原位肝移植术后丙型肝炎的防治

目的 研究肝移植术后丙型肝炎的预防及复发后治疗方法。方法 收集我院2001年8月至2004年3月4例因丙型肝炎所致肝功能衰竭或原发性肝癌行同种异体原位肝移植术的病人资料，探讨肝移植后丙型肝炎预防及肝炎复发后的治疗措施。结果4名病人中，2名病人术后血丙肝病毒RNA检测阳性，以干扰素（IFN—a2b）和病毒唑（Ribavirin）行预防性治疗。在15个月的随访中，1名病人病毒完全清除；另1名病人在预防性治疗过程中，丙肝复发。治疗后，生化指标、病毒学指标及组织学检查皆有改善，但病毒未获得完全清除。另外2名病人术后血丙肝病毒RNA检测阴性，未进行预防性治疗，1名病人随访12个月，病毒学检查仍为阴性；1名病人围手术期死亡。结论初步结果表明，IFN—a2b联合Ribavirin在肝移植后丙型肝炎的预防和治疗中是比较有效、完全的。     

肝移植术后乙型肝炎复发2例临床分析

拉米夫定联合乙型肝炎高效价免疫球蛋白(hepatitis b immunoglobulin,hbig)可有效预防原位肝移植术后乙型肝炎复发.然而,移植后核苷(酸)类药物使用不规范及疗程的不确切性给广大医务人员及患者带来诸多困扰.本文介绍2例乙型肝炎相关性终末期肝病患者行原位肝移植术后坚持拉米夫定治疗6年出现乙型肝炎复发的病例,为预防肝移植术后乙型肝炎复发及核苷(酸)类药物使用疗程提供借鉴.     

Prognostic factors for hepatitis C recurrence in patients undergoing orthotopic liver transplantation

End-stage liver disease caused by the hepatitis C virus (HCV) is a major indication for liver transplantation. HCV re-infection after LT is constant, and it significantly impairs patient and graft survival. Factors that may influence histological recurrence in the graft remain unclear. The aim of our study is to analyse the factors that influence the histological recurrence of HCV in a series of 142 patients undergoing orthotopic liver transplantation. In this series, donors age until 1995 were mostly younger than 30 years, however, from 2000 onwards most of the cases had graft implants from elderly donors. Histological recurrence was 92% after a mean follow-up of 60 months (12-120 months), 17% of which had poor-prognostic recurrence. Half of the patients presenting with recurrence did so in the first six months and more than two thirds developing hepatitis in the graft did so in the first year. The accumulated probability of histological recurrence is 40.1%, 51.5%, 70.3%, 83.5% and 92% at 6, 12, 24, 36 and 60 months respectively. In our experience, the variables associated with the development of histological recurrence in the graft, in the multivariate analysis, are donors age > or =31 years and immunosuppressive treatment without mycophenolate mophetil (MMF). Treatment with MMF still acts as a protection factor and is associated with histological non-recurrence.     

重型肝炎肝移植的围手术期处理

目的 总结重型肝炎病人肝移植围手术期若干问题的处理经验.方法 对中山大学附属第三医院肝移植中心2004年6月至2006年6月完成的218例重型肝炎肝移植病例资料进行回顾性分析.结果 218例重型肝炎肝移植围手术期成活率92.7%(202/218),其中急性重型肝炎肝移植为90.4%(57/63),慢性重型肝炎肝移植为93.5%(145/155).术后常见的并发症分别为感染(74.7%)、肝移植相关性脑病(65.6%)和.肾功能不全(14.7%).结论 重型肝炎肝移植的围手术期死亡率高.重视围手术期的处理足提高重型肝炎肝移植成功率的关键.     

Incidence and clinical relevance of recurrent hepatitis C infection after orthotopic liver transplantation

Abstract From September 1988 to November 1992 318 liver transplants were performed at our hospital. Of these patients 68 had end-tage cirrhosis due to non-A, non-B, hepatitis, 44 of whom (64.7%) had hepatitis C virus RNA in the serum. Of this subgroup 35 patients (79.5%) were also anti-HCV positive. Postoperatively most recipients remained anti-HCV positive and after 1 year more than 90% had HCV RNA in the serum. About 40% developed a mild, chronic hepatitis and 50% were carriers of HCV without histo-pathological signs. Two patients suffered from a temporary severe acute hepatitis and one patient had a fulminant liver failure due to reinfection. In general, in liver recipients transplanted for end-tage HCV hepatitis there was a high incidence of reinfection with HCV. The clinical course, however, was less severe than in hepatitis B recurrence.     

Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation

BACKGROUND: Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. METHODS: Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. RESULTS: The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F>or=1, 9.9 kPa for F>or=2, 15.4 kPa for F>or=3, and 26.5 kPa for F>or=4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F>or=2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. CONCLUSIONS: These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation.     

Outcome after liver re-transplantation in patients with recurrent chronic hepatitis C

Long-term outcome after liver retransplantation for recurrent hepatitis C has been reported to be inferior to other indications. The identification of factors associated which improved long-term results may help identify hepatitis C positive patients who benefit from liver retransplantation. Outcome after liver retransplantation for recurrent hepatitis C was analyzed in 18 patients (group 1) and compared with hepatitis C positive patients undergoing liver retransplantation for initial nonfunction (group 2, n=11) and patients with liver retransplantation for other indications (group 3, n=169). Five-year patient survival following retransplantation for groups 1, 2 and 3 was 59% 84% and 60%. Increased alanine aminotransferase (ALT) and serum bilirubin, as well as white cell count and MELD score at day of retransplantation were associated with impaired patient outcome. Five-year survival after retransplantation in patients with recurrent hepatitis C is similar to that in patients undergoing liver retransplantation for other indications. Our analysis showed MELD score, bilirubin, ALT levels and white cell counts preorthotopic liver transplantation are important predictive factors for outcome. This observational study may help select patients and identify the optimal time-point of liver retransplantation in 'Hepatitis C' virus positive patients in the future.     

聚乙二醇化干扰素联合利巴韦林治疗肝移植术后丙型肝炎复发

目的 探讨聚乙二醇化干扰素(PEG-IFNα)联合利巴韦林治疗肝移植术后丙型肝炎复发的效果及安全性.方法 回顾性分析9例丙型肝炎相关终末期肝病患者接受肝移植的临床资料,其中5例受者术后出现丙型肝炎复发,均给予PEG-IFNα-2a联合利巴韦林抗HCV治疗,疗程为48周.观察治疗前后血红蛋白、白细胞计数、移植肝功能及HCV RNA复制水平等指标的变化,评估治疗后的早期病毒应答(EVR)、持续性病毒应答(SVR)及不良反应等.结果 5例受者中有3例在治疗12周内达到EVR,并在治疗后获得SVR,移植肝功能也恢复正常;1例因在治疗12周后HCVRNA的下降达不到2个对数级而停药,1例虽HCV RNA下降2个对数级以上,但治疗至24周时HCV RNA未转阴而停药,至48周时HCV RNA均维持在较低水平.5例丙型肝炎复发受者在治疗后均发生白细胞减少和(或)发热等不良反应,给予对症处理后好转.结论 PEG-IFNα联合利巴韦林治疗肝移植后丙型肝炎复发安全性好,多数受者可取得持续性病毒学应答.     

乙型肝炎相关性肝病肝移植术后的急性排斥反应

目的 研究乙型肝炎相关性肝病肝移植术后急性排斥反应的发病率、治疗和预防。方法前瞻性地研究用肝移植术治疗乙型肝炎相关性肝病100例，分析急性排斥反应的发病相关因素，急性排斥反应和免疫抑制剂治疗的动态监测及二者间的联系。结果临床型急性排斥反应的发病率为12％，急性排斥反应发生前3～5d，有明显的免疫抑制剂浓度降低的过程。FKS06为基础的免疫抑制方案，加用骁悉，可有效地终止、逆转急性排斥反应；和以甲基强的松龙冲击治疗急性排斥反应相比较，副作用少，但肝功能的完全恢复时间相对较慢。结论乙型肝炎相关性肝病的肝移植术后急性排斥反应的发生率相对较低；和急性排斥反应发生相关的免疫抑制剂低浓度是诱导急性排斥反应的重要相关因素；FK506为基础的免疫抑制方案，可有效地终止、逆转急性排斥反应，且副作用少。     

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation

OBJECTIVE: We discuss the prevention of hepatitis B virus reinfection following orthotopic liver transplantation. METHODS: Sixty-eight cases of chronic fulminant hepatitis B, the end stage of liver cirrhosis and liver carcinoma complicated with HBV cirrhosis, were given antiviral drugs pre- and posttransplantation to prevent hepatitis B virus reinfection. Lamivudine was administered to two cases and lamivudine + HBIG to 63 cases. Adefovir + HBIG was administered to three cases. The serum HBV, HBV DNA, liver biopsy immunohistochemistry and clinical examinations were performed. RESULTS: One of two cases given lamivudine developed reinfection with serum HBSAg, HbeAb, HBcAb, HBV DNA, and positive and liver biopsy immunohistochemistry showing HBSAg phenotype. Two of the 63 cases given lamivudine + HBIG developed reinfection with serum HBSAg, HBeAb, HBcAb positive and liver biopsy immunohistochemistry showing HBSAg phenotype. The serum HBV DNA was positive in one of the two cases. Three cases given adefovir developed no reinfection with HBV. CONCLUSION: Orthotopic liver transplantation is an effective treatment for HBV infection; lamivudine + HBIG or adefovir + HBIG prevent hepatitis B virus reinfection.     

Recurrent postinfantile syncytial giant cell hepatitis after orthotopic liver transplantation

Syncytial giant cell hepatitis is a severe form of hepatitis characterized by diffuse giant cell transformation of hepatocytes. The disease may evolve to chronic cholestatic cirrhosis necessitating liver transplantation. We report the case of an adult liver transplant recipient presenting with early recurrent disease without concomitant clinicobiochemical syndrome. Early recurrence of giant cell hepatitis after liver transplantation favors the hypothesis of a transmissible agent as the etiology of the disease. Routine follow-up liver biopsy is necessary in these cases in order to gain more information about the precise incidence and aggressivity of disease recurrence in the allograft. Received: 4 July 1997 Received after revision: 12 January 1998 Accepted: 11 February 1998     

Recurrence of hepatitis C after liver transplantation

Cirrhosis due to hepatitis C is currently the most common indication for liver transplantation in the United States as well as in Europe. The prognosis for patients transplanted due to hepatitis C has changed over the years. Today there is growing concern as to the prognosis of these patients and how we should treat them. This is an overview of the developments in this field concerning treatment of recurrence and the role of preemptive treatment.     

Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation.

Recurrence of hepatitis C after liver transplantation (LT) is the main cause of graft loss and retransplantation. Frequent liver biopsies are essential to follow-up hepatitis C virus (HCV)-induced liver damage. However, liver biopsy is an invasive and expensive procedure. We evaluated prospectively the diagnostic accuracy of noninvasive measurement of liver stiffness (by transient elastography) to assess the severity of hepatitis C recurrence after LT. For this purpose, we included 124 HCV-infected liver transplant recipients who underwent 169 liver biopsies and 129 hepatic hemodynamic studies with determination of hepatic venous pressure gradient (HVPG). Simultaneously, patients underwent measurement of liver stiffness. Liver fibrosis was mild (F0-F1) in 96 cases (57%) and significant (F2-F4) in 73 (43%). HVPG was normal (<6 mm Hg) in 69 cases (54%) and elevated (>or=6 mm Hg) in 60 (46%). Using a liver stiffness cutoff value of 8.5 kilopascals, the sensitivity, specificity, negative predictive value, and positive predictive value for diagnosis of fibrosis >or=F2 were 90%, 81%, 79%, and 92%, respectively. The area under the curve (AUC) for diagnosis of fibrosis >or=F2, >or=F3 and F4 were 0.90, 0.93, and 0.98, respectively. There was a close direct correlation between liver stiffness and HVPG (Pearson coefficient, 0.84; P < 0.001) and the AUC for diagnosis of portal hypertension (HVPG >or=6 mm Hg) was 0.93. Importantly, none of the individuals with liver stiffness below the cutoff value had either bridging fibrosis (F3) or cirrhosis (F4) or significant portal hypertension (HVPG >or=10 mm Hg). In conclusion, determination of liver stiffness is an extremely valuable tool to assess the severity of HCV recurrence after LT and in reducing the need of follow-up liver biopsies.     

Outcomes after orthotopic liver transplantation in 15 HIV-infected patients

BACKGROUND: Human immunodeficiency virus (HIV) infection has been associated with poor outcomes after orthotopic liver transplantation (OLT). Highly active antiretroviral therapy (HAART) has led to an increasing number of successful OLTs. The aim of this study was to examine survival and cause-specific mortality in HIV-infected patients after OLT at our institution. METHODS: A retrospective analysis of all HIV patients that underwent OLT was compared to all non-HIV patients undergoing OLT during the same period. Cumulative patient and cause-specific survival were calculated using Kaplan-Meier methods; the log-rank test was used to compare the two cohorts. Fifteen HIV-infected patients and 857 non-HIV patients underwent OLT between June 1, 1999 and May 1, 2006. RESULTS: The actuarial 1-, 2-, and 3-year survival rates posttransplant (+/-standard error) were 73.3% (+/-11.4%) for the HIV group (unchanged from 1 to 3 years) versus 86.9% (+/-1.2%), 82.0% (+/-1.4%), and 79.4% (+/-1.5%) for the non-HIV group. Cumulative survival among HIV-infected recipients was not different from the non-HIV population (P=0.20). A difference was observed between the two groups in mortality rates due to infectious causes: the percentage of HIV patients dying from infection was 26.7% (4 of 15) vs. 8.2% (70 of 857) in the non-HIV group (P=0.006). CONCLUSIONS: PostOLT survival was comparable in HIV and non-HIV recipients; however, HIV patients had significantly higher mortality from infectious complications. This difference occurred despite adequate control of HIV postOLT. These findings suggest that OLT can be safely performed for HIV-infected patients; however, these patients are at higher risk of mortality from infectious complications.     

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.