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 mul...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.展开更多
AIM To explore the role of killer immunoglobulin receptor(KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus.METHODS We recruited 101 voluntary participants between March 2010 ...AIM To explore the role of killer immunoglobulin receptor(KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus.METHODS We 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 ofinfection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction.RESULTS Sera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection(≥ 10 mI U/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 mI U/ml, 22%(16/74) had antiHBs ranging between 10-100 mI U/ml, and 20%(15/74) had values of less than 10 mI U/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 KIR3 Dl 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. KIR2Dl5 B was significantly different among different groups of vaccinated participants(group Ⅰ > 100 mI U/ml, group Ⅱ 10-100 mI U/ml, group Ⅲ < 10 mI U/ml and group Ⅳ with undetectable levels of protective antibodies). CONCLUSION To 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.展开更多
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...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。展开更多
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...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.展开更多
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 preve...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.展开更多
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 transplan...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.展开更多
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 hepatocel...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.展开更多
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 firs...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.展开更多
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 a...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.展开更多
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 patien...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.展开更多
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 t...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.展开更多
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,th...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.展开更多
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 ...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].展开更多
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,...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.展开更多
It has been accepted that bone marrow transplantation (BMT) is the only curative therapeutic option for certain hematologic malignancies. The southeast Asia region is an endemic area of hepatitis B virus (HBV) infecti...It has been accepted that bone marrow transplantation (BMT) is the only curative therapeutic option for certain hematologic malignancies. The southeast Asia region is an endemic area of hepatitis B virus (HBV) infection; thus, BMT using a hepatitis B surface antigen (HBsAg)- positive donor is occasionally unavoidable. Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation. In this report, a four-level approach was designed for a patient with chronic myeloid leukemia, beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor. Prior to BMT, the HBV viral load of the donor was reduced to an undetectable level by antiviral therapy. After BMT, hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug, lamivudine. One year after discontinuation of lamivudine, the patient is still free of HBV infection.展开更多
BACKGROUND Patients with chronic hepatitis B(CHB)with long-term nucleos(t)ide therapy may experience renal insufficiency.Traditional renal function indicators,such as urine protein,serum urea nitrogen(BUN),and serum c...BACKGROUND Patients with chronic hepatitis B(CHB)with long-term nucleos(t)ide therapy may experience renal insufficiency.Traditional renal function indicators,such as urine protein,serum urea nitrogen(BUN),and serum creatinine,are normal when early mild lesions occur.Therefore,more sensitive renal function indicators are needed.AIM To investigate the significance of early renal injury indicators in evaluating renal injury in patients with CHB with long-term nucleos(t)ide therapy.METHODS We collected the clinical data of 69 outpatients with CHB at Peking University First Hospital from March 2018 to January 2020 who had been treated with longterm nucleos(t)ide therapy and analyzed the results of early renal injury indicators.Continuous normal distribution data were analyzed by the t-test to determine the difference between two groups.Continuous non-normally distributed data were analyzed by the Mann-Whitney U-test between two groups.The Kruskal-Wallis H test was used to determine the differences among multiple groups.Enumeration data were analyzed by the chi-square test.The related factors of early renal injury indicators were analyzed by logistic regression analysis.RESULTS The average treatment duration with nucleos(t)ide analogs of the 69 patients with CHB was 99.7±28.7 mo.The cases of patients with elevated BUN and hypophosphatemia were 6(8.7%)and 13(18.8%),respectively;31(44.9%)patients had abnormal early renal injury indicators,including 9 patients with abnormal urine microalbumin,7 patients with abnormal urine immunoglobulin,6 patients with abnormal urine transferrin,and 19 patients with abnormalα1 microglobulin.There were no significant differences in the mean values of age,sex,BUN,estimated glomerular filtration rate(eGFR),serum uric acid,serum calcium,or serum phosphorus between the two groups of patients with and without early renal injury indicators.However,the mean levels of serum creatinine and urine creatinine,N-acetyl-β-D-glucosidase enzyme,α1 microglobulin,and urine immunoglobulin in the former group of patients were significantly higher than those in the latter group of patients(P<0.05).The incidence of early renal injury in patients with eGFR≥90,60-89,and 30-59 mL/(min·1.73 m2)was 36.4%(8/22),47.6%(20/42),and 60%(3/5),respectively.Logistic regression analysis results showed that gamma-glutamyl transpeptidase[odds ratio(OR)=1.05(1.008-1.093),P=0.020],direct bilirubin[OR=1.548(1.111-2.159),P=0.010],serum creatinine[OR=1.079(1.022-1.139),P=0.006],and age[OR=0.981(0.942-1.022),P=0.357]were independent predictors of early renal injury.CONCLUSION Patients with CHB treated with long-term nucleos(t)ide analog therapy had a high probability of early renal injury,and early renal injury indicators were highly sensitive and could be used to monitor early renal impairment.展开更多
文摘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.
基金Supported by The University Review Board at the American University of Beirut,No.A88507the Lebanese National Council for Scientific Research,No.A522185
文摘AIM To explore the role of killer immunoglobulin receptor(KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus.METHODS We 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 ofinfection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction.RESULTS Sera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection(≥ 10 mI U/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 mI U/ml, 22%(16/74) had antiHBs ranging between 10-100 mI U/ml, and 20%(15/74) had values of less than 10 mI U/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 KIR3 Dl 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. KIR2Dl5 B was significantly different among different groups of vaccinated participants(group Ⅰ > 100 mI U/ml, group Ⅱ 10-100 mI U/ml, group Ⅲ < 10 mI U/ml and group Ⅳ with undetectable levels of protective antibodies). CONCLUSION To 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.
文摘目的: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。
基金supported by grants from the Key Program of National Natural Science Foundation of China(30730085)the National High Technology Research and Development Program of China (863 Program2006AA 02A412)
文摘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.
文摘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.
文摘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.
基金the Canadian Cancer Society, Environment-Cancer Fundthe Canadian Institutes of Health Research for operating research grant support
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by A Grant-in-Aid for the Research of Hepatitis and BSE from the Japanese Ministry of Health,Labour and Welfare
文摘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.
基金Project supported by the grant from Science Foundation of Ministry of Health of China, No. 96-1-347.
文摘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].
文摘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.
文摘It has been accepted that bone marrow transplantation (BMT) is the only curative therapeutic option for certain hematologic malignancies. The southeast Asia region is an endemic area of hepatitis B virus (HBV) infection; thus, BMT using a hepatitis B surface antigen (HBsAg)- positive donor is occasionally unavoidable. Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation. In this report, a four-level approach was designed for a patient with chronic myeloid leukemia, beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor. Prior to BMT, the HBV viral load of the donor was reduced to an undetectable level by antiviral therapy. After BMT, hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug, lamivudine. One year after discontinuation of lamivudine, the patient is still free of HBV infection.
基金Supported by the National 12th Five-Year Plan for Science and Technology,No.2018ZX10725-506.
文摘BACKGROUND Patients with chronic hepatitis B(CHB)with long-term nucleos(t)ide therapy may experience renal insufficiency.Traditional renal function indicators,such as urine protein,serum urea nitrogen(BUN),and serum creatinine,are normal when early mild lesions occur.Therefore,more sensitive renal function indicators are needed.AIM To investigate the significance of early renal injury indicators in evaluating renal injury in patients with CHB with long-term nucleos(t)ide therapy.METHODS We collected the clinical data of 69 outpatients with CHB at Peking University First Hospital from March 2018 to January 2020 who had been treated with longterm nucleos(t)ide therapy and analyzed the results of early renal injury indicators.Continuous normal distribution data were analyzed by the t-test to determine the difference between two groups.Continuous non-normally distributed data were analyzed by the Mann-Whitney U-test between two groups.The Kruskal-Wallis H test was used to determine the differences among multiple groups.Enumeration data were analyzed by the chi-square test.The related factors of early renal injury indicators were analyzed by logistic regression analysis.RESULTS The average treatment duration with nucleos(t)ide analogs of the 69 patients with CHB was 99.7±28.7 mo.The cases of patients with elevated BUN and hypophosphatemia were 6(8.7%)and 13(18.8%),respectively;31(44.9%)patients had abnormal early renal injury indicators,including 9 patients with abnormal urine microalbumin,7 patients with abnormal urine immunoglobulin,6 patients with abnormal urine transferrin,and 19 patients with abnormalα1 microglobulin.There were no significant differences in the mean values of age,sex,BUN,estimated glomerular filtration rate(eGFR),serum uric acid,serum calcium,or serum phosphorus between the two groups of patients with and without early renal injury indicators.However,the mean levels of serum creatinine and urine creatinine,N-acetyl-β-D-glucosidase enzyme,α1 microglobulin,and urine immunoglobulin in the former group of patients were significantly higher than those in the latter group of patients(P<0.05).The incidence of early renal injury in patients with eGFR≥90,60-89,and 30-59 mL/(min·1.73 m2)was 36.4%(8/22),47.6%(20/42),and 60%(3/5),respectively.Logistic regression analysis results showed that gamma-glutamyl transpeptidase[odds ratio(OR)=1.05(1.008-1.093),P=0.020],direct bilirubin[OR=1.548(1.111-2.159),P=0.010],serum creatinine[OR=1.079(1.022-1.139),P=0.006],and age[OR=0.981(0.942-1.022),P=0.357]were independent predictors of early renal injury.CONCLUSION Patients with CHB treated with long-term nucleos(t)ide analog therapy had a high probability of early renal injury,and early renal injury indicators were highly sensitive and could be used to monitor early renal impairment.