Where you live matters: Area deprivation predicts poor survival and liver transplant waitlisting.

Social determinants of health (SDOH) are important predictors of poor clinical outcomes in chronic diseases, but their associations among the general cirrhosis population and liver transplantation (LT) are limited. We conducted a retrospective, multiinstitutional analysis of adult (≥18-years-old) patients with cirrhosis in metropolitan Chicago to determine the associations of poor neighborhood-level SDOH on decompensation complications, mortality, and LT waitlisting. Area deprivation index and covariates extracted from the American Census Survey were aspects of SDOH that were investigated. Among 15 101 patients with cirrhosis, the mean age was 57.2 years; 6414 (42.5%) were women, 6589 (43.6%) were non-Hispanic White, 3652 (24.2%) were non-Hispanic Black, and 2662 (17.6%) were Hispanic. Each quintile increase in area deprivation was associated with poor outcomes in decompensation (sHR [subdistribution hazard ratio] 1.07; 95% CI 1.05-1.10; P < .001), waitlisting (sHR 0.72; 95% CI 0.67-0.76; P < .001), and all-cause mortality (sHR 1.09; 95% CI 1.06-1.12; P < .001). Domains of SDOH associated with a lower likelihood of waitlisting and survival included low income, low education, poor household conditions, and social support (P < .001). Overall, patients with cirrhosis residing in poor neighborhood-level SDOH had higher decompensation, and mortality, and were less likely to be waitlisted for LT. Further exploration of structural barriers toward LT or optimizing health outcomes is warranted.

Societal costs and survival of patients with biopsy-verified non-alcoholic steatohepatitis: Danish nationwide register-based study.

INTRODUCTION AND OBJECTIVES: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups. MATERIALS AND METHODS: Nationwide Danish healthcare registers were used to include all patients (≥18 years) diagnosed with biopsy-verified NAFLD (1997-2021). Patients were classified as having simple steatosis or non-alcoholic steatohepatitis (NASH) with or without cirrhosis, and all matched with liver-disease free reference groups. Healthcare costs and labour market outcomes were compared from 5 years before to 11 years after diagnosis. Patients were followed for 25 years to analyse risk of disability insurance and death. RESULTS: 3,712 patients with biopsy-verified NASH (n = 1,030), simple steatosis (n = 1,540) or cirrhosis (n = 1,142) were identified. The average total costs in the year leading up to diagnosis was 4.1-fold higher for NASH patients than the reference group (EUR 6,318), 6.2-fold higher for cirrhosis patients and 3.1-fold higher for simple steatosis patients. In NASH, outpatient hospital contacts were responsible for 49 % of the excess costs (EUR 3,121). NASH patients had statistically significantly lower income than their reference group as early as five years before diagnosis until nine years after diagnosis, and markedly higher risk of becoming disability insurance recipients (HR: 4.37; 95 % CI: 3.17-6.02) and of death (HR: 2.42; 95 % CI: 1.80-3.25). CONCLUSIONS: NASH, simple steatosis and cirrhosis are all associated with substantial costs for the individual and the society with excess healthcare costs and poorer labour market outcomes.

Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study.

BACKGROUND AND AIMS: Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/or transplant. APPROACH AND RESULTS: We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P < 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver-related death (subdistribution HR, 1.26; 95% CI, [1.15-1.38]; P < 0.001). CONCLUSIONS: Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology.

Characteristics and Outcomes of Children With Cystic Fibrosis Hospitalized With Cirrhosis in the United States.

INTRODUCTION: To describe the characteristics and outcomes of children with cystic fibrosis (CF) hospitalized with cirrhosis in the United States. METHODS: We conducted a population-based cohort study of hospitalizations among children with CF using the 2016 Kid's Inpatient Database. RESULTS: In total, 9,615 admissions were analyzed. Diagnosis of cirrhosis was present in 509 (5.3%) and was significantly associated with increased mortality, length of stay, and hospital charges compared with those without cirrhosis. Hepatic encephalopathy was significantly associated with death in children with cirrhosis. DISCUSSION: Future interventions should be designed to support children with CF who have cirrhosis to improve clinical outcomes.

Compound Sarcopenia in Hospitalized Patients with Cirrhosis Worsens Outcomes with Increasing Age.

BACKGROUND: There are limited data on outcomes of older patients with chronic diseases. Skeletal muscle loss of aging (primary sarcopenia) has been extensively studied but the impact of secondary sarcopenia of chronic disease is not as well evaluated. Older patients with chronic diseases have both primary and secondary sarcopenia that we term compound sarcopenia. We evaluated the clinical impact of compound sarcopenia in hospitalized patients with cirrhosis given the increasing number of patients and high prevalence of sarcopenia in these patients. DESIGN: The Nationwide Inpatients Sample (NIS) database (years 2010-2014) was analyzed to study older patients with cirrhosis. Since there is no universal hospital diagnosis code for "muscle loss", we used a comprehensive array of codes for "muscle loss phenotype" in the international classification of diseases-9 (ICD-9). A randomly selected 2% sample of hospitalized general medical population (GMP) and inpatients with cirrhosis were stratified into 3 age groups based on age-related changes in muscle mass. In-hospital mortality, length of stay (LoS), cost of hospitalization (CoH), comorbidities and discharge disposition were analyzed. RESULTS: Of 517,605 hospitalizations for GMP and 106,835 hospitalizations for treatment of cirrhosis or a cirrhosis-related complication, 207,266 (40.4%) GMP and 29,018 (27.7%) patients with cirrhosis were >65 years old, respectively. Muscle loss phenotype in both GMP and inpatients with cirrhosis 51-65 years old and >65 years old was significantly (p < 0.001 for all) associated with higher mortality, LoS, and CoH compared to those ≤50 years old. Patients >65 years old with cirrhosis and muscle loss phenotype had higher mortality (adjusted OR: 1.06, 95% CI [1.04, 1.08] and CoH (adjusted odds ratio (OR): 1.10, 95% confidence interval (CI) [1.04, 1.08])) when compared to >65 years old GMP with muscle loss phenotype. Muscle loss in younger patients with cirrhosis (≤50 years old) was associated with worse outcomes compared to GMP >65 years old. Non-home discharges (nursing, skilled, long-term care) were more frequent with increasing age to a greater extent in patients with cirrhosis with muscle loss phenotype for each age stratum. CONCLUSION: Muscle loss is more frequent in older patients with cirrhosis than younger patients with cirrhosis and older GMP. Younger patients with cirrhosis had clinical outcomes similar to those of older GMP, suggesting an accelerated senescence in cirrhosis. Compound sarcopenia in older patients with cirrhosis is associated with higher inpatient mortality, increased LoS, and CoH compared to GMP with sarcopenia.

Disparities in Mortality and Health Care Utilization for 460,851 Hospitalized Patients with Cirrhosis and Hepatic Encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a common cause of hospitalizations and readmissions for patients with decompensated cirrhosis. In this study, we proposed to investigate recent trends in in-hospital mortality and utilization for patients with cirrhosis and HE and to explore the effect of various sociodemographic, hospital, and clinical factors on mortality. METHODS: We performed an observational study using serial cross-sectional data from the 2009-2013 National Inpatient Sample to examine hospitalizations of patients with cirrhosis and HE. We collected data on in-hospital mortality, length of stay, and total hospital costs. We used negative binomial regression and logistic regression to investigate trends in utilization and multilevel modeling to examine the association between sociodemographic, hospital, and clinical factors and in-hospital mortality. RESULTS: The annual total number of hospitalizations from HE has steadily risen from 75,475 in 2009 to 106,915 in 2013 (P < 0.001). Annual in-hospital mortality (11.9-10.2%, P < 0.001) and length of stay (7.5-7.1 days, P = 0.015) have significantly decreased over this timeframe. The presence of septicemia, GI bleeding, and being uninsured were associated with 29.6%, 16.7%, and 15.7% of in-hospital death, respectively. Patients hospitalized in the South, Medicare beneficiaries, and patients hospitalized in the Midwest had a 9.8%, 9.2%, and 8.9% chance of dying in the hospital. CONCLUSION: The number of hospitalizations from HE has increased while in-hospital mortality has concomitantly decreased from 2009 to 2013. Both traditional risk factors (sepsis and GI bleeding) strongly influence the probability of in-hospital death. However, disparities in mortality by sociodemographic factors (insurance status and geography) also exist.

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.

Cannabis use may reduce healthcare utilization and improve hospital outcomes in patients with cirrhosis.

INTRODUCTION AND OBJECTIVES: Previous studies reveal conflicting data on the effect of cannabis use in patients with cirrhosis. This research evaluates the impact of cannabis on hepatic decompensation, health care utilization, and mortality in patients with cirrhosis. MATERIAL AND METHODS: A retrospective analysis of the State Inpatient Database (SID) was performed evaluating patients from Colorado and Washington in 2011 to represent pre-cannabis legalization and 2015 to represent post-cannabis legalization. Multivariable analysis was performed to study the impact of cannabis on the rate of admissions with hepatic decompensations, healthcare utilization, and mortality in patients with cirrhosis. RESULTS: Cannabis use was detected in 370 (2.1%) of 17,520 cirrhotics admitted in 2011 and in 1162 (5.3%) of 21,917 cirrhotics in 2015 (p-value <0.001). On multivariable analysis, cirrhotics utilizing cannabis after its legalization experienced a decreased rate of admissions related to hepatorenal syndrome (Odds Ratio (OR): 0.51; 95% Confidence Interval (CI): 0.34-0.78) and ascites (OR: 0.73; 95% CI: 0.63-0.84). Cirrhotics with an etiology of disease other than alcohol and hepatitis C had a higher risk of admission for hepatic encephalopathy if they utilized cannabis [OR: 1.57; 95% CI: 1.16-2.13]. Decreased length of stay (-1.15 days; 95% CI: -1.62, -0.68), total charges (-$15,852; 95% CI: -$21,009, -$10,694), and inpatient mortality (OR: 0.68; 95% CI: 0.51-0.91) were also observed in cirrhotics utilizing cannabis after legalization compared to cirrhotics not utilizing cannabis or utilizing cannabis prior to legalization. CONCLUSION: Cannabis use in patients with cirrhosis resulted in mixed outcomes regarding hospital admissions with hepatic decompensation. A trend towards decreased hospital utilization and mortality was noted in cannabis users after legalization. These observations need to be confirmed with a longitudinal randomized study.

County Differences in Liver Mortality in the United States: Impact of Sociodemographics, Disease Risk Factors, and Access to Care.

BACKGROUND AND AIMS: Data have demonstrated state-wide variability in mortality rates from liver disease (cirrhosis + hepatocellular carcinoma), but data are lacking at the local level (eg, county) to identify factors associated with variability in liver disease-related mortality and hotspots of liver disease mortality. METHODS: We used Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research data from 2009 to 2018 to calculate county-level, age-adjusted liver disease-related death rates. We fit multivariable linear regression models to adjust for county-level covariates related to demographics (ie, race and ethnicity), medical comorbidities (eg, obesity), access to care (eg, uninsured rate), and geographic (eg, distance to closest liver transplant center) variables. We used optimized hotspot analysis to identify clusters of liver disease mortality hotspots based on the final multivariable models. RESULTS: In multivariable models, 61% of the variability in among-county mortality was explained by county-level race/ethnicity, poverty, uninsured rates, distance to the closest transplant center, and local rates of obesity, diabetes, and alcohol use. Despite adjustment, significant within-state variability in county-level mortality rates was found. Of counties in the top fifth percentile (ie, highest mortality) of fully adjusted mortality, 60% were located in 3 states: Oklahoma, Texas, and New Mexico. Adjusted mortality rates were highly spatially correlated, representing 5 clusters: South Florida; Appalachia and the eastern part of the Midwest; Texas and Oklahoma; New Mexico, Arizona, California, and southern Oregon; and parts of Washington and Montana. CONCLUSIONS: Our data demonstrate significant intrastate differences in liver disease-related mortality, with more than 60% of the variability explained by patient demographics, clinical risk factors for liver disease, and access to specialty liver care.

Socioeconomic and marital status among liver cirrhosis patients and associations with mortality: a population-based cohort study in Sweden.

BACKGROUND: The importance of socioeconomic status for survival in cirrhosis patients is more or less pronounced within different populations, most likely due to cultural and regional differences combined with dissimilarities in healthcare system organisation and accessibility. Our aim was to study the survival of patients with cirrhosis in a population-based Swedish cohort, using available data on marital status, employment status, and occupational skill level. METHODS: We conducted a retrospective cohort study of 582 patients diagnosed with cirrhosis in the Region of Halland (total population 310,000) between 2011 and 2018. Medical and histopathologic data, obtained from registries, were reviewed. Cox regression models were used to estimate associations between survival and marital status (married, never married, previously married), employment status (employed, pensioner, disability retired, unemployed), and occupational skill level (low-skilled: level I; medium-skilled: level II; medium-high skilled: level III; professionals: level IV); adjusting for sex, age, aetiology, Model for End-stage Liver Disease (MELD) score, Child-Pugh class, and comorbidities. RESULTS: Alcohol was the most common aetiology (51%). Most patients were male (63%) and the median age was 66 years. Occupational skill level was associated with the severity of cirrhosis at diagnosis and the prevalence of Child-Pugh C gradually increased from professionals through low-skilled. The mean survival for professionals (6.39 years, 95% CI 5.54-7.23) was higher than for low-skilled (3.00 years, 95% CI 2.33-3.67) and medium-skilled (4.04 years, 95% CI 3.64-4.45). The calculated hazard ratios in the multivariate analysis were higher for low-skilled (3.43, 95% CI 1.89-6.23) and medium-skilled (2.48, 95% CI 1.48-4.12), compared to professionals. When aggregated, low- and medium-skilled groups also had poorer mean survival (3.79 years, 95% CI 3.44-4.14; vs 5.64 years, 95% CI 5.00-6.28) and higher hazard ratios (1.85, 95% CI 1.32-2.61) compared to the aggregated medium-high skilled and professional groups. Marital and employment status were not statistically significant predictors of mortality in the multivariate analysis. CONCLUSIONS: Occupational skill level was strongly associated with mean survival and mortality risk. Poorer prognosis among patients with low and medium occupational skill level could not be explained by differences in sex, age, marital status, employment status, MELD score, Child-Pugh class, or comorbidity.

ICD-10-AM codes for cirrhosis and related complications: key performance considerations for population and healthcare studies.

OBJECTIVE: The utility of International Classification of Diseases (ICD) codes relies on the accuracy of clinical reporting and administrative coding, which may be influenced by country-specific codes and coding rules. This study explores the accuracy and limitations of the Australian Modification of the 10th revision of ICD (ICD-10-AM) to detect the presence of cirrhosis and a subset of key complications for the purpose of future large-scale epidemiological research and healthcare studies. DESIGN/METHOD: ICD-10-AM codes in a random sample of 540 admitted patient encounters at a major Australian tertiary hospital were compared with data abstracted from patients' medical records by four blinded clinicians. Accuracy of individual codes and grouped combinations was determined by calculating sensitivity, positive predictive value (PPV), negative predictive value and Cohen's kappa coefficient (κ). RESULTS: The PPVs for 'grouped cirrhosis' codes (0.96), hepatocellular carcinoma (0.97) ascites (0.97) and 'grouped varices' (0.95) were good (κ all >0.60). However, codes under-detected the prevalence of cirrhosis, ascites and varices (sensitivity 81.4%, 61.9% and 61.3%, respectively). Overall accuracy was lower for spontaneous bacterial peritonitis ('grouped' PPV 0.75; κ 0.73) and the poorest for encephalopathy ('grouped' PPV 0.55; κ 0.21). To optimise detection of cirrhosis-related encounters, an ICD-10-AM code algorithm was constructed and validated in an independent cohort of 116 patients with known cirrhosis. CONCLUSION: Multiple ICD-10-AM codes should be considered when using administrative databases to study the burden of cirrhosis and its complications in Australia, to avoid underestimation of the prevalence, morbidity, mortality and related resource utilisation from this burgeoning chronic disease.

Hepatitis C Management at Federally Qualified Health Centers during the Opioid Epidemic: A Cost-Effectiveness Study.

BACKGROUND: The opioid epidemic has been associated with an increase in hepatitis C virus (HCV) infections. Federally qualified health centers (FQHCs) have a high burden of hepatitis C disease and could serve as venues to enhance testing and treatment. METHODS: We estimated clinical outcomes and the cost-effectiveness of hepatitis C testing and treatment at US FQHCs using individual-based simulation modeling. We used individual-level data from 57 FQHCs to model 9 strategies, including permutations of HCV antibody testing modality, person initiating testing, and testing approach. Outcomes included life expectancy, quality-adjusted life-years (QALY), hepatitis C cases identified, treated and cured; and incremental cost-effectiveness ratios. RESULTS: Compared with current practice (risk-based with laboratory-based testing), routine rapid point-of-care testing initiated and performed by a counselor identified 68% more cases after (nonreflex) RNA testing in the first month of the intervention and led to a 17% reduction in cirrhosis cases and a 22% reduction in liver deaths among those with cirrhosis over a lifetime. Routine rapid testing initiated by a counselor or a clinician provided better outcomes at either lower total cost or at lower cost per QALY gained, when compared with all other strategies. Findings were most influenced by the proportion of patients informed of their anti-HCV test results. CONCLUSIONS: Routine anti-HCV testing followed by prompt RNA testing for positives is recommended at FQHCs to identify infections. If using dedicated staff or point-of-care testing is not feasible, then measures to improve immediate patient knowledge of antibody status should be considered.

Trends and outcomes of peptic ulcer disease in patients with cirrhosis.

BACKGROUND: Peptic ulcer disease (PUD) is more prevalent in cirrhotic patients and it has been associated with poor outcomes. However, there are no population-based studies from the United States (U.S.) that have investigated this association. Our study aims to estimate the incidence trends, predictors, and outcomes PUD patients with underlying cirrhosis. METHODS: We analyzed Nationwide Inpatient Sample (NIS) and Healthcare Cost and Utilization Project (HCUP) data for years 2002-2014. Adult hospitalizations due to PUD were identified by previously validated ICD-9-CM codes as the primary diagnosis. Cirrhosis was also identified with presence of ICD-9-CM codes in secondary diagnosis fields. We analyzed trends and predictors of PUD in cirrhotic patients and utilized multivariate regression models to estimate the impact of cirrhosis on PUD outcomes. RESULTS: Between the years 2002-2014, there were 1,433,270 adult hospitalizations with a primary diagnosis of PUD, out of which 70,007 (4.88%) had cirrhosis as a concurrent diagnosis. There was a significant increase in the proportion of hospitalizations with a concurrent diagnosis of cirrhosis, from 3.9% in 2002 to 6.6% in 2014 (p < 0.001). In an adjusted multivariable analysis, in-hospital mortality was significantly higher in hospitalizations of PUD with cirrhosis (odd ratio [OR] 1.78; 95% confidence interval [CI] 1.63-1.97; P < 0.001), however, there was no difference in the discharge to facility (OR 1.00; 95%CI 0.94 - 1.07; P = 0.81). Moreover, length of stay (LOS) was also higher (6 days vs. 4 days, P < 0.001) among PUD with cirrhosis. Increasing age and comorbidities were associated with higher odds of in-hospital mortality among PUD patients with cirrhosis. CONCLUSION: Our study shows that there is an increased hospital burden as well as poor outcomes in terms of higher in-hospital mortality among hospitalized PUD patients with cirrhosis. Further studies are warranted for better risk stratification and improvement of outcomes.

Aflatoxin B1 exposure and liver cirrhosis in Guatemala: a case-control study.

OBJECTIVE: In Guatemala, cirrhosis is among the 10 leading causes of death, and mortality rates have increased lately. The reasons for this heavy burden of disease are not clear as the prevalence of prominent risk factors, such as hepatitis B virus, hepatitis C virus and heavy alcohol consumption, appears to be low. Aflatoxin B1 (AFB1) exposure, however, appears to be high, and thus could be associated with the high burden of cirrhosis. Whether AFB1 increases the risk of cirrhosis in the absence of viral infection, however, is not clear. DESIGN: Cirrhosis cases (n=100) from two major referral hospitals in Guatemala City were compared with controls (n=200) from a cross-sectional study. Logistic regression was used to estimate the ORs and 95% CIs of cirrhosis and quintiles of AFB1 in crude and adjusted models. A sex-stratified analysis was also conducted. RESULTS: The median AFB1 level was significantly higher among the cases (11.4 pg/mg) than controls (5.11 pg/mg). In logistic regression analyses, higher levels of AFB1 was associated with cirrhosis (quintile 5 vs quintile 1, OR: 11.55; 95% CI 4.05 to 32.89). No attenuation was observed with adjustment by sex, ethnicity, hepatitis B virus status, and heavy alcohol consumption. A significantly increasing trend in association was observed in both models (p trend <0.01). Additionally, the cirrhosis-AFB1 association was more prominent among men. CONCLUSIONS: The current study found a significant positive association between AFB1 exposure and cirrhosis. Mitigation of AFB1 exposure and a better understanding of additional risk factors may be important to reduce the burden of cirrhosis in Guatemala.

Weekend admissions with ascites are associated with delayed paracentesis: A nationwide analysis of the 'weekend effect'.

INTRODUCTION AND OBJECTIVES: Weekend admissions has previously been associated with worse outcomes in conditions requiring specialists. Our study aimed to determine in-hospital outcomes in patients with ascites admitted over the weekends versus weekdays. Time to paracentesis from admission was studied as current guidelines recommend paracentesis within 24h for all patients admitted with worsening ascites or signs and symptoms of sepsis/hepatic encephalopathy (HE). PATIENTS: We analyzed 70 million discharges from the 2005-2014 National Inpatient Sample to include all adult patients admitted non-electively for ascites, spontaneous bacterial peritonitis (SBP), and HE with ascites with cirrhosis as a secondary diagnosis. The outcomes were in-hospital mortality, complication rates, and resource utilization. Odds ratios (OR) and means were adjusted for confounders using multivariate regression analysis models. RESULTS: Out of the total 195,083 ascites/SBP/HE-related hospitalizations, 47,383 (24.2%) occurred on weekends. Weekend group had a higher number of patients on Medicare and had higher comorbidity burden. There was no difference in mortality rate, total complication rates, length of stay or total hospitalization charges between the patients admitted on the weekend or weekdays. However, patients admitted over the weekends were less likely to undergo paracentesis (OR 0.89) and paracentesis within 24h of admission (OR 0.71). The mean time to paracentesis was 2.96 days for weekend admissions vs. 2.73 days for weekday admissions. CONCLUSIONS: We observed a statistically significant "weekend effect" in the duration to undergo paracentesis in patients with ascites/SBP/HE-related hospitalizations. However, it did not affect the patient's length of stay, hospitalization charges, and in-hospital mortality.

Nonalcoholic fatty liver disease progression rates to cirrhosis and progression of cirrhosis to decompensation and mortality: a real world analysis of Medicare data.

BACKGROUND: Risk factors and timing associated with disease progression and mortality in nonalcoholic fatty liver disease (NAFLD) are poorly understood. AIMS: To evaluate the impact of disease severity, demographics and comorbidities on risk of mortality and time to progression in a large, real-world cohort of diagnosed NAFLD patients. METHODS: Claims data from a 20% Medicare representative sample between 2007 and 2015 were analysed retrospectively. Adults were categorised into disease severity groups: NAFLD/nonalcoholic steatohepatitis (NASH) alone, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma. Cumulative incidence of mortality and disease progression were calculated for each group and multivariate analyses performed adjusting for demographics, comorbidities and disease severity. RESULTS: A total of 10 826 456, patients were assessed and the prevalence of NAFLD was 5.7% (N = 621 253). Among patients with NAFLD, 71.1% had NAFLD/NASH alone and 28.9% had NAFLD cirrhosis. Overall, 85.5% of patients had hypertension, 84.1% dyslipidemia, 68.7% had cardiovascular disease and 55.5% diabetes. The cumulative risk of progression of NAFLD to cirrhosis, and compensated cirrhosis to decompensated cirrhosis was 39% and 45%, respectively, over 8 years of follow-up. The independent predictors of progression included cardiovascular disease, renal impairment, dyslipidemia and diabetes. The cumulative risk of mortality for NAFLD, NAFLD cirrhosis, decompensated cirrhosis and hepatocellular carcinoma was 12.6%, 31.1%, 51.4% and 76.2%, respectively. CONCLUSIONS: The present report (a) demonstrates that NAFLD is grossly underdiagnosed in real-world clinical settings and (b) provides new evidence on the progression rates of NAFLD and risk factors of mortality across the spectrum of severity of NAFLD and cirrhosis.

Cost-Effectiveness of Rifaximin Treatment in Patients with Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis of the liver causing neuropsychiatric abnormalities. Clinical manifestations of overt HE result in increased health care resource utilization and effects on patient quality of life. While lactulose has historically been the mainstay of treatment for acute HE and maintenance of remission, there is an unmet need for additional therapeutic options with a favorable adverse event profile. Compared with lactulose alone, rifaximin has demonstrated proven efficacy in complete reversal of HE and reduction in the incidence of HE recurrence, mortality, and hospitalizations. Evidence suggests the benefit of long-term prophylactic therapy with rifaximin; however, there is a need to assess the economic impact of rifaximin treatment in patients with HE. OBJECTIVE: To assess the incremental cost-effectiveness of rifaximin ± lactulose versus lactulose monotherapy in patients with overt HE. METHODS: A Markov model was developed in Excel with 4 health states (remission, overt HE, liver transplantation, and death) to predict costs and outcomes of patients with HE after initiation of maintenance therapy with rifaximin ± lactulose to avoid recurrent HE episodes. Cost-effectiveness of rifaximin was evaluated through estimation of incremental cost per quality-adjusted life-year (QALY) or life-year (LY) gained. Analyses were conducted over a lifetime horizon. One-way deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in results. RESULTS: The rifaximin ± lactulose regimen provided added health benefits despite an additional cost versus lactulose monotherapy. Model results showed an incremental benefit of $29,161 per QALY gained and $27,762 per LY gained with rifaximin ± lactulose versus lactulose monotherapy. Probabilistic sensitivity analyses demonstrated that the rifaximin ± lactulose regimen was cost-effective ~99% of the time at a threshold of $50,000 per QALY/LY gained, which falls within the commonly accepted threshold for incremental cost-effectiveness. CONCLUSIONS: The clinical benefit of rifaximin, combined with an acceptable economic profile, demonstrates the advantages of rifaximin maintenance therapy as an important option to consider for patients at risk of recurrent HE. DISCLOSURES: This analysis was funded by Salix Pharmaceuticals, a division of Bausch Health US. Salix and Xcenda collaborated on the methods, and Salix, Xcenda, Jesudian, and Ahmad collaborated on the writing of the manuscript and interpretation of results. Bozkaya and Migliaccio-Walle are employees of Xcenda. Ahmad reports speaker fees from Salix Pharmaceuticals, unrelated to this study. Jesudian reports consulting and speaker fees from Salix Pharmaceuticals, unrelated to this study. The results from this model were presented at AASLD: The Liver Meeting 2014; November 7-11; Boston, MA.

Association between liver fibrosis scores and the risk of mortality among patients with coronary artery disease.

BACKGROUND AND AIMS: Fatty liver diseases are highly prevalent in patients with coronary artery disease (CAD) and might progress to irreversible liver fibrosis. Whether baseline liver fibrosis (LF) scores are associated with long-term mortality among patients with CAD requires investigation. METHODS: The analysis was conducted based on a prospective cohort study among 3263 patients with CAD in China. Cox models were used to assess the association of baseline levels of LF scores, including non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 score (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), gamma-glutamyltransferase to platelet ratio (GPR), and Forns score, with the risk of all-cause and cardiovascular mortality among CAD patients. RESULTS: During a median follow-up period of 7.56 (inter-quartile range: 6.86-8.31) years, 538 deaths were identified, 319 of those were due to cardiovascular diseases. Compared with patients with lowest score levels, multivariable-adjusted HRs (95% CI) for those with highest levels of NFS, FIB-4, APRI, GPR and Forns score were 2.89 (2.14-3.91), 2.84 (2.14-3.76), 1.77 (1.33-2.36), 1.47 (1.19-1.83) and 3.10 (1.88-5.11) for all-cause mortality, 3.02 (2.05-4.45), 3.34 (2.29-4.86), 1.99 (1.40-2.83), 1.80 (1.36-2.39) and 2.43 (1.28-4.61) for cardiovascular mortality, respectively. These associations were consistent when we excluded those who died within the first year of follow-up or stratified patients by different sex, age, BMI, diabetes status, metabolic syndrome status, CAD type and hsCRP level. CONCLUSIONS: Higher LF scores are associated with increased risks of all-cause and cardiovascular mortality among CAD patients. LF scores might play a potential role in CAD prognosis prediction.

Skeletal muscle loss phenotype in cirrhosis: A nationwide analysis of hospitalized patients.

BACKGROUND & AIMS: There are very limited data on the healthcare burden of muscle loss, the most frequent complication in hospitalized cirrhotics. We determined the healthcare impact of a muscle loss phenotype in hospitalized cirrhotics. METHODS: The Nationwide Inpatient Sample (NIS) database (years 2010-2014) was analyzed. Search terms included cirrhosis and its complications, and an expanded definition of a muscle loss phenotype that included all conditions associated with muscle loss. In-hospital mortality, length of stay (LOS), post-discharge disposition, co-morbidities and cost during admission were analyzed. Univariate and multivariate analyses were performed to identify associations between a muscle loss phenotype and outcomes. Impact of muscle loss in cirrhotics was compared to that in a random sample (2%) of general medical inpatients. RESULTS: A total of 162,694 hospitalizations for cirrhosis were reported, of which 18,261 (11.2%) included secondary diagnosis codes for a muscle loss phenotype. A diagnosis of muscle loss was associated with a significantly (p < 0.001 for all) higher mortality (19.3% vs 8.2%), LOS (14.2 ± 15.8 vs. 4.6 ± 6.9 days), and median hospital charge per admission ($21,400 vs. $8573) and a lower likelihood of discharge to home (30.1% vs. 60.2%). All evaluated outcomes were more severe in cirrhotics than general medical patients (n = 534,687). Multivariate regression analysis showed that a diagnosis of muscle loss independently increased mortality by 130%, LOS by 80% and direct cost of care by 119% (p < 0.001 for all). Alcohol use, female gender, malignancies and other organ dysfunction were independently associated with muscle loss. CONCLUSIONS: Muscle loss contributed to higher mortality, LOS, and direct healthcare costs in hospitalized cirrhotics.

Hospitalisation for cirrhosis in Australia: disparities in presentation and outcomes for Indigenous Australians.

BACKGROUND: Indigenous Australians experience greater health disadvantage and have a higher prevalence of many chronic health conditions. Liver diseases leading to cirrhosis are among the most common contributor to the mortality gap between Indigenous and other Australian adults. However, no comparative data exist assessing differences in presentation and patient outcomes between Indigenous and non-Indigenous Australians hospitalised with cirrhosis. METHODS: Using data from the Hospital Admitted Patient Data Collection and the Death Registry, this retrospective, population-based, cohort study including all people hospitalised for cirrhosis in the state of Queensland during 2008-2017 examined rate of readmission (Poisson regression), cumulative survival (Kaplan-Meier), and assessed the differences in survival (Multivariable Cox regression) by Indigenous status. Predictor variables included demographic, health service characteristics and clinical data. RESULTS: We studied 779 Indigenous and 10,642 non-Indigenous patients with cirrhosis. A higher proportion of Indigenous patients were younger than 50 years (346 [44%] vs. 2063 [19%] non-Indigenous patients), lived in most disadvantaged areas (395 [51%) vs. 2728 [26%]), had alcohol-related cirrhosis (547 [70%] vs. 5041 [47%]), had ascites (314 [40%] vs. 3555 [33%), and presented to hospital via the Emergency Department (510 [68%] vs. 4790 [47%]). Indigenous patients had 3.04 times the rate of non-cirrhosis readmissions (95%CI 2.98-3.10), 1.35 times the rate of cirrhosis-related readmissions (95%CI 1.29-1.41), and lower overall survival (17% vs. 27%; unadjusted hazard ratio (HR) = 1.16 95%CI 1.06-1.27), compared to non-Indigenous patients. Most of the survival deficit was explained by Emergency Department presentation (adj-HR = 1.03 95%CI 0.93-1.13), and alcohol-related aetiology (adj-HR = 1.08 95%CI 0.99-1.19). The remaining survival deficit was influenced by the other clinico-demographic and health service factors (final adj-HR = 1.08 95%CI 0.96-1.20). CONCLUSIONS: There was evidence of differential presentation, higher rates of readmissions, and poorer survival for Indigenous Australians with cirrhosis, compared to other Australians. The increased prevalence of Emergency Department presentation among Indigenous patients suggests missed opportunities for early intervention to prevent progressive cirrhosis complications and hospital readmissions.