Gut and bladder fermentation syndromes: a narrative review.

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.

Alcohol use disorder in alcohol-associated liver disease: Two sides of the same coin.

Alcohol-associated liver disease (ALD) has emerged as the leading indication for liver transplantation (LT) worldwide, with 40% of LTs in the United States performed for ALD in 2019. The ALD-related health care burden accelerated during the COVID-19 pandemic, especially in young individuals. Alcohol use disorder (AUD), which focuses on the negative effects of alcohol on psychosocial, physical, and mental health, is present in the majority of patients with ALD, with moderate to severe AUD in 75%-80%. During the last decade, early liver transplantation (eLT) has emerged as a lifesaving treatment for selected patients with alcohol-associated hepatitis; these patients may have a higher risk of using alcohol after LT. The risk of alcohol use recurrence may be reduced during the pretransplant or post-transplant period with AUD treatment using behavioral and/or pharmacological therapies and with regular monitoring for alcohol use (self-reported and complemented with biomarkers like phosphatidylethanol). However, AUD treatment in patients with ALD is challenging due to patient, clinician, and system barriers. An integrated model to provide AUD and ALD care by hepatologists and addiction experts in a colocated clinic starting from LT evaluation and selection to monitoring listed candidates and then to following up on recipients of LT should be promoted. However, the integration of addiction and hepatology teams in an LT program in the real world is often present only during evaluation and candidate selection for LT. Data are emerging to show that a multidisciplinary integrated AUD treatment within an LT program reduces recurrent alcohol use after LT. If we want to continue using early liver transplantation for patients with severe alcohol-associated hepatitis, LT programs should focus on building integrated multidisciplinary care teams for the integrated treatment of both AUD and ALD.

Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.

BACKGROUND & AIMS: Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification. METHODS: A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center. RESULTS: Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%. CONCLUSIONS: We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

Definition and measurement of alcohol-associated insight in early liver transplantation for acute alcohol-associated hepatitis: A systematic review.

BACKGROUND: Alcohol accounts for a large disease burden in hepatology and liver transplantation (LT) and across the globe. Clinical evaluations and decisions about LT candidacy are challenging because they rely on detailed psychosocial assessments and interpretations of psychiatric and substance use disorder data, which often must occur rapidly according to the acuity of end-stage liver disease. Such difficulties commonly occur during the process of candidate selection and liver allocation, particularly during early LT (eLT) in patients with acute alcohol-associated hepatitis (AAH). Patients with AAH commonly have very recent or active substance use, high short-term mortality, psychiatric comorbidities, and compressed evaluation and treatment timetables. LT clinicians report that patients' alcohol-associated insight (AAI) is among the most relevant psychosocial data in this population, yet no studies exist examining how LT teams define and use AAI in eLT or its effect on clinical outcomes. In April 2022, we searched Ovid MEDLINE, Elsevier Embase, EBSCOhost PsycInfo and CINAHL, and Wiley Cochrane Central Register of Controlled Trials for reports describing AAH populations who underwent eLT, which also described psychosocial evaluation parameters. The searches retrieved 1603 unique reports. After eligibility screening, 8 were included in the qualitative analysis. This systematic review reveals that AAI is a poorly defined construct that is not measured in a standardized way. Yet it is a commonly cited parameter in articles that describe the psychosocial evaluation and decision-making of patients undergoing eLT for AAH. This article also discusses the general challenges of assessing AAI during eLT for AAH, existing AAI definitions and rating scales, how AAI has been used to date in the broader hepatology and LT literature, and future areas for clinical and research progress.

Challenges and Solutions for Monitoring Alcohol Use in Patients With Alcohol-Related Liver Disease: Pilot Study of a Wearable Alcohol Biosensor.

OBJECTIVES: Early alcohol use identification can prevent morbidity/mortality for alcohol-associated liver disease (ALD). Innovative wearable alcohol biosensors (biosensors) that identify alcohol use through perspiration are an emerging technology with potential application for patients with ALD. Our primary aim was to determine biosensor acceptability and feasibility for patients with ALD. We describe participant acceptance and challenges using biosensor technology in a pilot study of biosensors with patients with ALD. DESIGN: Participants had a recent diagnosis or hospitalization for decompensated ALD, had to be drinking within the past 3 months, and had to be followed at our center. Participants wore the biosensor daily for 3 months. Quantitative data using the Technology Acceptance Model 2 (TAM2) measure were collected at intake and study conclusion. The TAM2's 13 items cover four scales: perceived usefulness, ease of use, attitude toward technology, and intention to use on a 7-point Likert scale. Lower scores indicate higher acceptance. Participants were asked open-ended questions about issues wearing the biosensor. RESULTS: Among 27 participants, 60% were women with an average age of 45 (10) years, and 89% were White. TAM2 subscales indicated initially high acceptance (mean scores = 1.2-2.2) and remained high (mean scores = 1.3-2.3) without a statistically significant decline at study conclusion. From open-ended questions, several themes regarding problems with device wear emerged a) uncomfortable or cumbersome to wear, b) problems with biosensor appearance, and c) issues with usability. Challenges to biosensor usage included data being lost when devices were damaged and devices being lost during the study. CONCLUSIONS: Alcohol biosensors seem to be acceptable to ALD participants. However, improving the appearance, comfort, durability, and functionality of biosensor devices is critical to clinical deployment.Trial Registration:Clinicaltrials.gov identifier NCT03533660: Alcohol biosensor monitoring for alcohol liver disease.

Alcohol treatment discussions and clinical outcomes among patients with alcohol-related cirrhosis.

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.

Sequential liver and kidney living donors: Making the ultimate gift twice.

There are nearly 150 living donors in the United States who donated more than one solid organ. Using our divisional database, we found 20 individuals who donated a liver and a kidney at different times. We performed a retrospective chart review of these donors, studying their motivating factors, complications and outcomes. The donors included 11 (55%) males and nine females. Thirteen (65%) donated the kidney before the liver. Fourteen (70%) were nondirected donors at the first donation, and four of the six directed donors in the first donation became nondirected in the second donation. Seventeen (85%) were nondirected at the second donation. Common reasons for donating the second time were a good experience with the first donation and knowing that one can donate again. Outcomes and the incidence of early complications were not significantly different after the 2nd versus the 1st donation. All donors recovered and currently are doing well. Our results show a significant number of dual organ donors are nondirected and motivated by their strong desire to help. A positive experience with the 1st donation often was the driving factor for the 2nd. A history of previous organ donation did not negatively impact the 2nd donation.

Health-related quality of life and psychological indicators of thriving 15-19 years after heart or lung transplantation.

BACKGROUND: Survival into the second decade after cardiothoracic transplantation (CTX) is no longer uncommon. Few data exist on any health-related quality of life (HRQOL) impairments survivors face, or whether they may even experience positive psychological outcomes indicative of "thriving" (e.g., personal growth). We provide such data in a long-term survivor cohort. METHODS: Among 304 patients prospectively studied across the first 2 years post-CTX, we re-interviewed patients ≥15 years post-CTX. We (a) examined levels of HRQOL and positive psychological outcomes (posttraumatic growth related to CTX, purpose in life, life satisfaction) at follow-up, (b) evaluated change since transplant with mixed-effects models, and (c) identified psychosocial and clinical correlates of study outcomes with multivariable regression. RESULTS: Of 77 survivors, 64 (83%) were assessed (35 heart, 29 lung recipients; 15-19 years post-CTX). Physical HRQOL was poorer than the general population norm and earlier post-transplant levels (P's < .001). Mental HRQOL exceeded the norm (P < .001), with little temporal change (P = .070). Mean positive psychological outcome scores exceeded scales' midpoints at follow-up. Life satisfaction, assessed longitudinally, declined over time (P < .001) but remained similar to the norm at follow-up. Recent hospitalization and dyspnea increased patients' likelihood of poor physical HRQOL at follow-up (P's ≤ .022). Lower sense of mastery and poorer caregiver support lessened patients' likelihood of positive psychological outcomes (P's ≤ .049). Medical comorbidities and type of CTX were not associated with study outcomes at follow-up. CONCLUSIONS: Despite physical HRQOL impairment, long-term CTX survivors otherwise showed favorable outcomes. Clinical attention to correlates of HRQOL and positive psychological outcomes may help maximize survivors' well-being.

Identifying Alcohol Use Disorder in Patients With Cirrhosis Reduces 30-Days Readmission Rate.

AIMS: Readmission is frequent among patients with cirrhosis and is a complex multifactorial process. To examine the association of alcohol use disorder (AUD) and risk of readmission in patients with alcohol-associated cirrhosis. METHODS AND RESULTS: National Readmission Dataset (2016-2017) was used to extract a retrospective cohort of 53,348 patients with primary or secondary discharge diagnosis code of alcohol-associated cirrhosis with their first admission (26,674 patients with vs. propensity matched 26,674 without a primary or secondary discharge diagnosis code of AUD). Readmission within 30-day was lower (43.9 vs. 48%, P < 0.001) among patients identified to have AUD at the time of discharge. In a conditional logistic regression model, a diagnosis of AUD was associated with 15% reduced odds of 30-day readmission, 0.85 (0.83-0.88). Furthermore, the reason for readmission among patients identified vs. not identified to have AUD was less likely to be liver disease complication. The findings remained similar in a matched cohort of patients where the AUD diagnosis at discharge was listed as one of the secondary diagnoses only. CONCLUSION: Although, our study findings suggest that identification of AUD at the time of discharge among patients hospitalized for alcohol-associated cirrhosis reduces the risk of 30-day readmission, unavailable information on patient counseling, referral for mental health specialist and treatment received for AUD limit the causality assessment. Future studies are needed overcoming the inherent limitations of the database to establish the role of identification and treatment of AUD in reducing readmission and liver decompensation in patients with alcohol-associated cirrhosis.

Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis.

BACKGROUND AND AIMS: Despite the significant medical and economic consequences of coexisting alcohol use disorder (AUD) in patients with cirrhosis, little is known about AUD treatment patterns and their impact on clinical outcomes in this population. We aimed to characterize the use of and outcomes associated with AUD treatment in patients with cirrhosis. APPROACH AND RESULTS: This retrospective cohort study included Veterans with cirrhosis who received Veterans Health Administration care and had an index diagnosis of AUD between 2011 and 2015. We assessed the baseline factors associated with AUD treatment (pharmacotherapy or behavioral therapy) and clinical outcomes for 180 days following the first AUD diagnosis code within the study time frame. Among 93,612 Veterans with cirrhosis, we identified 35,682 with AUD, after excluding 2,671 who had prior diagnoses of AUD and recent treatment. Over 180 days following the index diagnosis of AUD, 5,088 (14%) received AUD treatment, including 4,461 (12%) who received behavioral therapy alone, 159 (0.4%) who received pharmacotherapy alone, and 468 (1%) who received both behavioral therapy and pharmacotherapy. In adjusted analyses, behavioral and/or pharmacotherapy-based AUD treatment was associated with a significant reduction in incident hepatic decompensation (6.5% vs. 11.6%, adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.52, 0.76), a nonsignificant decrease in short-term all-cause mortality (2.6% vs. 3.9%, AOR, 0.79; 95% CI, 0.57, 1.08), and a significant decrease in long-term all-cause mortality (51% vs. 58%, AOR, 0.87; 95% CI, 0.80, 0.96). CONCLUSIONS: Most Veterans with cirrhosis and coexisting AUD did not receive behavioral therapy or pharmacotherapy treatment for AUD over a 6-month follow-up. The reductions in hepatic decompensation and mortality suggest that future studies should focus on delivering evidence-based AUD treatments to patients with coexisting AUD and cirrhosis.

Meeting Report: The Dallas Consensus Conference on Liver Transplantation for Alcohol Associated Hepatitis.

Liver transplantation (LT) for alcohol associated hepatitis (AH) remains controversial. We convened a consensus conference to examine various aspects of LT for AH. The goal was not to unequivocally endorse LT for AH; instead, it was to propose recommendations for programs that perform or plan to perform LT for AH. Criteria were established to determine candidacy for LT in the setting of AH and included the following: (1) AH patients presenting for the first time with decompensated liver disease that are nonresponders to medical therapy without severe medical or psychiatric comorbidities; (2) a fixed period of abstinence prior to transplantation is not required; and (3) assessment with a multidisciplinary psychosocial team, including a social worker and an addiction specialist/mental health professional with addiction and transplantation expertise. Supporting factors included lack of repeated unsuccessful attempts at addiction rehabilitation, lack of other substance use/dependency, acceptance of diagnosis/insight with a commitment of the patient/family to sobriety, and formalized agreement to adhere to total alcohol abstinence and counseling. LT should be avoided in AH patients who are likely to spontaneously recover. Short-term and longterm survival comparable to other indications for LT must be achieved. There should not be further disparity in LT either by indication, geography, or other sociodemographic factors. Treatment of alcohol-use disorders should be incorporated into pre- and post-LT care. The restrictive and focused evaluation process described in the initial LT experience for AH worldwide may not endure as this indication gains wider acceptance at more LT programs. Transparency in the selection process is crucial and requires the collection of objective data to assess outcomes and minimize center variation in listing. Oversight of program adherence is important to harmonize listing practices and outcomes.

Updates in Consultation-Liaison Psychiatry: 2019.

BACKGROUND: The scientific literature in consultation-liaison psychiatry continually expands, and remaining familiar with the most current literature is challenging for practicing clinicians. The Guidelines and Evidence-Based Medicine Subcommittee of the Academy of Consultation-Liaison Psychiatry writes quarterly annotations of articles of interest to help Academy members gain familiarity with the most current evidence-based practices. These annotations are available on the Academy Website. OBJECTIVE: We identify the 10 most important manuscripts for clinical practice in consultation-liaison psychiatry from 2019. METHODS: Sixty-four abstracts were authored in 2019. Manuscripts were rated on clinical relevance to practice and quality of scholarship. The 10 articles with the highest aggregate scores from 19 raters are described. RESULTS: The resulting articles provide practical guidance for consultation psychiatrists on several topic areas including the treatment of substance use disorders. CONCLUSION: We suggest that these clinical findings should be familiar to all consultation-liaison psychiatrists regardless of practice area. Regular article reviews and summaries help busy clinicians deliver cutting-edge care and maintain a high standard of care across the specialty.

The Approach to the Psychosocial Evaluation of Cardiac Transplant and Mechanical Circulatory Support Candidates.

PURPOSE OF REVIEW: We update evidence underlying the recommendations of a 2018 multi-society consensus report regarding the psychosocial evaluation of individuals for cardiothoracic transplantation and mechanical circulatory support (MCS). In the present review, we focus on heart transplantation and MCS. RECENT FINDINGS: Expert opinion and new evidence support the inclusion of ten core content areas in the psychosocial evaluation. Prospective data indicate that psychosocial factors can predict post-transplantation/post-implantation outcomes. Such factors include treatment adherence history, mental health and substance use history, cognitive impairment, knowledge about treatment options, and social factors such as socioeconomic status. For other factors (e.g., coping, social support), new evidence is weaker because it derives largely from cross-sectional studies. Concerning evaluation process issues, expert opinion remains consistent with consensus recommendations, but there is a dearth of empirical evidence. The psychosocial evaluation can identify factors relevant for candidacy for heart transplantation and MCS implantation. It enables the provision of interventions to improve patients' viability as candidates, and facilitates care planning.

Fatigue, Pain, and Other Physical Symptoms of Living Liver Donors in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study.

Little is known about living liver donors' perceptions of their physical well-being following the procedure. We collected data on donor fatigue, pain, and other relevant physical outcomes as part of the prospective, multicenter Adult-to-Adult Living Donor Liver Transplantation Cohort Study consortium. A total of 271 (91%) of 297 eligible donors were interviewed at least once before donation and 3, 6, 12, and 24 months after donation using validated measures when available. Repeated measures regression models were used to identify potential predictors of worse physical outcomes. We found that donors reported more fatigue immediately after surgery that improved by 2 years after donation, but not to predonation levels. A similar pattern was seen across a number of other physical outcomes. Abdominal or back pain and interference from their pain were rated relatively low on average at all study points. However, 21% of donors did report clinically significant pain at some point during postdonation study follow-up. Across multiple outcomes, female donors, donors whose recipients died, donors with longer hospital stays after surgery, and those whose families discouraged donation were at risk for worse physical well-being outcomes. In conclusion, although not readily modifiable, we have identified risk factors that may help identify donors at risk for worse physical outcomes for targeted intervention. Liver Transplantation 00 000-000 2018 AASLD.

The 2018 ISHLT/APM/AST/ICCAC/STSW Recommendations for the Psychosocial Evaluation of Adult Cardiothoracic Transplant Candidates and Candidates for Long-term Mechanical Circulatory Support.

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals.

Post-transplant Outcomes of Persons Receiving a Liver Graft for Alcoholic Liver Disease.

AIMS: Liver transplantation (LT) for alcoholic liver disease (ALD) remains controversial yet following transplantation outcomes for patients with this disease are generally similar to patients transplanted for other types of liver diseases. METHODS: In this review, we cover critical literature of ALD LT including established and recent findings of medical and psychosocial outcomes for ALD patients and compare their outcomes to other liver transplant recipients where evidence exists. RESULTS: Overall medical and psychosocial outcomes for ALD LT recipients compare favorably to patients transplanted for other types of liver diseases. While alcohol relapse occurs following transplant, the rates of return to heavy alcohol use, especially at amounts that are health harmful, are low at ~20%-substantially under rates of relapse for non-transplant patients with alcohol use disorders. However, ALD LT recipients are more likely to be smokers and experience causes of death different than other LT recipients with cardiovascular and malignancies being more common. Depression is one of the more common mental health disorders experienced by ALD LT recipients and is especially important to consider due to increasing evidence of its negative impact on post-transplant survival. In general, ALD LT recipients' quality of life is as good as recipients transplanted for other types of liver disease. Post-LT re-employment and social reintegration are also comparable. CONCLUSIONS: Early identification may improve outcomes with the first post-transplant year being an important time for close monitoring. Additionally, efforts to identify and treat tobacco use and depression may also improve overall outcomes in this specific population. SHORT SUMMARY: In this review, we cover medical and psychosocial outcomes for ALD patients and compare their outcomes to other liver transplant recipients. While alcohol relapse occurs following transplant, the rates of return to heavy alcohol use, especially at amounts that are health harmful, are low at ~20%.

Frailty as Tested by Gait Speed is an Independent Risk Factor for Cirrhosis Complications that Require Hospitalization.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The gap between clinically assessed physical performance and objective physical activity in liver transplant candidates.

Frailty with sarcopenia in cirrhosis causes liver transplant wait-list attrition and deaths. Regular physical activity is needed to protect patients with cirrhosis from frailty. We subjectively assess physical performance in selecting patients for transplant listing, but we do not know whether clinical assessments reflect the extent of activity patients actually perform. To investigate this question, 53 wait-listed patients self-assessed their performance of ordinary physical tasks using the Rosow-Breslau survey, and clinicians assessed their physical performance status with the Karnofsky index. We compared these assessments with actual activity measured using an accelerometer/thermal sensing armband worn from 4 to 7 days. We found that their measured activity was among the lowest reported in chronic disease, similar to that of patients with advanced chronic pulmonary disease or renal failure. Their percentages of waking hours spent in sedentary, light, and moderate-vigorous activity were 75.9% ± 18.9%, 18.9% ± 14.3%, and 4.9% ± 6.9%, respectively. Higher mean sedentary and lower mean moderate-vigorous activity was significantly associated with 9 wait-list deaths (P = 0.004). Compared with a range of 7000-13,000 steps/day in healthy adults, patients' mean steps/day were 3164 ± 2842. Both their activity percentage and step data were typical of other severely inactive populations. Neither their Rosow-Breslau scores (mean 2.3 ± 0.8, maximum 3.0) nor their Karnofsky scores (mean 79 ± 12, maximum 100) suggested major impairment or showed a correlation with patients' actual physical performance. In conclusion, physical activity in patients with cirrhosis wait-listed for transplantation is highly sedentary. Self-assessments and provider assessments of physical activity do not reliably indicate actual performance. Whether the gap between assessed and actual performance may be favorably modified by interventions to improve activity and ameliorate frailty merits further study. Liver Transplantation 22 1324-1332 2016 AASLD.