Systemic hematologic, metabolic, and inflammatory dysregulation in liver cirrhosis and hepatocellular carcinoma: diagnostic utility of novel indices in an Egyptian cohort

The transition from chronic liver disease to cirrhosis and ultimately hepatocellular carcinoma (HCC) is accompanied by progressive systemic alterations involving hematologic, metabolic, and inflammatory pathways. Understanding these interconnected changes may refine disease characterization and support early diagnostic or prognostic stratification, especially in high-burden regions such as Egypt. This study aimed to delineate the comprehensive clinical, hematologic, metabolic, and inflammatory profiles distinguishing Egyptian patients with HCC and liver cirrhosis from healthy controls, and to evaluate the diagnostic and discriminative utility of novel systemic inflammatory indices. In this comparative cross-sectional study, 211 participants were enrolled: 70 with HCC, 71 with HCV-related cirrhosis, and 70 healthy controls. Clinical, biochemical, and hematologic parameters were measured, including liver and renal function, lipid profile, and alpha-fetoprotein (AFP). Composite inflammatory indices were calculated: Systemic Inflammation Response Index (SIRI = neutrophils × monocytes/lymphocytes) and GGT-to-Lymphocyte Ratio (GLR = GGT / lymphocytes). Group comparisons were performed using non-parametric tests. Correlations between indices and clinical or tumor features were analyzed by Spearman’s coefficient. Diagnostic performance was assessed using ROC curve analysis and multivariable logistic regression adjusted for age and sex. Both patient groups demonstrated marked systemic dysregulation relative to controls. Hemoglobin, platelet count, albumin, and HDL-C were significantly reduced, whereas bilirubin, transaminases, ALP, INR, AFP, and insulin were progressively elevated (all P < 0.001). Gamma-glutamyl transferase (GGT) was significantly elevated in both patient groups compared to controls, with the highest levels observed in the HCC group. The inflammatory indices SIRI and GLR were significantly higher in cirrhosis and HCC (median SIRI: 1.25 vs. 1.2 vs. 0.6; P < 0.001). GLR, in particular, demonstrated strong discriminatory performance for distinguishing HCC from cirrhosis (AUC = 0.881; 95% CI 0.842–0.921; P < 0.001), achieving significantly higher diagnostic accuracy than SIRI (AUC = 0.742). Subgroup analysis confirmed its superior diagnostic accuracy, especially in patients with advanced liver dysfunction (Child-Pugh B/C; AUC = 0.92). Furthermore, a high GLR (> 22.5) was an independent predictor of reduced overall survival in the HCC cohort (adjusted HR = 2.95; P = 0.004). In multivariable models, elevated GLR and low albumin independently predicted HCC presence (adjusted ORs 2.31 and 0.54, respectively; P < 0.01). Distinct and progressively severe hematologic, metabolic, and inflammatory disturbances characterize the continuum from cirrhosis to HCC. The Gamma-Glutamyl Transferase-to-Lymphocyte Ratio (GLR) showed a strong association with the presence of HCC and demonstrated strong discriminatory performance (AUC = 0.881) for its differentiation from cirrhosis, suggesting it is a promising candidate worthy of further validation in surveillance programs for high-risk Egyptian patients.