Management of recurrence of hepatitis C infection following liver transplantation

Liver disease secondary to hepatitis C infection is the most common indication for liver transplantation. Infection of the allograft begins at the time of transplantation. The histological progression of hepatitis C infection is greatly accelerated in liver transplant recipients when compared to the natural history in immunocompetent patients. Chronic allograft injury is apparent in >50% of HCV-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients die or lose their allograft secondary to hepatitis C-associated allograft failure and a further 30% will have cirrhosis by the end of the fifth postoperative year. Cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histological recurrence. In contrast to non-HCV-infected recipients, treatment for acute cellular rejection is associated with attenuated patient survival among recipients with hepatitis C. Therapy with pegylated IFN (+/- ribavirin), although less efficacious than in immunocompetent patients, should be considered in recipients with histologically apparent recurrence of hepatitis C before jaundice develops. Ribavirin is poorly tolerated in liver transplant recipients, limiting efficacy of combination therapy. Ribavirin dosing should be adjusted for renal insufficiency. Passive immunity, through anti-HCV antibody preparations, has not been efficacious to date. The role of hepatitis C new immunosuppression agents in the management of posttransplant hepatitis C infection is still evolving.     

A Practical Guide to the Management of HCV Infection Following Liver Transplantation

Hepatitis C-associated liver failure is the most common indication for liver transplantation, with virological recurrence near ubiquitous. Approximately 30% of HCV-infected recipients will die or lose their allograft or develop cirrhosis secondary to hepatitis C recurrence by the fifth postoperative year, with the proportion increasing with duration of follow-up. Strategies for minimizing the frequency of severe HCV recurrence include avoidance of older donors, early diagnosis/treatment of CMV and minimization of immunosuppression, particularly T-cell depleting therapies and pulsed corticosteroid treatment of acute cellular rejection. Patients should be offered treatment with peginterferon and ribavirin before LT if MELD ≤ 17 or as soon as histological evidence of recurrence of HCV is apparent post-LT. Because of the high frequency of hemotoxicity and renal insufficiency, ribavirin should be dosed according to renal function.     

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.)     

Renal transplantation offers a better survival in HCV-infected ESRD patients

Sezer S, Ozdemir FN, Akcay A, Arat Z, Boyacioglu S, Haberal M. Renal transplantation offers a better survival in HCV-infected ESRD patients. Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00252.x Copyright Blackwell Munksgaard, 2004Abstract: The presence of hepatitis C virus (HCV) infection has been found to adversely affect the morbidity and mortality rates in the dialysis population. Renal transplantation is a treatment option after a careful pre-transplant evaluation. We designed this study to find the impact of HCV infection on patient survival, co-morbidity and allograft survival in a selected group of hemodialysis (HD) and transplant population. We retrospectively analyzed 116 renal transplant patients (94 HCV-negative, 22 HCV-positive) and 136 HD patients (106 HCV-negative, 30 HCV-positive) who had renal transplantation or underwent dialysis before 1996. The HCV-infected patients were evaluated by liver biopsy for the absence of advanced liver disease before transplantation. There was no clinical or laboratory decompensation of liver disease in transplant and dialysis patient groups. The overall 5-yr survival rates were 85.2% for renal transplant recipients and 74.5% for those on HD. The comparison results revealed a significant difference between HCV-infected patients with and without transplantation. The 3-yr renal allograft survival rates were comparable in HCV-positive and -negative patients, but the risk of chronic allograft nephropathy (CAN) and graft failure were higher at the fifth year in HCV-positive patients. In conclusion, renal transplantation should the preferred therapy in HCV-infected dialysis patients as it improves the survival rates. The presence of HCV infection increases the CAN rate and the influence on allograft survival is evident at the fifth year of assessment.     

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.     

Heart retransplantation for heart allograft failure in Chinese heart transplant recipients: NTUH experience

We investigated the short- and long-term results after heart retransplantation in terms of different causes of heart allograft failure. We sought to establish the data of heart retransplantation in Chinese compared with Western counterparts due to differences in heart allograft vasculopathy. From March 1995 to May 2005, eight heart transplantation recipients with allograft failure underwent retransplantation. Heart allograft failure was due to coronary vasculopathy (CAV) in six patients (75%) and acute rejection in two patients (25%). The mean interval to retransplantation was 32 to 84 months (mean 54.3 months). There were five patients who survived after heart retransplantation for CAV and no patient survived after an earlier diagnosis of acute rejection. Heart retransplantation is a feasible method with acceptable long-term survival rate for heart allograft failure. After careful pretransplant evaluation, retransplantation is acceptable. The survival after retransplantation for CAV is notably great than that after acute rejection. Heart retransplantation is the only way for patients who have cardiac allograft failure to achieve long-term survival.     

Double-blind comparison of hepatitis C histological recurrence Rate in HCV+ Liver transplant recipients given basiliximab + steroids or basiliximab + placebo, in addition to cyclosporine and azathioprine

BACKGROUND: Hepatitis C virus (HCV) recurrence in HCV+ liver transplant recipients is almost inevitable and may be promoted by immunosuppression. We compared the amount of liver damage with regard to usage of steroids and basiliximab. METHODS: A total of 140 HCV+ adult liver transplant recipients were randomly allocated to basiliximab + steroids or basiliximab + placebo (plus cyclosporine and azathioprine). Primary endpoint: hepatitis C histological recurrence (liver damage as for Ishak grading score >or=8 by biopsy at 12 months); secondary endpoints: treatment failure (death, graft loss, patient withdrawal), biopsy proven acute rejection (BPAR), treated acute rejection (tAR), allograft and patient survival rates at 12 months. RESULTS: Any significant difference has been observed in the 12-month hepatitis C histological recurrence rate (41.2% basiliximab + steroids, 37.5% basiliximab + placebo, P = 0.354). The treatment failure rate was significantly higher in basiliximab + steroids (28.8%) than in basiliximab + placebo (15.6%), P = 0.03; the combination test for the evaluation of the joint hypothesis resulted in a borderline nonsignificant overall result (P = 0.059). BPAR rate was significantly lower in the group treated with steroids (24.3% basiliximab + steroids, 39.4% basiliximab + placebo, P = 0.04), while the tAR rate was similar (29.7% basiliximab + steroids and 37.9% basiliximab + placebo). Any significant differences in 1-year graft and patient survival rates have been observed (72.9% and 84.8% basiliximab+steroids; 81.5% and 89.0% basiliximab + placebo). CONCLUSIONS: Results suggest that steroid-free therapy is associated with a significantly lower treatment failure rate, although histological recurrence rate of hepatitis C is similar in the two groups. This benefit is not offset by an evident increase in graft rejection rate requiring treatment.     

Management of chronic viral hepatitis before and after renal transplantation

Hepatitis C virus (HCV) infection is present in 2-50% of renal transplant recipients and patients receiving hemodialysis. Renal transplantation confers an overall survival benefit in HCV positive (HCV+) hemodialysis patients, with similar 5-year patient and graft survival to those without HCV infection. However, longer-term studies have reported increased liver-related mortality in HCV-infected recipients. Unfortunately, attempts to eradicate HCV infection before transplant have been disappointing. Interferon is poorly tolerated in-patients with end-stage renal disease and ribavirin is contraindicated because reduced renal clearance results in severe hemolysis. Antiviral therapy following renal transplantation is also poorly tolerated, because of interferon-induced rejection and graft loss. Although the prevalence of hepatitis B virus (HBV) infection has declined in hemodialysis patients and renal transplant recipients since the introduction of routine vaccination and other infection control measures, it remains high within countries with endemic HBV infection (especially Asia-Pacific and Africa). Renal transplantation is associated with reduced survival in HBsAg+ hemodialysis patients. Unlike interferon, lamivudine is a safe and effective antiviral HBV treatment both before and after renal transplantation. Lamivudine therapy commenced at transplantation should prevent early posttransplant reactivation and subsequent progression to cirrhosis and late liver failure. This preemptive therapy should also eradicate early liver failure from fibrosing cholestatic hepatitis. Because cessation of treatment may lead to severe lamivudine-withdrawal hepatitis, most patients require long-term therapy. The development of lamivudine-resistance will be accelerated by immunosuppression and may result in severe hepatitis flares with decompensation. Regular monitoring with liver function tests and HBV DNA measurements should enable early detection and rescue with adefovir. Chronic HCV and HBV infections are important causes of morbidity and mortality in renal transplant recipients. The best predictor for liver mortality is advanced liver disease at the time of transplant, and liver biopsy should be considered in all potential HBsAg+ or HCV+ renal transplant candidates without clinical or radiologic evidence of cirrhosis. Established cirrhosis with active viral infection should be considered a relative contraindication to isolated renal transplantation.     

乙、丙型肝炎病毒感染对肾移植患者长期存活的影响

目的　了解乙型肝炎病毒（ＨＢＶ） 及丙型肝炎病毒（ＨＣＶ） 感染对肾移植患者长期存活的影响。方法　对８０ 例感染ＨＢＶ、ＨＣＶ 者肾移植术后肝病及排斥的发生情况、死亡原因及长期存活率进行分析。结果　移植后慢性肝病发生率为２１ ．２５％ , 死亡率为１８ ．７５ ％ , 显著高于非感染组（１ ．１９ ％ , Ｐ＜ ０．０１） ;ＨＣＶ 组超急性排斥及加速性排斥的发生率（６ ．０６％ ,９ ．０９ ％ ） 显著高于非感染组（０ ．７２ ％ ,２ ．７４ ％ ; Ｐ＜ ０ ．０１ , Ｐ＜ ０ ．０５）。结论　ＨＢＶ及ＨＣＶ感染显著影响肾移植受者的长期存活率; 移植后肝病及感染是其主要死因; 对ＨＢＶ 及ＨＣＶ 感染患者应采取合理的免疫抑制治疗。     

Adult Living Donor Versus Deceased Donor Liver Transplantation: A 6-Year Single Center Experience

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.     

Intractable recurrent hepatitis A virus infection requiring repeated liver transplantation: a case report

Although hepatitis A virus (HAV) infection is usually self-limited, it may induce fulminant hepatitis. We present an unusual case of a 40-year-old, otherwise healthy man with intractable recurrent HAV infection requiring retransplantation after primary liver transplantation for HAV-associated fulminant liver failure. After the first living-donor liver transplantation, allograft function recovered uneventfully; however, beginning at 35 days, his serum total bilirubin concentration increased, reaching 40 mg/dL, with a slight increase in liver enzymes. Detection of genomic HAV RNA in serum at the time of graft dysfunction led to a diagnosis of recurrent HAV infection. Fifty-one days after the first transplant, he underwent a deceased donor retransplantation. His allograft function recovered; the patient was discharged from the hospital. Sixty-five days later, however, he was readmitted for colitis-like symptoms and was again treated for acute rejection, but died owing to overwhelming sepsis and persistence of HAV infection. These findings indicate that patients who undergo liver transplantation for HAV-associated liver disease may be at risk of HAV reinfection, particularly if they require anti-rejection therapy. Routine measurements of anti-HAV immunoglobulin M and HAV RNA during the early posttransplant period in HAV-associated liver transplant recipients may differentiate reinfection from an acute cellular rejection episode.     

Liver transplantation: role of immunosuppression, renal dysfunction and cardiovascular risk factors

In the past decades, advances in immunosuppression, organ preservation, surgical techniques and better management of post-transplantation complications have led to improvement in survival of liver transplant patients. Such extended survival of liver graft recipients in their fifties and sixties has resulted in a greater prevalence of complications, in particular chronic kidney (CKD) and cardiovascular diseases (CVD). Renal failure and cardiovascular complications in the setting of liver transplantation are associated to an increase of morbidity and mortality. A 4-fold increased risk of death is reported among patients developing post-transplant CKD, and CVD is the leading cause of death with a functioning allograft, accounting for as much as 30% of post-transplant mortality. The onset is multifactorial, with pre-transplant conditions involved, including pre-transplant renal insufficiency, hepatitis C virus infection and pretransplant diabetes. Acute renal dysfunction in the setting of transplantation is also responsible of post-transplant CKD. Immunosuppressive therapy is primarily responsible for the development of CKD. Metabolic syndrome and its individual components, including diabetes mellitus, systemic hypertension, dyslipidemia, and obesity, are increasingly being identified as closely related to immunosuppressive therapy and actively contribute to cardiovascular morbidity and mortality in transplant patients. Treatment of modifiable risk factors is mandatory aiming to prevent the development and progression of serious complications. Early recognition, prevention and treatment of these conditions may further improve long-term survival after liver transplantation.     

Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation.

Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94 units before and after treatment, respectively; P =.016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection.     

The natural history of hepatitis C virus in pediatric liver transplant recipients.

Although rare in the pediatric population, the natural history of hepatitis C virus (HCV) recurrence in pediatric patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease secondary to HCV has not been well described. We performed an analysis of all 67 pediatric patients (< 17 years old) who have undergone OLT for HCV in the United States between 1/1988 and 6/2005. The 67 pediatric patients received a total of 83 OLTs for HCV. Following initial OLTs performed for HCV, the patient and allograft survival rates were 71.6% and 55.0%, respectively, at 5 years. Following retransplantation these rates decreased to 55.0% and 33.8%, respectively, following retransplantation. Recipients were listed for retransplantation after 31.3% of all OLTs, and overall recipients were retransplanted after 19.3% of OLTs. The overwhelming majority of retransplants were performed for HCV recurrence. A mean of 1.2 OLTs were performed per patient for HCV. The median time between OLTs for HCV was 290 days. In conclusion, the risk of HCV recurrence in pediatric OLT recipients is high and is associated with a high rate of retransplantation. Still, OLT represents the only treatment option that may achieve long-term survival in pediatric patients with end-stage liver disease secondary to HCV that is recalcitrant to medical management.     

Heart transplantation

Heart transplantation is the definitive treatment for selected patients with end-stage heart failure refractory to medical, interventional and surgical treatment. However, due to limited number of donor organs, most patients wait a long time for heart transplantation and a significant proportion die or become unsuitable for transplantation while waiting. Although post-transplant survival outcomes continue improving, a fifth of recipients die within 1 year after transplantation. In addition, recipients face constant threats from infection, rejection, malignancy and chronic allograft vasculopathy. Therefore, it is imperative to increase donor heart utilization to reduce waiting list mortality, and maintain allograft quality during transportation and optimize post-transplant care to improve outcomes. This review summarizes the process of heart transplantation from recipient and donor selection and matching to post-transplant management with a focus on the surgical aspects, and highlights the recent advancement, including donation after circulatory death programme, mechanical circulatory support, and ex-vivo heart perfusion.     

Seroprevalence and outcome of hepatitis C in liver transplantation

A recombinant enzyme-linked immunosorbent assay (ELISA) followed by a neutralization test (NT) and recombinant immunoblot assay (RIBA) were used for the detection of antibody to hepatitis C virus (anti-HCV) in 71 patients receiving 84 orthotopic liver grafts between 1984 and 1990. Before the liver transplantation (LTX) anti-HCV was present in six of the 71 recipients (8.5%) who were accepted for LTX because of acute or chronic liver failure. After LTX anti-HCV could not be detected in one of the patients, but it was continuously present in the others for more than 12 months. Detectable HCV antibodies were not present in the three patients who underwent LTX because of clinical evidence of fulminant NANB hepatitis. Two of 48 (4.2%) previously HCV seronegative recipients, who survived more than 3 months, seroconverted 9 and 16 months, respectively, after transplantation. The postoperative seroconversion was probably due to the transfer of virus via perioperative blood transfusions. Thus, these liver recipients may be able to respond by producing anti-HCV despite immuno-suppressive therapy. None of the seven post-transplant HCV-seropositive patients developed symptoms such as icterus or fatigue, which would suggest the presence of liver insufficiency due to HCV infection. However, two of them had increased transaminase levels and histological signs of mild hepatitis. No significant difference was found in 1-year survival, prothrombin complex, albumin levels or the risk for retransplantation in post-transplant anti-HCV-seropositive patients, compared with those without detectable HCV antibodies (71% vs 69%, respectively). Thus, during the study period of 1–5 years, the clinical course of HCV infection was milder than that reported for hepatitis B infection in liver recipients.     

Pediatric cardiac retransplantation: intermediate-term results

BACKGROUND: Cardiac retransplantation (re-CTx) in children is a controversial therapy, yet it remains the best treatment option to recipients with failing grafts. Our objective was to determine the incidence of re-CTx in a large pediatric population of recipients and evaluate the outcome of such therapy. METHODS: Between November 1985 and November 1999, 347 children underwent cardiac transplantation at the Loma Linda University Medical Center. Of these, 32 children were listed for re-CTx. Ten patients died while waiting, and 22 recipients underwent re-CTx. Median age at re-CTx was 7.1 years (range, 52 days to 20.1 years). RESULTS: Indications for re-CTx were allograft vasculopathy (n = 16), primary graft failure (n = 5), and acute rejection (n = 1). Two patients with primary graft failure underwent retransplantation within 24 hours of the first transplantation procedure while on extracorporeal membrane oxygenation support. Median time interval to re-CTx for the others was 7.2 years (range, 32 days to 9.4 years). Operative mortality for all cardiac re-CTx procedures was 13.6%. Causes of hospital mortality were pulmonary hypertension with graft failure (n = 2) and multiorgan failure (n = 1). Median hospital stay after re-CTx was 14.1 days (range, 6 to 45 days). There was one late death from severe rejection. Actuarial survival at 3 years for re-CTx was 81.9% +/- 8.9% compared with 77.3% +/- 2.6% for primary cardiac transplantation recipients (p = 0.70). CONCLUSIONS: Elective re-CTx can be performed with acceptable mortality. Although the number of patients undergoing retransplantation in this report is small and their long-term outcome is unknown, the intermediate-term survival after re-CTx is similar to that of children undergoing primary cardiac transplantation.     

Outcome of 28 split liver grafts

Our aim is to present our experience with split liver transplantation. From 1992-2002, 14 livers were split to obtain 28 grafts that were transplanted to 12 adults and 16 children. Ex situ splitting was performed in all cases. The left graft consisted of the left lateral segment (segments II-III) in 11 cases and the left lobe in three, depending on the size of the pediatric recipient. Pediatric recipients were of mean age 3, 4 years; mean weight 13 kg; six emergency cases for fulminant hepatic failure or urgent retransplantation and seven of 10 elective cases for biliary atresia. Postoperative mortality rate was 31% (five cases), including four of six emergency cases and one elective case (10%). The main cause was multiorgan failure. Technical complications were: one arterial thrombosis, one portal vein thrombosis, and four biliary complications. Eleven patients are alive and well. Adult recipients were of mean age 53 years. The indications were hepatocellular carcinoma in six cases, liver cirrhosis of various etiologies in five, and one recurrence of hepatitis C in a graft. Two patients died during the postoperative period from sepsis after retransplantation for primary nonfunction of the split graft and multiorgan failure with sepsis. One-year actuarial survival was 84%. CONCLUSIONS: The results of split liver transplantation in elective cases are similar to whole liver transplantation, whereas patient survival among emergency cases is low due to the critical condition of the patients.     

Allograft Survival Following Adult-to-Adult Living Donor Liver Transplantation

Adult-to-adult living donor liver transplantation (AALDLT) is emerging as a method to treat patients with end-stage liver disease. The aims of this study were to identify donor and recipient characteristics of AALDLT, to determine variables that affect allograft survival, and to examine outcomes compared with those achieved following cadaveric transplantation. Cox proportional hazards models were fit to examine characteristics associated with the survival of AALDLT. Survival of AALDLT was then compared with cadaveric allografts in multivariable Cox models. Older donor age (>44 years), female-to-male donor to recipient relationship, recipient race, and the recipient medical condition before transplant were factors related to allograft failure among 731 AALDLT. Despite favorable donor and recipient characteristics, the rate of allograft failure, specifically the need for retransplantation, was increased among AALDLT (hazard ratio 1.66, 95% C.I. = 1.30-2.11) compared with cadaveric recipients. In conclusion, among AALDLT recipients, selecting younger donors, placing the allografts in recipients who have not had a prior transplant and are not in the ICU, may enhance allograft survival. Analysis of this early experience with AALDLT suggests that allograft failure may be higher than among recipients of a cadaveric liver.     

心脏移植后存活时间超过10年者的临床分析

目的 总结单中心13例心脏移植后存活超过10年受者的治疗及随访情况.方法 13例受者在1995年8月至2001年6月期间接受心脏移植,前8例受者采用环孢素A+硫唑嘌呤+皮质激素的经典免疫抑制方案,后5例在该方案基础上进行了免疫诱导,有6例在吗替麦考酚酯(MMF)上市后将硫唑嘌呤替换为MMF.围手术期对主要并发症及时进行防治,术后对受者进行定期随访,建立个人长期随访档案,监测急性排斥反应(AR)和移植物血管病(CAV)发生情况,采用生存质量调查表分析生活状况.结果 13例存活超过10年的受者占同期心脏移植总例数的48.1%(13/27),术后受者心理状态较好,生存质量良好,均能够正常的学习、生活及工作.术后近期(1年内)发生的并发症包括AR 3例、感染4例、肾功能不全3例、移植物右心功能不全5例、移植后新发糖尿病2例及肝功能不全5例,经对症治疗后均好转;术后远期(1年后)发生的并发症包括CAV 2例、AR 4例、高胆固醇血症5例、高血压病4例、高尿酸血症10例及慢性肾功能损害3例等.1例受者于移植后13年因并发肝癌死亡.结论 心脏移植受者长期存活与其心理状态、经济条件、依从性及良好的随访制度等密切相关,并受社会因素的影响.

Abstract：

Objective To retrospectively analyze the clinical management and follow-up of 13 recipients with survival of over ten years after cardiac transplantation. Methods Thirteen male recipients underwent orthotopic heart transplantation between August 1995 and June 2001 in our center and received standard immunosuppressive therapy protocols (8 cases) or induction therapy protocols (5 cases). Cyclosporine, azathioprine or mycophenolate mofetil, and prednisolone were applied as maintenance immunosuppressive regimens. Six recipients switched from azathioprine to mycophenolate mofetil when mycophenolate mofetil was available. Perioperative complications were prevented and treated. After operation, the recipients were followed up regularly to set up personnel long-term follow-up files. The incidence of acute rejection (AR) and (cardiac allograft vasculopathy (CAV) was monitored. Results The 13 survived recipients accounted for 48. 1 % of the total number in the corresponding period (13/27). All survivals recovered well and had a good quality of life. The recent (1 year) complications included acute allograft rejection (3 cases), infection (4 cases), renal insufficiency (3 cases), allograft right ventricular dysfunction (5 cases), post-transplant diabetes (2 cases) and liver dysfunction (5 cases). The long-term (1 year later) complications included acute allograft rejection (2 cases), CAV (2 cases), hypercholesterolemia (5 cases), hypertension (4 cases), hyperuricemia (10 cases) and chronic renal impairment (3 cases). One hepatitis B virus carrier died of liver cancer 13 years after transplantation. Conclusion The long-term survival of cardiac allograft recipients is closely associated with psychological state, financial condition, compliance and follow-up medical system, while the sociological and environmental factors may play important roles.