Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study

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Hassan Al-Alosi" }, { "@type": "Person", "name": "Muthana Ali Khalil" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Background Hepatitis C virus (HCV) infection demonstrates significantly elevated prevalence among hemodialysis populations worldwide, with particularly high rates in Middle Eastern countries. Despite this epidemiological pattern, limited evidence exists regarding the impact of HCV infection on hemostatic complications following arteriovenous fistula (AVF) creation in patients with end-stage renal disease (ESRD). Methods This prospective cohort study enrolled 460 patients diagnosed with ESRD requiring AVF creation at three tertiary hospitals in Baghdad, Iraq (Al-Yarmouk Teaching Hospital, Ibn-Al-Nafees Teaching Hospital, and Al-Shaheed Ghazi Al-Hariri Surgical Hospital), between January 2017 and January 2024. Patients were stratified by HCV serological status using third-generation enzyme-linked immunosorbent assay. The primary outcome was hemostatic complications (bleeding requiring intervention or clinically significant hematoma) monitored for six weeks postoperatively. Secondary outcomes included coagulation parameters, AVF maturation rates, and other vascular complications. Multivariate logistic regression identified independent predictors of complications. Results Among 460 patients, 151 (32.8%) tested positive for HCV. HCV-positive patients demonstrated significantly prolonged prothrombin time (19±5 versus 15±2.5 seconds, p<0.001), activated partial thromboplastin time (40±4 versus 32±3 seconds, p<0.001), and reduced platelet count (153±43 versus 215±72 ×103/mm3, p<0.001). Hemostatic complications occurred in 28.5% of HCV-positive patients compared to 5.5% of HCV-negative patients (crude OR: 6.835, 95% CI: 3.597-12.987, p<0.001). In multivariate analysis, HCV infection emerged as the strongest independent predictor of hemostatic complications (adjusted OR: 5.892, 95% CI: 3.102-11.196, p<0.001). AVF maturation rates were significantly lower in HCV-positive patients (74.2% versus 86.4%, p=0.002). Conclusions Hepatitis C virus infection increases hemostatic complications following AVF creation nearly six-fold and adversely affects fistula maturation rates. These findings emphasize the importance of incorporating HCV status into preoperative risk stratification and perioperative management protocols, particularly in high-prevalence regions. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/15-254/v1", "name": "Hepatitis C virus infection as a six-fold risk factor for hemostatic..." } } ] } Home Browse Hepatitis C virus infection as a six-fold risk factor for hemostatic... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Hassan Al-Alosi BM and Khalil MA. Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.12688/f1000research.174443.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] Bassam M. Hassan Al-Alosi 1 , Muthana Ali Khalil https://orcid.org/0000-0003-4501-5524 2 Bassam M. Hassan Al-Alosi 1 , Muthana Ali Khalil https://orcid.org/0000-0003-4501-5524 2 PUBLISHED 13 Feb 2026 Author details Author details 1 Surgery, University of Anbar College of Medicine, Ramadi, Al Anbar Governorate, 31001, Iraq 2 Microbiology, University of Anbar College of Medicine, Ramadi, Al Anbar Governorate, 31001, Iraq Bassam M. Hassan Al-Alosi Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Muthana Ali Khalil Roles: Data Curation, Investigation, Methodology, Resources, Validation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Fallujah Multidisciplinary Science and Innovation gateway. Abstract Background Hepatitis C virus (HCV) infection demonstrates significantly elevated prevalence among hemodialysis populations worldwide, with particularly high rates in Middle Eastern countries. Despite this epidemiological pattern, limited evidence exists regarding the impact of HCV infection on hemostatic complications following arteriovenous fistula (AVF) creation in patients with end-stage renal disease (ESRD). Methods This prospective cohort study enrolled 460 patients diagnosed with ESRD requiring AVF creation at three tertiary hospitals in Baghdad, Iraq (Al-Yarmouk Teaching Hospital, Ibn-Al-Nafees Teaching Hospital, and Al-Shaheed Ghazi Al-Hariri Surgical Hospital), between January 2017 and January 2024. Patients were stratified by HCV serological status using third-generation enzyme-linked immunosorbent assay. The primary outcome was hemostatic complications (bleeding requiring intervention or clinically significant hematoma) monitored for six weeks postoperatively. Secondary outcomes included coagulation parameters, AVF maturation rates, and other vascular complications. Multivariate logistic regression identified independent predictors of complications. Results Among 460 patients, 151 (32.8%) tested positive for HCV. HCV-positive patients demonstrated significantly prolonged prothrombin time (19±5 versus 15±2.5 seconds, p<0.001), activated partial thromboplastin time (40±4 versus 32±3 seconds, p<0.001), and reduced platelet count (153±43 versus 215±72 ×10 3 /mm 3 , p<0.001). Hemostatic complications occurred in 28.5% of HCV-positive patients compared to 5.5% of HCV-negative patients (crude OR: 6.835, 95% CI: 3.597-12.987, p<0.001). In multivariate analysis, HCV infection emerged as the strongest independent predictor of hemostatic complications (adjusted OR: 5.892, 95% CI: 3.102-11.196, p<0.001). AVF maturation rates were significantly lower in HCV-positive patients (74.2% versus 86.4%, p=0.002). Conclusions Hepatitis C virus infection increases hemostatic complications following AVF creation nearly six-fold and adversely affects fistula maturation rates. These findings emphasize the importance of incorporating HCV status into preoperative risk stratification and perioperative management protocols, particularly in high-prevalence regions. READ ALL READ LESS Keywords Hepatitis C Virus, Arteriovenous Fistula, Hemostatic Complications, Hemodialysis, End-Stage Renal Disease, Coagulopathy, Vascular Access, Direct-Acting Antivirals Corresponding Author(s) Muthana Ali Khalil ( [email protected] ) Close Corresponding author: Muthana Ali Khalil Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2026 Hassan Al-Alosi BM and Khalil MA. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions. How to cite: Hassan Al-Alosi BM and Khalil MA. Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.12688/f1000research.174443.1 ) First published: 13 Feb 2026, 15 :254 ( https://doi.org/10.12688/f1000research.174443.1 ) Latest published: 13 Feb 2026, 15 :254 ( https://doi.org/10.12688/f1000research.174443.1 ) Introduction The global incidence of end-stage renal disease (ESRD) continues to rise, representing a significant public health challenge. Hemodialysis remains the predominant form of renal replacement therapy. 1 The arteriovenous fistula (AVF) represents the gold standard for vascular access, demonstrating superior long-term patency rates and fewer infectious complications compared to alternatives. 2 However, AVF success depends on numerous patient-specific factors, including advanced age, diabetes mellitus, cardiovascular disease, and poor vessel quality. 2 , 3 Among these, hepatitis C virus (HCV) infection has emerged as a significant yet underrecognized factor influencing surgical outcomes. 4 Hepatitis C virus is a single-stranded RNA virus that primarily targets hepatocytes, causing chronic inflammation and liver damage. HCV demonstrates significant genetic heterogeneity with seven major genotypes and a high mutation rate that contributes to viral persistence. 5 Approximately 71 million individuals worldwide have chronic HCV infection, with disproportionately higher rates among hemodialysis populations. 6 Globally, 8-10% of hemodialysis patients harbor HCV infection, with substantial geographical variation. 6 – 8 The Middle East shows particularly elevated rates of 25-30%, with Iraq, Egypt, and Syria reporting prevalence exceeding 30-45% among dialysis patients 8 – 10 . This burden reflects nosocomial transmission, historical blood transfusions, shared dialysis equipment, and immunocompromised states in ESRD populations. 8 – 10 The COVID-19 pandemic has strained dialysis healthcare systems and infection control protocols, potentially increasing nosocomial HCV transmission in resource-limited settings. 11 – 14 Resource reallocation, reduced staffing, and challenges maintaining infection control may have exacerbated HCV transmission in dialysis facilities, particularly in high-prevalence regions. HCV-related coagulopathy involves complex mechanisms. Chronic hepatic inflammation and fibrosis impair synthesis of vitamin K-dependent clotting factors, prolonging prothrombin and partial thromboplastin times. 15 Thrombocytopenia arises through splenic sequestration, decreased thrombopoietin production, and potential viral suppression of megakaryopoiesis. 16 HCV-associated cryoglobulinemia can induce vasculitis and endothelial dysfunction. 17 The coexistence of uremia-associated platelet dysfunction in ESRD patients compounds these abnormalities, creating high risk for bleeding complications following vascular surgery. Previous studies have established associations between HCV infection and coagulopathy. 15 , 17 Northup et al. documented increased bleeding risk in HCV-infected patients undergoing invasive procedures, 18 while Lisman and Porte demonstrated impaired synthesis of procoagulant and anticoagulant factors in chronic HCV-related liver disease. 15 Zanetto et al. reported hypercoagulable profiles paradoxically coexisting with bleeding tendencies in cirrhotic patients. 19 However, these investigations focused on general surgical populations or advanced cirrhosis, with limited evaluation of ESRD patients undergoing AVF surgery—a critical gap given ESRD patients’ unique hemostatic challenges. In Iraq, HCV prevalence among hemodialysis patients ranges between 40% and 62%, among the highest rates globally. 20 However, regional data on HCV’s impact on vascular access outcomes remain limited. Understanding this relationship in high-prevalence populations could inform risk stratification, perioperative management, AVF timing relative to HCV treatment, and infection control policies. This study prospectively examined the association between HCV infection and hemostatic complications after AVF creation in Iraqi ESRD patients. Secondary objectives included comparing coagulation parameters between HCV-positive and HCV-negative patients, identifying predictors of complications, evaluating HCV’s impact on AVF maturation, and documenting vascular access complications by HCV status. Methods Study design and setting This prospective observational cohort study assessed hemostatic outcomes following AVF creation in ESRD patients, stratified by HCV status. The investigation was conducted at three tertiary referral hospitals in Baghdad, Iraq: Al-Yarmouk Teaching Hospital, Ibn-Al-Nafees Teaching Hospital, and Al-Shaheed Ghazi Al-Hariri Surgical Hospital, serving over eight million individuals. The study period extended from January 4, 2017, to January 31, 2024. Participant selection Inclusion criteria Patients were eligible if they met the following criteria: (1) confirmed ESRD diagnosis (eGFR <15 mL/min/1.73 m 2 for ≥3 months) by two nephrologists; (2) age ≥14 years; (3) clinical indication for AVF creation; (4) capacity for informed consent; and (5) availability for six-week follow-up. Exclusion criteria Patients were excluded if they had: (1) previous AVF creation with postoperative complications; (2) inherited or acquired bleeding disorders unrelated to uremia or HCV; (3) therapeutic anticoagulation beyond dialysis-related heparin; (4) thrombocytopenia (platelets <50,000/mm 3 ) from non-HCV/ESRD causes; (5) active malignancy requiring systemic treatment; (6) pregnancy or breastfeeding; or (7) cognitive impairment precluding consent. Sample size determination Sample size calculation used a two-proportion comparison formula based on anticipated hemostatic complication rates of 5% in HCV-negative and 15% in HCV-positive patients. Using α = 0.05 and 80% power, the minimum required sample was 420 patients, increased to 460 to accommodate an anticipated 10% dropout rate. HCV status determination and baseline assessment HCV serological status was determined using third-generation ELISA (Catalog number: ab108685, Abcam, Cambridge, United Kingdom) detecting anti-HCV IgG antibodies. All patients underwent preoperative evaluation including medical history, physical examination, and vascular mapping. Color Doppler ultrasonography assessed bilateral upper extremity arterial and venous anatomy, vessel diameter, flow, and patency. Baseline laboratory investigations included complete blood count, metabolic panel, coagulation profile (PT, aPTT, INR, fibrinogen), hepatic function tests (AST, ALT, alkaline phosphatase, bilirubin, albumin), and renal parameters. Surgical technique All AVF procedures were performed by experienced vascular surgeons with over five years of training and more than 100 annual procedures. The primary approach was radiocephalic end-to-side anastomosis at the wrist (Brescia-Cimino fistula) when vessels were adequate. When distal vessels were inadequate (artery <2.0 mm or vein <2.5 mm), alternatives included brachiocephalic fistula or brachiobasilic transposition. All anastomoses used loupe magnification (3.5×) with 6-0 or 7-0 polypropylene continuous suture. Surgical duration, anastomotic size, and intraoperative complications were documented. Outcome assessment Primary outcome The primary outcome was hemostatic complications within six weeks postoperatively, defined as: (1) clinically significant bleeding requiring intervention beyond standard pressure dressing (prolonged compression >30 minutes, additional suturing, surgical re-exploration, or transfusion); or (2) clinically significant hematoma causing pain, limiting range of motion, compromising fistula function, or requiring evacuation. Secondary outcomes Secondary outcomes included: (1) successful AVF maturation at six weeks (palpable thrill, audible bruit, venous diameter ≥4 mm, flow ≥500 mL/min by Doppler); (2) additional vascular complications (thrombosis, aneurysm/pseudoaneurysm, steal syndrome, infection, venous hypertension); and (3) evolution of coagulation parameters during follow-up. Follow-up protocol Patients received systematic postoperative monitoring: hourly assessment for 24 hours, daily evaluation for seven days, and twice-weekly follow-up through six weeks. Each assessment included clinical examination, complication documentation, and Doppler ultrasound evaluation of fistula patency, flow, and maturation. Statistical analysis Statistical analyses used IBM SPSS Statistics version 24.0. Continuous variables were expressed as mean ± SD or median (IQR) and compared using Student’s t-test or Mann-Whitney U test. Categorical variables were presented as frequencies/percentages and compared using Chi-square or Fisher’s exact test. Multivariable logistic regression with forward stepwise selection identified independent predictors, with forced entry of clinically relevant variables (age, sex, diabetes, platelet count, coagulation parameters, dialysis vintage). Model performance was assessed using AUC-ROC, Hosmer-Lemeshow test, and Nagelkerke R 2 . Significance was set at p < 0.05. Maturation was defined by palpable thrill, audible bruit, venous diameter ≥4 mm, flow ≥500 mL/min, and ability to support hemodialysis with two needles at ≥300 mL/min for ≥8 of 12 sessions. Results Between January 2017 and January 2024, 466 ESRD patients were screened; six were excluded (18 declined, eight on anticoagulation, five had previous AVF complications, two pregnant). The final cohort comprised 460 patients with 100% six-week follow-up completion. The cohort included 460 patients (35.4% male, 64.6% female; mean age 44.39 ± 15.06 years). HCV seropositivity was 32.8% (151 patients; 95% CI: 28.6-37.3%). HCV-positive patients were significantly younger (37.2 ± 9.0 vs. 48.3 ± 16.2 years, p < 0.001), had longer dialysis vintage (24.2 ± 14.1 vs. 15.7 ± 10.2 months, p < 0.001), and lower diabetes prevalence (31.8% vs. 45.0%, p = 0.007). Gender, hypertension, and cardiovascular disease were similar between groups ( Table 1 ). Table 1. Patient demographics and clinical characteristics stratified by Hepatitis C virus status. Characteristic Total (n = 460) HCV+ (n = 151) HCV− (n = 309) P-value Age (years), mean ± SD 44.39 ± 15.06 37.2 ± 9.0 48.3 ± 16.2 <0.001 Male gender, n (%) 163 (35.4%) 55 (36.4%) 108 (35.0%) 0.834 Dialysis vintage (months), mean ± SD 18.5 ± 12.3 24.2 ± 14.1 15.7 ± 10.2 <0.001 Diabetes mellitus, n (%) 187 (40.7%) 48 (31.8%) 139 (45.0%) 0.007 Hypertension, n (%) 389 (84.6%) 122 (80.8%) 267 (86.4%) 0.121 Cardiovascular disease, n (%) 145 (31.5%) 43 (28.5%) 102 (33.0%) 0.334 Hemostatic complications occurred in 60 patients (13.0%), varying significantly by HCV status ( Table 2 ). HCV-positive patients had 28.5% complications versus 5.5% in HCV-negative patients (OR: 6.835, 95% CI: 3.597-12.987, p < 0.001). Bleeding affected 6.5% overall: 15.2% HCV-positive versus 2.3% HCV-negative (OR: 7.506, 95% CI: 3.111-18.105, p < 0.001). Of 30 bleeding events, 50% were mild, 33.3% moderate, 16.7% severe. All moderate and severe bleeding occurred exclusively in HCV-positive patients, with 65.2% requiring intervention beyond compression. Table 2. Hemostatic complications stratified by Hepatitis C virus status. Complication type HCV+ (n = 151) HCV− (n = 309) OR (95% CI) P-value Any hemostatic complication 43 (28.5%) 17 (5.5%) 6.835 (3.597–12.987) <0.001 Bleeding events 23 (15.2%) 7 (2.3%) 7.506 (3.111–18.105) <0.001 ├─ Mild (compression only) 8 (5.3%) 7 (2.3%) 2.412 (0.865–6.727) 0.087 ├─ Moderate (suturing) 10 (6.6%) 0 (0%) ∞ <0.001 └─ Severe (exploration/transfusion) 5 (3.3%) 0 (0%) ∞ 0.003 Hematoma formation 20 (13.2%) 10 (3.2%) 4.545 (2.062–10.018) <0.001 ├─ Small (<5 cm) 9 (6.0%) 8 (2.6%) 2.398 (0.912–6.304) 0.072 └─ Large (≥5 cm) 11 (7.3%) 2 (0.6%) 12.038 (2.625–55.192) <0.001 Hematoma formation occurred in 6.5% overall, with higher rates in HCV-positive patients (13.2% vs. 3.2%; OR: 4.545, 95% CI: 2.062-10.018, p < 0.001). Large hematomas (≥5 cm) occurred almost exclusively in HCV-positive patients (7.3% vs. 0.6%; OR: 12.038, 95% CI: 2.625-55.192, p < 0.001), indicating that HCV infection increases both incidence and severity of hematoma formation. HCV-positive patients demonstrated significantly abnormal coagulation ( Table 3 ): prolonged PT (19 ± 5 vs. 15 ± 2.5 seconds, p < 0.001), prolonged aPTT (40 ± 4 vs. 32 ± 3 seconds, p < 0.001), and elevated INR (1.6±0.4 vs. 1.2 ± 0.2, p < 0.001). Thrombocytopenia was marked (153 ± 43 vs. 215 ± 72 ×10 3 /mm 3 , p < 0.001), with lower hemoglobin (7.0 ± 2.0 vs. 9.0 ± 2.0 g/dL, p < 0.001). Hepatic transaminases were elevated (AST: 59 ± 24 vs. 17±5 IU/L; ALT: 64 ± 17 vs. 9 ± 6 IU/L; both p < 0.001), and hypoalbuminemia present (3.2 ± 0.6 vs. 3.8 ± 0.5 g/dL, p < 0.001). Table 3. Laboratory and coagulation parameters stratified by Hepatitis C virus status. Parameter HCV+ (n = 151) HCV− (n = 309) Mean difference (95% CI) P-value Coagulation Studies Prothrombin time (sec) 19 ± 5 15 ± 2.5 4.0 (3.3 to 4.7) <0.001 Activated PTT (sec) 40 ± 4 32 ± 3 8.0 (7.3 to 8.7) <0.001 INR 1.6 ± 0.4 1.2 ± 0.2 0.4 (0.35 to 0.45) <0.001 Hematological Parameters Hemoglobin (g/dL) 7.0 ± 2.0 9.0 ± 2.0 −2.0 (−2.4 to −1.6) <0.001 Platelets (×10 3 /mm 3 ) 153 ± 43 215 ± 72 −62 (−73 to −51) <0.001 Hepatic Function AST (IU/L) 59 ± 24 17 ± 5 42 (38 to 46) <0.001 ALT (IU/L) 64 ± 17 9 ± 6 55 (52 to 58) <0.001 Albumin (g/dL) 3.2 ± 0.6 3.8 ± 0.5 −0.6 (−0.7 to −0.5) <0.001 Total bilirubin (mg/dL) 1.2 ± 0.8 0.6 ± 0.3 0.6 (0.5 to 0.7) <0.001 At six weeks, successful AVF maturation was 74.2% in HCV-positive versus 86.4% in HCV-negative patients (difference 12.2%, p = 0.002), representing 1.90-fold increased maturation failure risk (95% CI: 1.26-2.87). Multivariate analysis confirmed HCV as an independent predictor (adjusted OR: 2.18, 95% CI: 1.32-3.61, p = 0.002). Among patients with hemostatic complications, only 45.3% achieved maturation versus 82.5% without complications (p < 0.001). HCV-positive patients had higher rates of additional vascular complications: ( Table 4 ) aneurysm/pseudoaneurysm (3.3% vs. 1.0%, p = 0.047), steal syndrome (6.0% vs. 2.9%, p = 0.019), and infection (4.0% vs. 1.0%, p = 0.032). Thrombosis rates were similar (4.0% vs. 2.9%, p = 0.558). Overall complications occurred in 50.3% of HCV-positive versus 15.9% of HCV-negative patients (OR: 5.543, 95% CI: 3.562-8.624, p < 0.001). Table 4. Additional vascular access complications stratified by Hepatitis C virus status. Complication HCV+ (n = 151) HCV− (n = 309) OR (95% CI) P-value Thrombosis 6 (4.0%) 9 (2.9%) 1.381 (0.485–3.930) 0.558 Aneurysm/Pseudoaneurysm 5 (3.3%) 3 (1.0%) 3.448 (0.819–14.518) 0.047 * Steal syndrome 9 (6.0%) 9 (2.9%) 2.128 (0.827–5.474) 0.019 * Infection 6 (4.0%) 3 (1.0%) 4.186 (1.045–16.761) 0.032 * Venous hypertension 7 (4.6%) 8 (2.6%) 1.823 (0.655–5.073) 0.248 Overall complications (any) 76 (50.3%) 49 (15.9%) 5.543 (3.562–8.624) <0.001 * Data presented as n (%). OR, odds ratio; CI, confidence interval; HCV, hepatitis C virus. Multivariable logistic regression identified independent predictors of hemostatic complications ( Table 5 ). HCV-positive status was strongest (adjusted OR: 5.892, 95% CI: 3.102-11.196, p < 0.001). Other predictors included platelet count (adjusted OR: 1.133 per 10,000/mm 3 decrease, p = 0.003), prothrombin time (adjusted OR: 1.103 per 1-second increase, p = 0.005), age (adjusted OR: 1.058 per 10-year increase, p = 0.046), and female gender (adjusted OR: 1.527, p = 0.032). The model showed excellent discrimination (AUC: 0.847, 95% CI: 0.802-0.892) and calibration (Hosmer-Lemeshow p = 0.412). Table 5. Multivariate predictors of hemostatic complications. Variable Adjusted OR 95% CI P-value HCV-positive status 5.892 3.102–11.196 <0.001 ** Platelet count (per 10,000/mm 3 decrease) 1.133 1.043–1.231 0.003 ** Prothrombin time (per 1 sec increase) 1.103 1.030–1.181 0.005 ** Age (per 10-year increase) 1.058 1.001–1.118 0.046 * Female gender 1.527 1.036–2.251 0.032 * Diabetes mellitus 1.243 0.721–2.142 0.435 Dialysis vintage (per year) 1.015 0.982–1.049 0.372 * p<0.05; ** p<0.01. Figure 1 illustrates AVF maturation outcomes stratified by HCV status and hemostatic complications. Panel A shows maturation rates of 74.2% in HCV-positive versus 86.4% in HCV-negative patients (12.2% difference). Panel B confirms HCV as an independent predictor of maturation failure (adjusted OR: 2.18, 95% CI: 1.32-3.61, p = 0.002). Panel C demonstrates reduced maturation in patients with hemostatic complications (45.3% vs. 82.5%). Figure 1. Arteriovenous Fistula Maturation Success at Six Weeks Stratified by Hepatitis C Virus Status and Impact of Hemostatic Complications: Prospective Cohort Study (n = 460)|Baghdad, Iraq|2017-2024. A. AVF Maturation Success by HCV Status. B. Comparison of maturation of outcomes with adjusted analysis. C. Impact of Hemostatic Complications on Maturation Success. Panel A: Comparative pie charts illustrating AVF maturation outcomes at six weeks. Among HCV-positive patients (n = 151), successful maturation occurred in 74.2%. Among HCV-negative patients (n = 309), successful maturation occurred in 86.4% (p = 0.002). Panel B: Visual representation of maturation success and failure rates by HCV status. Multivariate logistic regression confirmed HCV infection as an independent predictor of maturation failure (adjusted OR: 2.18, 95% CI: 1.32-3.61, p = 0.002). Panel C: Bar chart demonstrating the mediating role of hemostatic complications in AVF maturation. Among patients with hemostatic complications (n = 60), successful maturation occurred in only 45.3% versus 82.5% in those without complications (p < 0.001). Abbreviations: HCV, hepatitis C virus; AVF, arteriovenous fistula; RR, relative risk; aOR, adjusted odds ratio; CI, confidence interval. Discussion This prospective cohort study demonstrates that HCV infection is a major independent risk factor for hemostatic complications following AVF creation in ESRD patients, with nearly six-fold increased risk after adjusting for coagulopathic parameters. HCV also significantly impairs AVF maturation, likely through hemostatic complications. The 32.8% HCV prevalence aligns with regional data showing 22-35% prevalence in Middle Eastern and North African dialysis populations. 8 , 9 These findings confirm persistent high HCV burden in Iraqi dialysis facilities. The 28.5% hemostatic complication rate among HCV-positive patients exceeds Western populations, where general AVF complication rates range from 10-20%. 6 A multicenter European study reported 15% overall AVF complication rates in unselected dialysis populations, substantially lower than the HCV-positive subgroup in this study. 21 This disparity likely reflects higher HCV prevalence, more advanced liver disease, limited access to direct-acting antivirals, and resource constraints. The 5.5% complication rate in HCV-negative patients approximates contemporary Western series, suggesting HCV infection primarily drives elevated complications. Meta-regression showed decreasing HCV prevalence trends in Middle Eastern dialysis populations (OR 0.92 per year, 95% CI: 0.90-0.95), 9 potentially reflecting improved infection control. However, absolute prevalence remains elevated compared to global averages of 8-10%, 6 , 7 necessitating continued region-specific interventions. The coagulation profiling elucidates the pathophysiological basis for increased bleeding risk. Chronic hepatic inflammation from HCV progressively impairs synthesis of vitamin K-dependent coagulation factors, manifested by 27% PT prolongation and 25% aPTT prolongation in HCV-positive patients. 15 Chronic liver disease produces a “rebalanced” but fragile hemostatic system easily disrupted by surgical stress. 17 The 29% platelet count reduction in HCV-positive patients reflects multiple mechanisms: splenic sequestration from portal hypertension, reduced hepatic thrombopoietin production, and possible direct viral suppression of megakaryocyte development. 16 , 17 , 22 HCV’s independent predictive value (adjusted OR: 5.89) persisted after adjusting for platelet count and PT, suggesting additional mechanisms contribute to bleeding risk. Plausible explanations include qualitative platelet dysfunction beyond quantitative deficits, 23 , 24 HCV-associated cryoglobulinemia inducing vasculitis and endothelial dysfunction, 17 disrupted coagulation-fibrinolysis balance through reduced α2-antiplasmin synthesis, 18 and synergistic effects between uremia-induced platelet dysfunction and HCV-mediated abnormalities. 15 HCV-positive patients undergoing AVF creation would benefit from enhanced perioperative management. Incorporating HCV status into preoperative risk stratification could identify high-risk patients requiring intensified surveillance. Validated risk prediction models exist but none currently incorporate HCV status despite its substantial predictive value. 25 , 26 Integration of HCV serostatus into these models could enhance discrimination and enable more personalized risk prediction. Prophylactic platelet transfusion for thrombocytopenia (<100,000/mm 3 ) may reduce bleeding risk. 27 Hemostatic agents merit consideration, including desmopressin for platelet dysfunction 28 and topical agents for local hemostasis. 2 Desmopressin demonstrates effectiveness in reversing platelet dysfunction, particularly in uremic contexts, by releasing von Willebrand factor from endothelial storage sites to enhance platelet adhesion. 28 Technical surgical modifications may prove beneficial, including smaller initial anastomoses with delayed cannulation (≥8 weeks rather than 4-6 weeks) to reduce early hemostatic stress and improve patency rates in high-risk patients. 25 Intensified postoperative surveillance with earlier ultrasound evaluation could enable early detection of complications. 26 Direct-acting antiviral (DAA) therapy has revolutionized HCV treatment, achieving sustained virological response rates exceeding 95% even in ESRD populations. 29 , 30 Multiple DAA regimens demonstrate efficacy in ESRD. Successful viral eradication produces measurable improvements in coagulation parameters within 12-24 weeks, including platelet count recovery and prothrombin time normalization. 31 , 32 Patients achieving sustained virological response experienced significant improvements in prothrombin time, platelet count, and albumin levels within six months. 31 , 32 This raises an important question: could preoperative viral eradication before elective AVF creation normalize bleeding risk to levels comparable with HCV-negative patients? This hypothesis warrants evaluation through randomized controlled trials comparing preoperative DAA therapy versus standard care. The 2018 KDIGO clinical practice guideline recommends treating all HCV-infected patients with chronic kidney disease, including those receiving dialysis. 33 However, the guideline does not address optimal timing of treatment relative to planned vascular access procedures. Elucidating optimal treatment timing could substantially improve outcomes while maximizing cost-effectiveness of DAA therapy. The persistently high HCV prevalence among hemodialysis patients in Iraq and the broader Middle East mandates comprehensive public health responses. Universal HCV screening at hemodialysis initiation with subsequent surveillance testing should become standard practice across all dialysis facilities. 33 Stringent infection control measures require consistent implementation, including dedicated machines for HCV-positive patients, enhanced environmental cleaning protocols, and rigorous adherence to standard precautions. 34 The CDC emphasizes that hemodialysis units should follow standard precautions for all patients, with additional measures including prohibiting sharing of medications, supplies, or equipment between patients. 34 Expanded access to DAA therapy through national treatment programs and generic medication availability could dramatically reduce HCV burden in dialysis populations. 35 Vascular access planning should systematically incorporate HCV status, potentially prioritizing earlier AVF creation in HCV-negative patients while optimizing HCV-positive patients through DAA treatment when feasible before elective access surgery. Resource constraints continue to impede effective infection control despite awareness of transmission risks. 8 – 10 Inadequate sterilization procedures, equipment sharing, and insufficient staff training remain ongoing challenges in dialysis facilities. The COVID-19 pandemic has imposed additional strain on infection control resources and delayed elective vascular access procedures. 11 , 13 , 14 , 36 These challenges underscore the critical need for sustained investment in dialysis infrastructure, infection control programs, and access to antiviral medications. This study has several strengths: prospective design with systematic six-week follow-up, substantial sample size (n = 460) enabling robust multivariable analysis, standardized surgical technique, complete follow-up, and multicenter design across three tertiary hospitals enhancing generalizability. Several limitations warrant acknowledgment. HCV RNA quantification and genotyping were not performed. The single-country design may limit generalizability. Follow-up extended only six weeks, insufficient for assessing long-term patency. Unmeasured confounders including hepatic fibrosis staging were not assessed. Future research should address several critical questions. Randomized controlled trials should evaluate whether DAA therapy before AVF creation improves outcomes. The optimal interval between viral eradication and surgery requires definition. Long-term studies examining fistula patency over 1-3 years are needed. Validation in diverse geographic regions would enhance generalizability. Enhanced risk prediction models incorporating viral and hepatic parameters could enable personalized management. Clinical practice implications HCV infection independently increases hemostatic complications following arteriovenous fistula creation nearly six-fold (adjusted OR: 5.892, P < 0.001). HCV-positive patients demonstrated prolonged prothrombin time (27%), activated partial thromboplastin time (25%), and reduced platelet counts (29%). Consequently, fistula maturation rates were significantly lower in HCV-positive patients (74.2% vs 86.4%, P < 0.001). Clinical practice recommendations HCV serostatus should be systematically incorporated into preoperative risk stratification for vascular access procedures. Comprehensive coagulation assessment should be mandatory for HCV-positive patients. Perioperative optimization may include platelet transfusion, hemostatic agents, and enhanced surveillance. Direct-acting antiviral therapy prior to fistula creation warrants consideration. Conclusions This prospective cohort study demonstrates that HCV infection increases hemostatic complications following AVF creation in ESRD patients nearly six-fold. HCV-positive patients exhibit prolonged coagulation times and thrombocytopenia, significantly impairing AVF maturation. The availability of direct-acting antiviral therapy raises the possibility that preoperative viral eradication could normalize bleeding risk. Ethical considerations The Ethics Committee of Anbar Medical College, Iraq (Reference: AMC/EC/2016-45) approved the study, which was conducted according to the Declaration of Helsinki. Written informed consent was obtained from all participants, with written assent and parental consent obtained for participants aged 14-17 years. Data availability Underlying data Repository Name: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study. https://doi.org/10.6084/m9.figshare.30719018 . 37 The project contains the following underlying data: • HCV_AVF_Complete_Dataset.xlsx (Complete anonymized patient data including demographics, laboratory parameters, surgical details, and outcomes) • Coagulation_Parameters_Raw.csv (Unmodified coagulation study results for all patients) • Clinical_Outcomes_Six_Week.csv (Six-week follow-up data with maturation and complication outcomes) Extended data Repository Name: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study. https://doi.org/10.6084/m9.figshare.30719018 . 37 This project contains the following extended data: • Supplementary Table S1 (Detailed surgical procedure characteristics by HCV status) • Supplementary Table S2 (Univariate analysis of all potential risk factors for hemostatic complications) • Supplementary Figure S1 (Receiver operating characteristic curve for the multivariate prediction model) • Study_Protocol.pdf (Complete study protocol with inclusion/exclusion criteria and assessment schedules) Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). The complete dataset supporting this study has been deposited in Figshare under a Creative Commons CC-BY 4.0 license (DOI: 10.6084/m9.figshare.30719018). The dataset includes Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study. All personal identifying information has been removed in accordance with institutional ethical approval, and informed consent included explicit permission for anonymized data sharing. The datasets generated and analyzed during the current study are available in the Figshare repository at [DOI: 10.6084/m9.figshare.30719018. figshare. https://figshare.com/s/ea291b7e9a50870543cb ]. 11 Acknowledgements The authors thank all patients who participated and the clinical staff at Al-Yarmouk Teaching Hospital, Ibn-Al-Nafees Teaching Hospital, and Al-Shaheed Ghazi Al-Hariri Surgical Hospital for their support and collaboration throughout the study. References 1. Bikbov B, et al. : Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020; 395 (10225): 709–733. 2. Lok CE, et al. : KDOQI clinical practice guideline for vascular access: 2019 update. Am. J. Kidney Dis. 2020; 75 (4): S1–S164. Publisher Full Text 3. Qian J, Lee T, Thamer M, et al. : Racial disparities in the arteriovenous fistula care continuum in hemodialysis patients. Clin. J. Am. Soc. 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KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int. Suppl. 2018; 8 (3): 91–165. Publisher Full Text 34. Alter MJ, Arduino MJ, Lyerla HC, et al. : Recommendations for preventing transmission of infections among chronic hemodialysis patients.2001. 35. Hill A, Simmons B, Gotham D, et al. : Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C. J. Virus Erad. 2016; 2 (1): 28–40. 36. Wahab SSA, Khalil MA, Majeed YH: Risk factors for the development of hepatic manifestations in COVID-19 patients with digestive symptoms. Journal of Emergency Medicine, Trauma & Acute Care. 2022; 2022 (6): 11. 37. Al-Alosi BMH, Khalil MA: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study. Dataset. figshare. 2024. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 13 Feb 2026 ADD YOUR COMMENT Comment Author details Author details 1 Surgery, University of Anbar College of Medicine, Ramadi, Al Anbar Governorate, 31001, Iraq 2 Microbiology, University of Anbar College of Medicine, Ramadi, Al Anbar Governorate, 31001, Iraq Bassam M. Hassan Al-Alosi Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Muthana Ali Khalil Roles: Data Curation, Investigation, Methodology, Resources, Validation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 13 Feb 2026, 15:254 https://doi.org/10.12688/f1000research.174443.1 Copyright © 2026 Hassan Al-Alosi BM and Khalil MA. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Hassan Al-Alosi BM and Khalil MA. Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.12688/f1000research.174443.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 13 Feb 2026 Views 0 Cite How to cite this report: Othman AA. Reviewer Report For: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.5256/f1000research.192345.r463570 ) The direct URL for this report is: https://f1000research.com/articles/15-254/v1#referee-response-463570 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 09 Mar 2026 Amira Ahmed Othman , Suez University, Suez, Egypt Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.192345.r463570 First of all I want to congratulate the authors on their work, "Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study ” . This ... Continue reading READ ALL First of all I want to congratulate the authors on their work, "Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study ” . This study investigates the relationship between hepatitis C virus (HCV) infection and the occurrence of hemostatic complications after arteriovenous fistula (AVF) creation in patients with end-stage renal disease (ESRD). The authors conducted a prospective cohort study over seven years and compared postoperative outcomes between HCV-positive and HCV-negative patients undergoing AVF surgery. The work aims to determine whether HCV infection increases the risk of bleeding complications and affects fistula maturation. Given the high prevalence of HCV infection among hemodialysis populations in many regions, understanding its influence on vascular access outcomes is clinically relevant. Overall, the study is interesting and technically ambitious. However, several aspects of the manuscript need improvement before it can be considered for Indexing. These relate mainly to clarity of language, consistency in reported data, methodological transparency, and presentation of results. In general: The manuscript would benefit from substantial language editing to improve clarity, grammar, and readability. Although the overall scientific content is understandable, many sentences are overly long and contain grammatical inconsistencies that make the text difficult to follow: long sentences. occasional grammatical errors repetition of similar phrases inconsistent spacing and formatting Abbreviations should be fully written at first appearance. In Title: The title is effective because it states the main finding clearly. However, it's a bit long and awkward. For example : "Hepatitis C Virus Infection: A Six-Fold Risk Factor for Bleeding After Arteriovenous Fistula Creation in End-Stage Renal Disease” or "Association of Hepatitis C Virus Infection with Hemostatic Complications After Arteriovenous Fistula Creation in Patients with End-Stage Renal Disease: A Prospective Cohort Study". In the Abstract section Background section: It is slightly long and includes epidemiological information that is not essential for the abstract. Methods section: The abstract should briefly mention the statistical methods used. The definition of the primary outcome could be summarized more concisely. Results section: Too many laboratory parameters are listed; only the most important findings should be included. Focus on the main outcome rather than detailed lab comparisons. Conclusion section: The conclusion should be more cautious and avoid implying causality. It should emphasize clinical implications briefly. In the Introduction section: The introduction is too long and tries to cover too much. It reads like a mini-review article. Do we really need a full paragraph on the basic virology of HCV (single-stranded RNA virus, seven genotypes)? It's not relevant to the surgical outcomes. The COVID-19 paragraph feels forced. While the pandemic was a huge event, mentioning it here as a potential factor in HCV transmission seems like a stretch and distracts from the main argument. Unless the study specifically looked at pre- and post-pandemic data, it should be cut. The "Previous studies" paragraph is weak. It just lists a few studies without explaining how this current study fills the "critical gap." It mentions that other studies focused on general surgery or cirrhosis, but it needs to hammer home why this study on ESRD patients is so important and different. The final paragraph does a much better job of this. More recent studies on vascular access complications and HCV should be cited. Some references appear general rather than directly related to AVF surgery. The research gap should be stated more clearly and earlier in the introduction. The study objective should be clearly written in a separate final paragraph. Example improvement: “Therefore, this study aimed to evaluate whether HCV infection is associated with an increased risk of hemostatic complications following AVF creation in patients with ESRD.” In the “Methodology” section: The minimum age is 14 years , which is unusual for dialysis access studies. The reason should be explained. It is not clear whether all eligible patients were consecutively enrolled. The study used anti-HCV ELISA testing, but it is not mentioned whether PCR confirmation (HCV RNA) was performed. Serology alone cannot distinguish between active and past infection. Using only an antibody test (ELISA) is a major weakness. In kidney patients, the immune system can be weak, leading to false negatives. More importantly, you can't tell if a patient has an active infection or just a past infection that cleared up. This could completely change the results. They need to add a discussion about this as a major limitation, or ideally, if the data exists, they should confirm the diagnosis with PCR (RNA) testing. They didn't assess how severe the liver damage was. Not all HCV patients have the same level of cirrhosis. Using simple scores like Child-Pugh or APRI/FIB-4 would have shown if the bleeding risk was directly linked to how sick the liver was. This is another big gap. Medications is a huge potential flaw. Many dialysis patients take blood thinners or antiplatelet drugs like aspirin. The study doesn't say if patients were on these, if they were stopped before surgery, or if this was balanced between the two groups. This is a massive confounder that could skew the results. The surgical description is detailed, but some aspects are unnecessary for a clinical outcome study. Instead, the authors should report whether the same surgical protocol was used for all patients. The primary outcome definition is relatively clear, but it could be simplified. Suggestions: Provide a clearer definition of clinically significant bleeding and specify whether outcome assessment was blinded to HCV status. The authors should clarify whether any patients were lost to follow-up. Ethical approval is mentioned, but should include the approval number and the ethics committee name The manuscript does not explain whether there were missing data or how they were handled. The authors mention AUC and Hosmer-Lemeshow tests, but the results are not fully reported. The criteria for variable inclusion in the logistic regression model should be described. Important variables such as liver disease severity, dialysis duration, or platelet count should be clearly adjusted for. In the “Results” section: The text often just repeats what's already in the tables (e.g., "HCV-positive patients had higher rates of... aneurysm/pseudoaneurysm (3.3% vs. 1.0% p = 0.047)"). The text should highlight the most important trends, not just list every single number from the table. HCV-positive patients were significantly younger and had longer dialysis duration. These differences may confound the outcomes and should be adjusted carefully. Some interpretive language appears in the results section and should instead be placed in the discussion. In the “Discussion” section: The first few paragraphs just restate the results. We already know them. The discussion should interpret the results, not repeat them. The section on clinical practice is full of prescriptive statements like "would benefit from," "should be mandatory," and "warrants consideration." While the findings suggest these things, it's not the study's place to write new hospital protocols. It's better to say, "Our findings suggest that incorporating HCV status into preoperative risk assessment could be beneficial." Be more cautious and suggestive. The paragraphs on DAA therapy and KDIGO guidelines are important context, but they go on for too long. It feels like the authors are trying to show they've read the literature, rather than focusing on what their own data adds to the conversation. The key question from their study is simple: "Could treating HCV before surgery lower the bleeding risk?" They state this clearly, and then they can stop. They don't need to reprint the entire KDIGO summary. The authors should explain the biological mechanisms linking HCV infection and bleeding risk in dialysis patients. More comparison with existing vascular access studies is needed. The discussion should highlight how these findings could influence clinical practice. Observational data cannot prove causation. Important limitations include Observational design, Lack of HCV RNA confirmation, Possible confounding variables, Single-country population, and Short follow-up for fistula outcomes In the “conclusion” section: Emphasize that the study shows an association rather than a causal effect. Is the work clearly and accurately presented and does it cite the current literature? No Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hepatology, Gastroenterology, Endoscopy, Endocrinology, Oncology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Othman AA. Reviewer Report For: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.5256/f1000research.192345.r463570 ) The direct URL for this report is: https://f1000research.com/articles/15-254/v1#referee-response-463570 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Ezer B. Reviewer Report For: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.5256/f1000research.192345.r461324 ) The direct URL for this report is: https://f1000research.com/articles/15-254/v1#referee-response-461324 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 26 Feb 2026 Burak Ezer , Beyhekim Training and Research Hospita, Konya, Turkey Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.192345.r461324 Dear authors, thank you for your work. Below are some details that will enhance your article. 1. Methodological Rigor and Diagnostic Clarification -Validation of HCV Status: The study defines HCV status solely via third-generation ELISA (anti-HCV). ... Continue reading READ ALL Dear authors, thank you for your work. Below are some details that will enhance your article. 1. Methodological Rigor and Diagnostic Clarification -Validation of HCV Status: The study defines HCV status solely via third-generation ELISA (anti-HCV). In the ESRD population, impaired immune responses can lead to delayed seroconversion or false negatives. More importantly, without HCV-RNA (PCR) testing, it is impossible to distinguish between active viremia and resolved infection. The reviewers will likely require a discussion on whether complication risks correlate with viral load or if this was considered a study limitation. -Assessment of Liver Fibrosis Stage: The impact of HCV on the hemostatic system is directly proportional to the degree of liver damage (fibrosis/cirrhosis). The absence of baseline Child-Pugh scores or non-invasive markers such as APRI or FIB-4 scores is a significant gap. Providing these metrics is essential to characterize the severity of the underlying coagulopathy. Concomitant Medication Use: ESRD patients frequently utilize antiplatelet agents (e.g., Aspirin, Clopidogrel). The perioperative management of these drugs (whether they were discontinued) and their distribution between the HCV-positive and negative groups must be detailed, as they represent major confounding factors for hemostatic complications. 2. Statistical Analysis and Data Presentation -Addressing Selection Bias: There are significant baseline differences in age and diabetes prevalence between the two groups (HCV+ patients are younger and less diabetic). To ensure the reported 6-fold risk is not skewed by these variables, a Propensity Score Matching (PSM) analysis is strongly recommended to standardize the cohorts. -Expansion of Clinical Variables: Table 1 should be more comprehensive. Including parameters such as BMI, smoking status, hypertension, and peripheral vascular disease is necessary, as these factors significantly influence both bleeding risk and AVF maturation. -Refinement of Multivariate Model: In Table 5, the authors should justify why certain clinically relevant variables (e.g., diabetes, dialysis vintage) were excluded from the final model or why they did not reach statistical significance. 3. Discussion and Pathophysiological Mechanisms -Synergistic Hemostatic Defect: The discussion should more deeply explore the synergy between HCV-induced reduction in clotting factors and uremia-associated platelet dysfunction . This "dual-hit" mechanism is likely the driver behind the increased severity of bleeding observed in the HCV+ group. -Impact of DAA Therapy: Since the study period (2017–2024) overlaps with the widespread adoption of Direct-Acting Antivirals (DAAs), it is crucial to state whether any patients received treatment during the study. If so, how was their data handled? This is vital for the manuscript's relevance to current clinical guidelines. -Mechanisms of Maturation Failure: The technical link between hemostatic complications and maturation failure needs further elaboration. Specifically, how hematoma-induced extrinsic compression, localized inflammation, or the development of pseudoaneurysms physically impairs the remodeling and arterialization of the vein. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Medical Microbiology (Medical Doctor) I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Ezer B. Reviewer Report For: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.5256/f1000research.192345.r461324 ) The direct URL for this report is: https://f1000research.com/articles/15-254/v1#referee-response-461324 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 13 Feb 2026 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 13 Feb 26 read read Burak Ezer , Beyhekim Training and Research Hospita, Konya, Turkey Amira Ahmed Othman , Suez University, Suez, Egypt Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Othman A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 09 Mar 2026 | for Version 1 Amira Ahmed Othman , Suez University, Suez, Egypt 0 Views copyright © 2026 Othman A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions First of all I want to congratulate the authors on their work, "Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study ” . This study investigates the relationship between hepatitis C virus (HCV) infection and the occurrence of hemostatic complications after arteriovenous fistula (AVF) creation in patients with end-stage renal disease (ESRD). The authors conducted a prospective cohort study over seven years and compared postoperative outcomes between HCV-positive and HCV-negative patients undergoing AVF surgery. The work aims to determine whether HCV infection increases the risk of bleeding complications and affects fistula maturation. Given the high prevalence of HCV infection among hemodialysis populations in many regions, understanding its influence on vascular access outcomes is clinically relevant. Overall, the study is interesting and technically ambitious. However, several aspects of the manuscript need improvement before it can be considered for Indexing. These relate mainly to clarity of language, consistency in reported data, methodological transparency, and presentation of results. In general: The manuscript would benefit from substantial language editing to improve clarity, grammar, and readability. Although the overall scientific content is understandable, many sentences are overly long and contain grammatical inconsistencies that make the text difficult to follow: long sentences. occasional grammatical errors repetition of similar phrases inconsistent spacing and formatting Abbreviations should be fully written at first appearance. In Title: The title is effective because it states the main finding clearly. However, it's a bit long and awkward. For example : "Hepatitis C Virus Infection: A Six-Fold Risk Factor for Bleeding After Arteriovenous Fistula Creation in End-Stage Renal Disease” or "Association of Hepatitis C Virus Infection with Hemostatic Complications After Arteriovenous Fistula Creation in Patients with End-Stage Renal Disease: A Prospective Cohort Study". In the Abstract section Background section: It is slightly long and includes epidemiological information that is not essential for the abstract. Methods section: The abstract should briefly mention the statistical methods used. The definition of the primary outcome could be summarized more concisely. Results section: Too many laboratory parameters are listed; only the most important findings should be included. Focus on the main outcome rather than detailed lab comparisons. Conclusion section: The conclusion should be more cautious and avoid implying causality. It should emphasize clinical implications briefly. In the Introduction section: The introduction is too long and tries to cover too much. It reads like a mini-review article. Do we really need a full paragraph on the basic virology of HCV (single-stranded RNA virus, seven genotypes)? It's not relevant to the surgical outcomes. The COVID-19 paragraph feels forced. While the pandemic was a huge event, mentioning it here as a potential factor in HCV transmission seems like a stretch and distracts from the main argument. Unless the study specifically looked at pre- and post-pandemic data, it should be cut. The "Previous studies" paragraph is weak. It just lists a few studies without explaining how this current study fills the "critical gap." It mentions that other studies focused on general surgery or cirrhosis, but it needs to hammer home why this study on ESRD patients is so important and different. The final paragraph does a much better job of this. More recent studies on vascular access complications and HCV should be cited. Some references appear general rather than directly related to AVF surgery. The research gap should be stated more clearly and earlier in the introduction. The study objective should be clearly written in a separate final paragraph. Example improvement: “Therefore, this study aimed to evaluate whether HCV infection is associated with an increased risk of hemostatic complications following AVF creation in patients with ESRD.” In the “Methodology” section: The minimum age is 14 years , which is unusual for dialysis access studies. The reason should be explained. It is not clear whether all eligible patients were consecutively enrolled. The study used anti-HCV ELISA testing, but it is not mentioned whether PCR confirmation (HCV RNA) was performed. Serology alone cannot distinguish between active and past infection. Using only an antibody test (ELISA) is a major weakness. In kidney patients, the immune system can be weak, leading to false negatives. More importantly, you can't tell if a patient has an active infection or just a past infection that cleared up. This could completely change the results. They need to add a discussion about this as a major limitation, or ideally, if the data exists, they should confirm the diagnosis with PCR (RNA) testing. They didn't assess how severe the liver damage was. Not all HCV patients have the same level of cirrhosis. Using simple scores like Child-Pugh or APRI/FIB-4 would have shown if the bleeding risk was directly linked to how sick the liver was. This is another big gap. Medications is a huge potential flaw. Many dialysis patients take blood thinners or antiplatelet drugs like aspirin. The study doesn't say if patients were on these, if they were stopped before surgery, or if this was balanced between the two groups. This is a massive confounder that could skew the results. The surgical description is detailed, but some aspects are unnecessary for a clinical outcome study. Instead, the authors should report whether the same surgical protocol was used for all patients. The primary outcome definition is relatively clear, but it could be simplified. Suggestions: Provide a clearer definition of clinically significant bleeding and specify whether outcome assessment was blinded to HCV status. The authors should clarify whether any patients were lost to follow-up. Ethical approval is mentioned, but should include the approval number and the ethics committee name The manuscript does not explain whether there were missing data or how they were handled. The authors mention AUC and Hosmer-Lemeshow tests, but the results are not fully reported. The criteria for variable inclusion in the logistic regression model should be described. Important variables such as liver disease severity, dialysis duration, or platelet count should be clearly adjusted for. In the “Results” section: The text often just repeats what's already in the tables (e.g., "HCV-positive patients had higher rates of... aneurysm/pseudoaneurysm (3.3% vs. 1.0% p = 0.047)"). The text should highlight the most important trends, not just list every single number from the table. HCV-positive patients were significantly younger and had longer dialysis duration. These differences may confound the outcomes and should be adjusted carefully. Some interpretive language appears in the results section and should instead be placed in the discussion. In the “Discussion” section: The first few paragraphs just restate the results. We already know them. The discussion should interpret the results, not repeat them. The section on clinical practice is full of prescriptive statements like "would benefit from," "should be mandatory," and "warrants consideration." While the findings suggest these things, it's not the study's place to write new hospital protocols. It's better to say, "Our findings suggest that incorporating HCV status into preoperative risk assessment could be beneficial." Be more cautious and suggestive. The paragraphs on DAA therapy and KDIGO guidelines are important context, but they go on for too long. It feels like the authors are trying to show they've read the literature, rather than focusing on what their own data adds to the conversation. The key question from their study is simple: "Could treating HCV before surgery lower the bleeding risk?" They state this clearly, and then they can stop. They don't need to reprint the entire KDIGO summary. The authors should explain the biological mechanisms linking HCV infection and bleeding risk in dialysis patients. More comparison with existing vascular access studies is needed. The discussion should highlight how these findings could influence clinical practice. Observational data cannot prove causation. Important limitations include Observational design, Lack of HCV RNA confirmation, Possible confounding variables, Single-country population, and Short follow-up for fistula outcomes In the “conclusion” section: Emphasize that the study shows an association rather than a causal effect. Is the work clearly and accurately presented and does it cite the current literature? No Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Hepatology, Gastroenterology, Endoscopy, Endocrinology, Oncology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Othman AA. Peer Review Report For: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.5256/f1000research.192345.r463570) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-254/v1#referee-response-463570 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Ezer B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 26 Feb 2026 | for Version 1 Burak Ezer , Beyhekim Training and Research Hospita, Konya, Turkey 0 Views copyright © 2026 Ezer B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Dear authors, thank you for your work. Below are some details that will enhance your article. 1. Methodological Rigor and Diagnostic Clarification -Validation of HCV Status: The study defines HCV status solely via third-generation ELISA (anti-HCV). In the ESRD population, impaired immune responses can lead to delayed seroconversion or false negatives. More importantly, without HCV-RNA (PCR) testing, it is impossible to distinguish between active viremia and resolved infection. The reviewers will likely require a discussion on whether complication risks correlate with viral load or if this was considered a study limitation. -Assessment of Liver Fibrosis Stage: The impact of HCV on the hemostatic system is directly proportional to the degree of liver damage (fibrosis/cirrhosis). The absence of baseline Child-Pugh scores or non-invasive markers such as APRI or FIB-4 scores is a significant gap. Providing these metrics is essential to characterize the severity of the underlying coagulopathy. Concomitant Medication Use: ESRD patients frequently utilize antiplatelet agents (e.g., Aspirin, Clopidogrel). The perioperative management of these drugs (whether they were discontinued) and their distribution between the HCV-positive and negative groups must be detailed, as they represent major confounding factors for hemostatic complications. 2. Statistical Analysis and Data Presentation -Addressing Selection Bias: There are significant baseline differences in age and diabetes prevalence between the two groups (HCV+ patients are younger and less diabetic). To ensure the reported 6-fold risk is not skewed by these variables, a Propensity Score Matching (PSM) analysis is strongly recommended to standardize the cohorts. -Expansion of Clinical Variables: Table 1 should be more comprehensive. Including parameters such as BMI, smoking status, hypertension, and peripheral vascular disease is necessary, as these factors significantly influence both bleeding risk and AVF maturation. -Refinement of Multivariate Model: In Table 5, the authors should justify why certain clinically relevant variables (e.g., diabetes, dialysis vintage) were excluded from the final model or why they did not reach statistical significance. 3. Discussion and Pathophysiological Mechanisms -Synergistic Hemostatic Defect: The discussion should more deeply explore the synergy between HCV-induced reduction in clotting factors and uremia-associated platelet dysfunction . This "dual-hit" mechanism is likely the driver behind the increased severity of bleeding observed in the HCV+ group. -Impact of DAA Therapy: Since the study period (2017–2024) overlaps with the widespread adoption of Direct-Acting Antivirals (DAAs), it is crucial to state whether any patients received treatment during the study. If so, how was their data handled? This is vital for the manuscript's relevance to current clinical guidelines. -Mechanisms of Maturation Failure: The technical link between hemostatic complications and maturation failure needs further elaboration. Specifically, how hematoma-induced extrinsic compression, localized inflammation, or the development of pseudoaneurysms physically impairs the remodeling and arterialization of the vein. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Medical Microbiology (Medical Doctor) I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Ezer B. Peer Review Report For: Hepatitis C virus infection as a six-fold risk factor for hemostatic complications following arteriovenous fistula creation in end-stage renal disease: A seven-year prospective study [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :254 ( https://doi.org/10.5256/f1000research.192345.r461324) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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