Liver transplantation in people with alcohol‐related liver disease
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Abstract:
Alcoholic liver cirrhosis is a leading cause of liver transplantation around the world. Nevertheless, selection of alcoholic candidates remains controversial. We estimate that 20–50% of patients who receive a liver transplant because of end-stage alcoholic liver disease acknowledge some alcohol use in the first 5 years after liver transplantation, whereas 10–15% will resume heavy drinking. Currently, the majority of alcoholic patients who are placed on the liver transplant waiting list have established extended periods of abstinence from alcohol prior to evaluation. This chapter looks at assessment of the alcoholic patient before the decision to undertake liver transplantation is made, and the management and outcome of liver transplantation in this population, including specific issues related to alcohol use.Keywords:
Liver disease
Although alcoholic liver disease (ALD) is an accepted indication for liver transplantation (LT), there are several controversial issues. The aim of this study is to examine the applicability of the 6-month abstinence rule prior to LT and to evaluate the results in living donor LT for patients with ALD.A retrospective study of 102 patients with ALD referred for LT was performed. Clinical data, including alcohol consumption history, were analyzed. A period of abstinence from drinking alcohol of at least 6 months was strictly required.Among 102 patients, 21 abstained from drinking for at least 6 months. Of these, 13 patients (12%) underwent LT, five patients (5%) recovered without LT and three patients (3%) were listed for deceased donor LT. LT was not indicated for the remaining 81 patients (80%). Eight patients died within 6 months of referral to our program. The Child-Pugh score was higher in these eight patients than in the 21 who achieved 6-month abstinence, although the alcohol consumption history variables did not significantly differ between the two groups. The 5-year overall survival rates after LT in 13 patients with ALD (91%) were similar to those in 387 non-ALD patients (83%). The rate of alcohol consumption relapse after LT was 8% (n = 1/13).Living donor LT for patients with ALD who complied with the 6-month abstinence rule provides sufficient survival benefit with good compliance, compensating for the potential risks to the donors.
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Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.
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There is a worldwide tendency towards a reduction in the rates of deaths due to cirrhosis. In Chile, a decrease in the number of hospital admissions due to this disease has been recorded.To assess general characteristics and temporal evolution of liver cirrhosis mortality in Chile between 1990 and 2007.National death records and population databases were reviewed. Crude and age-adjusted mortality rates for alcoholic and non-alcoholic cirrhosis were calculated, evaluating their evolution in the study period and the relative risk by gender.In the study period, 44,894 deaths caused by cirrhosis were recorded. Mortality rate was 16.6 deaths per 100,000 inhabitants. 54% of deaths were attributed to non-alcoholic cirrhosis. There was a reduction in mortality rates for both types of cirrhosis. Males accounted for 83 and 65% of deaths caused by alcoholic and non-alcoholic cirrhosis, respectively. The figures for relative risk of death were 5 and 1.9, respectively.Alcoholic cirrhosis was the preponderant cause among liver cirrhosis deaths. A decrease in mortality rates was observed in the study period. Improvements in disease treatment and control could possibly explain this trend.
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Alcoholic liver disease(ALD) is the second most common diagnosis among patients undergoing liver transplantation(LT).The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma.Inthe case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months.The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period.Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy.Patients with severe advanced ALD should have legal access to LT.The mere lack of pre-LT abstinence should not be an obstacle for being listed.
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Although alcoholic liver disease(ALD) is regarded as a common indication for liver transplantation(LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.
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Context: Alcoholic liver cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). The importance of tumour-associated cirrhosis in the development or progression of HCC is not understood. MiRNAs are important regulators for HCC development, but their role in HCC due to alcoholic liver cirrhosis is unclear.Objective: The aim of this study is the detection of miRNA expression in alcoholic liver cirrhosis, tumour-associated cirrhosis, and HCC.Materials and methods: We analysed the differences in the miRNA profiles of HCC, tumour-associated cirrhosis, and cirrhosis without HCC samples from 30 patients who underwent liver transplantation because of alcoholic liver disease.Results: Microarray analyses revealed 40 significantly differentially expressed miRNAs between HCC tissue and tumour-associated cirrhosis tissue. Furthermore, the microarray analysis discovered 56 differentially expressed miRNAs in tumour-associated cirrhosis and cirrhosis without HCC.Discussion: The differences of miRNA profile in alcoholic liver cirrhosis with and without HCC could improve understanding of HCC development, as well as lead to a new diagnostic tool in HCC screening.Conclusion: We were able to show for the first time, the differences of miRNA profile as promising biomarker in HCC, tumour-associated cirrhosis, and cirrhosis without HCC in context of alcoholic liver disease.
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The dietary intake of eight alcoholic patients with liver cirrhosis following complete abstinence was compared with that of non-alcoholic cirrhotics. Protein and lipid amounts actually ingested were much lower, even following abstinence, in alcoholic cirrhotics than in non-alcoholic cirrhotics, suggesting that dietary customs of alcoholics with liver disease do not change easily. Therefore, dietary education is necessary for abstaining alcoholics and should be aggressively applied in the out-patient clinic.
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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.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.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.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.
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Two hundred seventy-one patients with various forms of alcoholic liver disease were followed up for an average of 87.9 months. The survival was the lowest for alcoholic cirrhosis (average 10-year survival: 23.8%). Prognosis was grave especially in cirrhotic patients who continued drinking, owing mainly to the increased death due to gastrointestinal bleeding. The development of hepatocellular carcinoma (HCC) was observed during the first six years only in cirrhosis. The average 5-year probability rate of developing HCC for cirrhosis was 16.3%. The rate was significantly higher for the cirrhotic patients who abstained than for those who continued drinking. Serial biopsies were performed on 66 non-cirrhotic patients who continued drinking. The mean duration of histological follow-up 46.0 months. Cirrhosis developed eventually in 30.3% of the cases. In conclusion, the present study indicates that continued drinking causes progressive liver damage and a poor prognosis. Our data also suggest that abstinence is associated with an increased risk of HCC in cirrhosis. Thus, it is important to recover from alcoholism before cirrhosis develops.
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