Low incidence of hepatitis B virus reactivation during chemotherapy among diffuse large B‐cell lymphoma patients who are HBsAg‐negative/ HBcAb‐positive: a multicenter retrospective study

Background: Reactivation of hepatitis B virus (HBV) is less common in lymphoma patients with prior resolved HBV infection [characterized by hepatitis B surface antigen (HBsAg)‐negative/hepatitis B core antibody (HBcAb)‐positive status] compared with chronic HBV infection (HBsAg positive) when receiving chemotherapy alone. The use of rituximab in chemotherapy regimen might increase the risk of HBV reactivation in patients with prior resolved HBV infection. However, the incidence of HBV reactivation is uncertain, and prophylactic antiviral treatment for this group of patients during rituximab‐containing chemotherapy is controversial. The objective of this study was to determine the incidence of HBV reactivation in HBsAg‐negative/HBcAb‐positive patients diagnosed of diffuse large B‐cell lymphoma (DLBCL) and treated with CHOP‐like or RCHOP‐like regimen. In addition, this study also aims to explore the relationship of HBV reactivation and HBV serology. Methods: Patients were identified using data from six university hospitals collected between January 1998 and November 2008. Four hundred and thirty‐seven patients with complete data were selected based on the diagnosis of CD20+ DLBCL, availability of HBV serum markers prior to initiation of chemotherapy and during the development of hepatitis, completion of at least four cycles of chemotherapy using CHOP‐like or RCHOP‐like regimen, and follow‐up for at least 6 months after completion of treatment. The characteristics of the HBsAg‐negative/HBcAb‐positive patients treated with CHOP‐like regimen were compared to those treated with RCHOP‐like regimen. Results: Eighty‐eight patients of the total 437 patients had pretreatment serology of prior resolved hepatitis B, with a prevalence of 20.1%. Among them, 45 patients received CHOP‐like regimen while 43 patients received RCHOP‐like regimen. Five patients developed hepatitis during treatment, two from CHOP group and three from RCHOP group. Only one patient treated with RCHOP had hepatitis associated with HBV reactivation, while the other four patients did not have evidence of HBV reactivation. Those four patients also demonstrated positive HBsAb at baseline, while the only patient who suffered from HBV reactivation had negative HBsAb status. This patient was successfully treated with antiviral medications. There were no statistically significant risk factors predictive of HBV reactivation. Conclusions: The present study revealed a low HBV reactivation rate of 2.3% in prior resolved hepatitis B among DLBCL patients undergoing RCHOP‐like therapy.     

Hepatitis B virus reactivation during belatacept treatment after kidney transplantation

We report a case of HBV reactivation following belatacept treatment in a patient who underwent kidney transplantation in 2015 for HIV‐associated nephropathy (HIVAN). Human immunodeficiency virus viral load was undetectable prior to transplantation, and CD4+ lymphocyte count was greater than 300/mL. Baseline HBV serology at transplantation was HBsAg negative, anti‐HBcAb positive, anti‐HBsAb 312 UI/L, and HBeAg negative/anti‐HBeAb positive. Liver function tests were normal, and viral DNA was undetectable. Two years later, the patient presented with severe acute hepatitis after a progressive disappearance of anti‐HbsAb, quickly followed by HBV reactivation. Immunosuppressive treatment was drastically reduced, and treatment with entecavir was started. The outcome was favorable, and HBV DNA became undetectable after 9 weeks of treatment. This is the first report of acute hepatitis related to HBV reactivation in a kidney transplant recipient treated with belatacept. The risk for HBV reactivation in patients treated with belatacept should not be underestimated, especially in those with resolved HBV infection.     

Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region

Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.     

HBsAg阳性患者异基因造血干细胞移植后的临床研究

目的 探讨HBsAg阳性患者接受异基因造血干细胞移植(allo-HSCT)后的肝脏不良事件的发生及影响该类患者长期存在的危险因素.方法 回顾性分析本所2001年3月至2006年11月接受allo-HSCT治疗的26例HBsAg阳性患者的临床资料.造血干细胞来源:18例为HLA配型相合同胞,7例为HLA配型不合亲缘供者,1例为无关供者.所有患者移植前后均排除丙型肝炎病毒感染.2例移植前HBV DNA阳性,其余均表达阴性.结果 26例患者急性移植物抗宿主病(Agvhd)累积发生率为50.0%.在可评估的20例中,5例发生了慢性GVHD,累积发生率25.0%.移植后出现肝功能异常共有15例(57.7%).出现肝功能受损的病因主要为:乙型肝炎及肝脏GVHD.移植后乙型肝炎再燃5年累积发生率33.4%,发生中位时间为82(65～159)d.拉米夫定预防性应用13例,1例发生乙型肝炎事件;未给药组为11例,7例发生乙型肝炎事件,两者累积发生率差异有统计学意义(P=0.006);预防用药组未发生一例肝衰竭,未预防用药组发生4例肝衰竭.死亡原因:5例肝衰竭,3例肺部感染,2例移植后疾病复发.26例患者中共有10例死亡,5年生存率(OS)为59.0%.多因素分析最终确定与OS发生相关的危险因素为肝衰竭(P=0.000).结论 HBsAg阳性患者接受allo-HSCT治疗后常出现肝功能异常表现,其首要病因为乙型肝炎,所导致的肝衰竭严重影响患者预后.而对HBsAg阳性患者预防性应用拉米夫定能够有效预防移植后乙型肝炎的复燃.     

Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg‐negative and anti‐HBc antibodies‐positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer

Summary. We studied clinical outcome and clinico‐virological factors associated with hepatitis B virus reactivation (HBV‐R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)‐negative/anti‐hepatitis B core antibodies (anti‐HBcAb)‐positive patients. Between 11/2003 and 12/2005, HBV‐R occurred in 7/84 HBsAg‐negative/anti‐HBcAb‐positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV‐R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV‐R involved non‐A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV‐R is a concern in HBsAg‐negative/anti‐HBcAb‐positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti‐HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV‐R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.     

Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy

With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with malignant lymphoma, other hematological malignancies, oncological or rheumatological disease. In the survey, rituximab plus steroid‐containing chemotherapy was identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg) negative patients with malignant lymphoma. In this setting, HBV reactivation resulted in fatal fulminant hepatitis regardless of the treatment of nucleoside analog. The Intractable Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for HBsAg by a sensitive method before the start of immunosuppressive therapy. Second, hepatitis B core antigen (HBcAb) and hepatitis B surface antibody (HBsAb) testing should be performed in HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with nucleoside analogs is essential for preventing HBV reactivation in HBsAg positive patients. In contrast, HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV DNA during and 12 months after completion of chemotherapy. Nucleoside analogs should be administrated immediately when HBV DNA becomes positive during this period. This strategy facilitates commencement of nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe hepatitis.     

Direct‐acting antivirals and hepatitis B virus (HBV) reactivation in co‐infected HBV/HCV kidney‐transplant recipients

Direct‐acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg‐positive and HBsAg‐negative patients. We report on 3 cases of HBV reactivation that were detected after achieving a DAA‐associated sustained virological response in 3 kidney‐transplant recipients initially HBsAg‐negative. In the first case, retrospective virological analysis revealed that HBsAgs had become positive and HBV DNA was detectable before initiating DAA therapy. In the second and third cases, HBV reactivation occurred 2 months and more than 1 year after stopping anti‐HCV therapy. These cases underline the discrepancies and highlight the need for comprehensive information before making definitive conclusions regarding the causal link between DAAs and HBV reactivation.     

Hepatitis B reactivation after kidney transplantation in hepatitis B surface antigen‐negative,core antibody‐positive recipients

Nowadays, intensive immunosuppressive therapy including rituximab is commonly used prior to kidney transplantation (KT), raising concerns over hepatitis B virus (HBV) reactivation among hepatitis B surface antigen (HBsAg)‐negative and anti‐hepatitis B core (HBc)‐positive KT recipients. Recent practice guidelines suggested watchful monitoring or antiviral prophylaxis for the first 6‐12 months, the period of maximal immunosuppression. However, the actual risk for HBV reactivation, and whether short‐term antiviral therapy in the early period is necessary, remains unclear. A total of 449 HBsAg‐negative and anti‐HBc‐positive KT recipients were analysed for HBV reactivation. During a median follow‐up of 6.7 (interquartile range: 4.2‐9.4) years, HBV reactivation was observed in 9 patients (2.0%). The median time of HBV reactivation from KT was 2.8 years (range: 1.4‐11.5 years), with cumulative incidence rates of 0%, 1% and 2% for 1, 3 and 5 years, respectively. There were no severe adverse outcomes, including liver transplantation or mortality related to HBV reactivation. The risk of HBV reactivation was not high, even in anti‐HBs‐negative patients (n = 60, 4% at 5 years), ABO mismatch (n = 92, 4% at 5 years), use of rituximab (n = 66, 3% at 5 years) or plasmapheresis (n = 17, 7% at 5 years), and acute rejection (n = 169, 3% at 5 years). In conclusion, the HBV reactivation risk was not high and the time of detection was not clustered in the early post‐KT period. Our findings favour continued watchful monitoring over antiviral prophylaxis in the early period.     

HBV-related events after allogeneic hematopoetic stem cell transplantatıon in a center from Turkey

To investigate the frequency of hepatitis B virus (HBV)-related events after allogeneic HCT in a moderate endemic area for HBV infection. The data of 197 patients who underwent allogeneic hematopoetic stem cell transplatation (HCT) from September 2003 through December 2010 were reviewed retrospectively with respect to HBV-related events. Resolved HBV infection was described as negative HBsAg, positive HBcAb, and positive HBsAb. Latent HBV infection was defined in patients with HBcAb positivity in the abscence of HBV DNA and HBsAb. Hepatitis B naive patients are defined as the patiens with no serological or molecular marker related to HBV. Seropositive patients were the patients with positive HBsAg and HBV-DNA. Median age was 28 (range, 15–64) years, with 128 male and 69 female patients. Median follow-up of the cohort was 8 (range, 0.5–78) months. We detected HBV-related events in 7 (3.6 %) recipients after allogeneic HCT. Five (71.4 %) of these events were HBV reactivation, while two cases (28.6 %) had acute hepatitis B infection. Four of the five reactivations were in the seropositive group (80 %), while one ocurred in a patient with resolved hepatitis. Two patients who developed acute hepatitis B were HBV naive and previously immunized patients, respectively. Hepatitis B virus reactivation remains a problem in seropositive patients and might require more effective treatment strategies.     

Four-year follow-up of two chronic hepatitis B recipients of hepatitis B surface antigen-positive cadaveric liver grafts from asymptomatic carriers

Aim: Only seven cases of liver transplantation (OLT) with positive serum hepatitis B surface antigen (HBsAg) grafts have been reported in the world till now. Here we report the 4‐year follow‐up results and clinical pathologic characteristics of two recipients of chronic hepatitis B transplanted with HBsAg‐positive cadaveric liver grafts from asymptomatic carriers. Methods: Lamivudine combined with hepatitis B immune globulin were used for the control of hepatitis B virus (HBV) infection in both of the recipients post‐OLT. The liver functions, virus status and pathologic characteristics of two recipients were followed up according to the rounte protocol of Liver Transplantation Center of West China Hospital. Results: The serum HBV deoxyribonucleic acid (DNA) turned negative within 30 days post‐OLT, but HBsAg remained positive for both of the recipients during follow up. HBV breakthrough occurred in one recipient at the month 12 post‐OLT, with detectable serum HBV‐DNA (740 copies/mL) and tyrosine‐methionine‐aspartate‐aspartate motif mutation (rtM204I and rtM204V). After the replacement of lamivudine by adefovir dipivoxil 10 mg daily for 2 months, serum HBV‐DNA of this recipient became undetectable again and maintained undetectable during follow up. Both of the recipients have survived for more than 4 years post‐OLT, with stable liver function and mild hepatitis. Conclusion: Due to extreme scarcity of liver graft, we think that HBsAg‐positive liver graft without active HBV‐DNA replication and severe pathological manifestation from asymptomatic carriers may deserve consideration when no other graft is available in a bearable waiting time.     

乙型肝炎表面抗原阳性供肝在肝移植中的应用

目的 探讨HBsAg阳性供肝在成人肝移植中应用的安全性及其对患者预后的影响.方法 回顾性分析本中心2007年1月至2010年2月23例接受HBsAg阳性供肝的成人肝移植患者临床资料,患者全部为男性,中位年龄42.5岁(29 ～ 61岁),原发病均为乙型肝炎相关终末期肝病,其中13例术前HBsAg、HBeAg和抗-HBc为阳性,10例术前HBsAg、抗-HBe和抗-HBc为阳性.供体HBsAg均为阳性,术后口服恩替卡韦0.5mg,1次/d,静脉滴注乙型肝炎免疫球蛋白(HBIG),术后1周每天滴注2000 IU.术中及术后采用无激素的免疫抑制方案,术后第1、7、14、21、30天检测患者血清HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc、HBV DNA水平,并行肝脏彩色多普勒超声检查.1个月后每月检测及检查1次,并记录患者术后肝功能、肾功能、急性排斥反应、感染、血管并发症、胆道并发症、乙型肝炎复发、肿瘤复发及患者生存等数据.结果 围手术期2例患者死于严重肺部感染,其余21例患者随访至2010年12月(10 ～ 38个月),所有患者术后乙型肝炎未转阴,其中1例患者于术后5个月因胆道缺血再次行肝移植,3例肿瘤患者分别于术后9、14、18个月死于肿瘤复发,18例患者生存,肝功能良好,彩色多普勒超声监测显示肝脏形态、质地良好,HBV DNA监测显示其均为阴性.随访期内,23例患者的生存率为78.3％(18/23),移植肝生存率为73.9％(17/23),未出现乙型肝炎复发所致的肝功能异常、移植肝丢失和病死患者.结论 HBsAg阳性供肝可以安全地应用于乙型肝炎相关终末期肝病的患者.     

Anti-hepatitis B surface immunoglobulin reduction in early postoperative period after liver transplantation in hepatitis B virus-positive patients

Aim: We investigated a protocol that lowered the necessary dose of anti‐hepatitis B surface immunoglobulin (HBIg) with frequent monitoring of hepatitis B surface antigen (HBsAg) and antibody (HBsAb) levels in the early post‐transplant period. Methods: Fifteen hepatitis B virus (HBV)‐positive patients were studied. We administered a nucleoside analog from the preoperative period, high dose HBIg was used intraoperatively (200 IU/kg in the patients who weighed less than 50 kg, and 10 000 IU in those who weighed more than or equal to 50 kg) and was continued every day (5000–10 000 IU/day). Thereafter, HBIg was administered to keep the target trough titers. We evaluated the effectiveness and safety of this protocol for preventing HBV reactivation. Results: The average use of HBIg during the first three postoperative months (POM) was 27.9 ± 9.6 Kilo International Units. The average cost was $US11 800 in the first three postoperative months, compared with other previously reported protocols (about $20 000–40 000). HBV reactivation was detected in only one patient (6.7%) during the median follow up of 64 months (range: 12–86 months). Conclusions: The present protocol for HBIg administration, which used frequent monitoring of HBsAg and HBsAb levels to determine the minimum required dose, was both safe and effective, and contributed to overall cost saving after liver transplantation.     

Natural history of hepatitis B virus infection in renal transplant recipients--a fifteen-year follow-up

Hepatitis B virus (HBV) markers were measured in 83 immunosuppressed renal transplant patients who were followed for periods of 2 to 15 years. Sixty-nine patients were negative for HBsAg before transplantation, of whom 14 were positive for anti-HBs. The remaining 14 patients were HBsAg positive prior to transplantation. Eighteen patients were identified as being HBsAg positive during the follow-up period. Four patients acquired primary type B hepatitis; one died of submassive hepatic necrosis and the remaining three became chronic HBV carriers with positive HBeAg, DNA polymerase, and HBV DNA. Several patterns of HBV expression were observed in HBsAg-positive patients. Four patients were HBsAg, HBeAg, DNA polymerase, and HBV DNA positive prior to transplantation, and these markers persisted. Reactivation of HBV replication occurred in eight patients, seven of whom were HBsAg positive and HBeAg and anti-HBe negative originally; one patient was anti-HBc positive. A single patient was HBsAg and anti-HBe positive and remained so for 22 months. The remaining previously HBsAg-positive patient is currently HBsAg negative. These serological data suggest that reactivation of HBV replication or continued hepatitis B virion replication occurs as commonly or more commonly than de novo infection in renal transplant recipients. The presence of HBeAg in serum predisposes to long-term Dane particle expression in immunosuppressed patients, whereas anti-HBe-positive carriers may not always be susceptible to reactivation of HBV replication despite immunosuppression.     

Reactivation of hepatitis B virus after autologous peripheral blood stem cell transplantation in patients with positive hepatitis B surface antibodies

Hepatitis B virus (HBV) reactivation in patients with positive hepatitis B surface antibody (HBsAb) has been reported in some cases of allogenic bone marrow transplantation, acquired immunodeficiency syndrome (AIDS), and organ transplantation. However, to our knowledge, no reports have been made on the frequency and risk factors involved in HBV reactivation after autologous peripheral blood stem cell transplantation (APBSCT). Forty seven patients who underwent APBSCT were retrospectively analyzed. Three patients who were HBsAb positive before APBSCT contracted post-transplant HBV acute hepatitis. All 3 patients had multiple myeloma. HBV DNA could not be demonstrated in preserved samples of transfused blood. Therefore, we speculated that reactivation of latent HBV had occurred. The 3 patients with HBV hepatitis had relatively lower titers of pre-transplant HBsAb, and the total dose of steroids they received after APBSCT was significantly higher than for other patients who did not experience post-transplant HBV reactivation. There were no significant differences in pre-transplant hepatitis B core antibody (HBcAb) titer or total post-transplant blood transfusion volume. Our study suggested that immunocompromised states, especially those induced by high-dose steroid therapy, may allow the reactivation of HBV after APBSCT, even in patients who had HBsAb before APBSCT.     

Indications for liver transplantation in patients with chronic hepatitis B and C virus infection and hepatocellular carcinoma

Patients with chronic hepatitis B virus (HBV) infection were not accepted for liver transplantation in Asia in the past because the hepatitis B immune globulin (HBIG) used to prevent post‐transplantation recurrence was very expensive and it was generally believed that Asians with hepatitis B fared worse than Caucasians after liver transplantation. The availability of lamivudine has altered the indication of liver transplantation for these patients. Twenty‐five Chinese patients with chronic HBV infection were given lamivudine as primary prophylaxis against HBV re‐infection before transplantation. Five patients died within 40 days of transplantation. After a median follow‐up period of 14 months (range, 5–39), 17 patients had lost serum HBsAg from 4 days to 27 months post transplantation, but it reappeared in three patients 4–12 months later. Antibody to HBsAg was detected periodically in the serum of 11 patients who had lost HBsAg. At the last follow‐up, six patients were HBsAg‐positive and HBV DNA was detected in only one of them. The indication for liver transplantation for chronic hepatitis C virus (HCV) infection is not as strict as for patients with chronic HBV infection because the long‐term survival is similar to that of non‐hepatitis C patients, even though re‐infection by HCV in the recipients is nearly universal. The main issue in the selection of patients with HCV for liver transplantation is therefore identification of criteria that can predict re‐infection and development of cirrhosis. These include factors such as multiple episodes of rejection, use of OKT3, pre‐transplant viral load and genotype, but reports are not consistent and so there are no well‐defined selection criteria. The selection criteria for patients with hepatocellular carcinoma are now well defined. Many studies have confirmed that a tumour > 5 cm, and showing vascular invasion, and poor differentiation adversely affects survival. In practice, only patients with a tumour < 5 cm and Child’s C cirrhosis are accepted for liver transplantation. Transarterial oily chemoembolization and intralesional alcohol injection are used to control or down‐stage the tumour while patients wait for a cadaveric liver graft.     

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

AIM: To evaluate pretreatment hepatitis B virus(HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration(VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment(2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status(from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during antiCD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV(hepatitis B surface antigen positive or HBs Ag+), past HBV(HBs Ag-, hepatitis B core antibody positive or HBc Ab+), resolved HBV(HBs Ag-, HBc Ab+, hepatitis B surface antibody positive or HBs Ab+), likely prior vaccination(isolated HBs Ab+), HBV negative(HBs Ag-, HBc Ab-), or unknown. Acute hepatitis B was defined by the appearance of HBs Ag+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group.RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224(53%) had pretreatment HBs Ag testing during the study period, with 49% and 43% tested for HBs Ag and HBc Ab, respectively within 6 mo pretreatment in 2014. Of those tested, 2%(167/10224) had chronic HBV, 4%(326/7903) past HBV, 5%(427/8110) resolved HBV, 8%(628/8110) likely prior HBV vaccination, and 76%(6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative(P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16(0.3%) developed acute hepatitis B of 4947 tested during anti-CD20 Ab treatment and followup. CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.     

Short and long term outcome of kidney transplanted patients with chronic viral hepatitis B and C

Introduction. Liver disease related to chronic viral hepatitis is a major cause of morbidity and mortality in renal transplant patients. There is no agreement upon the influence of chronic hepatitis B (HBV) and hepatitis C (HCV) infection in patient and graft survival.Aims. The aim of the study was to evaluate the influence of HBV and HCV on patient and graft short and long term survival, in the patients transplanted at our institution.Materials and methods. We evaluated the influence of antiHCV and HBsAg status (positive vs. negative); sex; age (> 49 years vs. < 49 years at transplantation); time on dialysis (> 3 vs. < 3 years); acute rejection; kind of graft (deceased vs. living donor, and kidney versus kidney and pancreas); number of transplantations; use of induction immunosuppression; and maintenance immunosuppression treatment (comparing the traditional triple therapy containing azathioprine, cyclosporine and prednisone vs. newer regimens which include tacrolimus, mycophenolate mofetil, sirolimus, etc) on the survival, long term and within the first month of transplantation, of the graft and the patients transplanted in our Institution between January 1991 and August 2009.Results. We included 542 patients, 60% males’ median age of 42.03 years (SD 13.06 years). 180 patients (33%) were antiHCV positive and 23 (4%) were HBsAg positive. AntiHCV positive, traditional triple therapy and acute rejection were associated with diminished graft survival. Older age, antiHCV positive, HBsAg positive, deceased donor, kidney-pancreas transplantation and traditional triple therapy were associated with diminished patient survival. Traditional triple therapy was associated with diminished one month graft survival; and older age and antiHCV positive were associated with diminished one month patient survival.Conclusion. In our experience, antiHCV positive status was associated with diminished long term patient and graft survival, and diminished six month graft survival; and HBsAg positive was associated with diminished patient survival.     

Risk factors for de novo hepatitis B infection in pediatric living donor liver transplantation

AIM: To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection.METHODS: The clinical and laboratory data of children who underwent LDLT from June 2010 to September 2012 in First Center Hospital in Tianjin, China, were retrospectively included in the study. Intrahepatic HBV DNA in donors and recipients was quantified by real-time polymerase chain reaction using DNA extracted from formalin-fixed, paraffin-embedded tissues.RESULTS: Between June 2010 to September 2012, 32 consecutive pediatric patients underwent LDLT in our institute. Thirty LDLT patients (13 girls and 17 boys) were followed up for a median of 15 mo, of whom 53.3% (16/30) were hepatitis B core antibody (HBcAb) positive and 36.7% (11/30) were hepatitis B surface antibody (HBsAb)/HBcAb positive before transplantation. Sixteen of the children received HBcAb-positive allografts, and 43.7% (7/16) of the grafts were found to be intrahepatic HBV DNA positive. De novo HBV infection developed in 16.1% (5/30) of the children within a median of 11 mo after transplantation. All five of the HBV-infected children had received HBcAb-positive allografts, four of which were intrahepatic HBV DNA positive. Two of the children developed de novo HBV infection despite the preoperative presence of both HBsAb and HBcAbCONCLUSION: In pediatric recipients, positive intrahepatic HBV DNA in allografts could be a risk factor for de novo HBV infection from HBcAb-positive allografts. HBsAb/HBcAb positivity in pediatric LDLT patients before transplantation exhibited only weak effectiveness in protecting them against de novo HBV infection from HBcAb-positive allografts.     

Retrospective Study on the Impact of Hepatitis B and Hepatitis C Virus Infection on Hematopoietic Stem Cell Transplantation in Japan

We performed a retrospective survey in 62 hematopoietic cell transplantation (HCT) centers in Japan in which all HCTs performed between 1986 and 1998 were reviewed, and those involving hepatitis B virus surface antigen (HBsAg)-positive donors were identified. One hundred and thirty-five patients who underwent allogeneic HCT (alloHCT) were studied for complications related to hepatitis B virus (HBV) or hepatitis C virus (HCV). The median follow-up period was 24 months. Positivity for HBsAg was observed in 32 patients (24%) throughout the study. Twenty-six of the 32 patients were HBsAg carriers before alloHCT, whereas the remaining 6 became HBsAg(+) after alloHCT. Forty-two recipients were anti-HBs antibody (HBsAb)-positive, and 58 recipients (43%) were HCV Ab(+). Eleven of 26 (42%) HBsAg(+) recipients survived between >4 and >119 months. Six of 26 cases received transplants from HBsAg(+) donors, and, although they had not developed acute graft-versus-host disease, 4 of 6 died of hepatic and renal failure within 10 months after HCT. After transplantation, 5 patients showed serologic evidence of HBV reactivation, whereas 4 patients showed evidence of an immune response to HBV. Viral reactivation occurred during the tapering of the immunosuppressive agent. However, 3 of 5 were alive at the time of this report, suggesting that reactivation is not directly correlated with severe liver dysfunction. Seventeen patients (13%) of 135 recipients developed hepatic failure. Eight (47%) of 17 were diagnosed with fulminant hepatitis and 5 (29%) with veno-occlusive disease (VOD). VOD was observed in 12% of both HBsAg(+) and HCVAb(+) patients. In this study, the relatively high incidence of HBV events occurred after alloHCT, and, therefore, we should consider a protocol for active immunization of donors and recipients against HBV. Moreover, although the presence of HBV or HCV is not a contraindication for alloHCT, we recommend a careful follow-up of recipients after transplantation, especially during immunosuppression tapering.     

Donor derived hepatitis B virus infection: Analysis of the Organ Procurement & Transplantation Network/United Network for Organ Sharing Ad Hoc Disease Transmission Advisory Committee

Hepatitis B virus (HBV) can be transmitted from organ donor to recipient, but details of transmission events are not widely published. The Disease Transmission Advisory Committee (DTAC) evaluated 105 cases of potential donor derived transmission events of HBV between 2009‐2017. Proven, probable or possible transmission of HBV occurred in 25 (23.8%) cases. Recipients of liver grafts were most commonly infected (20 of 21 exposed recipients) compared to 9 of 21 exposed non‐hepatic recipients. Eleven of 25 donors were HBV core antibody (HBcAb) positive/HBV surface antigen (HBsAg) negative and infected 8/20 recipients. Of the 10 liver recipients and 1 liver‐kidney recipient who received organs from these donors: six were not given antiviral prophylaxis, two developed infection after antiviral prophylaxis was discontinued, two developed HBV while on lamivudine prophylaxis, one was on antiviral prophylaxis and did not develop HBV viremia or antigenemia. One recipient of a HBcAb positive/HBsAg negative kidney developed active HBV infection. Unexpected donor‐derived transmission of HBV was a rare event in reports to DTAC, but was often detected in the recipient late post‐transplant. Six of 11 recipients (54.5%) of a liver from a HBcAb positive donor did not receive prophylaxis; all of these were potentially preventable with the use of anti‐viral prophylaxis.