Management of alcohol use disorder in patients with cirrhosis in the setting of liver transplantation.

The prevalence of alcohol use disorder (AUD) has been steadily increasing over the past decade. In parallel, alcohol-associated liver disease (ALD) has been increasing at an alarming rate, especially among young patients. Data suggest that most patients with ALD do not receive AUD therapy. Although liver transplantation is the only curative therapy for end-stage ALD, transplant candidacy is often a matter of debate given concerns about patients being under-treated for AUD and fears of post-transplantation relapse affecting the allograft. In this Review, we discuss diagnosis, predictors and effects of relapse, behavioural therapies and pharmacotherapies, and we also propose an integrative, multidisciplinary and multimodality approach for treating AUD in patients with cirrhosis, especially in the setting of liver transplantation. Notably, this approach takes into account the utility of AUD pharmacotherapy in patients on immunosuppressive medications and those with renal impairment after liver transplantation. We also propose a comprehensive and objective definition of relapse utilizing contemporary biomarkers to guide future clinical trials. Future research using the proposed approach and definition is warranted with the goal of optimizing AUD treatment in patients with cirrhosis, the transplant selection process and post-transplantation care of patients with AUD.

Gender Disparities in Alcohol Use Disorder Treatment Among Privately Insured Patients with Alcohol-Associated Cirrhosis.

BACKGROUND: The burden of alcohol-associated cirrhosis (AC) is high, and though alcohol cessation improves mortality, many patients fail to engage in alcohol use disorder (AUD) treatment and continue drinking. Our aim was to determine rates, predictors, and outcomes of AUD treatment utilization in AC patients with private insurance. METHODS: We collected data from persons with AC (diagnosed by ICD-9/ICD-10 codes), aged 18 to 64 years, enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009 to 2016). We determined rates and predictors of substance abuse treatment visits as well as rates of alcohol relapse prevention medication prescriptions, weighted to the national employer-sponsored insured population. Effects of AUD treatment utilization on decompensation rates were calculated using proportional hazards regression with propensity score adjustment. RESULTS: A total of 66,053 AC patients were identified, 32% were female, and mean age at diagnosis was 54.5 years. About 72% had insurance coverage for substance abuse treatment. Overall, AUD treatment utilization rates were low, with only 10% receiving a face-to-face mental health or substance abuse visit and only 0.8% receiving a Food and Drug Administration (FDA)-approved relapse prevention medication within 1 year of index diagnosis. Women were less likely to receive a face-to-face visit (hazard ratio [HR] 0.84, p < 0.001) or an FDA-approved relapse prevention medication (0.89, p = 0.05) than men. AC patients who had a clinic visit for AUD treatment or used FDA-approved relapse medication showed decreased risk of decompensation at 1 year (HR 0.85, p < 0.001 for either). CONCLUSIONS: AUD treatment utilization is associated with lower decompensation rates among privately insured patients with AC. Women were less likely to utilize AUD treatment visits. Efforts to reduce gender-specific barriers to treatment are urgently needed to improve outcomes.

Social support for patients undergoing liver transplantation in a Public University Hospital.

BACKGROUND: Several diseases may lead to the need for liver transplantation due to progressive organ damage until the onset of cirrhosis, resulting in changes in interpersonal relationships. Social Support for transplant candidates is an important variable, providing them with psychological and social well-being. This study aims to assess social support in chronic hepatic patients, waiting for liver transplantation. METHODS: A cross-sectional study was conducted with 119 patients, for convenience sampling, from the liver transplant waiting list at a Brazilian University Hospital Outpatients. The information was collected through semistructured questionnaires, in four stages: 1) socioeconomic and demographic information 2) clinical aspects 3) feelings 4) Social Support Network Inventory (SSNI), to Brazilian Portuguese. The statistical analysis was conducted using ANOVA and multivariate linear regression analysis to evaluate the relationship between the scales of social support and the collected co-variables. RESULTS: Average age was 50.2 ± 11.6, and 87 (73.1%) were men. Patients with alcohol and virus liver disease etiology had the same frequency of 28%. The MELD, without extrapoints, was 16.7 ± 4.9. Global social support family score was 3.72 ± 0.39, and Cronbach's alpha = 0.79. The multivariate analysis presented the following associations, age = [- 0.010 (95% CI = - 0.010 - -0.010); P = 0.001], etiology of hepatic disease = [- 0.212 (95% CI = - 0.37 - -0.05); P = 0.009], happiness = [- 0.214(95% CI = - 0.33 - -0.09) P = 0.001) and aggressiveness = [0.172 (95% CI = 0.040-0.030); P = 0.010). CONCLUSIONS: The social support was greater when the patients were younger (18 to 30 years). Patients with alcoholic cirrhosis, regardless of whether or not they were associated with virus, had less social support. As for feelings, the absence of happiness and the presence of aggressiveness showed a negative effect on social support.

One year of baclofen in 100 patients with or without cirrhosis: a French real-life experience.

BACKGROUND: Several studies have suggested the efficacy of baclofen in reducing alcohol consumption, leading to a temporary recommendation for use in France. AIM: Our aim was to report our experience in using baclofen in alcohol-dependant patients with or without liver cirrhosis. PATIENTS AND METHODS: Consecutive patients from two liver and alcohol units were recruited over a 3-year period and received increasing doses of baclofen associated with social, psychological, and medical care. RESULTS: One hundred patients were treated, of whom 65 were cirrhotic. After 1 year, 86 patients were still being followed up. At a mean dosage of 40 mg/day (extremes: 30-210), the median daily alcohol consumption reduced from 80 to 0 g/day (P<0.001). Twenty patients drank a small amount of alcohol of up to 30 g/day and 44 patients were completely abstinent. These declarative results were associated with a significant improvement in alcohol-related biological markers in this 'low-consumption' group of 64 patients: the median γ-glutamyl transferase decreased from 3.9 to 2.0 UNL (P<0.001), the mean aspartate transaminase decreased from 2.6 to 1.2 UNL (P<0.001), and the mean corpuscular volume decreased from 101 to 93 µm (P<0.001). In cirrhotic patients, bilirubinemia decreased significantly from 22 to 11 µmol/l (P=0.026), prothrombin time increased from 68 to 77% (P<0.001), and albuminemia increased from 34.1 to 37.4 g/l (P<0.001). Twenty patients reported grades 1-2 adverse events. No liver or renal function deterioration occurred in cirrhotic patients. CONCLUSION: In our cohort, baclofen associated with a global care was very well tolerated even in cirrhotic patients. The marked reduction in alcohol consumption in 64 patients translated into a significant improvement in biological markers and in liver function tests. Baclofen could be very useful, especially in cases of severe alcoholic liver disease.

Anxiety and Stress Levels on Liver Transplantation Candidates.

The objective of the present study was to determine the anxiety and stress levels of liver transplant candidates during the preoperative period. A cross-sectional, prospective study was conducted on 52 liver transplantation candidates seen at a specialized public hospital outpatient clinic in the interior of the state of São Paulo, Brazil. Data were collected from November 2014 to April 2015 using a self-applicable questionnaire for the assessment of anxiety (State-Trait Anxiety Inventory, short version) and stress (Perceived Stress Scale), in addition to sociodemographic and clinic characterization. The mean (±SD) anxiety level detected was 23.06 ± 5.51 points, with 1.92% of the subjects showing minimum levels (0 to 12 points), 59.62% a medium level (12 to 24 points), 36.54% a moderate level (24 to 36 points), and 1.92% a severe level (36 to 48 points) of anxiety. The mean level on the stress scale was 12.10 ± 5.62 points, with 7.69% of the subjects showing high stress levels. When individuals with good and poor stress levels were compared, a significant difference was observed between them (P = .0004). The Spearman correlation test showed that the higher the stress, the higher the levels of anxiety (r = 0.4258), P < .0001. The present study contributes to the analysis of the mental health of liver transplantation candidates in view of the need for interventions for the improvement of anxiety and stress levels since the waiting period for the organ generates emotional changes that can affect the quality of life of the patient and the success of this complex therapeutic modality.

Subjective parameters markedly limit the referral of transplantation candidates to liver transplant centres.

BACKGROUND & AIMS: Equality of access to organ transplantation is a mandatory public health requirement. Referral from a local to a university hospital and then registration on the national waiting list are the two key steps enabling access to liver transplantation (LT). Although the latter procedure is well defined using the Model for End-stage Liver Disease score that improves equality of access, the former is mostly reliant on the practices of referring physicians. The aim of this study was to clarify the factors determining this initial step. METHODS: This observational study included consecutive inpatients with cirrhosis of whatever origin in a cohort constituted between 2003 and 2008, using medical records and structured questionnaires concerning patient characteristics and the opinions of hospital clinicians. Candidates for LT were defined in line with these opinions. RESULTS: Four hundred and thirty-three patients, mostly affected by alcoholic cirrhosis, were included, 21.0% of whom were considered to be candidates for LT. Factors independently associated with their candidature were: physician empathy [odds ratio (OR) = 10.8; 95% CI: 4.0-29.5], adherence to treatment (OR = 16.6; 95% CI: 3.7-75.2), geographical area (OR = 6.8; 95% CI: 2.2-21.3) and the patient's physiological age (OR = 2.3; 95% CI: 1.1-4.7). CONCLUSIONS: Several subjective markers restrict the referral of patients from local hospitals to liver transplant centres. Their advancement to this second step is thus markedly weakened by initial subjectivity. The development of objective guidelines for local hospital physicians to assist them with their initial decision-making on LT is now necessary.

Assessment of depression and anxiety in patients with chronic liver disease.

BACKGROUND/AIM: In recent years mental health of patients including those with chronic liver disease (CLD), has become interesting because its disturbance leads to reduced quality of life, that is associated with worsening of clinical outcome, reduced compliance and increased mortality. The aim of the study was to determinate the frequency and severity of depression and frequency of anxiety in patients with CLD and to assess the contribution of selected socio-demographic, clinical and laboratory risk factors for depression and anxiety. METHODS: In this cross-sectional study, we used the Hamilton depression rating scale (HDRS) and Hamilton anxiety rating scale (HARS) in patients with CLD. RESULTS: The study included 54 male and 43 female patients. Depression was present in 62.9%, and anxiety in 13.4% of the patients. A higher HDRS was noted in the patients older than 50 years (p = 0.022) and unemployed patients (p = 0.043). The patients with at least one episode of gastrointestinal bleeding had a significantly higher frequency of anxiety than those without bleeding (p = 0.018). A higher HARS score was present in the women (p = 0.011), unemployed patients (p = 0.008) and those with non-alcoholic liver disease (p = 0.007). There was a significant correlation between the mean corpuscular volume (MCV) and the value of the HDRS score, and between serum potassium and sodium levels and HDRS score. CONCLUSION: Age and the mean corpuscular volume have significant influence on the HDRS score while unemployment, gastrointestinal bleeding, serum potassium and serum sodium have predictive value for HARS score.

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.

Biopsychosocial functioning in liver patients of alcoholic etiology as a function of self-perceived pain level.

OBJECTIVE: To compare the biopsychosocial functioning among liver transplantation and cirrhotic patients as a function of self-perceived pain level. METHODS: We selected two groups of liver patients of the same gender (men) and disease etiology (alcoholic): there were 39 liver transplant recipients and 34 severe cirrhotic patients. The Hospital Anxiety and Depression Scale and the SF-36 Health Questionnaire were used. We applied analysis of covariance, with age and model end-stage liver disease (MELD) scores as covariates to assess the influence of two independent factors: (1) group (liver transplant recipients and cirrhotic patients), and (2) self-perception of pain (mild and high). We also calculated Cohen's d as an effect size index. RESULTS: No interactive effects were found between factors group and self-perceived pain in any of the variables studied. With regard to the main effects, we found statistically significant differences in the following variables between: a) liver transplant recipients and cirrhotic patients: anxiety (P = .000), depression (P = .003), role-physical (P = .001), mental health (P = .016), general health (P = .000), vitality (P = .000), and physical functioning (P = .000); and b) liver patients with mild and high self-perceived pain: anxiety (P = .008), depression (P = .000), role-physical (P = .002), mental health (P = .000), vitality (P = .000), and physical functioning (P = .001). In all the indicated variables, with medium and large effect sizes (Cohen's ds from 0.58 to 1.64), the cirrhotic patients and patients with a high level of self-perceived pain had much poorer mental health and quality of life. CONCLUSION: Alcoholic cirrhotic male patients with a high level of self-perceived pain had the greatest biopsychosocial impairment, even exceeding the clinical threshold in the anxiety and depression scales; and the highest biopsychosocial well-being was associated with liver transplant recipients with a mild level of self-perceived pain.

Emotional-type psychopathologic symptoms among patients with terminal chronic alcohol-induced liver cirrhosis.

INTRODUCTION: Patients with toxic substance abuse syndrome, such as alcohol abuse, have elevated psychopathologic morbidity and mortality such as mood disorders. OBJECTIVE: To evaluate the emotional-type psychopathologic symptoms in patients with alcohol-induced hepatic cirrhosis on the liver transplant waiting list. MATERIALS AND METHODS: Patients with alcoholic liver cirrhosis who were candidates for liver transplant (n = 41) completed the SA-45 questionnaire (González y Cuevas; 88), which assesses nine dimensions: somatizations, obsessive-compulsivity, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. A control group consisted of patients with chronic nonalcoholic terminal hepatopathies (n = 22). RESULTS: Seventy-six percent of patients had some kind of psychopathologic symptom compared to 68% of the patients in the control group with other nonalcoholic etiologies (P > .05). The emotional-type clinical symptoms were: (1) somatizations: 37% of patients with alcoholic cirrhosis had this type of clinical symptoms compared to 32% of the control group (P > .05); (2) obsessive-compulsivity: 56% versus 46%, respectively (P > .05); (3) interpersonal sensitivity: 19% versus 9%, respectively (P > .05); (4) depression: 54% versus 27%, respectively (P = .045); (5) anxiety: 59% versus 46%, respectively (P > .05); (6) hostility: 29% versus 5%, respectively (P = .021); (7) phobic anxiety: 10% versus 14%, respectively (P > .05); (8) paranoid Ideation: 7% versus 5%, respectively (P > .05); (9) psychoticism: 5% versus 4%, respectively (P > .05). CONCLUSIONS: The patients with alcoholic liver cirrhosis on the liver transplant waiting list had elevated psychopathologic symptoms. Depressive- and hostile-type emotional alterations were most frequent in this type of patients.

Regional reduction in gray and white matter volume in brains of cirrhotic patients: voxel-based analysis of MRI.

Chronic hepatic encephalopathy is a characteristically reversible neuropsychiatric disorder that occurs mainly in patients with liver cirrhosis. The brain regions critically involved in the pathophysiology of cirrhosis are not clear. Magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) is a valuable tool for evaluating structural brain changes in many neurodegenerative diseases. We performed an MRI scan on 18 patients with liver cirrhosis and 16 age-matched healthy controls. We evaluated brain regional structural changes, regional differences and the relationship of these changes with the blood levels of ammonia and the results of neuropsychological tests in patients with cirrhosis. The VBM showed reduction in the volume of gray matter in the cerebellum and occipital lobe and in the volume of white matter in the cingulate, parietal, temporal, occipital lobe and precentral area in cirrhotic patients compared with controls. There were significant correlations between the volume of these regions with the plasma levels of ammonia and the results of neuropsychological tests. Voxel-based analysis of MRI revealed evidence for structural abnormalities of brain in patients with cirrhosis. Abnormal function in the above regions may account for the ammonia-mediated changes and neuropsychological deficits in hepatic encephalopathy.

Coping strategies and quality of life among liver transplantation candidates.

The maintenance of self-reported quality of life (QL) among people on the liver transplantation waiting list is one of the priority objectives of transplantation teams. Although there are different determinant factors of QL, results are not conclusive. In our study, the goal was to evaluate both the influence of cirrhosis etiology (ethylic and non-ethylic) and the coping strategies used concerning QL. A sample of 93 patients was selected, divided into two groups: ethylic cirrhosis (EC) and non-ethylic cirrhosis (NEC). QL was evaluated through the SF-36 Health Survey, and coping strategies through the Medical Coping Modes Questionnaire (MCMQ). Our results indicated that subjects with EC obtained similar QL levels to subjects with NEC, on all the SF-36 and MCMQ subscales. Furthermore, negative correlations were found between avoidance and acceptance-resignation coping strategies with the SF-36 components. Consequently, the acceptance-resignation strategy was associated with a worse perception of physical functioning, general and mental health, and vitality and role-emotional. Overall, these results suggest that cirrhosis etiology is not a determinant factor of QL, whereas the acceptance-resignation coping strategy might lead to lower self-perception of QL.

Anxiety levels observed in candidates for liver transplantation.

INTRODUCTION: Anxiety can be considered an emotional state that does not present itself at the same intensity in all patients, and can be classified into 3 levels: mild, moderate, and severe. The patient, upon entering the waiting list for transplantation, reflects on the decision taken, which leaves him constantly anxious about the idea of possible death. OBJECTIVE: This study had the aim of evaluating the degree of anxiety observed in orthotopic liver transplantation (OLT) candidates and whether there was a correlation between anxiety and etiologic diagnosis. METHODS: This study was a prospective study where the patients underwent psychological evaluation by Beck Anxiety Inventory (BAI). The anxiety level was minimal, mild, moderate, or severe. The Model for End-Stage Liver Disease (MELD) score and etiology were recorded. RESULTS: The level of anxiety found were as follows: 55% minimal, 27% mild, 12% moderate, and 7% severe. The correlation between level of anxiety and etiologic diagnosis showed that 71% of patients with alcoholic cirrhosis and 60% of those with liver cancer showed a minimal degree of anxiety and 27% of patients with autoimmune cirrhosis had severe anxiety. CONCLUSION: We found that in patients with autoimmune hepatitis, the degree of anxiety was more pronounced. It is believed that the absence of physical symptoms is an important factor when observing anxiety in OLT candidates.

Understanding and treating patients with alcoholic cirrhosis: an update.

Alcoholic cirrhosis represents the terminal stage of alcoholic liver disease (ALD) and one of the main causes of death among alcohol abusers. The aim of this review was to provide an update on alcoholic cirrhosis, with an emphasis on recent findings. Increased alcohol consumption in developing countries is expected to increase cirrhosis mortality. There is a need, therefore, to develop new approaches to the prevention of ALD, including more attention to co-factors that may increase risk of ALD (i.e., obesity and diabetes, chronic HCV infection, and smoking). Furthermore, a better understanding of the pathological mechanisms on the basis of alcohol cirrhosis represents a cornerstone in order to develop new pharmacological treatments. Inflammatory and immune responses along with oxidative stress and alterations in adipokine secretion might contribute in different ways to the evolution of alcohol-induced fibrosis/cirrhosis. As of this date, patients with severe alcoholic hepatitis with a Maddrey Discriminant Factor (MDF) 32 should be offered pentoxifylline and/or corticosteroids unless contraindications exist. For ambulatory patients, S-adenosylmethionine (SAMe) may be considered in a motivated patient with nutritional support. Current studies do not support use of anti-tumor necrosis factor (TNF)-alpha antibody. Finally, achieving total alcohol abstinence should represent the main aim in the management of patients affected by any stage of cirrhosis. In the last decades, several drugs able to increase abstinence and prevent alcohol relapse have been evaluated and some of them have obtained approval for alcohol dependence. Patients with alcoholic cirrhosis; however, are usually excluded from such treatments. A recent study demonstrated the efficacy and safety of baclofen in inducing and maintaining alcohol abstinence in cirrhotic alcohol-dependent patients with cirrhosis. All together the information available suggests the need of a multimodal approach in the clinical management of these patients.

Subjective satisfaction and quality of life in patients prior to listing for liver transplantation.

OBJECTIVES: Differences in health-related quality of life (HR-QoL) perception between alcohol abusing and non-substance-dependent subjects with liver cirrhosis could depend on differences in personality profile and influence management of patients awaiting liver transplant. METHODS: We compared the perceptions of disease state in 78 male patients of similar disease severity divided into 2 groups based on etiology of cirrhosis: 47% had alcoholic cirrhosis, and 53% had hepatitis C virus(HCV)-related cirrhosis without alcohol abuse. Patients' perception of disease state was determined using the SAT-P questionnaire (a self-administered questionnaire that provides a global assessment of perceived HR-QoL and subjective well-being). The assessment yields 2 scales: an analytic scale based on 32 variables and a synthetic scale based on 5 factors. RESULTS: In patients with alcohol-related disease, ''psychological function'' was found to be more impaired,while ''sleep, diet, and free time'' was less impaired compared with subjects with HCV-related cirrhosis, suggesting dysfunction related to substance abuse with personality disturbance. CONCLUSIONS: The perception of disease state is different in alcohol-abusing patients with cirrhosis compared with those with cirrhosis unrelated to alcohol.