Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 18, 2015; 7(29): 2920-2926
Published online Dec 18, 2015. doi: 10.4254/wjh.v7.i29.2920
PAI-1 4G-4G and MTHFR 677TT in non-hepatitis C virus/hepatitis B virus-related liver cirrhosis
Linda Pasta, Francesca Pasta
Linda Pasta, Francesca Pasta, Department of Medicine, Clinica Candela, 90141 Palermo, Italy
Author contributions: Pasta L designed and performed the research, analyzed the data and wrote the paper; Pasta F performed the research, analyzed the data and wrote the paper.
Institutional review board statement: The local human research committee of AOOR of Palermo approved this retrospective study.
Informed consent statement: All participants gave their informed consent prior to their inclusion in the study, according to the Code of Ethics of the World Medical Association (Declaration of Helsinki, 1964, as revised in 2004).
Conflict-of-interest statement: All the authors declare that they have no competing interests.
Data sharing statement: The technical appendix, statistical code and dataset are available from the corresponding author at: lindpas@yahoo.it.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Linda Pasta, MD, Department of Medicine, Clinica Candela, Via Villareale 54, 90141 Palermo, Italy. lindpas@yahoo.it
Telephone: +39-091-587122 Fax: +39-091-589544
Received: May 29, 2015
Peer-review started: June 2, 2015
First decision: August 22, 2015
Revised: September 4, 2015
Accepted: November 23, 2015
Article in press: November 25, 2015
Published online: December 18, 2015
Processing time: 195 Days and 13 Hours
Abstract

AIM: To evaluate the different roles of thrombophilia in patients with and without viral etiology. The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and prothrombin 20210A, were studied as risk factors in 1079 patients with liver cirrhosis (LC), enrolled from January 2000 to January 2014.

METHODS: All Caucasian LC patients consecutively observed in a fourteen-year period were included; the presence of portal vein thrombosis (PVT) and Budd Chiari syndrome (BCS) was registered. The differences between the proportions of each THRGF with regard to the presence or absence of viral etiology and the frequencies of the THRGF genotypes with those predicted in a population by the Hardy-Weinberg equilibrium were registered.

RESULTS: Four hundred and seventeen/one thousand and seventy-six patients (38.6%) showed thrombophilia: 217 PAI-1 4G-4G, 176 MTHFR C677TT, 71 V Leiden factor and 41 prothrombin G20210 A, 84 with more than 1 THRGF; 350 presented with no viral liver cirrhosis (NVLC) and 729 with, called viral liver cirrhosis (VLC), of whom 56 patients were hepatitis C virus + hepatitis B virus. PAI-1 4G-4G, MTHFR C677TT, the presence of at least one TRHGF and the presence of > 1 THRGF, were statistically more frequent in patients with NVLC vs patients with VLC: All χ2 > 3.85 and P < 0.05. Patients with PVT and/or BCS with at least one TRHGF were 189/352 (53.7%). The Hardy-Weinberg of PAI-1 and MTHFR 677 genotypes deviated from that expected from a population in equilibrium in patients with NVLC (respectively χ2 = 39.3; P < 0.000 and χ2 = 27.94; P < 0.05), whereas the equilibrium was respected in VLC.

CONCLUSION: MTHFR 677TT was nearly twofold and PAI-1 4G-4G more than threefold more frequently found in NVLC vs patients with VLC; the Hardy-Weinberg equilibrium of these two polymorphisms confirms this data in NVLC. We suggest that PAI-1 4G-4G and MTHFR 677TT could be considered as factors of fibrosis and thrombosis mechanisms, increasing the inflammation response, and causing the hepatic fibrosis and augmented intrahepatic vascular resistance typical of LC. PAI-1 4G-4G and MTHFR 677TT screening of LC patients could be useful, mainly in those with NVLC, to identify patients in which new drug therapies based on the attenuation of the hepatic stellate cells activation or other mechanisms could be more easily evaluated.

Keywords: PAI-1 4G-4G; MTHFR 677TT; V Leiden 506Q; Prothrombin 20210A; Liver cirrhosis; Portal vein thrombosis; Budd Chiari syndrome; Fibrogenesis

Core tip: This study on thrombophilia in 1079 patients with liver cirrhosis showed that PAI-1 4G-4G and MTHFR C677TT were statistically more frequent in 350 patients with no viral liver cirrhosis vs 729 patients with viral liver cirrhosis. In the same patients, PAI-1 and MTHFR 677 genotypes deviated from that expected from a population in the Hardy-Weinberg equilibrium. PAI-1 4G-4G and MTHFR 677TT could be considered as factors increasing the inflammation response mechanisms, causing fibrogenesis and augmented intrahepatic vascular resistance, typical of liver cirrhosis. New drug therapies based on the attenuation of these mechanisms could be very easily evaluated in these patients.