Visceral adiposity in cirrhosis: Association with disease severity and impact of liver transplantation.

BACKGROUND: Changes in adipose tissue distribution in liver cirrhosis are poorly characterized and may affect clinical outcomes. METHODS: Adult liver transplant (LT) January 2008-August 2017 recipients with abdominal MRI within 6 months pre-LT were retrospectively assessed. Visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle area (cm2) were determined at L3. Visceral-to-subcutaneous adipose tissue ratio (VSR) was used to define relative adipose distribution, stratified by sex. Correlation was tested with Pearson. Body composition measures were compared by Child-Turcotte-Pugh (CTP) class, before and after LT, and evaluated as predictors of clinical outcomes. RESULTS: A total of 318 patients were studied. Mean age was 56 years, 33.64% were female, and 47.80% had CTP C cirrhosis. CTP C was associated with a 0.42-point increase in VSR compared with CTP A (95% CI = 0.13-0.71, p < 0.01), adjusting for age, sex, diabetes, and HCC. Among the 79 (24.84%) patients with repeat MRI 1-2 years after LT, VSR significantly improved from before LT (1.31 vs. 0.95, p < 0.01). In adjusted analysis, CTP C was associated with a 0.86-point decrease in post-LT VSR compared with pre-LT VSR (95% CI = -1.27 to -0.44, p < 0.01). Body mass index poorly correlated with VSR before and after LT. Elevated pre-LT VSR trended toward an association with a 7.17-point decrease in pre-LT glomerular filtration rate (95% CI = -14.35 to -0.02, p = 0.05), adjusting for CTP C, age, sex, diabetes, hypertension, pre-LT sarcopenia, and hepatocellular carcinoma. Elevated pre-LT VSR did not affect 3-year post-LT mortality (log-rank p = 0.24). CONCLUSIONS: Poorly represented by body mass index, visceral adiposity is increased in cirrhosis and is associated with CTP class. However, this adipose redistribution may be modifiable by LT.

Factors associated with cardiovascular events after simultaneous liver-kidney transplant from the US Multicenter Simultaneous Liver-Kidney Transplant Consortium.

Cardiovascular disease is a leading complication after both liver and kidney transplantation. Factors associated with and rates of cardiovascular events (CVEs) after simultaneous liver-kidney transplant (SLKT) are unknown. This was a retrospective cohort study of adult SLKT recipients between 2002 and 2017 at six centers in six United Network for Organ Sharing regions in the US Multicenter SLKT Consortium. The primary outcome was a CVE defined as hospitalization due to acute coronary syndrome, arrhythmia, congestive heart failure, or other CV causes (stroke or peripheral vascular disease) within 1 year of SLKT. Among 515 SLKT subjects (mean age ± SD, 55.4 ± 10.6 years; 35.5% women; 68.1% White), 8.7% had a CVE within 1 year of SLKT. The prevalence of a CVE increased from 3.3% in 2002-2008 to 8.9% in 2009-2011 to 14.0% in 2012-2017 ( p  = 0.0005). SLKT recipients with a CVE were older (59.9 vs. 54.9 years, p < 0.0001) and more likely to have coronary artery disease (CAD) (37.8% vs. 18.4%, p  = 0.002) and atrial fibrillation (AF) (27.7% vs. 7.9%, p  = 0.003) than those without a CVE. There was a trend toward older age by era of SLKT ( p  = 0.054). In multivariate analysis adjusted for cardiac risk factors at transplant, age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02, 1.11), CAD (OR, 3.62; 95% CI, 1.60, 8.18), and AF (OR, 2.36; 95% CI, 1.14, 4.89) were associated with a 1-year CVE after SLKT. Conclusion : Among SLKT recipients, we observed a 4-fold increase in the prevalence of 1-year CVEs over time. Increasing age, CAD, and AF were the main potential explanatory factors for this trend independent of other risk factors. These findings suggest that CV risk protocols may need to be tailored to this high-risk population.

Predictors of Length of Stay and Mortality During Simultaneous Liver-Kidney Transplant Index Admission: Results From the US-Multicenter SLKT Consortium.

Length of stay (LOS) during index solid organ transplant impacts morbidity and healthcare costs. To date, there are no studies evaluating characteristics and outcomes of simultaneous liver-kidney transplant (SLKT) index hospitalization. We examined factors associated with LOS and mortality during index SLKT admission. Methods: Adult SLKT recipients between 2002 and 2017 at 6 transplant centers across 6 UNOS regions were retrospectively enrolled in the US-Multicenter SLKT Consortium. Multivariable regression analyses assessed predictors of SLKT LOS and death during index admission. Results: Median age of cohort (N = 570) was 58 y (interquartile range: 51-64); 63% male, 75% White, 32.3% hepatitis C, 23.3% alcohol-related, 20.1% nonalcoholic steatohepatitis with median MELD-Na at SLKT 28 (23-34). Seventy-one percent were hospitalized at the time of SLKT with median LOS pretransplant of 10 d. Majority of patients were discharged alive (N = 549; 96%)' and 36% were discharged to subacute rehab facility. LOS for index SLKT was 19 d (Q1: 10, Q3: 34 d). Female sex (P = 0.003), Black race (P = 0.02), advanced age (P = 0.007), ICU admission at time of SLKT (P = 0.03), high MELD-Na (P = 0.003), on cyclosporine during index hospitalization (P = 0.03), pre-SLKT dialysis (P < 0.001), and kidney delayed graft function (P < 0.001) were the recipient factors associated with prolonged LOS during index SLKT hospitalization. Prolonged LOS also contributed to overall mortality (HR = 1.007; P = 0.03). Conclusions: Despite excellent survival, index SLKT admission was associated with high-resource utilization with more than half the patients with LOS >2 wk and affected overall patient survival. Further investigation is needed to optimize healthcare resources for these patients in a financially strained healthcare landscape.

A Prediction Model Incorporating Peripheral Eosinopenia as a Novel Risk Factor for Death After Hospitalization for Clostridioides difficile Infection.

BACKGROUND AND AIMS: Clostridioides difficile infection (CDI) is associated with a range of outcomes, and existing prediction models for death among patients with CDI are imprecise. Peripheral eosinopenia has been proposed as a novel risk factor for death among patients with CDI but has not been incorporated into prediction models. This study aimed to develop and validate a prediction model for death among patients hospitalized with CDI that incorporated peripheral eosinopenia. METHODS: Eosinopenia was defined as 0 eosinophils/µL on the soonest peripheral blood drawn within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of 3 large, unaffiliated hospital networks, tested positive for CDI by stool polymerase chain reaction, and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days. RESULTS: There were 4518 unique hospitalized adults with CDI included (2142 in the derivation cohort and 2376 in the validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts. In the validation cohort, the factors most strongly associated with death were eosinopenia (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.77-3.50), albumin <3 g/dL (aOR 3.26, 95% CI 2.13-3.49), and creatinine >1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A 6-variable clinical prediction model was developed that improved on existing classification schemes for CDI severity (area under the receiver operating characteristic curve of 0.75 vs 0.68). CONCLUSION: Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification.

Burden of early hospitalization after simultaneous liver-kidney transplantation: Results from the US Multicenter SLKT Consortium.

The burden of early hospitalization (within 6 months) following simultaneous liver-kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional on 6-month survival. We used data from the US Multicenter SLKT Consortium cohort study of all adult SLKT recipients between 2002 and 2017 who were discharged alive following SLKT. We used Poisson regression to model rates of early hospitalizations after SLKT. Cox regression was used to identify risk factors associated with mortality conditional on survival at 6 months after SLKT. Median age (N = 549) was 57.7 years (interquartile range [IQR], 50.6-63.9) with 63% males and 76% Whites; 33% had hepatitis C virus, 20% had non-alcohol-associated fatty liver disease, 23% alcohol-associated liver disease, and 24% other etiologies. Median body mass index (BMI) and Model for End-Stage Liver Disease-sodium scores were 27.2 kg/m2 (IQR, 23.6-32.2 kg/m2 ) and 28 (IQR, 23-34), respectively. Two-thirds of the cohort had at least one hospitalization within the first 6 months of SLKT. Age, race, hospitalization at SLKT, diabetes mellitus, BMI, and discharge to subacute rehabilitation (SAR) facility after SLKT were independently associated with a high incidence rate ratio of early hospitalization. Number of hospitalizations within the first 6 months did not affect conditional survival. Early hospitalizations after SLKT were very common but did not affect conditional survival. Although most of the risk factors for early hospitalization were nonmodifiable, discharge to SAR after initial SLKT was associated with a significantly higher incidence rate of early hospitalization. Efforts and resources should be focused on identifying SLKT recipients at high risk for early hospitalization to optimize their predischarge care, discharge planning, and long-term follow-up.

Individualized Provider Feedback Increased HIV and HCV Screening and Identification in a New York City Emergency Department.

Efforts to end the HIV and hepatitis C virus (HCV) epidemics begin with ascertainment of a person's infection status through screening. Despite its importance as a site of testing, missed opportunities for screening in the Emergency Department (ED) are common. We describe the impact of implementing an individualized provider feedback intervention on HIV and HCV testing in a quaternary ED. We conducted an interrupted time series analysis to evaluate the impact of the intervention on weekly HIV and HCV screening in an observational cohort of patients seeking care in the ED. The intervention included a physician champion individualized feedback with peer comparisons to all providers in the ED and an existing HIV/HCV testing and response team. Data were abstracted from the electronic medical record (EMR) for 30 weeks before, during, and after implementing the intervention. We used Poisson regression analysis to estimate changes in the weekly counts and rates of HIV and HCV testing. The incidence rate ratios (IRRs) of HIV testing were 1.94 [95% confidence interval (CI) 1.85-2.04] and 1.38 (95% CI 1.31-1.45) times higher for the intervention and post-intervention period compared with the pre-intervention period. The IRRs of HCV testing was 6.96 (95% CI 6.40-7.58) and 4.70 (95% CI 4.31-5.13) for the intervention and post-intervention periods. There were no meaningful differences in demographic characteristics during the observation period. The intervention meaningfully increased HIV and HCV testing volume and positive case detection, including testing in high-risk groups like young adults and individuals without prior testing. Although diminished, the intervention effect sustained in the 30-week period following implementation.

Temporal Trends and Evolving Outcomes After Simultaneous Liver-Kidney Transplantation: Results from the US SLKT Consortium.

We aimed to understand the contemporary changes in the characteristics and the determinants of outcomes among simultaneous liver-kidney transplantation (SLKT) recipients at 6 liver transplantation centers in the United States. We retrospectively enrolled SLKT recipients between 2002 and 2017 in the US Multicenter SLKT Consortium. We analyzed time-related trends in recipient characteristics and outcomes with linear regression and nonparametric methods. Clustered Cox regression determined the factors associated with 1-year and overall survival. We enrolled 572 patients. We found significant changes in the clinical characteristics of SLKT recipients: as compared with 2002, recipients in 2017 were older (59 versus 52 years; P < 0.001) and more likely to have chronic kidney disease (71% versus 33%; P < 0.001). There was a marked improvement in 1-year survival during the study period: 89% in 2002 versus 96% in 2017 (P < 0.001). We found that the drivers of 1-year mortality were SLKT year, hemodialysis at listing, donor distance, and delayed kidney allograft function. The drivers of overall mortality were an indication of acute kidney dysfunction, body mass index, hypertension, creatinine at SLKT, ventilation at SLKT, and donor quality. In this contemporary cohort of SLKT recipients, we highlight changes in the clinical characteristics of recipients. Further, we identify the determinants of 1-year and overall survival to highlight the variables that require the greatest attention to optimize outcomes.

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

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 m2 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 (ß = -6.22 ± 2.16 mL/minute/1.73 m2 ; P = 0.004), NASH (ß = -7.27 ± 3.27 mL/minute/1.73 m2 ; P = 0.027), and delayed kidney graft function (ß = -7.25 ± 2.26 mL/minute/1.73 m2 ; 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.

Successful liver transplantation in a patient recovered from COVID-19.

Transplantation in potential candidates who have recently recovered from COVID-19 is a challenge with uncertainties regarding the diagnosis, multi-organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID-19. At the time of transplant, he was SARS-CoV-2 PCR negative for 24 days and had a MELD score of 33. His post-operative course was complicated by acute rejection which responded to intense immune-suppression using T-cell depletion and steroids. He was discharged with normal end-organ function and no evidence of any active infection including COVID-19. Prospective organ transplant recipients who have recovered from COVID-19 can be considered for transplantation after careful pre-transplant evaluation, donor selection, and individualized risk-benefit analysis.

Does Addition of Intravenous Metronidazole to Oral Vancomycin Improve Outcomes in Clostridioides difficile Infection?

BACKGROUND: Guidelines recommend adding intravenous (IV) metronidazole to oral vancomycin for fulminant Clostridioides difficile infection (CDI). In this study, we compared dual therapy with IV metronidazole and vancomycin vs vancomycin monotherapy. We assessed prevalence of use and effectiveness of dual therapy in nonfulminant and fulminant CDI. METHODS: This was a 2-center retrospective study conducted from 2010 to 2018. Adult inpatients were included if they had a positive C. difficile polymerase chain reaction (PCR) performed on an unformed stool and received vancomycin within 2 days of testing. Patients were classified as having received dual therapy if IV metronidazole was given within the same time window, and otherwise classified as vancomycin monotherapy. The primary outcome was death or colectomy within 90 days after the index test. Logistic regression modeling was used to adjust for CDI severity and other established predictors of CDI outcomes. CDI recurrence was examined as a secondary outcome, adjusting for death as a competing risk. RESULTS: The study included 2114 patients (dual therapy, 993; monotherapy, 1121); 23% met the primary outcome. There was no association between dual therapy and the primary outcome (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], .79-1.45), which remained true when the analysis was restricted to patients with fulminant CDI (aOR, 1.17; 95% CI, .65-2.10). There was also no association between dual therapy and CDI recurrence. CONCLUSIONS: Dual therapy with IV metronidazole and vancomycin was common for nonfulminant and fulminant CDI but was not associated with improved outcomes compared with vancomycin alone.

Clostridioides difficile infection and recurrence among 2622 solid organ transplant recipients.

BACKGROUND: Clostridioides difficile infection (CDI) is common after solid organ transplant (SOT) and is associated with high morbidity and mortality. METHODS: We assessed incidence, risk factors, and outcomes of CDI among SOT patients at a large multi-organ transplant center. Multivariable logistic regression was used to identify risk factors for initial and recurrent CDI. RESULTS: A total of 2622 SOT patients were included. 224 (8.5%) had CDI 1 year post-SOT. The highest incidence of CDI was among pancreas recipients (12.5%) followed by lung (11.7%), liver (11.0%), heart (10.8%), and kidney (5.8%). Median time to CDI was 56 days (range 2-354) post-SOT. About 64% of patients had severe CDI. About 56.3% were treated with metronidazole, 13.8% with oral vancomycin, and 28.6% with both. About 28.6% of patients had recurrent CDI. In multivariable modeling, lung transplant recipient status was the only significant predictor of recurrent CDI (OR 4.97, 95% CI 2.11-11.78, P < .001) controlling for age, severe CDI, and pre-SOT CDI. Post-SOT CDI nearly doubled the risk of mortality at one year, in particular among those with severe CDI. CONCLUSIONS: In summary, CDI is highly prevalent, occurs early in the post-transplant period, usually severe, with a high rate of recurrence, and associated with increased mortality within 1 year after transplant. The early post-transplant period may be a crucial window to reduce CDI rates.

Opioid epidemic and liver disease.

Opioid use in the United States and in many parts of the world has reached epidemic proportions. This has led to excess mortality as well as significant changes in the epidemiology of liver disease. Herein, we review the impact of the opioid epidemic on liver disease, focusing on the multifaceted impact this epidemic has had on liver disease and liver transplantation. In particular, the opioid crisis has led to a significant shift in incident hepatitis C virus infection to younger populations and to women, leading to changes in screening recommendations. Less well characterized are the potential direct and indirect hepatotoxic effects of opioids, as well as the changes in the incidence of hepatitis B virus infection and alcohol abuse that are likely rising in this population as well. Finally, the opioid epidemic has led to a significant rise in the proportion of organ donors who died due to overdose. These donors have led to an overall increase in donor numbers, but also to new considerations about the better use of donors with perceived or actual risk of disease transmission, especially hepatitis C. Clearly, additional efforts are needed to combat the opioid epidemic. Moreover, better understanding of the epidemiology and underlying pathophysiology will help to identify and treat liver disease in this high-risk population.