Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool

The use of livers from anti-hepatitis B core (HBc) positive donors can alleviate donor shortage. Nineteen of 367 (6%) adults receiving anti-HBc positive allografts [three were hepatitis B antigen (HBsAg) negative, hepatitis B antibody (HBsAb) positive; four were HBsAg positive and 12 were not exposed to hepatitis B viral (HBV) infection] were retrospectively reviewed. In HBsAg negative recipients, immunoprophylaxis (IP) was guided by viral serology and immunohistochemistry (IH) of day 0 and day 7 liver biopsies. If IH was negative, IP was stopped. None of three HBsAg negative, HBsAb positive recipients infected; one (replicating) of four HBsAg positive recipients reinfected and seven of eight (87.5%) HBsAg, HBsAb negative recipients, who did not receive long-term IP, infected after a median time of 2 years (range 1-5); one patient died of liver failure. Four HBsAg, HBsAb negative recipients, receiving life-long IP, remained infection free. Anti-HBc positive donor livers must be directed selectively first to HBsAg positive recipients, next to recipients having HBV antibodies and finally to HBV-naive recipients. Identification of both donor and recipient risk factors for HBV infection before transplantation allows indiscriminate use of antiviral prophylaxis. The necessity for IP therapy should be guided by HBV-DNA testing of donor liver tissue and serum. IH of early liver biopsies is an unreliable marker for predicting antiviral treatment requirements.     

Prevention of hepatitis B virus recurrence after liver transplantation

Abstract:  Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.     

Prevention of perinatal hepatitis B transmission in Haimen City,China: Results of a community public health initiative

In regions where hepatitis B virus (HBV) is endemic, perinatal transmission is common. Infected newborns have a 90% chance of developing chronic HBV infection, and 1 in 4 will die prematurely from HBV-related liver disease. In 2010, the Hepatitis B Foundation and the Haimen City CDC launched the Gateway to Care campaign in Haimen City, China to improve awareness, prevention, and control of HBV infection citywide. The campaign included efforts to prevent perinatal HBV transmission by screening all pregnant women for hepatitis B surface antigen (HBsAg), following those who tested positive, and administering immunoprophylaxis to their newborns at birth. Of 5407 pregnant women screened, 185 were confirmed HBsAg-positive and followed until delivery. At age one, 175 babies were available for follow up testing. Of those, 137 tested negative for HBsAg and positive for antibodies to HBsAg, indicating protection. An additional 34 HBsAg-negative babies also tested negative for antibodies to HBsAg or had indeterminate test results, were considered to have had inadequate immune responses to the vaccine, and were given a booster dose. A higher prevalence of nonresponse to HBV vaccine was observed among babies born to hepatitis B e antigen (HBeAg)-positive mothers and mothers with high HBV DNA titers. The remaining 4 babies tested positive for HBsAg and negative for antibodies, indicative of active HBV infection. The mothers of all 4 had viral loads ≥8 × 10⁶ copies/ml in the third trimester. Although inadequate response or nonresponse to HBV vaccine was more common among babies born to HBeAg-positive and/or high viral load mothers, these risk factors did not completely predict nonresponsiveness. All babies born to HBV-infected mothers should be tested upon completion of the vaccine series to ascertain adequate protection. Some babies of HBeAg-positive mothers with high viral load may still become HBV infected despite timely immunoprophylaxis with HBV vaccine and HBIG.     

旋毛虫排泄分泌抗原的成分及应用价值

旋毛虫病是一种重要的人畜共患寄生虫病，长期以来用于免疫诊断和免疫预防的旋毛虫抗原，尤其是排泄分泌（ES）抗原引起了国内外众多学者的关注。本文综述了近年来旋毛虫ES抗原有效成分的研究及其在免疫诊断和免疫预防方面的应用价值，并且提出应用DNA重组技术在体外大量表达ES抗原和利用多肽合成技术在体外大量合成抗原用于免疫诊断和免疫预防将是今后的研究方向。     

被动免疫对HBV携带孕妇母婴传播及乳汁中HBVM的影响

目的探讨高效价乙肝免疫球蛋白（HBIG）被动免疫对乙肝病毒（HBV）母婴传播及HBV携带孕妇初乳中HBV感染性标志物（HBVM）的影响。方法将326例HBV携带而肝功能正常的孕妇按知情自愿原则分成2组，其中实验组210例，于孕晚期注射HBIG共3次；对照组116例，孕妇不接受HBIG注射。前瞻性追踪所有孕妇的新生儿外周血HBVM情况及产妇初乳中HBVM及HBV-DNA情况。结果试验组新生儿HBV宫内感染率为10．48％（22／210），对照组新生儿HBV宫内感染率为27．59％（32／116），二者比较差异有统计学意义（P：0．0000）。HBsAg单阳性的220例孕妇中，试验组和对照组新生儿HBV宫内感染率分别为7．64％和26．32％，二者比较差异有统计学意义（P=0．0000）。HBsAg和HBeAg均阳性的106例孕妇中，试验组和对照组新生儿HBV宫内感染率分别为22．73％和32．50％，二者比较差异无统计学意义（P〉0．05）。试验组产妇初乳中HBsAg阳性率、HBeAg阳性率和HBV．DNA滴度比对照组均低，但二者分别比较差异均无统计学意义（P〉0．05）。结论孕晚期HBIG被动免疫仅可降低HBsAg单阳孕妇HBV宫内传播率，而对HBsAg和HBeAg阳性孕妇并无明显阻断作用；HBIG被动免疫对HBV携带产妇初乳中HBVM及HBV-DNA无明显影响。     

The combination of X-ray-mediated radiosurgery and gene-mediated immunoprophylaxis for advanced intracerebral gliosarcomas in rats

Rats with advanced, imminently lethal, 4mm diameter, left-sided intracerebral 9L gliosarcoma (9LGS), a well characterized malignant tumor with some similarities to human high-grade astrocytomas, were used as a therapy model 14 days post-implantation of 10⁴ cells. Such tumor-bearing rats die within two weeks (median, 6 days) thereafter if untreated. However, if these tumors are exposed on day 14 to 12–25Gy of an electron-equilibrated 6MV photon beam (radiosurgery), survival is extended about 5–6 fold to a median of 34 days, but long-term survival (> 1 year) is increased only to 18%. Multiple subcutaneous inoculations of radiation-disabled 9LGS cells post-radiosurgery (immunoprophylaxis) extended lifespan and long-term (> 1 year) survival minimally (median, 37 days; 25%, respectively). In sharp contrast, radiosurgery followed by multiple subcutaneous inoculations of radiation-disabled 9LGS cells that had been transfected with granulocyte macrophage colony stimulating factor (GMCSF), a cytokine with demonstrated immune-enhancing properties (i.e. gene-mediated immunoprophylaxis, GMIMPR) increased long-term survival to 67%. To our knowledge, these results are the first to show that the combination of photon radiosurgery and GMIMPR is effective for an advanced, imminently lethal brain tumor in a mammal. These data raise the possibility that GMIMPR following radiation therapy might prove effective for the treatment of some human malignant gliomas.     

Cost-effective and safe ambulatory long-term immunoprophylaxis with intramuscular instead of intravenous hepatitis B immunoglobulin to prevent reinfection after orthotopic liver transplantation

BACKGROUND: Hepatitis B (HBV)-infected patients receive an anti-HBs immunoprophylaxis [hepatitis B immunoglobulin (HBIG) titre of more than 100 IU/L] in combination with lamivudine to prevent reinfection after orthotopic liver transplantation (OLT). In comparison with intramuscular (i.m.) HBIG, costs for intravenous (i.v.) HBIG are found to be extremely high. We therefore studied patients' outcome (i) after a switch from i.v. to i.m. HBIG and (ii) the outcome after the patients were initially treated with i.m. HBIG after discharge from the hospital. METHODS: (i) Six outpatients were switched from 2000 IU i.v. HBIG (Hepatect) administered every 2 wk to 2000 IU i.m. HBIG (Hepatitis-B-Immunoglobulin Behring) given once a month. (ii) Six other outpatients were directly treated with i.m. HBIG every 4 wk after OLT. All patients also received 100 mg lamivudine/d. RESULTS: Patients switched from i.v. to i.m. HBIG had stable anti-HBs titres (i.v. HBIG: 180 +/- 37 IU/L vs. i.m. HBIG: 173 +/- 23 IU/L). Patients directly treated with i.m. HBIG also had sufficient anti-HBs titres (176 +/- 31 IU/L). Intramuscular application of HBIG was well tolerated by all patients and no side-effects were observed in patients receiving i.m. HBIG. In comparison with the protocol using i.v. HBIG, the costs of i.m. treatment were 60% lower. CONCLUSION: Long-term administration of i.m. HBIG saves up to 60% of the usual costs for i.v. prophylaxis of HBV reinfection in patients after OLT. In combination with lamivudine, long-term i.m. HBIG therapy is as efficient as i.v. HBIG treatment, but its lower costs clearly favour its use in preventing HBV reinfection after OLT.     

乙型肝炎病毒感染母亲的新生儿免疫预防后远期保护效果

目的:探讨母亲感染乙型肝炎病毒(HBV)后,新生儿免疫预防措施及远期保护效果。方法:选择2013年1月至2014年12月定期产检并顺利分娩的240例HBV感染孕产妇及其新生儿(240例)作为研究对象。将接受免疫预防措施的120例孕产妇及其新生儿作为观察组,将未接受免疫预防措施的120例孕产妇及其新生儿作为对照组。比较2组新生儿HBV感染率,出生时、出生1年后乙型肝炎表面抗体(HBsAb)阳性率。随访5年,根据新生儿免疫预防效果,将母亲分为免疫成功组和失败组,分析影响免疫预防效果的因素。结果:观察组新生儿HBV感染率为0,低于对照组的16.67%(P0.05);出生时、出生1年后,观察组新生儿HBsAb阳性率分别为22.50%、96.67%,高于对照组(5.00%、78.33%,P0.001);观察组5年内加强接种乙肝疫苗率为26.67%,低于对照组(55.00%,P0.001)。免疫成功组与失败组母亲血清乙型肝炎病毒e抗原(HBeAg)滴度、HBV-DNA浓度、是否使用抗病毒药物、病毒变异情况差异均有统计学意义(P0.05)。结论:同时给予HBV感染孕产妇及其新生儿乙型肝炎免疫球蛋白(HBIg)、乙肝疫苗预防HBV母婴传播,可有效降低新生儿感染HBV风险,提高HBsAb阳性率,获得远期保护效果。     

Is vaccine therapy the future in cancer prevention?

One vaccine designed to prevent cancer by preventing a precursor infection is already in common use, and at least one more is in the latter stages of clinical development. These vaccines are part of a new era of cancer immunoprophylaxis. Several further vaccines are in preclinical and clinical development, targeted at preventing cancer precursor infections, and these should add to our ability to prevent this common human disorder. However, vaccines to prevent cancers not triggered by infection are a more remote prospect, for a variety of reasons.     

Immunoprophylactic potential of a 120 kDa Brugia malayi adult antigen fraction, BmA-2, in lymphatic filariasis

A 120 kDa antigen containing SDS-PAGE fraction BmA-2 isolated from Brugia malayi adult parasite was highly reactive with normal sera from filarial endemic area. BmA-2 was analysed for its propylactic potential in in vitro and in vivo. Sera collected from BmA-2 immunized jirds induced a significant level (80 to 90%) of protection against infective larvae and microfilariae in in vitro ADCC assay as well as in in situ micropore chamber implantation studies. Mastomys natalensis immunized with BmA-2 showed a significant level of protective response against circulating microfilariae by clearing 90% of them from circulation by fifth day after challenge infection. Immunization of jirds with BmA-2 resulted in an enhanced level of antibody response against BmA-2 and 88% reduction in the development of the parasites to the adult stage. Passive transfer of immunesera from jirds immunized with BmA-2 to naive jirds resulted in 71% reduction in adult worm recovery as observed 90 days after challenge infection with B. malayi. On the other hand the passive transfer of nonadherent spleen cells from immune jirds did not show any significant effect on the development of parasite. Administration of jirds anti BmA-2 serum to microfilaraemic jirds showed a temporary decrease in micrqfilarial count which was increased to pretherapeutic level within 100 days and there was no effect on the adult worms. This implies that the immune protective effect of BmA-2 is mainly antibody dependent and active immunization with BmA-2 is effective against filarial infection.,