Diagnostic role of Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and its correlation with serum Lipid Profiles in HCV Iraqi patients
DOI:
https://doi.org/10.32792/utq/utjsci/v13i1.1445Abstract
This study aimed to understand the role of serum Protein induced by Vitamin K Absence or Antagonist II (PIVKA-II) and its correlation with lipid profiles as diagnostic biomarkers in patients with different stages of hepatitis C virus infection. A case-control study involved 150 participants aged 5 to ≥81 years, 50 individuals were healthy, and 100 had HCV infection. The mean serum levels of PIVKA-II were significantly increased in acute hepatitis C (AHC), chronic hepatitis C (CHC), Hepatitis C virus-induced liver cirrhosis (HCV-LC) and sustained virologic response (SVR) groups compared to healthy control group. PIVKA-II showed significant negative correlation with Triglycerides (TG) and very low-density lipoprotein (VLDL) in both acute and chronic hepatitis C groups, and negative correlation with low density lipoprotein (LDL) in HCV-LC group. Receiver Operating Characteristic (ROC) curve analysis of PIVKA-II in HCV patients showed higher sensitivity and specificity in all four included HCV stages. Elevated serum PIVKA-II in HCV patients in this study predict its possibility in using as biomarker for diagnosing different HCV stages - acute, chronic, cirrhosis, and sustained virologic response from healthy individuals. However, the small differences in mean serum PIVKA-II levels between HCV groups make it unsuitable biomarker to differentiate between studied stages of HCV infection. The negative correlation between PIVKA-II and serum lipid profiles in treatment naïve HCV patients can be used as a prognostic biomarker for liver disease severity and the risk of Hepatocellular carcinoma (HCC).
Received: 10-07-2025
Revised:12-08-2025
Accepted: 28-08-2025
References
M.Y.W. Zaki, A.M. Fathi, S. Samir, N. Eldafashi, K.Y. William, M.H. Nazmy, et al. “Innate and adaptive immunopathogeneses in viral hepatitis; crucial determinants of hepatocellular carcinoma”. Cancers (Basel), Vol., 14 No., 5 PP., 1255 2022.
N.F.A. Rasheed, H.S. Jassim, A.S. Hassan “Assessment of Some Heavy Metals and Trace Elements in a Sample of Patients with Viral Hepatitis in Baghdad”. Journal of Techniques, Vol., 4 No., 3 PP., 8 2022.
I. H. Dhefer “Liver damage during infections with corona virus”. Journal of Techniques, Vol., 3 No., 2 PP., 79-85 2022.
M. Wang, L. Li, Y. Xu, J. Du, C. Ling “Roles of hepatic stellate cells in NAFLD: from the perspective of inflammation and fibrosis” Front. Pharmacol, Vol., 13 PP., 958428 2022.
World Health Organization. Hepatitis C, fact sheet 2024. hhttp://www.who.int/mediacentre/factsheets/fs164/en/. Accessed 3 April 2025.
K.G.R. Al-Azzawi, A. Al-Naqeeb, M.A.K. Zeidan “Impact of Chronic Liver Diseases on Specific Health-Related Quality of Life among a Sample in Babylon Government”. Journal of Techniques, Vol., 4 No., 33 PP., 86-90 2022.
L. Dong, X. Qiu, F. Gao, K. Wang, X. Xu “Protein induced by vitamin K absence or antagonist II: Experience to date and future directions”. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Vol., 1878 No., 6 PP., 189016 2023.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al., “PIVKA II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 2 2024.
W. Elgretli, T. Chen, N. Kronfli, and G. Sebastiani. “Hepatitis C virus-lipid interplay: pathogenesis and clinical impact”. Biomedicines, Vol., 11 No., 2 PP., 271 2023.
R. Villani, F. Di Cosimo, A.D. Romano, et al. “Serum lipid profile in HCV patients treated with direct-acting antivirals: a systematic review and meta-analysis”. Sci Rep, Vol., 11 No., 1 PP., 13944 2021.
M. Abdel-Gawad, M. Nour, F. El-Raey, H. Nagdy, Y. Almansoury, M. El-Kassas “Gender differences in prevalence of hepatitis C virus infection in Egypt: a systematic review and meta-analysis”. Sci Rep. Vol., 13 No., 1 PP., 2499 2023.
N.A. Marzuk, L.J. Tawfiq, N.Sh. Mohammed "Assessment of Some Biochemical Parameters in a Sample of Patients with Chronic Hepatitis C virus in Iraq" Al-Nisour Journal for Medical Sciences: Vol., 6 No., 2 PP., 19-22 2024.
T. A. Hameed, “Gene Expression of IL32, 33, TNF with Nitric Oxide and GSH Measurement in Hepatitis C Patients of Co-infection with Toxoplasmosis”. Doctorate. Theses, Middle Technical University College of Health & Medical Technology / Baghdad. 2024.
Z.G. Mahran, H. Khalifa, N.A. Makhlouf, et al. “Effect of gender difference on psychiatric outcomes for hepatitis C virus patients receiving direct-acting antivirals in Egyptian population: a cohort study”. Egypt J Neurol Psychiatry Neurosurg, Vol., 58 No., 1 PP., 155 2022.
M. F. Alsaffar “Elevation of Some Biochemical and Immunological Parameters in Hemodialysis Patients Suffering from Hepatitis C Virus Infection in Babylon Province”. Indian Journal of Forensic Medicine & Toxicology, Vol., 15 No., 3 2021.
P. Simoes, A. Asaad, J. Abed, E.S. Engelson, D.P. Kotler “ Effect of Gender on the Response to Hepatitis C Treatment in an Inner-City Population”. Womens Health Issues. Vol., 25 No., 3 PP., 289-93 2015.
K. Hayashida, I. Shoji, L. Deng, D.P. Jiang, Y.H. Ide, H. Hotta “17β-estradiol inhibits the production of infectious particles of hepatitis C virus”. Microbiol Immunol. Vol., 54 PP., 684-690 2010.
R.Y. Mekky, N. Hamdi, W. El-Akel, G. Esmat, A.I. Abdelaziz “Estrogen-related MxA transcriptional variation in hepatitis C virus-infected patients”. Transl Res. Vol., 159 PP., 190-196. 2012
H.F. Hetta, H.M. Hamed, M.A. Mekky, et al. “Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma”. Egypt Liver Journal, Vol., 14 PP., 78 2024.
M.A. Al-Azzawy “Molecular and Immunological Study of Acute and Chronic Hepatitis B and C in Kirkuk City”. Ph.D. dissertation, Dept. Microbiology, College of Medicine, University of Tikrit, Tikrit, Iraq, 2019.
S. Tian, Y. Chen, Y. Zhang, X. Xu “Clinical value of serum AFP and PIVKA-II for diagnosis,treatment and prognosis of hepatocellular carcinoma”. J Clin Lab Anal, Vol., 37 PP., e24823 2023.
J. Ji, L. Liu, F. Jiang, X. Wen, Y. Zhang, Sh. Li, et al., “The clinical application of PIVKA-II in hepatocellular carcinoma and chronic liver diseases: A multi-center study in China”. Journal of Clinical Laboratory Analysis, Vol., 35 No., 11 PP., e24013 2021.
G.P. Caviglia, P. Fariselli, R. D'Ambrosio, P. Colombatto, E. Degasperi, G. Ricco, et al. “Development and Validation of a PIVKA-II-Based Model for HCC Risk Stratification in Patients With HCV-Related Cirrhosis Successfully Treated With DAA”. Aliment Pharmacol Ther; Vol., 61 No., 3 PP., 538-549 2025.
D.A. Sheridan, I.T. Shawa, E.L. Thomas, et al. “Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis”. Sci Rep; Vol., 12 PP. 5562 2022.
B.M. Kamath, E.M. Alonso, J.E. Heubi, S.J. Karpen, S.S. Sundaram, B.L. Shneider, et al., “Fat soluble vitamin assessment and supplementation in cholestasis”. Clinics in liver disease. Vol., 26 No.,3 PP., 537-53 2022.
G. Peschel, J. Grimm, K. Gulow, M. Muller, C. Buechler, K. Weigand, “Chemerin Is a Valuable Biomarker in Patients with HCV Infection and Correlates with Liver Injury”. Diagnostics, Vol., 10 PP., 974 2020.
H.A. AbdEl-maksoud, M.G. Elharrif, O. Abd El-hamid, S.M. Alsaab, E.M. El-sorady “Monitoring of iron, lipid and liver profiles in Egyptian hepatitis C virus patients on sofosbuvir therapy”, Journal of Infection and Public Health,Vol. 15 No. 3 PP. 277-281 2022.
F. Wrensch, E. Crouchet, G. Ligat, M.B. Zeisel, Z.Y. Keck, S.K.H. Foung, et al., “Hepatitis C Virus (HCV)–Apolipoprotein Interactions and Immune Evasion and Their Impact on HCV Vaccine Design”. Front. Immunol, Vol., 9 PP., 1436 2018.
M. Sidorkiewicz, “Hepatitis C Virus Uses Host Lipids to Its Own Advantage”. Metabolites, Vol., 11 No., 5 PP., 273 2021.
D. G. Mashek, “Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD, Molecular Metabolism, Volume 50, 2021, 101115,
Y. Nahmias, M. Casali, L. Barbe, F. Berthiaume, M.L. Yarmush “Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes”. Hepatology. Vol., 43 No., 2 PP., 257-65 2006.
R. Zampino, A. Marrone, L. Restivo, B. Guerrera, A. Sellitto, L. Rinaldi, et al., “Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations”. World J Hepatol. Vol., 5 No., 10 PP., 528-40 2013.
J.W. Liou, H. Mani, J.H. Yen “Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds”. International Journal of Molecular Sciences. Vol., 23 No., 7 PP., 3897 2022.
Ch.H. Lin, J.J. Chen, P.L. Lee, H.D. Tong, Ch.T. Cheng, H.J. Kao et al., “Lipid profile changes after direct acting antiviral treatment in different genotypes of chronic hepatitis C virus-infected patients”. Advances in Digestive Medicine, Vol., 8 No., 3 PP., 139-145 2020.
Y. Chen, Y. Yang, S. Li, M. Lin, X. Xie, H. Shi, et al., “Changes and clinical significance of PIVKA-II in hepatitis E patients”. Frontiers in Public Health. Vol., 9 PP., 784718 2022.
A.O. Pascual, D.D. Casas, C.C. Yagüe, J.M. Arbones, V.M. Bernal “Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication”. Pathogens. Vol., 13 No., 4 PP., 278 2024.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al. “PIVKA‑II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 1 pp., 2 2023.
M.Y.W. Zaki, A.M. Fathi, S. Samir, N. Eldafashi, K.Y. William, M.H. Nazmy, et al. “Innate and adaptive immunopathogeneses in viral hepatitis; crucial determinants of hepatocellular carcinoma”. Cancers (Basel), Vol., 14 No., 5 PP., 1255 2022.
N.F.A. Rasheed, H.S. Jassim, A.S. Hassan “Assessment of Some Heavy Metals and Trace Elements in a Sample of Patients with Viral Hepatitis in Baghdad”. Journal of Techniques, Vol., 4 No., 3 PP., 8 2022.
I. H. Dhefer “Liver damage during infections with corona virus”. Journal of Techniques, Vol., 3 No., 2 PP., 79-85 2022.
M. Wang, L. Li, Y. Xu, J. Du, C. Ling “Roles of hepatic stellate cells in NAFLD: from the perspective of inflammation and fibrosis” Front. Pharmacol, Vol., 13 PP., 958428 2022.
World Health Organization. Hepatitis C, fact sheet 2024. hhttp://www.who.int/mediacentre/factsheets/fs164/en/. Accessed 3 April 2025.
K.G.R. Al-Azzawi, A. Al-Naqeeb, M.A.K. Zeidan “Impact of Chronic Liver Diseases on Specific Health-Related Quality of Life among a Sample in Babylon Government”. Journal of Techniques, Vol., 4 No., 33 PP., 86-90 2022.
L. Dong, X. Qiu, F. Gao, K. Wang, X. Xu “Protein induced by vitamin K absence or antagonist II: Experience to date and future directions”. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Vol., 1878 No., 6 PP., 189016 2023.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al., “PIVKA II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 2 2024.
W. Elgretli, T. Chen, N. Kronfli, and G. Sebastiani. “Hepatitis C virus-lipid interplay: pathogenesis and clinical impact”. Biomedicines, Vol., 11 No., 2 PP., 271 2023.
R. Villani, F. Di Cosimo, A.D. Romano, et al. “Serum lipid profile in HCV patients treated with direct-acting antivirals: a systematic review and meta-analysis”. Sci Rep, Vol., 11 No., 1 PP., 13944 2021.
M. Abdel-Gawad, M. Nour, F. El-Raey, H. Nagdy, Y. Almansoury, M. El-Kassas “Gender differences in prevalence of hepatitis C virus infection in Egypt: a systematic review and meta-analysis”. Sci Rep. Vol., 13 No., 1 PP., 2499 2023.
N.A. Marzuk, L.J. Tawfiq, N.Sh. Mohammed "Assessment of Some Biochemical Parameters in a Sample of Patients with Chronic Hepatitis C virus in Iraq" Al-Nisour Journal for Medical Sciences: Vol., 6 No., 2 PP., 19-22 2024.
T. A. Hameed, “Gene Expression of IL32, 33, TNF with Nitric Oxide and GSH Measurement in Hepatitis C Patients of Co-infection with Toxoplasmosis”. Doctorate. Theses, Middle Technical University College of Health & Medical Technology / Baghdad. 2024.
Z.G. Mahran, H. Khalifa, N.A. Makhlouf, et al. “Effect of gender difference on psychiatric outcomes for hepatitis C virus patients receiving direct-acting antivirals in Egyptian population: a cohort study”. Egypt J Neurol Psychiatry Neurosurg, Vol., 58 No., 1 PP., 155 2022.
M. F. Alsaffar “Elevation of Some Biochemical and Immunological Parameters in Hemodialysis Patients Suffering from Hepatitis C Virus Infection in Babylon Province”. Indian Journal of Forensic Medicine & Toxicology, Vol., 15 No., 3 2021.
P. Simoes, A. Asaad, J. Abed, E.S. Engelson, D.P. Kotler “ Effect of Gender on the Response to Hepatitis C Treatment in an Inner-City Population”. Womens Health Issues. Vol., 25 No., 3 PP., 289-93 2015.
K. Hayashida, I. Shoji, L. Deng, D.P. Jiang, Y.H. Ide, H. Hotta “17β-estradiol inhibits the production of infectious particles of hepatitis C virus”. Microbiol Immunol. Vol., 54 PP., 684-690 2010.
R.Y. Mekky, N. Hamdi, W. El-Akel, G. Esmat, A.I. Abdelaziz “Estrogen-related MxA transcriptional variation in hepatitis C virus-infected patients”. Transl Res. Vol., 159 PP., 190-196. 2012
H.F. Hetta, H.M. Hamed, M.A. Mekky, et al. “Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma”. Egypt Liver Journal, Vol., 14 PP., 78 2024.
M.A. Al-Azzawy “Molecular and Immunological Study of Acute and Chronic Hepatitis B and C in Kirkuk City”. Ph.D. dissertation, Dept. Microbiology, College of Medicine, University of Tikrit, Tikrit, Iraq, 2019.
S. Tian, Y. Chen, Y. Zhang, X. Xu “Clinical value of serum AFP and PIVKA-II for diagnosis,treatment and prognosis of hepatocellular carcinoma”. J Clin Lab Anal, Vol., 37 PP., e24823 2023.
J. Ji, L. Liu, F. Jiang, X. Wen, Y. Zhang, Sh. Li, et al., “The clinical application of PIVKA-II in hepatocellular carcinoma and chronic liver diseases: A multi-center study in China”. Journal of Clinical Laboratory Analysis, Vol., 35 No., 11 PP., e24013 2021.
G.P. Caviglia, P. Fariselli, R. D'Ambrosio, P. Colombatto, E. Degasperi, G. Ricco, et al. “Development and Validation of a PIVKA-II-Based Model for HCC Risk Stratification in Patients With HCV-Related Cirrhosis Successfully Treated With DAA”. Aliment Pharmacol Ther; Vol., 61 No., 3 PP., 538-549 2025.
D.A. Sheridan, I.T. Shawa, E.L. Thomas, et al. “Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis”. Sci Rep; Vol., 12 PP. 5562 2022.
B.M. Kamath, E.M. Alonso, J.E. Heubi, S.J. Karpen, S.S. Sundaram, B.L. Shneider, et al., “Fat soluble vitamin assessment and supplementation in cholestasis”. Clinics in liver disease. Vol., 26 No.,3 PP., 537-53 2022.
G. Peschel, J. Grimm, K. Gulow, M. Muller, C. Buechler, K. Weigand, “Chemerin Is a Valuable Biomarker in Patients with HCV Infection and Correlates with Liver Injury”. Diagnostics, Vol., 10 PP., 974 2020.
H.A. AbdEl-maksoud, M.G. Elharrif, O. Abd El-hamid, S.M. Alsaab, E.M. El-sorady “Monitoring of iron, lipid and liver profiles in Egyptian hepatitis C virus patients on sofosbuvir therapy”, Journal of Infection and Public Health,Vol. 15 No. 3 PP. 277-281 2022.
F. Wrensch, E. Crouchet, G. Ligat, M.B. Zeisel, Z.Y. Keck, S.K.H. Foung, et al., “Hepatitis C Virus (HCV)–Apolipoprotein Interactions and Immune Evasion and Their Impact on HCV Vaccine Design”. Front. Immunol, Vol., 9 PP., 1436 2018.
M. Sidorkiewicz, “Hepatitis C Virus Uses Host Lipids to Its Own Advantage”. Metabolites, Vol., 11 No., 5 PP., 273 2021.
D. G. Mashek, “Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD, Molecular Metabolism, Volume 50, 2021, 101115,
Y. Nahmias, M. Casali, L. Barbe, F. Berthiaume, M.L. Yarmush “Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes”. Hepatology. Vol., 43 No., 2 PP., 257-65 2006.
R. Zampino, A. Marrone, L. Restivo, B. Guerrera, A. Sellitto, L. Rinaldi, et al., “Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations”. World J Hepatol. Vol., 5 No., 10 PP., 528-40 2013.
J.W. Liou, H. Mani, J.H. Yen “Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds”. International Journal of Molecular Sciences. Vol., 23 No., 7 PP., 3897 2022.
Ch.H. Lin, J.J. Chen, P.L. Lee, H.D. Tong, Ch.T. Cheng, H.J. Kao et al., “Lipid profile changes after direct acting antiviral treatment in different genotypes of chronic hepatitis C virus-infected patients”. Advances in Digestive Medicine, Vol., 8 No., 3 PP., 139-145 2020.
Y. Chen, Y. Yang, S. Li, M. Lin, X. Xie, H. Shi, et al., “Changes and clinical significance of PIVKA-II in hepatitis E patients”. Frontiers in Public Health. Vol., 9 PP., 784718 2022.
A.O. Pascual, D.D. Casas, C.C. Yagüe, J.M. Arbones, V.M. Bernal “Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication”. Pathogens. Vol., 13 No., 4 PP., 278 2024.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al. “PIVKA‑II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 1 pp., 2 2023.
M.Y.W. Zaki, A.M. Fathi, S. Samir, N. Eldafashi, K.Y. William, M.H. Nazmy, et al. “Innate and adaptive immunopathogeneses in viral hepatitis; crucial determinants of hepatocellular carcinoma”. Cancers (Basel), Vol., 14 No., 5 PP., 1255 2022.
N.F.A. Rasheed, H.S. Jassim, A.S. Hassan “Assessment of Some Heavy Metals and Trace Elements in a Sample of Patients with Viral Hepatitis in Baghdad”. Journal of Techniques, Vol., 4 No., 3 PP., 8 2022.
I. H. Dhefer “Liver damage during infections with corona virus”. Journal of Techniques, Vol., 3 No., 2 PP., 79-85 2022.
M. Wang, L. Li, Y. Xu, J. Du, C. Ling “Roles of hepatic stellate cells in NAFLD: from the perspective of inflammation and fibrosis” Front. Pharmacol, Vol., 13 PP., 958428 2022.
World Health Organization. Hepatitis C, fact sheet 2024. hhttp://www.who.int/mediacentre/factsheets/fs164/en/. Accessed 3 April 2025.
K.G.R. Al-Azzawi, A. Al-Naqeeb, M.A.K. Zeidan “Impact of Chronic Liver Diseases on Specific Health-Related Quality of Life among a Sample in Babylon Government”. Journal of Techniques, Vol., 4 No., 33 PP., 86-90 2022.
L. Dong, X. Qiu, F. Gao, K. Wang, X. Xu “Protein induced by vitamin K absence or antagonist II: Experience to date and future directions”. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Vol., 1878 No., 6 PP., 189016 2023.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al., “PIVKA II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 2 2024.
W. Elgretli, T. Chen, N. Kronfli, and G. Sebastiani. “Hepatitis C virus-lipid interplay: pathogenesis and clinical impact”. Biomedicines, Vol., 11 No., 2 PP., 271 2023.
R. Villani, F. Di Cosimo, A.D. Romano, et al. “Serum lipid profile in HCV patients treated with direct-acting antivirals: a systematic review and meta-analysis”. Sci Rep, Vol., 11 No., 1 PP., 13944 2021.
M. Abdel-Gawad, M. Nour, F. El-Raey, H. Nagdy, Y. Almansoury, M. El-Kassas “Gender differences in prevalence of hepatitis C virus infection in Egypt: a systematic review and meta-analysis”. Sci Rep. Vol., 13 No., 1 PP., 2499 2023.
N.A. Marzuk, L.J. Tawfiq, N.Sh. Mohammed "Assessment of Some Biochemical Parameters in a Sample of Patients with Chronic Hepatitis C virus in Iraq" Al-Nisour Journal for Medical Sciences: Vol., 6 No., 2 PP., 19-22 2024.
T. A. Hameed, “Gene Expression of IL32, 33, TNF with Nitric Oxide and GSH Measurement in Hepatitis C Patients of Co-infection with Toxoplasmosis”. Doctorate. Theses, Middle Technical University College of Health & Medical Technology / Baghdad. 2024.
Z.G. Mahran, H. Khalifa, N.A. Makhlouf, et al. “Effect of gender difference on psychiatric outcomes for hepatitis C virus patients receiving direct-acting antivirals in Egyptian population: a cohort study”. Egypt J Neurol Psychiatry Neurosurg, Vol., 58 No., 1 PP., 155 2022.
M. F. Alsaffar “Elevation of Some Biochemical and Immunological Parameters in Hemodialysis Patients Suffering from Hepatitis C Virus Infection in Babylon Province”. Indian Journal of Forensic Medicine & Toxicology, Vol., 15 No., 3 2021.
P. Simoes, A. Asaad, J. Abed, E.S. Engelson, D.P. Kotler “ Effect of Gender on the Response to Hepatitis C Treatment in an Inner-City Population”. Womens Health Issues. Vol., 25 No., 3 PP., 289-93 2015.
K. Hayashida, I. Shoji, L. Deng, D.P. Jiang, Y.H. Ide, H. Hotta “17β-estradiol inhibits the production of infectious particles of hepatitis C virus”. Microbiol Immunol. Vol., 54 PP., 684-690 2010.
R.Y. Mekky, N. Hamdi, W. El-Akel, G. Esmat, A.I. Abdelaziz “Estrogen-related MxA transcriptional variation in hepatitis C virus-infected patients”. Transl Res. Vol., 159 PP., 190-196. 2012
H.F. Hetta, H.M. Hamed, M.A. Mekky, et al. “Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma”. Egypt Liver Journal, Vol., 14 PP., 78 2024.
M.A. Al-Azzawy “Molecular and Immunological Study of Acute and Chronic Hepatitis B and C in Kirkuk City”. Ph.D. dissertation, Dept. Microbiology, College of Medicine, University of Tikrit, Tikrit, Iraq, 2019.
S. Tian, Y. Chen, Y. Zhang, X. Xu “Clinical value of serum AFP and PIVKA-II for diagnosis,treatment and prognosis of hepatocellular carcinoma”. J Clin Lab Anal, Vol., 37 PP., e24823 2023.
J. Ji, L. Liu, F. Jiang, X. Wen, Y. Zhang, Sh. Li, et al., “The clinical application of PIVKA-II in hepatocellular carcinoma and chronic liver diseases: A multi-center study in China”. Journal of Clinical Laboratory Analysis, Vol., 35 No., 11 PP., e24013 2021.
G.P. Caviglia, P. Fariselli, R. D'Ambrosio, P. Colombatto, E. Degasperi, G. Ricco, et al. “Development and Validation of a PIVKA-II-Based Model for HCC Risk Stratification in Patients With HCV-Related Cirrhosis Successfully Treated With DAA”. Aliment Pharmacol Ther; Vol., 61 No., 3 PP., 538-549 2025.
D.A. Sheridan, I.T. Shawa, E.L. Thomas, et al. “Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis”. Sci Rep; Vol., 12 PP. 5562 2022.
B.M. Kamath, E.M. Alonso, J.E. Heubi, S.J. Karpen, S.S. Sundaram, B.L. Shneider, et al., “Fat soluble vitamin assessment and supplementation in cholestasis”. Clinics in liver disease. Vol., 26 No.,3 PP., 537-53 2022.
G. Peschel, J. Grimm, K. Gulow, M. Muller, C. Buechler, K. Weigand, “Chemerin Is a Valuable Biomarker in Patients with HCV Infection and Correlates with Liver Injury”. Diagnostics, Vol., 10 PP., 974 2020.
H.A. AbdEl-maksoud, M.G. Elharrif, O. Abd El-hamid, S.M. Alsaab, E.M. El-sorady “Monitoring of iron, lipid and liver profiles in Egyptian hepatitis C virus patients on sofosbuvir therapy”, Journal of Infection and Public Health,Vol. 15 No. 3 PP. 277-281 2022.
F. Wrensch, E. Crouchet, G. Ligat, M.B. Zeisel, Z.Y. Keck, S.K.H. Foung, et al., “Hepatitis C Virus (HCV)–Apolipoprotein Interactions and Immune Evasion and Their Impact on HCV Vaccine Design”. Front. Immunol, Vol., 9 PP., 1436 2018.
M. Sidorkiewicz, “Hepatitis C Virus Uses Host Lipids to Its Own Advantage”. Metabolites, Vol., 11 No., 5 PP., 273 2021.
D. G. Mashek, “Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD, Molecular Metabolism, Volume 50, 2021, 101115,
Y. Nahmias, M. Casali, L. Barbe, F. Berthiaume, M.L. Yarmush “Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes”. Hepatology. Vol., 43 No., 2 PP., 257-65 2006.
R. Zampino, A. Marrone, L. Restivo, B. Guerrera, A. Sellitto, L. Rinaldi, et al., “Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations”. World J Hepatol. Vol., 5 No., 10 PP., 528-40 2013.
J.W. Liou, H. Mani, J.H. Yen “Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds”. International Journal of Molecular Sciences. Vol., 23 No., 7 PP., 3897 2022.
Ch.H. Lin, J.J. Chen, P.L. Lee, H.D. Tong, Ch.T. Cheng, H.J. Kao et al., “Lipid profile changes after direct acting antiviral treatment in different genotypes of chronic hepatitis C virus-infected patients”. Advances in Digestive Medicine, Vol., 8 No., 3 PP., 139-145 2020.
Y. Chen, Y. Yang, S. Li, M. Lin, X. Xie, H. Shi, et al., “Changes and clinical significance of PIVKA-II in hepatitis E patients”. Frontiers in Public Health. Vol., 9 PP., 784718 2022.
A.O. Pascual, D.D. Casas, C.C. Yagüe, J.M. Arbones, V.M. Bernal “Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication”. Pathogens. Vol., 13 No., 4 PP., 278 2024.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al. “PIVKA‑II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 1 pp., 2 2023.
M.Y.W. Zaki, A.M. Fathi, S. Samir, N. Eldafashi, K.Y. William, M.H. Nazmy, et al. “Innate and adaptive immunopathogeneses in viral hepatitis; crucial determinants of hepatocellular carcinoma”. Cancers (Basel), Vol., 14 No., 5 PP., 1255 2022.
N.F.A. Rasheed, H.S. Jassim, A.S. Hassan “Assessment of Some Heavy Metals and Trace Elements in a Sample of Patients with Viral Hepatitis in Baghdad”. Journal of Techniques, Vol., 4 No., 3 PP., 8 2022.
I. H. Dhefer “Liver damage during infections with corona virus”. Journal of Techniques, Vol., 3 No., 2 PP., 79-85 2022.
M. Wang, L. Li, Y. Xu, J. Du, C. Ling “Roles of hepatic stellate cells in NAFLD: from the perspective of inflammation and fibrosis” Front. Pharmacol, Vol., 13 PP., 958428 2022.
World Health Organization. Hepatitis C, fact sheet 2024. hhttp://www.who.int/mediacentre/factsheets/fs164/en/. Accessed 3 April 2025.
K.G.R. Al-Azzawi, A. Al-Naqeeb, M.A.K. Zeidan “Impact of Chronic Liver Diseases on Specific Health-Related Quality of Life among a Sample in Babylon Government”. Journal of Techniques, Vol., 4 No., 33 PP., 86-90 2022.
L. Dong, X. Qiu, F. Gao, K. Wang, X. Xu “Protein induced by vitamin K absence or antagonist II: Experience to date and future directions”. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Vol., 1878 No., 6 PP., 189016 2023.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al., “PIVKA II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 2 2024.
W. Elgretli, T. Chen, N. Kronfli, and G. Sebastiani. “Hepatitis C virus-lipid interplay: pathogenesis and clinical impact”. Biomedicines, Vol., 11 No., 2 PP., 271 2023.
R. Villani, F. Di Cosimo, A.D. Romano, et al. “Serum lipid profile in HCV patients treated with direct-acting antivirals: a systematic review and meta-analysis”. Sci Rep, Vol., 11 No., 1 PP., 13944 2021.
M. Abdel-Gawad, M. Nour, F. El-Raey, H. Nagdy, Y. Almansoury, M. El-Kassas “Gender differences in prevalence of hepatitis C virus infection in Egypt: a systematic review and meta-analysis”. Sci Rep. Vol., 13 No., 1 PP., 2499 2023.
N.A. Marzuk, L.J. Tawfiq, N.Sh. Mohammed "Assessment of Some Biochemical Parameters in a Sample of Patients with Chronic Hepatitis C virus in Iraq" Al-Nisour Journal for Medical Sciences: Vol., 6 No., 2 PP., 19-22 2024.
T. A. Hameed, “Gene Expression of IL32, 33, TNF with Nitric Oxide and GSH Measurement in Hepatitis C Patients of Co-infection with Toxoplasmosis”. Doctorate. Theses, Middle Technical University College of Health & Medical Technology / Baghdad. 2024.
Z.G. Mahran, H. Khalifa, N.A. Makhlouf, et al. “Effect of gender difference on psychiatric outcomes for hepatitis C virus patients receiving direct-acting antivirals in Egyptian population: a cohort study”. Egypt J Neurol Psychiatry Neurosurg, Vol., 58 No., 1 PP., 155 2022.
M. F. Alsaffar “Elevation of Some Biochemical and Immunological Parameters in Hemodialysis Patients Suffering from Hepatitis C Virus Infection in Babylon Province”. Indian Journal of Forensic Medicine & Toxicology, Vol., 15 No., 3 2021.
P. Simoes, A. Asaad, J. Abed, E.S. Engelson, D.P. Kotler “ Effect of Gender on the Response to Hepatitis C Treatment in an Inner-City Population”. Womens Health Issues. Vol., 25 No., 3 PP., 289-93 2015.
K. Hayashida, I. Shoji, L. Deng, D.P. Jiang, Y.H. Ide, H. Hotta “17β-estradiol inhibits the production of infectious particles of hepatitis C virus”. Microbiol Immunol. Vol., 54 PP., 684-690 2010.
R.Y. Mekky, N. Hamdi, W. El-Akel, G. Esmat, A.I. Abdelaziz “Estrogen-related MxA transcriptional variation in hepatitis C virus-infected patients”. Transl Res. Vol., 159 PP., 190-196. 2012
H.F. Hetta, H.M. Hamed, M.A. Mekky, et al. “Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma”. Egypt Liver Journal, Vol., 14 PP., 78 2024.
M.A. Al-Azzawy “Molecular and Immunological Study of Acute and Chronic Hepatitis B and C in Kirkuk City”. Ph.D. dissertation, Dept. Microbiology, College of Medicine, University of Tikrit, Tikrit, Iraq, 2019.
S. Tian, Y. Chen, Y. Zhang, X. Xu “Clinical value of serum AFP and PIVKA-II for diagnosis,treatment and prognosis of hepatocellular carcinoma”. J Clin Lab Anal, Vol., 37 PP., e24823 2023.
J. Ji, L. Liu, F. Jiang, X. Wen, Y. Zhang, Sh. Li, et al., “The clinical application of PIVKA-II in hepatocellular carcinoma and chronic liver diseases: A multi-center study in China”. Journal of Clinical Laboratory Analysis, Vol., 35 No., 11 PP., e24013 2021.
G.P. Caviglia, P. Fariselli, R. D'Ambrosio, P. Colombatto, E. Degasperi, G. Ricco, et al. “Development and Validation of a PIVKA-II-Based Model for HCC Risk Stratification in Patients With HCV-Related Cirrhosis Successfully Treated With DAA”. Aliment Pharmacol Ther; Vol., 61 No., 3 PP., 538-549 2025.
D.A. Sheridan, I.T. Shawa, E.L. Thomas, et al. “Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis”. Sci Rep; Vol., 12 PP. 5562 2022.
B.M. Kamath, E.M. Alonso, J.E. Heubi, S.J. Karpen, S.S. Sundaram, B.L. Shneider, et al., “Fat soluble vitamin assessment and supplementation in cholestasis”. Clinics in liver disease. Vol., 26 No.,3 PP., 537-53 2022.
G. Peschel, J. Grimm, K. Gulow, M. Muller, C. Buechler, K. Weigand, “Chemerin Is a Valuable Biomarker in Patients with HCV Infection and Correlates with Liver Injury”. Diagnostics, Vol., 10 PP., 974 2020.
H.A. AbdEl-maksoud, M.G. Elharrif, O. Abd El-hamid, S.M. Alsaab, E.M. El-sorady “Monitoring of iron, lipid and liver profiles in Egyptian hepatitis C virus patients on sofosbuvir therapy”, Journal of Infection and Public Health,Vol. 15 No. 3 PP. 277-281 2022.
F. Wrensch, E. Crouchet, G. Ligat, M.B. Zeisel, Z.Y. Keck, S.K.H. Foung, et al., “Hepatitis C Virus (HCV)–Apolipoprotein Interactions and Immune Evasion and Their Impact on HCV Vaccine Design”. Front. Immunol, Vol., 9 PP., 1436 2018.
M. Sidorkiewicz, “Hepatitis C Virus Uses Host Lipids to Its Own Advantage”. Metabolites, Vol., 11 No., 5 PP., 273 2021.
D. G. Mashek, “Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD, Molecular Metabolism, Volume 50, 2021, 101115,
Y. Nahmias, M. Casali, L. Barbe, F. Berthiaume, M.L. Yarmush “Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes”. Hepatology. Vol., 43 No., 2 PP., 257-65 2006.
R. Zampino, A. Marrone, L. Restivo, B. Guerrera, A. Sellitto, L. Rinaldi, et al., “Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations”. World J Hepatol. Vol., 5 No., 10 PP., 528-40 2013.
J.W. Liou, H. Mani, J.H. Yen “Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds”. International Journal of Molecular Sciences. Vol., 23 No., 7 PP., 3897 2022.
Ch.H. Lin, J.J. Chen, P.L. Lee, H.D. Tong, Ch.T. Cheng, H.J. Kao et al., “Lipid profile changes after direct acting antiviral treatment in different genotypes of chronic hepatitis C virus-infected patients”. Advances in Digestive Medicine, Vol., 8 No., 3 PP., 139-145 2020.
Y. Chen, Y. Yang, S. Li, M. Lin, X. Xie, H. Shi, et al., “Changes and clinical significance of PIVKA-II in hepatitis E patients”. Frontiers in Public Health. Vol., 9 PP., 784718 2022.
A.O. Pascual, D.D. Casas, C.C. Yagüe, J.M. Arbones, V.M. Bernal “Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication”. Pathogens. Vol., 13 No., 4 PP., 278 2024.
T. Honda, T. Ichikawa, M. Yamashima, S. Yamamichi, M. Koike, Y. Nakano, et al. “PIVKA‑II is associated with liver function, bone metabolism, and muscle function in patients with liver disease”. Biomedical Reports, Vol., 20 No., 1 pp., 2 2023.
Downloads
Published
License
Copyright (c) 2026 University of Thi-Qar Journal of Science
This work is licensed under a Creative Commons Attribution 4.0 International License.
