Lactulose therapy for patients with cirrhosis, portal hypertension, and poor patient-reported outcomes: The Mi-Kristal trial

• Published in: Hepatology (Baltimore, Md.) Vol. 78; no. 4; pp. 1159 - 1167
• Main Authors: Tapper, Elliot B., Ospina, Erin, Salim, Najat, Chen, Xi, Nikirk, Samantha
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.10.2023
• Subjects: Hepatic Encephalopathy - complications; Hepatic Encephalopathy - etiology; Humans; Hypertension, Portal - complications; Hypertension, Portal - etiology; Lactulose - therapeutic use; Liver Cirrhosis - complications; Liver Cirrhosis - drug therapy; Middle Aged; Patient Reported Outcome Measures; Quality of Life; Treatment Outcome
• ISSN: 0270-9139; 1527-3350; 1527-3350
• DOI: 10.1097/HEP.0000000000000408

Background and Aims: Poor patient-reported outcomes (PROs) are common in cirrhosis, including poor sleep and health-related quality of life (HRQOL). HE is a major driver of poor PROs. Many clinicians initiate lactulose therapy to address poor PROs. PRO-triggered therapy, however, has not been studied till date. Methods: We conducted a 28-day randomized trial of crystalline lactulose therapy (20 g BID) compared with no HE-directed therapy in 52 patients with cirrhosis, portal hypertension, no prior HE, and high Work Productivity and Activity Impairment scores (0-10) attributed to cirrhosis. The primary outcome was change in global HRQOL measured with Short Form-8 Health Survey. Secondary outcomes included change in Animal Naming Test score, Work Productivity and Activity Impairment, and sleep quality (scored "very bad" to "very good"). Approach and Results: Overall, 52 patients underwent randomization; 3 subjects withdrew from the crystalline lactulose arm (1 before medication initiation, 1 due to an unrelated condition, and 1 due to high baseline bowel movements). The average age was 60 years, the average Model for Endstage Liver Disease-Sodium score was 10.5, and 56% of the patients had ascites. Baseline bowel movements were 2.3/day, with 35% of the patients having Bristol Stool Scale >4. At 28 days, there was no improvement in HRQOL: patients receiving crystalline lactulose had an 8.1-point (95% CI: 3.7-12.4) increase compared with 6.6 (95% CI: 2.3-10.8) in the control group (p = 0.6). Lactulose was associated with a significantly (p = 0.002) increased Animal Naming Test score (3.7, 95% CI: 2.1-5.4) versus the control group (0.2, 95% CI: −1.7, 1.4). Lactulose users reported more good sleep (92% vs. 52%, p = 0.001) and lower activity impairment (3.0 vs. 4.8, p = 0.02). Conclusions: Lactulose improves sleep and activity impairment in patients with poor PROs. We did not observe any improvement in global HRQOL after 28 days using the Short Form-8 Health Survey instrument.