肝移植后丙型病毒性肝炎复发治疗时获得持续病毒应答的影响因素

目的 探讨聚二乙醇干扰素治疗肝移植后丙型病毒性肝炎复发的效果,分析影响产生持续病毒应答率(SVR)的因素.方法 将肝移植后丙型病毒性肝炎复发并使用聚乙二醇干扰素α-2a进行抗丙型肝炎病毒(HCV)治疗的39例患者纳入研究,其中有21例因为抗HCV治疗无效或发生不良反应而中途停药,其余18例接受了全疗程规范治疗.18例患者中,男性13例,女性5例,平均年龄54岁(27～67岁),疗程25～105周.治疗后4、12、24周,病毒转阴后24周及停药后24周,检测HCV RNA的复制水平.停药后24周HCV RNA复制持续阴性为产生SVR.对患者年龄,性别,治疗前HCV RNA水平,HCV基因型,是否获得早期病毒应答(EVR),治疗前血清AST水平等因素与获得SVR的相关性进行分析.结果 有4例(22.2%)患者获得了SVR,其平均治疗周期为57周.经统计分析显示,HCV基因型为非1B型(P=0.023),治疗前HCV RNA载量＜106拷贝/ml(P=0.044),以及获得EVR(P=0.019)等3个参数与获得SVR密切相关.结论 HCV基因型为非1B型、治疗前低水平HCV RNA复制和获得EVR可作为肝移植后丙型病毒性肝炎复发抗HCV治疗疗效的有效预测因子.

Abstract：

Objective To investigate the efficacy of pegylated interferon (Peg-IFN) plus ribavirin to treat hepatitis C virus (HCV) recurrence, and analyze possible factors associated with sustained viral responses (SVR). Methods The enrolled 39 patients, who had recurrence of hepatitis C after liver transplantation and received antiretroviral therapy, were analyzed. Treatment was discontinued in 21 patients due to side effects, and the remaining 18 patients [13 males, 5 female,median age of 54 (27-67) years, treatment duration of 25-105 weeks)] were subjected to whole standard treatment. During the treatment, HCV RNA was measured at 4, 12, 24, and 24 weeks after HCV negative change as well as drug withdrawal. SVR was defined as HCV RNA negativity within 24 weeks after the drug withdrawal. The following variables were analyzed: ages, gender,pretreatment viral load, genotype, early viral response (EVR), levels of alanine aminotransferase before treatment and their association with SVR. Results The mean treatment duration was 57weeks with an SVR achieved in 4/18 (22. 2 %). Statistical analysis revealed that the genotype of non1B (P=0.023), RNA ＜106 copy/ml (P= 0. 044) before treatment and EVR (P=0.019) were the variables associated with SVR. Conclusion Genotype of nor-1B, low level RNA before treatment and EVR were the effective predictors of interferon antiviral therapy for recurrent hepatitis C after liver transplantation.     

肝移植后丙型病毒性肝炎复发治疗时获得持续病毒应答的影响因素

Objective To investigate the efficacy of pegylated interferon (Peg-IFN) plus ribavirin to treat hepatitis C virus (HCV) recurrence, and analyze possible factors associated with sustained viral responses (SVR). Methods The enrolled 39 patients, who had recurrence of hepatitis C after liver transplantation and received antiretroviral therapy, were analyzed. Treatment was discontinued in 21 patients due to side effects, and the remaining 18 patients [13 males, 5 female,median age of 54 (27-67) years, treatment duration of 25-105 weeks)] were subjected to whole standard treatment. During the treatment, HCV RNA was measured at 4, 12, 24, and 24 weeks after HCV negative change as well as drug withdrawal. SVR was defined as HCV RNA negativity within 24 weeks after the drug withdrawal. The following variables were analyzed: ages, gender,pretreatment viral load, genotype, early viral response (EVR), levels of alanine aminotransferase before treatment and their association with SVR. Results The mean treatment duration was 57weeks with an SVR achieved in 4/18 (22. 2 %). Statistical analysis revealed that the genotype of non1B (P=0.023), RNA ＜106 copy/ml (P= 0. 044) before treatment and EVR (P=0.019) were the variables associated with SVR. Conclusion Genotype of nor-1B, low level RNA before treatment and EVR were the effective predictors of interferon antiviral therapy for recurrent hepatitis C after liver transplantation.     

肝移植术后丙型病毒性肝炎复发的影响因素、监测与治疗

欧美国家的丙型肝炎病毒（hepatitis C virus,HCV）感染人数已超过乙型病毒性肝炎（乙肝）的感染人数,HCV感染已成为终末期肝病患者进行肝移植最主要的病因。丙型病毒性肝炎（丙肝）呈全球性流行,我国的HCV感染率也相当高,全国病毒性肝炎血清流行病学调查结果显示,     

肝移植后丙型病毒性肝炎复发治疗时获得持续病毒应答的影响因素

Objective To investigate the efficacy of pegylated interferon (Peg-IFN) plus ribavirin to treat hepatitis C virus (HCV) recurrence, and analyze possible factors associated with sustained viral responses (SVR). Methods The enrolled 39 patients, who had recurrence of hepatitis C after liver transplantation and received antiretroviral therapy, were analyzed. Treatment was discontinued in 21 patients due to side effects, and the remaining 18 patients [13 males, 5 female,median age of 54 (27-67) years, treatment duration of 25-105 weeks)] were subjected to whole standard treatment. During the treatment, HCV RNA was measured at 4, 12, 24, and 24 weeks after HCV negative change as well as drug withdrawal. SVR was defined as HCV RNA negativity within 24 weeks after the drug withdrawal. The following variables were analyzed: ages, gender,pretreatment viral load, genotype, early viral response (EVR), levels of alanine aminotransferase before treatment and their association with SVR. Results The mean treatment duration was 57weeks with an SVR achieved in 4/18 (22. 2 %). Statistical analysis revealed that the genotype of non1B (P=0.023), RNA ＜106 copy/ml (P= 0. 044) before treatment and EVR (P=0.019) were the variables associated with SVR. Conclusion Genotype of nor-1B, low level RNA before treatment and EVR were the effective predictors of interferon antiviral therapy for recurrent hepatitis C after liver transplantation.     

肝移植后丙型病毒性肝炎复发治疗时获得持续病毒应答的影响因素

Objective To investigate the efficacy of pegylated interferon (Peg-IFN) plus ribavirin to treat hepatitis C virus (HCV) recurrence, and analyze possible factors associated with sustained viral responses (SVR). Methods The enrolled 39 patients, who had recurrence of hepatitis C after liver transplantation and received antiretroviral therapy, were analyzed. Treatment was discontinued in 21 patients due to side effects, and the remaining 18 patients [13 males, 5 female,median age of 54 (27-67) years, treatment duration of 25-105 weeks)] were subjected to whole standard treatment. During the treatment, HCV RNA was measured at 4, 12, 24, and 24 weeks after HCV negative change as well as drug withdrawal. SVR was defined as HCV RNA negativity within 24 weeks after the drug withdrawal. The following variables were analyzed: ages, gender,pretreatment viral load, genotype, early viral response (EVR), levels of alanine aminotransferase before treatment and their association with SVR. Results The mean treatment duration was 57weeks with an SVR achieved in 4/18 (22. 2 %). Statistical analysis revealed that the genotype of non1B (P=0.023), RNA ＜106 copy/ml (P= 0. 044) before treatment and EVR (P=0.019) were the variables associated with SVR. Conclusion Genotype of nor-1B, low level RNA before treatment and EVR were the effective predictors of interferon antiviral therapy for recurrent hepatitis C after liver transplantation.     

丙型肝炎病毒基因型和抗病毒治疗病毒学应答的相关性研究

目的探讨慢性丙型肝炎病毒（HCV）感染者病毒基因型对聚乙二醇化干扰素联合利巴韦林抗病毒治疗病毒学应答的影响。方法采用PCR产物直接测序法检测71例HCV感染者的HCV基因型。所有患者接受聚乙二醇化干扰素皮下注射,联合口服利巴韦林抗病毒治疗。分析HCV基因型对快速病毒学应答（RVR）、早期病毒学应答（EVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答（SVR）的影响。结果71例患者中,HCV基因1b型48例,占67.6%;2a型12例,占16.9%;3a型6例,占8.5%;3b型2例,占2.8%;6a型1例,占1.4%;未分型2例,占2.8%。治疗4周时,基因1型组和非1型组的RVR分别为27.1%和87.0%,差异具有统计学意义（χ2=22.4076,P=0.000002）。治疗12周时,基因1型组和非1型组的EVR分别为39.6%和13.0%,差异有统计学意义（χ2=5.1216,P=0.02363）。疗程结束时,基因1型组和非1型组的ETVR分别为68.8%和100%,差异无统计学意义（χ2=2.9520,P=0.08577）。已停药随访24周的患者出现SVR者,基因1型组、非1型组分别为62.22%和100%,差异具有统计学意义（χ2=8.3797,P=0.00379）。结论我国HCV感染者基因型以1b型和2a型为主。基因1型HCV感染者的RVR、EVR和SVR均低于非基因1型者。     

肝移植患者乙型肝炎病毒再感染的防治

目的 预防和早期诊断肝移植患者术后乙型肝炎病毒（ＨＢＶ）再感染和乙型肝炎（乙肝）的复发,以及探讨肝炎复发后的进一步治疗。方法 肝移植患者术后常规采用拉米夫定预防ＨＢＶ再感染,同时监测肝功能、乙型肝炎血清标记物、血清ＨＢＶ－ＤＮＡ、肝活检组织乙型肝炎标记物免疫组化。结果 ４例患者出现ＨＢＶ再感染,其中２例表现为复发的乙型肝炎,经治疗后,２例复发的乙肝患者１例继续发展成为慢必 症肝炎,１例好转。结论     

肝移植术后肝癌复发对HBV再感染的影响

目的 探讨肝移植术后肝癌复发对HBV再感染的影响.方法 回顾性分析285例原发病为乙肝相关性疾病且术后随访超过半年的原位肝移植患者资料.结果 285例肝移植患者随访时间为6～59个月,术后HBV再感染10例,再感染率为3.5%.其中9例患者合并肝癌复发,HBV再感染发生于肝癌复发后1～7个月.肝癌复发患者与肝癌未复发和良性肝病患者HBV再感染的差异具有统计学意义.13例肝癌复发或转移灶切除标本中有1例免疫组化染色HBsAg阳性、HBcAg弱阳性.结论 乙肝免疫球蛋白联合核苷类似物是预防肝移植术后乙肝复发的有效治疗措施,肝癌复发是肝移植术后HBV再感染的重要原因.     

肝移植后肝炎病毒再感染的防治进展

人体肝移植是目前各种终末期肝病及肝功能衰竭最有效的治疗手段。肝炎病毒特别是乙型肝炎病毒 (ＨＢＶ)与丙型肝炎病毒 (ＨＣＶ)所致的急慢性严重肝病是肝移植的重要适应证 ,但此类病人肝移植后常发生肝炎病毒的再感染或复发感染 ,再感染可导致植入肝脏发生炎症、纤维化及功能衰竭 ,严重影响移植肝存活率及病人生存率 ,是影响预后的关键因素。近年来国外在肝移植后ＨＢＶ及ＨＣＶ再感染防治方面积累了一些成功的经验 ,现就有关文献综述如下。一、 再感染的发病机制肝移植后发生肝炎病毒再感染的机制较为复杂 ,许多环节尚待进一步阐明。由于…     

一种肝脏持续表达丙型肝炎病毒核心蛋白的小动物模型

目的　建立肝脏持续表达丙型肝炎病毒核心 (HCVcore)蛋白的大鼠模型 ,为进一步研究HCV核心蛋白的功能和体内致病机制提供帮助。方法　应用聚合酶链反应法扩增出HCV Core区cDNA ,以重组腺伴随病毒载体介导的病毒重组技术制备含HCVCore的重组腺伴随病毒。重组病毒感染 2 0只雄性SD大鼠肝脏 ,感染后 1个月及 4个月行Southernblot印迹杂交法和Dotblot杂交法检测鼠肝内HCVCore区基因整合、mRNA形成情况。结果　测序证实成功克隆出HCVCorecDNA ,重组腺伴随病毒滴度为 2 .41× 10 11/ml。感染后 1个月及 4个月检测 ,实验大鼠肝脏Southernblot杂交结果均为阳性 ,HCVCore区基因非定点整合 ;肝细胞mRNA的Dotblot杂交结果均为阳性 ,提示正确表达HCVCoremRNA。结论　成功制备出一种肝脏持续表达HCVcore蛋白的大鼠模型。     

The effect of recurrence of HCV infection of life after liver transplantation

Abstract The present study evaluated the quality of life (QOL) of adult cirrhotic patients before orthotopic liver transplantation (OLT), the effect of OLT on QOL in the long-term and the effect of HCV recurrence within medical complications on QOL. Three groups of patients were studied: 19 pre-OLT, 33 during the first year post-OLT and 41 1 to 5 years post-OLT. The patients completed questionnaires on QOL and underwent liver function tests, immunosuppressive drug blood level determinations and medical complications evaluation. Somatization and depression and anxiety scores improved significantly during the first year post-OLT compared with pre-OLT, but they worsened again during the 1–5-year period post-OLT. Physical functioning and life satisfaction scores improved significantly during the first year post-OLT compared with pre-OLT and the improvement persisted 1–5-year during the period post- OLT. Patients with HCV recurrence compared with patients without HCV recurrence during the first year post-OLT showed a significant worsening of most of the domains of QOL. In conclusion, OLT improved most of the domains of QOL by the end of the first post-transplant year, though the improvements did not all persist in the long-term. Recurrence of HCV infection plays a major role in the impairment of QOL after OLT.     

Minimization of immunosuppression with thymoglobuline pre-treatment and HCV recurrence in liver transplantation

Induction with thymoglobuline, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LTx) has never been investigated. We report here on the outcome in 22 HCV+ patients receiving thymoglobuline pre-treatment and minimal immunosuppression after LTx. Patient survival and acute rejection rates were good, and remarkably low dosages and levels of immunosuppression were achieved with thymoglobuline, without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressor was also possible in the majority of patients without complications. The HCV recurrence rate was similar to what is reported in the literature, although lower HCV-RNA viral loads were obtained with thymoglobuline, with a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobuline is effective in protecting against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.     

基于索非布韦的方案联合利巴韦林治疗肝移植后HCV基因1型肝炎受者的Meta分析

目的  通过系统评价和Meta分析评估以索非布韦(SOF)为基础的直接抗病毒药物(DAAs)联合利巴韦林(RBV)(联合RBV)治疗肝移植术后丙型肝炎病毒(HCV)基因1型(GT1)肝炎受者能否获益。方法  系统检索国内外多个数据库,根据标准筛选文献,并进行文献质量评价,提取数据。将文献按肝移植术后HCV-GT1肝炎受者接受联合RBV或只用SOF的DAAs不联合RBV(不联合RBV)治疗分为两组。采用Rev Man 5.3和R3.4.3软件对数据进行Meta分析。对治疗结束后12周持续病毒学应答(SVR12)的发生率进行评估。结果  检索文献2 195篇,按纳入标准筛选共纳入6篇英文文献。Meta分析结果表明联合RBV组和不联合RBV组两组间SVR12的发生率差异无统计学意义(P=0.28),但是联合RBV组贫血的发生率明显增高(P < 0.01)。联合RBV或不联合RBV治疗方案对肝移植术后HCV-GT1a和HCV-GT1b两个亚型同样有效,两基因亚型间疗效差异无统计学意义(P=0.33)。将肝移植术后HCV-GT1肝炎受者的疗程从12周延长至24周的SVR率差异无统计学意义(P=0.95)。结论  采用基于SOF的DAAs方案治疗肝移植术后HCV-GT1肝炎受者时,联合RBV不仅不能提高病毒的清除率,反而增加了受者发生贫血的风险,不能从中获益。     

肝移植后乙肝复发的预防和治疗

目的 探讨原位肝移植治疗乙型肝炎相关疾病的效果及Lamivudine在防治肝移植后乙肝复发中的作用。方法　10例患者接受了原位肝移植,其中9例男性乙肝患者,1例女性为肝癌患者,术前无乙肝感染。9例乙肝患者6例并有不同程度的肝性脑病,1例并肝肾综合征,1例并上消化道大出血。9例乙肝中7例服用Lamivudine预防术后乙肝复发。结果8例存活2-15月,2例死亡。存活的8例中7例为乙肝患者,仅1例术后6月出现HBsAg（+）,但全部均肝功能良好;另1例为肝癌患者,术后出现乙肝。死亡的2例中1例为术后乙肝复发暴发性肝功能衰竭所致,另1例死于术后多器官功能衰竭。结论 原位肝移植加Lamivudine是治疗乙肝的有效方法,Lamivudine在观察期内可预防乙肝移植后乙肝复发。     

阿德福韦在预防肝移植后乙肝复发中的作用

目的评价adefovir在预防肝移植后乙肝复发中的应用效果及安全性.方法统计30例应用lamivudine出现耐药及病毒变异的肝移植病例加用adefovir后病人：ALT、HBV-DNA、Cr以及HBeAg的变化,以及观察adefovir的副作用.结果应用adefovir12周后,ALT恢复正常者占65.5%,HBVDNA转阴（＜10^4拷贝/ml）占76.7%,HBeAg转阴44%,未发现严重的肾功能异常及其它副作用.结论肝移植术后应用lamivudine出现耐药及病毒变异病例,及时加用adefovir可有效改善肝功能、抑制肝炎复发.     

肝移植术后乙型肝炎病毒再感染的防治

目的 探讨肝移植治疗乙型肝炎相关肝病的效果和术后乙型肝炎病毒再感染的防治。方法 观察17例乙型肝炎相关患者接受肝移植后，使用拉米夫定及乙型肝炎免疫球蛋白（HBIg)的治疗和随访情况。结果 17例肝移植后，仅2例出现HBsAg阳性，全部肝功能良好。结论 肝移植是治疗乙型肝炎的有效方法，拉米夫定及HBIg可有效预防肝移植术后乙型肝炎病毒的再感染。     

Liver transplantation and hepatitis C

End-stage liver disease caused by chronic hepatitis C viral infection is one of the major indications for liver transplantation. However, evidence for ongoing viral replication can already be found days after surgery and may lead sequentially to lobular hepatitis, chronic active hepatitis, fibrosis and liver cirrhosis. In some patients, this evolution is remarkably fast, most probably enhanced by the immunosuppressive therapy. A minority of patients develop a clinical picture of progressive cholestatic liver disease with histological signs of chronic rejection, which may necessitate retransplantation. While the 1- and 5-year survival rates for all patients transplanted because of hepatitis C virus (HCV)-induced liver cirrhosis are satisfactory, severe complications of disease recurrence are nonetheless expected during the first and second decade after liver transplantation. Larger and preferably randomized studies are needed to investigate whether combination therapy with interferon and ribavirin, preferably initiated as soon as possible after liver transplantation, prevents the fast evolution to cirrhosis without the appearance of chronic rejection and the expected complications of recurrent end-stage HCV-induced liver disease. The final goal should be the inhibition of viral replication even before liver transplantation, but other antiviral strategies should probably be used to attain this goal in patients with decompensated cirrhosis. Although the recurrence of a hepatitis C infection and concomitant disease in the liver graft may cause substantial morbidity, end-stage liver disease and liver failure caused by a chronic hepatitis C infection remain good indications for liver transplantation.     

肝移植术后肿瘤复发与免疫抑制剂的关系

目的:探究肝癌行肝移植患者术后肿瘤复发与免疫抑制剂使用种类及剂量的关系。方法:回顾性分析重庆医科大学附属第一医院肝胆外科2007年9月至2019年1月因肝癌行肝移植患者临床资料。按肝移植术后肿瘤复发与否将患者分为病例组及对照组,对比两组患者的病因、甲胎蛋白水平、肝功能Child-Pugh评分、终末期肝病模型(MELD)...     

丙型肝炎肝硬化临床治疗的研究进展

聚乙二醇干扰素联合利巴韦林是丙型肝炎的标准抗病毒治疗方案,但治疗过程中不良事件较常发生.丙型肝炎病毒（HCV）的基因型、治疗早期的病毒动力学、基因位点的多态性等可用于预测抗病毒治疗的疗效.低剂量快速摄入、预防并发症等治疗策略有助于丙型肝炎患者完成抗病毒治疗.目前,直接抗病毒药物已开始用于基因1型的HCV感染患者,使得抗病毒疗效得到明显提高.此外,亲环素类抑制剂、维生素D等制剂可能与抗病毒治疗的疗效有关.此文对丙型肝炎抗病毒疗效的相关预测因子、标准治疗方案、治疗策略、新型抗病毒治疗制剂的研究等作了综述.     

肝脏恶性肿瘤肝移植术后肿瘤复发的临床研究

目的 总结肝脏恶性肿瘤患者行肝移植术后肿瘤复发的临床特点,探讨术后复查的规范方法和治疗复发肿瘤的措施.方法 回顾性分析215例原位肝移植患者的临床资料,分析其中81例复发患者的肿瘤复发时间、复发部位和治疗效果.结果 81例患者的随访时间为6～108个月.首次发现肿瘤复发的时间为肝移植术后3～20个月,常见的复发部位为肺、腹腔种植或淋巴结转移、移植肝内复发和骨转移.复发肿瘤的治疗以局部治疗为主,包括肺转移瘤切除术6例次、伽马刀治疗74例次;腹盆腔转移癌切除术10例次,腹腔淋巴结伽马刀治疗8例次;肝转移癌切除术6例次、消融治疗5例次、伽马刀治疗15例次、TACE 33例次,二次肝移植3例次;骨转移瘤切除术15例、伽马刀治疗16例次以及病理性骨折内固定术3例;脑转移瘤伽马刀治疗4例次.本组患者治愈3例,带瘤生存6例,已存活21～56个月,中位生存时间为39个月.死亡72例,中位生存时间为15个月.结论 肝移植术后对恶性肿瘤患者要进行有针对性的规范检查、积极治疗复发肿瘤,尽量延长患者的生存时间.