Association of Blood Baseline Parameters with Alpha-Fetoprotein and Its Importance as a Prognostic Factor in Intrahepatic Ductal Carcinoma Patients: An Analytical Cross-Sectional Study: Blood Parameters and AFP as Prognostic Markers in Intrahepatic Ductal Carcinoma

Beenish Haleem Riaz; Khalida Anwar; Madeeha Mushtaq; Kamran Shauket; Ayesha Khan; Abeerah Zafar; Rubaida Mehmood; Tayyaba Yasin; Ayesha Arif; Hina Awais

doi:10.54393/pjhs.v7i5.3685

Authors

Beenish Haleem Riaz Department of Biochemistry, Nawaz Sharif Medical College, Gujrat, Pakistan
Khalida Anwar Department of Biochemistry, Rahim Yar Khan Medical and Dental College, Rahim Yar Khan, Pakistan
Madeeha Mushtaq Department of Biochemistry, University of Health Sciences, Lahore, Pakistan
Kamran Shauket Department of Medicine, Sahiwal Teaching Hospital, Sahiwal, Pakistan
Ayesha Khan Department of Biochemistry, Rashid Latif Medical College, Lahore, Pakistan
Abeerah Zafar Department of Gynecology and Obstetrics, Sahiwal Teaching Hospital, Sahiwal, Pakistan
Rubaida Mehmood Department of Diagnostic Lab, Multan Institute of Nuclear Medicine and Radiotherapy, Pakistan Atomic Energy Commission, Multan, Pakistan
Tayyaba Yasin Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
Ayesha Arif Department of Health Promotion, University of Palermo, Palermo, Italy
Hina Awais Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy

DOI:

https://doi.org/10.54393/pjhs.v7i5.3685

Keywords:

Intrahepatic Ductal Carcinoma, Alpha-Fetoprotein, Liver Function Tests, Complete Blood Count, Serum Creatinine, Prognostic Biomarkers

Abstract

Intrahepatic Ductal Carcinoma (IHDC), a subtype of cholangiocarcinoma, is an aggressive liver cancer with a poor prognosis and rising global incidence. Although Alpha-Fetoprotein (AFP) is a common tumor biomarker, its prognostic value in IHDC is limited when used alone. Objectives: To determine the association between AFP and blood baseline parameters to evaluate their combined prognostic significance in patients with IHDC. Methods: This analytical cross-sectional study was conducted at MINAR Cancer Hospital, Multan, Pakistan, from January 2019 to December 2020. A total of 107 histologically confirmed IHDC patients (61 males, 46 females; mean age = 56.8 ± 11.2 years) were included. CBC, LFTs, and serum creatinine were analyzed using standard automated methods, while AFP was measured via electro-chemiluminescence immunoassay (ECLIA). Data were analyzed using SPSS version 24.0. Results: Significant gender-based differences were found in eosinophil counts (p = 0.041) and serum creatinine (p = 0.024). Elderly patients (≥60 years) showed higher monocytes (p=0.030) and Mean Platelet Volume (p=0.002). Across tumor stages, neutrophils increased (66.8% → 78.2%, p<0.001), lymphocytes decreased (25.1% → 18.5%, p < 0.001), and ALP and bilirubin rose significantly (p = 0.021; p=0.008). AFP correlated positively with ALP (r=0.85), SGOT (r=0.79), bilirubin (r=0.86), serum creatinine (r=0.99), and blood urea (r=0.98), and negatively with lymphocytes (r = –0.83). Conclusions: AFP was associated with hepatic, renal, and inflammatory parameters in IHDC, suggesting its potential as a composite biomarker for staging and prognosis.

References

Guo Q, Zhu X, Beeraka NM, Zhao R, Li S, Li F et al. Projected Epidemiological Trends and Burden of Liver Cancer by 2040 Based on GBD, CI5plus, and WHO data. Scientific Reports. 2024 Nov; 14(1): 28131. doi: 10.1038/s41598-024-77658-2.

Chung T and Park YN. Up-to-date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Frontiers in medicine. 2022 Mar; 9: 857140. doi: 10.3389/fmed.2022.857140.

Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, Lind GE, Folseraas T, Forbes SJ, Fouassier L, Geier A. Cholangiocarcinoma: Current Knowledge and Future Perspectives Consensus Statement from the European Network for the Study of Cholangiocarcinoma. Nature Reviews Gastroenterology and Hepatology. 2016 May; 13(5): 261-280. doi: 10.1038/nrgastro.2016.51.

Rodrigues PM, Olaizola P, Paiva NA, Olaizola I, Agirre-Lizaso A, Landa A et al. Pathogenesis of Cholangiocarcinoma. Annual Review of Pathology: Mechanisms of Disease. 2021 Jan; 16(1): 433-463. doi: 10.1146/annurev-pathol-030220-020455.

Piñero F, Dirchwolf M, Pessôa MG. Biomarkers in Hepatocellular Carcinoma: Diagnosis, Prognosis, and Treatment Response Assessment. Cells. 2020 Jun; 9(6): 1370. doi: 10.3390/cells9061370.

Ali F, Hussain S, Memon SA, Iqbal SS. Recently, the Top Trending Cancers in a Tertiary Cancer Hospital in Pakistan. Dr. Sulaiman Al Habib Medical Journal. 2023 Jun; 5(2): 42-49. doi: 10.1007/s44229-023-00028-z.

Singal AG, Kanwal F, Llovet JM. Global Trends in Hepatocellular Carcinoma Epidemiology: Implications for Screening, Prevention, and Therapy. Nature reviews Clinical oncology. 2023 Dec; 20(12): 864-884. doi: 10.1038/s41571-023-00825-3.

Gatto M, Bragazzi MC, Semeraro R, Napoli C, Gentile R, Torrice A et al. Cholangiocarcinoma: update and future perspectives. Digestive and Liver Disease. 2010 Apr; 42(4): 253-260. doi: 10.1016/j.dld.2009.12.008.

Dar FS, Abbas Z, Ahmed I, Atique M, Aujla UI, Azeemuddin M et al. National Guidelines for the Diagnosis and Treatment of Hilar Cholangiocarcinoma. World Journal of Gastroenterology. 2024 Mar; 30(9): 1018. doi: 10.3748/wjg.v30.i9.1018.

Wong RJ, Ahmed A, Gish RG. Elevated Alpha-Fetoprotein: Differential Diagnosis-Hepatocellular Carcinoma and Other Disorders. Clinics in Liver Disease. 2015 May; 19(2): 309-323. doi: 10.1016/j.cld.2015.01.005.

Wei Z, Zhang Y, Lu H, Ying J, Zhao H, Cai J. Serum Alpha-Fetoprotein as a Predictive Biomarker for Tissue Alpha-Fetoprotein Status and Prognosis in Patients with Hepatocellular Carcinoma. Translational Cancer Research. 2022 Apr; 11(4): 669. doi: 10.21037/tcr-21-2334.

Shukla R, Silvanus V, Dahal S, Sitaula P, Niraula Z, Gupta CK et al. Complete Blood Count-Derived Indices at Admission and Short-Term Outcomes in Intensive Care Unit Patients: A Retrospective Study. Annals of Medicine. 2025 Dec; 57(1): 2522963. doi: 10.1080/07853890.2025.2522963.

Liu D, Heij LR, Czigany Z, Dahl E, Dulk MD, Lang SA et al. The Prognostic Value of Neutrophil-To-Lymphocyte Ratio in Cholangiocarcinoma: A Systematic Review and Meta-Analysis. Scientific Reports. 2022 Jul; 12(1): 12691. doi: 10.1038/s41598-022-16727-w.

Hashmi M, Haider G, Danish M, Hassan A, Irshad R, Khalil A. Raised Alpha-Fetoprotein Level and Its Association with Hepatocellular Carcinoma. Pakistan Armed Forces Medical Journal. 2023 Oct; 73(5): 1257. doi: 10.51253/pafmj.v73i5.5419.

Fu X, Wang J, Jiang S, Wu J, Mu Z, Tang Y et al. Mortality Trend Analysis of Ischemic Heart Disease in China Between 2010 and 2019: A Joinpoint Analysis. BioMed Central Public Health. 2023 Apr; 23(1): 644. doi: 10.1186/s12889-023-15549-3.

Hassan S, Khan S, Khan A, Khattak M, Khattak EK, Farrukh AM et al. Assessment of Liver Transplant Eligibility in Chronic Liver Disease Patients: A Cross-Sectional Study from a Tertiary Care Hospital of Pakistan. Cureus. 2024 May; 16(5): 1-6. doi: 10.7759/cureus.61028.

Chen J, Li K, Shao J, Lai Z, Feng Y, Liu B. The Correlation of Apolipoprotein B With Alterations in Specific Fat Depot Content in Adults. International Journal of Molecular Sciences. 2023 Mar; 24(7): 6310. doi: 10.3390/ijms24076310.

Taylor C, Cheema AS, Asleh K, Finn N, Abdelsalam M, Ouellette RJ. Sex-Specific Cytokine Signatures as Predictors of Anti-PD1 Therapy Response in Non-Small Cell Lung Cancer. Frontiers in Immunology. 2025 Jun; 16: 1583421. doi: 10.3389/fimmu.2025.1583421.

Beudeker BJ, Groothuismink ZM, van der Eijk AA, Debes JD, Boonstra A. Circulating Cytokines Reflect the Etiology-Specific Immune Environment in Cirrhosis and HCC. Cancers. 2022 Oct; 14(19): 4900. doi: 10.3390/cancers14194900.

Ji F, Kang Q, Wang L, Liu L, Ke Y, Zhu Y et al. Prognostic Significance of the Neutrophil-to-Lymphocyte Ratio in Patients with Distal Cholangiocarcinoma. Medicine. 2020 Oct; 99(43): 22827. doi: 10.1097/MD.0000000000022827.

Wang T and Zhang KH. New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma. Frontiers in Oncology. 2020 Aug; 10: 1316. doi: 10.3389/fonc.2020.01316.

Chicco D and Oneto L. Computational Intelligence Identifies Alkaline Phosphatase, Alpha-Fetoprotein, and Hemoglobin Levels as Most Predictive Survival Factors for Hepatocellular Carcinoma. Health Informatics Journal. 2021 Jan; 27(1): 1-26. doi: 10.1177/1460458220984205.

Ali S, Nazeer A, Tipu I. The Correlation Between Alpha-Fetoprotein and Liver Function Tests. BioScientific Review. 2019 Dec; 1(4): 10-19. doi: 10.32350/BSR.0104.02.

Das SS, Hossain MS, Sultana A, Rana FA, Hossen A, Maowla MS et al. The Influence of Chronic Kidney Disease on Hepatocellular Carcinoma. Journal of Primeasia. 2025 Apr; 6(1): 1-8. doi: 10.25163/primeasia.6110204.

Yap DY, Seto WK, Fung J, Chok SH, Chan SC, Chan GC et al. Serum and Urinary Biomarkers That Predict Hepatorenal Syndrome in Patients with Advanced Cirrhosis. Digestive and Liver Disease. 2017 Feb; 49(2): 202-206. doi: 10.1016/j.dld.2016.11.001.

Blanco Abad C, Gomila Pons P, Campos Ramirez S, Álvarez Alejandro M, Torres Ramón MI, Miramar Gallart MD et al. Hereditary Pancreatic Cancer: Advances in Genetic Testing, Early Detection Strategies, and Personalized Management. Journal of Clinical Medicine. 2025 Jan; 14(2): 367. doi: 10.3390/jcm14020367.

Munir M, Maqbool M, Ayyaz J, Anis S, Maqbool S. Correlation of Hepatocellular Carcinoma with Different Levels of Alpha-Fetoprotein in Pakistani Population. Annals of PIMS-Shaheed Zulfiqar Ali Bhutto Medical University. 2021 Nov; 17(3): 260-265. doi: 10.48036/apims.v17i3.565.