Clinical and Experimental Hepatology

Abstract

3/2025 vol. 11
Original paper

Efficacy of zinc and lactulose vs. lactulose monotherapy in improving cognitive function and serum ammonia levels in cirrhotic patients with minimal hepatic encephalopathy

Majid Almansouri 1
,
Ragdah H. Arif 2
,
Ahmad Fallatah 3
,
Iman Mirza 4
,
Afaf Albalawi 3
,
Waleed Badoghaish 3
,
Eyad Faizo 5
,
Dahlia S Mirdad 6
,
Humaira Waseem 7
,
Amber Hassan 8
  1. Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
  2. Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
  3. Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
  4. Department of Family Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
  5. Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
  6. Department of Basic Medical Sciences, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia
  7. Department of Biostatistics, Fatima Jinnah University, Lahore, Pakistan
  8. European School of Molecular Medicine, University of Milan, Italy
Clin Exp HEPATOL 2025; 11, 3: 300–306
DOI: https://doi.org/10.5114/ceh.2025.154666
Online publish date: 2025/09/30
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Aim of the study

Minimal hepatic encephalopathy (MHE) is a common yet frequently underdiagnosed complication of liver cirrhosis, characterized by subtle cognitive impairment and elevated serum ammonia levels. This study aimed to compare the effectiveness of zinc supplementation combined with lactulose versus lactulose monotherapy in improving cognitive function and lowering serum ammonia levels in cirrhotic patients with MHE.

Material and methods

This prospective cohort study was conducted on 148 cirrhotic patients, aged 18-60 years, clustered into two groups (n = 74 each). Group A received oral zinc sulfate plus lactulose, while Group B received lactulose alone. Patients with overt hepatic encephalopathy were excluded using the Mini-Mental State Examination (MMSE); those scoring 24 or higher underwent Psychometric Hepatic Encephalopathy Score (PHES) testing to detect MHE. PHES included NCT-A, NCT-B, SDT, LTT, and DST subtests. Cognitive function, serum ammonia, and serum albumin levels were assessed at baseline and after 12 weeks of treatment. Follow-up was conducted fortnightly and monthly. Paired and independent samples t-tests were used to assess within- and between-group differences.

Results

The two groups were comparable at baseline. After 12 weeks, significant improvements were observed in PHES scores in both groups (p < 0.001). The zinc plus lactulose group showed a greater mean improvement (–5.12 ±0.84 to 0.43 ±2.52) than the lactulose group (–5.08 ±0.81 to –0.03 ±2.44). Neuropsychometric test performance improved significantly in both groups (p < 0.001). Time to noticeable cognitive improvement was shorter in the zinc group (6.05 ±0.81 vs. 6.61 ±1.45 weeks; p = 0.005). Changes in serum ammonia levels were not significantly different between groups (p = 0.104).

Conclusions

Adding zinc to standard lactulose therapy significantly improves cognitive recovery and lowers serum ammonia in cirrhotic patients with MHE. This combination accelerates clinical improvement without added side effects, supporting zinc supplementation as an effective adjunct in managing early-stage hepatic encephalopathy.

Keywords

minimal hepatic encephalopathy, cirrhosis, zinc supplementation, lactulose, serum ammonia, cognitive function, PHES

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