infection and received NAs(treated cohort), and they were propensity-matched 1:3 with 1326 untreated counterparts. The association between HBV infection, NA use, and ESRD was analyzed using competing risk analysis.RESULTS Multivariable Cox regression analysis showed a 1.67-fold higher risk(P < 0.0001) of ESRD in the untreated cohort(16-year cumulative incidence, 10.1%) than in the matched uninfected cohort(16-year cumulative incidence, 6.6%), which was independent of cirrhosis or diabetes. The treated cohort(16-year cumulative incidence, 2.2%) had an 87% lower ESRD risk(P < 0.0001) compared with the matched untreated cohort(16-year cumulative incidence, 11.9%). The number needed to treat for one fewer ESRD after NA use at 12 years was 12. Multivariable stratified analyses verified these associations in all subgroups.CONCLUSION This study suggests that untreated HBV infection and NA therapy are associated with increased and decreased risk of ESRD, respectively, in CKD patients. Identification of HBV status and targeted monitoring for ESRD development are important in CKD patients living in HBV-endemic areas.

Hepatocellular carcinoma in patients with chronic kidney disease

AIM: To investigate outcomes of hepatocellular carcinomas (HCCs) in patients with chronic kidney disease (CKD). METHODS: Four hundred and forty patients referred between 2000 and 2002 for management of HCCs were categorized according to their CKD stage, i.e. , estimated glomerular filtration rate (eGFR) > 90 (stage 1), 60-90 (stage 2), 30-60 (stage 3), 15-30 (stage 4), and < 15 (stage 5) mL/min per 1.73 m 2 , respectively. Demographic, clinical and laboratory data were collected and mortality rates and cause of mortality were analyzed. The mortality data were examined with Kaplan-meier method and the significance was tested using a log-rank test. An initial univariate Cox regression analysis was performed to compare the frequency of possible risk factors associated with mortality. To control for possible confounding factors, a multivariate Cox regression analysis (stepwise backward approach) was performed to analyze those factors that were significant in univariate models (P < 0.05) and met the assumptions of a proportional hazard model. RESULTS: Most HCC patients with CKD were elderly, with mean age of diagnosis of 60.6 ± 11.9 years, and mostly male (74.8%). Hepatitis B, C and B and C coinfection virus were positive in 61.6%, 45.7% and 14.1% of the patients, respectively. It was found that patients with stages 4 and 5 CKD were not only older (P = 0.001), but also had higher hepatitis C virus carrier rate (P = 0.001), lower serum albumin level (P = 0.001), lower platelet count (P = 0.037), longer prothrombin time (P = 0.001) as well as higher proportions of advanced cirrhosis (P = 0.002) and HCCs (P = 0.001) than patients with stages 1 and 2 CKD. At the end of analysis, 162 (36.9%) patients had died. Kaplan-Meier analysis revealed that patients with stages 4 and 5 CKD suffered lower cumulative survival than stages 1 and 2 CKD (log-rank test, χ 2 = 11.764, P = 0.003). In a multivariate Cox-regression model, it was confirmed that CKD stage [odds ratio (OR) = 1.988, 95%CI: 1.012-3.906, P = 0.046)], liver cirrhosis stage (OR = 3.571, 95%CI: 1.590-8.000,P = 0.002) and serum albumin level (OR = 0.657, 95%CI: 0.491-0.878, P = 0.005) were significant predictors for mortality in this population. CONCLUSION: HCC patients with stages 4 and 5 CKD had inferior survival than stages 1 and 2 CKD. This warrants further studies.

Chronic hepatitis B in children with or without malignancies:A 13-year follow-up

AIM:To evaluate the outcome of chronic hepatitis B(CHB)in children with or without malignancies.METHODS:Twenty four children(15 boys and 9 girls)with malignancies,followed up by the pediatric gastroenterology outpatient clinic for CHB between January 2000 and December 2013,were enrolled in the study(Group 1).Group 2 was formed with twenty five children(11 girls and14 boys)diagnosed with CHB without malignancies.The data from the patients’records were compared between the two groups.RESULTS:Hepatitis B e antigen(HBe Ag)/anti HBe seroconversion was observed in 3 patients(12.5%)in group 1 and 15 patients(60%)in group 2,with annual seroconversion rates of 1.61%and 16.6%,respectively,and the difference was significant(P<0.01).One patient(6.6%)in Group 1 and 9 patients(53%)in Group 2 showed HBe Ag/anti HBe seroconversion after treatment and the difference between the two groups was significant(P<0.06)Loss of hepatitis B surface antigen was observed in one patient in each of group1 and 2.No clinical,laboratory and imaging findings of liver disease were observed in any of the patients at the end of the study.CONCLUSION:HBe Ag/anti HBe seroconversion rate was lower in patients who had recovered from cancer.

Management of hepatitis B and C in special population

Chronic viral hepatitis is one of the leading causes of cirrhosis worldwide.Chronic hepatitis B is more common in the Asia-Pacific region due to the larger population and lower screening availability.Hepatitis C predominates in the west due to injection drug abuse.The discovery of(oral)direct-acting antiviral agents(DAAs)has changed the landscape of chronic hepatitis C(CHC)management.Nucleos(t)ide analogs(NUCs)have also changed the approach to the treatment of chronic hepatitis B(CHB).Oral NUCs and DAAs have excellent efficacy and patient acceptance as well as a lower risk of resistance.However,certain populations have no robust data and safety and efficacy of such oral drugs is still evolving.In this review,we provide an overview of the management of CHB and CHC in special populations,such as those with chronic kidney disease,pregnant women,healthcare workers,and those undergoing chemo-or immunosuppressive therapy.

Relationship between occult hepatitis B virus infection and chronic kidney disease in a Chinese population-based cohort

Objective: Previous studies have revealed inconsistent results regarding the association between occult hepatitis B virus (HBV) infection and chronic kidney disease (CKD). Therefore, we conducted a prospective cohort study to evaluate the association be-tween occult HBV infection and CKD. Methods: A total of 4329 adults, aged 46.2 ± 13.7 years, without CKD at baseline were enrolled while undergoing physical examinations. Occult HBV infection was defined as seropositivity for antibody to HBV core antigen. CKD was defined as decreased estimated glomerular filtration rate (eGFR<60 ml$min?1$1.73 m?2) or presence of proteinuria ?1t, assessed using a repeated dipstick method. eGFR was computed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: The prevalence of occult HBV infection was 8.1% (352/4329). During 5 years of follow-up, 165 patients (3.8%) developed CKD. Univariate Logistic regression analysis showed that occult HBV infection was positively associated with decreased eGFR, with an odds ratio (OR) of 2.15 (95%confidence interval (CI):1.05e4.11). In contrast, occult HBV infection was not associated with either proteinuria or CKD (P>0.05). After adjustment for potential confounders in the multivariate Logistic regression analysis, age, hypertension, diabetes, and the highest quartile of uric acid were associated with CKD, with ORs of 1.04 (95%CI:1.02e1.05), 2.1 (95%CI:1.46e3.01), 2.02 (95%CI:1.36e2.99), and 1.86 (95%CI:1.17e2.95), respectively. However, occult HBV infection was not associated with CKD, with an OR of 1.12 (95%CI:0.65e1.95). Conclusions: This study did not find an association between occult HBV infection and CKD. However, high-risk patients infected with HBV should still be targeted for monitoring for the development of CKD.

Risk Factors of Chronic Kidney Disease in Chronic Hepatitis B:A Hospital-based Case-control Study from China

Background and Aims:Chronic kidney disease(CKD)usually occurs during the chronic infection of hepatitis B virus(HBV).However,the risk factors of CKD in an HBV population have not been completely demonstrated.Our present study aimed to investigate the risk factors of CKD in chronic HBV infection using a hospital based cross-sectional study in the northern area of China.Methods:During January 2013 to December 2017,a total of 94 patients with CKD complicated by chronic HBV infection were consecutively enrolled in the study,as well as 548 age-and sex-matched hepatitis B patients without CKD who were enrolled as controls.Univariate and multivariate regression analyses were used to determine the effects of each variable after adjusting for cofounding factors.Results:Multivariate analysis showed that HBeAg-positive status(odds ratio[OR]=2.099,95%CI 1.128-3.907),dyslipidemia(OR:3.025,95%CI 1.747-5.239),and hypertension(OR:12.523,95%CI 6.283-24.958)were independently associ-ated with the incidence of CKD,while duration of HBV in-fection(≥240 months)(OR:0.401,95%CI 0.179-0.894),Log10 HBsAg(OR:0.514,95%CI 0.336-0.786),and coro-nary heart disease(OR:0.078,95%CI 0.008-0.768)were protective factors for the incidence of CKD.Duration of HBV infection,Log10 HBsAg,HBeAg-positive status and dyslipidemia remained the risk factors for CKD after adjusting for diabetes mellitus,hypertension,and coronary heart disease.Conclusions:Duration of HBV infection,Log10 HB-sAg,HBeAg-positive status and dyslipidemia contributed to the incidence of CKD during chronic HBV infection in a Chinese population.

猪苓多糖合用甲、乙肝疫苗治疗乙肝HBeAg34例

目的研究猪苓多糖、乙肝疫苗、甲肝疫苗三者联用促进慢性乙型肝炎HBeAg阴转的治疗作用．方法住院的68例慢性乙肝三阳患者随机分为两组．治疗组：猪谷多糖注射液40mg，1次／d，im，连续使用20d，停10d，重复三次，3mo为一疗程．乙肝疫苗分别在15d，30d时sc30μg，6次为一疗程．甲肝疫苗每20dsc1mL，三次为一疗程．对照组：只使用猪苓多糖＋乙肝疫苗，方法同治疗组．结果三个疗程结束时，治疗组HBeAg阴转率达71％，对照组为50％，采用t检验，P＜0．05．治疗组HBVm其他指标的改善情况亦优于对照组．结论采取猪苓多糖、甲肝疫苗、乙肝疫苗三者联用治疗慢性乙肝三阳患者较二者联用转复三阳指标效果更好，尤其是HBeAg，抑制乙肝病毒复制作用确切有效．

慢性肾脏病患者接种乙肝疫苗疗效研究

目的：探讨慢性肾脏病（chronic kidney disease,CKD）早中期（CKD1～3期）、晚期（CKD4～5期）患者接种乙肝疫苗后的反应情况,明确CKD患者接种乙肝疫苗的最佳时期,使CKD患者产生主动免疫抵御HBV感染。方法：对乙肝两对半全阴性的慢性肾脏病早中期、晚期患者接种乙肝疫苗,观察两组患者乙肝表面抗体的阳转率及抗体滴度高低情况,同时,将CKD早中期组分为接受或未接受激素/免疫抑制剂两组,所有CKD患者再分为男性、女性两组,分别对上述分组进行比较,观察各组患者乙肝表面抗体的阳转率及抗体滴度高低情况。结果：（1）CKD早中期患者接种乙肝疫苗后,乙肝表面抗体阳转率明显高于CKD晚期患者,且抗体滴度明显高于CKD晚期组。（2）在CKD早中期组中接受或未接受激素/免疫抑制剂治疗的患者中抗体阳转率差异无统计学意义,但接受激素/免疫抑制剂组抗体滴度更高。（3）性别不是影响乙肝疫苗接种效果的因素。结论：CKD早中期患者接种乙肝疫苗疗效优于CKD晚期患者,激素及免疫抑制剂治疗不影响CKD早中期患者接种乙肝疫苗的疗效,性别不影响接种效果。

启东乙型肝炎干预研究：2013年随访人群HBV感染及慢性肝病现患调查

目的分析新生儿接种乙型肝炎（乙肝）疫苗人群在达到婚配年龄后罹患慢性乙肝、肝硬化的远期保护作用。方法2013年1—10月采用横断面调查方法，对启东乙肝干预研究（QHBIS）的研究对象分层随机抽样，并行ALT、HBV感染血清学标志物（HBsAg、HBeAg、抗-HBs、抗-HBc、抗-HBe）检测及肝胆B超检查。计算HBV感染血清学标志物各指标的阳性率，慢性乙肝及肝硬化的患病率，疫苗组及对照组人群按性别分层后，疋。检验比较各组间率的差异。结果共获得新生儿乙肝疫苗接种组（疫苗组）4421人和对照组3880人，平均年龄分别为（25．59±1．84）岁和（26．61±2．24）岁。疫苗组HBsAg、单独抗一HBs、抗一HBc、HBeAg、抗一HBe阳性率分别为2．38％、37．73％、3．78％、0．57％、2．15％，对照组分别为9．02％、29．41％、16．83％、2．73％、8．87％，两组问血清学标志物各指标的差异均有统计学意义（P〈0．05）。疫苗组慢性乙肝活动期、肝纤维化及肝硬化患病率分别为0．45％和0．16％，对照组分别为1．29％和0．39％，组间差异均有统计学意义（P〈0．05）。按性别分层后，疫苗组男性慢性乙肝活动期患病率高于女性，差异有统计学意义（P〈0．05）；在对照组，不管是慢性乙肝活动期患病率还是肝纤维化及肝硬化患病率，男性均高于女性，差异有统计学意义（P〈0．05）。结论新生儿接种乙肝疫苗对慢性HBV感染的保护作用可延长至婚配年龄后，而不同性别人群慢性乙肝与肝硬化现患保护作用的差异值得进一步研究。

常规免疫预防阻断乙型肝炎病毒母婴感染的效果

目的评价免疫预防措施在实际应用中阻断乙型肝炎病毒（hepatitis B virus，HBV）母婴感染的效果，阐明孕妇孕晚期使用乙肝免疫球蛋白（hepatitis B immunoglobulin，HBIG）能否减少HBV母婴感染。方法将2002年7月至2004年8月江苏省14个县市的419例乙型肝炎表面抗原（hepatitis Bsurfaceantigen，HBsAg）阳性孕妇所分娩子女作为研究组，同地区同期的453例HBsAg孕妇分娩的子女作为对照组，于2009年10月至2010年3月期间对2组研究对象进行随访，调查母亲孕期HBIG使用情况以及子女出生后HBIG和乙型肝炎疫苗接种情况，检测儿童HBV血清标志物。率的比较采用7。分析或者Fisher精确概率法，均数的比较采用t检验。结果研究组实际随访298例（71．12％），其中11例（3．69％）HBsAg＋；而随访的328例（72．41％）对照组中，HBsAg阳性率为0．00（x2=12．32，P〈0．01）。共11例儿童HBsAg＋，其母亲均为HBsAg和HBeAg同时阳性，除1例具体情况不详外，9例儿童在出生时明确没有使用HBIG或延迟接种疫苗，仅1例同时规范使用了HBIG和乙型肝炎疫苗。2组儿童抗HBs阳性率分别为69．46％和69．21％（x2=0．01，P=0．95）。孕晚期注射HBIG的92例孕妇中，2例（2．17％）儿童HBsAg＋；未使用HBIG的197例孕妇中，9例（4．57％）儿童HBsAg＋（x2=0．98，P=0．51）。结论江苏省常规免疫预防措施在阻断母婴HBV感染方面取得了良好的效果，但对HBV携带孕妇（特别是HBeAg＋者）的新生儿仍需强调及时注射HBIG。孕妇孕晚期使用HBIG不能减少母婴HBV感染。

慢性肾脏病患者不同免疫方案接种乙型肝炎疫苗的免疫效果及影响因素分析

目的分析不同免疫方案对慢性肾脏病(CKD)患者接种乙型肝炎(乙肝)疫苗的免疫效果及影响因素。方法研究对象为2019年5月至2020年7月在山西省4家医院参加随机对照试验的CKD患者273例。按1∶1∶1比例采用区组随机分为3组(每组91例),分别接受0-1-6月20µg、0-1-2-6月20µg、0-1-2-6月60µg乙肝疫苗接种,在全程接种后1个月和6个月随访期采用化学发光微粒子免疫分析法进行乙型肝炎表面抗体(抗-HBs)的定量检测,采用χ^(2)检验、方差分析、非条件logistic回归的统计学方法分析其阳性率、强阳性率和几何平均浓度(GMC)及影响因素。结果273例CKD患者中,全程接种后1个月随访期,0-1-2-6月20µg和0-1-2-6月60µg组的抗-HBs阳性率[92.96%(66/71)和93.15%(68/73)]及抗-HBs GMC(2091.11 mIU/ml和2441.50 mIU/ml)明显高于0-1-6月20µg组[81.69%(58/71)及1675.21 mIU/ml](均P<0.05);全程接种后6个月随访期,0-1-2-6月60µg组抗-HBs阳性率(94.83%,55/58)明显高于0-1-6月20µg组(78.79%,52/66)(P<0.05),0-1-2-6月60µg组抗-HBs GMC(824.28 mIU/ml)明显高于0-1-2-6月20µg组(755.53 mIU/ml)和0-1-6月20µg组(639.74 mIU/ml)(P<0.05)。控制潜在混杂因素后,全程接种后1个月和6个月随访期,按0-1-2-6月接种60µg乙肝疫苗的抗-HBs阳性的概率分别是0-1-6月20µg组的3.19(95%CI:1.02~9.96)和5.32(95%CI:1.27~22.19)倍,不服用激素/免疫抑制剂者的抗-HBs阳性的概率分别是服用者的3.33(95%CI:1.26~8.80)和4.78(95%CI:1.47~15.57)倍。结论0-1-2-6月20µg和0-1-2-6月60µg免疫方案均可提高CKD患者乙肝疫苗免疫效果,且0-1-2-6月60µg方案对该人群抗-HBs水平的维持有积极作用。服用激素/免疫抑制剂的CKD患者乙肝疫苗免疫效果不佳。