The Rising Threat of Liver Cancer in Patients with Cirrhosis: Are Indeterminate Liver Nodules Cause for Concern? Real-world, long-term follow-up data

Background: Several studies have shown a higher risk of liver cancer from indeterminate liver nodules, but the exact occurrence and predictors of liver cancer in this group are still unclear. Our aim is to study the development of liver cancer in this population and identify any potential risk factors. Methods: This retrospective study evaluated cirrhotic patients with indeterminate liver nodules from 2013 to 2023.Data from electronic patient records was analyzed to assess the association between HCC and baseline factors.Subgroup exploratory analysis compared characteristics of patients with de novo HCC and those with nodule transformation HCC. Results: Out of 116 patients with liver nodules, 19 (16%) developed HCC in up to 7.5-year follow-up. Univariate Cox regression analysis showed a significant association between HCC incidence and smoking [hazard ratio (HR) 2.60, 95% Confidence Interval [CI] 1.01-6.74), nodule diameter exceeding 2cm (HR 5.41, 95% CI 1.45-20.18), and baseline LI-RADS score 3 (HR 3.78, 95% CI 1.36-19.52). Multivariate Cox regression analysis revealed significant independent associations with nodule diameters 1 cm to <2cm (adjusted HR 3.35, 95% CI 1.06-10.60) and greater than 2cm (adjusted HR 5.85, 95% CI 1.10-31.16), as well as with LI-RADS 3 lesions (adjusted HR 3.75, 95% CI 1.16-12.11) with adjusting other potential predictors and covariates. Conclusion: Our findings show a higher incidence of HCC in patients with indeterminate liver nodules, increasing over time and reaching 30% at seven years. Nodules larger than 1-2 cm or LI-RADS 3 lesions pose increased risk for HCC. Enhanced surveillance is necessary given the lack of clear management guidelines.