Poor Performance Status is Associated with Increased Mortality in Patients with Cirrhosis

Background & Aims Functional status (a patient’s ability to perform activities that meet basic needs, fulfill usual roles, and maintain health and well being) has been linked to outcomes in patients with cirrhosis and can be measured by the Karnofsky performance status (KPS) scale. We investigated the association between KPS score and mortality in patients with cirrhosis. Methods We used the United Network for Organ Sharing database to perform a retrospective cohort study of patients listed for liver transplantation in the United States between 2005 and 2015. We used Cox proportional hazards and competing risk regression analyses to examine the association between KPS and mortality and transplantation. Results Of 79,092 patients, 44% were in KPS category A (KPS 80%–100%), 43% were in category B (KPS 50%–70%), and 13% were in category C (KPS 10%–40%). Between 2005 and 2015, the proportion of patients in category A decreased from 53% to 35%, whereas the proportions in categories B and C increased from 36% to 49% and from 11% to 16%, respectively. KPS was associated with mortality: compared to patients in KPS category A, the KPS B adjusted hazard ratio [HR] was 1.14 (95% confidence interval [CI], 1.11–1.18) and the KPS C adjusted HR was 1.63 (95% CI, 1.55–1.72). KPS was also associated with liver transplantation; compared to patients in KPS category A, the KPS B adjusted HR was 1.08 (95% CI, 1.06–1.11) and the KPS C adjusted HR was 1.35 (95% CI, 1.30–1.40). In competing risk analysis, only the relationship between KPS and mortality maintained significance and directionality. These relationships were most pronounced in patients without hepatocellular carcinoma. Conclusions Among patients with cirrhosis listed for liver transplantation, poor performance status, based on the KPS scale, is associated with increased mortality. In this population, performance status has decreased over time

Trends in Characteristics, Mortality, and Other Outcomes of Patients With Newly Diagnosed Cirrhosis

Importance: Changes in the characteristics of patients with cirrhosis are likely to affect future outcomes and are important to understand in planning for the care of this population. Objective: To identify changes in demographic and clinical characteristics and outcomes in patients with newly diagnosed cirrhosis. Design, Setting, and Participants: A retrospective cohort study of patients with a new diagnosis of cirrhosis was conducted using the Indiana Network for Patient Care, a large statewide regional health information exchange, between 2004 and 2014. Patients with at least 1 year of continuous follow-up before the cirrhosis diagnosis were followed up through August 1, 2015. The analysis was conducted from December 2018 to January 2019. Exposures: Age, cause of cirrhosis, and year of diagnosis. Main Outcomes and Measures: Overall rates for mortality, liver transplant, hepatocellular carcinoma, and hepatic decompensation (composite of ascites, hepatic encephalopathy, or variceal bleeding). Results: A total of 9261 patients with newly diagnosed cirrhosis were identified (mean [SD] age, 57.9 [12.6] years; 5109 [55.2%] male). A 69% increase in new diagnoses occurred over the course of the study period (620 in 2004 vs 1045 in 2014). The proportion of those younger than 40 years increased by 0.20% per year (95% CI, 0.04% to 0.36%; P for trend = .02), and the proportion of those aged 65 years and older increased by 0.81% per year (95% CI, 0.51% to 1.11%; P for trend < .001). The proportion of patients with alcoholic cirrhosis increased by 0.80% per year (95% CI, 0.49% to 1.12%), and the proportion with nonalcoholic steatohepatitis increased by 0.59% per year (95% CI, 0.30% to 0.87%), whereas the proportion with viral hepatitis decreased by 1.36% per year (95% CI, -1.68% to -1.03%) (P < .001 for all). In patients younger than 40 years, 40 to 64 years, and 65 years and older, mortality rates were 6.4 (95% CI, 5.4 to 7.6), 9.9 (95% CI, 9.5 to 10.4), and 16.2 (95% CI, 15.2 to 17.2) per 100 person-years, respectively (P < .001). Mortality rates decreased during the study period (11.9 [95% CI, 10.7-13.1] per 100 person-years in 2004 vs 10.0 [95% CI, 8.1-12.2] per 100 person-years in 2014; annual adjusted hazard ratio, 0.87 [95% CI, 0.86 to 0.88]) and were lower in those with alcoholic cirrhosis compared with patients with viral hepatitis (adjusted hazard ratio, 0.89 [95% CI, 0.80 to 0.98]). Rates of hepatocellular carcinoma were low in patients younger than 40 years (0.5 [95% CI, 0.2 to 0.9] per 100 person-years). Liver transplant rates were low throughout the study period (0.3 [95% CI, 0.3-0.4] per 100 person-years). In patients with compensated cirrhosis, rates of hepatic decompensation were lower in patients younger than 40 years (adjusted subhazard ratio 0.78; 95% CI, 0.62 to 0.99) and in patients with nonalcoholic steatohepatitis (adjusted subhazard ratio, 0.51; 95% CI, 0.43 to 0.60). Conclusions and Relevance: The population of patients with newly diagnosed cirrhosis in Indiana has experienced changes in the age distribution and cause of cirrhosis, with decreasing mortality rates. These findings support investment in the prevention and treatment of alcoholic liver disease and nonalcoholic steatohepatitis, particularly in younger and older patients. Additional study is needed to identify the reasons for decreasing mortality rates

Hospital Readmissions in Patients with Cirrhosis: A Systematic Review

BACKGROUND: Hospital readmission is a significant problem for patients with complex chronic illnesses such as liver cirrhosis. PURPOSE: We aimed to describe the range of readmission risk in patients with cirrhosis and the impact of the model for end-stage liver disease (MELD) score. DATA SOURCES: We conducted a systematic review of studies identified in Ovid MEDLINE, PubMed, EMBASE, CINAHL, the Cochrane Library, Scopus, Google Scholar, and ClinicalTrials.gov from 2000 to May 2017. STUDY SELECTION: We examined studies that reported early readmissions (up to 90 days) in patients with cirrhosis. Studies were excluded if they did not examine the association between readmission and at least 1 variable or intervention. DATA EXTRACTION: Two reviewers independently extracted data on study design, setting, population, interventions, comparisons, and detailed information on readmissions. DATA SYNTHESIS: Of the 1363 records reviewed, 26 studies met the inclusion and exclusion criteria. Of these studies, 21 were retrospective, and there was significant variation in the inclusion and exclusion criteria. The pooled estimate of 30-day readmissions was 26%(95% confidence interval [CI], 22%-30%). Few studies examined readmission preventability or the relationship between readmissions and social determinants of health. Reasons for readmission were highly variable. An increased MELD score was associated with readmissions in most studies. Readmission was associated with increased mortality. CONCLUSIONS: Hospital readmissions frequently occur in patients with cirrhosis and are associated with liver disease severity. The impact of functional and social factors on readmissions is unclear

Black Adult Patients With Acute Liver Failure Are Sicker and More Likely to Undergo Liver Transplantation Than White Patients

Racial and ethnic differences in the presentation and outcomes of patients wait‐listed with acute liver failure (ALF) have not been explored. Adult patients with ALF wait‐listed for liver transplantation (LT) from 2002 to 2016 were investigated using the United Network for Organ Sharing database. Clinical characteristics and causative etiologies were compared between white, black, Hispanic, and Asian patients with ALF who were wait‐listed as status 1. A competing risk analysis was used to explore differences in LT and wait‐list removal rates. Kaplan‐Meier survival curves were used to explore differences in 1‐year posttransplant survival. There were 8208 patients wait‐listed with a primary diagnosis of ALF; 4501 were wait‐listed as status 1 (55.3% of whites, 64.4% of blacks, 51.6% of Hispanics, 40.7% of Asians; P < 0.001). Black patients had higher bilirubin and Model for End‐Stage Liver Disease at wait‐listing than other groups. White patients were the most likely to have acetaminophen toxicity as a causative etiology, whereas black patients were the most likely to have autoimmune liver disease. Black patients were significantly more likely to undergo LT than white patients (hazard ratio, 1.20; 95% confidence interval, 1.08‐1.30). There was no difference in wait‐list removal because of death or clinical deterioration among racial/ethnic groups. The 1‐year posttransplant survival was lowest in black patients (79.6%) versus white (82.8%), Hispanic (83.9%), and Asian (89.3%) patients (P = 0.02). In conclusion, etiologies of ALF vary by race and ethnicity. Black patients with ALF were more likely to be wait‐listed as status 1 and undergo LT than white patients, but they were sicker at presentation. The 1‐year posttransplant survival rate was lowest among black patients

Paracentesis is Associated with Reduced Mortality in Patients Hospitalized with Cirrhosis and Ascites

Diagnostic paracentesis is recommended for patients with cirrhosis admitted to the hospital for ascites or encephalopathy. However, it is not known if clinicians in the United States adhere to this recommendation; a relationship between paracentesis and clinical outcome has not been reported. We analyzed a US database to determine the frequency of paracentesis and its association with mortality. Methods The 2009 Nationwide Inpatient Sample (which contains data from approximately 8 million hospital discharges each year) was used to identify patients with cirrhosis and ascites admitted with a primary diagnosis of ascites or encephalopathy. In-hospital mortality, length of stay, and hospital charges were compared for those who did and did not undergo paracentesis. Outcomes were compared for those who received an early paracentesis (within 1 day of admission) and those who received one later. Results Of 17,711 eligible admissions, only 61% underwent paracentesis. In-hospital mortality was reduced by 24% among patients who underwent paracentesis (6.5% vs 8.5%, adjusted odds ratio [OR], 0.55; 95% confidence interval [CI], 0.41–0.74). Most paracenteses (66%) occurred ≤1 day after admission. In-hospital mortality was lower among patients who received early paracentesis than those who received it later (5.7% vs 8.1%; P=.049), although this difference was not significant after adjustment for confounders (OR, 1.26; 95% CI, 0.78–2.02). Among patients who underwent paracentesis, the mean hospital stay was 14% longer, and hospital charges were 29% greater than for patients that did not receive the procedure. Conclusions Paracentesis is underused for patients admitted to the hospital with ascites; the procedure is associated with increased short-term survival. These data support practice guidelines derived from expert opinion. Studies are needed to identify barriers to guideline adherence

Alcoholic liver disease: Pathogenesis, management, and novel targets for therapy

Alcohol use is a leading cause of preventable morbidity and mortality worldwide, with much of its negative impact as the result of alcoholic liver disease (ALD). ALD is a broad term that encompasses a spectrum of phenotypes ranging from simple steatosis to steatohepatitis, progressive fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the development of these different disease stages are incompletely understood. Standard treatment of ALD, which includes abstinence, nutritional support, and corticosteroids, has not changed in the last 40 years despite continued poor outcomes. Novel therapies are therefore urgently needed. The development of such therapies has been hindered by inadequate resources for research and unsuitable animal models. However, recent developments in translational research have allowed for identification of new potential targets for therapy. These targets include: (i) CXC chemokines, (ii) IL-22/STAT3, (iii) TNF receptor superfamily, (iv) osteopontin, (v) gut microbiota and lipopolysaccharide (LPS), (vi) endocannabinoids, and (vii) inflammasomes. We review the natural history, risk factors, pathogenesis, and current treatments for ALD. We further discuss the findings of recent translational studies and potential therapeutic targets

Most Individuals With Advanced Cirrhosis Have Sleep Disturbances, Which Are Associated With Poor Quality of Life

Background & Aims Sleep disturbances are common in patients with cirrhosis, but their determinants and effects on health-related quality of life are not well-understood. We investigated the prevalence of disturbed sleep in these patients, factors associated with sleep disruption, and effects on quality of life. Methods We performed a prospective, cross-sectional study of 193 stable ambulatory patients with cirrhosis (154 with decompensated cirrhosis). Participants completed the Pittsburgh Sleep Quality Index (to assess sleep quality), the Chronic Liver Disease Questionnaire (CLDQ), and muscle cramp questionnaires and underwent neurocognitive testing. Actigraphy was performed in a subset of patients with normal and disturbed sleep. We collected serum samples from subjects with normal and disturbed sleep and performed non-targeted metabolomic analyses. Results Of the study subjects, 157 (81%) had disturbed sleep, with Pittsburgh Sleep Quality Index scores >5. Disturbed sleep was associated with muscle cramps, daytime somnolence, and decreased quality of life on the basis of CLDQ scores. Factors independently associated with disturbed sleep in logistic regression analysis included hypoalbuminemia, opiate therapy, and muscle cramps. Disturbed sleep was independently associated with CLDQ score (correlation parameter, –36.6; 95% confidence interval, –24 to –49; P < .001) on linear regression. Disturbed sleep was associated with neurocognitive impairment and with significantly delayed bedtime and decreased total sleep time, measured by actigraphy. Disturbed sleep was associated with metabolome signatures of alterations to the intestinal microbiome and lipid, arginine, and urea cycle metabolism. Conclusions Most patients with advanced cirrhosis (81%) have disturbed sleep. This has negative effects on quality of life and is associated with disruptions of several metabolic pathways, including metabolism by the intestinal microbiota

The confusion assessment method for the intensive care unit in patients with cirrhosis

In the intensive care unit (ICU), delirium is routinely measured with the widely-used, validated Confusion Assessment Method for the ICU (CAM-ICU), but CAM-ICU has not been studied in patients with cirrhosis. We studied a group of patients with cirrhosis to determine the relationship between delirium measured by CAM-ICU and clinical outcomes. Consecutive patients with cirrhosis admitted to the ICU from 2009 to 2012 were included in a retrospective cohort study. Patients were screened twice daily for coma and delirium during their ICU stay using the Richmond Agitation Sedation Scale (RASS) and CAM-ICU. The association between delirium/coma and mortality was determined using multiple logistic regression. RASS and CAM-ICU were also compared to a retrospective assessment of hepatic encephalopathy (HE). Of 91 patients with cirrhosis, 26 (28.6 %) developed delirium/coma. RASS/CAM-ICU had fair agreement with the HE assessment (κ 0.38). Patients with delirium/coma had numerically greater mortality in-hospital (23.1 vs. 7.7 %, p = 0.07) and at 90 days (30.8 vs. 18.5 %, p = 0.26), and they also had longer hospital length of stay (median 19.5 vs. 6 days, p < 0.001). Delirium/coma was associated with increased inpatient mortality, independent of disease severity (unadjusted OR 3.6; 95 % CI, 0.99-13.1; MELD-adjusted OR 5.4; 95 % CI, 1.3-23.8; acute physiology score-adjusted OR 2.2; 95 % CI, 0.53-8.9). Delirium/coma was also associated with longer length of stay after adjusting for disease severity. In critically ill patients with cirrhosis, delirium/coma as measured by the RASS and CAM-ICU is associated with increased mortality and hospital length of stay. For these patients, these measures provide valuable information and may be useful tools for clinical care. RASS and CAM-ICU need to be compared to HE-specific measures in future studies

Predicting Liver Transplant Capacity Using Discrete Event Simulation

The number of liver transplants (LTs) performed in the US increased until 2006 but has since declined despite an ongoing increase in demand. This decline may be due in part to decreased donor liver quality and increasing discard of poor-quality livers. We constructed a discrete event simulation (DES) model informed by current donor characteristics to predict future LT trends through the year 2030. The data source for our model is the United Network for Organ Sharing database, which contains patient-level information on all organ transplants performed in the US. Previous analysis showed that liver discard is increasing and that discarded organs are more often from donors who are older, are obese, have diabetes, and donated after cardiac death. Given that the prevalence of these factors is increasing, the DES model quantifies the reduction in the number of LTs performed through 2030. In addition, the model estimatesthe total number of future donors needed to maintain the current volume of LTs and the effect of a hypothetical scenario of improved reperfusion technology.We also forecast the number of patients on the waiting list and compare this with the estimated number of LTs to illustrate the impact that decreased LTs will have on patients needing transplants. By altering assumptions about the future donor pool, this model can be used to develop policy interventions to prevent a further decline in this lifesaving therapy. To our knowledge, there are no similar predictive models of future LT use based on epidemiological trends

Efficacy and Durability of Radiofrequency Ablation for Barrett's Esophagus: Systematic Review and Meta-analysis

In patients with Barrett’s esophagus (BE), radiofrequency ablation (RFA) safely and effectively eradicates dysplasia and intestinal metaplasia. We aimed to determine the efficacy and durability of RFA for patients with dysplastic and nondysplastic BE