Impact of HIV Co-infection and Antiretroviral Therapy on Tumor Necrosis Factor-Alpha (TNF-α), Fibrinogen, and Haptoglobin Markers in Hepatitis B and C Subjects

Authors

  • Ihionu Chidozie Department of Medical Laboratory Science, Imo State University, Owerri, Nigeria Author
  • Harrison Nwanjo Department of Medical Laboratory Science, Imo State University, Owerri, Nigeria Author
  • Nwosu Dennis Department of Medical Laboratory Science, Imo State University, Owerri, Nigeria Author

DOI:

https://doi.org/10.64229/gj6jrc79

Keywords:

HIV Co-infection, Antiretroviral Therapy, Inflammatory, Acute Phase Markers, Hepatitis B and C

Abstract

Chronic hepatitis B virus (HBV) infection, when co-occurring with human immunodeficiency virus (HIV), significantly exacerbates liver inflammation and disease progression. This study assessed the impact of HIV co-infection and antiretroviral therapy (ART) on key inflammatory and acute phase markers—tumor necrosis factor-alpha (TNF-α), fibrinogen, and haptoglobin—in HBV-infected individuals.In the first analysis, levels of these biomarkers were compared between HBV/HIV co-infected subjects and healthy controls. The TNF-α level was significantly elevated in co-infected individuals (206.15 ± 21.43 pg/ml) compared to controls (190.15 ± 21.99 pg/ml) with a t-value of 3.769 and a p-value of 0.044, indicating heightened systemic inflammation. Conversely, fibrinogen levels were significantly lower in the co-infected group (8.2 ± 0.69 g/L) than in controls (9.33 ± 4.26 g/L), with a t-value of 3.391 and p-value of 0.037, suggesting altered acute phase protein synthesis. Haptoglobin levels were markedly higher in co-infected subjects (3.05 ± 1.0 g/L) versus controls (1.08 ± 0.09 g/L), with a statistically significant difference (t = 3.054; p = 0.040). Further analysis explored the effect of ART by comparing untreated HBV/HIV co-infected subjects with those on therapy. TNF-α levels were lower in the treated group (191.10 ± 19.45 pg/ml) compared to the untreated group (206.15 ± 21.43 pg/ml), with a statistically significant p-value of 0.040. Fibrinogen levels declined substantially in those on therapy (3.37 ± 4.15 g/L) versus untreated individuals (8.2 ± 0.69 g/L), showing a significant reduction (p = 0.030). Similarly, haptoglobin levels decreased in treated subjects (2.05 ± 0.03 g/L) compared to untreated (3.05 ± 1.0 g/L), with a p-value of 0.040. These findings demonstrate that HBV/HIV co-infection significantly alters inflammatory and acute phase responses, as reflected by elevated TNF-α and haptoglobin levels and reduced fibrinogen. Importantly, antiretroviral therapy appears to mitigate these effects, reducing TNF-α, fibrinogen, and haptoglobin concentrations, though levels remain abnormal relative to healthy controls. This underscores the importance of early HIV diagnosis and initiation of ART in co-infected patients to manage inflammation and reduce the risk of liver-related complications.

References

[1]Hagos, Y.M.; Yalew, G.T.; Meles, H.N.; Tsegay, E.; Lemelem, M.; Wasihun, A.G (2024), Hepatitis B and C Viral Coinfection and Associated Factors among HIV-Positive Patients Attending ART Clinics of Afar Regional State, Northeast Ethiopia. PLoS ONE 19, e0302453.

[2]Jin, F.; Dore, G.J.; Matthews, G.; Luhmann, N.; Macdonald, V.; Bajis, S.; Baggaley, R.; Mathers, B.; Verster, A.; Grulich, A.E(2021). Prevalence and Incidence of Hepatitis C Virus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis. Lancet Gastroenterol. Hepatol. , 6, 39–56.

[3]Egberts JH, Cloosters V, Noack A, (2018). Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth. Cancer Res, 68(5):1443–50.

[4]Zarębska-Michaluk, D.; Rzymski, P.; Kanecki, K.; Tyszko, P.; Lewtak, K.; Goryński, P.; Genowska, A.; Parczewski, M.; Flisiak, R(2024). Hospitalizations and Deaths among People Coinfected with HIV and HCV. Sci. Rep. 14, 28586.

[5]Hohan, R.; Paraschiv, S.; Nicolae, I.; Oțelea, D (2024). Estimating the Current Routes of Transmission in HIV-1 F1 Subtype Infected Persons in Romania: Differences Between Self-Reporting and Phylogenetic Data. Pathogens 13, 960

[6]Seyoum, E.; Demissie, M.; Worku, A.; Mihret, A.; Abdissa, A.; Berhane, Y. (2022) Retention on Antiretroviral Therapy in Person with HIV and Viral Hepatitis Coinfection in Ethiopia: A Retrospective Cohort Study. BMC Public Health 22, 644

[7]Avihingsanon, A.; Lu, H.; Leong, C.L.; Hung, C.-C.; Koenig, E.; Kiertiburanakul, S.; Lee, M.-P.; Supparatpinyo, K.; Zhang, F.; Rahman, S.; (2023). Bictegravir, Emtricitabine, and Tenofovir Alafenamide versus Dolutegravir, Emtricitabine, and Tenofovir Disoproxil Fumarate for Initial Treatment of HIV-1 and Hepatitis B Coinfection (ALLIANCE): A Double-Blind, Multicentre, Randomised Controlled, Phase 3 Non-Inferiority Trial. Lancet HIV 10, e640–e652.

[8]Al-Shobaili, H.A., Salem, T.A., Alzolibani, A.A., Robaee, A.A. and Settin, A.A. (2012). Tumor necrosis factor-alpha -308 G/A and interleukin 10 -1082 A/G gene polymorphisms in patients with acne vulgaris. Journal of Dermatology Science, 68: 52–55

[9]Kulbe, H., Thompson, R., Wilson, J.L., et al. (2017). TNF-alpha generates autocrine tumor-promoting network. Cancer Research, 67(2): 585–592.

[10]Ateş, A., Kinikli, G., Düzgün, N. and Duman, M. (2016). Lack of association of tumor necrosis factor-alpha gene polymorphisms with disease susceptibility and severity in Behçet’s disease. Rheumatology, 26: 348–353.

[11]Olawumi, H.; Olanrewaju, D.; Shittu, A.; Durotoye, I.; Akande, A.; Nyamngee, A. (2014) Effect of Hepatitis-B Virus Co-Infection on CD4 Cell Count and Liver Function of HIV Infected Patients. Ghana. Med. J. , 48, 96–100.

[12]Kamal, H.; Fornes, R.; Simin, J.; Stål, P.; Duberg, A.-S.; Brusselaers, N.; Aleman, S. (2021) Risk of Hepatocellular Carcinoma in Hepatitis B and D Virus Co-Infected Patients: A Systematic Review and Meta-Analysis of Longitudinal Studies. J. Viral Hepat. 28, 1431–1442.

[13]Yan, B., Wang, H., Rabbani, Z.N., (2016). TNF-α as endogenous mutagen. Cancer Research, 66(24):11565–11570

[14]Hu, J.; Liu, K.; Luo, J(2019). HIV-HBV and HIV-HCV Coinfection and Liver Cancer Development. Cancer Treat. Res. , 177, 231–250.

[15]Rajbhandari, R.; Jun, T.; Khalili, H.; Chung, R.T.; Ananthakrishnan, A.N(2016). HBV/HIV Coinfection Is Associated with Poorer Outcomes in Hospitalized Patients with HBV or HIV. J. Viral Hepat. , 23, 820–829.

[16]Seth, A.; Sherman, K.E. (2019) Fatty Liver Disease in Persons With HIV Infection. Top. Antivir. Med. 27, 75–82.

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Published

2025-08-21

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