Soluble fibrin as a biomarker for intrahepatic microthrombosis in acute-on-chronic liver failure

Value of soluble fibrin as a biomarker for intrahepatic microthrombosis and its sequel acute-on-chronic liver failure in chronic hepatitis C patients

Ehab F. Mostafa, Waleed A. Ismail, Amr Elhwary1, Ayman M. Marei 2.

1. Internal medicine department, Hepatology divison, Zagazig University.
2. Microbiology department, Zagazig University.

International Journal of Bioscience and Medicine

Background: There is a lack in finding the precipitating factor in acute –on chronic liver failure (ACLF)insult in large number of patients and either this factor is hepatic or extra hepatic origin. Aim of the work : Our study aiming to evaluate the potential usefulness of a new plasma soluble fibirin polymer (SF) assay for diagnosing the possibility of occurrence of intrahepatic microthrombosis as a cause of ACLF in patients with chronic hepatitis C virus. Patients & Methods: The study was carried out in Zagazig University Hospital, internal medicine department in collaboration with microbiology department from February 2015 tell November 2015. 50 patients having chronic hepatitis c virus was enrolled in this study with ACLF developing new onset ascitis in 15 patient encephalopathy in 12 patients, jaundice in12 and elevated INR in 11 patients all having regular follow-up in hepatology clinic in Zagazig university Hospital with stable clinical course in the previous three months. Control subject was classified as normal subject 20 and 30 patients with compensated chronic hepatitis C virus infection. All patients and control groups were subjected to full history, complete clinical examination and laboratory tests including CBC, INR, serum albumin, serum bilirubin, liver enzymes, ascitic fluid examination and culture, blood culture, alpha-fetoprotein, d D-dimer, thrombin generation and soluble fibrin polymer., abdominal ultrasound, Doppler ultrasound for portal vein. Results: Our results showed significant difference between patients group and both  control groups regarding SF and D-dimer, also there were significant differences in patients group and other groups regarding ALT, total bilirubin especially direct bilirubin. There were marked reduction in portal flow mean velocity in patients group and other groups and we recorded further reduction in the portal flow mean velocity in patients group after 2 weeks from the starting time. There is significant positive correlation between SF and D-dimer with ALT, bilirubin, INR, portal flow mean velocity and increasing amount of ascitis and degree of encephalopathy. Conclusion: Evaluation the level of soluble fibrin polymer is a useful biomarker to predict ACLF development. Further studies are needed to insure its value and the best modality of treatment in this condition.

Research Highlights
1- Soluble fibrin as a biomarker for intrahepatic microthrombosis
2- The possibility of intrahepatic microthrombosis in developing acute-on-chronic liver failure in chronic hepatitis C patients

Keywords: Soluble fibrin, intrahepatic microthrombosis, chronic hepatitis C patients, sequel acute-on-chronic liver failure

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How to cite this article:
Ehab F. Mostafa, Waleed A. Ismail, Amr Elhwary, Ayman M. Marei, Value of soluble fibrin as a biomarker for intrahepatic microthrombosis and its sequel acute-on-chronic liver failure in chronic hepatitis C patients. International Journal of Bioscience and Medicine, 2017; 1:3. DOI: 10.28933/ijbm-2017-09-2001


1- Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G, et al. Acute-on chronic liver failure. J Hepatol. 2012;57:1336–1348.
2- Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality. Liver Int. 2013;33:40–52.
3- Olson JC, Kamath PS. Acute-on-chronic liver failure: concept, natural history, and prognosis. Curr Opin Crit Care. 2011;17:165–169.
4- Bajaj JS. Defining acute-on-chronic liver failure: will East and West ever meet? Gastroenterology. 2013;144:1337–1339.
5- Giannini E, Savarino V. Thrombocytopenia in liver disease. Curr Opin Hematol 2008; 15: 473–80.
6- Gatt A, Riddell A, Calvaruso V, Tuddenham E, Makris M, Burroughs AK. Enhanced thrombin generation in patients with cirrhosis- induced coagulopathy. J Thromb Haemost 2010; 8: 1994–2000.
7- Poujol-Robert A, Rosmorduc O, Serfaty L, Coulet F, Poupon R,Robert A. Genetic and acquired thrombotic factors in chronic hepatitis C. Am J Gastroenterol 2004; 99: 527–31.
8- Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portalhypertension. Hepatology 1995; 21: 1238–47.
9- Tribodi A , Anstee Q, Sogaard K, Primigani M and Valla D. Hypercoagulability in cirrhosis: causes and consequences. Journal of Thrombosis and Haemostasis,2011, 9: 1713–1723
10- Stravitz RT, Lisman T, Luketic VA, Sterling RK, Puri P, Fuchs M, Ibrahim A, Lee WM, Sanyal AJ. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol 2012; 56: 129–36.
11- Ganey PE, Luyendyk JP, Newport SW, Eagle TM, Maddox JF, Mackman N, Roth RA. Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice. Hepatology 2007; 46: 1177–86.
12- Weerasinghe SV, Moons DS, Altshuler PJ, Shah YM, Omary MB. Fibrinogen-gamma proteolysis and solubility dynamics during apoptotic mouse liver injury: heparin prevents and treats liver damage. Hepatology 2011; 53: 1323–32.
13- Duet M, Benelhadj S, Kedra W, Vilain D, Ajzenberg C. A new quantitative D-dimer assay appropriate in emergency: reliability of the assay for pulmonary embolism exclusion diagnosis. Thromb Res1998; 91: 1–5
14-. Lippi G, Franchini M, Biasiutti C, Dellagiacoma G, Salvagno GL. Increased D-dimer value and occult cancer in the absence of detectable thrombosis. Haematologica2007; 92: 53–5
15- Hetland O, Knudsen A, Dickstein K, Nilsen DW Characteristics and prognostic impact of plasma fibrin monomer (soluble fibrin) in patients with coronary artery disease. Blood Coagul Fibrinolysis 2002; 13: 301–8
16- Ginsberg JS, Siragusa S, Douketis J, Johnston M, Moffat K. Evaluation of a soluble fibrin assay in patients with suspected pulmonary embolism. Thromb Haemost 1996; 75: 551–4
17- Mirshahi S, Soria C, Kouchakji B, Kierzek G, Borg JY. New Combinational Assay Using Soluble Fibrin and D-Dimer Determinations: A Promising Strategy for Identifying Patients with Suspected Venous Thromboembolism 2014; PLoS ONE 9(3): e92379. doi:10.1371/journal.pone.0092379
18- Edoardo G, Roberto T, and Vincenzo S. Liver enzyme alteration: a guide for clinicians 2005; CMAJ 172(3):367-79
19-Ali Nawaz Khan.
20- Anstee Q, Wright M, Goldin R, Thursz MR. Parenchymal extinction: coagulation and hepatic fibrogenesis. Clin Liver Dis 2009; 13: 117–26.
21- Wanless IR, Liu JJ, Butany J. Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac cirrhosis). Hepatology 1995;21:12327.
22- Papatheodoridis G, Papakonstantinou E, Andrioti E, Cholongitas E, , Kontopoulou I, and Hadziyannis S Thrombotic risk factors and extent of liver fibrosis in chronic viral hepatitis. Gut. 2003 Mar; 52(3): 404–409. PMCID: PMC1773539.