Hepatitis A Virus Seropositivity as a Predictor of Thrombocytopenia and Disease Progression in Chronic Liver Disease

Abstract

Background: Thrombocytopenia represents a frequent complication in chronic liver disease, yet reliable non-invasive predictive biomarkers remain inadequately characterized. The tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-2 (MMP-2) participate in hepatic fibrogenesis and may serve as indicators of disease progression.

Aim: To evaluate hepatitis A virus seropositivity, serum TIMP-1, MMP-2, and their ratio as predictive biomarkers for thrombocytopenia in chronic liver disease patients.

Methods: This cross-sectional study enrolled 148 chronic liver disease patients. Participants underwent assessment of anti-HAV IgG status, serum TIMP-1, MMP-2 levels, and complete hematological profiles. Thrombocytopenia was defined as platelet count below 150 × 10⁹/L. Receiver operating characteristic analysis determined optimal cut-off values.

Results: HAV IgG-positive patients demonstrated significantly higher thrombocytopenia prevalence (65.0% vs. 42.6%, p=0.025). Serum TIMP-1 was markedly elevated in HAV-positive thrombocytopenic patients (180.46 ± 68.41 ng/mL) compared to HAV-negative patients without thrombocytopenia (80.90 ± 44.05 ng/mL, p<0.001). The TIMP-1/MMP-2 ratio showed excellent discriminative capacity for thrombocytopenia in HAV-positive patients (AUC=0.805, sensitivity 84.6%, specificity 71.4% at cut-off ≥1.15). Multivariate analysis confirmed HAV IgG positivity (OR=2.28, p=0.031), elevated TIMP-1 (OR=1.021 per ng/mL, p<0.001), and reduced MMP-2 (OR=0.988 per ng/mL, p<0.001) as independent thrombocytopenia predictors.

Conclusion: HAV seropositivity, serum TIMP-1, MMP-2, and particularly the TIMP-1/MMP-2 ratio represent valuable non-invasive biomarkers for predicting thrombocytopenia in chronic liver disease, potentially reducing dependence on invasive diagnostic procedures.