| Summary: | We investigated the prognostic role of the gut microbiome and clinical factors in chronic liver disease (hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]). Utilizing data from 227 patients whose stool samples were collected over the prior 3 years and a Cox proportional hazards model, we integrated clinical attributes and microbiome composition based on 16S ribosomal RNA sequencing. HCC was the primary cause of mortality, with the Barcelona Clinic Liver Cancer staging system-derived B/C significantly increasing the mortality risk (hazard ratio [HR] = 8.060; 95% confidence interval [CI]: 3.6509–17.793; <i>p</i> < 0.001). Cholesterol levels < 140 mg/dL were associated with higher mortality rates (HR = 4.411; 95% CI: 2.0151–9.6555; <i>p</i> < 0.001). <i>Incertae sedis</i> from <i>Ruminococcaceae</i> showed a protective effect, reducing mortality risk (HR = 0.289; 95% CI: 0.1282 to 0.6538; <i>p</i> = 0.002), whereas increased <i>Veillonella</i> presence was associated with a higher risk (HR = 2.733; 95% CI: 1.1922–6.2664; <i>p</i> = 0.017). The potential of specific bacterial taxa as independent prognostic factors suggests that integrating microbiome data could improve the prognosis and treatment of chronic liver disease. These microbiome-derived markers have prognostic significance independently and in conjunction with clinical factors, suggesting their utility in improving a patient’s prognosis.
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