Refractory Cytomegalovirus Colitis Followed by De Novo Inflammatory Bowel Disease Post-Orthotopic Liver Transplantation.

Cytomegalovirus (CMV) and inflammatory bowel disease (IBD) are both immune-mediated complications that affect orthotopic liver transplantation patients. In this report, we present a 60-year-old man who underwent orthotopic liver transplantation for cryptogenic cirrhosis with serologies notable for CMV-seropositive donor and seronegative recipient. His post-transplant course was initially complicated by probable refractory CMV colitis. However, his gastrointestinal symptoms persisted, eventually leading to a diagnosis of post-transplant de novo IBD. The discussion highlights theories regarding the association between CMV and IBD, a topic that has been widely debated for decades.

Physical Activity and Nonalcoholic Fatty Liver Disease: A Roundtable Statement from the American College of Sports Medicine.

ABSTRACT: Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist.

American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable report on physical activity and nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD. APPROACH AND RESULTS: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. CONCLUSIONS: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.

Loneliness in adults awaiting liver transplantation at 7 U.S. transplant centers.

INTRODUCTION: Loneliness, "a subjective feeling of being isolated", is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). METHODS: We surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; "lonely"=total ≥5. Liver Frailty Index (LFI) assessed frailty; "frail"=LFI≥4.4. Logistic regression associated loneliness and co-variables. RESULTS: Of 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for "lonely". Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness. CONCLUSION: Loneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population. Clinical Trial Registry Website: https://clinicaltrials.gov Trial Number: NCT03228290.

Frailty and the Risk of Acute Kidney Injury Among Patients With Cirrhosis.

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 . Our primary outcome, AKI, was defined as an increase in serum creatinine ≥0.3 mg/dL or a serum creatinine ≥1.5-fold increase. Wait-list mortality was defined as either a death on the wait list or removal for being too sick. We performed Cox regression analyses to estimate the hazard ratios (HRs) for AKI and wait-list mortality. Of 1,033 participants, 41% were frail and 23% had CKD. Twenty-one percent had an episode of AKI during follow-up. Frail versus nonfrail patients were more likely to develop AKI (25% vs. 19%) and wait-list mortality (21% vs. 13%) (P < 0.01 for each). In multivariable Cox regression, each of the following groups was associated with a higher risk of AKI as compared with not frail/no CKD: frail/no CKD (adjusted HR [aHR] = 1.87, 95% confidence interval [CI] = 1.29-2.72); not frail/CKD (aHR = 4.30, CI = 2.88-6.42); and frail/CKD (aHR = 4.85, CI = 3.33-7.07). We use a readily available metric, LFI, to identify those patients with cirrhosis most at risk for AKI. We highlight that serum creatinine and creatinine-based estimations of glomerular filtration rate may not fully capture a patient's vulnerability to AKI among the frail phenotype. Conclusion: Our work lays the foundation for implementing physical frailty in clinical practice to identify AKI earlier, implement reno-protective strategies, and expedite liver transplantation.

Cognitive Impairment and Physical Frailty in Patients With Cirrhosis.

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study.

BACKGROUND & AIMS: Cirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology. METHODS: Included were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; 'frail' = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness). RESULTS: Of 1,623 patients, rates of frailty differed by aetiology: 22% in chronic hepatitis C, 31% in alcohol-associated liver disease (ALD), 32% in non-alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic and 31% in 'other' (P < .001). In univariable logistic regression, ALD (OR 1.53, 95% CI 1.12-2.09), NAFLD (OR 1.64, 95% CI 1.18-2.29) and 'other' (OR 1.58, 95% CI 1.06-2.36) were associated with frailty. In multivariable logistic regression, only ALD (OR 1.40; 95% 1.01-1.94) and 'other' (OR 1.59; 95% 1.05-2.40) remained associated with frailty. A total of 281 (17%) patients died/were delisted for sickness. In multivariable competing risk regression, LFI was associated with waitlist mortality (sHR 1.05, 95% CI 1.03-1.06), but aetiology was not (P > .05 for each). No interaction between frailty and aetiology on the association with waitlist mortality was found (P > .05 for each interaction term). CONCLUSIONS: Frailty is more common in patients with ALD, NAFLD and 'other' aetiologies. However, frailty was associated with waitlist mortality independent of cirrhosis aetiology, supporting the applicability of frailty across all cirrhosis aetiologies.

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

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.

Wearables, Physical Activity, and Exercise Testing in Liver Disease.

Physical inactivity is a major cause of deterioration in all forms of advanced liver disease. It is especially important as a driver of the components of the metabolic syndrome, with nonalcoholic fatty liver disease rapidly becoming the dominant cause of liver-related death worldwide. Growing realization of the health benefits of moderate-to-vigorous physical activity has captured the interest of persons who desire to improve their health, including those at risk for chronic liver injury. They are increasingly adopting wearable activity trackers to measure the activity that they seek to improve. Improved physical activity is the key lifestyle behavior that can improve cardiorespiratory fitness, which is most accurately measured with cardiopulmonary exercise testing (CPET). CPET is showing promise to identify risk and predict outcomes in transplant hepatology. Team effort among engaged patients, social support networks, and clinicians supported by web-based connectivity is needed to fully exploit the benefits of physical activity tracking.

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

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.

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

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.

Direct-Acting Antivirals and Organ Transplantation: Is There Anything We Can't Do?

The opioid epidemic has resulted in an increase in organ donors with hepatitis C virus (HCV) infection in the United States. With the development of direct-acting antiviral regimens that offer high sustained virologic response rates even in the setting of immunosuppression after transplantation, these HCV-viremic organs are now being offered to transplant candidates with or without preexisting HCV infection. Strategies for HCV treatment with HCV-viremic organs have included delayed and preemptive approaches. This review will discuss key studies in the different solid organ transplants, recent reports of adverse events, and ethical and regulatory considerations. The efficacy of current HCV therapies has created this important opportunity to improve survival for patients with end-organ failure through greater access to organ transplantation and decreased waitlist mortality rate.

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

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.

Use of Skeletal Muscle Index as a Predictor of Wait-List Mortality in Patients With End-Stage Liver Disease.

The aim of this study is to validate a proposed definition of sarcopenia in predicting wait-list mortality. We retrospectively evaluated 355 adults (age ≥18 years) with cirrhosis listed for first-time LT from January 1, 2010, to April 1, 2018 from our center. Demographic, laboratory, and outcome data were collected in conjunction with computed tomography scans performed within 3 months of listing. Using imaging analysis software, the skeletal muscle index (SMI), which is a marker for sarcopenia-related mortality, was calculated. A survival analysis was performed to evaluate the association of the proposed sarcopenia definition of SMI <50 cm2 /m2 for men or <39 cm2 /m2 for women with wait-list mortality or delisting. Median SMI was 54.1 cm2 /m2 (range, 47-60 cm2 /m2 ). A total of 61 (17.2%) patients exhibited sarcopenia according to the proposed threshold, and 24.6% (57/232) of men were sarcopenic compared with 3.3% (4/123) of women (P < 0.001). Mean (standard deviation [SD]) SMI was also higher for men (56.6 ± 9.6 cm2 /m2 ) than for women (50.7 ± 8.0 cm2 /m2 ; P < 0.001). Median follow-up time among patients was 2.1 months (0-12 months), and 30 events were observed (hazard ratio, 0.98; 95% confidence interval, 0.95-1.02; P = 0.41). There was no statistically significant difference in time on the waiting list between patients with and without sarcopenia (P = 0.89) as defined at the threshold. Using the prespecified definitions of sarcopenia based on SMI, there was no statistically significant difference in mortality and delisting from the transplant waiting list between patients with and without sarcopenia in this population. Practice and region-specific patterns for pretransplant selection and median Model for End-Stage Liver Disease at transplant may affect SMI as a predictor of wait-list mortality.

Changes in frailty are associated with waitlist mortality in patients with cirrhosis.

BACKGROUND & AIMS: To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation. METHODS: Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk. RESULTS: We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35-3.09). CONCLUSION: Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty. LAY SUMMARY: Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.

Transplant Outcomes in Older Patients With Nonalcoholic Steatohepatitis Compared to Alcohol-related Liver Disease and Hepatitis C.

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) are waitlisted at older ages than individuals with other liver diseases, but the effect of age on liver transplantation (LT) outcomes in this population and whether it differs from other etiologies is not known. We aimed to evaluate the impact of age on LT outcomes in NASH. METHODS: The United Network for Organ Sharing database was used to identify adults with NASH, hepatitis C virus (HCV) infection, and alcohol-related liver disease (ALD) listed for LT during 2004-2017. Patients were split into age groups (18-49, 50-54, 55-59, 60-64, 65-69, ≥70), and their outcomes were compared. RESULTS: From 2004 to 2017, 14 197 adults with NASH were waitlisted, and the proportion ≥65 increased from 15.8% to 28.9%. NASH patients ages 65-69 had an increased risk of waitlist and posttransplant mortality compared to younger groups, whereas the outcomes in ages 60-64 and 55-59 were similar. The outcomes of individuals with NASH were similar to patients of the same age group with ALD or HCV. Functional status and dialysis were predictors of posttransplant mortality in individuals ≥65 with NASH, and cardiovascular disease was the leading cause of death. CONCLUSIONS: Older NASH patients (≥65) have an increased risk of waitlist and posttransplant mortality compared to younger individuals, although outcomes were similar to patients with ALD or HCV of corresponding age. These individuals should be carefully evaluated prior to LT, considering their functional status, renal function, and cardiovascular risk. Further studies are needed to optimize outcomes in this growing population of transplant candidates.

Impact of Malnutrition on Outcomes in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt Insertion.

BACKGROUND: Malnutrition is common in patients with cirrhosis and is associated with poor outcomes after hepatic resection and liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) is performed for complications of cirrhosis. AIM: To assess the impact of malnutrition on TIPS outcomes. METHODS: A retrospective analysis was performed using the Healthcare Cost and Utilization Project: National Inpatient Sample database for TIPS procedures from 2005 to 2014. The primary end point was in-hospital mortality. The association of specific malnutrition diagnostic codes and race-ethnicity on mortality was evaluated with survey-weighted logistic regression adjusted for age, gender, admission type, insurance payer, hospital region, comorbidities, and length of stay (LOS). RESULTS: From 2005 to 2014, an estimated 53,207 (95% CI 49,330-57,085) admissions with TIPS occurred. A diagnosis of malnutrition was present in 11%. In-hospital death post-TIPS occurred in 15.0% versus 10.7% (p value < 0.001) of patients with and without malnutrition, respectively. Patients with malnutrition had longer post-procedural LOS (median 6.7 vs. 2.9 days, p value < 0.001) and greater total hospital charges (median $144,752 vs. $79,781, p value < 0.001) and were more likely to be discharged to a skilled nursing facility (21.6% vs. 9.7%) than patients without malnutrition. Patients with malnutrition had increased odds of mortality (OR 1.31, 95% CI 1.07, 1.59) compared to patients with no malnutrition. CONCLUSION: Malnutrition was associated with worse outcomes after TIPS. Further research is needed to understand the mechanism of malnutrition in post-procedure outcomes and the ability of interventions for nutritional optimization to improve outcomes.