2026 Southeastern Residency Conference

Background/Purpose: 
Hepatic encephalopathy (HE) is a common and burdensome complication of cirrhosis, associated with significant morbidity, mortality, and frequent hospitalizations. Lactulose remains the cornerstone of therapy; however, its use is often limited by poor tolerability and adherence. Rifaximin is recommended as add-on therapy for prevention of recurrence, but in clinical practice, it is increasingly used as monotherapy, particularly in patients who are unable to tolerate lactulose. 

Despite this shift, there is limited real-world data evaluating the effectiveness of rifaximin monotherapy in the inpatient setting. The purpose of this study was to compare clinical outcomes between patients treated with rifaximin monotherapy and those treated with rifaximin in combination with lactulose for the treatment of overt HE across the Wellstar Health System. 
 
Methodology: 
Adult patients (≥18 years) with cirrhosis who had been hospitalized for an episode of overt hepatic encephalopathy (HE; ICD-10 K76.82) between January 1, 2015, and July 31, 2025, were enrolled into this retrospective cohort study. These patients were categorized according to the treatment they received while hospitalized: those treated with rifaximin as monotherapy, and those treated with rifaximin + lactulose. Patients with acute liver failure, active infection, intensive care unit admissions, or hospitalizations of < 24 hours were excluded. The primary outcome was improvement in hepatic encephalopathy, defined as a reduction of one or more points in the West Haven Score grade during hospitalization. Secondary outcome measures include changes in serum ammonia levels, length of stay (LOS), acute kidney injury (AKI) events, in-hospital mortality, 30-day mortality, and 30-day readmissions due to HE. The continuous data collected were compared using two-sample t-tests. Categorical data collected were compared using chi-squared analyses. A p-value of ≤ .05 was used to determine if observed differences are statistically significant. 
 
Results: 
A total of 104 patients were included, with 52 patients in each group. Baseline characteristics were well balanced between groups, including age (57.3 vs 56.8 years, p=0.84), Charlson Comorbidity Index (4.94 vs 4.79, p=0.48), and MELD score (~20 in both groups, p=0.91). 

Both treatment groups demonstrated meaningful reduction in WHS grade during hospitalization. The mean WHS decreased from 2.94 to 0.96 in the lactulose + rifaximin group and from 2.87 to 0.88 in the rifaximin monotherapy group. The degree of improvement was similar between groups (mean change: 1.98 vs 1.99, p=0.96).  

Ammonia levels decreased in both groups as well, from 75.7 to 53.9 µmol/L in the lactulose + rifaximin group and from 71.3 to 52.3 µmol/L in the rifaximin group, with no significant difference observed (p=0.61). 

Hospital length of stay was numerically shorter in the rifaximin monotherapy group (5.38 vs 6.85 days), though this did not reach statistical significance (p=0.17). 

Rates of AKI, 30-day readmission, and mortality were low and comparable between groups. AKI occurred in 3.8% vs 5.8% of patients (p=0.65), and 30-day readmission occurred in 0% vs 3.8% (p=0.15) in the lactulose + rifaximin and rifaximin groups, respectively. In-hospital mortality occurred in 0% of patients in the lactulose + rifaximin group and 5.8% in the rifaximin group; however, this difference was not statistically significant (p=0.08). 

Conclusions: 
Rifaximin monotherapy demonstrated similar effectiveness to combination therapy with lactulose in reducing WHS grade and reducing ammonia levels during hospitalization. 

No meaningful differences were observed in readmissions, AKI, or overall safety outcomes. While not statistically significant, the shorter LOS observed in the monotherapy group may suggest a potential advantage that warrants further investigation. 

These findings support the idea that rifaximin monotherapy may be a reasonable alternative in select patients, particularly those who are unable to tolerate lactulose. Given the limitations of retrospective data and potential confounding factors, larger prospective studies are needed to better define the role of rifaximin monotherapy in the management of hepatic encephalopathy.