The effect of hepatitis B vaccination on the incidence of childhood HBV-associated nephritis

The aim of the present study was to investigate the effect of a vaccination program for hepatitis B virus (HBV) on the incidence of HBV-associated glomerulonephritis (HBV-GN). In total, 727 renal biopsies were carried out at our hospital from November 1979 through March 2002. Two groups were established. Group A included those biopsied from November 1979 through December 1991 (prior to the HBV vaccination program) and group B from January 1992 through March 2002. Group B was divided into five subgroups (B₁ to B₅), with an interval of 2 years between each subgroup. Patients were divided into those with or without a history of HBV vaccination. Of the 727 renal biopsies, 64 fulfilled the criteria of HBV-GN, There were 28 cases of the 211 cases in group A and 36 cases of the 516 cases in group B (X ²=7.397,P<0.01). The incidence in group A and group B₁ through B₅ was 13.27% (28/211), 13.04% (9/69), 7.32 (6/82), 6.25% (4/64), 4.88% (4/82), and 5.94% (13/219), respectively (X ²=9.627, P<0.01). Only 8 of the 231 vaccinated children had HBV-GN, while there were 48 HBV-GN cases of the 381 non-vaccinated children (X ²=14.44, P<0.001). There were only 6 cases of membranous nephropathy (MN) in the vaccinated group, while 40 cases of MN occurred in the non-vaccinated group (X ²=12.92, P<0.01). There were 8 children that developed HBV-GN with abnormal serum HBV markers despite HBV vaccination. Two mothers of these 8 children had evidence of HBV infection. The incidence of HBV-GN in children has been decreasing each year since the implementation of the nationwide HBV vaccination program in Shanghai, China. Furthermore, since childhood MN is associated with HBV, vaccination can also reduce the incidence of childhood MN.     

小儿肾病患者肾组织病毒基因表达及临床意义

目的：探讨病毒感染在小儿肾脏病发病中的致病作用及临床意义。方法：应用聚合酶链反应（PCR）检测了224例小儿肾病患血清及肾活检组织中乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、EB病毒（EBV）和巨细胞病毒（CMV）基因表达情况。结果：小儿肾病患血清和肾组织中HVB DNA检出阳性率分别为21.4%和19.6%;HCVRNA阳性率为4.0%和3.1%;EBVDNA阳性率为1.8%和0.5%;CMV DNA阳性率为0.9%和0.5%。结论：HBV感染在小儿肾脏疾病发病因素上起着重要的作用,HCV感染与小儿肾病的关系尚不明确,而EBV和CMV感染导致小儿肾病比较罕见。     

大埔县乙型肝炎疫苗免疫成功率监测结果分析

目的了解大埔县乙型肝炎疫苗接种质量和效果,探讨免疫接种的有效性,找出可能影响免疫成功率的原因,为防治乙型肝炎制定科学的免疫策略提供科学依据。方法抽查辖区内2009年出生儿童163例,采集末梢血0.5mL,使用ELISA双抗原夹心法检测抗-HBs。结果大埔县乙肝疫苗免疫成功率为89.57。结论接种乙肝疫苗依然是阻断母婴传播、降低儿童HBsAg携带率的最经济有效的手段,效果确切。     

Levamisole treatment enhances protective antibody response to hepatitis B vaccination in hemodialysis patients

Hemodialysis shows a high risk for hepatitis B infection, and hepatitis B virus (HBV) vaccination has now become a routine procedure. Unfortunately, 40% to 50% of hemodialysis patients do not have adequate protective antibodies against the HBV vaccination which is thought to be due to depressed cell mediated immunity. Levamisole has been reported to stimulate depressed T-cell activity and enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. We studied the effects of levamisole, an immunomodulatory agent, on the protective antibody response of hemodialysis patients to the HBV vaccination. Our hemodialysis patients with negative anti-HBs antibody routinely received 40 microg doses of recombinant HBV vaccine intramuscularly at 0, 1, and 6 months, and we followed serum anti-HBs levels. Patients with a serum antibody level of >10 mIU/ml were considered as responders. Study groups were classified as follows. Group 1 was comprised of 96 chronic hemodialysis patients with negative anti-HBs and HBV core antibody (52 male, 44 female, mean age of 45 +/- 15 years and mean hemodialysis duration of 46 +/- 40 months) who received HBV vaccination; 55 patients (57%) were found to be responders. Group 2 was comprised of 19 randomly selected patients who had never received hepatitis B vaccine (13 male, 6 female, mean age of 42 +/- 14 years, mean duration of hemodialysis 31 +/- 27 months) and who were started on an HBV vaccination protocol with levamisole per os 80 mg after each hemodialysis session for 4 months and followed up on serum anti-HBs levels. Seventeen of the patients completed this levamisole treatment. Fourteen of the 17 patients had the levels of the protective serum antibody indicating a higher response rate when compared with patients who did not receive levamisole (82% versus 57%, respectively, p < 0.05). Group 3 was comprised of 19 patients randomly selected from persons who did not respond to previous vaccination programs (10 male, 9 female, mean age of 51 +/- 14 years, mean duration of hemodialysis 41 +/- 31 months). A second HBV vaccination program was started with the same levamisole protocol. In this group, 18 patients completed this treatment model. Fourteen of them responded to the vaccination model. In Group 4, a second HBV vaccination program was applied without levamisole to 20 randomly selected persons who did not respond to the previous routine vaccination program (12 male, 8 female, mean age of 53 +/- 17 years, mean duration of dialysis 51 +/- 38 months). Only 3 of them responded to a second vaccination program. Comparing Group 3 with Group 4, there was a higher responder rate to HBV vaccination (77% versus 15%, respectively, p < 0.0001). These results show that levamisole treatment increases the response rate to the first HBV vaccination and of the previously unresponsive cases by modulating possible cellular immune response.     

Challenges in containing the burden of hepatitis B infection in dialysis and transplant patients in India

Aim: Whether or not completing the hepatitis B vaccination in patients who have undergone kidney transplantation in the middle of incomplete vaccination schedule leads to development of protective antibody titres is not known. This study was designed to determine whether the strategy of completing hepatitis B virus (HBV) vaccination after transplantation is efficacious. Methods: Sixty‐four end‐stage renal disease (ESRD) patients were screened for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti‐HBs), hepatitis B e‐antigen (HBeAg) and HBV DNA. HBsAg negative patients received four doses of 40 µg recombinant HBV vaccine. Schedule was continued in after transplantation period if it was incomplete before transplant. Anti‐Hbs titres were evaluated at 1, 3, 6, 9 and 12 months. Results: Past HBV infection was noted in 12 patients: 10 by serology plus viraemia and two by viraemia alone. Of the 46 patients without current or past HBV infection who had received at least two doses of the vaccine before transplant, 17 each had received two and three doses and 12 had completed the schedule. Seventeen (37%) exhibited protective titres. Patients who had completed vaccination were more likely to have protective titres than those incompletely vaccinated (P = 0.02). Five patients responded to post‐transplant vaccination. Conclusion: Partially vaccinated patients do not mount an adequate antibody response despite continued vaccination in the post‐transplant period, whereas complete vaccination provides protection in 60%. The present study data highlights the need of administration of a full schedule of HBV vaccination before kidney transplantation. Nucleic acid‐based tests can identify occult HBV infection.     

Growth and PTH in prepubertal children on long-term dialysis

Growth failure is an important complication for children on dialysis. One possible influence on growth is renal bone disease. We reviewed the case notes of 35 children (23 boys), mean (range) age at inclusion 2.8 (0.25–8.9) years (17 children age <2 years), on dialysis for 2.0 (1–4.8) years, for growth, PTH, calcium and phosphate levels and medications. Data collection ended at age 10 years, commencement of growth hormone (rhGH) or renal transplantation. The mean (range) height standard deviation score (HtSDS) at the start of dialysis was −2.06 (−5.90 to 0.63). No change in HtSDS per year was observed; the median was −0.06 (−1.07 to 2.39). Children aged <2 years showed catch-up growth in the first year on dialysis; median change in HtSDS was 0.31 (−0.78 to 3.13). Mean plasma calcium and ionised calcium were approximately at the mid-point and phosphate just above the mid-point of the respective normal ranges. The median PTH level was 1.52 times the upper limit of normal and levels did not correlate with growth. Our results indicate that intensive nutritional therapy and phosphorus control aiming to keep PTH within the normal range prevents further loss of HtSDS in short children on dialysis. In some children under 2 years of age catch-up growth can be observed in the first dialysis year.     

乙型肝炎病毒表面抗原清除的相关因素研究进展

血清乙型肝炎病毒表面抗原（HBsAg）阳性是乙型肝炎病毒（HBV）感染的标志,而HBsAg清除是慢性乙型肝炎（CHB）最接近临床治愈的一个指标。HBsAg清除受宿主、病毒及抗病毒药物等因素的影响。该文就近年来关于CHB患者HBsAg清除的相关因素的研究进展作了综述。     

维持性血液透析患者感染乙型和丙型肝炎的分析

目的为了评价血液透析（血透）患者乙型和丙型肝炎（HBV、HCV）感染状态及对临床情况和肝功能的影响。方法对62例血透患者应用ELISA法和RT-PCR法检测抗-HCV和HCVRNA，采用斑点杂交法和固相放免法检测HBV标志，并检测肝功能和血浆蛋白电泳。结果62例患者中，抗-HCVIgM阳性27例（43．6％），抗-HCVIgG阳性29例（46．8％），HCVRNA阳性34例（54．8％），三项任一项阳性37例（59．7％），5例（8．1％）HBsAg阳性，其中HBeAg和HBVDNA阳性3例。结论向透患者中HCV感染严重，临床情况及预后差，检测血浆蛋白和电泳较肝功能酶学能更好地作为肝炎诊断和反映病情的指标。     

儿童慢性乙型肝炎抗病毒治疗新进展

通常血清HBsAg阳性超过6个月称为慢性HBV感染。我国约有1．25亿慢性HBV感染者,其中绝大多数是母婴传播或儿童期感染所致。尽管乙型肝炎疫苗能有效阻断乙型肝炎的传播,但由于感染人群基数庞大,儿童慢性HBV感染仍然是严重的社会问题。慢性乙型肝炎（CHB）是指HBV持续感染造成的肝脏慢性坏死性炎性反应,表现为血清HBV DNA升高,伴ALT水平持续或间歇升高或肝组织活检显示慢性肝炎。大约1／4的CHB患者可发展至肝硬化和肝细胞癌。     

Urea kinetics and other dialysis indices in children undergoing ambulatory peritoneal dialysis

Background. Peritoneal dialysis (PD) is an established treatment for children with end-stage renal failure. Creatinine clearance and urea kinetics are used to quantitate the dialysis treatment, but the means to assess the adequacy of dialysis in children are still controversial. Methods. We studied serum chemistry, dietary protein intake (DPI), protein catabolic rate (PCR), weekly urea clearance/body water (Kt/V_urea), weekly creatinine clearance (Ccr/week), clinical signs and symptoms during PD treatment, and peritoneal transport function in 17 children (4 to 18 years of age) with end-stage renal disease treated with PD. Fourteen children were on continuous ambulatory peritoneal dialysis (CAPD) and 3 were on automated peritoneal dialysis. Results. The mean values of the parameters tested were: blood urea nitrogen, 71 mg/dl; creatinine, 9.8 mg/dl; total protein, 6.4 g/dl; albumin, 4.0 g/dl; total Ccr, 70 l/week per 1.73 m²; DPI, 1.76 g/kg per day; PCR, 1.17 g/kg per day, and total Kt/V_urea, 2.28/week. The mean patient's clinical assessment score was 11.7, out of 15 and the mean doctor's clinical assessment score was 11.7, out of 14. The correlation between Kt/V_urea and creatinine clearance was 0.84 (P < 0.0001). Kt/V_urea and clinical assessment scores (patient's and doctor's scores) did not show a good correlation (r = 0.32; P = 0.228, and r = 0.47; P = 0.064, respectively). Peritoneal function seemed to be preserved after an average duration of 32 months on PD. Conclusions. These patients appeared to be fairly well dialyzed, judging from the values for the various dialysis indices obtained in this study and comparing them with adult indices. Received: January 7, 1999 / Accepted: March 22, 2000     

Reduced response to hepatitis B virus vaccination in boys with steroid-sensitive nephrotic syndrome

Vaccination against hepatitis B virus (HBV) was performed in 18 boys (aged 5.7±2.4 years) suffering from steroid-sensitive nephrotic syndrome (SSNS) and in a control group of 21 healthy boys (aged 5.6±3.8 years). The percentage of patients who responded to vaccination was significantly lower than the control group 1, 6, 8, 12, 18 and 24 months after the start of vaccination. The titre of antibodies to HBV surface antigen produced by responders at 6 and 24 months was significantly lower in patients than in the control group. Boys with SSNS have an impaired response to HBV vaccination.     

HBsAg定量在慢性乙型肝炎患者干扰素抗病毒治疗中的变化及临床意义

目的研究HBsAg定量在慢性乙型肝炎患者干扰素抗病毒治疗期间的变化及临床意义。 方法收集43例接受IFN-α治疗的HBeAg阳性慢性乙型肝炎患者为研究对象。分别在治疗前和治疗后1、3和6个月时定量检测患者血清HBsAg水平;并同时监测其HBV DNA、HBeAg、HBcAb及ALT的水平。 结果43例患者治疗前和治疗后1、3、6个月时血清HBsAg水平呈下降趋势,差异具有统计学意义（P = 0.029）;治疗1个月时较治疗前有所下降,但差异无统计学意义（t =-1.12、P = 0.304）;治疗3个月和6个月时均较治疗前显著下降,差异具有统计学意义（t =-2.71、P = 0.015,t =-2.71、P = 0.010）;其他不同时间点间比较差异均无统计学意义。IFN-α治疗6个月时患者血清HBsAg下降> 0.5 log₁₀IU/ml组患者ALT复常率高于下降< 0.5 log₁₀IU/ml组,差异具有统计学意义（χ² =5.536、P = 0.019）;下降> 0.5 log₁₀IU/ml组HBeAg阴转率高于下降< 0.5 log₁₀IU/ml组,差异具有统计学意义（χ² = 4.226、P = 0.040）;下降> 0.5 log₁₀IU/ml组HBeAg血清学转换率高于下降< 0.5 log₁₀IU/ml组,差异具有统计学意义（χ² = 4.226、P = 0.040）。 结论HBsAg定量在慢性乙型肝炎患者IFN-α治疗早期呈下降趋势。HBsAg定量在慢性乙型肝炎IFN-α治疗早期下降迅速的患者ALT复常率、HBeAg阴转率及HBeAg血清学转换率均高于下降缓慢者。     

Long-term outcome of chronic dialysis in children

As the prevalence of children on renal replacement therapy (RRT) increases world wide and such therapy comprises at least 2% of any national dialysis or transplant programme, it is essential that paediatric nephrologists are able to advise families on the possible outcome for their child on dialysis. Most children start dialysis with the expectation that successful renal transplantation is an achievable goal and will provide the best survival and quality of life. However, some will require long-term dialysis or may return intermittently to dialysis during the course of their chronic kidney disease (CKD). This article reviews the available outcome data for children on chronic dialysis as well as extrapolating data from the larger adult dialysis experience to inform our paediatric practice. The multiple factors that may influence outcome, and, particularly, those that can potentially be modified, are discussed.     

阿德福韦酯耐药慢性乙型肝炎患者HBsAg变异分析

目的探讨阿德福韦酯耐药慢性乙型肝炎患者相关S抗原变异、疫苗逃逸相关变异以及部分已知特异性T细胞表位变异情况。 方法收集2007年12月至2011年9月于首都医科大学附属北京地坛医院收治的阿德福韦酯治疗失败的慢性乙型肝炎患者70例,并随机选择ADV治疗非耐药患者70例作为对照。采用PCR产物直接测序法获得患者HBV反转录酶区与S抗原序列。应用PCR产物直接测序法与焦磷酸测序法明确阿德福韦酯耐药情况。比较阿德福韦酯耐药患者与无阿德福韦酯耐药患者耐药相关S抗原变异、疫苗逃逸相关变异以及HBV特异性T细胞表位变异情况。 结果ADV耐药组与对照组患者人口学等指标差异无统计学意义。本组患者中42例rtA181T耐药变异关联的HBsAg变异均为sW172^*。在rtA181T/ sW172^*变异患者体内,该变异株在病毒准种中所占平均比率为（42.6 ± 22.1）%（12.2%~100%）。与非ADV耐药组患者相比,ADV耐药组患者发生HBsAg疫苗逃逸变异（χ² = 12.8736、P = 0.0003）以及T细胞抗原表位变异（χ² = 4.8344、P = 0.0279）几率显著升高。 结论我国ADV耐药患者rtA181T变异关联的HBsAg变异主要为sW172^*变异,HBsAg抗原疫苗逃逸变异以及T细胞抗原表位变异与ADV耐药相互影响,相关机制尚待进一步研究。     

Effect of levamisole supplementation on hepatitis B virus vaccination response in hemodialysis patients

Aim:   As an immune-modulating agent, levamisole has been reported to stimulate depressed T-cell activity, enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. There are a number of recent studies claiming that levamisole can improve response rate to hepatitis B virus (HBV) vaccination in haemodialysis patients. The present study has examined this hypothesis amongst some Iranian patients, using double-blind randomized clinical trial.
Methods:   During a 12 month period, 70 patients on maintenance haemodialysis with negative anti-hepatitis B surface antibody (HBsAb) and HBV core antibody (HBcAb), from four different dialysis centres were enrolled into the study. The patients were randomized to two groups. The first group (levamisole group) received 40 μg doses of recombinant HBV vaccine i.m. at 0, 1 and 6 months, plus 100 mg levamisole p.o., after each haemodialysis session. The second group (placebo group) received the same vaccination protocol, except for the placebo instead of levamisole. The patients were followed on serum HBsAb level. Those with an HBsAb level of above 10 mIU/mL, 1 month after the third dose of vaccination, were considered as responders.
Results:   The levamisole group was comprised of 38 patients and the placebo group of 32 patients. Thirty-one patients (81.6%) of levamisole group and 26 patients (81.3%) of placebo group responded to vaccination. The difference between two groups was not significant.
Conclusion:   This study indicated that in a haemodialysis population with high response to HBV vaccination, levamisole might have no significant effect in enhancing the response. Further studies with higher power can give more accurate results.     

Vaccination against hepatitis B in renal dialysis units: short or normal vaccination schedule?

Three I.M. injections of hepatitis B vaccine (Merck Sharp & Dohme) were administered, according to the recommended schedule (0, 1, 6 mos), to seronegative individuals of one renal dialysis unit (33 patients, 58 health care personnel) and, according to a shorter regimen (0, 1, 3 mos), in another unit of similar characteristics (30 patients, 53 health care personnel). Staff members and renal patients received, respectively, 20 y 40 mcg of vaccine per injection. In the early vaccination phase, the two regimens did not lead to a difference in seroconversion rates nor in anti-HBs titers. After a 9-month surveillance, lower seroconversion rates, although not significant, were observed with the accelerated regimen among staff members (84.2%) and renal patients (79.2%) as compared with 93% and 87.5%, respectively, following the normal schedule. At the same time, anti-HBs titers were significantly lower (p less than 0.001) in the staff (316 RIA U) and patients (93 U) vaccinated according to the short regimen than in their respective counterparts (4196 and 1047 U) assigned to the normal schedule. A fourth dose of vaccine given to subjects with low and no anti-HBs titers significantly increased seroconversion and anti-HBs levels, although with little success among the former non-responders.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.