Does hepatitis C virus affect the reactivation of hepatitis B virus following renal transplantation?

BACKGROUND: Hepatitis B virus (HBV) is endemic in Taiwan. Transplantation followed by long-term immunosuppressive medications may precipitate HBV reactivation. Interference of hepatitis C virus (HCV) with HBV gene expression and replication has been confirmed in many studies involving non-transplant populations. This study investigates the incidence of HBV reactivation following renal transplantation and compares the clinical outcome, especially the liver outcome, of patients with or without HCV co-infection. METHODS: Fifty-one of 512 renal transplant recipients were positive for hepatitis B surface antigen before surgery, and were followed for 81.6+/-7.5 (4-120) months. Seventeen of 51 patients acquired HCV before transplantation and six patients acquired HCV after renal transplantation. RESULTS: At the end of this assessment, we had 28 patients who suffered HBV reactivation and another 23 patients who suffered no HBV reactivation. Initially, we found a significant difference of HCV carriage (P<0.05) between patients with (seven out of 28 or 25%) or without (21 out of 23 or 91.3%) HBV reactivation. Further inspection showed that 21 of the 28 patients without HCV co-infection and seven of the 23 patients with HCV co-infection suffered HBV reactivation. After comparison, we found a lower incidence of HBV reactivation in patients with HCV co-infection than in patients without HCV co-infection (P<0.05). In contrast to the latter, we found that patients with HCV co-infection suffering HBV reactivation tended to have a late onset of HBV reactivation (P<0.05). Otherwise, there was no difference in hepatitis severity, in terms of peak alanine aminotransferase, total bilirubin levels and hepatitis reactivation-related death, between these two groups of patients. Finally, a multivariable analysis also revealed that HCV carriage was indeed an independent variable leading to the reduced incidence of HBV reactivation in patients with HCV co-infection. CONCLUSION: HCV might affect the reactivation of HBV by decreasing the incidence or delaying the onset of HBV reactivation in renal transplant recipients carrying both HBV and HCV.     

Risk factors for cytomegalovirus reactivation after CD6+ T-cell-depleted allogeneic bone marrow transplantation

BACKGROUND: Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Recipients of T-cell-depleted (TCD) transplants may be more susceptible to CMV infection as a result of the reduction in transferred T cell immunity. We sought to determine the effect of prior donor and patient CMV exposure on the incidence of CMV infection after TCD allogeneic HSCT. METHODS: We retrospectively examined CMV antigen testing results in all patients who had undergone CD6+ TCD related and unrelated donor allogeneic HSCT at our institution from 1996 to 1999. All 124 patients who had documented donor and recipient CMV serologies pretransplant and had undergone CMV antigen testing before day +100 posttransplant were included in the analysis. RESULTS: Forty-one percent of seropositive recipients and 1% of seronegative recipients developed evidence of CMV reactivation (odds ratio 54.1, 95% confidence interval [CI] 6.9-424.1, P<0.001). Prior donor CMV exposure did not place seronegative recipients at increased risk of CMV conversion. Multivariable analysis indicated that prior donor CMV exposure significantly reduced the risk of CMV reactivation in seropositive recipients by 81% (odds ratio 0.19, 95% CI 0.04-0.91, P=0.04). Grades II to IV acute graft-versus-host disease (GVHD) was associated with CMV conversion (P=0.04) when seropositive recipients underwent HSCT from CMV-negative donors, but not when the donor was CMV-seropositive (P=0.54). CONCLUSIONS: The CMV serology status of the recipient, rather than the donor, was the primary determinant of risk for CMV conversion after TCD allogeneic HSCT. Despite CD6+ T-cell depletion, immunity against CMV seemed to be transferred with the donor graft and protected seropositive HSCT recipients from CMV reactivation.     

Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.     

肝移植术后HBV再感染的危险因素分析及对策

目的探讨肝移植术后乙型肝炎病毒(HBV)再感染的危险因素及相关对策。方法对2003年9月至2004年12月间在我院施行原位肝移植术病例进行前瞻性研究,选取符合研究标准的130例患者,采用肌注型乙型肝炎免疫球蛋白(HBIg)联合核苷类抗病毒药物预防HBV再感染,并长期随访,分析HBV再感染的危险因素。结果130例中128例术后血清HBsAg转为阴性,并检测到HBsAb,平均随访12.2个月,HBV再感染率为6.3%(8/128)。结论肝移植术前血清HBeAg阳性、术后第1天血清HBsAg阳性及HBsAb<200U/L是HBV再感染的危险因素。     

肝移植术后HBV再感染的危险因素分析及对策

目的探讨肝移植术后乙型肝炎病毒（HBV）再感染的危险因素及相关对策。方法对2003年9月至2004年12月间在我院施行原位肝移植术病例进行前瞻性研究，选取符合研究标准的130例患者，采用肌注型乙型肝炎免疫球蛋白（HBIg）联合核苷类抗病毒药物预防HBV再感染，并长期随访，分析HBV再感染的危险因素。结果130例中128例术后血清HBsAg转为阴性，并检测到HBsAb，平均随访12．2个月，HBV再感染率为6．3％（8／128）。结论肝移植术前血清HBeAg阳性、术后第1天血清HBsAg阳性及HBsAb〈200U／L是HBV再感染的危险因素。     

原位肝移植术后乙型肝炎病毒再感染的相关因素分析

目的 分析原位肝移植（OLT）术后HBV再感染的相关因素,评价联合应用乙型肝炎免疫球蛋白（HBIG）和核苷（酸）类似物预防HBV再感染的疗效.方法 收集2003年10月-2007年8月在中山大学附属第三医院行OLT治疗的160例HBV相关性终末期肝病患者,117例患者术前服用核苷（酸）类似物.所有患者术后长期肌肉注射HBIG,并联合服用核苷（酸）类似物,采用回顾性调查方法分析患者术前资料,并前瞻性长期随访OLT术后HBV再感染情况.正态分布计量资料2组间的比较采用独立样本t检验;组间率的比较采用Fisher＇s精确概率检验,P〈0.05表示差异具有统计学意义.结果 160例患者中,19例患者出现HBV再感染,再感染率为11.88%（19/160）.患者术前HBV DNA载量、HBeAg状态及抗病毒治疗时间与OLT术后HBV再感染之间无显著相关性（r值分别为0.108、0.127和0.033,P值均〉0.05）.19例HBV再感染患者中有17例是长期使用拉米夫定治疗的患者,其中8例酪氨酸-蛋氨酸-天门冬氨酸-天门冬氨酸（YMDD）变异株阳性,其HBV DNA载量为（7.0±2.0）log拷贝/mL,而YMDD变异阴性组为（3.2±2.5）log拷贝/mL,2组比较差异有统计学意义（t=3.531,P=0.003）.17例长期服用拉米夫定治疗的患者中,12例加用阿德福韦酯,3例改用恩替卡韦,均获得满意疗效.结论 OLT术后长期小剂量肌肉注射HBIG,并联合核苷（酸）类似物可有效预防HBV再感染.OLT术后使用拉米夫定易出现YMDD变异,而YMDD变异是HBV再感染的重要因素,临床上要予以重视.     

Long-term results of famciclovir for recurrent or de novo hepatitis B virus infection after liver transplantation

Since the introduction of famciclovir in the treatment of hepatitis B virus (HBV) infection after liver transplantation, promising results have been published. In this study, the long-term efficacy and safety of famciclovir were assessed. Twenty-four patients with recurrent hepatitis B and 6 patients with de novo infection after liver transplantation were enrolled in an open prospective trial. Patients received oral famciclovir, 500 mg three times daily. Serum HBV-DNA, viral serology, and liver enzymes were measured sequentially; liver histology was taken before and during treatment in 12 patients. In the reinfected patients, 17 patients initially responded well to treatment, with a mean decrease of HBV-DNA of 82%, 5 patients became HBV-DNA negative. The drug was effective for 1-51 months (mean 16 months), then viral replication increased again in 13 out of 17 patients. One patient did not respond to treatment. Six out of 24 patients already had severe cirrhosis at the time of enrollment and died shortly afterwards, due to the HBV infection. The 6 patients with de novo infection all had a decline of HBV-DNA for 2-42 months (mean 14 months); 1 patient converted to HBV-DNA negative. Five out of 6 patients experienced a viral breakthrough later on. No severe side-effects were observed. Therefore, famciclovir is effective in certain HBV-infected patients after orthotopic liver transplantation (OLT), but in the long term, most of the patients relapse.     

活体肝移植治疗HBV相关性急性亚急性肝功能衰竭

目的 探讨活体肝移植(living donor liver transplantation,LDLT)HBV感染导致的急性肝功能衰竭(acute liver failure,ALF)和亚急性肝功能衰竭(subacute liver failure,SALF)患者的可行性,并评价其疗效.方法 回顾性分析2000年11月至2007年10月完成的10例LDLT治疗ALF、SALF患者的临床资料.10例LDLT的供、受者均为成人,切取右半肝为移植物,8例含肝中静脉(middle hepatic vein,MHV).10例供者的评估均在确定实施LDLT的24 h内完成,供、受者手术均在确定供者后的12 h内完成.移植物质量与受者体质量比为(1.03±0.17)%(0.86%～1.22%),移植物体积与受者标准肝体积比为(52.2±11.8)%(47.6%～70.1%).结果 10例受者中,2例分别于术后7、28 d时因肺部感染、十二指肠球部溃疡穿孔腹腔感染死亡.1例胆管吻合口胆漏,经十二指肠镜下置入鼻胆管引流治愈.2例术后1周出现轻度急性排斥反应,增强免疫抑制强度后肝功能恢复正常.8例中位随访期9.6个月(2～84个月),生存质量优良.10例供者中,1例出现急性门静脉高压症导致脾脏破裂,行脾脏切除术,其后出现胆管断端胆漏,经鼻胆管引流结合经皮穿刺腹腔引流治愈.其余9例无并发症发生.结论 LDLT适宜治疗HBV感染导致的ALF、SALF,而且能获得较好的中、远期疗效.     

受体相关肝移植术后乙肝复发的危险因素分析

目的 本研究旨在探讨影响受体相关肝移植术后乙肝复发的危险因素.方法 回顾性搜集、随访、分析北京朝阳医院2013—2019年7年中连续320例有乙肝病史并行肝移植手术治疗的患者的临床资料,搜集可能与乙肝复发有关的围术期参数,并对可能影响患者术后乙肝复发的危险因素进行分析.结果 在320例患者中,原发疾病为乙肝所致肝恶性肿...     

肝移植术后乙型肝炎病毒再激活的分子机制研究进展

肝移植是治疗乙型病毒性肝炎（乙肝）相关性肝衰竭、肝硬化和肝细胞癌（肝癌）的最有效方法。然而,肝移植术后乙型肝炎病毒（HBV）再激活不利于移植肝功能恢复且导致预后不良,其防治问题是当前内、外科医师研究的焦点。目前的病毒抑制策略不能完全根除HBV,也不能完全预防HBV在未来复发感染。本文旨在探讨肝移植术后HBV再激活的分子机制,以期更有效预防肝移植术后乙肝复发。     

Changing of hepatitis B virus markers in patients with bone marrow transplantation

The hepatitis B virus (HBV) infection and its resulting hepatic abnormalities are very high in prevalence among the Taiwan population. They also seem to compose a major problem to patients subjected to bone marrow transplantation (BMT) due to intensive chemoradiotherapy. In this study, the sera of 42 patients were investigated before and after BMT to detect the presence of HBV markers and to test their liver function (LF). Being followed-up for 3-12 months after BMT, 12 out of 27 were found to have altered HBV markers according to the classification of the following: seroconversion of HBsAg, clearance of HBsAb, appearance of HBeAg, clearance of HBeAb, and acute hepatitis. Thirty-seven out of 42 patients (88.1%) were found in routine LF test to develop one or more abnormality; however, 90% of them turned normal within one year after BMT. Only one patient died of complications associated with fulminant hepatitis. In conclusion, the previous hepatic damage from HBV infection appears unlikely to increase the risk of posttransplant morbidity and mortality.     

Antiviral treatment for hepatitis B virus recurrence following liver transplantation

The purpose of this study was to identify the factors associated with the recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for HBV‐related disease and to recognize the outcome of treatment for HBV recurrence with oral nucleos(t)ide analogues. Six hundred and sixty‐seven LTs were performed for HBsAg‐positive adult patients in our institute from 1996 to 2010. HBV prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV recurrences during a median follow‐up of 51 months. The median time to HBV recurrence was 22 months. A preoperative HBV DNA load of more than 10⁵ IU/mL, HBIG monotherapy, and hepatocellular carcinoma in the explant liver were independent risk factors for HBV recurrence following LT in multivariate analysis. Patient survival at 10 yr was 54.2% for HBV‐recurrent patients. Among patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients (20.6%), but HBsAg seroclearance did not affect survival in these patients after the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in six cases. HBV recurrence should be prevented by strict management of pre‐transplant HBV viremia and an effective post‐transplant HBV prophylaxis.     

肝移植术后丙型肝炎病毒的再感染与丙肝复发

丙肝肝炎后肝移植病人均伴随不同程度的丙型肝炎病毒(HCV)复发,其发病机制因疾病的不同阶段而不同.影响复发的因素包括HCV基因型、病毒载量、供体和受体HLA匹配情况、复发的时间、供体的年龄等,而免疫抑制剂的使用是最重要的影响因素.治疗的效果通过持续病毒学应答来评价.目前认为聚二乙醇干扰素联合利巴韦林是治疗慢性丙型肝炎最好的选择和最佳的治疗方案.     

Sperm ultrastructure and meiotic segregation in a group of patients with chronic hepatitis B and C

Little is known about the effect of chronic hepatitis B and hepatitis C on sperm quality. In this study, we analysed sperm quality from selected patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. Semen samples were examined by light and transmission electron microscopy (TEM). TEM data were elaborated with a mathematical formula able to indicate a fertility index and the presence of the three main sperm pathologies: apoptosis, immaturity and necrosis. Meiotic chromosome segregation was investigated by fluorescence in situ hybridisation carried out on sperm nuclei, using probes for chromosomes 18, X and Y. Despite normal sperm concentration, we observed reduced motility. TEM analysis highlighted that 35.7% of patients showed generally good semen quality. However, significantly higher values of apoptosis and necrosis, compared with controls, were observed, demonstrating spermatogenetic alterations. Regarding meiotic segregation, we found an incidence of disomies similar to that observed in control samples, whereas diploidy resulted higher in HCV patients, without reaching statistical significance. In conclusion, sperm quality in the studied group was not impaired; however, apoptosis and necrosis resulted out of normal range and the fertility index was significantly lower in HCV- and HBV-infected patients versus controls.     

Definitions of cytomegalovirus disease after heart transplantation: Antigenemia as a marker for antiviral therapy

In this prospective study, cytomegalovirus (CMV) antigenemia was defined as the marker for initiation and episodes of antigenemia as the indicator for the duration of antiviral therapy (CMV hyperimmune globulin and ganciclovir). The CMV antigenemia assay and CMV-specific IgM and IgG antibody tests were used to monitor CMV infection in 22 heart transplant recipients who, between October 1992 and July 1994, were followed up for 6 months. A total of 178 out of 627 antigenemia assays tested positive. The highest number of positive cells was greater after primary infection than after either reactivation (43.3 vs 0.3; P<0.01) or reinfection (43.3 vs 9.3; P=NS). Sixty episodes of antigenemia were observed. More episodes of antigenemia were seen after primary infection than after either reactivation (4.6 vs 0.2; P<0.01) or reinfection (4.6 vs 2.2; P=NS). The detection of antigenemia indicated the initiation of antiviral therapy within 24 h after the blood sample was harvested. Therapy was stopped immediately after a subsequent negative result became available. Our experience indicates that antigenemia directed antiviral therapy prevents CMV disease after primary and secondary infection in heart transplant recipients.     

Fulminant hepatitis is significantly increased in hepatitis B carriers after allogeneic bone marrow transplantation.

BACKGROUND: Bone marrow transplantation (BMT) is effective treatment for many hematologic disease, but performed in a population with a high endemic hepatitis B virus carrier rate, the incidence of liver function impairment and fulminant hepatitis (FH) is expected to be raised. METHODS: Forty-three hepatitis B virus carriers received high-dose chemotherapy and BMT, 32 patients received an allogeneic graft, and 11 patients autologous marrow. Acute graft-versus-host disease prophylaxis consisted of methotrexate on day 1, 3, 6, and 11 and cyclosporine for 6 months. RESULTS: After a median follow-up period of 68 months (range: 1-11.5 years), 26 (81.3%) allogeneic BMT patients developed impaired liver function (LF), 5 progressed to FH on day 93, 169, 170, 180, and 468, respectively, and died after an average of 13.8 days (range: 1-45 days). Whereas only 4 (36.4%) autologous BMT patients developed impaired LF, and none FH. Impaired LF (P=0.026, chi-square), and FH (odds ratio=12.86, P=0.009 for coefficient) were significantly related to an allogeneic marrow graft, and the timing of liver function impairment coincided with cyclosporine withdrawal. Hepatitis B surface antigen (HbsAg) disappeared from the serum in 4/14 (28.6%) patients receiving a marrow graft from an HbsAg+ donor. HbsAg was not detected in the serum after BMT in 2/11 (18.2%) autologous BMT patients. CONCLUSIONS: Hepatitis B virus carriers receiving a marrow graft from an HbsAg+ donor have a significantly increased risk of FH.     

低剂量膦甲酸钠治疗骨髓移植后巨细胞病毒感染

目的 探讨采用低剂量膦甲酸钠治疗HLA单倍型相合骨髓移植后巨细胞病毒(CMV)感染的临床效果及不良反应.方法 行HLA单倍型相合未去T淋巴细胞骨髓移植的患者54例,移植前采集供、受者外周血,采用CMV Brite试剂盒检测CMV磷蛋白(CMV pp65)阳性细胞.受者于移植前9 d开始采用更昔洛韦预防CMV感染,至移植当天改为阿昔洛韦.患者的造血功能恢复后,每周检测CMV pp65,阳性者即给予膦甲酸钠60 mg·kg-1·d-1,至CMV pp65转为阴性3 d后停药.结果 54例均获得造血功能重建,其中18例移植后CMV pp65为阳性,发生时间为移植后30～93d,应用膦甲酸钠治疗7～21 d后全部转阴,其中1例考虑为CMV肠炎,将膦甲酸钠的剂量增加至120 mg·kg-1·d-1.膦甲酸钠治疗前后,患者的血电解质、肾功能、白细胞和血小板数等均无明显变化.结论 低剂量膦甲酸钠能有效控制骨髓移植后CMV感染,且无严重不良反应.     

原位肝移植术后乙型肝炎病毒再感染的预防(附68例报告)

目的探讨原位肝移植术后乙型肝炎病毒(HBV)再感染的预防。方法68例病人分别为慢性乙型重型肝炎、终末期肝硬化和肝硬化合并肝癌病人,移植前后给予抗病毒药物预防HBV再感染,拉米夫定2例,拉米夫定加乙型肝炎免疫球蛋白(HBIG)63例,阿德夫韦加HBIG3例;观察预防性治疗后的临床表现、血清HBV、HBVDNA及肝活检免疫组织化学法检测等指标。结果应用拉米夫定的2例病人,有1例发生再感染,其血清HBsAg、抗Hbe、抗HBc和HBVDNA均呈阳性,肝活检免疫组织化学检测有HBsAg表达。用拉米夫定加HBIG预防的63例中,有2例再感染,血清均呈HBsAg、抗HBe和抗HBc阳性,肝活检免疫组织化学法检测有HBsAg表达,其中1例血清HBVDNA阳性。用阿德夫韦加HBIG预防的3例中,血清学和肝活检免疫组织化学法检测均无HBsAg表达。结论原位肝移植术是治疗HBV感染相关的终末期肝病的有效手段,拉米夫定加HBIG或阿德夫韦加HBIG联合应用可以有效地预防HBV的再感染。     

Research advances in reactivation of hepatitis virus after chemotherapy for non-Hodgkin's lymphoma-combined hepatitis B virus infection

Infection rate of hepatitis B virus(HBV) in our country remains high. Many patients showed combined HBV infection; the most common blood system disease is non-Hodgkin's lymphoma(NHL)-combined HBV infection. Drugs used in treating lymphoma may induce different degrees of HBV reactivation. Such condition may lead to hepatic failure or death. Currently, scholars pay increasing attention to reactivation of HBV by rituximab and/or chemotherapy for NHL-combined HBV patients. This study summarizes research advances in this topic, with a view of providing background information for further research.