肝移植术后乙型肝炎复发的预防和治疗

目的探讨拉米夫定联合低剂量乙型肝炎（乙肝）免疫球蛋白（HBIG）预防肝移植术后乙肝复发的效果及乙肝复发后的治疗。方法对2000年12月至2003年5月因乙肝相关性终末期肝病和（或）合并肝细胞癌于我院接受肝移植手术并经随访的11例患者进行回顾性分析。所有患者均接受拉米夫定联合低剂量HBIG预防乙肝复发方案。观察术后近期乙肝转阴情况、术后较远期乙肝复发情况以及乙肝复发后的治疗情况。结果（1）所有患者HBsAg、HBeAg、HBV-DNA均于术后1-4d转为阴性,术后1周所有患者对HBIG均有反应,HBsAb滴度水平逐渐上升;（2）所有患者于观察期内生存情况均良好,对患者HBsAb滴度水平定期进行监测结果示大部分患者HBsAb滴度水平与预期治疗水平基本符合;（3）1例患者于术后25个月乙肝复发,通过改用阿德弗韦并加大HBIG用量,基本得到控制。结论拉米夫定联合低剂量HBIG预防肝移植后乙肝复发疗效确切,而且可显著降低治疗费用。     

乙型肝炎相关性肝脏疾病肝移植后乙型肝炎复发的预防

肝移植是目前唯一有效的治疗终末期肝脏疾病的方式［１］，但乙型肝炎相关性肝脏疾病肝移植后ＨＢＶ的再感染率可高达６７％～８０％，而复发后生存率明显下降，３年生存率仅４４％［２，３］。移植物感染后１～２年内会迅速发生肝硬化，导致肝功能异常，直至肝功能衰竭［４］。由于上述问题，９０年代初期许多移植中心将ＨＢＶ有关的肝脏疾病列为禁忌证，美国的ＨＣＦＡ（Ｈｅａｌｔｈ　Ｃａｒｅ　Ｆｉｎａｎｃｉｎｇ　Ａｄｍｉｎｉｓｔｒａｔｉｏｎ）也曾拒绝为这种病人肝移植的费用进行补偿［５］。９０年代中期以来，以新的抗病毒药物为…     

预防肝移植术后乙型肝炎复发的研究进展（文献综述）

肝移植后乙肝复发一直是影响肝移植患者预后的重要问题，未作预防的乙肝病毒(HBV)感染者移植术后HBV的再感染率在80％以上，居乙肝肝硬化肝移植后死亡原因的首位，积极而有效地防治肝移植术后乙型肝炎的复发已成为手术后面临的关键问题。本文就近期的一些进展作一综述。     

预防和治疗肝移植术后乙型肝炎复发(附3例报告)

乙型肝炎复发是直接影响肝移植术后患者长期存活的一个主要因素。人们一直在努力探索预防乙型肝炎复发的有效、经济、安全的方法。现将我们应用核苷类似物预防和治疗肝移植术后乙型肝炎复发的体会报道如下。一、资料与方法我院 1 997年 3月至 1 999年 1 1月为 3例患者进行了同种异体原位肝移植术。受者年龄 2 2～ 53岁 ,均为男性。 3例术前诊断均为乙型肝炎后肝硬化 ,肝功失代偿期。术前乙型肝炎病毒 (ＨＢＶ)血清学检查及血清ＰＣＲ定性检查如表 1所示。表 1　移植前ＨＢＶ感染状况病例 检测项目ＨＢｓＡｇ ＨＢｃＡｂＨＢｅＡｇ ＰＣＲ例 …     

小剂量抗乙型肝炎免疫球蛋白和拉米夫定预防肝移植后乙型肝炎复发

近来国外报道，抗乙型肝炎免疫球蛋白(HBIG)和拉米夫定在预防乙型肝炎、肝硬化患者肝移植后乙型肝炎的复发中取得了良好的效果。现将我院使用该方案预防乙型肝炎复发的临床资料报告如下。     

树突状细胞在预防肝移植术后乙型肝炎复发中的作用

乙型肝炎肝功能衰竭患者肝移植后的乙型肝炎复发率高达70%～80％，复发后的1年存活率为68％，3年存活率仅44％，使乙型肝炎病毒(HHV)相关肝病肝移植术后远期效果难以令人满意。近年，抗乙型肝炎免疫球蛋白(HBIG)及拉米夫定的应用在防治乙型肝炎复发方面取得了一定效果，但因其自身的缺点，如停药后复发、诱导病毒变异和耐药等，使其不能成为彻底预防乙型肝炎复发的方法。     

肝移植术后预防移植物HBV再感染的系列研究

肝移植作为治疗终末期肝病的惟一有效手段已成为一个日渐成熟的技术。在所有肝移植受体的原发病因中80％直接与乙肝病毒的早期感染有关。移植物HBV再感染及其后发生的乙型肝炎复发是影响乙肝相关性终末期良性肝病远期生存的决定因素。[第一段]     

拉米夫定及乙型肝炎免疫球蛋白预防肝移植后乙型肝炎复发的疗效观察

目的:研究单用拉米夫定或与乙型肝炎(乙肝)免疫球蛋白(HBIG)联合应用对乙肝相关肝病病人肝移植术后预防乙肝复发的效果。方法:应用酶联免疫试验(EIA)检测HBsAg、抗鄄HBs、HBeAg、抗鄄HBe及抗鄄HBc;用聚合酶链反应法(PCR)检测乙肝病毒(HBV)DNA。26例单用拉米夫定15例,联合应用拉米夫定和HBIG11例。结果:26例乙肝相关肝病病人于肝移植术后随访3～24个月,2例死亡,4例出现乙肝复发,其余20例病人HBsAg持续阴性。结论:肝移植是治疗乙肝终末期病人的有效方法,拉米夫定与HBIG联合应用可有效预防肝移植术后乙肝复发。     

乙型肝炎免疫球蛋白在预防肝移植后乙型肝炎复发中的作用

近年来认识到人乙型肝炎免疫球蛋白（HBIG）在乙型肝炎相关性肝病肝移植后预防原病复发中具有重要作用，但在其应用途径、剂量和持续时间方面观点不尽相同。本文重点综述乙型肝炎相关性肝病肝移植后原病复发的机制、HBIG干预原理以及HBIG的给予途径、剂量和策略性减量、停药等，旨在进一步提高HBIG的干预效果、降低干预费用、减少用药不良反应。     

预防肝癌肝移植术后复发转移的策略

<正>我国是世界上肝癌发病率最高的国家,占癌症死亡率的第二位。手术切除是肝癌病人获得长期生存的主要手段,但大部分肝癌病人就诊时已属晚     

肝移植术后乙肝复发的预防和治疗

目的 探讨乙肝相关疾病患者肝移植术后乙型肝炎病毒(HBV)再感染的防治。方法 复习有关文献并进行综述。结果 与HBV有关的急、慢性肝病是肝移植的主要适应证，但未作预防者移植后HBV再感染率可达80％～100％，对移植肝的存活和患者的生存有重大的影响。如何防治肝移植后乙型肝炎的复发，成为急需解决的问题。经过一系列的摸索，目前已有许多用于防治HBV再感染的药物，包括抗乙肝免疫球蛋白、干扰素、核苷类似物等，其各自有不同的应用特点，在单独及联合用药方面也有了新的研究进展。结论 肝移植是治疗乙肝相关疾病的有效方法，围手术期的积极药物治疗，对提高乙肝相关疾病患者肝移植的成功率至关重要。     

Combined Lamivudine and Hepatitis B Immunoglobulin for the Prevention of Hepatitis B Recurrence after Liver Transplantation: Long-Term Results

For the prevention of recurrent hepatitis B virus (HBV) infection after liver transplantation (LT), the efficacy of hepatitis B immunoglobulin (HBIg) has been largely demonstrated. The aim of this pilot study was to determine if the addition of lamivudine to HBIg in the prevention of HBV recurrence after LT could be more effective. Sixty HBsAg-positive/HBV DNA-negative patients underwent LT from October 1990 to December 2001. All 60 patients received intravenous HBIg to maintain serum anti-HB levels above 500 IU/L, indefinitely. Since 1997, 17 patients have received combined oral lamivudine (150 mg/day) and HBIg, and were compared with the historical cohort of 43 patients. In the historical control group, the recurrence rate was 10/43 (23%) after a 98-month median follow-up. Five patients died from HBV-related liver disease. After a 30-month median follow-up, none of the 17 patients in the combined prophylaxis group experienced HBV recurrence, and HBV DNA was undetectable by PCR in at least three serum samples per patient. HBV recurrence was significantly lower when compared with the historical control group (10/43 vs. 0/17, p < 0.01). Our results suggest that combined lamivudine and HBIg can avoid the recurrence of HBV infection in patients who are HBsAg-positive/HBV DNA negative before LT.     

Hepatitis C Virus Compartmentalization and Infection Recurrence after Liver Transplantation

Hepatitis C virus (HCV) compartmentalization may have important implications in the pathogenesis of HCV infection. The aim of this study was to investigate the presence and relevance of HCV compartmentalization in the setting of liver transplantation (LT). We collected samples of serum, peripheral blood mononuclear cells (PBMC), perihepatic lymph nodes (PLN) and liver explant at the time of LT, and serum and PBMC after transplantation from 57 HCV-infected cirrhotic patients undergoing LT: 38 individuals received antiviral treatment before LT and 19 were untreated controls. HCV-RNA levels were determined by real-time PCR and the hypervariable region 1 (HVR-1) was sequenced. HCV-RNA was detected in all samples from control patients. In virological responders, recurrence after LT was associated with residual HCV-RNA in the liver explant. Within the entire cohort, 47% of patients harbored differences in direct sequences from distinct compartments. Quasispecies analysis revealed that in most cases, HVR-1 sequences recovered after infection recurrence were identical or closely related to those isolated from the liver explant and serum at the time of LT. Our study shows that a significant proportion of HCV-infected cirrhotic patients exhibit compartmentalization. Viral variants originating within the liver appear to be the main cause of HCV recurrence after LT.     

Liver Transplantation for Hepatitis C: Recurrence and Disease Progression in 300 Patients

The time progression of allograft damage in patients with recurrent hepatitis C after orthotopic liver transplantation (OLT) is not precisely determined. The aim of this analysis is to study the progression of disease recurrence and its impact on patient and graft survival. Data for 300 patients who underwent OLT for hepatitis C were analyzed regarding the incidence of histological recurrence, risk factors, immunosuppressive regimen, rejection episodes, and survival. For patients with histological recurrence, the timing and risks for disease progression were analyzed. Data for 30 patients who underwent retransplantation were studied. Histological recurrence occurred in 40.3% of patients, 27.2% of whom progressed to bridging fibrosis or cirrhosis. Eighty-seven percent of the patients experienced recurrence of disease within 24 months of OLT. Patients with histological recurrence within 6 months of OLT had an increased risk for progression to cirrhosis compared with patients with recurrence later than 6 months (risk ratio, 2.3). Recurrence within 1 year was associated with decreased patient and graft survival rates at 1 and 5 years (65.1% and 56.4% versus 80.6% and 78.4%; P = .004 andP = .0008, respectively). Patients with histological recurrence had a greater incidence of acute cellular rejection, as well as multiple episodes of rejection, steroid-resistant rejections, and greater cumulative doses of corticosteroids. Histological recurrence after OLT for hepatitis C is common and usually occurs within 2 years of OLT. Early recurrence negatively affects patient and graft survival. Host factors impacting on recurrence need further study. A relation between the hepatitis C virus, allograft rejection, and immunosuppression exists and needs investigation. (Liver Transpl 2000;6:553-561.)     

Telbivudine Prophylaxis for Hepatitis B Virus Recurrence After Liver Transplantation Improves Renal Function

Introduction

Renal impairment after liver transplantation represents an important issue in the management of transplantation patients, particularly when those subjects may need prophylaxis for fungal or viral infection. Herein we report our experience with 12 transplantation patients receiving telbivudine 600 mg/d while on the waiting list, followed by treatment for 18 months after liver transplantation, showing an improvement on their renal function during the follow-up period.

Methods

Our series consisted of men with hepatitis B virus (HBV)–related end-stage liver disease. The viral load decreased rapidly while on the waiting list once the patient was started on antiviral treatment. Those subjects were compared with 12 patients on lamivudine prophylaxis. All patients were evaluated for liver and renal function, immunosuppression trough levels, and creatine phosphokinase (CPK) before liver transplantation (T0) and at 3, 6, 12, and 18 months (T3, T6, T12, T18).

Results

All patients received a calcineurin inhibitor immunosuppression-based regimen. Creatinine clearance (Modification of Diet in Renal Disease) was 67 mL/min at T0, with a statistically significant improvement after month 6 compared with those on lamivudine and with the value at the beginning of the prophylaxis (Mann-Whitney U test P < .05). Neither CPK nor transaminase serum levels increased throughout the study period. Once HBV DNA was cleared while on the waiting list, it remained negative throughout the follow-up period.

Conclusions

Telbivudine prophylaxis for HBV is safe and effective, without any significant deleterious effect on the liver; on the contrary, it seems to improve renal function after liver transplantation through 18 months. Further studies and larger series are warranted to confirm these findings.     

Lamivudine After Hepatitis B Immune Globulin Is Effective in Preventing Hepatitis B Recurrence After Liver Transplantation

The prevention of recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) with hepatitis B immunoglobulin (HBIG) is expensive and requires indefinite parenteral administration. Lamivudine is a nucleoside analogue capable of inhibiting HBV replication. The aim of this study is to determine the efficacy of lamivudine in the prevention of recurrent HBV infection after a course of HBIG in patients who were hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBeAg) negative before OLT. Patients at high risk for recurrent HBV infection (HBeAg positive and HBV DNA positive) were excluded. Thirty HBsAg-positive, HBeAg-negative patients underwent OLT from January 1993 to June 1997. All 30 patients were administered HBIG after OLT and, after 2 years, were given the option of continuing with HBIG or switching to lamivudine. Five patients were excluded: 3 patients were lost to follow-up and 2 patients died of technical complications. Three patients terminated HBIG therapy at 8, 24, and 29 months after OLT, and reinfection with HBV occurred in 1 patient. Six patients elected to continue HBIG therapy for life; 1 patient died of melanoma and the remaining 5 patients are HBsAg negative, with an average follow-up of 73 months. Sixteen patients were converted to lamivudine after a course of HBIG, and all 16 patients are HBsAg negative, with an average follow-up of 51 months after OLT. Five patients have been on lamivudine monotherapy for more than 24 months. These results suggest that lamivudine administered after a posttransplantation course of HBIG can effectively prevent the recurrence of HBV infection in patients who are HBsAg positive and HBeAg negative before OLT. (Liver Transpl 2000;6:434-439.)     

拉米夫定对肝移植术后乙肝病毒再感染的预防作用

目的 探讨单一应用拉米夫定预防良性乙肝相关性肝病肝移植术后乙肝病毒再感染的疗效。方法 总结单一应用拉米夫定预防肝移植术后生存时间大于3个月的31例良性乙肝相关性终末期肝病患者的乙肝病毒再感染情况，同时检测肝移植手术前、后血清及肝穿刺组织乙肝表面标志物及HBVDNA的变化。结果 31例患者随访时间平均为38．2个月（3．2～70．2个月），随访期间死亡8例。乙肝病毒总的再感染率为19．4％（6／31），术后1、3、5年乙肝再感染率分别为7．1％（2／28）、16．0％（4／25）及26．1％（6／23），生存率分别为87．1％（27／31）、80．6％（25／31）及66．1％（20．5／31）。术前HBeAg和HBVDNA的清除率分别为54．5％（6／11）和50．0％（5／10）。术前HBVDNA和HBeAg阳性患者术后乙肝病毒再感染率高。结论 拉米夫定可以有效地预防良性乙肝相关性肝病患者肝移植术后乙肝病毒的再感染；术前应尽可能使HBVDNA和HBeAg转阴。     

Natural History of Patients with Recurrent Chronic Hepatitis C Virus and Occult Hepatitis B Co-Infection after Liver Transplantation

It is uncertain whether occult hepatitis B virus co-infection will hasten progressive liver disease in chronic hepatitis C patients after liver transplantation. This study evaluated fibrosis progression and severe fibrosis in 118 consecutive hepatitis B surface antigen-negative patients with virological and histological evidence of recurrent chronic hepatitis C infection co-infected with occult hepatitis B virus after liver transplantation. HBV DNA was detected from serum at the time of recurrent chronic hepatitis C infection by polymerase chain reaction. Each subject underwent a repeat liver biopsy 5 years post-liver transplantation. Occult hepatitis B virus co-infection was present in 41 of the 118 (34.7%) patients. At 5 years post-liver transplantation, 13 of the 41 occult hepatitis B virus co-infected patients compared with 16 of the 77 patients without occult hepatitis B virus co-infection developed fibrosis progression (31.7% vs. 20.8%, respectively, p = 0.39). Eight of 41 the occult hepatitis B virus co-infected patients compared with 13 of the 77 patients without occult hepatitis B virus co-infection had severe fibrosis (19.5% vs. 16.9%, respectively, p = 0.97). In conclusion, occult hepatitis B virus co-infection in patients with recurrent chronic hepatitis C infection was not associated with accelerated fibrosis progression or severe fibrosis after liver transplantation.