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. 2025 Oct 17;14(20):7331.
doi: 10.3390/jcm14207331.

Lactulose, Rifaximin, and Survival in Hepatic Encephalopathy: A Cohort Study of 120 Patients

Luana Alexandrescu  1   2 , Ionut Tiberiu Tofolean  1   2 , Cristina Aftenie  1 , Daria Maria Alexandrescu  3 , Doina Ecaterina Tofolean  2   4 , Alina Doina Nicoara  5 , Alina Mihaela Stanigut  2   6 , Andreea Nelson Twakor  5 , Elena Rusu  3 , Eugen Dumitru  1   2 , Andrei Dumitru  1   2 , Cristina Tocia  1   2 , Alexandra Herlo  7 , Miruna Alexa Mihu  1 , Ioana Popescu  1 , Elena Dina  1 , Bogdan Cimpineanu  2   6
Affiliations

Lactulose, Rifaximin, and Survival in Hepatic Encephalopathy: A Cohort Study of 120 Patients

Luana Alexandrescu et al. J Clin Med. .

Abstract

Background: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of advanced liver disease, driven primarily by ammonia accumulation due to impaired hepatic detoxification and portosystemic shunting. Lactulose is a cornerstone therapy, while rifaximin serves as an effective adjunct for reducing recurrence and hospitalizations. Methods: We conducted a retrospective cohort study at Constanța Emergency County Hospital from January 2022 to March 2025, including 120 adult patients diagnosed with HE. Inclusion criteria were confirmed diagnosis of cirrhosis with clinical and/or biochemical evidence of HE. Patients with other primary neurological disorders or incomplete medical records were excluded. Data on demographics, comorbidities, laboratory results, and medications were collected. Statistical analyses were performed employing descriptive statistics, Friedman's two-way ANOVA by ranks for medication use, and Cox proportional hazards regression to assess survival associations. Results: The mean age was 61.19 years, with high prevalence of anemia (mean hemoglobin: 9.35 g/dL) and thrombocytopenia (mean: 121.86 × 103/µL). Inflammatory markers were elevated (mean CRP: 36.95 mg/L; ESR: 55.83 mm/h), and INR averaged 1.86. Lactulose was administered to 63.3% of patients, rifaximin to 52.5%, with diuretics, pantoprazole, and albumin being frequently used. Friedman's analysis ranked lactulose highest in usage frequency. Cox regression indicated no significant short-term survival difference associated with toxic encephalopathy or rifaximin use. Conclusion: In this cohort, lactulose remained the primary treatment for HE, often complemented by supportive pharmacotherapy. While rifaximin use was limited, the overall medication patterns reflected standard practice priorities in HE management.

Keywords: cirrhosis; hepatic encephalopathy; lactulose; liver failure; rifaximin; survival analysis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Stages of liver disease progression. Created with Biorender [5].
Figure 2
Figure 2
Related-samples Friedman’s two-way analysis of variance by ranks for selected medications in our study cohort.
Figure 3
Figure 3
Cox proportional hazards survival curves for patients with and without toxic encephalopathy.
Figure 4
Figure 4
Cox proportional hazards cumulative hazard curves for patients with and without toxic encephalopathy.
Figure 5
Figure 5
Distribution of Lactulose and Rifaximin use in relation to in-hospital mortality in patients with hepatic encephalopathy.
See this image and copyright information in PMC

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