OBJECTIVES : To compare healthcare resource utilization (HCRU) and non-drug medical costs among hepatic encephalopathy (HE) patients receiving lactulose monotherapy, rifaximin monotherapy, and combination of lactulose and rifaximin (LR).

METHODS : Humana claims from 1/1/2013 to 12/31/2015 were analyzed. Patients were included if they had ≥1 HE diagnosis codes (572.2, K72.90 or K72.91), were enrolled ≥12 months, had calculable Model for End-Stage Liver Disease (MELD) scores, and ≥2 claims of lactulose or rifaximin. Patients were considered as receiving LR if having both medications covered ≥60 days. Covariates (age, race, gender, insurance, comorbidity, MELD score, adherence [proportion of days covered (PDC) ≥0.8], and pre-index HCRU), were adjusted for using zero-inflated negative binomial regressions and generalized linear models with gamma distributions.

RESULTS : 610 patients (63.3±9.2 years) were included (lactulose: n=383 [62.8%]; rifaximin: n=121 [19.8%]; LR: n=116 [19.0%]). During the 6-month follow-up, the mean of inpatient visits and length of stay of the lactulose, rifaximin, and LR cohort were 1.4, 1.1, and 1.5 (p=0.037), and 9.9, 7.9, and 9.6 days (p=0.019), respectively. Compared to patients receiving lactulose, the rifaximin cohort was associated with significantly less HE-related emergency room visits (incidence rate ratio [IRR]=0.5, 95% CI=0.3-0.8). Unadjusted mean (SD) all-cause and HE-related non-drug medical costs for the three cohorts were $28,225 ($52,552), $28,319 ($57,696), $32,389 ($60,664), and $6,943 ($11,810), $5,009 ($12,003), $9,202 ($17,876), respectively. In the multivariate analyses, no association was found between drug therapy type and all-cause or HE-related inpatient costs. However, the rifaximin cohort had lower all-cause (cost ratio [CR]= 0.7, 95% CI=0.5-0.9) and HE-related non-drug medical costs (CR=0.6, 95% CI=0.4-0.9) than patients receiving lactulose. Patients who were older, non-adherent, had commercial insurance, higher MELD score, and more pre-index HCRU tended to have higher non-drug medical expenditures.

CONCLUSIONS : Compared to lactulose, use of rifaximin monotherapy was associated with lower HE-related HCRU and non-drug medical costs.