Exploring the impact of hepatitis B immunoglobulin and antiviral interventions to reduce vertical transmission of hepatitis B virus

Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.

Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey

BACKGROUND Hepatitis B immunoglobulin(HBIG)in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus(HBV)reinfection after liver transplantation for HBV-associated disease.AIM To evaluate patients’satisfaction,preferences,and requirements for subcutaneous(SC),intramuscular(IM),and intravenous(IV)HBIG treatments.METHODS A self-completion,cross-sectional,online,22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France,Italy,and Turkey.Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint(trade-off)exercise.RESULTS Ninety patients were enrolled;32%,17%,and 51%were SC,IM,and IV HBIG users,respectively.Mean duration of treatment was 36.2 months.SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient,easiest to administer,least painful,and had the highest self-rating of treatment compliance.More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive(67%,28%,and 28%,respectively).In the target product profile assessment,76%of patients were likely to use hypothetical SC HBIG.In the conjoint exercise,administration route,frequency,and duration were key drivers of treatment preferences.CONCLUSION Ease,frequency,duration,and side effects of HBIG treatment administration were key drivers of treatment preferences,and SC HBIG appeared advantageous over IM and IV HBIG for administration ease,convenience,and pain.A hypothetical SC HBIG product elicited a favorable response.Patient demographics,personal preferences,and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti

BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by 2030.Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti city.METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants.The study ran from January 2021 to May 2022,and infants were followed up to 7 mo of age.HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,Strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth.These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis.Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response.All statistical analyses were performed with version 4.0.1 of the R software.RESULTS Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 years.The MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/mL.Of the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HB<100 mIU/mL)after HBV vaccination and hepatitis B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels(>200000 IU/mL)and hepatitis B e antigen-positive status(odds ratio=158,95%confidence interval:5.05-4958,P<0.01).Birth weight<2500 g was associated with a poor immune response to vaccination(odds ratio=34,95%confidence interval:3.01-383.86,P<0.01).CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target,this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV.Therefore,further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

肝移植术后乙肝主动免疫重建受者停用HBIG和(或)核苷(酸)类似物的长期安全性和有效性

目的探讨乙型病毒性肝炎(乙肝)相关疾病肝移植受者接种乙肝疫苗成功后长期停用乙型肝炎免疫球蛋白(HBIG)和(或)核苷(酸)类似物(NAs)预防乙型肝炎病毒(HBV)再感染的安全性及有效性。方法回顾性分析76例接种乙肝疫苗后成功重建乙肝主动免疫的肝移植受者的基本资料,分析疫苗接种及应答情况、应答者停用HBIG和(或)NAs的随访结果、停用HBIG和(或)NAs后HBV再感染情况。结果肝移植术后至开始接种乙肝疫苗的时间间隔为26(20,40)个月。接种疫苗至应答时间为15(8,27)个月。初始76例受者全部停用HBIG,36例受者停用HBIG和NAs。随访期间,76例停用HBIG受者中12例恢复使用HBIG,36例停用HBIG和NAs者中16例恢复使用NAs。HBIG和NAs停用时间分别为135(98,150)个月与133(34,149)个月。16例应答者未接种过加强针,36例应答者定期接种加强针,第1次接种加强针的时间距离停用HBIG的间隔时间为44(11,87)个月,未接种加强针和接种加强针的应答者一般资料比较差异均无统计学意义(均为P>0.05)。截至随访日,9例受者失访,5例HBV再感染,3例受者死亡,1例受者移植物丢失并进行二次肝移植。5例HBV再感染受者中4例发生病毒变异。再感染者与未感染者是否停用过NAs、移植前乙型肝炎e抗原(HBeAg)是否为阳性差异有统计学意义(均为P<0.05)。结论乙肝相关疾病肝移植术后乙肝主动免疫重建成功的受者长期停用HBIG是可行和安全的,但能否同时停用NAs还需要进一步研究。

A randomized controlled clinical trial: Interruption of intrauterine transmission of hepatitis B virus infection with HBIG

AIM： To evaluate the efficacy of interruption of intrauterine infection of HBV with HBIG in pregnant women with positive HBeAg and HBsAg.METHODS： A prospective randomized controlled trial was adopted. Sixty cases with positive HBeAg and HBsAg were coincident with the criteria of inclusion, and 8 cases were excluded. Fifty-two cases were analyzed （28 cases in trial group and 24 in control group）. All cases in trial group received 200 IU HBIG intravenously every 4 wk for 3 times from the 28^th wk. The cases of control group received placebo in the same way. All pregnant women were detected for HBeAg and HBV-DNA at the beginning of the trial and end of the trial （delivery）. The cord blood of all newborns were collected for detecting HBeAg and HBV-DNA simultaneously.RESULTS： For investigation of HBeAg of newborns in trial group, 6 of 28 cases of newborns had positive HBeAg, the HBeAg positive rate being 21.4%, the total rate of 95% CI being 8%-41%. In control group, 19 of 24 cases of newborns had positive HBeAg, HBeAg positive rate was 79.2%, the rate of 95%CI being 5%-93%. By statistical analysis, 2= 17.26, P 〈 0.01, RR = 0.27, 95% CI （6.3 × 10^-6, 8.6 × 10^-5）. For investigation of HBV-DNA of newborns in trial group, 7 of 28 cases of newborns had positive HBV-DNA, HBV-DNA positive rate being 25%, the total rate of 95% CI being 11%-45%. In control group, 20 of 24 cases of newborns had positive HBV-DNA, HBV-DNA positive rate was 83.3%, the total rate of 95% CI being 63%-95%. By statistical analysis, X^2 = 17.62, P 〈 0.01, RR = 0.30, 95% CI （1.5 × 10^-5, 1.7× 10^-4）. The results indicated that there was significant difference in HBeAg positive rate and HBV-DNA positive rate of newborns between the two groups. In trial group, 7 of 28 newborns had HBV-DNA positive, but the HBV-DNA load of newborns was lower than that of their mothers. In control group, 20 of 24 newborns still had HBV-DNA positive, and the HBV-DNA load of newborns was close to those of their mothers. Statistical analysis indicated that there was no significant difference in HBV- DNA load between postnatal women without HBIG intervention and their filial generations （T = 81.5, P 〉 0.1）. CONCLUSION： It is effective and safe to prevent intrauterine infection of HBV with HBIG from the 28^th wk in pregnant women with positive HBeAg and HBsAg. In clinical application, those pregnant women with negative HBeAg and positive HBV-DNA also need to be interrupted by HBIG.

Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon

AIMTo explore the role of killer immunoglobulin receptor (KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus. METHODSWe recruited 101 voluntary participants between March 2010 and December 2011. Sera samples from vaccinated and non-vaccinated participants were tested for the presence of anti-HBs antibodies as a measure of protection against hepatitis B, hepatitis B surface antigen and hepatitis B core antibody as indicators of infection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction. RESULTSSera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection (&ge; 10 mIU/mL) following vaccination as defined by the World Health Organization international reference standard. Among the vaccinated participants, 47% (35/74) had anti-HBs titers above 100 mIU/mL, 22% (16/74) had anti-HBs ranging between 10-100 mIU/mL, and 20% (15/74) had values of less than 10 mIU/mL. We report the lack of significant association between the number of vaccine dosages and the titer of antibodies among our vaccinated participants. The inhibitory KIR2DL1, KIR2DL4, KIR3DL1, KIR3DL2, and KIR3DL were detected in more than 95%, whereas KIR2DL2, KIR2DL3, KIR2DL5 (KR2DL5A and KIR2DL5B) were expressed in 56%, 84% and 42% (25% and 29%) of participants, respectively. The observed frequency of the activating KIR genes ranged between 35% and 55% except for KIR2DS4, detected in 95% of the study participants (40.6% 2DS4*001/002; 82.2% 2DS4*003/007). KIR2DP1 pseudogene was detected in 99% of our participants, whereas KIR3DP*001/02/04 and KIR3DP1*003 had frequencies of 17% and 100%, respectively. No association between the frequency of KIR genes and anti-HBs antibodies was detected. When we compared the frequency of KIR genes between vaccinated individuals with protective antibodies titers and those who lost their protective antibody levels, we did not detect a significant difference. KIR2DL5B was significantly different among different groups of vaccinated participants (group I > 100 mIU/mL, group II 10-100 mIU/mL, group III CONCLUSIONTo our knowledge, this is the first study screening for the possible role of KIR genes among individuals vaccinated against hepatitis B virus (HBV). Our results can be used to design larger studies to better understand the role of KIR genes in protection against or susceptibility to HBV post vaccination.

LAM联合HBIG在HBV母婴传播中的阻断效果及安全性

目的:研究拉米夫定(Lamivudine,LAM)联合乙型肝炎免疫球蛋白(hepatitis B immunoglobulin,HBIG)对乙型肝炎病毒(hepatitis B virus,HBV)母婴传播的阻断效果及安全性。方法:回顾性选取2017年12月—2019年12月麻城市人民医院105例HBV感染孕妇为样本。根据治疗方案不同将其分为联合组(n=74)和LAM组(n=31)。LAM组接受LAM治疗,联合组接受LAM联合HBIG治疗。比较两组治疗前及临产前HBV标志物(HBVM)水平、HBV-DNA载量、肝功能指标,新生儿健康情况,新生儿HBV感染情况。分析药物安全性。结果:临产前,两组HBcAb、HBeAg及HBV-DNA水平均明显降低(P<0.05),且联合组HBeAg和HBV-DNA水平均低于LAM组(P<0.05)。临产前,两组谷丙转氨酶(ALT)、谷草转氨酶(AST)及总胆红素(TBIL)水平均明显升高(P<0.05),两组ALT、AST及TBIL水平比较差异均无统计学意义(P>0.05)。两组新生儿体重、10 min Apgar评分及新生儿肺炎、窒息和畸形发生率比较差异均无统计学意义(P>0.05)。接种疫苗前,联合组新生儿HBsAg阳性率低于LAM组(P<0.05),接种疫苗后1个月,两组HBsAg阳性率均明显降低,两组HBs Ag和抗-HBs阳性率比较差异均无统计学意义(P>0.05)。治疗期间,联合组孕妇发生一过性ALT水平轻度升高1例(1.89%),新生儿黄疸1例(1.89%),肌酸激酶升高2例(3.77%);LAM组孕妇未见明显异常,新生儿发生高胆红素血症1例(1.89%),均未予特殊处理,观察1周后自行恢复正常。结论:LAM联合HBIG阻断HBV母婴垂直传播可有效降低孕妇血液中病毒滴度和复制水平,降低新生儿宫内感染风险。

Clinical management of hepatitis B virus infection correlated with liver transplantation

BACKGROUND: As a radical cure for post-hepatitis B virus (HBV)-related liver cirrhosis and hepatocellular carcinoma, liver transplantation has been applied in many medical centers. Before the use of effective measures, hepatitis B recurrence and the existence of HBsAg(+) donors, patients with hepatitis B-related diseases are contraindicated for liver transplantation. Application of interferon, hepatitis B immunoglobulin (HBIG), and nucleotide analogues (e.g., lamivudine) has made great progress in the clinical care of HBV. However, there are still many shortcomings such as low viral suppression rate, rising expense, and the induction of HBV tyrosine-methionine-aspartate-aspartate (YMDD) mutation. This article systematically reviews the current evidence that immunotherapy, conventional drug combinations, and some special fields of HBV infection correlate with liver transplantation. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords 'hepatitis B virus', 'hepatitis B vaccination', 'lamivudine', 'adefovir', 'entecavir', 'tenofovir', 'HBV genotype', and 'liver transplantation' up to October 2009. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Hepatitis B vaccine and human monoclonal antibody have very good clinical prospects. Compared with traditional therapies, the new medical regimens have many benefits such as boosting viral suppression rate and decreasing medical expenses. The triple therapy for YMDD mutation also has an excellent therapeutic effect and a low barrier to resistance. New nucleos(t)ide analogues (entecavir and tenofovir) eliminate virus more effectively with few adverse reactions, and may replace lamivudine or HBIG in future. CONCLUSIONS: Hepatitis B vaccine needs further large-scale and rigorous randomized controlled trials to confirm its effective dose and injection frequency. Monoclonal antibody is still experimental, and the next step is to carry out the relevant animal and human studies. A consensus standard regimen for the treatment of hepatitis B should be developed.

Review of the pharmacological management of hepatitis B viral infection before and after liver transplantation

The progress in treatment against hepatitis B virus(HBV)with the development of effective and well tolerated nucleotide analogues(NAs)has improved the outcome of patients with HBV decompensated cirrhosis and has prevented post-transplant HBV recurrence.This review summarizes updated issues related to the management of patients with HBV infection before and after liver transplantation(LT).A literature search using the PubMed/Medline databases and consensus documents was performed.Pre-transplant therapy has been initially based on lamivudine,but entecavir and tenofovir represent the currently recommended first-line NAs for the treatment of patients with HBV decompensated cirrhosis.After LT,the combination of HBV immunoglobulin(HBIG)and NA is considered as the standard of care for prophylaxis against HBV recurrence.The combination of HBIG and lamivudine is related to higher rates of HBV recurrence,compared to the HBIG and entecavir or tenofovir combination.In HBIG-free prophylactic regimens,entecavir and tenofovir should be the first-line options.The choice of treatment for HBV recurrence depends on prior prophylactic therapy,but entecavir and tenofovir seem to be the most attractive options.Finally,liver grafts from hepatitis B core antibody(anti-HBc)positive donors can be safely used in hepatitis B surface antigen negative,preferentially anti-HBc/anti-hepatitis B surface antibody positive recipients.

Reactivation of hepatitis B after liver transplantation: Current knowledge, molecular mechanisms and implications in management

Chronic hepatitis B(CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma(HCC). Liver transplantation(LT) is considered gold standard for treatment of hepatitis B virus(HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin(HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressingviral replication and improving long-term survival. The combination of lamivudine(LAM) plus HBIG has been for many years the most widely used. However, life-long HBIG use is both cumbersome and costly, whereas long-term use of LAM results in resistant virus. Recently, in an effort to develop HBIG-free protocols, high potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried either as monotherapy or in combination with low-dose HBIG with excellent results. Current focus is on novel antiviral targets, especially for covalently closed circular DNA(ccc DNA), in an effort to eradicate HBV infection instead of viral suppression. However, there are several other molecular mechanisms through which HBV may reactivate and need equal attention. The purpose of this review is to address post-LT HBV reactivation, its risk factors, underlying molecular mechanisms, and recent advancements and future of anti-viral therapy.

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation

BACKGROUND: Hepatitis B virus reinfection is an impor-tant problem after liver transplantation. The aim of thisstudy was to discuss the prevention of hepatitis B virus rein-fection following orthotopic liver transplantation.METHODS: Sixty-eight cases of chronic fulminant hepatitisB, end-stage liver cirrhosis, and liver carcinoma complicat-ed with HBV cirrhosis were given anti-viral drugs beforeand after transplantation to prevent hepatitis B virus rein-fection. Lamivudine was administered in 2 patients, lami-vudine + hepatitis B immunoglobulin ( HBIG ) in 63, andadefovir + HBIG in 3. The measurement of serum HBV,HBV DNA, liver biopsy immunohistochemistry and clini-cal study were performed.RESULTS: In 1 of the 2 patients who developed reinfectionafter lamivudine administration, serum HBsAg, HBeAb,HBcAb, HBV DNA were positive and liver biopsy immu-nohistochemistry showed HBsAg phenotype. In 2 of 63 pa-tients who developed reinfection after use of lamivudine +HBIG, serum HBsAg, HBeAb, HBcAb were positive andliver biopsy immunohistochemistry showed HBsAg pheno-type. Serum HBV DNA was positive in one of them.Three patients developed no reinfection with HBV after useof adefovir.CONCLUSIONS: Orthotopic liver transplantation is effectivein the treatment of HBV-infected diseases. Lamivudine +HBIG or adefovir + HBIG could effectively prevent hepatitisB virus reinfection.

Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation

Prophylactic strategies against hepatitis B virus(HBV) recurrence after liver transplantation(LT) are essential for patients with HBV-related disease.Before LT, lamivudine(LAM) was proposed to be down-graded from first-to second-line therapy.In contrast, adefovir dipivoxil(ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance.Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy.Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT.After LT, low-dose intramuscular hepatitis B immunoglobulin(HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers.With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.

Humoral and cellular immunogenecity of DNA vaccine based on hepatitis B core gene in rhesus monkeys

INTRODUCTIONHepatitis B virus (HBV) is the most commonetiologic agent for infectious liver diseases. It isestimated that there are more than 250 millionchronic HBV carriersin the world today and thereis a significant association among persistentinfection, liver cirrhosis and hepatocellularcarcinoma[1-3].

Hepatitis B surface antigen escape mutations: Indications for initiation of antiviral therapy revisited

Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. Herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection.

Management of hepatitis B virus infection after liver transplantation

Chronic hepatitis B virus(HBV) infection is responsible for up to 30% of cases of liver cirrhosis and up to 53% of cases of hepatocellular carcinoma. Liver transplantation(LT) is the best therapeutic option for patients with end-stage liver failure caused by HBV. The success of transplantation, though, depends on receiving prophylactic treatment against post-transplant viral reactivation. In the absence of prophylaxis, liver transplantation due to chronic hepatitis B(CHB) is associated with high rates of viral recurrence and poor survival. The introduction of treatment with hepatitis B immunoglobulins(HBIG) during the 1990 s and later the incorporation of oral antiviral drugs have improved the prognosis of these patients. Thus, LT for CHB is now a universally accepted option, with an estimated 5 years survival of around 85% vs the 45% survival seen prior to the introduction of HBIG. The combination of lamivudine plus HBIG has for many years been the most widely used prophylactic regimen. However, with the appearance of new more potent oral antiviral agents associated with less resistance(e.g., entecavir and tenofovir) for the treatment of CHB, new prophylactic strategies are being designed, either in combination with HBIG or alone as a monotherapy. These advances have allowed for more personalized prophylaxis based on the individual risk profile of a given patient. In addition, the small pool of donors has required the use of anti-HBc-positive donors(with the resulting possibility of transmitting HBV from these organs), which has been made possible by suitable prophylactic regimens.

Current evidence on the management of hepatitis B in pregnancy

Hepatitis B virus(HBV) infection is one of the main public health problems across the globe,since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries,nevertheless the infection is still widespread also in its active form. In the areas of high endemicity(prevalence of hepatitis B surface antigen positivity > 7%),mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore,the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy,with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.

Prophylactic managements of hepatitis B viral infection inliver transplantation

Liver transplantation(LT)is a considerably effective treatment for patients with end-stage hepatitis B virus(HBV)-related liver disease.However,HBV infection often recurs after LT without prophylaxis.Since the1990s,the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin(HBIG)and nucleos(t)ide analogues(NAs),resulting in improved patient survival.The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence.However,mainly due to the high cost of HBIG treatment,an alternative protocol for reducing the dose and duration of HBIG has been evaluated.Currently,combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection.Recently,NA monotherapy and withdrawal of HBIG from combination therapy,along with the development of new,potent high genetic barrier NAs,have provided promising efficacy,especially for low-risk recipients.This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors.In addition,challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed.

EFFECTS OF ACUPUNCTURE ON THE IMMUNOLOGICAL FUNCTIONS IN HEPATITIS B VIRUS CARRIERS

A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.

Protocol liver biopsies in long-term management of patients transplanted for hepatitis B-related liver disease

AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis （CH） B after LT was classified as minimal, mild, moderate or severe. RESULTS： HBV recurred in 7/42 （16.6%） patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg＋/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients （7.1%）, minimal/non-specific changes were observed in 18 （64.2%）, and at least 1 biopsy showed CH in the remaining 8 （28.5%）. Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg＋ or HBsAg- liver diseases.CONCLUSION： Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.