Summary
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.
Nonalcoholic fatty liver disease (NAFLD) has reached high prevalence, paralleling the obesity pandemic. The aggressive form of the disease, nonalcoholic steatohepatitis (NASH), is characterized by ...fatty infiltration and inflammation of the liver, can progress to compensated cirrhosis (CC) and end-stage liver disease (ESLD: decompensated cirrhosis DCC and hepatocellular carcinoma HCC), and may ultimately require liver transplantation (LT). Real-world data on the burden of NAFLD/NASH are limited. This study aimed to evaluate the clinical and economic burden of NAFLD/NASH to the French hospital system.
This retrospective cohort study used data from the French PMSI-MCO database. Adults with NAFLD/NASH diagnosis identified between 2009 and 2015 were categorized into disease severity cohorts (NAFLD/NASH, CC, DCC, HCC, and LT). Demographic and clinical data were assessed at the index (diagnosis) date. Hospitalization resource utilization and costs were assessed in the pre- and post-index periods. Rates of liver disease progression and death were evaluated for each cohort.
During the median follow-up of 34.8 months, of the 131,656 patients included, 1491 patients developed CC (1.1%), 7846 developed DCC (5.9%), 1144 developed HCC (0.9%), and 52 required LT (0.04%). The diagnosis of NAFLD/NASH was associated with increasing annual costs: €7736 vs €5076 before the diagnosis. Rates of comorbidities, hospitalization resource utilization, and costs increased with disease progression. The rate of death at seven-year follow-up was 7.9% in NAFLD/NASH, CC: 18.0%, DCC: 34.9%, and HCC: 48.8%.
NAFLD/NASH is associated with high economic burden and imparts substantial risk of negative clinical outcomes and mortality at all stages of disease.
In a phase 3 randomized, double-blind, placebo-controlled trial, treatment with idelalisib, a phosphoinositol-3 kinase δ inhibitor, + bendamustine/rituximab improved progression-free survival (PFS) ...and overall survival (OS) in adult patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Here we report the results of health-related quality of life (HRQL) analyses from this study.
From June 15, 2012 to August 21, 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomized to the idelalisib arm and 209 to the placebo arm. In the 416 patients randomized to receive bendamustine/rituximab and either oral idelalisib 150 mg twice-daily or placebo, HRQL was assessed at baseline and throughout the blinded part of the study using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL Five-Dimension (EQ-5D) visual analogue scale (VAS) questionnaires. The assessments were performed at scheduled patient visits; every 4 weeks for the first 6 months from the initiation of treatment, then every 8 weeks for the next 6 months, and every 12 weeks thereafter until end of study. Least-squares mean changes from baseline were estimated using a mixed-effects model by including treatment, time, and treatment-by-time interaction, and stratification factors as fixed effects. Time to first symptom improvement was assessed by Kaplan-Meier analysis.
In mixed-effects model analysis, idelalisib + bendamustine/rituximab treatment led to clinically meaningful improvements from baseline in leukemia-associated symptoms. Moreover, per Kaplan-Meier analysis, the proportion of patients with symptom improvement was higher and time to improvement was shorter among patients in the idelalisib-containing arm compared with those who did not receive idelalisib. The physical and social/family FACT-Leu subscale scores, along with the self-rated health assessed by EQ-VAS, showed improvement with idelalisib over placebo, but the difference did not reach statistical significance. The functional and emotional FACT-Leu subscale scores remained similar to placebo.
Addition of idelalisib to bendamustine/rituximab, apart from improving PFS and OS, had a neutral to beneficial impact on HRQL in patients with R/R CLL, particularly by reducing leukemia-specific disease symptoms.
Clinicaltrials.gov NCT01569295. Registered April 3, 2012.
Red blood cell transfusion was previously the principle therapy for anemia in CKD but became less prevalent after the introduction of erythropoiesis-stimulating agents. This study used adaptive ...choice-based conjoint analysis to identify preferences and predictors of transfusion decision-making in CKD.
A computerized adaptive choice-based conjoint survey was administered between June and August of 2012 to nephrologists, internists, and hospitalists listed in the American Medical Association Masterfile. The survey quantified the relative importance of 10 patient attributes, including hemoglobin levels, age, occult blood in stool, severity of illness, eligibility for transplant, iron indices, erythropoiesis-stimulating agents, cardiovascular disease, and functional status. Triggers of transfusions in common dialysis scenarios were studied, and based on adaptive choice-based conjoint-derived preferences, relative importance by performing multivariable regression to identify predictors of transfusion preferences was assessed.
A total of 350 providers completed the survey (n=305 nephrologists; mean age=46 years; 21% women). Of 10 attributes assessed, absolute hemoglobin level was the most important driver of transfusions, accounting for 29% of decision-making, followed by functional status (16%) and cardiovascular comorbidities (12%); 92% of providers transfused when hemoglobin was 7.5 g/dl, independent of other factors. In multivariable regression, Veterans Administration providers were more likely to transfuse at 8.0 g/dl (odds ratio, 5.9; 95% confidence interval, 1.9 to 18.4). Although transplant eligibility explained only 5% of decision-making, nephrologists were five times more likely to value it as important compared with non-nephrologists (odds ratio, 5.2; 95% confidence interval, 2.4 to 11.1).
Adaptive choice-based conjoint analysis was useful in predicting influences on transfusion decisions. Hemoglobin level, functional status, and cardiovascular comorbidities most strongly influenced transfusion decision-making, but preference variations were observed among subgroups.
New treatments have improved outcomes and increased life expectancy for human immunodeficiency virus (HIV)–infected patients; however, their comorbidity burden has grown significantly and is greater ...than that in a matched non–HIV-infected cohort. This introduces important considerations for treatment choices and outcomes.
Abstract
Objective
Quantify proportion of human immunodeficiency virus (HIV)–infected patients with specific comorbidities receiving healthcare coverage from commercial, Medicaid, and Medicare payers.
Methods
Data from MarketScan research databases were used to select adult HIV-infected patients from each payer. Treated HIV-infected patients were matched to HIV-negative controls. Cross-sectional analyses were performed between 2003 and 2013 among HIV-infected patients to quantify the proportion with individual comorbidities over the period, by payer.
Results
Overall, 36298 HIV-infected patients covered by commercial payers, 26246 covered by Medicaid payers, and 1854 covered by Medicare payers were identified between 2003 and 2013. Essential hypertension (31.4%, 39.3%, and 76.2%, respectively), hyperlipidemia (29.2%, 22.1%, and 49.6%), and endocrine disease (21.8%, 27.2%, and 54.0%) were the most common comorbidities. Comparison of data from 2003 to data from 2013 revealed significant increases across payers in the percentage of patients with the comorbidities specified above (P < .05). Across all payers, the proportions of treated HIV-infected patients with deep vein thrombosis, hepatitis C, renal impairment, thyroid disease, and liver disease from 2003 to 2013 was significantly greater (P < .05) than for matched controls.
Conclusions
Comorbidities are common among the aging HIV-infected population and have increased over time. There should be a consideration in treatment choices for HIV infection, including the choices of antiretroviral regimens.
Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among ...hospitalized patients with AdvLD due to NASH in Italy.
Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017.
Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs.
NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.
•The real-world burden of hospitalized NAFLD/NASH patients in Italy was estimated.•NAFLD/NASH patients had high comorbidity burden.•Healthcare costs increased with liver severity stages observed in the study.•Inpatient costs were the most prominent driver of the high costs.
PDF
