Digital Polymerase Chain Reaction-Based Fecal Streptococcus Quantification for Liver Fibrosis Assessment in Chronic...

The aim of this study was to identify clinical factors associated with fecal Streptococcus spp. load in patients with chronic liver disease (CLD) and to evaluate its potential utility, measured through digital polymerase chain reaction (dPCR), as a noninvasive biomarker for liver fibrosis.

Data from 146 patients with CLD enrolled in a prospective single-center cohort were retrospectively analyzed. Fecal Streptococcus spp. load was quantified using dPCR with a 16S rRNA gene primer-probe set. Given the substantial effect of proton pump inhibitor (PPI) use, PPI users were analyzed separately and excluded from fibrosis-specific analyses. Associations with clinical parameters were examined using Spearman's rank correlation, and receiver operating characteristic (ROC) curve analysis was carried out to evaluate diagnostic performance for cirrhosis.

Among 146 patients, 45 (30.8%) were PPI users and 101 (69.2%) were nonusers. Median Streptococcus spp. load was significantly higher in PPI users than in nonusers (470.8 vs. 107.8 copies/μL and p < 0.001). In nonusers, cirrhotic patients had higher loads than noncirrhotic patients (276.8 vs. 43.6 copies/μL and p < 0.001). ROC analysis yielded an area under the curve of 0.728 (cutoff: 28.5 copies/μL; sensitivity 71.4% and specificity 71.4%), which was lower than that of liver stiffness and the Fibrosis-4 index. Streptococcus spp. load correlated positively with age and negatively with body mass index (BMI). Patients aged > 65 years with BMI ≤ 25 kg/m² showed higher loads.

Fecal Streptococcus spp. load measured by dPCR may complement existing noninvasive fibrosis markers in CLD, although host-related factors, such as age and BMI, may limit diagnostic accuracy.