SIBO-Associated Biochemical Activity in Patients with Metabolic and Viral Chronic Liver Diseases

Abstract

Background/Aim: Small intestinal bacterial overgrowth (SIBO) may contribute to gut–liver axis dysfunction through increased intestinal permeability, bacterial translocation, endotoxemia and systemic inflammation. However, it remains unclear whether SIBO positivity is associated with a distinct biochemical phenotype in chronic liver disease, especially when different etiologies are analyzed together. This study aimed to compare liver enzymes, inflammatory markers and non-invasive fibrosis-related parameters between SIBO-positive and SIBO-negative patients in a pooled cohort of metabolic liver disease and viral hepatitis.
Methods: A de-identified pooled dataset including 311 patients with chronic liver disease was analyzed. The cohort consisted of patients with metabolic liver disease and viral hepatitis who underwent evaluation for SIBO together with routine biochemical and liver-related assessment. SIBO status was available in 310 patients. Variables included age, sex, liver disease etiology, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, platelet count, hemoglobin, erythrocyte sedimentation rate, ultrasonographic findings and FIB-4 index. Continuous variables were summarized as median with interquartile range and compared using the Mann–Whitney U test. Categorical variables, including clinically relevant enzyme elevations, were analyzed using chi-square or Fisher’s exact test.
Results: Among 310 evaluable patients, 109 were SIBO-positive and 201 were SIBO-negative, resulting in an overall SIBO prevalence of 35.2%. SIBO-positive patients were slightly younger than SIBO-negative patients, with a median age of 43.5 [36.0–55.0] versus 46.0 [37.0–60.2] years (p=0.048). SIBO positivity was associated with higher hepatocellular enzyme levels. Median ALT was significantly higher in SIBO-positive patients than in SIBO-negative patients (42.0 [25.0–67.0] vs 31.5 [20.0–51.2] U/L, p=0.003). Median AST was also higher in the SIBO-positive group (33.5 [23.6–52.0] vs 27.1 [21.0–42.0] U/L, p=0.012). In addition, SIBO-positive patients had significantly higher ALP levels than SIBO-negative patients (95.9 [75.0–157.8] vs 81.0 [64.0–107.0] U/L, p=0.007), indicating a possible cholestatic component of the SIBO-associated biochemical profile. When enzyme elevations were analyzed categorically, ALT >40 U/L was more frequent among SIBO-positive patients than SIBO-negative patients (56/107 [52.3%] vs 77/200 [38.5%], p=0.020; OR 1.75, 95% CI 1.09–2.82). ALP >120 U/L was also more frequent in the SIBO-positive group (23/75 [30.7%] vs 28/149 [18.8%], p=0.045; OR 1.91, 95% CI 1.01–3.63) (Figure 1, Figure 2 ). In contrast, platelet count, hemoglobin, ESR and FIB-4 did not differ significantly according to SIBO status.
Conclusion: In this pooled cohort of metabolic and viral chronic liver diseases, SIBO positivity was associated with significantly higher ALT, AST and ALP levels and with increased rates of clinically relevant ALT and ALP elevation. The absence of significant differences in platelet count and FIB-4 suggests that SIBO may be more closely related to biochemical activity than to fibrosis burden in this dataset. These findings support further prospective studies to determine whether SIBO is a modifiable marker of hepatic biochemical activity and whether SIBO-directed therapy can improve liver-related outcomes.