Role of Both Protein C and Antithrombin III as Predictors of Stage of Liver Disease in Chronic Viral Hepatitis B or C Infected Patients

Author(s): Amany M. Abo-Elenein, Maaly M. Mabrouk, Sabry Abou-Saif, Ola M. Saeed, Samy Khodeir, Mahmoud Elkadeem, Heba Elashry, Tamer Haydara, Mariam S. Zaghloul, Waseem M. Seleem, Samah A. Elshweikh, Sherief Abd-Elsalam*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 20 , Issue 1 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background & Aims: Chronic liver disease is characterized by complex hemostatic disorders because the liver is the site where most of the coagulation factors and their inhibitors are synthesized. The aim of this study was the evaluation of protein C and antithrombin III in different stages of chronic hepatitis B and C and to determine their possible role as markers of liver cell damage in different clinical stages.

Methods: The study included 60 subjects who were subdivided into 4 groups: (Group I): 15 patients diagnosed as chronic viral hepatitis B or C, (Group II): 15 patients with compensated liver cirrhosis, (Group III): 15 patients with decompensated liver cirrhosis, and (Group IV) (control group): 15 healthy individuals. History taking, clinical examination and abdominal ultrasonography were made for all subjects. Investigations were done in the form of liver function tests (ALT, AST, ALP, serum bilirubin, and serum albumin), PT, PTT, CBC. Plasma levels of Antithrombin III & protein C were estimated by automated Stago compact coagulation analyzer.

Results: In all patient groups, the mean value of Protein C showed significant decrease when compared to control group, mean value of antithrombin III showed a significant decrease in compensated and decompensated subjects when compared to chronic hepatitis and control groups. Antithrombin III and protein C showed a significant negative correlation with (ALT, AST, PT, PTT, INR). However, this correlation was positive with Albumin.

Conclusion: Antithrombin III and protein C are natural anticoagulants and can be considered as markers of different stages of chronic liver disease. This is supported further by the comparison between the levels of these parameters and clinical stages of liver disease. Protein C is more sensitive than ATIII as a marker of hepatocellular damage.

Keywords: Chronic liver disease, antithrombin III, protein C, hepatitis C, hepatitis B, anticoagulants.

[1]
McCormick, P.A.; Murphy, K.M. Splenomegaly, hypersplenism and coagulation abnormalities in liver disease. Best Pract. Res. Clin. Gastroenterol., 2000, 14(6), 1009-1031.
[http://dx.doi.org/10.1053/bega.2000.0144] [PMID: 11139352]
[2]
Abd-Elsalam, S.; Habba, E.; Elkhalawany, W.; Tawfeek, S.; Elbatea, H.; El-Kalla, F.; Soliman, H.; Soliman, S.; Yousef, M.; Kobtan, A.; El Nawasany, S.; Awny, S.; Amer, I.; Mansour, L.; Rizk, F. Correlation of platelets count with endoscopic findings in a cohort of Egyptian patients with liver cirrhosis. Medicine (Baltimore), 2016, 95(23)e3853
[http://dx.doi.org/10.1097/MD.0000000000003853] [PMID: 27281094]
[3]
Tripodi, A.; Mannucci, P.M. Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research. J. Hepatol., 2007, 46(4), 727-733.
[http://dx.doi.org/10.1016/j.jhep.2007.01.015] [PMID: 17316874]
[4]
Al Ghumlas, A.K.; Abdel Gader, A.G.; Al Faleh, F.Z. Haemostatic abnormalities in liver disease: could some haemostatic tests be useful as liver function tests? Blood Coagul. Fibrinolysis, 2005, 16(5), 329-335.
[http://dx.doi.org/10.1097/01.mbc.0000174080.54871.6b] [PMID: 15970716]
[5]
Găman, A.M.; Găman, G.D. Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature. Curr. Health Sci. J., 2014, 40(2), 141-143.
[PMID: 25729597]
[6]
Picard, V.; Nowak-Göttl, U.; Biron-Andreani, C.; Fouassier, M.; Frere, C.; Goualt-Heilman, M.; de Maistre, E.; Regina, S.; Rugeri, L.; Ternisien, C.; Trichet, C.; Vergnes, C.; Aiach, M.; Alhenc-Gelas, M. Molecular bases of antithrombin deficiency: twenty-two novel mutations in the antithrombin gene. Hum. Mutat., 2006, 27(6), 600.
[http://dx.doi.org/10.1002/humu.9425] [PMID: 16705712]
[7]
Zhang, L.; Li, Y.; Liu, J.; Zeng, Y.; Zeng, R.; Cheng, J. Activation of human coagulation system by liver-derived clotting factors of Banna minipig inbred line. Transplant. Proc., 2004, 36(8), 2490-2491.
[http://dx.doi.org/10.1016/j.transproceed.2004.07.064] [PMID: 15561292]
[8]
Abdo, A.A.; Sanai, F.M.; Azzam, N.; Al Sawat, K.; Al Dukhayil, M.; Al Ghumlas, A.; Hersi, A.; Gader, A.G. Natural anticoagulants can be useful predictors of severity in chronic liver disease. Blood Coagul. Fibrinolysis, 2010, 21(2), 122-127.
[http://dx.doi.org/10.1097/MBC.0b013e328335d03a] [PMID: 20019598]
[9]
Rahimkhani, M.; Einollahi, N.; Khavari Daneshvar, H.; Dashti, N. Survey of serum procalcitonin in cirrhotic patients. Acta Med. Iran., 2013, 51(3), 153-156.
[PMID: 23605598]
[10]
Saray, A.; Mesihovic, R.; Vanis, N.; Gornjakovic, S.; Prohic, D. Clinical significance of haemostatic tests in chronic liver disease. Med. Arh., 2012, 66(4), 231-235.
[http://dx.doi.org/10.5455/medarh.2012.66.231-235] [PMID: 22919876]
[11]
Tripodi, A.; Primignani, M.; Lemma, L.; Chantarangkul, V.; Mannucci, P.M. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis. J. Hepatol., 2013, 59(2), 265-270.
[http://dx.doi.org/10.1016/j.jhep.2013.03.036] [PMID: 23583273]
[12]
Bhalli, A.; Saeed, T.; Rubab, Z.; Aftab, I.; Hussain, S.; Bashir, N.; Mohsin, S. Protein in chronic liver disease. Biomedica, 2014, 30, 255-257.
[13]
Saray, A.; Mesihovic, R.; Vanis, N.; Amila, M.; Protein, C.; Protein, C. Deficiency in Chronic Hepatitis C: Correlation With Histological Extent of Liver Fibrosis. Clin. Appl. Thromb. Hemost., 2017, 23(1), 72-77.
[http://dx.doi.org/10.1177/1076029615587356] [PMID: 26008227]
[14]
Tang, Z.D.; Wang, X.F.; Hu, X.E. [Estimation of plasma protein C, protein S and antithrombin III in patients with chronic liver diseases and its clinical significance] Zhonghua Nei Ke Za Zhi, 1989, 28(12), 722-724, 767-768.
[PMID: 2534591]
[15]
Ahmed, O.A.; Kaisar, H.H.; Hawash, N.; Samir, H.; Shabana, S.S.T.; Hassan, A.; Fouad, M.; Rizk, F.; Abd-Elsalam, S. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in treatment of a cohort of Egyptian patients with hepatitis C virus infection. Infect. Disord. Drug Targets, 2017, 17(2), 95-100.
[http://dx.doi.org/10.2174/1871526517666170417143216] [PMID: 28413993]
[16]
Abd-Elsalam, S.; Sharaf-Eldin, M.; Soliman, S.; Elfert, A.; Badawi, R.; Ahmad, Y.K. Efficacy and safety of sofosbuvir plus ribavirin for treatment of cirrhotic patients with genotype 4 hepatitis C virus in real-life clinical practice. Arch. Virol., 2018, 163(1), 51-56.
[http://dx.doi.org/10.1007/s00705-017-3573-0] [PMID: 28983675]
[17]
Ahmed, O.A.; Kaisar, H.H.; Badawi, R.; Hawash, N.; Samir, H.; Shabana, S.S.; Fouad, M.H.A.; Rizk, F.H.; Khodeir, S.A.; Abd-Elsalam, S. Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection. Infect. Drug Resist., 2018, 11, 295-298.
[http://dx.doi.org/10.2147/IDR.S153060] [PMID: 29535545]
[18]
Ahmed, O.A.; Elsebaey, M.A.; Fouad, M.H.A.; Elashry, H.; Elshafie, A.I.; Elhadidy, A.A.; Esheba, N.E.; Elnaggar, M.H.; Soliman, S.; Abd-Elsalam, S. Outcomes and predictors of treatment response with sofosbuvir plus daclatasvir with or without ribavirin in Egyptian patients with genotype 4 hepatitis C virus infection. Infect. Drug Resist., 2018, 11, 441-445.
[http://dx.doi.org/10.2147/IDR.S160593] [PMID: 29628768]
[19]
Mansour, L.; El-Kalla, F.; El-Bassat, H.; Abd-Elsalam, S.; El-Bedewy, M.; Kobtan, A.; Badawi, R.; Elhendawy, M. Randomized controlled trial of scleroligation versus band ligation alone for eradication of gastroesophageal varices. Gastrointest. Endosc., 2017, 86(2), 307-315.
[http://dx.doi.org/10.1016/j.gie.2016.12.026] [PMID: 28082116]
[20]
Ahmed, O.A.; Safwat, E.; Khalifa, M.O.; Elshafie, A.I.; Fouad, M.H.A.; Salama, M.M.; Naguib, G.G.; Eltabbakh, M.M.; Sherief, A.F.; Abd-Elsalam, S. Sofosbuvir Plus Daclatasvir in Treatment of Chronic Hepatitis C Genotype 4 Infection in a Cohort of Egyptian Patients: An Experiment the Size of Egyptian Village. Int. J. Hepatol., 2018. 20189616234
[http://dx.doi.org/10.1155/2018/9616234] [PMID: 29755792]
[21]
Abdelmoemen, G.; Khodeir, S.A.; Abou-Saif, S.; Kobtan, A.; Abd-Elsalam, S. Prevalence of occult hepatitis C virus among hemodialysis patients in Tanta university hospitals: a single-center study. Environ. Sci. Pollut. Res. Int., 2018, 25(6), 5459-5464.
[http://dx.doi.org/10.1007/s11356-017-0897-y] [PMID: 29214477]
[22]
Ministry of Health, Egyp, El‐Zanaty and Associates, Egypt and ICF International (2015). Egypt Health Issues Survey,. 2015.
[23]
Rahimkhani, M.; Ghofrani, H. Helicobacter pylori and peptic ulcer in cirrhotic patients. Pak. J. Med. Sci., 2008, 24, 849-852.
[24]
Abo-Amer, Y.E.; Abd-Elsalam, S.; Eldosoky, H. ELShenawy, A.K.; Awny, S.; Elagawy, W.; Abgeegy, M.E.; Elsergany, H.F.; Elashry, H.; Negm, M.S. Declining prevalence of hepatitis C virus among university students in one of the main governorates in Egypt. Infect. Drug Resist., 2018, 11, 2435-2441.
[25]
Shehata, M.A.; Talaat, R.; Soliman, S.; Elmesseri, H.; Soliman, S.; Abd-Elsalam, S. Randomized controlled study of a novel triple nitazoxanide (NTZ)-containing therapeutic regimen versus the traditional regimen for eradication of Helicobacter pylori infection. Helicobacter, 2017, 22(5) e12395


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 1
Year: 2020
Published on: 28 May, 2019
Page: [112 - 117]
Pages: 6
DOI: 10.2174/1871530319666190529092555
Price: $65

Article Metrics

PDF: 27
HTML: 3