Intestinal permeability assessed by serum zonulin in liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND

In recent years, increased intestinal permeability has been considered a hallmark of liver cirrhosis (LC), thereby exposing the liver to many bacteria and microbial components of a leaky gut, such as zonulin which is a recognized biomarker of intestinal permeability. The topic is underresearched and professional consensus regarding intestinal permeability in cirrhosis is still lacking. Our systematic review and meta-analysis aimed to investigate the intestinal permeability assessed by serum zonulin levels in patients with LC.

METHODS

The systematic search covered 3 databases with the following search key: "zonulin" AND "LC" OR "cirrhosis." Our investigated population (P) consisted of patients diagnosed with LC. Eligible studies compared the levels of serum zonulin in patients with LC (I) to the control group (C). Our primary outcome (O) was the difference in serum zonulin in patients with LC compared with controls (PROSPERO CRD42024580574).

RESULTS

In total, 4 studies fulfilled the eligibility criteria for the qualitative and quantitative analysis. The mean effect size estimate was 0.590 (95% confidence interval: 0.325-0.855) and statistically significant (t = 4.378, P < .001). For heterogeneity, Q-statistics and I2 values were examined. The Q-statistics (Q = 123.4974, df = 3, P < .0001) was found to be statistically significant. In addition, the I2 value was found to be 97.57% (95% confidence interval: 95.83-98.59). As a result, there was a statistically significant heterogeneity between studies.

CONCLUSION

In this systematic review and meta-analysis, we summarized the current evidence on the importance of zonulin. Currently, there is no clear evidence regarding the axis between the gut and liver, particularly cirrhosis, and zonulin is known as a surrogate biomarker for a leaky gut. An important aspect to consider is the fact that zonulin is primarily produced in the liver; in cases of LC, its synthesis is impaired, which is why zonulin cannot be considered a marker of intestinal permeability in this pathology. Further randomized controlled trials assessing this impaired intestinal permeability and gut-liver axis in patients with liver diseases will be necessary.