Lactulose therapy for patients with cirrhosis, portal hypertension, and poor patient reported outcomes – the Mi-Kristal RCT

Elliot B Tapper ¹, Erin Ospina, Najat Salim, Xi Chen, Samantha Nikirk

PMID: 37066820 DOI: 10.1097/HEP.0000000000000408

Abstract

Background: Poor patient reported outcomes (PROs) are common in cirrhosis including poor sleep and health-related quality of life (HRQOL). Hepatic encephalopathy (HE) is a major driver of poor PROs. Many clinicians initiate lactulose to address poor PROs. PRO-triggered therapy, however, has not been studied.

Methods: We conducted a 28-day randomized trial of crystalline lactulose (20g BID) compared to no HE-directed therapy in 52 patients with cirrhosis, portal hypertension, no prior HE, and high work-productive activity impairment (WPAI, 0-10) attributed to cirrhosis. The primary outcome was change in global HRQOL measured with the SF-8. Secondary outcomes include change in animal naming test (ANT), WPAI, and sleep quality (scored very bad to very good).

Results: Overall, 52 patients underwent randomization, 3 subjects withdrew from the Crystalline lactulose arm (1 prior to medication initiation, 1 due to an unrelated condition, 1 with high baseline bowel movements declined continuation). Average age was 60 years, MELD-Na was 10.5, and 56% had ascites. Baseline bowel movements were 2.3/day with 35% having Bristol stool scales > 4. At 28-days there was no improvement in HRQOL: patients receiving Crystalline lactulose had an 8.1 95%CI(3.7-12.4) point increase compared to 6.6 95%CI(2.3-10.8) in control (p = 0.6). Lactulose was associated with significantly (p = 0.002) increased ANT – 3.7 95%CI(2.1-5.4) versus control – -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).

Conclusion: Lactulose improves sleep and activity impairment in patients with poor PROs. We did not observe improved global HRQOL after 28-days using the SF-8 instrument.

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