{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:01:30Z","timestamp":1790758890971,"version":"4.1.0"},"reference-count":0,"publisher":"Cell Physiol Biochem Press GmbH and Co KG","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"abstract":"<jats:p>Background\/Aims: Chronic hepatitis C virus (HCV) infection is accompanied by persistent hepatic inflammation, progressive fibrogenesis and metabolic disturbance, of which insulin resistance (IR) is the most consistently reported. The neutrophil-to-lymphocyte ratio (NLR), derived from a routine complete blood count, has been proposed as an inexpensive index of systemic inflammatory activity, but its diagnostic accuracy for IR in fibrotic chronic hepatitis C has not been quantified in Iraqi patients. To quantify the cross-sectional diagnostic performance of NLR for the identification of insulin resistance in patients with fibrotic chronic hepatitis C, and to characterise its associations with metabolic, inflammatory and hepatic biochemical parameters. Methods: A case\u2013control study was conducted at the Baghdad Hospital for Gastroenterology and Hepatology, Medical City, Baghdad, Iraq, between December 2021 and January 2022. One hundred and fifty participants were enrolled consecutively until each of three groups reached its a priori target of 50: patients with fibrotic chronic hepatitis C and insulin resistance (CHC+IR), patients with fibrotic chronic hepatitis C without insulin resistance (CHC\u2212IR), and apparently healthy controls. Insulin resistance was defined a priori as a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value \u2265 2.6. Hepatic fibrosis was recorded as present or absent from clinical, ultrasonographic and available histological records; stage-level fibrosis data were not available. Complete blood count, liver function tests including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), fasting glucose, fasting insulin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-\u03b1) were measured. Groups were compared by Welch analysis of variance with Games\u2013Howell post hoc tests. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis with DeLong confidence intervals and Youden-optimal cut-offs; associations were quantified by Pearson and Spearman correlation with 95 % confidence intervals, and independence was examined by multivariable linear regression and by Firth penalised logistic regression. A sensitivity analysis in which the HOMA-IR threshold of 2.6 was applied strictly, so that a single clinically allocated patient with a recalculated value of 2.59 was reassigned, was performed for all principal outcomes. Results: The three groups were comparable for age (p = 0.075) and sex (p = 0.593). NLR increased stepwise across controls, CHC\u2212IR and CHC+IR (1.79 \u00b1 0.02, 1.95 \u00b1 0.13 and 2.53 \u00b1 0.15, respectively; Welch F = 625.5, p &lt; 0.001; all pairwise comparisons p &lt; 0.001). Within the chronic hepatitis C cohort (n = 100), NLR separated insulin-resistant from non-insulin-resistant patients completely, giving an area under the curve (AUC) of 1.000 at an exploratory, cohort-derived Youden-optimal cut-off of 2.24, with sensitivity and specificity of 100 % (95 % CI 92.9\u2013100 % for each). NLR discriminated fibrotic chronic hepatitis C from healthy controls with an AUC of 0.942 (95 % CI 0.885\u20130.972) at a cut-off of 1.85 (sensitivity 90.0 %, specificity 100 %), whereas the AST\/ALT ratio was uninformative (AUC 0.528, p = 0.583). NLR correlated strongly with HOMA-IR (r = 0.898, 95 % CI 0.852\u20130.930), fasting insulin (r = 0.903), CRP (r = 0.913), TNF-\u03b1 (r = 0.906) and IL-6 (r = 0.798) (all p &lt; 0.001). NLR remained independently associated with HOMA-IR after adjustment for age and sex (B = 2.31, 95 % CI 2.08\u20132.54, p &lt; 0.001) and after further adjustment for hepatic biochemical markers (B = 1.55, 95 % CI 1.16\u20131.94, p &lt; 0.001). Under strict application of the HOMA-IR threshold, which reassigned that patient and gave strata of 49 and 51 patients, the AUC for NLR was 0.9994 (95 % CI 0.9932\u20130.9999), the Youden-optimal threshold was recovered unchanged at 2.24, sensitivity remained 100 % and specificity fell to 98.0 % (95 % CI 89.7\u201399.7 %), and the regression estimates were essentially unaltered (B = 2.31, 95 % CI 2.08\u20132.54; odds ratio 12.04 per 0.1-unit increment in NLR); the direction, magnitude and statistical significance of every principal result were unchanged. Conclusion: In this cohort, NLR was strongly and independently associated with insulin resistance and discriminated insulin-resistant from non-insulin-resistant patients with fibrotic chronic hepatitis C with high accuracy. Because the groups were completely separated on NLR and the threshold was derived in the same sample, the cut-off of 2.24 is an exploratory, cohort-derived threshold rather than an established clinical cut-off, and the accuracy estimates are optimistic and require independent external validation. As all patients had fibrosis and no fibrosis staging was available, the present data support a diagnostic association with the presence of disease rather than prediction of fibrosis severity.<\/jats:p>","DOI":"10.33594\/000000892","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:22:33Z","timestamp":1790756553000},"page":"592-610","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Performance of the Neutrophil-to-Lymphocyte Ratio for the Identification of Insulin Resistance in Patients with Fibrotic Chronic Hepatitis C: a Case\u2013Control Study"],"prefix":"10.33594","volume":"60","author":[{"given":"Yaqot Raed","family":"Alnaqqash","sequence":"first","affiliation":[{"name":"Biochemistry Laboratory \"Molecular Basis of Human Diseases\", Sfax Medicine College, University of Sfax, Sfax, LR19ES13, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Amshawee","sequence":"additional","affiliation":[{"name":"Department of Radiology, College of Health and Medical Technology, University of Hilla, Babylon, Iraq,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Flayyih","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Techniques, College of Health and Medical Technology, Al-Farabi University, Baghdad, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Makni","family":"Ayadi","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory \"Molecular Basis of Human Diseases\", Sfax Medicine College, University of Sfax, Sfax, LR19ES13, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19235","published-online":{"date-parts":[[2026,9,30]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:22:34Z","timestamp":1790756554000},"score":1,"resource":{"primary":{"URL":"https:\/\/cellphysiolbiochem.com\/Articles\/000892\/index.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":0,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,9,30]]}},"URL":"https:\/\/doi.org\/10.33594\/000000892","relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}