Low incidence of acute rejection in hepatitis B virus positive liver transplant recipients and the impact of hepatitis B immunoglobulin

Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects.We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions.In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5–2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection.     

Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients

Background/Aims

We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease.

Methods

Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR.

Results

Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity.

Conclusions

Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.     

Anti-HBc IgM bei akuter und chronischer Hepatitis-B-Virus-Infektion

Summary Hepatitis B core antigen (HBcAg) synthesized in E. coli was used for determination of immunoglobulin M class-specific antibodies against HBcAg. It was found that 98% of cases with acute hepatitis B surface antigen (HBsAg) positive hepatitis type B were anti-HBc immunoglobulin M (IgM) positive. Atypical hepatitis B was detected in 33% of anti-HBc-positive HBsAg-negative cases with acute hepatitis. Anti-HBc IgM was positive for 6 months in acute resolving hepatitis type B, whereas cases resulting in chronic hepatitis B remained anti-HBc IgM-positive for up to 900 days. Chronic HBsAg carriers with severe liver disease had anti-HBc IgM more often than individuals with minor liver damage; 83% of HBsAg-positive liver cirrhoses, 63% of chronic aggressive hepatitis, 50% of HBsAg-positive liver carcinoma, but only 17% of chronic persistent hepatitis or 7% of healthy blood donors were anti-HBc IgM-positive. Determination of anti-HBc IgM is useful in detecting atypical hepatitis B virus infections without HBsAg in serum and, with some restrictions, in discriminating acute and chronic hepatitis type B.

     

Long-term incidence and predictors of hepatitis B surface antigen loss after discontinuing nucleoside analogues in noncirrhotic chronic hepatitis B patients

ObjectiveTo investigate the long-term incidence and predictors for hepatitis B surface antigen (HBsAg) loss after nucleoside analogue therapy.MethodsThe study included 411 noncirrhotic chronic hepatitis B patients (148 hepatitis B e antigen (HBeAg)-positive and 263 HBeAg-negative patients) who were treated with lamivudine (n = 110) or entecavir (n = 301) with posttreatment follow-up of at least 12 months.ResultsIn HBeAg-positive patients, the 8-year cumulative rates of virologic relapse, clinical relapse and HBsAg loss were 55.6%, 47.7% and 19.6%, respectively. In HBeAg-negative patients, the rates were 69.3%, 58.9% and 33.1%, respectively. Cox regression analysis showed that hepatitis B virus genotype C and lower end-of-treatment HBsAg levels were independent predictors of HBsAg loss in HBeAg-positive and -negative patients. The 5-year HBsAg loss rate was 47.3% in HBeAg-positive patients with end-of-treatment HBsAg levels <300 IU/mL, while the 8-year HBsAg loss rate was 69.3% in HBeAg-negative patients with end-of-treatment HBsAg levels <200 IU/mL. Five patients experienced hepatitis flares with decompensation after stopping nucleoside analogue therapy, and one died after retreatment. Of the 48 patients who developed off-therapy HBsAg loss, two developed hepatocellular carcinoma.ConclusionsThe rate of HBsAg loss was relatively high and the rate of hepatic events was low in noncirrhotic patients who discontinued nucleoside analogue therapy.     

Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos(t)ide analogue in chronic hepatitis B

Background/AimsWe investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg).MethodsSerum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36, and 48 of treatment. Patients were followed up thereafter and serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU.ResultsTwenty-eight hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients (median, 38.2 years old; 71.9% male) were recruited with median follow-up duration of 17.1 years (interquartile range, 12.8–18.2). For the entire cohort, 22/64 (34.4%) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR (5.49 vs. 4.32 log copies/mL, respectively; P=0.016). The area under the receiver-operating-characteristic curve (AUROC) for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% confidence interval [CI], 0.661–0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs. reduction of 2.98 log U/mL; P=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI, 0.596–0.982).ConclusionsEarly on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.     

抗HBc IgM阳性慢性乙型肝炎临床特性、病毒学和血清学研究

目的探讨抗HBcAg IgM阳性慢性阳性肝炎患者的临床特性及其与HBV病毒学和血清学的关系。方法收集河北省张家口市传染病医院和北京地坛医院2004—2006年经Abbott EIA检测试剂证实的所有抗HBcAg IgM阳性和同期随机抽样的抗HBcAg IgM阴性患者的临床资料,包括生化指标、血清HBV DNA载量和血清学指标,分析抗HBcAg IgM阳性和阴性患者的疾病程度和临床转归之间的差异及抗HBcAg IgM状态与HBV DNA载量和HBeAg状态的关系。结果收集了200例慢性乙型肝炎患者,其中抗HBc IgM阳性70例,阴性130例,轻、中和重度肝脏疾病患者分别为71、83、46例。抗HBc IgM阳性患者的年龄和发病年数高于抗HBc IgM阴性患者,抗HBc IgM阳性的轻度肝脏疾病患者百分比为45.71%,中重度患者为54.29%,低于抗HBc IgM阴性患者(30.00%和70.00%),差异有统计学意义(χ2=4.907,P=0.027)。抗HBc IgM阳性患者和阴性患者的HBV DNA载量,血清HBeAg/抗HBe状态、住院天数和转归差异无统计学意义。结论慢性乙型肝炎患者抗HBcAg IgM的状态与肝脏疾病的程度相关,但与HBV DNA载量和HBeAg/抗HBe状态无相关性。     

乙肝免疫球蛋白不能阻断乙肝病毒感染人绒毛膜癌细胞

目的: 观察不同浓度乙肝免疫球蛋白(HBIG)在体外对乙肝病毒(HBV)感染人绒毛膜癌细胞系JAR细胞的影响。方法: 实验分为HBIG实验组、空白对照组(胎牛血清)、阴性对照组(健康人血清)。HBIG实验组又分为高浓度HBIG组(HBV+10³IU/L HBIG、HBV+10² IU/L HBIG)、最低保护浓度HBIG组(HBV+10 IU/L HBIG)、低浓度HBIG组(HBV+1IU/L、HBV+0.1 IU/L)和HBV组;采用MTT法检测HBIG对细胞生长的影响;采用实时荧光定量PCR检测细胞内HBV-DNA的表达;采用细胞免疫荧光染色法检测细胞内乙肝表面抗原(HBsAg)的表达变化。结果: (1) 不同浓度的HBIG对JAR细胞生长无影响;(2) 不同浓度HBIG组的细胞内HBsAg的荧光强度无显著差异(P>0.05);(3)不同浓度HBIG组的细胞内HBV-DNA无显著差异(P> 0.05)。结论: HBIG不能阻断HBV感染体外培养的JAR细胞。     

不同剂量乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果对比

目的 探讨10 μg和20 μg乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果.方法 124例HBsAg阳性孕妇所生的婴儿随机分为两组,即10 μg乙肝疫苗组和20 μg乙肝疫苗组.婴儿于出生6h内及30 d分别注射200 IU HBIG,同时分别于出生24 h内、1个月及6个月注射3次10 μg或20 μg重组酵母乙肝疫苗.检测婴儿出生时以及1岁时血清HBV标志物.结果 两组新生儿血清HBsAg、HBeAg及抗-HBe阳性率与滴度之间差别均无统计学意义（P＞0.05）.所有新生儿血清HBV DNA水平均小于检测下限（500 U/ml）.出生12个月时,所有124例婴儿血清HBsAg和HBeAg检测结果均为阴性;血清HBV DNA水平均在检测下限以下;10 μg和20 μg乙肝疫苗组血清抗-HBs阳性率分别为90.3％和96.8％,差异无统计学意义（P＞0.05）;抗-HBs水平分别为325.5±342.2 mIU/ml和463.7±353.3 mIU/ml,后者显著高于前者（P=0.01）.而且,20 μg乙肝疫苗组产生高应答抗-HBs（＞ 100 mIU/ml）的比例显著高于10μg乙肝疫苗组（P =0.035）.结论 20 μg乙肝疫苗联合HBIG方案阻断HBV母婴传播的效果优于10 μg乙肝疫苗联合HBIG方案.     

Immunoprophylaxis of perinatal transmission of the hepatitis B virus: efficacy of hepatitis B immune globulin and hepatitis B vaccine in a low-prevalence area

One hundred eleven newborn infants born of Spanish hepatitis B surface antigen (HBsAg) carrier mothers were consecutively assigned to one of three treatment groups. Group A was treated with three or four doses of hepatitis B immune globulin (HBIG) in one of three different schedules. Group B received one dose of hepatitis B vaccine (Hevac-B, Pasteur) at birth and at 1, 2 and 12 months. Group C was treated with the same vaccination schedule as group B and in addition received a single dose of HBIG at birth. Comparisons were made in the 85 babies who had strictly completed the immunization schedule and had been followed for at least 12 months. The three immunization protocols were equally effective, since none of the children became a chronic HBsAg carrier or developed acute symptomatic infection. There were five transient and subclinical infections among children who received only HBIG (group A), one transient infection in group B, and one in group C. There seems to be some correlation between anti-HBs levels and degree of protection, since all transient infections in group A occurred in the subgroups who did not maintain protective antibodies during the first 6 months. Although the percentage of responders in the two vaccinated groups did not differ significantly, children who received only vaccine reached higher antibody levels than those who also received HBIG. Our results suggest that any immunization schedule able to maintain anti-HBs levels during the first 6 months of life would be useful to prevent mother-to-infant transmission of the hepatitis B virus in areas where most of the carrier women are expected to be anti-HBe positive and hence relatively less infectious.     

阻断乙型肝炎病毒母婴传播方案探讨

目的探讨阻断乙型肝炎病毒母婴传播的有效方法。方法将乙型肝炎病毒携带孕妇,根据她们的不同情况和就诊的不同时期分为6组,Ms组为乙肝表面抗原阳性乙肝e抗原阴性的孕妇,根据就诊的不同时期分为Ms1组、Ms2组、Ms3组。Mse组为乙肝表面抗原和乙肝e抗原双阳性孕妇。MF组为孕妇与配偶均为乙型肝炎病毒携带者。F组为孕妇为非乙型肝炎病毒携带者配偶为乙型肝炎病毒携带者的孕妇。各组采用不同的方法阻断乙型肝炎病毒的垂直传播。结果 Ms1组230例中有22例母亲孕期用过乙肝免疫球蛋白（占本组总数9.6%）。Ms2组：372例中有37例母亲孕期用过乙肝免疫球蛋白（占本组总数9.9%）。Ms3组287例中有4例母亲孕期检测乙型肝炎病毒脱氧核糖核酸阳性用过HBIG（占本组总数1.4%）,与Ms1组和Ms2组母亲用乙肝免疫球蛋白率9.6%和9.9%比较经统计学处理差异都非常显著（χ2=17.850,P=0.000）;（χ2=20.311,P=0.000）。Mse组32例母亲在孕期都用过乙肝免疫球蛋白（占本组总数100%）。MF组72例中有20例母亲在孕期用过乙肝免疫球蛋白（占本组总数27.7%）。F组：48例中3例母亲在孕期用过乙肝免疫球蛋白（占本组总数6.2%）;32例母亲在孕期用过乙肝疫苗接种（占本组总数66.6%）。各组共1041例新生儿生后24h内静脉血乙肝抗原抗体定性检测：乙肝表面抗原和乙肝e抗原均为阴性。生后3个月至1岁随访检测婴儿静脉血1041例乙肝抗原定性乙肝表面抗原和乙肝e抗原仍均为阴性。结论孕妇或配偶为乙型肝炎病毒携带者,如乙肝e抗原阳性或乙型肝炎病毒脱氧核糖核酸阳性孕妇孕期需要注射乙肝免疫球蛋白阻断乙型肝炎病毒传播,否则不需要。父母为乙型肝炎病毒携带者,如新生儿生后检测乙型肝炎病毒抗原检测阳性需要注射乙肝免疫球蛋白,否则不需要。所有新生儿必须接种乙肝疫苗。     

HBIG Remains Significant in the Era of New Potent Nucleoside Analogues for Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation

Advent of hepatitis B immunoglobulin (HBIG) as the mainstay of prophylaxis against hepatitis B recurrence after liver transplantation with antiviral drugs has resulted in excellent outcomes for liver transplantation in hepatitis B virus (HBV)-related cirrhosis in the last two decades. However, there is no consensus on a gold standard prophylaxis protocol and several controversies over the duration, dose, and route of administration of HBIG with or without different antivirals exist among liver transplantation centers. We present this review of different prophylaxis regimens including HBIG and antiviral monotherapy, combination of HBIG with antivirals, and withdrawal of HBIG and whole prophylaxis.

HBIG monotherapy in either the intramuscular or the subcutaneous form is an accepted choice for prevention of HBV re-infection after liver transplantation in low risk patients. Withdrawal of HBIG monotherapy may be considered but should only occur after transitioning to an oral antiviral therapy such as adefovir, tenofovir, or entecavir. Lamivudine monotherapy may be associated with a higher recurrence rate compared to more potent antivirals. In high risk patients, intramuscular or subcutaneous HBIG in combination with an antiviral, most commonly lamivudine, is currently considered the standard of care. Complete discontinuation of all preventative therapy cannot be recommended at this time and should only be performed in the setting of a clinical trial.     

Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance

Background/AimsThe role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.MethodsUsing probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.ResultsHBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.ConclusionsThe biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAg-serocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.     

Hepatitis B virus infection among pregnant women in Haiti: A cross-sectional serosurvey

BackgroundHepatitis B vaccine administered shortly after birth is highly effective in preventing mother to child transmission (MTCT) of infection. While hepatitis B vaccine was introduced in Haiti as part of a combined pentavalent vaccine in 2012, a birth dose is not yet included in the immunization schedule.ObjectivesDetermine the seroprevalence of hepatitis B virus (HBV) infection among pregnant women to evaluate the risk of MTCT.Study designWe selected 1364 residual serum specimens collected during a 2012 human immunodeficiency virus (HIV) sentinel serosurvey among pregnant women attending antenatal care clinics. Haiti was stratified into two regions: West, which includes metropolitan Port-au-Prince, and non-West, which includes all other departments. We evaluated the association between demographic and socioeconomic characteristics and HIV infection with HBV infection.ResultsOf 1364 selected specimens, 1307 (96%) were available for testing. A total of 422 specimens (32.7%) tested positive for total anti-HBc (38.2% in West vs. 27% in non-West, p < 0.001), and 33 specimens (2.5%) were HBsAg positive (2.1% in West vs. 3% in non-West, p = 0.4). Of HBsAg positive specimens, 79% had detectable HBV DNA. Women aged 30 and older had more than double the odds of positive total anti-HBc than women aged 15–19 years (p < 0.001). Women with secondary (adjusted odds ratio (aOR) = 0.54; 95% CI: 0.36–0.81) and post-secondary education (aOR = 0.40, 95% CI: 0.19–0.79) had lower odds of total anti-HBc positivity compared with women with no education. HIV-status was not associated with HBV infection.ConclusionsHaiti has an intermediate endemicity of chronic HBV infection with high prevalence of positive HBV DNA among chronically infected women. Introduction of a universal birth dose of hepatitis B vaccine might help prevent perinatal HBV transmission.     

Occult hepatitis B virus infection in patients with leprosy

Leprosy patients may present with immune system impairment and have a higher hepatitis B virus (HBV) seroprevalence, justifying the investigation of occult HBV infection in these individuals. The aim of this study was to verify the frequency and the clinical factors associated with occult HBV infection in leprosy patients. Between 2015 and 2016, leprosy patients from a reference center in Brazil were interviewed to assess clinical data. Blood samples were collected for the screening of HBV serological markers using enzyme-linked immunosorbent assay. Patients with negative hepatitis B surface antigen (HBsAg) that had positive anti-HBc and/or anti-HBs were selected for HBV DNA detection using real-time polymerase chain reaction. SPSS was used for data analysis. Among 114 selected patients, six were identified with occult infection (5.3%) and five of them with multibacillary leprosy. Three patients with occult infection had a history of a type 2 reaction (P = 0.072; OR, 4.97; 95% CI, 0.87-28.52). Only two patients with occult infection had isolated anti-HBc, while three had isolated anti-HBs, including those with the highest HBV DNA titers. In conclusion, in leprosy patients with negative HBsAg and positive anti-HBc and/or anti-HBs, occult HBV infection occurs in 5.3% and can be found even in patients with isolated anti-HBs.     

Significance of persisting IgM anti-HBc antibodies in hepatitis B virus infection

IgG and IgM antibodies to the core antigen of hepatitis B virus (HBV) were measured in 136 patients who developed acute HBV hepatitis and who were followed prospectively. After acute hepatitis all the patients developed transiently IgM anti-HBc lasting for two to five months. In contrast, IgM anti-HBc persisted 8 and 9 months in two patients who developed persistent hepatitis and were continuously detected for two years in nine patients who developed aggressive hepatitis. The results presented suggest that the determination of IgM anti-HBc might be useful to predict the outcome of chronic hepatitis B infection.     

HBsAg-negative chronic active hepatitis related to hepatitis B virus

Numerous cases of chronic hepatitis have been shown to be closely associated with persistent infection with hepatitis B virus (HBV).A group of 100 patients suffering from chronic active hepatitis (CAH) was investigated for HBV serologic markers. Of these, 35 patients were HbsA-gpositive; in 26 HBsAg-negative subjects, anti-HBc were detected using counterimmune electrophoresis and complement-fixation tests. These data suggest that chronic liver disease in patients who were only anti-HBc-positive might be related to a persistent infection with hepatitis B virus.Epidemiological, clinical and histopathological data were different when we compared CAH patients who were HBsAg-negative, but anti-HBc-positive, with HBsAg-positive CAH patients. A sequence is proposed leading from HBsAg-positive to HBsAg-negative CAH, cirrhosis, and hepatoma in temperate areas, according to a model similar to the one described in intertropical Africa.     

Successful postexposure vaccination against hepatitis B in chimpanzees

To study the effect of postexposure vaccination, four chimpanzees were vaccinated with hepatitis B (HB) vaccine 4, 8, 48, and 72 hr, respectively, after intravenous injection of an infectious hepatitis B virus (HBV) inoculum. The second and third vaccine inoculations were given 2 and 6 weeks later, i.e., at considerably shorter intervals than recommended either for ordinary prophylactic vaccination or for postexposure vaccination in combination with hepatitis B immune globulin (HBIG). The chimpanzees were followed for 1 year. None showed HBs-antigenemia, liver enzyme elevation (ALT), or histopathological alterations in liver biopsies. Late appearance of anti-HBc was observed only in the serum of the animal whose series of vaccination started 72 hr after HBV inoculation. An unvaccinated control chimpanzee, which received the HBV inoculum only, developed clinical hepatitis B with ALT-elevations and HBs-antigenemia within 2 months of the experimental HBV inoculation. These results indicate that postexposure vaccination against hepatitis B begun within 48 hr after HBV exposure, with short intervals between the vaccine injections, can protect against hepatitis B infection also when concomitant HBIG-prophylaxis is not given.     

Hepatitis B prophylaxis post liver transplantation with newer nucleos(t)ide analogues after hepatitis B immunoglobulin discontinuation

Newer nucleos(t)ide analogues (NUCs) have better resistance profiles making hepatitis B immunoglobulin (HBIG)-sparing protocol an attractive prophylactic approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). We evaluated the risk of HBV recurrence after withdrawal of HBIG in patients who had been under HBIG plus NUCs after LT. Stable patients without HBV recurrence after LT while receiving combination of HBIG plus NUCs for at least 12?months were eligible for HBIG discontinuation. The patients were at low risk for HBV recurrence (only 4.5% had detectable HBV DNA at the time of LT, and 32% had HBV/hepatitis D virus co-infection). All patients were followed up with HBV serum markers, HBV-DNA, and evaluation of renal function, including glomerular filtration rate. Forty-seven recipients discontinued HBIG and were maintained on newer NUCs. Median follow-up post-HBIG withdrawal was 24?months (range: 6-40?months). Twenty-eight (60%) patients continued on lamivudine in combination with adefovir dipivoxil (n?=?23, 82%) or tenofovir (n?=?5, 18%); 10 (21%) and 9 (19%) of the 47 patients continued on tenofovir and entecavir monoprophylaxis, respectively. Although 3 (6.3%) patients developed detectable hepatitis B surface antigen, all of them had undetectable HBV DNA and no clinical manifestations of HBV recurrence. Renal function was similar between the different groups of patients. In conclusion, maintenance therapy with newer NUCs after discontinuation of HBIG prophylaxis was effective, but further studies in larger cohorts with longer follow-up are needed.     

不同方案阻断乙型肝炎病毒母婴垂直传播的随访观察

目的探讨阻断乙型肝炎病毒母婴垂直传播的方法.方法将488例HBsAg阳性孕妇分成四组,单纯HBVac治疗组116例,单纯HBIG治疗组116例,左旋咪唑涂布剂加两者联合应用120例,未治疗组136例.治疗组均在孕26周起开始注射,孕妇和新生儿血清HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc检测采用ELISA法.随访产妇及新生儿的乙肝标志物(HBVM)变化.结果脐血中HBsAg阳性率:HBVaC治疗组为18.10%,HBIG治疗组为9%,联合治疗组为3.33%,未治疗组为24.26%.随访母亲HBVM多数转为HBSAg、抗-HBC、抗-HBc阳性,所生儿童抗-HBs＞70%.结论携带HBV孕妇于孕晚期给予HBVac、HBIG和左旋咪唑涂布剂联合两者治疗后,可有效阻断HBV母婴之间传播.     

The role of the hepatitis B virus infection in patients with chronic hepatitis in argentina

Over a seven-year period, we monitored 221 patients with chronic hepatitis from two medical centers. By using the counterelectrophoresis (CEP) test to detect the presence of HBsAg and anti-HBc, or both, we established that 87.7% of them had hepatitis B infection. Serum specimens originally found negative for HBsAg by CEP were further tested by reversed passive hemagglutination (RPH), and those originally found negative for anti-HBc by CEP were further tested by radioimmunoassay (RIA). Five patients were anti-HBc-positive and HBsAg-negative. No sex predominance was observed, but HBsAg incidence increased with increasing age. The HBeAg antigen was detected in 46.8% of the 161 cases tested for it; the most frequent subtype found was adw (63.7%). The present findings indicate that HBV infection largely contributes to the development of chronic hepatitis in Argentinian patients.