Liver transplantation in acute liver insufficiency: definitive replacement or auxiliary liver?

Orthotopic liver transplantation (OLT) has greatly improved the chances of survival in patients with acute hepatic failure. However, this mode of treatment requires lifelong immunosuppressive medication and negates the potential recovery of the host liver. In theory, auxiliary heterotopic liver transplantation (HLT) offers the diseased host liver a chance to regenerate, so that immunosuppression can be tapered off and eventually stopped. In the University Hospital Rotterdam Dijkzigt OLT and HLT were performed in two patients, with acute and subacute hepatic failure respectively. The patient undergoing OLT recovered quickly but needed a successful re-OLT after a serious rejection episode. The removed diseased liver showed no signs of regeneration at histology. The patient undergoing HLT also recovered well. HIDA scanning as well as liver biopsies of the host liver and the grafted liver 1 and 6 months after transplantation indicated full recovery of the host liver, so that immunosuppression is being tapered off.     

Immunity to poliomyelitis, diphtheria and tetanus in pediatric patients before and after renal or liver transplantation.

Few studies have considered the safety, efficacy and appropriateness of vaccinations in pediatric patients before and after solid organ transplantation. The aim of this study was to evaluate the immune status after primary vaccination to diphtheria, tetanus and poliomyelitis in pediatric patients before and after hepatic transplantation and to poliomyelitis in pediatric patients before and after renal transplantation. All the patients had received a complete primary immunization schedule for diphtheria and tetanus and poliomyelitis. Immunity to the three polioviruses was evaluated in 56 patients with renal transplant, 27 on chronic dialysis and 33 controls and in 39 patients with hepatic transplant, 25 with chronic hepatic failure and their 36 controls. Immunity to diphtheria and tetanus was evaluated in 52 liver transplant patients, 29 children with chronic hepatic failure and 54 healthy children. Renal transplant patients were less protected and had lower antibody geometric mean titers than healthy controls for polioviruses 1 and 2. Whereas, protection in the children liver transplant patients was similar to that in their controls. Patients with chronic hepatic failure had higher antibody geometric mean titers to diphtheria and polioviruses 1 and 3 than their control group. Immunosuppression after transplantation has a negative influence on the immune status after primary vaccination in children with renal transplant. Whereas children with chronic hepatic failure have higher antibodies than a normal population. When possible, it could be advisable to individualize immunization schedules in patients at high risk.     

Isolated orthotopic liver transplantation for parenteral nutrition-associated liver injury

BACKGROUND: Mild liver dysfunction is common after prolonged use of parenteral nutrition (PN), but end-stage liver failure occurs only rarely. Few treatment options other than combined liver-intestine transplantation exist for patients with liver failure associated with PN use, however. Herein, we report the results of a cohort of patients undergoing isolated orthotopic liver transplantation (OLT) for PN-associated liver injury. METHODS: A retrospective cohort study of 80 patients (73 pediatric patients and 7 adults) who have undergone isolated OLT for PN-associated liver injury as the primary indication for transplantation was performed. RESULTS: At the time of OLT, the mean total serum bilirubin was 19.5 mg/dL and the mean serum albumin level was 2.9 mg/dL. Severe hepatic encephalopathy was seen in 5%, spontaneous bacterial peritonitis was seen in 6.3%, and respiratory failure requiring mechanical ventilation was seen in 14% of patients at the time of OLT. Overall 1- and 5-year survival rates were 72% and 52%, respectively, with infection being the most common cause of death after OLT. Retransplantation was required in 25% of patients, and the 5-year posttransplant patient survival rate only reached 35% in these cases. CONCLUSIONS: Patients with end-stage liver disease associated with PN administration often have very severe liver disease, multiple comorbidities, and poor prognosis by the time they are listed for OLT. Nonetheless, isolated OLT is associated with good long-term survival and should be considered for selected patients with combined intestine-liver failure.     

Risk factors for orthotopic liver transplantation failure in Rio Grande do Sul, Brazil

Risk factors for failure of liver transplantation from cadaveric donors were investigated in this retrospective study using data from medical records of patients in Rio Grande do Sul, Brazil, who were submitted to liver transplantation for the first time from January 1999 to July 2003 and were over 15 years of age at the time of surgery. Some 13% of failures occurred in the first month, 11% from 2 to 12 months, and 5% after 12 months; 88% of failures resulted in death and 12% in retransplantation. In the multivariate models, rate ratios for failure were higher for total family income less than 10 times the minimum wage, recipient's age > 45 years, non-whites, high clinical risk, and donor's age > or = 56 years. Female gender showed an effect in the unadjusted model only. Special attention to patients at increased risk, with income support for those with low family income, and early diagnosis of the need for transplantation may improve the success of liver transplantation.     

The role of oxidative stress and arterial blood supply in the transplanted liver function

INTRODUCTION: Reperfusion injury and hepatic artery thrombosis are major causes of graft failure after liver transplantation. The magnitude of oxidative stress increases after reperfusion and the appearance of an arterial thrombosis presents a higher risk for the graft and patient survival. AIM OF THE STUDY: The aim of the study was to detect the level of oxidative stress in the perioperative period of transplantation. METHODS: Clinical documentations of 32 patients were investigated and the level of myeloperoxidase (MPO) was measured for the monitoring of the oxidative stress. RESULTS: The mean age of the patients was 43 years and hepatitis C cirrhosis was the most common indication (14 cases, 43%). Two retransplantations were done. In 24 cases (75%) the primary graft functions and patient survival were good. Eight patients died, in two cases because of acute liver failure, in two cases due to primary non function and in four cases due to late complications. The incidence of hepatic artery thrombosis was 11% (4 cases) and the incidence of acute rejection was 35% (12 cases). The level of MPO was higher (65 ng/ml) in all patients before operation. After the first 48 hours this level increased significantly (p < 0.0001) up to the mean level of 123 ng/ml and decreased after one week. In the cases with acute liver failure and hepatic artery thrombosis high levels of MPO were measured. CONCLUSION: This study provides evidence of increased oxidative stress before liver transplantation. The magnitude of these changes increased after operation, mostly in cases with acute liver failure and hepatic artery thrombosis. Reducing the reperfusion injury and performing an "ideal" arterial supply for the liver-graft present better survival.     

Determinants of hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation

BACKGROUND: Homocysteine metabolism may be impaired in chronic liver disease, possibly contributing to fibrogenesis and disease complications. OBJECTIVE: The goal was to investigate the prevalence and determinants of basal and postprandial hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation (OLT). DESIGN: This was a cross-sectional study of 323 patients with chronic liver disease (93 with hepatitis, 8 with fatty liver, 168 with cirrhosis, and 54 after OLT) and 25 healthy control subjects. Portohepatovenous gradients of total homocysteine (tHcy) and methionine and postload methionine and tHcy kinetics before and after 10 d of supplementation with folate plus vitamin B-6 were investigated in subgroups. RESULTS: Basal hyperhomocysteinemia was observed in all patient groups (34% of patients with hepatitis, 50% with fatty liver, 54% with cirrhosis, and 52% after OLT). It was more frequently seen in patients with elevated plasma creatinine concentrations and at advanced stages of liver disease. Mean plasma folate was normal in patients with liver disease, but vitamin B-12 was elevated in cirrhosis and vitamin B-6 was low after OLT. There were significant negative associations between tHcy and folic acid or vitamin B-12 concentrations in control subjects and in patients with hepatitis and after OLT. No systematic association between portohepatovenous differences in tHcy and methionine concentrations was found. Cirrhosis was accompanied by impaired methionine clearance. After vitamin supplementation, the area under the tHcy curve improved in cirrhosis at nearly unchanged basal tHcy concentrations. CONCLUSIONS: Basal hyperhomocysteinemia is seen in approximately 50% of patients with cirrhosis and after OLT. Basal tHcy concentrations do not change significantly after supplementation with folate and vitamin B-6, but postprandial Hcy metabolism improves.     

他克莫司个体内高变异度与肾移植受者移植结局的关系探讨

目的探讨他克莫司(tacrolimus，Tac)个体内变异度(intra-patient variability，IPV)是否与肾移植受者慢性移植物失功密切相关。 方法选取2009年1月至2016年12月在四川大学华西医院肾移植中心进行肾移植且在术后长期随访的肾移植受者共1167人，用移植后7~12月期间的Tac全血浓度计算得到Tac IPV。设定的结局(含终点)包括：(1)移植物衰竭，再移植，(再)开始透析，或肾小球滤过率(glomerular filtration rate，eGFR)≤15 ml/min，活检证实的急性排斥反应(biopsy-proven acute rejection，BPAR)；(2)组织学确定的移植肾小球病；(3)移植后12个月到最后一次随访期间，血清肌酐浓度加倍；(4)最后一次随访。分析不同IPV组肾移植受者肾脏功能差异，生存时间差异以及出现慢性移植物失功的情况。 结果纳入研究的1167位患者中，有79(6.8%)位到达了移植物失功的终点。肾移植受者移植后7~12月Tac IPV平均值为25.7%；高IPV组移植后第15个月血清肌酐显著高于低IPV组(P<0.05)，第15、21、24个月eGFR显著低于低IPV组(P<0.05)。多因素Cox回归分析结果显示：Tac IPV对肾移植预后的预测有一定作用，但并不显著(P=0.051，Harzards ratio：1.015，95%CI：1.000-1.031)。而受者的年龄、性别、移植后6 h的移植物功能，是移植物存活的独立预测因子。 结论高Tac IPV与肾移植受者移植物失功有一定临床相关性，同时高Tac IPV是预测肾移植受者移植后两年内肾脏功能的重要实验室指标。     

Liver transplantation in acute liver failure

Acetaminophen and idiosyncratic drug induced hepatotoxicity are the most commonly identified etiologies of acute liver failure in Western countries. Infectious complications and cerebral edema remain the leading causes of death. Moderate hypothermia and other medical interventions may improve cerebral edema in selected patients with acute liver failure. In addition, pilot studies suggest that recombinant factor VIIa infusions may allow for the safe placement of intracranial pressure monitoring devices in patients with cerebral edema and severe coagulopathy. Auxiliary liver transplantation and bioartificial liver devices offer the hope of temporary liver support for selected patients with a high likelihood of native liver regeneration. Prognostic survival models that include arterial lactate levels may improve our ability to identify acetaminophen overdose patients in urgent need of liver transplantation. The lower 1-year patient survival following liver transplantation for acute liver failure compared to chronic liver failure (60 vs 80%) is in part due to the emergent nature of surgery, concomitant vital organ failure, and the higher incidence of immunologically mediated graft dysfunction. Vaccination against hepatotrophic viruses and other public health measures designed to minimize the incidence of both intentional and non-intentional acetaminophen overdose may help reduce the future incidence of acute liver failure. In the meanwhile, it is recommended that acute liver failure patients be managed in experienced centers with ready access to liver transplantation to optimize outcomes in this rare but frequently fatal illness.     

Combined antiviral treatment in a patient with recurrent chronic hepatitis C after liver transplantation

BACKGROUND: Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of the patients. We report a case of orthotopic liver transplantation with more than five years survival despite the early recurrence of hepatitis C virus. CASE REPORT: A 49-year old woman underwent orthotopic liver transplantation because of liver cirrhosis following chronic hepatitis C virus infection. Twelve years before she received blood-transfusion. The chronic liver disease was diagnosed four years later. However, then it was thought to be a drug induced liver damage. After the liver transplantation hepatitis C chronic hepatitis recurred within one year. The serotype analysis (1b) proved the autoreinfection. The combined antiviral treatment (interferon plus ribavirin) resulted significant improvement. She was asymptomatic nearly for two years. The liver biopsy showed a significant histological improvement. However the virologic response and remission was transient. Four years after the transplantation recurrence occurred again. The liver biopsy proved cirrhosis. Antiviral therapy with pegylated interferon plus ribavirin was started but it had been stopped because of severe cytopenia. Lack of adequate antiviral treatment her condition became progressively worse. Finally, five years after the transplantation she died because of bilateral haemorrhagic ovarian necrosis and severe circulatory insufficiency thanks to the low albumin level. CONCLUSIONS: In the case of liver cirrhosis caused by hepatitis C virus the liver transplantation could prolongs the life with years. The presented case illustrate that the hepatitis C virus injures the transplanted liver by autoreinfection. However, the combined antiviral therapy could result sustained virologic response in these cases as well. Our patient survived five years thanks to the transplantation and the following antiviral therapy.     

Nutrition support for individuals with liver failure

The prevalence of liver diseases is increasing in the United States, particularly as a result of the recent hepatitis C epidemic. In the past, patients who developed fulminant hepatic failure or cirrhosis owing to a chronic liver disease were likely to expire. During the last 15-20 years, liver transplantation has given these patients a chance at survival. Progressive nutrition deficiencies and muscle wasting are universal problems in these patients. Left untreated, the progressive wasting of liver disease leads to infection and an increased risk of death owing to infection both before and after transplantation. Aggressive nutritional support is essential to optimize the care of these patients and to enable them to obtain and survive a liver transplant and gain access to a new life following a successful liver engraftment.     

Effectiveness and safety of immunization with live-attenuated and inactivated vaccines for pediatric liver transplantation recipients

BackgroundLiver transplantation recipients are at high risk for severe complications due to infections because of being treated with immunosuppressive drugs that affect the immune system. Vaccination for liver transplantation candidates is generally recommended before surgery, but the opportunities for vaccination prior to transplantation in pediatric candidates are often limited by severe disease conditions.MethodsThe participants in this study comprised 39 pediatric recipients of living donor liver transplantation performed between 2005 and 2013. Criteria for administering live-attenuated (measles, rubella, mumps, and varicella) and inactivated (hepatitis B, pertussis, and Japanese encephalitis) vaccines were as follows: (1) >1 year after transplantation; (2) no use of systemic steroids to treat acute rejection within the last 6 months; (3) serum trough concentration of tacrolimus <5 ng/mL; (4) no severe immunosuppression according to blood examinations; and (5) provision of written informed consent. Median age at transplantation was 17 months, and median period from transplantation to the beginning of immunization was 18 months.ResultsSeroprotection rates for measles, rubella, mumps, varicella, hepatitis B, pertussis, and Japanese encephalitis after post-transplant immunization were 44% (11/25), 70% (19/27), 48% (12/25), 32% (6/19), 83% (19/23), 87% (13/15), and 88% (7/8), respectively. Seroprotection rates for measles, rubella, mumps, and varicella after second vaccination for recipients with primary vaccine failure after first vaccination were 100% (8/8), 50% (1/2), 71% (5/7), and 50% (5/10), respectively. While four recipients contracted mumps and eight contracted varicella before immunization, one recipient developed varicella after immunization. No serious systemic adverse events were observed in vaccinated recipients.ConclusionsSeroprotection rates for measles, mumps, and varicella appeared low in children after the first post-transplantation vaccination. Immunizations with four live-attenuated and three inactivated vaccines were safe and effective for pediatric liver transplantation recipients who were not severely immunosuppressed.     

Does long-term home parenteral nutrition in adult patients cause chronic liver disease?

Sixty patients with gut failure were treated with home parenteral nutrition for 2000 patient months. Fifty-one of these 60 patients had either no abnormalities or mild and transient elevations of their liver chemistries and did not have liver biopsies. Nine (15%) of 60 patients had abnormalities of liver tests that persisted from 8 to 95 months (median, 18 months) which prompted one or more liver biopsies per patient. Three patients had prolonged jaundice, one died of hepatic encephalopathy, and another with protracted intrahepatic cholestasis died following a biliary tract exploration. A third patient remains ill with signs and symptoms of chronic liver disease. Steatohepatitis was found in eight of the nine patients and was characterized by centrilobular and midzonal microvesicular and macrovesicular fatty changes with fat cysts, focal necrosis, and mixed inflammatory infiltrates. Centrilobular fibrosis was present in three patients and evidence of nodular regeneration in one. In the three patients demonstrating cholestasis, bile pigment was identified both in hepatocytes and canaliculi. Ceroid pigment in Kupffer cells was a consistent finding and much more severe than expected from the mildness of the hepatitis. Persistent abnormalities of liver chemistries in nine patients and progressive liver disease while receiving home parenteral nutrition in three patients are quite worrisome and suggest that home parenteral nutrition-associated steatohepatitis with or without cholestasis may progress to chronic liver disease.     

Prospective study of the quality of life in patients assessed for liver transplantation: outcome in transplanted and not transplanted groups.

The quality of life in adult patients with chronic liver disease who were considered for transplantation was assessed prospectively over a 2 year period, for both those who did and did not subsequently receive transplants. The main outcome measures were the Nottingham Health Profile and survival. Of the 109 patients who completed an entry profile, 27 were transplanted, 71 not transplanted during the study period, and 11 rejected for transplant. Quality of life and severity of liver disease at entry was worse for the transplant group, whose survival at 15 months from entry was 81% compared with 78% for those not transplanted. Among transplant survivors there were marked improvements in quality of life, whilst amongst those not receiving transplants there was little change. In conclusion, liver transplantation was effective in improving quality of life in patients with chronic liver disease, but comparison between transplant and non-transplant patients is difficult because of differences between the groups.     

Is intestinal transplantation now an alternative to home parenteral nutrition?

Patients with irreversible intestinal failure and complications of parenteral nutrition should now be routinely considered for small intestine transplantation. Despite attempts for >40 years immunological graft intolerance presented an impenetrable barrier to successful engraftment until the development in the late 1970s of the powerful calcineurin-inhibitor immunosuppressive agents. Their use over the last 17 years has led to small intestinal transplantation being generally considered as a routine option for patients with irreversible intestinal failure and failing parenteral nutrition. The 1-year patient survival rates (%) are now excellent for renal (95), liver (78), heart (82) and lung (75) transplantation. In contrast, survival rates for small intestinal transplantation have been slow to improve, although they are now approaching those for lung and liver transplantation (intestine 78%, intestine and liver 60%, multivisceral 66%), and well-performing centres report recent 1-year graft survival rates as high as 92%. Patient 5-year survival (%) has also improved (intestine alone 50, intestine and liver 50 and multivisceral 62) and compares increasingly favourably with renal (85), liver (67), heart (67) and lung (46). Currently, small intestinal transplantation is reserved for patients with irreversible small intestinal failure who have a poor prognosis on parenteral nutrition. However, as 5-year patient survival following intestinal transplantation approaches that for parenteral nutrition there will be increasing pressure to offer this modality of treatment as an alternative to parenteral nutrition, especially for those patients who have a poor quality of life as a result of parenteral nutrition.     

Combined interferon-alfa-2b and ribavirin therapy in patients with recurrent chronic hepatitis c after liver transplantation

Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in liver transplants. AIM OF THE STUDY: Was to assess the efficacy of standard combination therapy (interferon plus ribavirin) of chronic hepatitis C in transplanted patients with recurrent severe HCV induced chronic hepatitis. METHODS: 12 patients with HCV-PCR positive reaction (genotype 1b) were treated with the therapy of interferon-alpha-2b (3 MU three times a week) and 800-1000 mg ribavirin daily. Liver biopsy had been done in every patients before and after the treatment. Study endpoints were the end of treatment and the 6 month post-therapy sustained virologic response. RESULTS: At the end of treatment 3 patients were negative for HCV-PCR and all of them had negative reaction after 6 month follow-up period. CONCLUSION: The results are in a good accordance with treatment of patients with chronic hepatitis C without liver transplantation.     

门脉高压症肝移植的治疗体会及围手术期处理(附23例报告)

目的探讨肝移植在肝硬化门脉高压治疗中的意义。方法回顾性分析本中心23例肝脏移植肝硬化门脉高压症患者的临床资料。结果23例患者中2例死于围手术期并发症，其余均存活，最长37个月，最短2个月，术后并发症发生率42．8％。结论肝移植是目前能从根本上治疗门静脉高压症的有效方法。     

Treatment of recurrent hepatitis C virus infection after liver transplantation

The main indication of liver transplantation is the final stage of liver cirrhosis developed in hepatitis C virus (HCV) infection. The recurrence of HCV infection after transplantation is a common situation. The recurrent hepatitis C is a progressive disease, in 20 percent of patients it produces liver cirrhosis without treatment beside immunosuppression within 5 years. The treatment of recurrent HCV infection is the most important factor of the survival in patients with transplantation. The authors review the factors influencing the progression of recurrent HCV infection on the basis of literary data and also on their observation. They discuss in details the effect of immunosuppressive treatment, the importance in the selection of corresponding immunosuppressive drugs. They review the main keypoints in the diagnosis of recurrent hepatitis C, underline the important role of liver biopsy carried out according to the protocol in the diagnosis, furthermore the hard consultation among pathologist, hepatologist and surgeon. They demonstrate the observations with the treatment of patients on the waiting list, the results in the early, preemptive treatment of recurrent chronic hepatitis, furthermore the treatment modalities and the results in patients with chronic hepatitis C histologically proved. The drug of choice of chronic hepatitis C after transplantation is the combined therapy with pegylated interferon and ribavirin. This therapy is able to assure virus-free stage in 20-50 percent of patients. In the virus-free patients the inflammatory activity in the liver significantly decreases, the histologic activity index improves. There are data showing the effect of treatment for inhibiting the fibrosis, but multicenter studies are necessary for the confirmation of these data. The advantage of early antiviral therapy without histologic alteration has not been confirmed by most of the trials. The anaemia and the neutropenia are frequent side effects in this patient group, that is why the applications of erythropoietin and granulocyte stimulating factor are recommended. Further trials and clinical studies are necessary for the optimal treatment of patients with recurrent hepatitis C, and to determine the dosage of pegylated interferon and ribavirin, to decrease the duration of therapy and the side effects, finally to achieve a healing phase of higher degree.     

Biochemical and virological response (by PCR) to interferon therapy in chronic hepatitis C

Interferon-alpha has been established for the treatment of chronic hepatitis C virus infection. However, the complete responding rate is not higher than 20-25%. Our study was carried out on sixty patients with chronic HCV infection with the following criteria: elevated serum ALT levels, positive antibodies to HCV (by second generation ELISA and RIBA tests) and positive HCV in serum by PCR. All patients had negative tests for hepatitis B virus and liver histopathological findings consistent with chronic hepatitis +/- cirrhosis. Patients were treated with 3 Mu interferon-alpha thrice weekly for 6 months. The results showed response in 14 out of the 60 patients (23.3%) with normalization of the ALT levels within 2-3 months of IFN therapy. Complete response (CR) was present in 6/14 (42.9%) of the responders with negative PCR in serum up to 6 months after stoppage of therapy. Response with relapse (unsustained response) was noticed in 8/14 (57.1%) of the responders with elevation of ALT level 2 months after stoppage of treatment. Forty six patients 46/60 (76.7%) were non-responders (NR) with significant elevation of ALT level and positive PCR in serum all through the course of treatment. The response in cirrhotic patients was significantly lower than in noncirrhotic cases. In conclusion, prolonged treatment courses should be further evaluated in controlled studies.     

集束化管理预防肝移植患者术后肺部感染的效果

目的探讨集束化管理预防肝移植患者术后肺部感染的效果,以降低肺部感染发病率。方法选择2016年1月—2017年12月某院肝胆外科行肝移植的患者为研究对象。2016年1月—2017年3月的患者为对照组,实施常规护理措施,2017年4—12月的患者为试验组,实施集束化肺部管理。比较两组患者肺部感染发病率、肺不张发生率、第一次下床活动时间、住院费用和患者满意度。结果对照组共110例肝移植患者,试验组67例肝移植患者。两组患者均顺利完成手术。试验组肺部感染发病率为6.0％,低于对照组的16.4％,差异有统计学意义（P＜0.05）。试验组肺不张发生率为7.5％,低于对照组的18.2％,差异有统计学意义（P＜0.05）。试验组第一次下床活动时间为（83.81±7.56）h ,短于对照组的（91.67±13.93）h,差异有统计学意义（P＜0.01）。试验组住院时间为（30.22±3.23）d ,短于对照组的（31.49±4.34）d,差异有统计学意义（P＜0.05）。试验组患者对护理的总体满意度为92.5％,优于对照组的78.2％,差异有统计学意义（P＜0.05）。结论采用集束化管理能有效降低肝移植患者术后肺部感染发病率、肺不张发生率,缩短卧床时间及住院时间,提高患者满意度。