Andrea DiMartini

Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Guidelines on Evaluation for Liver Transplantation (LT) were published in 2005 by the American Association for the Study of Liver Diseases (AASLD). In the interim there have been major advances in the management of chronic liver disease, most notably in antiviral therapy for chronic viral hepatitis. Nonalcoholic fatty liver disease (NAFLD) has assumed increasing prominence as a cause of cirrhosis and hepatocellular carcinoma (HCC) requiring liver transplant. Furthermore, individual disease indications for LT such as HCC have been refined and specific guidelines have appeared for chronic viral hepatitis. Reflecting the need for a multidisciplinary approach to the evaluation of this complex group of patients who have the comorbidities typical of middle age, recommendations have been developed to assist in their cardiac management. With an increasing number of long-term survivors of LT there has been a greater focus on quality of life and attention to comorbid conditions impacting recipient longevity. The purpose of the current Guidelines is to provide an evidence-based set of recommendations for the evaluation of adult patients who are potentially candidates for LT. These recommendations provide a data-supported approach. They are based on the following: (1) formal review and analysis of the recently published world literature on the topic; (2) guideline policies covered by the AASLDPolicy on Development and Use of Practice Guidelines; and (3) the experience of the authors in the specified topic. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the available evidence supporting the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The classifications and recommendations are based on three categories: the source of evidence in levels I through III; the quality of evidence designated by high (A), moderate (B), or low quality (C); and the strength of recommendations classified as strong or weak.*

Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease

For patients who receive a liver transplant (LTX) for alcoholic liver disease (ALD), investigators are focusing beyond survival to determine specific alcohol use outcomes. Studies suggest the use of alcohol ranges from 8 to 22% for the first post‐transplant year with cumulative rates reaching 30 to 40% by 5 years following transplantation. Yet while investigators are interested in determining specific rates of alcohol use and predictors of use, only three studies since 1990 have been prospective. In 1998, we began a prospective study of post‐LTX alcohol consumption in ALD recipients using multiple repeated measures of alcohol use. After 5 years of follow‐up, we found that 22% had used any alcohol by the first year and 42% had a drink by 5 years. By 5 years, 26% drank at a heavier use (binge) pattern and 20% drank in a frequent pattern. In a univariate model, predictors of alcohol use included pre‐transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation. Liver Transpl 12:813–820, 2006.

Liver transplantation for alcoholic cirrhosis: Long term follow-up and impact of disease recurrence

BACKGROUND Alcoholic liver disease has emerged as a leading indication for hepatic transplantation, although it is a controversial use of resources. We aimed to examine all aspects of liver transplantation associated with alcohol abuse. METHODS Retrospective cohort analysis of 123 alcoholic patients with a median of 7 years follow-up at one center. RESULTS In addition to alcohol, 43 (35%) patients had another possible factor contributing to cirrhosis. Actuarial patient and graft survival rates were, respectively, 84% and 81% (1 year); 72% and 66% (5 years); and 63% and 59% (7 years). After transplantation, 18 patients (15%) manifested 21 noncutaneous de novo malignancies, which is significantly more than controls (P=0.0001); upper aerodigestive squamous carcinomas were overrepresented (P=0.03). Thirteen patients had definitely relapsed and three others were suspected to have relapsed. Relapse was predicted by daily ethanol consumption (P=0.0314), but not by duration of pretransplant sobriety or explant histology. No patient had alcoholic hepatitis after transplantation and neither late onset acute nor chronic rejection was significantly increased. Multiple regression analyses for predictors of graft failure identified major biliary/vascular complications (P=0.01), chronic bile duct injury on biopsy (P=0.002), and pericellular fibrosis on biopsy (P=0.05); graft viral hepatitis was marginally significant (P=0.07) on univariate analysis. CONCLUSIONS Alcoholic liver disease is an excellent indication for liver transplantation in those without coexistent conditions. Recurrent alcoholic liver disease alone is not an important cause of graft pathology or failure. Potential recipients should be heavily screened before transplantation for coexistent conditions (e.g., hepatitis C, metabolic diseases) and other target-organ damage, especially aerodigestive malignancy, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease.

PTSD in Heart Transplant Recipients and Their Primary Family Caregivers

Posttraumatic stress disorder associated with transplantation (PTSD-T) is a complication for some heart transplant recipients. By using a structured, standardized interview and DSM-III-R criteria, the authors examined whether recipients (n = 158) and their family caregivers (n = 142) showed similar PTSD-T rates and clinical characteristics during the first year posttransplant. Among the recipients, 10.5% met full criteria for the disorder and an additional 5% were probable cases. Among the caregivers, 7.7% met full criteria and an additional 11.0% were probable cases. Severity and duration of disorder were similar across the groups. Being female, having a history of psychiatric illness, and having lower friend support were increased risks for PTSD-T.

Trajectories of alcohol consumption following liver transplantation.

Any use of alcohol in the years following liver transplantation (LTX) approaches 50% of patients transplanted for alcoholic liver disease (ALD). We collected detailed prospective data on alcohol consumption following LTX for ALD to investigate ongoing patterns of use. Using trajectory modeling we identified four distinct alcohol use trajectories. One group had minimal use over time. Two other groups developed early onset moderate‐to‐heavy consumption and one group developed late onset moderate use. These trajectories demonstrate that alcohol use varies based on timing of onset, quantity and duration. Using discriminant function analysis, we examine characteristics of recipients pre‐LTX alcohol histories and early post‐LTX psychological stressors to identify the profile of those at risk for these specific trajectories. We discuss the relevance of these findings to clinical care and preliminarily to outcomes.

Long-term follow-up after liver transplantation for alcoholic liver disease under tacrolimus.

BACKGROUND Liver transplantation (LTx) for alcohol-related liver disease (ALD) is an accepted modality of treatment and is one of the most common indications for LTx in the United States. The present report examines the long-term patient survival, graft survival, rates of recidivism, and development of de novo cancers in this group, and compares these results with a contemporaneous group of patients who were transplanted for non-ALD indications. METHODS Between August 1989 and December 1992, 185 adults received LTx for ALD (group I). During the same time interval, 649 adults received LTx for non-ALD (group II). The mean follow-up time was 94+/-10.7 months for group I vs. 92+/-11 months for group II. Kaplan-Meier survival estimates and the incidence of cancers using Surveillance Epidemiologic End Result data were compared in both groups. RESULTS At 5 years after orthotopic LTx, the overall patient survival and graft survival for group I were 72.0% and 66.5% vs. 66.5% and 60.3% for group II, respectively. After 5 years, the patient survival and graft survival for the alcoholic group were significantly lower (P=0.001) compared to the non-alcoholic group. The rate of de novo oropharyngeal cancer and lung cancer was 25.5 times and 3.7 times higher, respectively, in ALD group compared with the general population matched for age, sex, and length of follow-up (P=0.001), whereas this was not higher in the non-ALD group. Prior pretransplant length of sobriety and alcohol rehabilitation was not associated with the rate of post-LTx rate of recidivism, which was 20%. Out of 79 deaths in group I, only 1 was attributed to recidivism and 3 to noncompliance with recidivism. The other deaths occurred from de novo cancer (n=13), posttransplant lymphoproliferative disorder (n=5), age-related complications (n=23), and other infection or miscellaneous causes (n=34). CONCLUSIONS Patient and graft survival past 5 years after orthotopic LTx is significantly lower for ALD for a variety of reasons (P=0.001). The rate of upper airway malignances was significantly higher in ALD patients than for non-ALD post-LTx patients and the general public. Graft loss/death related to recidivism or chronic rejection was extremely low. More attention is needed for early diagnosis of de novo cancer and prevention of cardiorespiratory and cerebrovascular complications.

Quality of Life After Small Intestinal Transplantation and Among Home Parenteral Nutrition Patients

BACKGROUND The purpose of the study was to quantify changes in the quality of life of small bowel recipients before and after transplantation and of home parenteral nutrition (HPN)-dependent patients before and after therapy. We examined quality of life across multiple areas of function including physical, social, and emotional indices. METHODS The Quality of Life Instrument in the form of a self-administered questionnaire was completed voluntarily by the recipients of small intestinal transplants and by a cohort of HPN-dependent patients. RESULTS Small intestinal transplant recipients reported significant improvement in the quality of their life and function. They also rated their quality of life and function during the pretransplant, TPN-dependent period to be worse than before the development of chronic intestinal failure. Similarly, HPN recipients reported significant worsening across most areas of quality of life when they compared their premorbid period to the HPN-dependent state. CONCLUSIONS TPN dependence causes significant impairment in the quality of life in most areas of functioning. In contrast, small intestinal transplantation restores the quality of life among recipients with functioning grafts.

QUALITY OF LIFE OF PATIENTS AFTER INTESTINAL TRANSPLANTATION

BACKGROUND Quality of life is an important consideration in evaluating new medical or surgical treatments. Intestinal transplantation is now available for patients with irreversible intestinal failure. We compared quality of life among patients with intestinal failure receiving home parenteral nutrition (HPN) to that among patients who underwent intestinal transplantation (ITx) at the University of Pittsburgh Medical Center. METHODS The results of the Quality of Life Inventory, a self-administered questionnaire, were compared among 10 ITx recipients and 10 HPN patients. Change in quality of life was examined longitudinally over a 2-year period with repeat testing in four patients in each group. RESULTS ITx recipients were evaluated at mean time of 2.7 years after transplantation and after a mean period of 5.3 years of intestinal failure. HPN patients were evaluated after a mean period of 5.1 years of intestinal failure and were similar to the transplant recipients in age, gender, race, social status, education, etiology, and duration of disease. Assessed quality of life was markedly similar between HPN-dependent patients and ITx recipients, with significant differences in only 2 of 25 domains, despite the difficult early postoperative course and complex management that accompany intestinal transplantation. In longitudinal follow-up (n=4), ITx recipients reported significant improvement in anxiety (P=0.02), sleep (P=0.03), and impulsiveness/control (P<0.001), reflecting a progressive adjustment to their posttransplant status. CONCLUSION The quality of life in ITx recipients is similar to that in HPN-dependent patients. Quality of life among ITx recipients improves over time with decreased anxiety over physical functioning. Further research and efforts to improve quality of life in transplant recipients are needed.

Tobacco use following liver transplantation for alcoholic liver disease: An underestimated problem†

Alcohol and tobacco use commonly co‐occur, with at least 90% of those with an alcohol problem also using tobacco. Thus, 3 years ago when we discovered higher rate of late deaths due to lung and oropharyngeal cancer in patients who had received a transplant for alcoholic liver disease (ALD), we hypothesized that these patients were continuing to expose themselves to tobacco after liver transplantation (post‐LTX) and that this behavior was increasing their risk for cancer. We subsequently began a prospective investigation of post‐LTX tobacco use in patients having undergone LTX for ALD (n = 172). For 33 recipients we had data starting from our first assessment at 3 months post‐LTX and for this subgroup we report on the details of the timing of tobacco use resumption and the redevelopment of nicotine addiction. We found that on average more than 40% are smoking across all time periods. ALD recipients resume smoking early post‐LTX, increase their consumption over time, and quickly become tobacco dependent. These data highlight an underrecognized serious health risk for these patients and demonstrate our need for more stringent clinical monitoring and intervention for tobacco use in the pre‐ and post‐LTX periods. (Liver Transpl 2005;11:679–683.)

Psychiatric Aspects of Organ Transplantation in Critical Care

Intensive care unit teams are a critical part of the solid organ transplant process. The psychosocial issues involved during critical periods of transplantation are important for intensive care physicians and clinicians to understand to provide comprehensive care to transplant patients. This article provides a brief overview of transplant epidemiology, followed by a review of the psychosocial issues relevant to the phases of the transplant process. Considered are the pretransplant evaluation phase, psychiatric disorders in transplant patients, and cognitive impairments and delirium with additional issues specific to particular organs. Also covered are the side effects of immunosuppressive medications and special issues arising with living donors.