The Public Health Burden of Chronic Kidney Disease-Associated Hepatocellular Carcinoma

Rathashri Mallik¹, Birupaksha Biswas², Nadia Islam³, Md. Musfiqur Rahman⁴, Esrat Jahan Elora⁴, Md. Abul Hossain⁵, Md Mahedi Hasan Shabuj⁶, Asika Ayrin Naher⁷

Understanding CKD’s effect on HCC biomarkers is essential to protect liver health, enhance public health strategies, and improve patient health outcomes.

Abstract

Background: Hepatocellular carcinoma (HCC) ranks additional as the deadliest cancer, and around newly available literature proposes that the existence of chronic kidney illness may worsen the difficulty of important indicators like alpha-fetoprotein (AFP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and even platelet total. Methods: We confirmed a reflective cross-sectional study in three tertiary care centers which consisted of 255 patients with chronic liver bug (CLD) and had different degrees of renal meaning - normal, mild CKD, and simple CKD groups. Creatinine levels, eGFR, AFP, ALT, AST, and palates levels were gained and analyzed using ANOVA, correlation, and multivariate regression models. Results: There was a notable positive relationship between serum creatinine and AFP (r=0.62, p<0.001), whereby the most severely affected CKD patients had serum creatinine levels that were at least four-fold greater than those with normal renal functioning on AFP. With advancing CKD, ALT and AST levels gradually elevated while platelet counts markedly declined. Multivariate regression analysis showed that creatinine level independently predicted elevated AFP with the strongest relation amongst all age factors and liver damage proxies. Conclusion: The effects of chronic kidney disease (CKD) on hepatocellular carcinoma (HCC) biomarkers equal modifications cross with the well-known benchmarks, cumulative the indicative difficulty. Considering the rising global prevalence of CKD and liver disease, it leftovers important to evaluate renal function as part of the HCC surveillance system to facilitate earlier diagnosis and enhance management.

Keywords: Chronic Kidney Disease (CKD), Hepatocellular Carcinoma (HCC), Biomarkers, Liver Health, Public Health.

References

Agidew, M. M., Abebe, E. C., Muche, Z. T., Mengstie, M. A., Mulu, A. T., Admasu, F. T., ... & Dejenie, T. A. (2023). Evaluation of liver function biomarkers, blood pressure, and anthropometric parameters among chronic kidney disease patients: Laboratory-based cross-sectional study in Northwest Ethiopia. Metabolism Open, 19, 100254.

Ahn, J. C., Lee, Y., Agopian, V. G., Zhu, Y., You, S., Tseng, H., & Yang, J. D. (2022). Hepatocellular carcinoma surveillance: current practice and future directions. Hepatoma Research. https://doi.org/10.20517/2394-5079.2021.131

Almaguer, M., Herrera, R., & Orantes, C. M. (2014). Chronic kidney disease of unknown etiology in agricultural communities. MEDICC review, 16(2), 09-15.

Armstrong, D., Kline-Rogers, E., Jani, S. M., Goldman, E. B., Fang, J., Mukherjee, D., Nallamothu, B. K., & Eagle, K. A. (2005). Potential impact of the HIPAA privacy rule on data collection in a registry of patients with acute coronary Syndrome. Archives of Internal Medicine, 165(10), 1125. https://doi.org/10.1001/archinte.165.10.1125

Bashir, M. S., Hossian, M., Uddin, M. K. M., Sayem, M. A., Sultana, A., Rana, F. A., Akter, T., Das, N., Rana, M. S., & Das, S. S. (2025). Association between hepatocellular carcinoma and diabetes mellitus. Journal of Primeasia, 6(1), 1–7. https://doi.org/10.25163/primeasia.6110193

Bashir, M. S., Sayem, M. A., Das, S. S., Das, N., Sultana, A., Rahman, M. M., Shamsuzzaman, M., Paul, P., Hossian, M., & Uddin, M. K. M. (2025). High viral load is a risk factor for hepatocellular carcinoma: Clinical and laboratory insights from a cross-sectional study. Journal of Angiotherapy, 9(1), 1–8. https://doi.org/10.25163/angiotherapy.9110219

Cullaro, G., Kanduri, S. R., & Velez, J. C. Q. (2022). Acute Kidney Injury in Patients with Liver Disease. Clinical Journal of the American Society of Nephrology, 17(11), 1674–1684. https://doi.org/10.2215/cjn.03040322

Das, S. S., Hossain, M. S., Sultana, A., Rana, F. A., Hossen, A., Maowla, M. S., Uddin, M. K. M., Sayem, M. A., Hossian, M., & Bashir, M. S. (2025). The influence of chronic kidney disease on hepatocellular carcinoma. Journal of Primeasia, 6(1), 1–8. https://doi.org/10.25163/primeasia.6110204

Dekkers, I., De Mutsert, R., De Vries, A., Rosendaal, Cannegieter, S., Jukema, J., Cessie, S. L., Rabelink, T., Lamb, H., & Lijfering, W. (2017). Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population. Journal of Thrombosis and Haemostasis, 16(3), 519–528. https://doi.org/10.1111/jth.13935

Elsayed, M. O. K. (2023). Hepatocellular carcinoma surveillance in cirrhotic patients: Beyond guidelines. Gastroenterology and Functional Medicine, 1(1). https://doi.org/10.54844/gfm.2023.439

Hamilton, C. M., Strader, L. C., Pratt, J. G., Maiese, D., Hendershot, T., Kwok, R. K., Hammond, J. A., Huggins, W., Jackman, D., Pan, H., Nettles, D. S., Beaty, T. H., Farrer, L. A., Kraft, P., Marazita, M. L., Ordovas, J. M., Pato, C. N., Spitz, M. R., Wagener, D., . . . Haines, J. (2011). The PhenX toolkit: Get the most from your measures. American Journal of Epidemiology, 174(3), 253–260. https://doi.org/10.1093/aje/kwr193

Hossian, M., Hasan, M. M., Sultana, A., Das, S. S., Paul, P., Shamsuzzaman, M., Rahman, M. M., Uddin, M. K. M., Sayem, M. A., & Bashir, M. S. (2024). Potential role of Helicobacter pylori infection in hepatocellular carcinoma: A clinical and laboratory-based study. Journal of Angiotherapy, 8(12), 1–9. https://doi.org/10.25163/angiotherapy.81210217

Hussain, J., Grubic, N., Akbari, A., Canney, M., Elliott, M. J., Ravani, P., Tanuseputro, P., Clark, E. G., Hundemer, G. L., Ramsay, T., Tangri, N., Knoll, G. A., & Sood, M. M. (2023). Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study. BMJ, e075062. https://doi.org/10.1136/bmj-2023-075062

Islam, M. R., Yesmin, T., Prapty, A. N., Biswash, M. A. R., Rana, M. S., & Rashid, M. H. O. (2024). Natural environmental sources of resveratrol and its therapeutic role in cancer prevention. Australian Herbal Insight, 7(1), 1-11. https://doi.org/10.25163/ahi.719931

Jagdish, R. K., Roy, A., Kumar, K., Premkumar, M., Sharma, M., Rao, P. N., Reddy, D. N., & Kulkarni, A. V. (2023). Pathophysiology and management of liver cirrhosis: from portal hypertension to acute-on-chronic liver failure. Frontiers in Medicine, 10. https://doi.org/10.3389/fmed.2023.1060073

Kanubhai, D. M., & Sabirali, S. M. (2023). Hepatocellular carcinoma: a review. Asian Journal of Research in Pharmaceutical Sciences, 171–179. https://doi.org/10.52711/2231-5659.2023.00030

Kleber, M., Ihorst, G., Deschler, B., Jakob, C., Liebisch, P., Koch, B., Sezer, O., & Engelhardt, M. (2009). Detection of renal impairment as one specific comorbidity factor in multiple myeloma: multicenter study in 198 consecutive patients. European Journal of Haematology, 83(6), 519–527. https://doi.org/10.1111/j.1600-0609.2009.01318.x

Kubota, N., Fujiwara, N., & Hoshida, Y. (2020). Clinical and molecular prediction of hepatocellular carcinoma risk. Journal of Clinical Medicine, 9(12), 3843. https://doi.org/10.3390/jcm9123843

Kuster, N., Cristol, J., Cavalier, E., Bargnoux, A., Halimi, J., Froissart, M., Piéroni, L., & Delanaye, P. (2013). Enzymatic creatinine assays allow estimation of glomerular filtration rate in stages 1 and 2 chronic kidney disease using CKD-EPI equation. Clinica Chimica Acta, 428, 89–95. https://doi.org/10.1016/j.cca.2013.11.002 Eckardt, K., & Kasiske, B. L. (2012). KDIGO Clinical Practice Guideline for Glomerulonephritis. https://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25868939

Lee, C. (2013). Hepatocellular carcinoma in patients with chronic kidney disease. World Journal of Gastroenterology, 19(16), 2466. https://doi.org/10.3748/wjg.v19.i16.2466

Lisboa, U. De. (2021). Targeting liver cell metabolism and function in non-alcoholic fatty liver disease.

Neugarten, J., & Golestaneh, L. (2019). Liver disease and chronic kidney disease. In Elsevier eBooks (pp. 863–882). https://doi.org/10.1016/b978-0-12-815876-0.00053-x

Nourie, N., Ghaleb, R., Lefaucheur, C., & Louis, K. (2024). Toward precision Medicine: Exploring the landscape of biomarkers in acute kidney injury. Biomolecules, 14(1), 82. https://doi.org/10.3390/biom14010082

Poropat, G. (2024). FROM ORIGINS TO OUTCOMES: INVESTIGATING THE COMPLEXITY OF PORTAL HYPERTENSION IN ETIOLOGY, DIAGNOSIS, TREATMENT AND COMPLICATIONS. https://zir.nsk.hr/islandora/object/medri:8807

Rana, M. S., Bashir, M. S., Das, S. S., Hossain, M., & Barua, S. (2024). Biomarkers for hepatocellular carcinoma: Diagnosis, prognosis, and treatment response assessment – A systematic review. Journal of Primeasia, 5(1), 1–8. https://doi.org/10.25163/primeasia.519784

Sahu, N., Rakshit, S., & Bhaskar, L. (2022). Risk factors and pathogenic mechanism–associated hepatocellular carcinoma. In Elsevier eBooks (pp. 33–49). https://doi.org/10.1016/b978-0-323-98806-3.00023-4

Salam, M. T., Mou, M. A., Bari, K. F., Roy, N. C., Al-Mamun, A., Ullah, M. S., Hussen, M. A., Rana, M. S., & Hossain, M. B. (2025). Assessment of lipid profile in hepatocellular carcinoma patients: A prospective study in Bangladesh. Journal of Primeasia, 5(1), 1–8. https://doi.org/10.25163/primeasia.519787

Septiarini, N. N. A., Wardhani, N. P., Maimunah, N. U., & Indrasari, N. Y. N. (2024). Demographics, risk factors, clinical manifestations, staging and liver function tests of hepatocellular Carcinoma: A literature review. World Journal of Advanced Research and Reviews, 24(3), 2087–2093. https://doi.org/10.30574/wjarr.2024.24.3.3853

Song, P., Tang, Q., Feng, X., & Tang, W. (2016). Biomarkers: evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma. Scandinavian Journal of Clinical and Laboratory Investigation, 76(sup245), S70–S76. https://doi.org/10.1080/00365513.2016.1210328

Suraweera, D., Konyn, P., Vu, T., & Saab, S. (2018). Clinical epidemiology of chronic liver disease: Hepatocellular carcinoma. In Springer eBooks (pp. 229–249). https://doi.org/10.1007/978-3-319-94355-8_15

Thomas, M. E., Blaine, C., Dawnay, A., Devonald, M. A., Ftouh, S., Laing, C., Latchem, S., Lewington, A., Milford, D. V., & Ostermann, M. (2014). The definition of acute kidney injury and its use in practice. Kidney International, 87(1), 62–73. https://doi.org/10.1038/ki.2014.328

Tufael, M., Kar, A., Rashid, M. H. O., Sunny, A. R., Raposo, A., Islam, M. S., Hussain, M. A., Hussen, M. A., Han, H., Coutinho, H. D. M., Ullah, M. S., & Rahman, M. M. (2024). Diagnostic efficacy of tumor markers AFP, CA19-9, and CEA in hepatocellular carcinoma patients.Journal of Angiotherapy, 8(4), 1-10. https://doi.org/10.25163/angiotherapy.849513

Tufael, M., Kar, A., Upadhye, V. J., Dutta, A., Islam, M. R., Sattar, A., Ali, M. E., Akter, J., Bari, K. F., Salam, M. T., Banik, P. C., Khan, M. S. S., & Sunny, A. R. (2024). Significance of serum biomarkers in early diagnosis of hepatocellular carcinoma in patients with Fisher groups. Journal of Angiotherapy, 8(1), 1-9. https://doi.org/10.25163/angiotherapy.819440

Tufael, M., Rahman, M. M., Upadhye, V. J., Hossain, M. F., & Uddin, N. (2024). Combined biomarkers for early diagnosis of hepatocellular carcinoma. Journal of Angiotherapy, 8(5), 1-12. https://doi.org/10.25163/angiotherapy.859665

Uddin, M. K. M., Sultana, A., Rahman, M. M., Shamsuzzaman, M., Paul, P., Hasan, M. M., Sayem, M. A., Bashir, M. S., Das, S. S., & Hossian, M. (2025). Cardiovascular complications in patients with hepatocellular carcinoma. Journal of Angiotherapy, 9(1), 1–8. https://doi.org/10.25163/angiotherapy.9110218

World Medical Association Declaration of Helsinki. (2024). JAMA. https://doi.org/10.1001/jama.2024.21972