Patient-Reported Outcome Screens for Cognitive Dysfunction and Predicts Admissions in Cirrhosis.

INTRODUCTION: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. MATERIALS AND METHODS: We studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Twenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). CONCLUSIONS: A brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

Utilizing a novel MRI technique to identify adverse muscle composition in end-stage liver disease: A pilot study.

INTRODUCTION AND OBJECTIVES: Sarcopenia is a common complication of end-stage liver disease (ESLD), but its exact relationship to myosteatosis and frailty remains unclear. In this pilot study, we tested the feasibility of a specialized MRI protocol and automated image analysis in patients with ESLD. MATERIALS AND METHODS: In a single-center prospective study, adult liver transplant candidates with ESLD underwent assessment of muscle composition between 3/2022 and 6/2022 using the AMRA® MAsS Scan. The primary outcome of interest was feasibility of the novel MRI technique in patients with ESLD. We also tested if thigh muscle composition correlated with validated measures of frailty and sarcopenia. RESULTS: Eighteen subjects (71 % male, mean age 59 years) were enrolled. The most common etiologies of cirrhosis were alcohol-related liver disease (44 %) and non-alcohol-associated fatty liver disease (33 %), with a mean MELD-Na of 13 (± 4). The mean time needed to complete the MRI protocol was 14.9 min and only one patient could not complete it due to metal hardware in both knees. Forty-one percent of patients had adverse muscle composition (high thigh fat infiltration and low-fat free muscle volume) and these patients were more likely to have undergone a recent large volume paracentesis (43 % vs. 0 %, p < 0.02). The adverse muscle composition group performed significantly worse on the 6-minute walk test compared to the remainder of the cohort (379 vs 470 m, p < 0.01). CONCLUSIONS: The AMRA® MAsS Scan is feasible to perform in patients with ESLD and can be used to quantify myosteatosis, a marker of muscle quality and potentially muscle functionality in ESLD.

Brief PROMIS Assessment Screens for Frailty and Predicts Hospitalizations in Liver Transplant Candidates.

BACKGROUND: Frailty is prevalent in patients with end-stage liver disease and predicts waitlist mortality, posttransplant mortality, and frequency of hospitalizations. The Liver Frailty Index (LFI) is a validated measure of frailty in liver transplant (LT) candidates but requires an in-person assessment. METHODS: We studied the association between patient-reported physical function and LFI in a single-center prospective study of adult patients with cirrhosis undergoing LT evaluation from October 2020 to December 2021. Frailty was assessed with the LFI and 4-m gait speed. Patient-reported physical function was evaluated using a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Eighty-one LT candidates were enrolled, with a mean model of end-stage liver disease-sodium of 17.6 (±6.3). The mean LFI was 3.7 (±0.77; 15% frail and 59% prefrail) and the mean PROMIS Physical Function score was 45 (±8.6). PROMIS Physical Function correlated with LFI ( r = -0.54, P < 0.001) and 4-m gait speed ( r = 0.48, P < 0.001). The mean hospitalization rate was 1.1 d admitted per month. After adjusting for age, sex, and model of end-stage liver disease-sodium, patient-reported physical function-predicted hospitalization rate ( P = 0.001). CONCLUSIONS: This study suggests that a brief patient-reported outcome measure can be used to screen for frailty and predict hospitalizations in patients with cirrhosis.

Personality Traits in Patients With Cirrhosis Are Different From Those of the General Population and Impact Likelihood of Liver Transplantation.

BACKGROUND: Personality traits influence clinical outcomes in chronic diseases, but their impact in cirrhosis is unknown. We studied the personality of patients with cirrhosis undergoing liver transplant (LT) evaluation and determined their correlation to clinical outcomes. METHODS: A multicenter' prospective study of adult patients undergoing LT evaluation was performed from January 2018 to October 2019. The "Big Five" personality traits of conscientiousness, extraversion, openness, neuroticism, and agreeableness plus agency were assessed with the Midlife Development Inventory Personality Scale and compared with the general population. Frailty was assessed with the Liver Frailty Index. RESULTS: Two hundred sixty-three LT candidates were enrolled. Twenty-four percent had hepatitis C virus, 25% nonalcoholic steatohepatitis, and 25% ethyl alcohol (mean model for end-stage liver disease = 15.7). Compared with the general population, LT candidates had higher openness (3.1 versus 2.9; P < 0.001), extraversion (3.2 versus 3.1; P < 0.001), agreeableness (3.5 versus 3.4; P = 0.04), agency (2.9 versus 2.6; P < 0.001), neuroticism (2.2 versus 2.1; P = 0.001), and lower conscientiousness (3.3 versus 3.4; P = 0.007). Patients with higher conscientiousness were more likely to receive an LT (HR = 2.76; P = 0.003). CONCLUSIONS: Personality traits in LT candidates differ significantly from the general population, with higher conscientiousness associated with a higher likelihood of receiving a transplant.

Evaluation of Charcot Triad, Reynolds Pentad, and Tokyo Guidelines for Diagnosis of Cholangitis Secondary to Choledocholithiasis Across Patient Age Groups.

OBJECTIVE: To determine the prevalence of Charcot triad, Reynolds pentad, and Tokyo Guidelines criteria and clinical outcomes among patients with cholangitis across different age groups. PATIENTS AND METHODS: We conducted a retrospective analysis of 257 consecutive hospitalized adult patients with acute cholangitis due to endoscopic retrograde cholangiopancreatography-confirmed choledocholithiasis between January 1, 2015, and December 31, 2019. Patients were divided into 3 age groups: less than 65 years, 65 to 79 years, and 80 years or older. Symptoms, vital signs, and laboratory data on admission were collected. Outcomes included length of hospitalization, intensive care unit stay, and 3-month mortality. Nominal variables were tested with the Pearson χ2 test, and continuous variables were tested with the Wilcoxon rank sum test. RESULTS: Charcot triad decreased with older ages. In the group that was age 80 years or older, malaise was the most common symptom; 33.6% (37 of 110) presented with altered sensorium, 9.1% (10 of 110) had no pain, fever, or jaundice, and positive blood culture results were more frequent. Tokyo cholestasis criterion was present in 96.0% (247 of 257), while inflammation (considered essential for diagnosis) was present in 75.9% (195 of 257). Patients 80 years or older had significantly higher mean length of hospital stay (P<.001) and mean length of intensive care unit stay (P=.021). CONCLUSION: Compared with patients in younger age groups, patients with cholangitis who are 80 years or older are less likely to have Charcot triad, are more likely to have features of Reynolds pentad, or present with unexplained malaise. Within the Tokyo Guidelines, cholestasis should replace inflammation as an essential diagnostic criterion.

Donor quality of life after living donor liver transplantation: a review of the literature.

Living donor liver transplantation (LDLT) provides a source for transplant in the setting of the deceased donor organ shortage. Seeing as living donors do not derive any medical benefit from the procedure, fully understanding the impact of donation on donor health-related quality of life (HRQOL) is essential. A systematic search of the MEDLINE database was performed from 2008-2020, using relevant Medical Subject Headings. Articles were evaluated for study design, cohort size and follow-up time and excluded if they contained significant methodological flaws. A total of 43 articles were included: 20 (47%) were cross-sectional and 23 (53%) were longitudinal. The mean number of donors per study was 142 (range:8-578) with follow-up ranging from 12-132 months. Forty-two unique HRQOL metrics were implemented across the 43 studies, the majority of which were questionnaires. Of the 31 studies that used the Medical Outcomes Study Short Form 36 questionnaire, 9.1% of donors reported physical QOL did not return to pre-LDLT levels for at least 2 years after donation. Mental QOL remained stable or improved after LDLT, with mean mental composite scores increasing from 50 to 52 at 3 months post-LDLT in one study. The predicted probability of poor sexual desire decreased at 1-year post-LDLT (male: 0.08, female: 0.26) relative to pre-LDLT (male: 0.44, female: 0.76; P<0.001) and three months post-LDLT (male: 0.35, female 0.69; P=0.001). Forty percent of donors found LDLT to be financially burdensome at 3 months and 19% at 2 years post-LDLT. Female gender and obesity were consistent predictors of worse HRQOL. Laparoscopy-assisted donor hepatectomy was associated with shorter hospitalizations than open donor hepatectomy (10.3 vs. 18.3 days, P=0.02). No studies used the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) measures of HRQOL. Our review demonstrates that LDLT can have a long-lasting negative impact on physical QOL in 9.1% of donors and can cause both sexual dysfunction and significant financial strain. Future studies should consider using standardized and extensively validated patient reported outcomes measures, such as PROMIS, in order to directly compare outcomes across studies and gain further insight into the impact of LDLT on D-HRQOL.

Poor Graft and Patient Survival After Liver Transplantation in Sarcoidosis.

GOALS AND BACKGROUND: There are limited data on post-liver transplantation (LT) outcomes of patients with sarcoidosis. STUDY: We examined the clinical characteristics and post-LT outcomes of patients with sarcoidosis using the United Network for Organ Sharing database from 1985 to 2016 and compared them to patients (entire cohort as well as age, gender, and year of LT-matched counterparts) with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). For the matched design, a conditional logistic regression was used for categorical variables and marginal generalized estimating equation regression models for continuous variables. Survival functions were constructed using the Kaplan-Meier estimator. RESULTS: A total of 206 patients with sarcoidosis, transplanted during the study period, were compared with 3933 patients with PBC and 5323 with PSC. In total, 197 patients with sarcoidosis were compared with 576 with PBC and 576 with PSC in the 1:3 matched analysis. The sarcoidosis group had a higher proportion of blacks (53.3%) and a higher prevalence of obesity and type II diabetes mellitus. The graft and patient survival for sarcoidosis patients were lower when compared with unmatched PBC and PSC patients. The results remained unchanged in the matched analysis. At 5-year, patient survival was ~15% lower for the sarcoidosis group when compared with PBC and PSC. In multivariate analysis using matched data, hazard ratios (HRs) for graft (HR=1.68, 95% confidence interval=1.03-2.75, P=0.04), and patient (HR=2.01, confidence interval=1.22-3.34, P<0.01) survival were higher for sarcoidosis. CONCLUSIONS: Patients who underwent LT for sarcoidosis had a lower graft and patient survival when compared with those with PBC or PSC. That being said, 66% of patients survived 5 years after transplantation, suggesting that LT is an acceptable option in this population.

Use of HCV-Positive Livers in HCV-Negative Recipients.

INTRODUCTION: There are only limited data on the survival outcomes after transplanting HCV RNA-positive liver into HCV RNA-negative recipients. The objective of our study was to determine whether there were graft and patient survival differences when HCV-negative patients received HCV RNA (nucleic acid amplification testing [NAT] positive)-positive liver grafts. METHODS: We queried the United Network for Organ Sharing data sets from January 2014 to December 2018, and recipients (N = 24,724) were stratified into 6 groups based on the status of HCV antibody and RNA of recipients and donors. The Cox proportional hazard regression was used to estimate the relationship between groups and 1-year post-LT graft or patient survival. RESULTS: During the study period, 1,358 recipients received NAT-positive liver grafts. Two hundred ten of the recipients were HCV negative. During the same period, 707 HCV antibody-positive but NAT-negative grafts were transplanted into 516 HCV-positive and 191 HCV-negative recipients. There were no differences in survival in HCV-positive recipients whether they received NAT-positive grafts (n = 1,148) or HCV antibody-negative/NAT-negative grafts (n = 6,321). Recipients of grafts from HCV antibody-positive/NAT-negative donors had similar survival whether recipients were HCV-negative patients (n = 191) or HCV-positive patients (n = 516), and their survival probabilities were similar to those of HCV-negative recipients (n = 6,321) receiving grafts from HCV antibody-negative/NAT-negative donors. Patient survival was lower (P = 0.049) when HCV-negative recipients (n = 210) received NAT-positive grafts compared with HCV-positive patients (n = 1,148) receiving NAT-positive grafts; however, when adjusted for recipient and donor characteristics, the difference was not significant. DISCUSSION: HCV-negative recipients receiving HCV-positive liver grafts (NAT positive) have excellent 1-year survival outcomes.

Karnofsky Performance Status Following Liver Transplantation in Patients With Multiple Organ Failures and Probable Acute-on-Chronic Liver Failure.

BACKGROUND & AIMS: Little is known about outcomes of patients who underwent liver transplantation for acute on chronic liver failure (ACLF) and multiple organ failures. We compared Karnofsky Performance Status (KPS) before and after liver transplantation among patients with different numbers of organ failures and probable ACLF. METHODS: We performed a retrospective cohort study of adults who underwent liver transplantation within 30 days of listing with the United Network for Organ Sharing (UNOS) network from January 1, 2006, through September 30, 2016. We determined the prevalence of organ failures using a modified version of the Chronic Liver Failure-Sequential Organ Failure Assessment scale and collected KPS scores at the time of transplantation and at intervals of 3 to 12 months after liver transplantation. Multivariate analyses were performed to adjust for confounders including UNOS region. RESULTS: At the time of liver transplantation, 2838 patients had no organ failure, 2944 had 1 to 2 organ failures, and 1342 patients had 3 or more organ failures. KPS scores following liver transplantation improved significantly in all groups; scores ranged from 81 in patients with no organ failure to 72 in patients with 5 to 6 organ failures. Excellent performance status (KPS score, ≥80) by 1 year after transplantation was achieved by 60% of patients with 5 to 6 organ failures, 64% to 66% of patients with 3 to 4 organ failures, and 70% to 71% of patients with 1 to 2 organ failures, compared with 72.5% of patients without organ failure. Patients with 1 to 4 organ failure were more likely to achieve KPS scores of 80 or more than patients without organ failure, after we adjusted for other covariates and UNOS region. In addition, black patients were less likely, and patients with alcoholic cirrhosis were more likely, to have KPS scores of 80 or more after liver transplantation. CONCLUSIONS: In a retrospective cohort study of patients with probable ACLF who underwent liver transplantation within 30 days of listing with the UNOS network, 60% to 66% of patients with 3 or more organ failures achieved excellent performance 3 to 12 months later.

Survival Outcomes Are Not Affected When Liver Transplant Surgery Is Done at Night, During Weekends, or Summer Months.

BACKGROUND: It has been suggested that hospitalized patients may get suboptimal care in nights or on weekends or summer holidays due to sleep deprivation, physician fatigue, or reduced medical staffing. Our objective was to determine whether there were differences in outcomes when surgery was performed in the night (10 pm-6 am), on weekends (Saturday or Sunday), or during summer months (June-August). METHODS: We used United Network for Organ Sharing (UNOS) data sets of adults transplanted between February 27, 2002, and September 30, 2016. We estimated the start time of liver transplant surgery by utilizing the cross-clamp time and cold ischemia time (cross-clamp time + cold ischemia time - 2 h). The survival outcomes were estimated by Kaplan-Meier survival analysis. Patients with hepatocellular carcinoma (HCC) were analyzed separately. The independent effect of time of transplant on outcomes was analyzed after adjusting for common confounders, including Model for End-stage Liver Diseases scores and transplant center volume. RESULTS: During the study period, 4 434 (9.6%) were done in the night, 12 147 (26.4%) over weekends, and 11 976 (26%) during summer months. The graft and patient survival and complications were not influenced by the time of transplant for both HCC and non-HCC population. Cox regression analysis after adjusting for risk factors, including Model for End-stage Liver Diseases, donor risk index, and liver center volume, confirmed that there were no significant differences in outcomes. CONCLUSIONS: Our study showed that the time of transplant surgery whether done during nights, weekends, or summer months had no effect on graft or patient survival irrespective of center volume, patient, or donor risk factors.

Poor Health Literacy and Medication Burden Are Significant Predictors for Inadequate Bowel Preparation in an Urban Tertiary Care Setting.

GOALS: The goal of this study was to identify factors impacting the quality of bowel preparation in an urban tertiary care setting. BACKGROUND: Inadequate bowel preparation is encountered in 17% to 32% of colonoscopies performed in the United States. Suboptimal colonic visualization reduces the yield of screening colonoscopies and increases healthcare costs because of longer procedure times and aborted procedures. STUDY: We performed a cross-sectional survey in patients undergoing outpatient colonoscopy within the Johns Hopkins Health System. A Boston Bowel Preparation Score (BBPS) score of <5 was considered inadequate. Fisher's exact, χ tests and univariate and multivariate binary logistic regression were performed to assess the strength of the association for selected factors with a BBPS<5. RESULTS: In total, 467 patients (76.3% response rate) completed the survey between August 2017 and October 2017. The median BBPS score was 7, and 81.4% of patients had an adequate bowel preparation (BBPS≥5). There was significant association between bowel preparation adequacy and level of education, health literacy, functional status, income, and medication burden. When adjusted for other factors, poor confidence in filling forms (OR, 24.1; P<0.001), multiple daily prescription medications (OR, 12.49; P=0.02) and poor functional status (OR, 2.82; P=0.03) had the highest odds of predicting inadequate bowel preparation. CONCLUSIONS: Inadequate bowel preparation is a significant problem accounting for reduced yield of screening and increased health care costs. Poor health literacy, functional status, and number of daily medications are significant factors predicting inadequate bowel preparation in the tertiary care setting.

Poor Survival After Retransplantation in NASH Cirrhosis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) cirrhosis is a common indication for liver transplantation (LT) in the United States. There is a paucity of data on retransplantation (re-LT) in those who were initially transplanted for NASH. METHODS: We queried the United Network for Organ Sharing data sets from 2002 to 2016 to analyze the outcomes of adults with NASH (n = 128) and compared them with groups that received re-LT for cryptogenic cirrhosis (n = 189), alcoholic cirrhosis (n = 300) or autoimmune hepatitis cirrhosis (n = 118) after excluding multiple-organ re-LT and individuals with hepatocellular carcinoma. We estimated survival probabilities using a Kaplan-Meier estimator, and a relative risk of patient and graft mortality using proportional hazards regression. RESULTS: The NASH group was older and had a higher prevalence of obesity, type II diabetes mellitus, renal insufficiency, portal vein thrombosis, and poor performance status. The median interval between the first and the second LT was shorter in the NASH group (27 days). The graft and patient 5-year survival rates were lower for the NASH group after re-LT compared with the other 3 groups. After adjusting for demographic and disease complication factors, the factors that increased a risk of patient or graft failure were a poor performance status (hazard ratio [HR], 1.64; 1.19-2.26), Donor Risk Index (HR, 1.51; 1.08-2.12), and a high Model for End-stage Liver Disease score (HR, 1.02; 1.00-1.04). CONCLUSIONS: Despite the comparable outcomes reported for initial LT among the various etiologies, the outcome of re-LT is significantly worse for NASH cirrhosis.

Liver transplantation in patients with multiple organ failures: Feasibility and outcomes.

BACKGROUND & AIMS: Multiple organ failures (OFs) are common in patients with cirrhosis, but the independent effect of the number or type of OFs on liver transplantation (LT) outcomes is not well defined. METHOD: United Network for Organ Sharing data were analyzed from 2002 to 2016 for all adults listed for LT who received an LT within 30 days after listing. We estimated post-LT survival stratified by number and type of pre-transplant OFs before and after adjusting for confounding variables. RESULTS: During the study period, 4,714 (4.1%) patients died and 19,375 (16.6%) patients were transplanted within 30 days of listing. One or more OF were more common in those who were transplanted (57.4%) compared to those without LT (9.5%). The probability of staying alive more than 30 days on the waiting list without LT decreased with increasing number of OFs; while 90% were alive without OF, only 20% were alive with two OFs, and 2-8% with three or more OFs. The interval between listing and transplantation decreased with an increase in OFs, and the median time to transplant after listing was only 4-5 days with three or more OFs. Although the risk of post-LT mortality increased with increasing number of OFs, the 90-day patient survival was 90% and one-year survival was 81% in the presence of 5-6 OFs. The number of OFs was an independent predictor of survival, but the maximum difference in one-year graft or patient survival between those without OF and those with 5-6 OFs was only 9%. Additionally, the type of OF had minimal impact on outcomes. CONCLUSIONS: Liver transplantation is feasible with excellent outcomes, even in the presence of five or six OFs. LAY SUMMARY: Multiple organ failures, ranging from 1-6, are common in hospitalized patients with cirrhosis. The survival without liver transplant is dismal in the presence of three or more organ failures. Small retrospective studies have shown that liver transplant is feasible with good outcomes even in the presence of multiple organ failures. In this study, using a large national dataset, we show that survival chances for more than 30 days in those with three or more organ failures are less than 8%. However, if a liver transplant is performed quickly, the survival chances are very high with one-year survival ranging from 84% with three organ failures to 81% with 5-6 organ failures.

Karnofsky performance status before and after liver transplantation predicts graft and patient survival.

BACKGROUND & AIMS: The Karnofsky performance status (KPS) has been used for almost 70 years for clinical assessment of patients. Our objective was to determine whether KPS is an independent predictor of post-liver transplant (LT) survival after adjusting for known confounders. METHOD: Adult patients listed with the United Network for Organ Sharing (UNOS) from 2006 to 2016 were grouped into low (10-40%, n = 15,103), intermediate (50-70%, n = 22,183) and high (80-100%, n = 13,131) KPS groups based on KPS scores at the time of LT, after excluding those on ventilators or life support. We determined the trends in KPS before and after LT, and survival probabilities based on KPS. RESULTS: There was a decline in KPS scores between listing and LT and there was significant improvement after LT. The graft and patient survival differences were significantly lower (p <0.0001) in those with low KPS. After adjusting for other confounders, the hazard ratios for graft failure were 1.17 (1.12-1.22, p <0.01) for the intermediate and 1.38 (1.31-1.46, p <0.01) for the low group. Similarly, hazard ratios for patient failure were 1.18 (1.13-1.24, p <0.01) for the intermediate and 1.43 (1.35-1.52, p <0.01) for the low group. Other independent negative predictors for graft and patient survival were older age, Black ethnicity, presence of hepatic encephalopathy and donor risk index. Those who did not show significant improvements in post-LT KPS scores had poorer outcomes in all three KPS groups, but it was most obvious in the low KPS group with one-year patient survival of 33%. CONCLUSION: The KPS, before and after LT, is an independent predictor of graft and patient survival after adjusting for other important predictors of survival. LAY SUMMARY: The overall health of liver transplant recipients could be assessed by a simple clinical assessment tool called the Karnofsky performance status, which assesses an individual's overall functional status on an 11-point scale, in increments of 10, where a score of 0 is considered dead and 100 is considered perfect health. In this study, using a large dataset, we show that the performance status before and after liver transplant is a predictor of survival. More importantly, those who have low performance status before transplant and do not show an improvement in performance status between 3-12 months after liver transplant have very poor survival.