Background: Rifaximin, a nonsystemic antibiotic, may be used alone or in combination with lactulose for reducing the risk of overt hepatic encephalopathy (OHE) recurrence in adults. This analysis evaluated rifaximin alone and rifaximin + lactulose (combination) on health-related quality of life (QOL) and caregiver burden in patients with a history of OHE.
Methods: In a phase 4, randomized, open-label trial, adults with cirrhosis with a history of ≥1 OHE episode during the prior 6 months, currently in HE remission (Conn score ≤1), received rifaximin 550 mg twice daily (BID) or rifaximin 550 mg BID + lactulose (titrated to produce 2-3 soft stools/d) for 24 wks. Chronic Liver Disease Questionnaire (CLDQ) and Caregiver Burden Inventory (CBI) were measured at baseline (BL) and Wks 4, 8, 12, 16, 20, and 24, with CBI measured at Wks 4, 8, 12, 16, and 20 only if the caregiver was present. A higher CLDQ score meant better QOL, while higher CBI score meant greater feelings of burden.
Results: 221 patients received rifaximin alone (n=113) or rifaximin + lactulose combination (n=108). For rifaximin alone versus combination, mean age was 58.1 vs 58.8 y; male sex, 61.1% vs 64.8%; mean MELD score (standard deviation [SD]) was 11.9 (3.6) vs 11.8 (3.2); and BL CLDQ total score (SD) was 4.1 (1.1) vs 4.3 (1.2). Significant improvements from BL were observed for CLDQ total score for both treatment groups at Wks 4, 8, and 12 (Wk 12, rifaximin alone, 0.28 [P=0.006] and combination, 0.27 [P=0.008]); however, these significant improvements from BL were maintained only in rifaximin-alone group, starting at Wk 16 through Wk 24 (P≤0.002; for Wk 24, rifaximin alone, 0.41 [P<0.0001] and combination, 0.11 [P=0.39]). Change from BL in several CLDQ domains differed between the 2 groups, with significant differences from BL with rifaximin alone for 5 of the 6 domains at Wk 24. For between-treatment comparisons, significantly larger improvements for rifaximin alone versus combination (least-squares means data) were observed at some time points for domains of “abdominal symptoms” (Wk 20, 0.27 vs −0.21; P=0.03), “activity” (Wk 20, 0.57 vs 0.14; P=0.04), “emotional function” (Wk 16, 0.43 vs 0.05; P=0.01; Wk 24, 0.47 vs 0.07; P=0.01), and “systemic symptoms” (Wk 16, 0.29 vs −0.12; P=0.007). For “worry” at Wk 12, a smaller increase was observed with rifaximin alone (0.10) vs combination (0.51; P=0.04). Change from BL in total CBI indicated a greater caregiver burden with combination versus rifaximin alone, although there were no significant differences from BL in either group at timepoints assessed (Wk 24, rifaximin alone, −0.55 [P=0.14] and combination, +0.59 [P=0.07]). For between-treatment comparisons, rifaximin alone significantly reduced mean score or produced smaller increases (burden) in mean score versus combination for some domains, (eg, “social burden” [Wks 16, 20, and 24; P value range at 75th percentile of baseline, 0.003–0.02]).
Conclusions: Rifaximin alone for reducing the risk of overt HE recurrence in adults improved several patient QOL and caregiver burden measures.
Support provided by Salix Pharmaceuticals.