Liver Transplantation For Alcoholic Liver Disease Research Articles

Update on liver transplantation-newer aspects

Liver transplantation (LT) remains the only therapeutic option offering gold standard treatment for end-stage liver disease (ESLD) and acute liver failure (ALF), as well as for certain early-stage liver tumors. Currently, the greatest challenge facing LT is the simple fact that there are not enough adequate livers for all the potential patients that could benefit from LT. Despite efforts to expand the donor pool to include living and deceased donors, organ shortage is still a major problem in many countries. To solve this problem, the use of marginal liver grafts has become an inevitable choice. Although the definition of marginal grafts or criteria for expanded donor selection has not been clarified yet, they are usually defined as grafts that may potentially cause primary nonfunction, impaired function, or late loss of function. These include steatotic livers, older donors, donors with positive viral serology, split livers, and donation after cardiac death (DCD). Therefore, to get the best outcome from these liver grafts, donor-recipient selection should be vigilant. Alcohol-related liver disease (ALD) is one of the most common indications for LT in Europe and North America. Traditionally, LT for alcoholic liver disease was kept limited for patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Besides, the initial results of early liver transplantation (ELT) without waiting for 6 months of abstinence period are satisfactory in severe alcoholic hepatitis (SAH). It will be important to take care of these patients from a newer perspective.

Hepatitis C remains leading indication for listings and receipt of liver transplantation for hepatocellular carcinoma

Background and aimsWith the availability of direct acting antivirals (DAA) for hepatitis C virus (HCV) infection, alcoholic liver disease (ALD) has evolved as the leading indication for listing and receipt of liver transplantation (LT) followed by non-alcoholic steatohepatitis and HCV infection. However, data are limited on etiology specific trends on listings and need for LT for hepatocellular carcinoma (HCC). MethodsWe analyzed UNOS database to examine etiology specific listings and receipt of LT for patients with and without HCC. Listings and receipt of LT in the pre-DAA (2007–2012) era were compared to the DAA (2013–2018) era. ResultsThe analysis shows that among patients without HCV, there is a decreasing trend on the proportion of patients listed and transplanted for HCV, with simultaneous increase on listings and LT for NASH and ALD. Specifically for listings and transplants for HCC, the leading etiology remains HCV infection followed by NASH and ALD. The analysis also showed that LT for AH contributes to about 20% of increase in listings and receipt of LT for ALD.

Liver transplantation and alcoholic liver disease: History, controversies, and considerations.

Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease (ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation (LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a “self-inflicted disease”. One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this “6-mo rule” is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.

Orthotopic Liver Transplantation in Alcoholic Liver Disease Patients.

Alcoholic Liver Disease (ALD) represents the second most common indication for Liver Transplantation (LT) worldwide. Outcomes of LT for ALD are comparable with those of liver transplantation for other aetiologies of liver disease; however, it's still considered a controversial indication to LT, mainly because ALD is considered a self inflicted disease, and for the risk of relapse after LT. Most transplant programs require 6 months of abstinence in order to consider a patient suitable for LT, however the role of the length of pre transplant abstinence as predictor of alcohol relapse after LT is still controversial. A psycho-social assessment to establish the likelihood of long-term abstinence after LT should be performed in patients with ALD potential candidates for LT. Acute alcoholic hepatitis is considered a contraindication to transplantation in most transplant centers. However, early LT, in selected patients, with a first episode of severe alcoholic hepatitis not responding to medical therapy, has been shown to improve survival. Further studies are needed to better assess the risk of alcohol relapse after LT in patients with acute alcoholic hepatitis.

Severe alcoholic relapse after liver transplantation: What consequences on the graft? A study based on liver biopsies analysis.

Alcoholic liver disease (ALD) is a major indication for liver transplantation (LT), but up to 20% of patients experience severe alcoholic relapse. The aims of this study were to evaluate the impact of severe alcoholic relapse on the graft (based on histological examination) and to identify predictive factors associated with recurrent alcoholic cirrhosis (RAC). From 1990 to 2010, 369 patients underwent LT for ALD at Edouard Herriot Hospital (Lyon, France) and survived more than 1 year. All patients who presented severe alcoholic relapse and histological follow-up were included. Liver biopsies were performed at 1 and 5 years and at every 5 years after LT, and when clinically indicated. The median follow-up after LT was 11 years (range, 3-18 years). Severe alcoholic relapse was observed in 73 (20%) of the 369 patients, from whom 56 patients with histological evaluation were included. RAC was diagnosed in 18 (32%) of the 56 patients included, which represents 5% of the 369 patients transplanted for ALD. The median delay between LT and RAC was 6 years (range, 3-10 years) and 4.5 years (range, 2-8 years) after severe alcoholic relapse. The median cumulated years of alcohol use before RAC was 3.5 years (range, 2-7 years). The cumulative risk for F4 fibrosis was 15% at 3 years, 32% at 5 years, and 54% at 10 years after severe alcoholic relapse. A young age at LT (≤50 years old) and an early onset of heavy drinking (within the first 3 years after LT) were associated with RAC. In conclusion, severe alcoholic relapse usually occurs in the first years after LT and is responsible for accelerated severe graft injury. Liver Transplantation 22 773-784 2016 AASLD.

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post-transplant CDT monitoring for alcohol relapse assessment - a retrospective study.

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post-LT long-term observation is challenging, and biomarkers as carbohydrate-deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow-up was 73 months (0-213). One- and five-year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post-transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single-center analysis showed good post-transplant long-term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post-LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.

Liver transplantation for alcoholic liver disease: Lessons learned and unresolved issues.

The use of liver transplantation (LT) as a treatment for alcoholic liver disease (ALD) has been highly controversial since the beginning. The ever increasing shortage of organs has accentuated the low priority given to patients suffering from ALD, which is considered a "self-inflicted" condition. However, by improving the long-term survival rates, making them similar to those from other indications, and recognizing that alcoholism is a primary disease, ALD has become one of the most common indications for LT in Europe and North America, a situation thought unfathomable thirty years ago. Unfortunately, there are still many issues with the use of this procedure for ALD. There are significant relapse rates, and the consequences of excessive drinking after LT range from asymptomatic biochemical and histological abnormalities to graft failure and death. A minimum three-month period of sobriety is required for an improvement in liver function, thus making LT unnecessary, and to demonstrate the patient's commitment to the project, even though a longer abstinence period does not guarantee lower relapse rates after LT. Recent data have shown that LT is also effective for severe alcoholic hepatitis when the patient is unresponsive to corticosteroids therapy, with low relapse rates in highly selected patients, although these results must be confirmed before LT becomes a standard procedure in this setting. Finally, LT for ALD is accompanied by an increased risk of de novo solid organ cancer, skin cancer, and lymphoproliferative disorders, which has a large impact on the survival rates.

Impact of the 2011 Great East Japan Earthquake on the Resumption of Alcohol Consumption After Living-Donor Liver Transplantation for Alcoholic Cirrhosis: A Report of Two Cases

Alcoholic liver disease (ALD) is a leading indication for liver transplantation (LT) in Western countries. The rate of resumption of alcohol abuse is 7% to 95% after LT for ALD. A high prevalence of alcohol abuse has been observed in disaster-exposed populations; however, little is known about the association between resumption of alcohol abuse after LT and disasters. Between June 2007 and March 2011, 3 patients with alcoholic cirrhosis (2 men and 1 woman) underwent living-donor LT (LDLT) at Tohoku University Hospital, Sendai, Japan. The female patient died of graft failure 6 months after LDLT. The other patients (ages 55 and 56 years), who survived to discharge, resumed alcohol abuse after the 2011 Great East Japan Earthquake. Before transplantation, both patients had been abusing alcohol for >35 years, with a daily ethanol intake of 110 g and 140 g, respectively. The period of abstinence from alcohol consumption ranged from 4 to 6 months. After transplantation, patients showed good compliance with treatment and seemed at low risk of relapse until the earthquake. One patient was living in the nuclear evacuation zone at Fukushima, and resumed alcohol consumption after the evacuation. Another patient resumed alcohol consumption while temporarily living apart from his family during restoration work after the disaster. Extreme stress and changes in living arrangements after the Great East Japan Earthquake seemed to trigger the desire to drink. This is the first report on patients who underwent LT for ALD and who resumed alcohol consumption after a disaster.

Liver transplantation for end-stage alcoholic liver disease: a single-center experience from mainland China

There has been a gradual increase in the number of patients with end-stage alcoholic liver disease (ALD) undergoing liver transplantation (LT) in mainland China. However, few studies have focused on the post-transplant outcomes of this population. The aim of this study was to evaluate the efficacy of LT in patients with ALD, mainly focusing on survival rates, complications, and alcohol recidivism. The results were retrospectively analyzed from 20 patients, who underwent LT for ALD from December 2003 to September 2007 at Liver Transplant Center of Third Affiliated Hospital of Sun Yat-sen University. The 1-, 2-, and 3-year survival rates of the ALD group and non-ALD group were 90.0, 80.0, 80.0% and 90.3, 84.7, 79.8%, respectively. There was no significant difference in 1-, 2-, and 3-year survival rates between these two groups ( P = .909). No significant difference was observed in complications such as pulmonary infection (50.0 vs. 31.9%, P = .137), biliary complications (15.0 vs. 27.4%, P = .297), hepatic arterial complications (10.0 vs. 6.9%, P = .641), and rejection (15.0 vs. 8.1%, P = .394) after LT between the ALD group and non-ALD group. There was only one person who resumed mild, intermittent drinking after LT. End-stage ALD is a good indication for LT, with similar results in non-ALD patients. The major cause of death in ALD patients after LT was infectious complications. More attention is needed for the prophylaxis of infectious complications after LT.

Alcohol relapse after liver transplantation for alcoholic liver disease: does it matter?

Background/Aims: The aim of this study was to distinguish the types of alcohol consumption after liver transplantation (LT) for alcoholic cirrhosis and to assess the consequences of heavy drinking. Methods: Patients transplanted for alcoholic cirrhosis were studied. Alcoholic relapse diagnosis was based upon patient's and family members' reports, liver enzyme tests, graft biopsy, and use of urine alcohol test. Results: One hundred twenty-eight patients were studied, with a mean follow-up of 53.8 months. After LT, 69% of patients were abstinent, 10% were occasional drinkers, and 21% were heavy drinkers. Actuarial survival rates were not different, but three of the seven deaths observed among heavy drinkers were directly related to alcohol relapse. Although there was no difference between the three groups concerning the rejection rates, all rejection episodes observed in the group of heavy drinkers were related to poor compliance with immunosuppressive drugs. One heavy drinker developed alcoholic cirrhosis. Conclusions: The present study indicates that patients can resume heavy alcohol consumption after LT for alcoholic liver disease (ALD) and their grafts can be injured because of poor compliance with immunosuppressive drugs and alcohol-related liver injury. Although patient survival was not influenced by alcohol relapse, heavy alcohol consumption can be responsible for patients' death.

Liver transplantation for alcoholic liver disease: Executive statement and recommendations

A lcoholic liver disease (ALD) is a major cause of cirrhosis and a leading cause of death of end-stage liver disease in the United States and most of the Western world. The only means of restoring health in patients with end-stage liver disease at present is orthotopic liver transplantation. In the United States, between 3,000 and 4,000 liver transplants are performed each year, and a similar number are done yearly in Western Europe. Of the total, 20% to 25% are performed for ALD. The increasing demand for liver transplantation and lack of a similar increase in the supply of donor livers make it important to reassess the use of this precious resource on a regular basis. What criteria should be used in selecting patients with ALD for liver transplantation? How can survival and quality of life after liver transplantation for ALD be made optimal? These issues were addressed in a focused 2-day workshop, ‘‘Liver Transplantation for Alcoholic Liver Disease,’’ held under the auspices of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute for Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Maryland, December 6-7, 1996. This executive statement summarizes the issues raised at this conference and provides overall recommendations regarding treatment of patients with ALD who require liver transplantation. Most importantly, this summary focuses on important needs and directions for clinical research in liver transplantation for ALD. Alcohol is used by a majority of adults in the Western world. Population-based surveys indicate that 68% of adult Americans drink at least one alcoholic beverage per month, and 10% drink two or more per day, the usual definition used for ‘‘heavy drinking.’’ Heavy drinking is more common among men (18%) than women (3%) and among whites than blacks or Hispanics. Alcohol use is a major cause of morbidity and mortality; in the United States, 5% of deaths, approximately 100,000 per year, are either directly or indirectly attributable to alcohol abuse. Why some individuals are able to drink alcohol without dependence while others cannot is unknown. Among the factors associated with the development of alcoholism, both social and genetic factors are important. A family history of alcoholism is perhaps the major risk factor for developing alcohol dependence or abuse. The recent identification of genetic linkages to alcohol-seeking activity in laboratory animals promises to provide critical information on the genetic basis of alcoholism. Research into the nature of addiction is of central importance for the future of prevention and treatment of alcoholism. Encouragement of temperance and moderation should be the cornerstone to societal attempts to decrease alcoholism. ALD is perhaps the most widely recognized complication of chronic alcohol abuse. Nevertheless, only 15% to 20% of alcoholic subjects develop cirrhosis. The disease is more common in men than in women, and the average age of onset is in the mid-40s, typically after 10 to 20 years of heavy alcohol use. The average intake of alcohol in patients with ALD is more than 100 g of alcohol (approximately 8 drinks) per day, but the lower