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

Abstract

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.

Artificial Intelligence Evaluation of Stool Quality Guides Management of Hepatic Encephalopathy Using a Smartphone App

“…BSS awareness can potentially reduce the tendency to modify lactulose based on BMs/day rather than the characteristics of the BMs (8). BMs/day do not correlate with cognition, and even lower doses of lactulose improve quality of life in cirrhosis (3,9). Operationalizing this in HE using the Dieta app showed that although most controls were agreeable, some patients had reservations with photographing stools, privacy concerns, and lack of smartphones.…”

Diagnosis and Treatment of Cirrhosis—Reply

“…For example, lactulose therapy improves sleep for patients with covert hepatic encephalopathy . Following the publication of our Review, we showed that many patients with cirrhosis experienced improved sleep with use of lactulose even if they had not been diagnosed with hepatic encephalopathy …”

Time to embrace PROMIS-29 as the standard health-related quality of life instrument for patients with cirrhosis

“…Many HRQOL scales are predictive of poor outcomes but may not be responsive to therapeutic interventions. [8] Such change data are necessary to determine the minimum clinically important difference for PROMIS-29 among people with cirrhosis. These aims will be addressed with forthcoming data from the longitudinal cohort study of the NIH-funded Liver Cirrhosis Network (NCT05740358) and Transitional Liver Clinic (NCT05733832) and the PCORIfunded LIVE-SMART (NCT05794555), a randomized trial of lactulose and Tai-Chi, all of which utilize PROMIS-29 + 2.…”