Publications by authors named "Matthew R Kappus"

23 Publications

  • Page 1 of 1

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 04;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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ajg.0000000000001113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178511PMC
April 2021

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

Semin Liver Dis 2021 May 14;41(2):128-135. Epub 2021 Jan 14.

Healthy Lifestyle Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1716564DOI Listing
May 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2020.5674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774043PMC
March 2021

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

J Infect Dis 2020 11;222(Suppl 9):S794-S801

Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa420DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.25863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960487PMC
November 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710552PMC
March 2021

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

Liver Transpl 2020 09 6;26(9):1090-1099. Epub 2020 Aug 6.

Division of Gastroenterology and Hepatology, Duke University Medical Center, Durham, NC.

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 cm /m for men or <39 cm /m for women with wait-list mortality or delisting. Median SMI was 54.1 cm /m (range, 47-60 cm /m ). 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 cm /m ) than for women (50.7 ± 8.0 cm /m ; 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.25802DOI Listing
September 2020

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

J Hepatol 2020 09 30;73(3):575-581. Epub 2020 Mar 30.

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

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2020.03.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438309PMC
September 2020

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

Transplantation 2020 06;104(6):e164-e173

Division of Gastroenterology, Department of Medicine, Duke University, Durham, NC.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003219DOI Listing
June 2020

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

Dig Dis Sci 2020 11 21;65(11):3332-3340. Epub 2020 Jan 21.

Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC 3923, Durham, NC, 27710, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-019-06038-yDOI Listing
November 2020

Relative Sarcopenia With Excess Adiposity Predicts Survival After Transjugular Intrahepatic Portosystemic Shunt Creation.

AJR Am J Roentgenol 2020 01 31;214(1):200-205. Epub 2019 Oct 31.

Department of Radiology, Division of Abdominal Imaging, Duke University Medical Center, Durham, NC.

The purpose of this study was to assess the impact of relative sarcopenia with excess adiposity on mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, patients underwent abdominal CT scans within 100 days before or 30 days after TIPS creation. Subcutaneous and visceral adipose tissue and muscle were segmented at the L3 vertebral level. Relative sarcopenia with excess adiposity was defined as the lowest sex-specific quartile of muscle area divided by muscle plus adipose. Dates of death, liver transplantation, TIPS occlusion, and hepatic encephalopathy (HE) after TIPS creation were identified. Mortality was evaluated using competing risks survival analysis. Number of HE episodes and time to first episode were analyzed using negative binomial regression and competing risks survival analysis, respectively. A total of 141 patients (91 men; mean age, 56 years) were included in this study. In univariate analyses, Model for End-Stage Liver Disease (MELD) score (hazard ratio [HR], 1.09 per point; CI, 1.05-1.13; < 0.001) and relative sarcopenia with excess adiposity (HR, 2.70; CI, 1.55-4.69; < 0.001) were significant risk factors for shorter survival after TIPS. In multivariate analysis, both MELD score (HR, 1.09; CI, 1.03-1.15; = 0.003) and relative sarcopenia with excess adiposity (HR, 2.65; CI, 1.56-4.51; < 0.001) were significant predictors of worse survival. The C-index at 30 days was 0.71 for MELD score, 0.72 for relative sarcopenia with excess adiposity, and 0.80 for a model including both. There was no association between relative sarcopenia with excess adiposity and number of HE episodes (incidence rate ratio, 1.08; CI, 0.49-2.40; = 0.84) or time to first HE episode (HR, 0.89; CI, 0.51-1.54; = 0.67). Relative sarcopenia with excess adiposity is a risk factor for mortality after TIPS and contributes additional prognostic information beyond MELD score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.19.21655DOI Listing
January 2020

Association Between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index.

JAMA Surg 2019 12;154(12):1103-1109

Department of Medicine, University of California, San Francisco.

Importance: Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements.

Objective: To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates.

Design, Setting, And Participants: A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma.

Exposures: At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0).

Main Outcomes And Measures: The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI.

Results: Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P = .57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P = .04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P = .06; P = .75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P < .001; P = .047 for interaction).

Conclusions And Relevance: This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2019.2845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739734PMC
December 2019

Frailty in liver transplantation: An expert opinion statement from the American Society of Transplantation Liver and Intestinal Community of Practice.

Am J Transplant 2019 07 8;19(7):1896-1906. Epub 2019 May 8.

Cirrhosis Care Clinic, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.

Frailty has emerged as a powerful predictor of outcomes in patients with cirrhosis and has inevitably made its way into decision making within liver transplantation. In an effort to harmonize integration of the concept of frailty among transplant centers, the AST and ASTS supported the efforts of our working group to develop this statement from experts in the field. Frailty is a multidimensional construct that represents the end-manifestation of derangements of multiple physiologic systems leading to decreased physiologic reserve and increased vulnerability to health stressors. In hepatology/liver transplantation, investigation of frailty has largely focused on physical frailty, which subsumes the concepts of functional performance, functional capacity, and disability. There was consensus that every liver transplant candidate should be assessed at baseline and longitudinally using a standardized frailty tool, which should guide the intensity and type of nutritional and physical therapy in individual liver transplant candidates. The working group agreed that frailty should not be used as the sole criterion for delisting a patient for liver transplantation, but rather should be considered one of many criteria when evaluating transplant candidacy and suitability. A road map to advance frailty in the clinical and research settings of liver transplantation is presented here.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814290PMC
July 2019

Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study.

Gastroenterology 2019 05 19;156(6):1675-1682. Epub 2019 Jan 19.

Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.

Background & Aims: Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated Liver Frailty Index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality.

Methods: Adults without hepatocellular carcinoma who were on the liver transplantation waitlist at 9 centers in the United States (N = 1044) were evaluated using the LFI; LFI scores of at least 4.5 indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate sub-hazard ratios (sHRs) of waitlist mortality (death or removal from the waitlist).

Results: Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio 1.56, 95% confidence interval [CI] 1.15-2.14) or HE (odd ratio 2.45, 95% CI 1.80-3.33) than for those without these features. Larger proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared with patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR 1.52, 95% CI 1.14-2.05), HE (sHR 1.84, 95% CI 1.38-2.45), and frailty (sHR 2.38, 95% CI 1.77-3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR 1.82, 95% CI 1.31-2.52); ascites and HE were not.

Conclusions: Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be used to objectively quantify risk of death related to frailty-in excess of liver disease severity-in patients with cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2019.01.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475483PMC
May 2019

Poor performance of psoas muscle index for identification of patients with higher waitlist mortality risk in cirrhosis.

J Cachexia Sarcopenia Muscle 2018 12 29;9(6):1053-1062. Epub 2018 Sep 29.

Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada.

Background: Sarcopenia, characterized by low muscle mass, associates with mortality in patients with cirrhosis. Skeletal muscle area in a single computed tomography image at the level of the third lumbar vertebrate (L3) is a valid representative of whole body muscle mass. Controversy remains regarding applicability of psoas muscle to identify patients at greater risk of mortality. We aimed to determine psoas muscle index (PMI) association with skeletal muscle index (SMI) and to evaluate the capacity of PMI to predict liver transplant waitlist mortality.

Methods: We evaluated listed adult patients with cirrhosis from 2012 to 2013 at four North American liver transplant centres. From L3 computed tomography images within 3 months of listing, we determined SMI and PMI expressed by cm /m . Low SMI was defined as SMI <39 cm /m in women and <50 cm /m in men as published by us earlier. Cut-offs for PMI to predict mortality were established using a receiver-operating characteristic analysis. Mortality predictors were determined using competing-risk analysis with reported results as subdistribution hazard ratios (sHRs).

Results: Of 353 waitlist candidates, 68% were men, mean age 56 ± 9 years, and Model for End-stage Liver Disease of 16 ± 8 points. Low SMI was present more frequently in men than women (51 vs. 36%, P = 0.02). Moderately strong correlation between SMI and PMI was observed (r > 0.7, P < 0.001). Low PMI (males < 5.1 cm /m ; females < 4.3 cm /m ) yielded poor and moderate concordance with low SMI in men and women, respectively (Kappa coefficient 0.31 and 0.63). SMI (39 ± 9 vs. 43 ± 7 cm /m ; P = 0.009) and PMI (4.4 ± 1.3 vs. 5.2 ± 1.1 cm /m ; P = 0.001) were lower in women who died and/or were delisted (compared with non-deceased patients) whereas men who died and/or were delisted had only lower SMI (47 ± 7 vs. 51 ± 9 cm /m ; P = 0.003), but not PMI compared with non-deceased patients. In women, both SMI (sHR 0.94, P = 0.048) and PMI (sHR 0.58, P = 0.002) were predictors of mortality, while in men, SMI was significant (sHR 0.95, P = 0.001) and PMI showed a trend to be (sHR 0.85, P = 0.09) associated with mortality. Overall, 104 patients (29%) were misclassified between SMI and PMI categories. Using PMI cut-offs, 66% and 28% of low SMI men and women, who have a higher risk of mortality, were incorrectly classified as low risk.

Conclusions: Skeletal muscle index is a more complete and robust measurement than PMI, especially in men with cirrhosis. Low PMI identifies an incomplete subset of patients at increased risk of mortality indicated by low SMI. Given the poor performance of PMI, SMI should not be substituted by PMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcsm.12349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240754PMC
December 2018

Patient and Caregiver Attitudes and Practices of Exercise in Candidates Listed for Liver Transplantation.

Dig Dis Sci 2018 12 3;63(12):3290-3296. Epub 2018 Sep 3.

Division of Gastroenterology and Hepatology, Mayo Clinic in Arizona, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA.

Background: Impaired physical capacity increases peri-liver transplant complications. Patient perceptions regarding exercise prior to transplantation are not known.

Aims: This study aimed to assess patient and caregiver activity levels, perceptions of willingness to exercise, and of provider advice.

Methods: Consecutive patients listed for liver transplant and caregivers presenting for routine outpatient visits were evaluated over a 3-month interval. Anonymous surveys adapted to patients and caregivers addressed the importance and safety of exercise, type and duration of exercise performed, barriers, willingness to wear a monitoring device, and perceived provider recommendations. Responses were logged on a Likert scale from 1 to 5.

Results: Three hundred and sixty-eight responses were received. Most participants perceived exercise as important. Patients exercised three times per week for 30 min. Eighty percent endorsed walking (median response: 2-agree; IQR 1-2). Most did not jog, swim, cycle, or strength train. Fatigue, reported by 70%, was the major barrier (2, IQR 1-3). Over 90% of caregivers endorsed exercise as important (1-strongly agree, IQR 1-2) and encouraged exercise (median response 2, IQR 1-2). Over 60% of patients (median response 2, IQR 1-3) and caregivers (median response 2, IQR 2-3) felt providers encouraged exercise.

Conclusions: Patients and caregivers are willing to exercise to optimize physical fitness prior to liver transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-018-5271-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532051PMC
December 2018

Erratum to: Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise?

Curr Gastroenterol Rep 2016 Nov;18(11):57

Department of Medicine, School of Medicine, University of Louisville, Louisville, KY, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11894-016-0533-xDOI Listing
November 2016

Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise?

Curr Gastroenterol Rep 2016 Aug;18(8):43

Department of Medicine, School of Medicine, University of Louisville, Louisville, KY, USA.

Sarcopenia, a loss of muscle mass, is being increasingly recognized to have a deleterious effect on outcomes in patients with chronic liver disease. Factors related to diet and the inflammatory nature of chronic liver disease contribute to the occurrence of sarcopenia in these patients. Sarcopenia adversely influences quality of life, performance, morbidity, success of transplantation, and even mortality. Specific deficiencies in macronutrients (protein, polyunsaturated fatty acids) and micronutrients (vitamins C, D, and E, carotenoids, and selenium) have been linked to sarcopenia. Lessons learned from nutritional therapy in geriatric patient populations may provide strategies to manage sarcopenia in patients with liver disease. Combining diet modification and nutrient supplementation with an organized program of exercise may help ameliorate or even reverse the effects of sarcopenia on an already complex disease process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11894-016-0516-yDOI Listing
August 2016

Extrahepatic manifestations of acute hepatitis B virus infection.

Gastroenterol Hepatol (N Y) 2013 Feb;9(2):123-6

Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754772PMC
February 2013

Effect of obstructive sleep apnea on the sleep architecture in cirrhosis.

J Clin Sleep Med 2013 Mar 15;9(3):247-51. Epub 2013 Mar 15.

Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA 23249, USA.

Study Objectives: Sleep disturbances in cirrhosis are assumed to be due to hepatic encephalopathy (HE). The interaction between cirrhosis, prior HE, and obstructive sleep apnea (OSA) has not been evaluated. We aimed to evaluate the additional effect of cirrhosis with and without prior HE on the sleep architecture and perceived sleep disturbances of OSA patients.

Methods: A case-control review of OSA patients who underwent polysomnography (PSG) in a liver-transplant center was performed. OSA patients with cirrhosis (with/without prior HE) were age-matched 1:1 with OSA patients without cirrhosis. Sleep quality, daytime sleepiness, sleep quality, and sleep architecture was compared between groups.

Results: Forty-nine OSA cirrhotic patients (age 57.4 ± 8.3 years, model for end-stage liver disease (MELD) 8.3 ± 5.4, 51% HCV, 20% prior HE) were age-matched 1:1 to OSA patients without cirrhosis. Apnea-hypopnea index, arousal index, sleep efficiency, daytime sleepiness, and effect of sleepiness on daily activities were similar between OSA patients with/ without cirrhosis. Sleep architecture, including %slow wave sleep (SWS), was also not different between the groups. MELD was positively correlated with time in early (N1) stage (r = 0.4, p = 0.03). All prior HE patients (n = 10) had a shift of the architecture towards early, non-restorative sleep (higher % [N2] stage [66 vs 52%, p = 0.005], lower % SWS [0 vs 29%, p = 0.02], lower REM latency [95 vs 151 minutes, p = 0.04]) compared to the rest. Alcoholic etiology was associated with higher latency to N1/N2 sleep, but no other effect on sleep architecture was seen.

Conclusions: OSA can contribute to sleep disturbance in cirrhosis and should be considered in the differential of sleep disturbances in cirrhosis. Prior HE may synergize with OSA in worsening the sleep architecture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.2488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578691PMC
March 2013

Tetomilast: new promise for phosphodiesterase-4 inhibitors?

Expert Opin Investig Drugs 2012 Dec 8;21(12):1845-9. Epub 2012 Oct 8.

Virginia Commonwealth University Medical Center, VCUHS Center for Inflammatory Bowel Disease, MCV Campus, Box 980341, Richmond, VA 23298-0341, USA.

Introduction: Tetomilast is a novel thiazole phosphodiesterase-4 (PDE-4) inhibitor, which may prove useful in both the treatment of inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD). Here, the authors review the pharmacology of the drug, and offer critical review of the available data for use of tetomilast in the treatment of IBD.

Areas Covered: Peer-reviewed publications, including Phase I and II clinical trials, all other formats included.

Expert Opinion: Tetomilast may be beneficial in IBD. Small differences in molecules and in recombinant proteins can translate into substantial differences in clinical effects and toxicity in IBD. This is a reasonable approach when exploring new options like tetomilast.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1517/13543784.2012.732065DOI Listing
December 2012

Covert hepatic encephalopathy: not as minimal as you might think.

Clin Gastroenterol Hepatol 2012 Nov 19;10(11):1208-19. Epub 2012 Jun 19.

Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia 23249, USA.

Hepatic encephalopathy (HE) is a serious neuropsychiatric and neurocognitive complication of acute and chronic liver disease. Symptoms are often overt (confusion, disorientation, ataxia, or coma) but can also be subtle (difficulty with cognitive abilities such as executive decision-making and psychomotor speed). There is consensus that HE is characterized as a spectrum of neuropsychiatric symptoms in the absence of brain disease, ranging from overt HE (OHE) to minimal HE (MHE). The West Haven Criteria are most often used to grade HE, with scores ranging from 0-4 (4 being coma). However, it is a challenge to diagnose patients with MHE or grade 1 HE; it might be practical to combine these entities and name them covert HE for clinical use. The severity of HE is associated with the stage of liver disease. Although the pathologic mechanisms of HE are not well understood, they are believed to involve increased levels of ammonia and inflammation, which lead to low-grade cerebral edema. A diagnosis of MHE requires dedicated psychometric tests and neurophysiological techniques rather than a simple clinical assessment. Although these tests can be difficult to perform in practice, they are cost effective and important; the disorder affects patients' quality of life, socioeconomic status, and driving ability and increases their risk for falls and the development of OHE. Patients with MHE are first managed by excluding other causes of neurocognitive dysfunction. Therapy with gut-specific agents might be effective. We review management strategies and important areas of research for MHE and covert HE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2012.05.026DOI Listing
November 2012

Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests).

Clin Liver Dis 2012 Feb;16(1):43-55

Division of Gastroenterology, Hepatology and Nutrition, McGuire VA Medical Center, Virginia Commonwealth University, 1201 Broad Rock Boulevard, Richmond, VA 23249, USA.

Minimal hepatic encephalopathy (MHE) is associated with a high risk of development of overt hepatic encephalopathy, impaired quality of life, and driving accidents. The detection of MHE requires specialized testing because it cannot, by definition, be diagnosed on standard clinical examination. Psychometric and neurophysiologic techniques are often used to test for MHE. Paper-pencil psychometric batteries and computerized tests have proved useful in diagnosing MHE and predicting its outcomes. Neurophysiologic tests also provide useful information. The diagnosis of MHE is an important issue for clinicians and patients alike. Testing strategies depend on the normative data available, patient comfort, and local expertise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cld.2011.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312030PMC
February 2012