Andrei Racila

The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady‐state prevalence model to quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incidence and remission rates were calculated by calibrating against real‐world prevalence rates. The data were validated using a computerized disease model called DisMod II. NAFLD patients transitioned between nine health states (nonalcoholic fatty liver, nonalcoholic steatohepatitis [NASH], NASH‐fibrosis, NASH‐compensated cirrhosis, NASH‐decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, post‐liver transplant, and death). Transition probabilities were sourced from the literature and calibrated against real‐world data. Utilities were obtained from NAFLD patients using the Short Form‐6D. Costs were sourced from the literature and local fee schedules. In the United States, over 64 million people are projected to have NAFLD, with annual direct medical costs of about

Development and validation of a primary sclerosing cholangitis-specific patient-reported outcomes instrument: The PSC PRO

103 billion (

Viral eradication is required for sustained improvement of patient-reported outcomes in patients with hepatitis C

1,613 per patient). In the Europe‐4 countries (Germany, France, Italy, and United Kingdom), there are ∼52 million people with NAFLD with an annual cost of about €35 billion (from €354 to €1,163 per patient). Costs are highest in patients aged 45‐65. The burden is significantly higher when societal costs are included. Conclusion: The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577‐1586)

Effects of Treatment of Chronic Hepatitis B Virus Infection on Patient-Reported Outcomes

Primary sclerosing cholangitis (PSC) is a chronic liver disease associated with inflammation and biliary fibrosis that leads to cholangitis, cirrhosis, and impaired quality of life. Our objective was to develop and validate a PSC‐specific patient‐reported outcome (PRO) instrument. We developed a 42‐item PSC PRO instrument that contains two modules (Symptoms and Impact of Symptoms) and conducted an external validation. Reliability and validity were evaluated using clinical data and a battery of other validated instruments. Test‐retest reliability was assessed in a subgroup of patients who repeated the PSC PRO after the first administration. One hundred two PSC subjects (44 ± 13 years; 32% male, 74% employed, 39% with cirrhosis, 14% with a history of decompensated cirrhosis, 38% history of depression, and 68% with inflammatory bowel disease [IBD]) completed PSC PRO and other PRO instruments (Short Form 36 V2 [SF‐36], Chronic Liver Disease Questionnaire [CLDQ], Primary Biliary Cholangitis – 40 [PBC‐40], and five dimensions [5‐D Itch]). PSC PRO demonstrated excellent internal consistency (Cronbach alphas, 0.84‐0.94) and discriminant validity (41 of 42 items had the highest correlations with their own domains). There were good correlations between PSC PRO domains and relevant domains of SF‐36, CLDQ, and PBC‐40 (R = 0.69‐0.90; all P < 0.0001), but lower (R = 0.31‐0.60; P < 0.001) with 5‐D Itch. Construct validity showed that PSC PRO can differentiate patients according to the presence and severity of cirrhosis and history of depression (P < 0.05), but not by IBD (P > 0.05). Test‐retest reliability was assessed in 53 subjects who repeated PSC PRO within a median (interquartile range) of 37 (27‐47) days. There was excellent reliability for most domains with intraclass correlations (0.71‐0.88; all P < 0.001). Conclusion: PSC PRO is a self‐administered disease‐specific instrument developed according to U.S. Food and Drug Administration guidelines. This preliminary validation study suggests good psychometric properties. Further validation of the instrument in a larger and more diverse sample of PSC patients is needed. (Hepatology 2018;68:155‐165).

Burden of Illness and Economic Model for Patients with Non‐Alcoholic Steatohepatitis (NASH) in the United States

Clearance of chronic HCV infection improves quality of life and other patient‐reported outcomes (PROs). Lack of placebo‐controlled data led to concerns about the extent of contribution of viral eradication to PRO improvement.

Prediction of Health Utility Scores in Patients with Chronic Hepatitis C Using the Chronic Liver Disease Questionnaire-Hepatitis C Version (CLDQ-HCV)

Background & Aims Chronic infection with hepatitis B virus (HBV) causes liver disease and cirrhosis. It is not clear how treatment of chronic HBV infection affects patient‐reported outcomes (PROs). We aimed to assess changes in PROs in patients treated for chronic HBV infection. Methods We collected and analyzed PRO data from 242 patients with chronic HBV infection (without advanced fibrosis or cirrhosis) enrolled in 2 international phase 2 blinded controlled clinical trials from 2015 through 2017. In these trials, patients were treated with an approved oral antiviral regimen (tenofovir, entecavir, adefovir, lamivudine, or telbivudine) and then randomly assigned to groups given vesatolimod (an oral agonist of Toll‐like receptor 7) or placebo. PROs were collected using the Short Form‐36, the Chronic Liver Disease Questionnaire, and the Work Productivity and Activity Impairment: Specific Health Problem questionnaires before treatment and during treatment weeks 12, 24, and 48. Results We did not observe significant differences in PROs between patients receiving vesatolimod vs placebo. At baseline, patients with viral suppression (HBV DNA level, <20 IU/mL) had higher PRO scores (by up to +10.6% of a PRO range size). During treatment, there were significant increases in scores for some domains of the Chronic Liver Disease Questionnaire and in General Health scores of Short Form‐36 (increases of up to 4.9%; P < .05). Patients with a decrease of at least 2.7 log10 IU/mL in level of HBV DNA had substantially larger increases in PRO scores (P < .05 for 10 of 22 studied PROs). In multivariate analysis, a reduction in viral load was independently associated with increases in PROs (&bgr; values up to 1.6% per log10 IU/mL decrease; P < .05). Conclusions In an analysis of data from phase 2 trials, we associated active treatment of chronic HBV infection with increased PRO scores. These findings support inclusion of PRO end points in assessments of efficacy and safety in clinical trials of treatments for HBV infection.

Implementation of baby boomer hepatitis C screening and linking to care in gastroenterology practices: a multi-center pilot study

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease. Our aim was to estimate the total economic burden of NASH and advanced NASH in the United States. We constructed lifetime Markov models for all stages of NASH and a separate model to specifically identify the increased burden of advanced NASH (fibrosis stage >3). The models comprised patients aged 18+, who moved through seven different health states. We used a lifetime horizon with 1‐year cycles for each transition. Cohort size was estimated using US population data, and prevalence and incidence rates were obtained from the literature. Transition probabilities between states were derived from meta‐analyses. Costs included inpatient, outpatient, professional services, emergency department, and drug costs, which were obtained from the Center for Medicare and Medicaid Services Fee Schedule 2017 and published data. All future costs were discounted at an annual rate of 3%. Our models estimated that there are 6.65 million adults (18+ years old) with NASH in the United States and that there were 232,000 incident cases in 2017. Lifetime costs of all NASH patients in the United States in 2017 will be

Long-term outcomes of liver transplantation in patients with hepatitis C infection are not affected by HCV positivity of a donor

222.6 billion, and the cost of the advanced NASH population will be

P0724 : Direct medical costs associated with the extrahepatic manifestations of hepatitis C infection in the United States

95.4 billion. Conclusion: NASH, especially advanced NASH, is associated with high lifetime economic burden; in the absence of treatment, the total direct costs of illness for these patients will continue to grow, and these costs would be even greater if the societal costs are included.

Sustainable improvement of patient-reported outcomes in cirrhotic patients with hepatitis C who achieved sustained virologic response

BACKGROUND Preference-based health utilities are used in economic analyses of disease burden and health care interventions. When specifically designed instruments cannot be applied, mapping algorithms for non-preference-based instruments can be used for prediction of health utility scores. OBJECTIVES To develop a mapping algorithm for the Chronic Liver Disease Questionnaire-Hepatitis C Version (CLDQ-HCV), the hepatitis C virus-specific quality-of-life instrument. METHODS We used a sample of patients with HCV who completed the short form 36 health survey and the CLDQ-HCV in clinical trials; six-dimensional health state short form (SF-6D) utilities were derived from the 36-item short form health survey. Regression models with components of the CLDQ-HCV being predictors and SF-6D being the outcome were developed and tested in an independent testing set and in clinically significant subpopulations. RESULTS The sample of 34,822 records was split (4:1) into training and testing set. Simple mixed models had a root mean square error up to 0.088; predicted and observed utilities were highly correlated (Pearson correlation 0.81-0.82) although predicted utilities were underestimated in the range closest to perfect scores. Generalized linear models had better average accuracy (root mean square error up to 0.0839; correlations up to 0.844) and significantly better accuracy in the highest values (median error up to 0.065). Accuracy in the independent testing set was nearly identical, and so was accuracy in patients with compensated and decompensated cirrhosis; the errors of group means were less than 0.015. CONCLUSIONS A number of linear models for mapping domains or items of CLDQ-HCV to SF-6D health utilities have been developed. The models have excellent accuracy at the group level. Predicted health utility scores can be used in further economic analyses involving patients with HCV.