General compliance after liver transplantation for alcoholic cirrhosis

In recent years, alcoholic cirrhosis has been accepted as an indication for OLT, compliance of patients suffering from alcoholic cirrhosis is still under discussion, however. 118 patients who had undergone OLT for alcoholic cirrhosis were considered for analysis. The mean follow-up time of the study population was 53.7 ± 38.9 months. Compliance was defined by 3 parameters: 1. Sobriety. Fifteen (13 %) out of 118 recipients suffered an alcohol relapse during the observation period. There was no difference between the groups with or without alcohol relapse concerning compliance with medication, incidence of rejection, or adherence to check-ups. 2. Drug-compliance. Nineteen recipients (16 %) were not within the target range with the immunosuppressive medication. Comparison of the compliant- and non-compliant groups produced a significant difference for late acute rejection, the other parameters being similar in the subgroups. 3. Adherence to appointments. Nearly all patients in the study population ( > 95 %) were compliant with both transplant and psychological appointments in the outpatient clinic. In conclusion, analysis of our data indicates that patients with OLT for alcoholic cirrhosis are compliant, although alcohol relapse occurs in 13 % of recipients. Received: 4 June 1999/Revised: 23 November 1999/Accepted: 15 December 1999     

Liver transplantation for alcoholic cirrhosis

Abstract Because of the donor shortage, there are concerns for liver transplantation in patients with alcoholic cirrhosis. We therefore analyzed patients transplanted for alcoholic cirrhosis at our center with respect to patient and graft survival, recurrence of disease, and postoperative complications. Out of 1000 liver transplantations performed in 911 patients, 167 patients were transplanted for alcoholic cirrhosis; 91 patients received CsA‐ and 76 patients FK506‐based immunosuppression. Recurrence was diagnosed by patient's or relative's declaration, blood alcohol determination, and delirium. Diagnosis and treatment of acute and chronic rejection was performed as previously described. One‐ (96.8 % versus 91.3 %) and 9‐year patient survival (83.3 % versus 80%) compared well with other indications. Five of 15 patients died due to disease recurrence. Recurrence of disease was significantly related to the duration of alcohol abstinence prior to transplantation. In patients who were abstinent for less than 6 months (17.1 %), recurrence rate was 65 %, including four of the five patients who died of recurrence. Recurrence rate decreased to 11.8%, when abstinence time was 6‐12 months and to 5.5%, when the abstinence times was > 2 years. Next to duration of abstinence, alcohol relapse was significantly related to sex, social environment, and psychological stability. The incidence of acute rejection compared well with other indications (38.1%); CsA: 40.1% versus 33.3% in FK506 patients. In all, 18.2% of CsA patients experienced steroid‐resistant rejection compared with 2.6 % of FK506 patients. Seven patients (7.6%) in the CsA group and one patient (1.3%) in the FK506 group developed chronic rejection. A total of 57.1% developed infections; 5.7% were life‐threatening. CMV infections were observed in 14.3% (versus 25% for other indications). New onset of insulin‐dependent diabetes was observed in 8.6% and hypertension in 32.4%. In conclusion, alcoholic cirrhosis is a good indication for liver transplantation with respect to graft and patient survival and development of postoperative complications. FK506 therapy was favourable to CsA treatment. Patient selection is a major issue and established criteria should be strictly adhered to. Patients with alcohol abstinence times shorter than 6 months should be excluded, since recurrence and death due to recurrence was markedly increased in this group of patients.     

Carbohydrate deficient transferrin for detection of alcohol relapse after orthotopic liver transplantation for alcoholic cirrhosis.

Early diagnosis and monitoring of an alcohol relapse in patients after orthotopic liver transplantation for alcoholic cirrhosis is of importance for the long-term outcome. A prospective study of 97 patients who underwent orthotopic liver transplant for alcoholic cirrhosis has been performed. All of the recipients considered for analysis survived for at least 3 months and were under the care of one specialist psychologist. Mean follow-up amounted to 48.5+/-1.4 months. The rates of alcohol relapse at 1 and 3 years after orthotopic liver transplant were 6 and 9%, respectively. Carbohydrate-deficient transferrin is a biological marker for alcohol abuse independently of liver disease and has been used for the first time ever in liver graft recipients. A total of 830 values were included prospectively in the study population. Detection of alcohol relapse had a sensitivity of 92% and a specificity of 98%. Changes in carbohydrate-deficient transferrin levels indicated clandestine and sporadic drinking after transplantation. Furthermore, clinical events were not found to influence carbohydrate-deficient transferrin, either in patients with or without alcoholic relapse. In our opinion, carbohydrate-deficient transferrin is a useful screening marker for alcohol relapse in patients after orthotopic liver transplant for alcoholic cirrhosis, to select those patients who need special attention from the psychologist.     

Liver transplantation for alcoholic liver disease.

BACKGROUND. Alcoholism is the leading cause of end-stage liver failure in the United States, but the application of liver transplantation to the treatment of alcoholic liver disease remains controversial because of medical and ethical concerns. Information about the outcome of patients who undergo transplantation for alcoholic cirrhosis would help to resolve these concerns. METHODS. The results of 41 patients (Group 1) with alcoholic liver disease were compared with those of patients who underwent liver transplantation for other medical problems (group 2) at this center. Thirty of the 32 survivors from group 1 and 30 matched subjects from group 2 were interviewed to assess substance dependence, recidivism, and activity level. RESULTS. Compared with control subjects, patients with alcoholic liver disease had equivalent patient and graft survival rates and achieved an equal level of postoperative health. These results were achieved even though patients with alcoholic liver disease had significantly worse liver failure and more morbidity before surgery, and one third of the patients in this group were not abstinent before transplantation. CONCLUSIONS. We conclude that patients with alcoholic liver disease merit equal consideration for liver transplantation compared with other causes of liver failure. Treatment of the addictive disorder should be included before and after surgery.     

Increased incidence of oropharyngeal squamous cell carcinomas after liver transplantation for alcoholic cirrhosis

BACKGROUND: THE aim of this study was to describe the features of posttransplantation tumors observed in a series of liver transplant recipients with special reference to patients receiving a transplant for alcoholic cirrhosis. METHODS: Among 171 consecutive liver transplant recipients, 90 patients who had received a first liver allograft for cirrhosis were studied. After liver transplantation, detection of de novo malignancies was prospectively undertaken and the characteristics of the patients in whom tumors occurred were compared with those in whom tumors did not develop. RESULTS: With a follow-up of 45.2+/-21.2 months, 11 tumors were observed in 90 patients (overall incidence of 12.2%). The incidence of tumors was higher in patients receiving a transplant for alcoholic cirrhosis than in patients receiving a transplant for nonalcoholic cirrhosis (26.7% vs. 5.0%, P<0.01). Squamous cell carcinoma (SCC) of the oropharynx or esophagus and posttransplant lymphoproliferative disorders were mainly observed. SCC (uvula in two cases, tongue in one case, esophagus in one case, pharynx in one case) occurred exclusively in patients transplanted for alcoholic cirrhosis (16.7% vs. 0%, P=0.001). The incidence of posttransplant lymphoproliferative disorders was similar in alcoholics and nonalcoholics (6.7% vs. 5%, NS). Survival was not influenced by the occurrence of SCC. CONCLUSION: The incidence of oropharyngeal SCC could be high in patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of posttransplantation immunosuppression in patients exposed to alcohol and tobacco before transplant. Careful posttransplantation screening of oropharyngeal SCC is warranted after liver transplantation for alcoholic cirrhosis.     

Long-term outcome of living donor liver transplantation for primary biliary cirrhosis

In living donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC), the majority of donors are genetically related to their recipients, leading to concerns of an earlier recurrence of PBC and a poorer prognosis due to genetic susceptibility. Totally 81 patients who underwent LDLT for PBC were the subjects of the present study. Immunosuppressive agents consisted of tacrolimus and methylprednisolone. In the outpatient clinic, when the aspartate and alanine aminotransferase level exceeded the upper limit of the normal range, the dose of methylprednisolone was increased from 4 to 6 mg/day for several months. Blood was examined every 2 weeks for 3 months and a liver biopsy was performed when aminotransferase levels did not decrease to the upper limit of the normal range after more than 3 months. Five-year survival and recurrence rates were estimated and the prognostic factors were analyzed. The mean observation period was 6.2 years. Five years after LDLT for PBC, the biopsy-proven PBC recurrence rate was 1%. The 5-year patient survival rate was 80%. The nonrelated or blood-related donor factor and number of human leukocyte antigen matches did not correlate with prognosis. PBC recurrence rate after LDLT in our series was lower than that in previous studies.     

酒精性肝硬变病人的肝移植

５例终末期酒精性肝硬变病人在香港大学玛丽医院肝胆外科施行原位肝移植手术。男４例，女１例。年龄４１～５５岁，平均４６８岁。病人均经心理医学医生评估适合作肝移植，并且在肝移植前至少戒酒６个月。供肝全部来自脑干死亡病人。供肝灌注和保存应用ＵＷ液。４例肝移植术中应用静脉转流技术，１例采用Ｐｉｇｇｙｂａｃｋ法。术后应用类固醇、硫唑嘌呤和环胞霉素Ａ作免疫抑制治疗。移植肝脏和患者的存活率均为１００％，并已分别生存６月～３年，情况良好。肝移植可使末期酒精性肝硬变病人延长生命和恢复正常生活。     

Liver transplantation for alcoholic cirrhosis with anti-HCV antibodies

The results of orthotopic liver transplantation (OLT) in patients with alcoholic liver cirrhosis (ALC) are currently similar to those obtained in patients with other indications. However, the frequent association of ALC with hepatitis C virus (HCV) infection may impair these results. We retrospectively studied the consequences of HCV infection on survival and graft function in 59 patients with ALC undergoing OLT. Patients were classified into two groups depending on their HCV serology before transplantation: group 1 comprised 24 anti-HCV-positive patients, and group 2, 35 anti-HCV-negative patients. Patient and graft survival were similar in both groups. Liver function tests 1 and 4 years after OLT showed AST and ALT values that were significantly higher in group 1 patients and post-transplant histologically proven chronic hepatitis was found in 45 % and 61 % of these patients at 1 and 4 years, respectively. We conclude that pretransplant HCV infection in patients with ALC does not affect survival after OLT. However, one must bear in mind the high incidence of post-transplant chronic hepatitis secondary to recurrence of HCV infection and be cautious when drawing this conclusion. Received: 1 October 1996 Received after revision: 3 March 1997 Accepted: 17 March 1997     

Gene network profiling before and after transplantation in alcoholic cirrhosis liver transplant recipients

The main objective of this study was to define a gene network profile network in liver transplant recipients with alcoholic cirrhosis before and after liver transplantation. Genes were selected from data obtained in a previous study of liver transplant recipients with alcoholic cirrhosis. Selected up-regulated genes were further validated by quantitative real-time polymerase chain reaction in different groups of liver transplant recipients with alcoholic cirrhosis (n=5). Selected genes up-regulated before transplantation were: TNFRSF9 (tumor necrosis factor [TNF] receptor superfamily, member 9); IL2RB (interleukin-2 receptor beta); BCL2L2 (BCL2-like 2); NOX5 (NADPH) oxidase, EF-hand calcium binding domain 5); PEX5 (peroxisomal biogenesis factor 5); PPARG (peroxisome proliferator-activated receptor gamma); NIBP (IKK2 binding protein); NKIRAS2 (NFKappaBeta inhibitor interacting Ras-like 2); IL4 (interleukin-4); IL-4R (interleukin 4 receptor); ADH1A (alcohol dehydrogenase 1A, class 1); ALDH1L1 (aldehyde dehydrogenase 1 family, member L1); MPO (myeloperoxidase); NPPA (natriuretic peptide precursor A); BCL2A1 (BCL2-related protein A1); GADD45A (growth arrest and DNA-damage-inducible alpha); TEGT (Bax inhibitor 1); PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide); IFNGR2 (interferon gamma receptor 2); JAK2 (Janus Kinase 2); FAS (Fas, TNF receptor superfamily, member 6); TANK (TRAF family member-associated NFKB activator); TTRAP (TRAF and TNF receptor-associated protein); and ANXA5 (annexin A5).     

Liver transplantation for alcoholic liver disease

Alcoholic cirrhosis is a major public health issue in France. The prevalence of alcoholic cirrhosis and the number of potential candidates for liver transplantation is unknown but certainly underestimated. Despite physicians' ethical reserves concerning this self-inflicted disease and the public's misgivings, liver transplantation for alcoholic cirrhosis can provide survival rates comparable with those observed for other chronic liver diseases. in this indication, liver transplantation if often associated with a low risk of acute rejection and a high rate cancer of the upper respiratory and digestive tracts. The risk of recurrent alcoholism after liver transplantation is also a major problem. Its prevalence varies from 10 to 50%, depending on the assessment criteria, and the rate recurrent risk for the liver graft (alcohol intake>40 g/d) is to the order of 10%. These figures illustrate the importance of careful management and support for these patients. At least 6 months weaning from alcohol is a commonly accepted selection criterion for transplantation candidates. Criteria for liver transplantation generally include patients aged under 65 years, weaned for more than 6 months, with Child C cirrhosis or less, uncontrollable digestive tract hemorrhage, spontaneous severe infection, hepatorenal syndrome, hepatopulmonary syndrome, or multifocal hepatocellular carcinoma if the largest nodule measures less than 3 cm. Acute alcoholic hepatitis is a severe disease, fatal in 50% of the cases, and resistant tot corticosteroid therapy. Liver transplantation in this subpopulation of often young patient who have not achieved weaning merits further evaluation.     

The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation.

Patients with clinical acute alcoholic hepatitis (AAH) are not considered suitable candidates for orthotopic liver transplantation (OLT). The histological correlates of AAH are often seen in the explanted liver at the time of transplantation. The importance of these findings remains inconclusive regarding their role as a prognostic marker for patient or allograft health. Our aim was to examine the explanted liver of patients with purely alcoholic liver disease (ALD) for findings of histologic AAH and to correlate these to patient and graft outcomes. We compared patients with and without histological AAH with patients transplanted for non-ALD. Of 1,097 liver transplant recipients, 148 had ALD and 125 were non-ALD control patients with similar demographics. Thirty-two of 148 ALD patients had histologic AAH, and 116 had bland alcoholic cirrhosis (BAC). Twenty-eight percent of the ALD patients reported <6 months abstinence, and 54% reported <12 months abstinence. There was a statistically significant relationship between the presence of histologic AAH and abstinence durations<12 months (P=0.009), but not <6 months. Overall, posttransplantation patient and graft survival between the ALD and non-ALD groups was not significantly different (P=0.53). Furthermore, patient and graft survival between ALD patients with histologic AAH and BAC were similar (P=0.13 and P=0.11, respectively). The rate of posttransplantation relapse among ALD patients was 16%; however, there was no increase in graft loss, nor was there decreased survival compared with controls. The patients with histologic AAH and those with BAC had no differences in posttransplantation relapse (P=0.13). In multivariate analysis, patient and graft survival was not influenced by pretransplantation abstinence or posttransplantation relapse. In conclusion, histological alcoholic hepatitis in the explant did not predict worse outcome regarding relapse, and allograft or patient survival for liver transplant recipients. Caution should be exercised when liver histology is used to discriminate among suitable candidates for OLT concerning alcoholic patients.     

Herpes zoster infection after liver transplantation: a case-control study.

Prior case series have suggested that herpes zoster (HZ) after orthotopic liver transplantation (OLT) may lead to serious complications due to visceral involvement. We sought to determine the incidence, risk factors, and long term outcomes of HZ after OLT. Clinical data from September 1993 to April 2004 were collected on all cases of HZ after OLT, and at the same post-OLT time points in age, gender, and transplant-year-matched HZ-negative controls. Risk factors for HZ infection and long-term outcomes were compared between cases and controls. A total of 29 patients developed HZ at a median of 4.9 years (range .5-12.9) after OLT. All HZ infections except 1 were localized to a single dermatome. Only 8 (28%) were hospitalized and 16 (55%) were treated with oral antivirals alone. No patients developed visceral involvement or died of HZ infection. No risk factors for HZ infection were identified on multivariate analysis. Of the long-term outcomes, the estimated 10-year survival was lower (P = .05) for cases than controls. The lower survival in HZ cases was not directly attributable to HZ infection. In conclusion, this study is the largest series on HZ after OLT. HZ is neither a common nor a serious infection after OLT and can be managed with antiviral therapy with a low likelihood of visceral dissemination.