Kamath, Patrick S.

Acute on chronic liver failure (ACLF) is associated with multisystem organ failure and poor prognosis in hospitalized patients with cirrhosis. We aimed to determine time trends in the epidemiology, economic burden, and mortality of ACLF in the United States. The National Inpatient Sample database was queried between 2001 and 2011. ACLF was defined as two or more extrahepatic organ failures in patients with cirrhosis. The primary outcomes were trends in hospitalizations, hospital costs, and inpatient mortality. The number of hospitalizations for cirrhosis in the United States nearly doubled from 371,000 in 2001 to 659,000 in 2011. The prevalence of ACLF among those hospitalizations increased from 1.5% (n = 5,400) to 5% (n = 32,300). The inpatient costs increased 2‐fold for cirrhosis ($4.8 billion to $9.8 billion) and 5‐fold ($320 million to $1.7 billion) for ACLF. In 2011, the cost per hospitalization for ACLF was 3.5‐fold higher than that for cirrhosis ($53,570 versus $15,193). The in‐hospital fatality rates decreased from 65% to 50% for ACLF and from 10% to 7% for cirrhosis. The organ failure trends in ACLF showed an increasing proportion of cardiovascular and cerebral and decreasing proportion of respiratory and renal failure. Age, male sex, and the number and types of organ failure were predictors of death in ACLF. Conclusion: Cirrhosis and ACLF represent a substantial and increasing health and economic burden in the United States; these data highlight an urgent need for research on pathophysiological mechanisms and effective therapy as well as for education of health care providers of its importance in the care of patients with cirrhosis. (H epatology 2016;64:2165‐2172).

Abstract Rationale There is sparse published literature on the causes and outcomes of hospitalization of patients with hereditary hemorrhagic telangiectasia (HHT). Objectives To evaluate rates of various complications, comorbidities, and in-hospital outcomes of patients with HHT using a large, multihospital inpatient database. Methods We identified patients with HHT in the U.S. Nationwide Inpatient Sample between 2000 and 2012. Rates of hemorrhagic, neurological, hepatic, and cardiopulmonary complications among hospitalized patients with HHT were evaluated. We also studied procedure use rates for blood transfusion, endoscopy, and epistaxis treatment. Hospitalization outcomes, including in-hospital mortality, discharge status, charges, and length of stay, were evaluated. Measurements and Main Results: We identified 10,293 patients with HHT. The mean age of the HHT population was 60.7 years. Sixty percent of patients were female. More than 75% of HHT hospitalizations occurred in those older than 50 years of age. Patients with HHT had high rates of bleeding-related complications, including anemia (53.3%), epistaxis (16.2%), and gastrointestinal bleeding (10.8%). Overall, bleeding complications accounted for 62.7% of HHT-related complications. Thirty-eight percent of hospitalized patients with HHT received one or more transfusions of a blood product. Cardiopulmonary complications were present in 41.0% of the cases. Congestive heart failure was the second most common individual complication among patients with HHT, affecting 19.9% of patients. The in-hospital mortality rate was 1.9%. Conclusions In this large, nationwide study, we found that nearly two-thirds of patients hospitalized with HHT experienced a bleeding-related complication. Nearly 40% of hospitalized patients with HHT required transfusion of blood products. Cardiopulmonary complications, including congestive heart failure, were the second most common complication. The high burden of bleeding-related complications points to a significant unmet clinical need for these patients.

Treatment of polycystic liver disease (PLD) focuses on symptom improvement. Generic questionnaires lack sensitivity to capture PLD‐related symptoms, a prerequisite to determine effectiveness of therapy. We developed and validated a disease‐specific questionnaire that assesses symptoms in PLD (PLD‐Q). We identified 16 PLD‐related symptoms (total score 0‐100 points) by literature review and interviews with patients and clinicians. The developed PLD‐Q was validated in Dutch (n = 200) and United States (US; n = 203) PLD patients. We assessed the correlation of PLD‐Q total score with European Organization for Research and Treatment of Cancer (EORTC) symptom scale, global health visual analogue scale (VAS) of EQ‐5D, and liver volume. To test discriminative validity, we compared PLD‐Q total scores of patients with different PLD severity stages (Gigot classification) and PLD‐Q total scores of PLD patients with general controls and polycystic kidney disease patients without PLD. Reproducibility was tested by comparing original test scores with 2‐week retest scores. In total, 167 Dutch and 124 US patients returned the questionnaire. Correlation between PLD‐Q total score and EORTC symptom scale (The Netherlands [NL], r = 0.788; US, r = 0.811) and global health VAS (NL, r = −0.517; US, r = −0.593) was good. There was no correlation of PLD‐Q total score with liver volume (NL, r = 0.138; P = 0.236; US, r = 0.254; P = 0.052). Gigot type III individuals scored numerically higher than type II patients (NL, 46 vs. 40; P = 0.089; US, 48 vs. 36; P = 0.055). PLD patients scored higher on the PLD‐Q total score than general controls (NL, 42 vs. 17; US, 40 vs. 13 points) and polycystic kidney disease patients without PLD (22 points). Reproducibility of PLD‐Q was excellent (NL, r = 0.94; US, 0.96). Conclusion: PLD‐Q is a valid, reproducible, and sensitive disease‐specific questionnaire that can be used to assess PLD‐related symptoms in clinical care and future research. (Hepatology 2016;64:151–160)

Treatment options for refractory hepatic encephalopathy (HE) are limited. Patients who fail medical management may harbor large portosystemic shunts (PSSs) which are possible therapeutic targets. This study aims to describe patient selection, effectiveness, and safety of percutaneous PSS embolization in those with medically refractory HE. A retrospective evaluation of consecutive adult patients with medically refractory HE referred for PSS embolization at a tertiary center was performed (2003‐2015). Patient data collected included the type of HE, medications, Model for End‐Stage Liver Disease (MELD) score, shunt type, embolization approach, and materials used. Outcomes of interest were immediate (7 days), intermediate (1‐4 months), and longer‐term (6‐12 months) effectiveness and periprocedural safety. Effectiveness was determined based on changes in hospitalization frequency, HE medications, and symptoms. Twenty‐five patients with large PSS were evaluated for shunt embolization. Five were excluded due to high MELD scores (n = 1), comorbid conditions (n = 1), or technical considerations (n = 3). Of 20 patients who underwent embolization, 13 had persistent and 7 had recurrent HE; 100% (20/20) achieved immediate improvement. Durable benefit was achieved in 100% (18/18) and 92% (11/12) at 1‐4 and 6‐12 months, respectively. The majority (67%; 8/12) were free from HE‐related hospitalizations over 1 year; 10% developed procedural complications, and all resolved. Six developed new or worsening ascites. In conclusion, PSS embolization is a safe and effective treatment strategy that should be considered for select patients with medically refractory HE. Liver Transplantation 22 723–731 2016 AASLD.

In smaller single‐center studies, patients with cirrhosis are at a high readmission risk, but a multicenter perspective study is lacking. We evaluated the determinants of 3‐month readmissions among inpatients with cirrhosis using the prospective 14‐center North American Consortium for the Study of End‐Stage Liver Disease cohort. Patients with cirrhosis hospitalized for nonelective indications provided consent and were followed for 3 months postdischarge. The number of 3‐month readmissions and their determinants on index admission and discharge were calculated. We used multivariable logistic regression for all readmissions and for hepatic encephalopathy (HE), renal/metabolic, and infection‐related readmissions. A score was developed using admission/discharge variables for the total sample, which was validated on a random half of the total population. Of the 1353 patients enrolled, 1177 were eligible on discharge and 1013 had 3‐month outcomes. Readmissions occurred in 53% (n = 535; 316 with one, 219 with two or more), with consistent rates across sites. The leading causes were liver‐related (n = 333; HE, renal/metabolic, and infections). Patients with cirrhosis and with worse Model for End‐Stage Liver Disease score or diabetes, those taking prophylactic antibiotics, and those with prior HE were more likely to be readmitted. The admission model included Model for End‐Stage Liver Disease and diabetes (c‐statistic = 0.64, after split‐validation 0.65). The discharge model included Model for End‐Stage Liver Disease, proton pump inhibitor use, and lower length of stay (c‐statistic = 0.65, after split‐validation 0.70). Thirty percent of readmissions could not be predicted. Patients with liver‐related readmissions consistently had index‐stay nosocomial infections as a predictor for HE, renal/metabolic, and infection‐associated readmissions (odds ratio = 1.9‐3.0). Conclusions: Three‐month readmissions occurred in about half of discharged patients with cirrhosis, which were associated with cirrhosis severity, diabetes, and nosocomial infections; close monitoring of patients with advanced cirrhosis and prevention of nosocomial infections could reduce this burden. (Hepatology 2016;64:200–208)