Society: AASLD

Background and Aims: Screening tools are needed for early detection of NAFLD-fibrosis. We aimed to identify risk factors for NAFLD-fibrosis in the multiethnic population of the U.S. and thus accelerate development of equitable screening tools.
Methods: National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 datasets were analyzed. The study group included 6,661 adults (age ≥ 20 years) with vibration controlled transient elastography (VCTE) data. NAFLD-fibrosis thresholds were set by optimizing the sensitivity and specificity of the VCTE-CAP score and the stiffness score for differentiating steatosis grade 0 from grades 1-3 and distinguishing fibrosis stages 0-1 from stages 2-4. Logistic regression was used to determine odds ratios (ORs). Independent variables included age, sex, body mass index (BMI), smoking history, alcohol use, poverty, diabetes, and hypertension. Diabetes was defined by self-report, and/or hemoglobin A1c (HbA1c) ≥ 6.5%, and/or fasting plasma glucose ≥ 126 mg/dL. Participants with past and current viral hepatitis and alcohol-associated liver disease were excluded.
Results: NHANES 2017-March 2020 had 372 individuals with NAFLD-fibrosis, defined as VCTE-CAP ≥ 285 dB/m and stiffness ≥ 8.6 kPa. Non-Hispanic Black persons had a lower prevalence of NAFLD-fibrosis than non-Hispanic Whites (Fig.1A). The age-standardized weighted prevalence of NAFLD-fibrosis was about 7-fold higher in those with diabetes in the total population and in non-Hispanic White, Mexican American and Other race, but not in non-Hispanic Black (Fig.1C). The prevalence of NAFLD-fibrosis did not differ significantly between non-Hispanic Black persons with and without diabetes. After adjusting for age, sex, BMI, alcohol use, smoking status, and hypertension in multivariate logistic regression models, diabetes was not significantly associated with NAFLD-fibrosis in non-Hispanic Black persons (OR=1.26, 95%CI: 0.57-2.77), but it was associated in non-Hispanic White (OR=4.46, 95%CI: 2.87-6.91) and Mexican American persons (OR=5.61, 95%CI: 2.61-12.04) (Table 1). Similar results were obtained when NAFLD-fibrosis was defined by liver stiffness ≥8.6 kPa and CAP ≥ 263 dB/m, which had 90% sensitivity for detecting steatosis grade 0 vs.1-3. Of interest, non-Hispanic Black persons had a higher prevalence of diabetes than whites (Fig.1B). Thus, the disconnection between diabetes and NAFLD-fibrosis in non-Hispanic Black persons does not stem from a low prevalence of diabetes.
Conclusions: NHANES provides nationally representative data about the residential population of the U.S. NAFLD-fibrosis was not associated with diabetes in non-Hispanic Black persons, indicating that screening algorithms that rely on diabetes to identify people at high risk for NAFLD-fibrosis may inadvertently disadvantage non-Hispanic Black individuals (Supported in part by Pfizer).

Introduction: Overt hepatic encephalopathy (OHE) is a serious clinical complication of cirrhosis. Risk of recurrence is estimated to be as high as 40% within one year of a first OHE episode, resulting in costly and burdensome readmissions. Among patients with an initial OHE hospitalization, little is known about the impact of rifaximin use post-discharge on OHE-related rehospitalization and associated costs in real-world practice.

Methods: Claims data from MarketScan® Commercial Subset (10/01/2015–03/31/2020) were used to identify adults (18-64 years) with an OHE hospitalization (index hospitalization). Based on treatment following index hospitalization, patients were classified into mutually exclusive cohorts: rifaximin treated (with/without lactulose) and not rifaximin treated. The two cohorts were further stratified into four subgroups representing decreasing quality of care (QOC): Type 1 received rifaximin without any gap in treatment following index hospitalization; Type 2 received rifaximin within 30 days post-discharge; Type 3 received lactulose within 30 days post-discharge; Type 4 received no treatment. The length of stay (LOS) for index hospitalization, 30-day OHE-related rehospitalizations, and all-cause healthcare costs were reported. The association of rifaximin use with 30-day OHE-related rehospitalizations and costs were assessed.

Results: Baseline demographics and clinical characteristics were well balanced between the rifaximin treated (N=1,452; Type 1: N=1,138, Type 2: N=314) and not rifaximin treated (N=560; Type 3: N=337, Type 4: N=223) cohorts. Mean age was 54.2 and 55.2 years and 39.3% and 42.7% were female, respectively. The index OHE hospitalization of the rifaximin treated cohort had an average LOS of 10.8 and an average cost of $48,225 compared to 8.0 days and $29,108 for the not rifaximin treated cohort. The 30-day risk of OHE-related rehospitalization following the index hospitalization was lower for the rifaximin treated cohort (6.8%) vs not rifaximin treated (10.5%; adjusted odds ratio (OR) 0.56, p<0.01; Figure 1). Following the index OHE hospitalization, decreasing QOC (from Type 1 to Type 4) resulted in higher 30-day risk of OHE-related rehospitalization; compared to Type 1, the ORs were 1.31 for Type 2 (p=0.28), 1.74 for Type 3 (p=0.01), and 1.90 for Type 4 (p=0.01; Figure 2). Among the rifaximin treated cohort, increased pharmacy costs were offset by an equivalent reduction in medical costs, which led to no significant annual cost differences between the two cohorts.

Conclusions: Patients receiving rifaximin at discharge of their OHE hospitalization were less likely to experience 30-day OHE-related rehospitalizations compared to patients who did not receive rifaximin. The reduction in medical costs offset the increased pharmacy costs among the rifaximin treated cohort, demonstrating that rifaximin use is cost neutral.

<i><b>Figure 1. 30-day risk OHE-related rehospitalization (%)</b></i><br /> <i>*Significant at the 5% level</i><br /> <b>Note: </b><br /> [1] An odds ratio less than 1 indicates that the odds of experiencing an OHE-related rehospitalization in rifaximin treated patients are lower than those of not rifaximin treated patients.

Figure 1. 30-day risk OHE-related rehospitalization (%)
*Significant at the 5% level
Note:
[1] An odds ratio less than 1 indicates that the odds of experiencing an OHE-related rehospitalization in rifaximin treated patients are lower than those of not rifaximin treated patients.

<i><b>Figure 2. Adjusted 30-day risk of OHE-related rehospitalization (%)</b></i><br /> <i>*Significant at the 5% level</i><br /> <b>Notes: </b><br /> [1] An odds ratio greater than 1 indicates that the odds of experiencing an OHE-related rehospitalization in patients with Type 2, 3, or 4 care are greater than those of patients with Type 1 care.<br /> [2] The four subgroups represent decreasing quality of care and are defined as follows: Type 1 received rifaximin without any gap in treatment following hospitalization; Type 2 received rifaximin within 30 days post-discharge; Type 3 received lactulose within 30 days post-discharge; Type 4 received no treatment.

Figure 2. Adjusted 30-day risk of OHE-related rehospitalization (%)
*Significant at the 5% level
Notes:
[1] An odds ratio greater than 1 indicates that the odds of experiencing an OHE-related rehospitalization in patients with Type 2, 3, or 4 care are greater than those of patients with Type 1 care.
[2] The four subgroups represent decreasing quality of care and are defined as follows: Type 1 received rifaximin without any gap in treatment following hospitalization; Type 2 received rifaximin within 30 days post-discharge; Type 3 received lactulose within 30 days post-discharge; Type 4 received no treatment.

Zeev Heimanson

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