Preliminary clinical experience in liver retransplantation

BACKGROUND: The past several decades have witnessed increasingly successful rates of liver transplantation. However, retransplantation remains the only choice for patients with irreversible graft failure after primary transplantation. This article aimed to summarize our clinical experience in liver retransplantation. METHODS: From June 2002 to December 2005, a total of 185 cases of liver transplantation including 8 cases of retransplantation were performed in our hospital. The clinical data were analyzed retrospectively. RESULTS: The rate of liver retransplantation was 4.32%. Retransplantation was indicated for the following reasons: biliary complication (3 cases), chronic rejection (2), hepatic artery thrombosis (1), uncontrollable acute rejection (1) and hepatitis B recurrence (1). The mean model of end-stage liver disease (MELD) scores before primary transplantation and retransplantation were 15.6 and 23.9, respectively (P<0.05). The MELD score reflected the severity of liver disease more precisely than the Child classification. The mean interval between the first and second transplantation was 316 days (78-725 days). The first three patients, with mean interval of 101 days, died of severe infection combined with multiple organ failure after retransplantation. The patients who underwent retransplantation more than six months after the first transplant had better outcomes. The one-year survival rate for retransplantation in our group was 62.5%. CONCLUSIONS: Liver retransplantation is the only means of saving the patient with hepatic allograft failure. Understanding of the indications for retransplantation,careful selection of operation timing, excellent surgical skills and meticulous postoperative management all contribute to the success of each case of retransplantation.     

肝移植相关心血管并发症的发生与防治

肝移植是治疗急性肝衰竭、失代偿期肝硬化及肝细胞癌等终末期肝病的有效方法。近年,随着患者对医疗技术水平的认识和对术后生活质量要求的提高,肝移植已逐渐成为临床常见手术。从肝移植术前、术中及术后3个方面,阐述肝移植相关心血管并发症发生的原因和防治方法,旨在更好的认识和指导肝移植临床工作。     

The Italian experience on paediatric liver transplantation: 1988–1999 report

Background. Liver transplantation is the treatment of choice for end-stage liver disease in both adult and paediatric patients. The Italian experience in paediatric liver transplantation during the period 1988–1999 is reported herein.Patients and methods. This report concerns 228 liver transplantations performed in 207 patients (100 male, 107 female, mean age 5.1±4.4 years) in 11 Italian centres. The mean waiting time on the transplantation list was 6. 1±8.9 months and the main indications for the procedure were biliary atresia, inborn metabolic disorders, liver cirrhosis, liver neoplasms, Alagille syndrome, and fulminant hepatic failure.Results. The cumulative survival rate was 77%, 76%, 73%, and 71 at 1, 3, 5, and 7 years. The overall prevalence of acute rejection was 54%. Survival was significantly affected by re-transplantation (p=0.0002), by United Network for Organ Sharing 4 status at transplantation (p=0.016), and, among the indications for the procedure, by fulminant hepatic failure (p=0.004). Fifty patients (24%) died during the observation period. The main causes of death were primary non-function of the graft and sepsisConclusions. This study shows that liver transplantation in paediatric age, in Italy, is an effective procedure providing a 5-year survival rate comparable to that attained in the largest published series.     

Selection criteria and decisions in 375 patients with liver disease,considered for liver transplantation during 1977–1985

ABSTRACT— We performed a prospective study on 375 patients with liver disease, 60% female, for whom orthotopic liver transplantation (OLT) was considered during 1977–1985. Fifty-four per cent had cirrhosis, 8.5% congenital/hereditary disorders, 25% malignant tumour, 6% benign tumour, 2% Budd-Chiari syndrome, 1.5% acute hepatic failure, 3% other diagnoses, and 10% were under 15 years of age. As of July Ist, 1985, 99 patients (47 chronic active/inactive cirrhosis (CAC/CIC), 28 primary biliary cirrhosis (PBC), five hepatocellular carcinoma (HCC), 19 other diagnoses) were accepted for OLT (median age 40 years, 10% under age 15). By that date, 45 patients (median age 42), had had an OLT (20 CAC/CIC, 15 PBC, three biliary atresia, two HCC, five other diagnoses). Fifty-four per cent (201 patients) were rejected for transplantation. The primary reasons for rejection were: no indication (11%), age (5%), other surgical procedures possible (3%), severe liver failure (14%), extrahepatic spread of liver tumour (11%), cardiovascular or pulmonary problems (2%), severe hepatic bone disease (1%), and miscellaneous (7%). Thirty per cent of the patients with CAC/CIC, 38% with PBC, 88% with HCC and 71% with biliary atresia were rejected. In the CAC/CIC, PBC and biliary atresia patients severe liver failure was the most frequent reason for rejection (62%, 50% and 60%, respectively). In HCC, extrahepatic tumour spread was the most frequent reason (72%) for rejection. In this category only two patients (7%) ultimately underwent liver transplantation.     

The Italian experience on paediatric liver transplantation: 1988-1999 report.

BACKGROUND: Liver transplantation is the treatment of choice for end-stage liver disease in both adult and paediatric patients. The Italian experience in paediatric liver transplantation during the period 1988-1999 is reported herein. PATIENTS AND METHODS: This report concerns 228 liver transplantations performed in 207 patients (100 male, 107 female, mean age 5.1+/-4.4 years) in 11 Italian centres. The mean waiting time on the transplantation list was 6.1+/-8.9 months and the main indications for the procedure were biliary atresia, inborn metabolic disorders, liver cirrhosis, liver neoplasms, Alagille syndrome, and fulminant hepatic failure. RESULTS: The cumulative survival rate was 77%, 76%, 73%, and 71% at 1, 3, 5, and 7 years. The overall prevalence of acute rejection was 54%. Survival was significantly affected by re-transplantation (p=0.0002), by United Network for Organ Sharing 4 status at transplantation (p=0.016), and, among the indications for the procedure, by fulminant hepatic failure (p=0.004). Fifty patients (24%) died during the observation period. The main causes of death were primary non-function of the graft and sepsis CONCLUSIONS: This study shows that liver transplantation in paediatric age, in Italy, is an effective procedure providing a 5-year survival rate comparable to that attained in the largest published series.     

The timing of liver transplantation in primary biliary cirrhosis.

Primary biliary cirrhosis, the most common chronic cholestatic liver disease in adults, usually progresses to cirrhosis and its complications. Ursodeoxycholic acid therapy delays disease progression, but most patients will ultimately succumb. Liver transplantation is now accepted as the standard treatment for end-stage PBC. Development of major complications of portal hypertension and liver failure, poor quality of life and short survival without transplantation are the major indications for this surgical intervention in patients with primary biliary cirrhosis. Resource use is another key variable to be considered in the timing of liver transplantation. Prognostic models have been developed to predict survival and resource utilization with and without liver transplantation. Prognostic models aid the clinician in the selection and timing of liver transplantation in the patient with primary biliary cirrhosis.     

Liver transplantation: the Italian experience

BACKGROUND: Liver transplantation is the standard treatment for patients with end-stage liver disease no longer responsive to conventional medical treatment AIMS: To report the long-term experience of liver transplantation in Italy. PATIENTS AND METHODS: Data were obtained retrospectively by means of a multiple-item form collected from 15 Italian liver transplant centres. The filing centre was centralized. RESULTS: A total of 3323 liver transplants were performed on 3026 patients, with a cumulative proportional survival of 72.4%. Three, 5 and 10 years' patient survival rates were 72.3%, 68.8% and 61.3%, respectively. The most common indication for liver transplantation were hepatitis B virus (+/- hepatitis D virus)- and hepatitis C virus-related cirrhosis (59.4%). Excellent survival rates were observed particularly in controversial indications, such as alcoholic cirrhosis, hepatitis B virus-related cirrhosis and hepatocellular carcinoma. Retransplantation was required in 8.9% of the cases. The overall prevalence of acute cellular rejection episodes was 43.5%. In our study population, primary non-function and disease recurrence were the most common causes of graft failure (28.7% and 25.4%, respectively). Infections and/or sepsis were the most common causes of death after transplantation (42%). CONCLUSION: This study confirms that patients with controversial indications to liver transplantation such as alcoholic cirrhosis, HBV-related cirrhosis and hepatocellular carcinoma can achieve excellent survival when properly selected.     

Current developments in pediatric liver transplantation

In 1953, the pioneer of human orthotopic liver transplantation(LT), Thomas E Starzl, was the first to attempt an orthotopic liver transplant into a 3 years old patient suffering from biliary atresia. Thus, the first LT in humans was attempted in a disease, which, up until today, remains the main indication for pediatric LT(p LT). During the last sixty years, refinements in diagnostics and surgical technique, the introduction of new immunosuppressive medications and improvements in perioperative pediatric care have established LT as routine procedure for childhood acute and chronic liver failure as well as inherited liver diseases. In contrast to adult recipients, p LT differs greatly in indications for LT, allocation practice, surgical technique, immunosuppression and postoperative life-long aftercare. Many aspects are focus of ongoing preclinical and clinical research. The present review gives an overview of current developments and the clinical outcome of p LT, with a focus on alternatives to full-size deceased-donor organ transplantation.     

Living-related liver transplantation in a patient with end-stage hepatolithiasis and a biliary-bronchial fistula

Liver transplantation in patients with end-stage hepatolithiasis is complicated by the high incidence of the suppurative cholangitis and systemic infection. A 43-year-old Korean-Japanese woman with hepatolithiasis, biliary cirrhosis, suppurative cholangitis, and biliary-bronchial fistula underwent living-related liver transplantation (LRLT) using a right lobe graft of her sister. The risk of infection was minimized by preoperative percutaneous transhepatic biliary drainage initiated 2 months before transplantation. The native liver was resected en bloc with the extrahepatic bile ducts and the infected section of the right hemidiaphragm. Opportunistic infection was prevented by limiting antimicrobial therapy to the interval from preoperative day 3 to postoperative day 4. Immunosuppressive agents were given below standard dose. The postoperative course following LRLT was uncomplicated, and hepatic function was good. Careful management of infection and adequate graft size are essential for successful LRLT in patients with end-stage hepatolithiasis.     

同种异体原位肝移植14例次治疗经验

目的：总结终末期肝病患者同种异体肝移植手术的临床经验,介绍肝移植供体获取和受体手术的方法和术后处理方案。方法：对13例患者行14次手术(再次肝移植1例),其中乙肝肝硬化并肝癌7例,终末期乙肝肝硬化1例,丙肝肝硬化并“意外癌”1例,重症肝炎肝衰4例(1例为肝移植术后10个月,因乙肝复发,重型肝炎行二次肝移植术)。手术行改良背驮式5例,经典非转流术式9例次,其中1例行减体积肝移植(左肝外叶切除)。结果：手术移植物成活率100％,无原发性移植肝无功能和功能延迟恢复发生。手术成功率：良性终末期肝病和肝癌100％(9／9),重症肝炎为60％(3／5),总成功率为85．7％(12／14)。远期存活8例,存活1年以上5例。结论肝移植是治疗由各种急、慢性肝病导致的终末期肝功能衰竭和肝癌的有效方法。良性终末期肝病和早期肝癌的手术效果良好,明显优于重症肝炎和晚期肝癌。选择适当的手术时机,合理的手术方式,良好的供体质量,术中麻醉管理和术后早期ICU的围手术期管理,术后免疫抑制剂的应用,术后并发症处理是保证手术成功的重要条件。乙肝和肝癌等移植后易复发疾病的控制,对于提高肝移植术后患者的长期存活率非常重要。     

Outcome of liver transplantation in patients with alcoholic liver disease

BACKGROUND: Liver transplantation is accepted as effective therapeutic option for end-stage liver disease, including alcoholic liver disease AIM: To evaluate the outcome of liver transplantation for alcoholic liver disease in the Liver Transplantation Program at "Hospital de Clínicas" of the Federal University of Paraná, Curitiba, PR, Brazil. PATIENTS AND METHODS: It was performed a retrospective study of the patients who underwent liver transplantation for alcoholic end-stage liver disease between September 1991 and January 2001. The minimum abstinence period required was 6 months before liver transplantation. Identification of alcohol consumption after liver transplantation was determinated by information provided by patient or family and biochemical or histological anormalities. RESULTS: Twenty patients underwent liver transplantation for alcoholic liver disease in the study period, 95% (19/20) were men and the median age was 50 years (29-61 years). Seventy-five percent of the patients (15/20) had severe liver disfunction (Child C class) in the pre-transplant period. In six of them (30%) there was association with viral hepatitis and in one, with hepatocarcinoma. Median abstinence period before liver transplantation was 24 months, varying from 9 to 120 months. One-year and 3-year survival rate were 75% and 50%, respectively. The main complications were: acute cellular rejection (40%), chronic rejection (5%), hepatic artery thrombosis (15%), biliary complications (15%), bacterial or fungal infections (45%), cytomegalovirus infection (20%). Three patients returned to alcohol use after liver transplantation CONCLUSION: The survival of patients who received liver transplant for alcoholic cirrhosis are satisfactory. In the present study there was a small index of alcohol use after liver transplantation.     

肝移植治疗原发性胆汁性肝硬化的疗效分析

目的 观察原发性胆汁性肝硬化(PBC)患者和移植肝的实际生存时间,肝移植后死亡的原因及肝移植后的复发率。 方法 根据QLTS的数据库中的随访资料,回顾性分析52例共接受54次肝移植的PBC患者。52例PBC肝移植患者中,平均年龄(5 3.2±6.7)岁,平均随访时间是(5 5.4±11.3)个月。分析术前的临床特征、移植后生存情况和死亡原因,采用欧洲模式计算未接受肝移植患者和接受肝移植的患者的生存率。 结果 PBC肝移植患者的1、5、1 0年的实际生存率分别为8 8.4％、80.1％和76.9％,未接受肝移植患者实际生存率分别为80.9％、6 5.4％和19.8％。PBC患者移植后的生存率比未接受肝移植的患者(欧洲模型)预期生存率高。有6例患者经肝活检后证实PBC复发,平均复发时间(34.1±10.2)个月。肝移植术后死亡的原因是多器官功能衰竭、腹腔内出血、肾功能衰竭、败血症及心血管疾病。 结论 肝移植可提高P B C患者的生存率,延长其生存时间。     

Clinical analysis of liver transplantation in autoimmune liver diseases

Background: Autoimmune liver diseases(ALDs) consist of autoimmune hepatitis(AIH), primary biliary cirrhosis(PBC), primary sclerosing cholangitis(PSC), Ig G4-associated cholangitis and overlap syndromes.Patients with these diseases may gradually progress to end-stage liver diseases and need liver transplantation. The present study aimed to explore the prognosis of patients with ALDs after liver transplantation.Methods: The clinical data of 80 patients with ALD(24 cases of AIH, 35 of PBC, 15 of PSC and 6 of AIHPBC overlap syndromes) who underwent liver transplantation in Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2004 to September 2016 were collected retrospectively. The causes of death were analyzed and the postoperative cumulative survival rate was estimated by the Kaplan–Meier method. Recurrence and other complications were also analyzed.Results: Of the 80 patients, 18 were males and 62 were females. The average age was 50.5 years and the average Model for End-stage Liver Disease(MELD) score was 14.1. After a median follow-up of 19.8 months, 8 patients died. The 1-, 3-and 5-year cumulative survival rates were all 89.0%. Three cases of recurrent ALDs were diagnosed(3.8%) but they were not totally consistent with primary diseases. Biliary tract complication occurred in 10 patients(12.5%). The new onset of tumor was observed in 1 patient(1.3%). De novo HBV/CMV/EBV infection was found in 3, 8 and 3 patients, respectively.Conclusion: Liver transplantation is an effective and safe treatment for end-stage ALD.     

Liver transplantation for hepatocellular carcinoma: Recent advances in China

Orthotopic liver transplantation is currently the best treatment option for selected patients with hepatocellular carcinoma (HCC). From 1980 to 2011, 8874 patients with HCC in China underwent liver transplantation. The organ donation classification criteria of China (China criteria), which are established by the Government of China, are divided into three parts: China criteria I, donation after brain death; China criteria II, donation after cardiac death and China criteria III, donation after dual brain‐cardiac death. Data from the China Liver Transplant Registry (CLTR) System shows that patients within the Milan criteria have higher survival rates than those who are beyond these criteria. Based on CLTR data, altogether 416 patients received living‐donor liver transplantation (LDLT) in China. Their 1‐year and 3‐year survival rates were significantly higher than those of the non‐LDLT recipients. The most common early stage (<30 days after liver transplantation) complications include pleural effusion, diabetes, peritoneal effusion or abscess, postoperative infection, hypertension and intraperitoneal hemorrhage; while the most common late stage (≥30 days after liver transplantation) complications were diabetes, hypertension, biliary complications, postoperative infection, tacrolimus toxicity and chronic graft rejection. The incidence of vascular complication, which is the main reason for acute graft failure and re‐transplantation, was 2.4%. Liver transplantation is an effective treatment for patients with HCC in China.     

Aetiology and outcome of acute liver failure

Background:

Acute liver failure (ALF) is a clinical syndrome characterized by the sudden onset of coagulopathy and encephalopathy. The outcome is unpredictable and is associated with high morbidity and mortality. We reviewed our experience to identify the aetiology and study the outcome of acute liver failure.

Methods:

A total of 1237 patients who presented with acute liver failure between January 1992 and May 2008 were included in this retrospective study. Liver transplantation was undertaken based on the King''s College Hospital criteria. Data were obtained from the units prospectively collected database. The following parameters were analysed: patient demographics, aetiology, operative intervention, overall outcome, 30-day mortality and regrafts.

Results:

There were 558 men and 679 women with a mean age of 37 years (range: 8–78 years). The most common aetiology was drug-induced liver failure (68.1%), of which 90% was as a result of a paracetamol overdose. Other causes include seronegative hepatitis (15%), hepatitis B (2.6%), hepatitis A (1.1%), acute Budd–Chiari syndrome (1.5%), acute Wilson''s disease (0.6%), subacute necrosis(3.2%) and miscellaneous (7.8%). Three hundred and twenty-seven patients (26.4%) were listed for liver transplantation, of which 263 patients successfully had the procedure (80.4%). The current overall survival after transplantation was 70% with a median follow-up of 57 months. After transplantation for ALF, the 1-year, 5-year and 10-year survival were 76.7%, 66% and 47.6%, respectively. The 30-day mortality was 13.7%. Out of the 974 patients who were not transplanted, 693 patients are currently alive. Among the 281 patients who died without transplantation, 260 died within 30 days of admission (26.7%). Regrafting was performed in 31 patients (11.8%), the most common indication being hepatic artery thrombosis (11 patients).

Conclusion:

Paracetamol overdose was the most common cause of acute liver failure. Liver transplantation, when performed for acute liver failure, has good long-term survival.     

背驮式肝移植治疗急性肝衰竭15例

目的探讨肝移植治疗急性肝衰竭（ALF）的临床疗效，总结移植前处理、手术时机的选择以及术中关键技术应用的经验。方法回顾性分析了1999年9月2006年2月采用背驮式肝移植治疗15例ALF患者的临床资料。结果患者均获随访，术后1年生存率87％（13／15）。其中2例急性肝衰竭型威尔逊氏病患者术后角膜K—F环消失，血清铜蓝蛋白恢复正常。1例术后第11天死于多系统器官功能衰竭，1例患者术后第6天死于严重肺部感染，其余11例HBsAg转阴。结论肝移植是治疗ALF的有效方法，能提高ALF患者的生存率；年龄不应作为ALF患者肝移植的禁忌证；充分的术前准备和恰当的移植时机选择以及术中关键技术的使用是提高术后生存率的关键。     

Cirrhosis and autoimmune liver disease:Current understanding

Primary biliary cirrhosis(PBC),primary sclerosing cholangitis(PSC) and autoimmune hepatitis(AIH) constitute the classic autoimmune liver diseases(AILDs).While AIH target the hepatocytes,in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells.Persistent liver injury,associated with chronic AILD,leads to un-resolving inflammation,cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts.Liver cirrhosis,and the resultant loss of normal liver function,inevitably ensues.Patients with cirrhosis have higher risks or morbidity and mortality,and that in the decompensated phase,complications of portal hypertension and/or liver dysfunction lead to rapid deterioration.Accurate diagnosis and monitoring of cirrhosis is,therefore of upmost importance.Liver biopsy is currently the gold standard technique,but highly promising non-invasive methodology is under development.Liver transplantation(LT) is an effective therapeutic option for the management of endstage liver disease secondary to AIH,PBC and PSC.LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy;in addition,LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids.     

Primary biliary cirrhosis and primary sclerosing cholangitis

Primary biliary cirrhosis and primary sclerosing cholangitis are the most common chronic cholestatic liver diseases in adults that lead to biliary cirrhosis and its inherent complications such as portal hypertension and liver failure. Although important advances in the understanding of the pathogenesis of these conditions have been accomplished in the last two decades, much work is needed to uncover the interaction of genetic and immunologic mechanisms involved in their pathogenesis. Ursodeoxycholic acid at dosage of 13 to 15 mg/kg/d is the only agent that can currently be recommended in the treatment of PBC. No medical therapy aimed at disrupting disease progression is available for patients with primary sclerosing cholangitis, although several agents with different properties are currently under evaluation. Liver transplantation is the treatment of choice for patients with primary biliary cirrhosis and primary sclerosing cholangitis with end-stage liver disease.     

Selection criteria and decisions in 375 patients with liver disease, considered for liver transplantation during 1977-1985

We performed a prospective study on 375 patients with liver disease, 60% female, for whom orthotopic liver transplantation (OLT) was considered during 1977-1985. Fifty-four per cent had cirrhosis, 8.5% congenital/hereditary disorders, 25% malignant tumour, 6% benign tumour, 2% Budd-Chiari syndrome, 1.5% acute hepatic failure, 3% other diagnoses, and 10% were under 15 years of age. As of July 1st, 1985, 99 patients (47 chronic active/inactive cirrhosis (CAC/CIC), 28 primary biliary cirrhosis (PBC), five hepatocellular carcinoma (HCC), 19 other diagnoses) were accepted for OLT (median age 40 years, 10% under age 15). By that date, 45 patients (median age 42), had had an OLT (20 CAC/CIC, 15 PBC, three biliary atresia, two HCC, five other diagnoses). Fifty-four per cent (201 patients) were rejected for transplantation. The primary reasons for rejection were: no indication (11%), age (5%), other surgical procedures possible (3%), severe liver failure (14%), extrahepatic spread of liver tumour (11%), cardiovascular or pulmonary problems (2%), severe hepatic bone disease (1%), and miscellaneous (7%). Thirty per cent of the patients with CAC/CIC, 38% with PBC, 88% with HCC and 71% with biliary atresia were rejected. In the CAC/CIC, PBC and biliary atresia patients severe liver failure was the most frequent reason for rejection (62%, 50% and 60%, respectively). In HCC, extrahepatic tumour spread was the most frequent reason (72%) for rejection. In this category only two patients (7%) ultimately underwent liver transplantation.     

Split liver transplantation for hepatocellular carcinoma

BACKGROUND/AIMS: Liver transplantation (LTx) is recognized as the treatment of choice for small hepatocellular carcinomas (HCC) in patients with end-stage liver failure. However, because of limited organ availability, not all those who qualify can benefit from full-size LTx. METHODOLOGY: Over a 28-month period, we transplanted 6 deceased donor split liver allografts in stable recipients with HCC and cirrhosis. RESULTS: There were 5 men and one woman with a median age of 60 years. Median waiting time to LTx was 82 days. Extended right split grafts (segments I, IV-VIII) were transplanted in 5 patients. One patient received a right split graft. In situ harvesting was performed in 4 instances and ex situ in the remaining 2. Median cold ischemia time was 10 hours. Primary non-function was not observed. Median intensive care unit stay was 4 days. There were neither vascular nor biliary complications. The postoperative course was uneventful in half of the patients. Two patients were re-operated because of an abscess caused by a liver necrosis in the marginal zone of segment IV. One patient died for reasons unrelated to liver function or to the surgical intervention. The remaining 5 patients are alive after a median follow-up of 20 months. CONCLUSIONS: Deceased donor split LTx constitutes an additional option for patients with HCC and cirrhosis. The potential risks of using "split livers" as well as the potential benefits of transplanting patients unlikely to survive the waiting list period must be evaluated on an individual basis.