Publications by authors named "Jennifer C Lai"

128 Publications

Outcomes of SARS-CoV-2 Infection in Patients with Chronic Liver Disease and Cirrhosis: a N3C Study.

medRxiv 2021 Jun 7. Epub 2021 Jun 7.

Background And Aims: In patients with chronic liver diseases (CLD) with or without cirrhosis, existing data on the risk of adverse outcomes with SARS-CoV-2 infection have been mixed or have limited generalizability. We used the National COVID Cohort Collaborative (N3C) Data Enclave, a harmonized electronic health record (EHR) dataset of 5.9 million nationally-representative, diverse, and gender-balanced patients, to describe outcomes in patients with CLD and cirrhosis with SARS-CoV-2.

Methods: We identified all chronic liver diseases patients with and without cirrhosis who had SARS-CoV-2 testing documented in the N3C Data Enclave as of data release date 5/15/2021. The primary outcome was 30-day all-cause mortality. Survival analysis methods were used to estimate cumulative incidences of death, hospitalization, and mechanical ventilation, and to calculate the associations of SARS-CoV-2 infection, presence of cirrhosis, and demographic and clinical factors to 30-day mortality.

Results: We isolated 217,143 patients with CLD: 129,097 (59%) without cirrhosis and SARS-CoV-2 negative, 25,844 (12%) without cirrhosis and SARS-CoV-2 positive, 54,065 (25%) with cirrhosis and SARS-CoV-2 negative, and 8,137 (4%) with cirrhosis and SARS-CoV-2 positive. Among CLD patients without cirrhosis, 30-day all-cause mortality rates were 0.4% in SARS-CoV-2 negative patients and 1.8% in positive patients. Among CLD patients with cirrhosis, 30-day all-cause mortality rates were 4.0% in SARS-CoV-2 negative patients and 9.7% in positive patients.Compared to those who tested SARS-CoV-2 negative, SARS-CoV-2 positivity was associated with more than two-fold (aHR 2.43, 95% CI 2.23-2.64) hazard of death at 30 days among patients with cirrhosis. Compared to patients without cirrhosis, the presence of cirrhosis was associated with a three-fold (aHR 3.39, 95% CI 2.96-3.89) hazard of death at 30 days among patients who tested SARS-CoV-2 positive. Age (aHR 1.03 per year, 95% CI 1.03-1.04) was associated with death at 30 days among patients with cirrhosis who were SARS-CoV-2 positive.

Conclusions: In this study of nearly 220,000 CLD patients, we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.43-times mortality hazard, and the presence of cirrhosis among CLD patients infected with SARS-CoV-2 were associated with 3.39-times mortality hazard. Compared to previous studies, our use of a nationally-representative, diverse, and gender-balanced dataset enables wide generalizability of these findings.
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http://dx.doi.org/10.1101/2021.06.03.21258312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202438PMC
June 2021

Sarcopenia and frailty in decompensated cirrhosis.

J Hepatol 2021 Jul;75 Suppl 1:S147-S162

Department of Clinical Medicine, Gastroenterology, Sapienza University of Rome, Italy. Electronic address:

In patients with decompensated cirrhosis, sarcopenia and frailty are prevalent. Although several definitions exist for these terms, in the field of hepatology, sarcopenia has commonly been defined as loss of muscle mass, and frailty has been broadly defined as the phenotypic manifestation of the loss of muscle function. Prompt recognition and accurate assessment of these conditions are critical as they are both strongly associated with morbidity, mortality, poor quality of life and worse post-liver transplant outcomes in patients with cirrhosis. In this review, we describe the complex pathophysiology that underlies the clinical phenotypes of sarcopenia and frailty, their association with decompensation, and provide an overview of tools to assess these conditions in patients with cirrhosis. When available, we highlight data focusing on patients with acutely decompensated cirrhosis, such as inpatients, as this is an area of unmet clinical need. Finally, we discuss management strategies to reverse and/or prevent the development of sarcopenia and frailty, which include adequate nutritional intake of calories and protein, as well as regular exercise of at least moderate intensity, with a mix of aerobic and resistance training. Key knowledge gaps in our understanding of sarcopenia and frailty in decompensated cirrhosis remain, including best methods to measure muscle mass and function in the inpatient setting, racial/ethnic variation in the development and presentation of sarcopenia and frailty, and optimal clinical metrics to assess response to therapeutic interventions that translate into a reduction in adverse outcomes associated with these conditions.
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http://dx.doi.org/10.1016/j.jhep.2021.01.025DOI Listing
July 2021

Inpatient frailty assessment is feasible and predicts non-home discharge and mortality in decompensated cirrhosis.

Liver Transpl 2021 May 21. Epub 2021 May 21.

University of Pittsburgh Medical Center and Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Objective inpatient frailty assessments in decompensated cirrhosis are understudied. We examined the feasibility of inpatient frailty measurement, and associations with non-home discharge, readmission, and all-cause mortality among patients admitted for cirrhosis complications. We conducted a prospective study at three large liver transplant (LT) centers. Frailty was assessed using the Liver Frailty Index (LFI). Multivariable logistic and competing risk models evaluated associations between frailty and clinical outcomes adjusted for age and MELDNa. Inpatient frailty assessments were implemented among 211 patients. Median MELDNa was 21 (interquartile range [IQR]:15-27); 96 (45%) were women; 102 (48%) were LT waitlisted. At a median follow-up of 8.3 months, 29 (14%) had non-home discharge, 144 (68%) were readmitted, 70 (33%) underwent LT, and 44 (21%) died. A total of 124 (59%) patients were frail with median LFI of 4.71 ([IQR] 4.07-5.54). Patients with frailty were older (mean of 59 vs. 54 years), more likely to have chronic kidney disease (40% vs. 20%, P=0.002) and coronary artery disease (17% vs. 7%, P=0.03). Frailty was associated with hospital-acquired infections (8% among frail vs. 1% among non-frail, P=0.02). In multivariable models, LFI as a continuous measure was associated with non-home discharge (aOR 1.81 per 1-point increase, 95%CI: 1.14-2.86). Frailty (LFI ≥4.5) was associated with all-cause mortality in models accounting for LT as competing risk (sHR 2.4, 95%CI 1.13-5.11); results were similar with LFI as continuous variable (sHR 1.62 per 1-point increase, 95%CI 1.15-2.28). CONCLUSION: A brief, objective inpatient frailty assessment was feasible and predicted non-home discharge and mortality in decompensated cirrhosis. Inpatient point-of-care frailty assessment prior to hospital discharge can be useful for risk-stratification and targeted interventions to improve physical fitness and reduce adverse outcomes.
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http://dx.doi.org/10.1002/lt.26100DOI Listing
May 2021

Admission urinary and serum metabolites predict renal outcomes in hospitalized patients with cirrhosis.

Hepatology 2021 May 18. Epub 2021 May 18.

University of Toronto, Toronto, Ontario, Canada.

Acute kidney injury (AKI) has a poor prognosis in cirrhosis. Given the variability of creatinine, the prediction of AKI and dialysis by other markers are needed. Aim: Determine the role of serum and urine metabolomics in prediction of AKI and dialysis in an inpatient cirrhosis cohort. Cirrhosis inpatients from 11 NACSELD (North American Consortium of End-stage Liver Disease) centers who provided admission serum/urine when they were AKI and dialysis-free were included. ANCOVA adjusted for demographics, infection and cirrhosis severity was performed to identify metabolites that differed between patients (a) who developed AKI/not (b) required dialysis/not and (c) within AKI subgroups who needed dialysis/not. We performed random forest and AUC analyses to identify specific metabolite(s) associated with outcomes. Logistic regression with clinical variables with/without metabolites was performed. 602 patients gave serum (218 developed AKI, 80 needed dialysis) and 435 gave urine (164 developed AKI, 61 needed dialysis). AKI prediction: Clinical factor-adjusted AUC was 0.91 for serum and 0.88 for urine. Major metabolites such as uremic toxins (DMTPA, N2N2dimethylguanosine, uridine/pseudouridine), tryptophan/tyrosine metabolites (kynunerate, 8-methoxykyunerate, quinolinate) were higher in patients that developed AKI. Dialysis prediction: Clinical factor-adjusted AUC was 0.93 for serum and 0.91 for urine. Similar metabolites as AKI were altered here. Dialysis prediction in those with AKI: AUC was 0.81 and 0.79 for serum/urine. Lower branched-chain amino-acid metabolites but higher cysteine, tryptophan, glutamate and DMTPA were seen in AKI patients needing dialysis. Serum/urine metabolites were additive to clinical variables for all outcomes. CONCLUSIONS: Specific admission urinary and serum metabolites were significantly additive to clinical variables to predict AKI development and dialysis initiation in inpatients with cirrhosis. These observations can potentially facilitate earlier initiation of renoprotective measures.
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http://dx.doi.org/10.1002/hep.31907DOI Listing
May 2021

A Multicenter Pilot Randomized Clinical Trial of a Home-Based Exercise Program for Patients With Cirrhosis: The Strength Training Intervention (STRIVE).

Am J Gastroenterol 2021 Apr;116(4):717-722

1Department of Medicine, University of California-San Francisco, San Francisco, California, USA; 2Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; 3Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; 4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Introduction: We developed the strength training intervention (STRIVE), a home-based exercise program targeting physical function in patients with cirrhosis. In this pilot study, we aimed to evaluate the safety and efficacy of STRIVE.

Methods: Eligible were adult patients with cirrhosis at 3 sites. Patients were randomized 2:1-12 weeks of STRIVE, a 30-minute strength training video plus a health coach or standard of care (SOC). Physical function and quality of life were assessed using the Liver Frailty Index (LFI) and Chronic Liver Disease Questionnaire (CLDQ), respectively.

Results: Fifty-eight and 25 were randomized to STRIVE and SOC arms, respectively: 43% women, median age was 61 years, MELDNa, Model for End-Stage Liver Disease Sodium was 14, and 54% were Child-Pugh B/C. Baseline characteristics were similar in the STRIVE vs SOC arms except for rates of hepatic encephalopathy (19 vs 36%). LFI @ 12 weeks was available in 43 STRIVE and 20 SOC participants. After 12 weeks, the median LFI improved from 3.8 to 3.6 (ΔLFI -0.1) in the STRIVE arm and 3.7 to 3.6 (ΔLFI -0.1) in the SOC arm (P = 0.65 for ΔLFI difference). CLDQ scores improved from 4.6 to 5.2 in STRIVE participants (ΔCLDQ 0.38) and did not change in SOC participants (4.2-4.2; ΔCLDQ -0.03) (P = 0.09 for ΔCLDQ difference). One patient died (SOC arm) of bleeding. Only 14% of STRIVE participants adhered to the strength training video for 10-12 weeks. No adverse events were reported by STRIVE participants.

Discussion: STRIVE, a home-based structured exercise program for patients with cirrhosis, was safely administered at 3 sites, but adherence was low. Although all participants showed minimal improvement in the LFI, STRIVE was associated with a substantial improvement in quality of life.
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http://dx.doi.org/10.14309/ajg.0000000000001113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178511PMC
April 2021

Association of Cognitive Function Screening Results with Adherence and Performance in a Pedometer-Based Intervention.

Am J Nephrol 2021 May 12:1-9. Epub 2021 May 12.

Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota, USA.

Introduction: A randomized, controlled trial of a pedometer-based walking intervention with weekly activity goals led to increased walking among dialysis patients. We examined whether impairment per cognitive function screening is associated with adherence and performance in the intervention.

Methods: Thirty dialysis patients were randomly assigned to a 3-month pedometer-based intervention with weekly goals. Participants were administered the Telephone Interview of Cognitive Status (TICS), a test of global mental status. We examined the association of levels of impairment on the TICS (≥33: unimpaired, 26-32: ambiguous impairment, 21-25: mild cognitive impairment [MCI]) with adherence, achieving weekly goals, and increasing steps, physical performance (Short Physical Performance Battery, SPPB), and self-reported physical function (PF) through multivariable linear mixed-model and logistic regression analyses adjusted for age, sex, BMI, dialysis modality, baseline steps, baseline SPPB, and stroke status.

Results: One-third of participants were unimpaired, and 13% had MCI. Participants with worse results on cognitive function screening missed more calls and completed fewer weekly goals than participants with better results. During the intervention, a worse result on cognitive function screening was associated with smaller increases in steps compared to those without impairment: (ambiguous: -620 [95% CI -174, -1,415], MCI: -1,653 [95% CI -120, -3,187]); less improvement in SPPB (ambiguous: -0.22 points [95% CI -0.08, -0.44], MCI: -0.45 [95% CI -0.13, -0.77]); and less improvement in PF (ambiguous: -4.0 points [95% CI -12.2, 4.1], MCI: -14.0 [95% CI -24.9, -3.1]). During the postintervention period, a worse result on cognitive function screening was associated with smaller increases in SPPB (ambiguous: -0.54 [95% CI -1.27, 0.19], MCI: -0.97 [95% CI -0.37, -1.58]) and PF (ambiguous: -3.3 [95% CI -6.5, -0.04], MCI: -10.5 [95% CI -18.7, -2.3]).

Discussion/conclusion: Participants with worse results on cognitive function screening had worse adherence and derived less benefit from this pedometer-based intervention. Future exercise interventions should be developed incorporating methods to address cognitive impairment, for example, by including caregivers when planning such interventions.
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http://dx.doi.org/10.1159/000516130DOI Listing
May 2021

National Early Career Transplant Hepatologist Survey: Compensation, Burnout, and Job Satisfaction.

Hepatol Commun 2021 Apr 5;5(4):701-712. Epub 2021 Jan 5.

Department of Medicine University of California, San Francisco San Francisco CA USA.

Despite the growth of transplant hepatology as a subspecialty over the past decade, data on professional roles and compensation models remain lacking. Furthermore, the prevalence of physician burnout and job satisfaction are unknown in this profession. We aimed to conduct a comprehensive assessment of early career transplant hepatologists to fill these voids in knowledge and to inform current and future transplant hepatologists. An online survey designed to quantify clinical and nonclinical roles, compensation and structure, job satisfaction, and burnout was sent to 256 early career transplant hepatologists. Respondents were divided into three practice settings: university hospital clinical (n = 79), non-university hospital clinical (n = 35), and research (n = 25). The median age of respondents was 38 (interquartile range [IQR] 36-40) years, and 44% were women. The median half-days/week spent in clinic was 4 (IQR 3-6) and in endoscopy was 1 (IQR 1-2). Most of the respondents provided inpatient care (88%) for a median of 9 (IQR 6.5-10) weeks/year. The median base compensation was $300,000 (IQR US $263,750-$326,250), and most (76%) had salary-based compensation. Although only 8% of respondents were dissatisfied with their position, the prevalence of burnout was high at 35%. This survey is a comprehensive assessment focusing on early career transplant hepatologists, is reflective of the current training paradigm and practice of transplant hepatology, and provides transparency to guide professional negotiations and empower both trainees pursuing careers in transplant hepatology and early career transplant hepatologists.
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http://dx.doi.org/10.1002/hep4.1666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034566PMC
April 2021

Osmotic Demyelination Syndrome in Hospitalized Patients With Cirrhosis: Analysis of the National Inpatient Sample (NIS).

J Clin Gastroenterol 2021 Mar 18. Epub 2021 Mar 18.

Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA.

Goal: Characterize prevalence of osmotic demyelination syndrome (ODS) in hospitalized patients with cirrhosis.

Background: ODS is a serious complication of rapid serum sodium correction. Patients with cirrhosis experience labile sodium levels related to portal hypertension and diuretic use, often with rapid correction-intentional or unintentional-during hospitalizations.

Study: We used validated International Classification of Diseases, Ninth Revision (ICD-9) codes to identify inpatients 18 years and older with cirrhosis from the 2009-2013 National Inpatient Sample, excluding those with liver transplantation during hospitalization. The primary outcome was ODS (ICD-9 341.8). Baveno IV defined decompensated cirrhosis (stages 3 and 4); Charlson Comorbidity Index identified severe comorbid illness (score >3). Logistic regression modeled factors associated with ODS.

Results: Of 547,544 adult inpatients with cirrhosis, 94 (0.02%) had ODS. Inpatients with versus without ODS were younger (54 vs. 57 y, P=0.0001), and more likely to have alcohol-related cirrhosis (58% vs. 33%, P<0.0001). ODS did not associate with decompensated cirrhosis (33% vs. 37%, P=0.43), specific complications (ascites 33% vs. 33%, P=0.97; hepatic encephalopathy 24% vs. 17%, P=0.06), or severe comorbid illness (12% vs. 16%, P=0.24). In both univariable and multivariable analysis, age [adjusted odds ratio (ORadj): 0.97, 95% confidence interval (CI): 0.95-0.99], female gender (ORadj: 1.53, 95% CI: 1.01-2.30), Hispanic race (ORadj: 0.41, 95% CI: 0.19-0.89), alcohol-related cirrhosis (ORadj: 2.65, 95% CI: 1.71-4.09), and congestive heart failure (ORadj: 0.37, 95% CI: 0.15-0.95) significantly associated with ODS.

Conclusion: In hospitalized patients with cirrhosis, ODS is extremely rare, and associated with alcohol-related cirrhosis, younger age, and female gender. ODS is not associated with liver disease severity, specific complications including ascites, or comorbid disease.
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http://dx.doi.org/10.1097/MCG.0000000000001529DOI Listing
March 2021

Frailty is strongly associated with self-reported symptom burden among patients with cirrhosis.

Eur J Gastroenterol Hepatol 2021 Mar 12. Epub 2021 Mar 12.

Department of Medicine Division of Palliative Medicine Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, California, USA.

Objectives: Although patients with cirrhosis often experience debilitating symptoms, few are referred for palliative care. Frailty is increasingly incorporated in liver transplantation evaluation and has been associated with symptom burden in other populations. We hypothesized that frail patients with cirrhosis are highly symptomatic and thus are likely to benefit from palliative care.

Methods: Patients with cirrhosis undergoing outpatient liver transplantation evaluation completed the Liver Frailty Index (grip strength, chair stands and balance) and a composite of validated measures including the Edmonton Symptom Assessment Scale, distress and quality of life (QOL) measures.

Results: Of 233 patients (median age 61 years, 43% women), 22% were robust, 59% prefrail and 19% frail. Overall, 38% of patients reported ≥1 severe symptoms based on preestablished Edmonton Symptom Assessment Scale criteria. Higher frailty categories were associated with increased prevalence of pain, dyspnea, fatigue, nausea, poor appetite, drowsiness, depression and poor well-being (test for trend, all P < 0.05). Frail patients were also more likely to report psychological distress and poor QOL (all P < 0.01). In univariate analysis, each 0.5 increase in liver frailty index was associated with 44% increased odds of experiencing ≥1 severe symptoms [95% confidence interval (CI), 1.2-1.7, P < 0.001], which persisted (odds ratio, 1.3, 95% CI, 1.0-1.6, P = 0.004) even after adjusting for Model for End Stage Liver Disease-Sodium, ascites, hepatic encephalopathy and age.

Conclusion: In patients with cirrhosis, frailty is strongly associated with physical/psychological symptoms, including pain and depression and poor QOL. Frail patients with cirrhosis may benefit from palliative care co-management to address symptoms and improve QOL.
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http://dx.doi.org/10.1097/MEG.0000000000002113DOI Listing
March 2021

Advance Care Planning in Liver Transplant-Preparing for Both Life and Death.

JAMA Intern Med 2021 May;181(5):660-661

Department of Medicine, University of California, San Francisco, San Francisco.

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http://dx.doi.org/10.1001/jamainternmed.2021.0149DOI Listing
May 2021

Renal Outcomes After Simultaneous Liver-Kidney Transplantation: Results from the US Multicenter Simultaneous Liver-Kidney Transplantation Consortium.

Liver Transpl 2021 Feb 28. Epub 2021 Feb 28.

Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY.

Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51-64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol-related liver disease; 68% developed ≥ stage 3 CKD at the end of follow-up. The 1-year, 3-year, and 5-year incidence rates of post-SLKT stage 4-5 CKD were 10%, 12%, and 16%, respectively. Pre-SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00-2.15), NASH (HR, 1.58; 95% CI, 1.01-2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10-2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22-0.89) reduced the risk. Women (β = -6.22 ± 2.16 mL/minute/1.73 m ; P = 0.004), NASH (β = -7.27 ± 3.27 mL/minute/1.73 m ; P = 0.027), and delayed kidney graft function (β = -7.25 ± 2.26 mL/minute/1.73 m ; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow-up. Stage 4-5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.
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http://dx.doi.org/10.1002/lt.26032DOI Listing
February 2021

Center variation in long-term outcomes for socioeconomically deprived children.

Am J Transplant 2021 Feb 10. Epub 2021 Feb 10.

University of California San Francisco, San Francisco, California.

Neighborhood socioeconomic deprivation is associated with adverse outcomes after pediatric liver transplant. We sought to determine if this relationship varies by transplant center. Using SRTR, we included patients <18 years transplanted 2008-2013 (N = 2804). We matched patient ZIP codes to a deprivation index (range [0,1]; higher values indicate increased socioeconomic deprivation). A center-level patient-mix deprivation index was defined by the distribution of patient-level deprivation. Centers (n = 66) were classified as high or low deprivation if their patient-mix deprivation index was above or below the median across centers. Center quality was classified as low or high graft failure if graft survival rates were better or worse than the overall 10-year graft survival rate. Primary outcome was patient-level graft survival. We used random-effect Cox models to evaluate center-level covariates on graft failure. We modeled center quality using stratified Cox models. In multivariate analysis, each 0.1 increase in the patient-mix deprivation index was associated with increased hazard of graft failure (HR 1.32; 95%CI: 1.05, 1.66). When stratified by center quality, patient-mix deprivation was no longer significant (HR 1.07, 95%CI: 0.89, 1.28). Some transplant centers care for predominantly high deprivation children and maintain excellent outcomes. Revealing and replicating these centers' practice patterns should enable more equitable outcomes.
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http://dx.doi.org/10.1111/ajt.16529DOI Listing
February 2021

Implementing a Height-Based Rule for the Allocation of Pediatric Donor Livers to Adults: A Liver Simulated Allocation Model Study.

Liver Transpl 2021 Jan 18. Epub 2021 Jan 18.

Department of Mathematics, United States Naval Academy, Annapolis, MD.

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http://dx.doi.org/10.1002/lt.25986DOI Listing
January 2021

Evaluating the Associations Between the Liver Frailty Index and Karnofsky Performance Status With Waitlist Mortality.

Transplant Direct 2021 Feb 7;7(2):e651. Epub 2021 Jan 7.

Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA.

Frailty has emerged as a critical determinant of mortality in patients with cirrhosis. Currently, the United Network for Organ Sharing registry only includes the Karnofsky Performance Status (KPS) scale, which captures a single component of frailty. We determined the associations between frailty, as measured by the Liver Frailty Index (LFI), and KPS with waitlist mortality.

Methods: Included were 247 adult patients with cirrhosis listed for liver transplantation without hepatocellular carcinoma from February 2014 to June 2019, who underwent outpatient assessments using the LFI and KPS within 30 days of listing. "Frail" was defined using the established LFI cutoff of ≥4.4. Competing risk models assessed associations between the LFI and KPS with waitlist mortality (death/delisting for sickness).

Results: At a median 8 months follow-up, 25 (10%) patients died/were delisted. In this cohort, median Model for End-Stage Liver Disease-Sodium was 17, LFI was 3.9 (interquartile range 3.4-4.5), and KPS was 80 (interquartile range 70-90). In multivariable analysis, LFI (sub-hazard ratio 1.07, per 0.1 unit; 95% confidence interval, 1.01-1.12) was associated with waitlist mortality while KPS was not (sub-hazard ratio 1.00, per 10 units; 95% confidence interval, 0.78-1.29).

Conclusions: Our data suggest that frailty, as measured by the LFI, may be more appropriate at capturing mortality risk than KPS and provide evidence in support of using the LFI more broadly in clinical transplant practice in the outpatient setting.
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http://dx.doi.org/10.1097/TXD.0000000000001097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793347PMC
February 2021

Association of Frailty and Sex With Wait List Mortality in Liver Transplant Candidates in the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

JAMA Surg 2021 Mar;156(3):256-262

Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, New York.

Importance: Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown.

Objective: To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation.

Design, Setting, And Participants: This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020.

Exposures: At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance).

Main Outcomes And Measures: The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men.

Results: Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty.

Conclusions And Relevance: These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.
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http://dx.doi.org/10.1001/jamasurg.2020.5674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774043PMC
March 2021

Frailty and Risk of Serious Infections in Biologic-treated Patients With Inflammatory Bowel Diseases.

Inflamm Bowel Dis 2020 Dec 16. Epub 2020 Dec 16.

Division of Geriatrics and Gerontology, Department of Medicine, University of California San Diego, La Jolla, California, USA.

Background: Identifying biologic-treated patients with inflammatory bowel diseases (IBDs) at higher risk of serious infections is a priority. We conducted a retrospective cohort study evaluating frailty and risk of serious infections in biologic-treated patients with IBD.

Methods: Using an administrative claims database, we identified biologic-treated patients with IBD between 2014 and 2018 with follow-up 1 year before and after treatment initiation. Using a validated claims-based hospital frailty risk scoring system, patients were classified as frail and nonfrail. We compared the risk of serious infections (infections requiring hospitalization) between frail and nonfrail patients using Cox proportional hazard analysis adjusting for age, comorbidities, disease characteristics, health care utilization, use of corticosteroids, immunomodulators, and opiates.

Results: We included 5987 biologic-treated patients with IBD (4881 on TNFα antagonists, 1106 on vedolizumab), of whom 2350 (39.3%) were classified as frail; over 7115 person-years of follow-up was included, and 520 patients developed serious infection. Frailty was not associated with increased risk of serious infection (adjusted hazard ratio [aHR], 1.12; 95% CI, 0.93-1.36), whereas advanced age (older than 60 years), high comorbidity burden, corticosteroid use, opiate use, and prior serious infection were associated with increased risk of serious infection. On stratified analysis, frailty was associated with increased risk of serious infections in vedolizumab-treated patients (aHR, 1.69; 95% CI, 1.03-2.79) but not in TNFα antagonist-treated patients (aHR, 1.03; 95% CI, 0.83-1.27).

Conclusions: In biologic-treated patients with IBD, frailty assessed using a claims-based frailty index was not independently associated with increased risk of serious infections. Future studies evaluating objective and biological measures of frailty are warranted to risk-stratify older patients with IBD.
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http://dx.doi.org/10.1093/ibd/izaa327DOI Listing
December 2020

Sex-Based Disparities in Hepatocellular Carcinoma Recurrence After Liver Transplantation.

Transplantation 2020 Dec 14. Epub 2020 Dec 14.

Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA.

Background: Women with chronic liver disease have lower rates of hepatocellular carcinoma (HCC) as compared to men; it is unknown if there are sex-based differences in HCC recurrence post-liver transplant.

Methods: We conducted an analysis of patients who underwent liver transplant for HCC in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2012 through December 31, 2017.

Results: A total of 12,711 patients underwent liver transplant for HCC: 2,909 (23%) women and 9,802 (73%) men. Women had significantly lower rates of post-liver transplant HCC recurrence than men (4.0 v. 5.4%, p=0.002). A cox-regression analysis for post-liver transplant HCC recurrence highlighted that even after accounting for etiology of cirrhosis, alpha-fetoprotein (AFP) at liver transplant, tumor diameter, tumor pathology, and vascular invasion, female sex was associated with a 25% lower risk of post-liver transplant HCC recurrence (95CI 0.57-0.99). There were no interactions between female sex and the following variables: age, type of locoregional therapy, AFP, donor sex, body mass index, or nonalcoholic steatohepatitis etiology (p>0.05 for each).

Conclusions: This study demonstrates an independent effect of sex on risk for HCC recurrence post-liver transplant. Our data highlight an opportunity to better understand HCC tumor biology by investigating the drivers of this sex-based difference in HCC recurrence.
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http://dx.doi.org/10.1097/TP.0000000000003575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200371PMC
December 2020

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

Liver Transpl 2021 02 2;27(3):329-340. Epub 2021 Jan 2.

Department of Radiology and Biomedical Imaging, University of California-San Francisco, San Francisco, CA.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.
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http://dx.doi.org/10.1002/lt.25949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053375PMC
February 2021

Increased Risk of ACLF and Inpatient Mortality in Hospitalized Patients with Cirrhosis and Hepatic Hydrothorax.

Dig Dis Sci 2020 Nov 13. Epub 2020 Nov 13.

Department of Medicine, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.

Background: Hepatic hydrothorax (HH) remains a difficult-to-treat complication of cirrhosis.

Aim: To define the mortality, length of stay (LOS), and risk of ACLF in patients admitted with HH.

Methods: We utilized the North American Consortium for the Study of End-stage Liver Disease, a prospective cohort of 2868 non-electively hospitalized patients with cirrhosis from 14 tertiary care hepatology centers in North America. A total of 121 patients who required an inpatient thoracentesis (HH group) were compared to 736 patients with refractory ascites without HH, and to 1639 patients without these complications (Other). Patients with a TIPS before or during admission were excluded.

Results: There were no differences between the groups in age, gender, or liver disease etiology. Admission MELD (20.5, 21.6 vs. 18.7; p < 0.0001) was lower in HH than RA patients but lowest in other patients, respectively. In hospital, HH patients' rate of second infections and ICU transfer were the highest, and their LOS was the longest of all groups. Despite a similar mean discharge MELD compared to RA patients, the 90-day transplant rate was lower. Multivariable modeling showed patients with HH had an increased risk of ACLF (HR = 2.37 vs. RA, HR = 2.56 vs. Other; p = 0.01) even when controlling for MELD score, AKI, second infection, and history of prior 6-month hospitalization. Multivariable modeling also showed that HH increased the risk of inpatient mortality (HR = 2.22 vs. RA alone, HR = 2.31 vs. Other; p = 0.04).

Conclusions: HH that required a therapeutic thoracentesis more than doubled the risk of ACLF and inpatient mortality among hospitalized patients with cirrhosis.
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http://dx.doi.org/10.1007/s10620-020-06677-6DOI Listing
November 2020

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

Liver Transpl 2020 11 13;26(11):1492-1503. Epub 2020 Oct 13.

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, CA.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.
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http://dx.doi.org/10.1002/lt.25863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960487PMC
November 2020

Low Predictability of Readmissions and Death Using Machine Learning in Cirrhosis.

Am J Gastroenterol 2021 02;116(2):336-346

Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.

Introduction: Readmission and death in cirrhosis are common, expensive, and difficult to predict. Our aim was to evaluate the abilities of multiple artificial intelligence (AI) techniques to predict clinical outcomes based on variables collected at admission, during hospitalization, and at discharge.

Methods: We used the multicenter North American Consortium for the Study of End-Stage Liver Disease (NACSELD) cohort of cirrhotic inpatients who are followed up through 90-days postdischarge for readmission and death. We used statistical methods to select variables that are significant for readmission and death and trained 3 AI models, including logistic regression (LR), kernel support vector machine (SVM), and random forest classifiers (RFC), to predict readmission and death. We used the area under the receiver operating characteristic curve (AUC) from 10-fold crossvalidation for evaluation to compare sexes. Data were compared with model for end-stage liver disease (MELD) at discharge.

Results: We included 2,170 patients (57 ± 11 years, MELD 18 ± 7, 61% men, 79% White, and 8% Hispanic). The 30-day and 90-day readmission rates were 28% and 47%, respectively, and 13% died at 90 days. Prediction for 30-day readmission resulted in 0.60 AUC for all patients with RFC, 0.57 AUC with LR for women-only subpopulation, and 0.61 AUC with LR for men-only subpopulation. For 90-day readmission, the highest AUC was achieved with kernel SVM and RFC (AUC = 0.62). We observed higher predictive value when training models with only women (AUC = 0.68 LR) vs men (AUC = 0.62 kernel SVM). Prediction for death resulted in 0.67 AUC for all patients, 0.72 for women-only subpopulation, and 0.69 for men-only subpopulation, all with LR. MELD-Na model AUC was similar to those from the AI models.

Discussion: Despite using multiple AI techniques, it is difficult to predict 30- and 90-day readmissions and death in cirrhosis. AI model accuracies were equivalent to models generated using only MELD-Na scores. Additional biomarkers are needed to improve our predictive capability (See also the visual abstract at http://links.lww.com/AJG/B710).
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http://dx.doi.org/10.14309/ajg.0000000000000971DOI Listing
February 2021

Progression of Stage 2 and 3 Acute Kidney Injury in Patients With Decompensated Cirrhosis and Ascites.

Clin Gastroenterol Hepatol 2020 Aug 13. Epub 2020 Aug 13.

Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Health Care System, Richmond, Virginia.

Background & Aims: Progression of stages 2 and 3 acute kidney injury (AKI) in cirrhosis has not been characterized adequately. Patients with higher stages of AKI are believed to have worse outcomes. We assessed outcomes and factors associated with stages 2 and 3 AKI in patients with cirrhosis in the North American Consortium for the Study of End-stage Liver Disease cohort.

Methods: We collected data from 2297 hospitalized patients with cirrhosis and ascites from December 2011 through February 2017. Our final analysis included 760 patients who developed AKI per the International Ascites Club 2015 definition (419 with maximum stage 1 and 341 with maximum stage 2 or 3; 63% male; mean age, 58 y). We compared demographic features, laboratory values, AKI treatment response, and survival between patients with maximum stage 1 vs patients with stage 2 or 3 AKI.

Results: Patients with stage 2 or 3 AKI had higher Model for End-Stage Liver Disease scores (25.9 ± 7.3) than patients with stage 1 AKI (21.9 ± 7.5) (P < .0001). More patients fulfilled systemic inflammatory response syndrome criteria on admission, and more developed a second nosocomial infection (P < .05 for both comparisons). More patients with stage 2 or 3 AKI also had progression of AKI and required dialysis and admission into intensive care units when compared to stage 1 AKI patients (P < .0001 for both). A lower proportion of patients with stage 2 or 3 AKI survived their hospital stay (80% vs 99% with stage 1 AKI; P < .0001), or survived for 30 days without a liver transplant (56% vs 81%; P < .0001). The development of stage 2 or 3 AKI was associated with a higher Model for End-Stage Liver Disease score at the time of admission (P < .0001), presence of systemic inflammatory response on admission (P = .039), and second infection (P < .0001).

Conclusions: Based on an analysis of data from the North American Consortium for the Study of End-stage Liver Disease cohort, we found that patients with cirrhosis and more advanced liver disease, as well as a second infection, are more likely to develop stages 2 or 3 AKI, with a progressive course associated with decreased 30-day transplant-free survival. Prevention of AKI progression in patients with cirrhosis and stage 2 or 3 AKI might improve their outcomes.
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http://dx.doi.org/10.1016/j.cgh.2020.08.025DOI Listing
August 2020

Unforeseen consequences of the COVID pandemic.

Am J Transplant 2020 11 18;20(11):2973-2974. Epub 2020 Aug 18.

Department of Gastroenterology, University of California San Francisco, San Francisco, California, USA.

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http://dx.doi.org/10.1111/ajt.16235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436819PMC
November 2020

Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis.

Gastroenterology 2020 11 17;159(5):1715-1730.e12. Epub 2020 Jul 17.

Microbiome Analysis center, George Mason University, Manassas, Virginia.

Background & Aims: Inpatients with cirrhosis have high rates of acute-on-chronic failure (ACLF) development and high mortality within 30 days of admission to the hospital. Better biomarkers are needed to predict these outcomes. We performed metabolomic analyses of serum samples from patients with cirrhosis at multiple centers to determine whether metabolite profiles might identify patients at high risk for ACLF and death.

Methods: We performed metabolomic analyses, using liquid chromatography, of serum samples collected at time of admission to 12 North American tertiary hepatology centers from 602 patients in the North American Consortium for the Study of End-Stage Liver Disease sites from 2015 through 2017 (mean age, 56 years; 61% men; mean model for end-stage liver disease score, 19.5). We performed analysis of covariance, adjusted for model for end-stage liver disease at time of hospital admission, serum levels of albumin and sodium, and white blood cell count, to identify metabolites that differed between patients who did vs did not develop ACLF and patients who did vs did not die during hospitalization and within 30 days. We performed random forest analysis to identify specific metabolite(s) that were associated with outcomes and area under the curve (AUC) analyses to analyze them in context of clinical parameters. We analyzed microbiomes of stool samples collected from 133 patients collected at the same time and examined associations with serum metabolites.

Results: Of the 602 patients analyzed, 88 developed ACLF (15%), 43 died in the hospital (7%), and 72 died within 30 days (12%). Increased levels of compounds of microbial origin (aromatic compounds, secondary or sulfated bile acids, and benzoate) and estrogen metabolites, as well as decreased levels of phospholipids, were associated with development of ACLF, inpatient, and 30-day mortality and were also associated with fecal microbiomes. Random forest analysis and logistic regression showed that levels of specific microbially produced metabolites identified patients who developed ACLF with an AUC of 0.84 (95% confidence interval [CI] 0.78-0.88; P = .001), patients who died while in the hospital with an AUC of 0.81 (95% CI 0.74-0.85; P = .002), and patients who died within 30 days with an AUC of 0.77 (95% CI 0.73-0.81; P = .02). The metabolites were significantly additive to clinical parameters for predicting these outcomes. Metabolites associated with outcomes were also correlated with microbiomes of stool samples.

Conclusions: In an analysis of serum metabolites and fecal microbiomes of patients hospitalized with cirrhosis at multiple centers, we associated metabolites of microbial origin and lipid moieties with development of ACLF and death as an inpatient or within 30 days, after controlling for clinical features.
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http://dx.doi.org/10.1053/j.gastro.2020.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680282PMC
November 2020

Neighborhood socioeconomic deprivation, racial segregation, and organ donation across 5 states.

Am J Transplant 2021 03 4;21(3):1206-1214. Epub 2020 Aug 4.

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

One in 10 people die awaiting transplantation from donor shortage. Only half of Americans register as organ donors. In this cross-sectional study, we evaluated population-level associations of neighborhood socioeconomic deprivation and racial segregation on organ donor registration rates. We analyzed state identification card demographic and organ donor registration data from 5 states to estimate the association between a neighborhood socioeconomic deprivation index (range [0, 1]; higher values indicate more deprivation) and a racial index of concentration at the extreme (ICE) (range [-1, 1]; lower values indicate predominantly black neighborhoods, higher values indicate predominantly white neighborhoods) on organ donor registration rates within a specified geography (census tract or ZIP code tabulation area [ZCTA]). Among 26 720 738 registrants, 32% of the sample were registered organ donors. At the census tract level, with each 0.1 decrease in the deprivation index, the organ donor registration rate increased by 6.8% (95% confidence interval [CI]: 6.6%, 7.0%). With each 0.1 increase in the racial ICE, the rate increased by 1.5% (95% CI: 1.5%, 1.6%). These associations held true at the ZCTA level. Areas with less socioeconomic deprivation and a higher concentration of white residents have higher organ donor registration rates. Public health initiatives should consider neighborhood context and novel data sources in designing optimal intervention strategies.
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http://dx.doi.org/10.1111/ajt.16186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191504PMC
March 2021

Frailty as an Immune-Mediated Condition That Leads to an Increased Risk of Acute Cellular Rejection in Liver Transplant Recipients.

Clin Liver Dis (Hoboken) 2020 Jun 30;15(6):243-245. Epub 2020 Jun 30.

Division of Gastroenterology and Hepatology Department of Medicine University of California, San Francisco San Francisco CA.

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http://dx.doi.org/10.1002/cld.960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326634PMC
June 2020

Psychological contributors to the frail phenotype: The association between resilience and frailty in patients with cirrhosis.

Am J Transplant 2021 01 21;21(1):241-246. Epub 2020 Jul 21.

Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA.

We examined whether a key psychological trait-resilience, defined as one's ability to recover quickly from difficulties-contributes to the frail phenotype in patients with cirrhosis. Included were 300 adult patients with cirrhosis who underwent outpatient physical frailty testing using the Liver Frailty Index and resilience testing using the Connor-Davidson Resilience Scale (CD-RISC). The Liver Frailty Index was categorized as robust, prefrail-robust, prefrail-frail, and frail; CD-RISC was categorized using population norms as: least, less, more, and most resilient. Linear regression was used to assess factors associated with frailty (by the Liver Frailty Index per 0.1 unit change). Among the most resilient, only 10% were frail; among the least resilient, 29% were frail. In univariable analysis, resilience was strongly associated with the Liver Frailty Index (coef = -0.13 per point increase; 95% confidence interval [CI], -0.20 to -0.60; P < .001) and remained significantly associated with frailty in multivariable adjustment (coef = -0.13, 95% CI -0.19 to -0.07; P < .001). Low resilience is strongly associated with the frail phenotype in patients with cirrhosis. Given that resilience is modifiable, our data suggest that effective interventions to mitigate frailty should include strategies to build resilience in patients with low baseline resilience.
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http://dx.doi.org/10.1111/ajt.16131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725888PMC
January 2021

Low Rates of Advance Care Planning (ACP) Discussions Despite Readiness to Engage in ACP Among Liver Transplant Candidates.

Dig Dis Sci 2021 May 4;66(5):1446-1451. Epub 2020 Jun 4.

Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, 513 Parnassus Avenue, UCSF Box 0538, San Francisco, CA, 94143, USA.

Background: Patients with end-stage liver disease awaiting liver transplantation (LT) are seriously ill and experience fluctuating periods of clinical decompensation. Discussion of a patient's advance care planning (ACP) wishes early in their dynamic disease course is critical to providing value-aligned care while awaiting LT. We aimed to evaluate current ACP documentation and assess readiness to engage in ACP in this population.

Methods: We conducted a retrospective study of adults undergoing LT evaluation from January 2017 to June 2017 and assessed characteristics associated with documentation using logistic regression. We then administered a survey to LT candidates from March 2018 to May 2018 to determine self-reported readiness to engage in ACP (range 1 = not at all ready to 5 = very ready).

Results: Among 170 LT candidates, median (interquartile range) age was 58 (53-65), 65% were men, MELDNa was 15 (11-21), and Child-Pugh A/B/C were 33/38/29%. Nine percent reported completing ACP prior to LT evaluation, but 0% had legal ACP forms or end-of-life wishes documented in the medical record. A durable power of attorney (DPOA) was discussed with 10%. In univariable analysis, white race (OR 4.16, p = 0.03) and female sex (OR 3.06, p = 0.04) were associated with ACP documentation, but Child-Pugh score and MELDNa were not. Of the 41 LT candidates who completed the ACP survey, 93% were ready to appoint a DPOA and 85% were ready to discuss end-of-life care.

Conclusion: There is a paucity of ACP documentation and identification of DPOA among LT candidates, despite patients reporting readiness to complete ACP and appoint a DPOA. These results reveal an opportunity for tools to facilitate discussions around ACP between clinicians, patients, and their caregivers.
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http://dx.doi.org/10.1007/s10620-020-06369-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714700PMC
May 2021

Identifying an Optimal Liver Frailty Index Cutoff to Predict Waitlist Mortality in Liver Transplant Candidates.

Hepatology 2021 Mar 30;73(3):1132-1139. Epub 2020 Oct 30.

Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Background And Aims: Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality.

Approach And Results: Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79.

Conclusions: LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.
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http://dx.doi.org/10.1002/hep.31406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710552PMC
March 2021

Association of motivations and barriers with participation and performance in a pedometer-based intervention.

Nephrol Dial Transplant 2020 08;35(8):1405-1411

Division of Nephrology, Hennepin County Medical Center, Minneapolis, MN, USA.

Background: A randomized trial of a pedometer-based intervention with weekly activity goals led to increased walking among dialysis patients. However, the association of participant-expressed motivations and barriers to participation and performance in such an intervention has not been determined.

Methods: Thirty dialysis patients were randomized to a 12-week pedometer-based intervention with weekly step goals. Participants were asked about motivations and barriers to the increasing activity via weekly semi-scripted telephone interviews. We examined the association of these motivations and barriers with achieving weekly goals, reaching overall targets and increasing steps through multivariable linear and logistic regression analyses adjusted for age, sex, body mass index, dialysis modality and baseline steps.

Results: The most common motivations were desire to maintain/improve functional ability (30%) and activity (30%). The most common barriers were health-related (33%). Motivation to maintain/improve functional ability was associated with achieving weekly goals 17.9% more often [95% confidence interval (CI) 1.7-34.2] and with a greater increase in steps (1524 steps; 95% CI 61-2989) than those lacking this motivation. Experiencing a health-related barrier was not associated with the decreased achievement of weekly goals but was associated with lower odds of reaching overall targets (odds ratio = 0.06; 95% CI 0.01-0.53) and a smaller increase in steps (-1640 steps, 95% CI -3244 to -36). No patients who reported weather/environmental barriers or safety concerns reached overall targets.

Conclusions: Participants who express a desire to maintain/improve functional ability may be particularly suited for activity interventions. Health-related setbacks should be met with revised goals. Reporting environmental or safety concerns may merit lowering overall targets.
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http://dx.doi.org/10.1093/ndt/gfaa047DOI Listing
August 2020