Expensive Treatment Associated With Low Retention Rates Among Patients With Hepatic Encephalopathy


Investigators highlighted an association between treatment retention over time and the out-of-pocket cost for patients with hepatic encephalopathy taking rifaximin.

Elizabeth Aby, MD | Credit: M Health Fairview

Elizabeth Aby, MD

Credit: M Health Fairview

Results from a retrospective cohort study highlighted low rifaximin treatment retention rates among patients with hepatic encephalopathy (HE), a trend associated with increased 30-day out-of-pocket costs.

A major complication of cirrhosis, HE can often be resolved through early detection and efficient treatment. However, the condition can quickly worsen if triggering factors are left untreated. Despite an emphasis on treatment adherence, cost of therapy can pose problems for patient access.1

“Individuals with scarred livers, who have a higher out-of-pocket cost, are more likely to not fill their prescription for their medication, which can result in falls, hospitalizations and other poor outcomes,” said Elizabeth Aby, MD, assistant professor at the University of Minnesota Medical School and transplant hepatologist at M Health Fairview.2 “Clinicians and policy makers need to be aware of the impact that out-of-pocket costs have on patients’ medication adherence for rifaximin. Active measures must be taken to address this issue.”

With a team of colleagues, Aby sought to assess the impact of OOP rifaximin cost on treatment retention through a retrospective cohort study of more than 6800 patients with cirrhosis and HE. Using health insurance payment data from the IBM MarketScan Commercial Claims and Encounters Database between 2011 to 2021, investigators obtained information related to the 30-day out-of-pocket rifaximin retention and hospitalizations.3

For the purpose of analysis, HE was defined as diagnosis of HE or treatment of HE combined with a diagnosis or hospitalization for liver-related complications. In total, 6839 adult patients with HE were included. Among this group, 4274 patients were prescribed rifaximin. Investigators defined treatment retention as ≥80% eligible days with rifaximin supply and calculated OOP rifaximin cost as the sum of patients’ associated co-pay, co-insurance, and deductible.3

Investigators used regression models to estimate associations between patients’ 30-day OOP rifaximin cost and rifaximin retention at 180, 360, and 540 days after treatment induction. An additional analysis was performed to assess the impact of rifaximin retention on all-cause hospitalizations over a 6-month period, comparing patients who remained on rifaximin for at least 180 days to those who discontinued the medication. Investigators noted models were controlled for age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use.3

Upon analysis, the likelihood of rifaximin treatment retention decreased with time. Over 180 days, 42% of the patients took rifaximin regularly and decreased to 25% over 360 days and 16% over 540 days. The risk of discontinued treatment at 180 days, 360 days, and 540 days was 0.97 (95% confidence interval [CI], 0.96–0.98; P < 0.0001), 0.96 (95% CI, 0.94–0.97; P < 0.0001), and 0.95 (95% CI, 0.93–0.97; P < 0.0001), respectively.3

Individuals who did not have treatment retention in the first 180 days had a significantly higher number of hospitalization days (relative risk [RR], 1.03; 95% CI, 1.00–1.06; P = 0.0216) after adjusting for covariates, although investigators did not find a significant association between the 30-day OOP cost for rifaximin and all-cause hospitalizations or HE-related hospitalizations.3

Investigators noted patients who continued treatment had reduced average 30-day OOP costs compared to those who stopped treatment for all three retention periods. A 30-day out-of-pocket cost more than $150 was associated with a decreased likelihood of treatment retention during the 180 (RR, 0.67; 95% CI, 0.56–0.82), 360 (RR, 0.62; 95% CI, 0.48–0.80), and 540 days (RR, 0.60; 95% CI, 0.43–0.83) treatment periods.3

“Our findings support previous research showing that the cost of rifaximin negatively impacts adherence. While initiatives aimed at improving medication adherence, including interventions to improve health literacy and leveraging technology (such as text alerts, mobile phone applications, and automated medication dispensing technologies), can help improve adherence, multipronged efforts, including tackling cost barriers, are needed,” concluded investigators.3


1. American Liver Foundation. Treating Hepatic Encephalopathy. Complications of Liver Disease. Accessed August 30, 2023. https://liverfoundation.org/liver-diseases/complications-of-liver-disease/hepatic-encephalopathy/treating-hepatic-encephalopathy/

2. University of Minnesota Medical School. High drug price associated with decreased treatment retention for patients with chronic liver disease. EurekAlert! August 24, 2023. Accessed August 30, 2023. https://www.eurekalert.org/news-releases/999551.

3. Aby, Elizabeth S, Shen, Tsung-Hua, Murugappan, Meena N, Stenehjem, David D, Leventhal, Thomas M. High rifaximin out-of-pocket costs are associated with decreased treatment retention among patients with hepatic encephalopathy. Hepatology Communications. August 2023. DOI: 10.1097/HC9.0000000000000215

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