Outcomes, Mortality, and Cost Burden of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

BACKGROUND AND AIMS: Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data. METHODS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens. RESULTS: The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay. CONCLUSIONS: AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.

Real-world clinical features, health-care utilization, and economic burden in decompensated cirrhosis patients: A national database.

BACKGROUND: Patients with decompensated cirrhosis are well known to experience morbidity and mortality. AIM: We assessed clinical characteristics, health-care utilization, and economic burden according to the type, number, and combination of decompensation-related complications. METHODS: We used recent nationally representative sample data from 2016 to 2018, covering approximately 13% of hospitalized patients in South Korea annually. Decompensation-related complications included ascites, hepatic encephalopathy (HE), gastroesophageal variceal (GEV) bleeding, and hepatorenal syndrome (HRS). RESULTS: Among 14 601 patients with decompensated cirrhosis, 11 201 (76.7%) experienced ≥ 1 decompensation-related complications, and approximately three-quarters underwent hospitalization. The most prevalent decompensation-related complications were ascites (54.8%), GEV bleeding (33.2%), HE (27.4%), and HRS (3.6%). Patients with GEV bleeding exhibited the highest hospitalization rate (95.7%), and patients with HE or HRS underwent hospitalization for 4 weeks/year due to decompensated cirrhosis. Hospitalization costs were 1.9 times higher in patients with HRS than in those with ascites alone ($9022 vs $4673; P < 0.01). Once patients developed decompensation-related complications, 41.3% had ≥ 2 types of decompensation-related complications. As the number of decompensation-related complications increased from 0 to ≥ 3, health-care utilization and economic burden significantly increased in a stepwise manner; patients with ascites, GEV bleeding, and HE visited medical institutions 2.2 times more (11 vs 5/year; P < 0.01) and incurred 6.4 times greater medical expenditure ($11 060 vs $1728/year; P < 0.01) than those with ascites only. CONCLUSION: A substantial proportion of patients had multiple decompensation-related complications and socioeconomic burdens for decompensated cirrhosis considering admission rate, hospital stay, and costs increased markedly, depending on the number of decompensation-related complications.

Analysis of Survival Benefits of Living Versus Deceased Donor Liver Transplant in High Model for End-Stage Liver Disease and Hepatorenal Syndrome.

BACKGROUND AND AIMS: Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End-Stage Liver Disease (MELD) > 25 and hepatorenal syndrome (HRS). APPROACH AND RESULTS: Patients who were listed with MELD > 25 from 2008 to 2017 were analyzed with intention-to-treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT-LDLT, whereas those who had none belonged to ITT-deceased donor liver transplantation (DDLT) group. ITT-overall survival (OS) was analyzed from the time of listing. Three hundred twenty-five patients were listed (ITT-LDLT n = 212, ITT-DDLT n = 113). The risk of delist/death was lower in the ITT-LDLT group (43.4% vs. 19.8%, P < 0.001), whereas the transplant rate was higher in the ITT-LDLT group (78.3% vs. 52.2%, P < 0.001). The 5-year ITT-OS was superior in the ITT-LDLT group (72.6% vs. 49.5%, P < 0.001) for patients with MELD > 25 and patients with both MELD > 25 and HRS (56% vs. 33.8%, P < 0.001). Waitlist mortality was the highest early after listing, and the distinct alteration of slope at survival curve showed that the benefits of ITT-LDLT occurred within the first month after listing. Perioperative outcomes and 5-year patient survival were comparable for patients with MELD > 25 (88% vs. 85.4%, P = 0.279) and patients with both MELD > 25 and HRS (77% vs. 76.4%, P = 0.701) after LDLT and DDLT, respectively. The LDLT group has a higher rate of renal recovery by 1 month (77.4% vs. 59.1%, P = 0.003) and 3 months (86.1% vs, 74.5%, P = 0.029), whereas the long-term estimated glomerular filtration rate (eGFR) was similar between the 2 groups. ITT-LDLT reduced the hazard of mortality (hazard ratio = 0.387-0.552) across all MELD strata. CONCLUSIONS: The ITT-LDLT reduced waitlist mortality and allowed an earlier access to transplant. LDLT in patients with high MELD/HRS was feasible, and they had similar perioperative outcomes and better renal recovery, whereas the long-term survival and eGFR were comparable with DDLT. LDLT should be considered for patients with high MELD/HRS, and the application of LDLT should not be restricted with a MELD cutoff.

Same- vs Different-Hospital Readmissions in Patients With Cirrhosis After Hospital Discharge.

INTRODUCTION: There is a lack of data on the impact of readmission to the same vs a different hospital following an index hospital discharge in cirrhosis patients. METHODS: We sought to describe rates and predictors of different-hospital readmissions (DHRs) among patients with cirrhosis and also determine the impact on cirrhosis outcomes including all-cause inpatient mortality and hospital costs. Using the national readmissions database, we identified cirrhosis hospitalizations in 2013. Regression analysis was used to determine the predictors of DHRs. A time-to-event analysis was performed to assess the impact on subsequent readmissions and all-cause inpatient mortality. RESULTS: In 2013, there were 109,039 cirrhosis readmissions with 67% of these being same-hospital readmissions and 33% being DHRs (P < 0.001). Two percent of readmitted patients were treated at ≥4 different hospitals. The 30-day readmission rate was 29.1%. Predictors of DHR included Medicaid payer (adjusted odds ratio [OR] 1.07, 95% confidence interval [95% CI] 1.01-1.14), age (OR 0.98, 95% CI 0.978-0.982), elective admission (OR 1.09, 95% CI 1.01-1.17), hepatic encephalopathy (OR 1.20, 95% CI 1.16-1.25), hepatorenal syndrome (OR 1.09, 95% CI 1.03-1.16), and low socioeconomic status (OR 1.15, 95% CI 1.06-1.25). No difference was observed in 30-day readmission risk following a DHR (adjusted hazard ratio 1.044, 95% CI 0.975-1.118). In addition, there was no increased risk of inpatient death observed during a DHR within 30 days (adjusted hazard ratio 1.08, 95% CI 0.94-1.23). However, patients with DHR had significantly higher hospital costs and length of stay. CONCLUSIONS: Majority of cirrhosis readmissions are same-hospital readmissions. Different-hospital readmissions do not increase the risk of 30-day readmissions and inpatient mortality but are associated with higher hospital costs.

Epidemiology, Pathophysiology, and Management of Hepatorenal Syndrome.

Acute kidney injury (AKI) is a common presentation in patients with advanced cirrhosis hospitalized with acute decompensation. A new revised classification now divides AKI in cirrhotic patients into two broad subgroups: hepatorenal syndrome AKI (HRS AKI) and non-hepatorenal syndrome AKI (non-HRS AKI). HRS AKI represents the end-stage complication of decompensated cirrhosis with severe portal hypertension and is characterized by worsening of renal function in the absence of prerenal azotemia, nephrotoxicity, and intrinsic renal disease. Non-HRS AKI may be caused by prerenal hypoperfusion, bile acid nephropathy, nephrotoxicity, or acute parenchymal insult. There have been several mechanisms proposed to explain the pathophysiology of HRS AKI and non-HRS AKI, and a number of biomarkers have been suggested to aid in differentiation between these types of AKI and to act as prognostic indicators. The standard of care clinical management for patients with HRS AKI is to exclude other etiologies of AKI, followed by volume expansion with human albumin solution and then the introduction of vasopressors. However, some 40% of patients treated for HRS AKI fail to respond. In this review, we discuss the current and recent data about classification, pathophysiology, and management of AKI in general, with specific insight about the treatment of HRS AKI.

The burden of hepatorenal syndrome among commercially insured and Medicare patients in the United States.

BACKGROUND: This study evaluated the characteristics, healthcare resource utilization (HCRU), and costs, from the payer perspective, of hepatorenal syndrome (HRS) patients covered by commercial and Medicare insurance. Mortality was assessed as a secondary outcome. METHODS: Patients were identified from claims databases of commercially insured patients (OptumHealth Care Solutions Inc.) in 1998-2014 and Medicare beneficiaries in 2009-2013 (5% Standard Analytic Files). At the time of their first inpatient admission ("index date") with an HRS diagnosis (ICD-9 code 572.4), commercially insured patients must be aged 18-64 and Medicare patients must be aged 65 and older. RESULTS: A total of 784 commercially insured and 1061 Medicare HRS patients met the sample selection criteria. Patients were disproportionately male (commercial: 63.0%; Medicare: 57.9%) with a mean age of 54.1 among commercially insured and 74.1 among Medicare patients. Within the first 30 days, the average hospital length of stay (LOS) was 12.3 days among commercially insured and 10.8 days among Medicare patients. Based on Kaplan-Meier analyses, 36% of commercially insured and 26% of Medicare patients were readmitted within the next 30 days. During follow-up, many patients received dialysis (commercial: 33.0%; Medicare: 22.1%) or liver transplant (commercial: 10.7%; Medicare: 1.6%). Average costs within the 90 day follow-up were $157,665 for commercially insured and $48,322 for Medicare patients, with 68.3% and 78.3% of the costs incurred within the first 30 days. The primary cost driver was inpatient visits (commercial: 90.3% of costs; Medicare: 83.1% of costs), with differences between the populations consistent with lower mortality, higher dialysis rates, and higher transplant rates (both liver and kidney) among the commercially insured. Using US population and prevalence statistics, these results suggest that HRS imposes an annual total direct medical cost burden of approximately $3.0-$3.8 billion to payers over the period. CONCLUSIONS: HRS imposes a significant economic burden.