Multimarker model for non-invasive assessment of variceal bleeding in chronic hepatitis C cirrhotic patients

Abstract

BACKGROUND

Despite the success of direct-acting antivirals, a large global population with established hepatitis C virus (HCV)-related cirrhosis remains at lifelong risk for portal hypertensive complications like variceal bleeding. This persistent burden, coupled with the rising incidence of cirrhosis from other etiologies, underscores the critical need for accessible, non-invasive risk stratification tools.

AIM

To evaluated a multimarker panel, including free triiodothyronine (FT3), platelet count (PLT), international normalized ratio (INR), and portal vein diameter (PVD), for the non-invasive stratification of variceal bleeding risk.

METHODS

A case-control study was conducted on 93 participants, categorized into three groups: 31 chronic HCV cirrhotic patients with variceal bleeding (group I), 31 chronic HCV cirrhotic patients without variceal bleeding (group II), and 31 healthy controls (group III). Thyroid function tests (thyroid-stimulating hormone, FT3, free thyroxine), PLT, INR, spleen size, and PVD were assessed. Doppler ultrasound was used to evaluate portal venous blood flow, while upper gastrointestinal endoscopy determined the variceal grades. Statistical analysis included one-way analysis of variance, Pearson correlation, multivariate ordinal logistic regression, and receiver operating characteristic curve analysis.

RESULTS

FT3 levels were significantly lower in cirrhotic patients, with the lowest levels in group I (P < 0.01). Higher variceal grades (III/IV) were associated with lower FT3, lower PLT, and higher INR (P < 0.01). In multivariate analysis, lower FT3, lower PLT, and higher INR were independent predictors of variceal severity (all P < 0.01). FT3 < 2.5 pmol/L predicted high-grade varices with an area under the curve (AUC) of 0.88 (sensitivity 85.7%, specificity 78.3%). PVD ≥ 13 mm also showed strong predictive value (AUC = 0.85). A novel Variceal Risk Score (VRS) integrating FT3, PLT, INR, and PVD demonstrated outstanding accuracy (AUC = 0.94).

CONCLUSION

This study validates a multimarker approach, identifying a core panel of non-invasive predictors-FT3, PLT, and INR for variceal bleeding risk. The derived VRS can accurately identify high-risk cirrhotic patients, suggesting its potential use as a triage tool to make endoscopic screening programs more efficient.

Keywords: Thyroid dysfunction; Hepatitis C virus; Cirrhosis; Portal hypertension; International normalized ratio; Platelet count; Portal hemodynamics

Core Tip: This study validates a novel, non-invasive multimarker approach for identifying chronic hepatitis C cirrhotic patients at high risk for variceal bleeding. We identified a core panel of independent predictors: Low free triiodothyronine levels, low platelet count, and high international normalized ratio. A composite Variceal Risk Score integrating these with portal vein diameter demonstrated outstanding accuracy (area under the curve = 0.94). This strategy can efficiently triage patients for endoscopic screening, potentially reducing procedural burden in resource-limited settings.