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We recently reported the first clinical case of bladder fermentation syndrome (BFS) or urinary auto-brewery syndrome, which caused the patient to fail abstinence monitoring. In BFS, ethanol is generated by Crabtree-positive fermenting yeast Candida glabrata in a patient with poorly controlled diabetes. One crucial characteristic of BFS is the absence of alcoholic intoxication, as the bladder lumen contains transitional epithelium with low ethanol permeability. In contrast, patients with gut fermentation syndrome (GFS) or auto-brewery syndrome can spontaneously develop symptoms of ethanol intoxication even without any alcohol ingestion because of alcoholic fermentation in the gut lumen. In abstinence monitoring, a constellation of laboratory findings with positive urinary glucose and ethanol, negative ethanol metabolites, and the presence of yeast in urinalysis should raise suspicion for BFS, whereas endogenous ethanol production needs to be shown by a carbohydrate challenge test for GFS diagnosis. GFS patients will also likely fail abstinence monitoring because of the positive ethanol blood testing. BFS and GFS are treated by yeast eradication of fermenting microorganisms with antifungals (or antibiotics for bacterial GFS cases) and modification of underlying conditions (diabetes for BFS and gut dysbiosis for GFS). The under-recognition of these rare medical conditions has led to not only harm but also adverse legal consequences for patients, such as driving under the influence (DUI). GFS patients may be at risk of various alcohol-related diseases.

Frailty is a known risk factor for major life-threatening liver transplant complications, deaths, and waitlist attrition. Whether frailty indicates risk for adverse outcomes in cirrhosis short of lethality is not well defined. We hypothesized that clinical measurements of frailty using gait speed and grip strength would indicate the risk of subsequent hospitalization for the complications of cirrhosis. We assessed frailty as gait speed and grip strength in a 1-year prospective study of 373 cirrhotic patients evaluated for or awaiting liver transplantation. We determined its association with the outcome of subsequent hospital days/100 days at risk for 7 major complications of cirrhosis. We tested potential covariate influences of Model for Endstage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores, age, sex, height, depression, narcotic use, vitamin D deficiency, and hepatocellular carcinoma using multivariable modeling. Patients experienced 2.14 hospital days/100 days at risk, or 7.81 days/year. Frailty measured by gait speed was a strong risk factor for hospitalization for all cirrhosis complications. Each 0.1 m/s gait speed decrease was associated with 22% greater hospital days (P<0.001). Grip strength showed a similar but nonsignificant association. Gait speed remained independently significant when adjusted for MELD, CTP, and other covariates. At hospital costs of $4,000/day, patients with normal 1 m/s gait speed spent 6.2 days and $24,800/year; patients with 0.5 m/s speed spent 21.2 days and $84,800/year; and patients with 0.25 m/s speed spent 40.2 days and $160,800/year. Frailty as measured by gait speed is an independent and potentially modifiable risk factor for cirrhosis complications requiring hospitalization. The potential clinical value of frailty measurements to help define such risk merits broader evaluation.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions. Alcohol-associated liver disease is the main cause of liver-related morbidity and mortality globally. This Consensus Statement makes recommendations for the design, best practice and conduct of clinical trials to evaluate the effects of alcohol use in alcohol-associated liver disease and alcohol use disorder.

Background Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use disorder (AUD) treatment, AUD treatment engagement, and mortality. Methods This retrospective cohort study included all patients with ICD-10 diagnosis codes for cirrhosis and AUD who were engaged in hepatology care in a single healthcare system in 2015. Baseline demographic, medical, liver disease, and AUD treatment data were assessed. AUD treatment discussions and initiation, alcohol cessation, and subsequent 5-year mortality were collected. Multivariable models were used to assess the factors associated with subsequent AUD treatment and 5-year mortality. Results Among 436 patients with cirrhosis due to alcohol, 65 patients (15%) received AUD treatment at baseline, including 48 (11%) receiving behavioral therapy alone, 11 (2%) receiving pharmacotherapy alone, and 6 (1%) receiving both. Over the first year after a baseline hepatology visit, 37 patients engaged in AUD treatment, 51 were retained in treatment, and 14 stopped treatment. Thirty percent of patients had hepatology-documented AUD treatment recommendations and 26% had primary care-documented AUD treatment recommendations. Most hepatology (86%) and primary care (88%) recommendations discussed behavioral therapy alone. Among patients with ongoing alcohol use at baseline, AUD treatment one year later was significantly, independently associated with AUD treatment discussions with hepatology (adjusted odds ratio (aOR): 3.23, 95% confidence interval (CI): 1.58, 6.89) or primary care (aOR: 2.95; 95% CI: 1.44, 6.15) and negatively associated with having Medicaid insurance (aOR: 0.43, 95% CI: 0.18, 0.93). When treatment was discussed in both settings, high rates of treatment ensued (aOR: 10.72, 95% CI: 3.89, 33.52). Over a 5-year follow-up period, 152 (35%) patients died. Ongoing alcohol use, age, hepatic decompensation, and hepatocellular carcinoma were significantly associated with mortality in the final survival model. Conclusion AUD treatment discussions were documented in less than half of hepatology and primary care encounters in patients with alcohol-related cirrhosis, though such discussions were significantly associated with receipt of AUD treatment.

Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort.

For people with alcohol excess and liver disease, successful management must be two-fold with management of both their psychological/physical addiction to alcohol and their liver disease.  Alcohol Abuse and liver disease, with its joint focus on hepatology and psychiatry, provides both hepatologists and psychiatrists of all levels with a practical, concise and didactic guide to the investigation and clinical management of those with alcohol-related problems. Edited by a practicing hepatologist in the UK and a practising specialist in psychiatry/substance abuse in the US, it covers areas such as: •     Risk factors for alcoholic liver disease •     Interaction of alcohol with other co-morbidities •     Clinical assessment of alcohol intake •     Detoxification and management of withdrawal •     Psychotherapeutic and pharmaceutical interventions •     Treatment of liver disease Key points, management diagrams and high-quality images are all be supported by the very latest in clinical guidelines from the major hepatology and psychiatry societies such as the APA, EPA, AASLD and EASL. With increasing emphasis on multi-disciplinary speciality care in this area, this is the ideal tool to consult in order to provide the best care possible care for what are very challenging patients to manage.

Background An association between fibromyalgia and hepatitis C virus (HCV) has been previously described. However, the relationship between nonalcoholic steatohepatitis (NASH) and fibromyalgia symptoms has not been assessed, though they share several risk factors. Aim We aimed to assess the factors associated with fibromyalgia symptoms across etiologies of liver disease. Methods Patients with cirrhosis due to HCV, NASH, or alcohol were recruited from an outpatient hepatology clinic and administered the Hospital Anxiety and Depression Score, Pittsburgh Sleep Quality Index, and the modified 2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia. Serum inflammatory markers were measured with standard luminex assays. Results Of 193 participants, 53 (27 %) met criteria for fibromyalgia. Fibromyalgia symptoms were significantly associated with etiology of liver disease (HCV: 35 %, NASH: 30 %, alcohol-related liver disease: 12 %, p  < 0.01). Using logistic regression, mood symptoms (OR 1.14, 95 % CI 1.06, 1.22), sleep disturbance (OR 1.32, 95 % CI 1.16, 1.52), and etiology of liver disease (NASH vs. HCV not different, alcohol vs. HCV OR 0.19, 95 % CI 0.05, 0.63) were associated with fibromyalgia symptoms. If abdominal pain was included in the model, etiology became nonsignificant, indicating that it may be central sensitization due to abdominal pain in patients with chronic liver disease that explains fibromyalgia symptoms rather than the etiology of liver disease or inflammation. Conclusions Fibromyalgia symptoms were significantly associated with HCV and NASH cirrhosis and with psychiatric symptoms. Future work should focus on the underlying pathophysiology and management of widespread pain in patients with cirrhosis.

This study was designed to assess unique baseline factors associated with subsequent hospitalizations in a cohort of outpatients with cirrhosis. A cohort of 193 patients with cirrhosis was recruited from an outpatient liver disease clinic at a single, tertiary medical center. Comorbidities, prescription medications, liver disease symptoms and severity, and psychiatric and pain symptoms were assessed at baseline using validated instruments. Inflammatory markers were measured using standardized Luminex assays. Subsequent hospitalizations and the primary admission diagnoses were collected via chart review. Multivariable models were used to evaluate which baseline factors were associated with time to hospitalization and number of hospitalizations. The cohort consisted of 193 outpatients, with an average age of 58±9 and model for end-stage liver disease (MELD) score of 12±5. Over follow-up, 57 (30%) were admitted to the hospital. The factors associated with time to hospitalization included the severity of liver disease (HR/MELD point:1.10, 95% CI:1.04,1.16), ascites (HR: 1.90, 95% CI: 1.01, 3.58), baseline symptoms of depression (HR:2.34, 95% CI:1.28,4.25), sleep medications (HR:1.81, 95% CI:1.01, 3.22) and IL-6 (HR:1.43, 95% CI: 1.10, 1.84). Similarly the number admissions was significantly associated with MELD (IIR: 1.08, CI: 1.07,1.09), ascites (IIR: 4.15, CI:3.89, 4.43), depressive symptoms (IIR:1.54, CI:1.44,1.64), IL-6 (IIR:1.26, CI:1.23,1.30), sleep medications (IIR:2.74, CI:2.57, 2.93), and widespread pain (IIR: 1.61, CI: 1.50, 1.73). In conclusion, consistent with prior studies, MELD and ascites were associated with subsequent hospitalization. However, this study also identified other factors associated with hospitalization including inflammation, depressive symptoms, sleep medication use, and pain.

Background. Family members adopt key caregiving roles in the maintenance of transplant recipients' health. While the bulk of the caregiving literature suggests that rates of psychiatric disorder should be high in these caregivers, the potential benefits of transplantation may instead lead to less distress than in other caregiving situations. We examined prevalence and risk factors for depressive and anxiety-related disorders in caregivers throughout 3 years after their family member's heart transplant. Method. A total of 190 caregivers (97% of eligible respondents) were enrolled. They received psychiatric and psychosocial evaluations at 2, 7, 12 and 36 months post-transplant. Survival analysis determined cumulative rates of psychiatric disorders and the impact of potential risk factors. Results. Rates of depressive and anxiety-related disorders met or exceeded other caregiver populations' rates. By 3 years post-transplant, cumulative onset rates were: Major Depressive Disorder (MDD), 31·6%, Adjustment disorders, 35·4% (29·4% with anxious mood); Post-Traumatic Stress Disorder related to the transplant (PTSD-T), 22·5%, Generalized Anxiety Disorder, 7·3%, and any assessed disorder, 56·3%. PTSD-T occurred primarily during the first year post-transplant. Other disorders' rates increased over the entire study period. Risk for disorder was elevated by positive lifetime history of psychiatric disorder, greater post-transplant caregiving responsibilities, and a poorer relationship with the patient. Risk for MDD was further increased by caregiver unemployment, and risk for anxiety disorders was further increased by younger age, low sense of personal mastery, and high use of avoidance coping strategies. Conclusions. Transplantation is associated with costs and benefits for not only patients but family caregivers. Caregivers' risk for psychiatric illness should be considered when developing interventions to promote families' long-term adjustment to the transplant process.