Early transplantation maximizes survival in severe acute-on-chronic liver failure: Results of a Markov decision process model.

BACKGROUND & AIMS: Uncertainties exist surrounding the timing of liver transplantation (LT) among patients with acute-on-chronic liver failure grade 3 (ACLF-3), regarding whether to accept a marginal quality donor organ to allow for earlier LT or wait for either an optimal organ offer or improvement in the number of organ failures, in order to increase post-LT survival. METHODS: We created a Markov decision process model to determine the optimal timing of LT among patients with ACLF-3 within 7 days of listing, to maximize overall 1-year survival probability. RESULTS: We analyzed 6 groups of candidates with ACLF-3: patients age ≤60 or >60 years, patients with 3 organ failures alone or 4-6 organ failures, and hepatic or extrahepatic ACLF-3. Among all groups, LT yielded significantly greater overall survival probability vs. remaining on the waiting list for even 1 additional day (p <0.001), regardless of organ quality. Creation of 2-way sensitivity analyses, with variation in the probability of receiving an optimal organ and expected post-transplant mortality, indicated that overall survival is maximized by earlier LT, particularly among candidates >60 years old or with 4-6 organ failures. The probability of improvement from ACLF-3 to ACLF-2 does not influence these recommendations, as the likelihood of organ recovery was less than 10%. CONCLUSION: During the first week after listing for patients with ACLF-3, earlier LT in general is favored over waiting for an optimal quality donor organ or for recovery of organ failures, with the understanding that the analysis is limited to consideration of only these 3 variables. LAY SUMMARY: In the setting of grade 3 acute-on-chronic liver failure (ACLF-3), questions remain regarding the timing of transplantation in terms of whether to proceed with liver transplantation with a marginal donor organ or to wait for an optimal liver, and whether to transplant a patient with ACLF-3 or wait until improvement to ACLF-2. In this study, we used a Markov decision process model to demonstrate that earlier transplantation of patients listed with ACLF-3 maximizes overall survival, as opposed to waiting for an optimal donor organ or for improvement in the number of organ failures.

Limitations of current liver donor allocation systems and the impact of newer indications for liver transplantation.

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty.

Rural-Urban Geographical Disparities in Hepatocellular Carcinoma Incidence Among US Adults, 2004-2017.

INTRODUCTION: To evaluate impact of urbanicity and household income on hepatocellular carcinoma (HCC) incidence among US adults. METHODS: HCC incidence was evaluated by rural-urban geography and median annual household income using 2004-2017 Surveillance, Epidemiology, and End Results data. RESULTS: Although overall HCC incidence was highest in large metropolitan regions, average annual percent change in HCC incidence was greatest among more rural regions. Individuals in lower income categories had highest HCC incidence and greatest average annual percent change in HCC incidence. DISCUSSION: Disparities in HCC incidence by urbanicity and income likely reflect differences in risk factors, health-related behaviors, and barriers in access to healthcare services.

Gender Differences Among Patients Hospitalized With Cirrhosis in the United States.

BACKGROUND AND AIMS: Gender disparities exist in outcomes among patients with cirrhosis. We sought to evaluate the role of gender on hospital course and in-hospital outcomes in patients with cirrhosis to help better understand these disparities. STUDY: We analyzed data from the National Inpatient Sample (NIS), years 2009 to 2013, to identify patients with any diagnosis of cirrhosis. We calculated demographic and clinical characteristics by gender, as well as cirrhosis complications. Our primary outcome was inpatient mortality. We used logistic regression to associate baseline characteristics and cirrhosis complications with inpatient mortality. RESULTS: Our cohort included 553,017 patients with cirrhosis admitted from 2009 to 2013. Women made up 39% of the cohort; median age was 57 with 66% non-Hispanic white. Women were more likely than men to have noncirrhosis comorbidities, including diabetes and hypertension but were less likely to have most cirrhosis complications, including ascites and variceal bleeding. Women were more likely than men to have acute bacterial infections (34.9% vs. 28.2%; P<0.001), and were less likely than men to die in the hospital on univariable (odds ratio, 0.88; 95% confidence interval, 0.86-0.90; P<0.001) and multivariable (odds ratio, 0.86; 95% confidence interval, 0.83-0.88; P<0.001) analysis. CONCLUSIONS: In patients hospitalized with cirrhosis, women have lower rates of hepatic decompensating events and higher rates of nonhepatic comorbidities and infections, resulting in lower in-hospital mortality. Understanding differences in indications for and disposition following hospitalization may help with the development of gender-specific cirrhosis management programs to improve long-term outcomes in women and men living with cirrhosis.

Osteoporotic Fracture Risk and Health Care Burden in Patients With Cirrhosis.

BACKGROUND AND AIMS: Risk factors for osteoporotic fracture as well as inpatient utilization and mortality have not been thoroughly studied in patients with cirrhosis. We analyzed data from a national database to determine fracture risk in patients with cirrhosis, specific risk factors, and the effect of fractures on health care utilization. METHODS: We performed an observational study using serial cross-sectional data to examine fracture-related hospitalizations of patients with cirrhosis using the National Inpatient Sample from 2012 to 2013. We collected data on fracture-related hospitalizations and utilization in the form of length of stay (LOS), total hospital costs, and inpatient mortality. We used multivariate regression to determine risk factors for fracture and fracture-related mortality. RESULTS: Patients with cirrhosis and an osteoporotic fracture had a mean LOS of 10.4 days and incurred $26,582 per hospitalization, which were statistically different from noncirrhotic patients with fracture (LOS: 6.60 d, cost: $17,918) and cirrhotic patients without fracture (LOS: 7.84 d, $18,912). Malnutrition was associated with increased odds of fracture [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.20-1.39] and inpatient mortality (OR, 1.40; 95% CI, 1.12-1.76). Obesity was protective against both fracture (OR, 0.78; 95% CI, 0.71-0.85) and fracture-related mortality (OR, 0.82; 95% CI, 0.59-1.14). CONCLUSIONS: Hospitalizations for osteoporotic fractures in patients with cirrhosis are a significant source of health care burden and mortality. More attention should be paid to screening patients with cirrhosis for low bone mass. Malnutrition is associated with increased fracture risk and fracture-related mortality, representing a modifiable risk factor worthy of addressing in patients with cirrhosis.

The impact of race and ethnicity on mortality and healthcare utilization in alcoholic hepatitis: a cross-sectional study.

BACKGROUND: Alcoholic Hepatitis (AH) is major source of alcohol-related mortality and health care expenditures in the United States. There is insufficient information regarding the role of race and ethnicity on healthcare utilization and outcomes for patients with AH. We aimed to determine whether there are racial/ethnic differences in resource utilization and inpatient mortality in patients hospitalized with AH. METHODS: We analyzed data from the Nationwide Inpatient Sample (NIS), years 2008-2011. We calculated demographic, clinical, and healthcare utilization characteristics by race. We then performed logistic regression and generalized linear modeling with gamma distribution (log link), respectively, to determine predictors of inpatient morality and total hospital costs (THC). RESULTS: We identified 11,304 AH patients from 2008 to 2011. Mean age was 47.0 years, and 62.1 % were male, 61.9 % were white, 9.8 % were black, and 9.7 % were Hispanic. Mean LOS was 6.3 days and significantly longer in whites (6.5 d) than both blacks (5.4 d) and Hispanics (5.9 d). In adjusted models, inpatient mortality was lower for blacks than for whites (adj. OR = 0.50; 95 % CI = 0.32-0.78). THC was significantly higher for Hispanics than whites (fold increase = 1.25; 95 % CI = 1.01-1.49). CONCLUSIONS: We identified differences in healthcare utilization and mortality by race/ethnicity. THC was significantly higher among Hispanics than for whites and blacks. We also demonstrated lower inpatient mortality in blacks compared to whites. These variations may implicate racial and ethnic differences in access to care, quality of care, severity of AH on presentation, or other factors.

Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions.

Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy.

Hospitalized Patients with Cirrhosis Should Be Screened for Clostridium difficile Colitis.

BACKGROUND: Clostridium difficile infection (CDI) is an important public health problem in hospitalized patients. Patients with cirrhosis are particularly at risk of increased associated morbidity, mortality, and healthcare utilization from CDI. AIM: The aim of this study was to assess the pharmacoeconomic impact of CDI screening on hospitalized patients with cirrhosis. METHODS: A Markov model was used to compare costs and outcomes of two strategies for the screening of CDI. The first strategy consisted of screening all patients for CDI and treating if detected (screening). In the second strategy, only patients found to have symptomatic CDI were treated (no screening). The probability of underlying CDI prevalence, symptomatic CDI infection, and likelihood of recurrent infection were varied in a sensitivity analysis. The costs of antibiotics and hospitalization were also assessed. Differences in outcome were expressed in ratio of the total costs associated with screening to the total costs associated without screening. RESULTS: The results of our model showed that screening for CDI was consistently associated with improved healthcare outcomes and decreased healthcare utilization across all variables in the one- and two-way sensitivity analyses. Using baseline assumptions, the costs associated with the no screening strategy were 3.54 times that of the screening strategy. Moreover, the mortality for symptomatic CDI was lower in the screening strategy than the no screening strategy. CONCLUSION: The screening strategy results in less healthcare utilization and improved clinical outcomes. Screening for CDI measures favorably.

Effects of Clostridium difficile infection in patients with alcoholic hepatitis.

BACKGROUND & AIMS: Infection increases mortality in patients with alcoholic hepatitis (AH). Little is known about the association between Clostridium difficile infection (CDI) and AH. We examined the prevalence and effects of CDI in patients with AH, compared with those of other infections. METHODS: We performed a cross-sectional analysis using data collected from the Nationwide Inpatient Sample, from 2008 through 2011. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with AH. We used multivariable logistic regression to determine risk factors that affect mortality, negative binomial regression to evaluate the effects of CDI on predicted length of stay (LOS), and Poisson regression to determine the effects of CDI on predicted hospital charges. Chi-square and Wilcoxon rank-sum analyses were used to compare mortality, LOS, and hospital charges associated with CDI with those associated with urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP). RESULTS: Of 10,939 patients with AH, 177 had CDI (1.62%). Patients with AH and CDI had increased odds of inpatient mortality (adjusted odds ratio, 1.75; P = .04), a longer predicted LOS (10.63 vs 5.75 d; P < .001), and greater predicted hospital charges ($36,924.30 vs $29,136.58; P < .001), compared with those without CDI. Compared with UTI, CDI was associated with similar mortality but greater LOS (9 vs 6 d; P < .001) and hospital charges ($45,607 vs $32,087; P < .001). SBP was associated with higher mortality than CDI (17.3% vs 10.1%; P = .045), but similar LOS and hospital charges. CONCLUSIONS: In patients with AH, CDI is associated with greater mortality and health care use. These effects appear similar to those for UTI and SBP. We propose further studies to determine the cost effectiveness of screening for CDI among patients with AH.