Role of signal transducer and activator of transcription 3 in liver fibrosis progression in chronic hepatitis C-infected patients

Abstract Human genetic variants play major roles in predicting and prognosis of several diseases. The effect of rs58542926 variant in transmembrane 6 superfamily member 2 (TM6SF2) gene on liver fibrosis among patients with chronic hepatitis C (CHC) is still debatable. The aim of this study is to investigate the possible effects of this variant in CHC patients. The study comprised 351 subjects: 250 CHC patients with different fibrosis stages (F0-F4) and 101 healthy volunteers. TM6SF2 (rs58542926) genotype was determined for all subjects. Blood samples were collected for complete blood count and biochemical analysis and cohort subjects were genotyped for the variant TM6SF2 rs58542926. Fibrosis staging was performed using Fibrotest and Fibroscan standard tests. The presence of the minor allele was significantly associated with severe liver fibrosis, as well as thrombocytopenia as an extrahepatic alteration. In addition, there was a significant association between the minor allele and lower thrombopoietin levels. The association of TM6SF2 genotype with thrombocytopenia was explored by measuring plasma thrombopoietin (TPO) levels for CHC patients. The results showed an association with extrahepatic alteration (thrombocytopenia) through its effect on plasma TPO level, and consequently on platelets production, which raises questions about the role of this variant in HCV treatment outcome. In conclusion, the occurrence of the minor allele of the variant rs58542926 can be linked to severe fibrosis stages as well as thrombocytopenia, enabling this variant to be used as a diagnostic pharmacogenetic marker for predicting the risk of fibrosis onset in CHC patients.

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Risk factors for liver fibrosis progression in patients with chronic hepatitis C

Annals of Hepatology ◽

10.1016/s1665-2681(19)32152-0 ◽

2003 ◽

Vol 2 (1) ◽

pp. 5-11 ◽

Cited By ~ 43

Author(s):

Mercedes de Torres ◽

Thierry Poynard

Keyword(s):

Risk Factors ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Liver Fibrosis ◽

Chronic Hepatitis C ◽

Fibrosis Progression

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The Role of Signal Transducer and Activator of Transcription 5 and Transforming Growth Factor-β1 in Hepatic Fibrosis Induced by Chronic Hepatitis C Virus Infection in Egyptian Patients

Medical Principles and Practice ◽

10.1159/000487308 ◽

2018 ◽

Vol 27 (2) ◽

pp. 115-121

Author(s):

Mona A. Abu El Makarem ◽

Ghada M. El-Sagheer ◽

Moustafa A. Abu El-Ella

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Liver Fibrosis ◽

Hepatic Stellate Cells ◽

Stellate Cells ◽

Serum Levels ◽

Signal Transducer ◽

Egyptian Patients ◽

Tgf Β1

Objective: To investigate the possible role of signal transducer and activator of transcription 5 (STAT5) in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSC). Subjects and Methods: Sixty-five patients (46 males and 19 females) were divided into 4 groups based on the severity of fibrosis as detected by Fibroscan as follows: F1, n = 15; F2, n = 21; F3, n = 13; and F4, n = 16. Twenty age- and gender-matched healthy persons volunteered as controls. The serum levels of STAT5, TGF-β1, α-smooth muscle actin (α-SMA), fasting blood sugar, and fasting insulin, as well as homeostasis model assessment of insulin resistance (HOMA-IR), were determined and compared for all groups. The usefulness of the studied serum biomarkers for predicting liver fibrosis was evaluated using a receiver operating characteristic curve. Results: Serum levels of STAT5 were significantly lower in patients compared to controls (9.69 ± 5.62 vs. 14.73 ± 6.52, p ≤ 0.001); on the contrary, TGF-β1, α-SMA, and HOMA-IR were significantly higher in patients compared to controls (mean: 1,796.04 vs. 1,636.94; 14.94 vs. 8.1; and 7.91 vs. 4.18; p ≤ 0.01 and 0.001, respectively). TGF-β1 and α-SMA showed a progressive increase with advancing severity of hepatic fibrosis (mean TGF-β1: 2,058.4 in F1-F2 and 1,583.8 in F3-F4, p ≤ 0.04; mean α-SMA: 13.59 in F1-F2 and 16.62 in F3-F4, p ≤ 0.05). STAT5 had a significant negative correlation with TGF-β1 (p ≤ 0.001), while no correlation was detected with α-SMA (p ≤ 0.8). Conclusions: STAT5 may play a significant role in hepatic fibrogenesis through the induction of TGF-β1 but not through the activation of hepatic stellate cells.

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MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study

Frontiers in Medicine ◽

10.3389/fmed.2020.582666 ◽

2020 ◽

Vol 7 ◽

Author(s):

Daniel Pineda-Tenor ◽

Ana Zaida Gómez-Moreno ◽

Juan José Sánchez-Ruano ◽

Tomas Artaza-Varasa ◽

Ana Virseda-Berdices ◽

...

Keyword(s):

Chronic Hepatitis ◽

Retrospective Study ◽

Hepatitis C ◽

Liver Fibrosis ◽

Chronic Hepatitis C ◽

Fibrosis Progression

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Factors accelerating liver fibrosis progression in renal transplant patients receiving ribavirin monotherapy for chronic hepatitis C

Journal of Medical Virology ◽

10.1002/jmv.20323 ◽

2005 ◽

Vol 76 (1) ◽

pp. 61-68 ◽

Cited By ~ 25

Author(s):

Nassim Kamar ◽

Anne Boulestin ◽

Janick Selves ◽

Laure Esposito ◽

Karine Sandres-Saune ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Renal Transplant ◽

Liver Fibrosis ◽

Chronic Hepatitis C ◽

Fibrosis Progression ◽

Transplant Patients ◽

Renal Transplant Patients

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397 ROLE OF ACOUSTIC RADIATION FORCE IMPULSE (ARFI) ELASTOGRAPHY FOR THE STAGING OF LIVER FIBROSIS IN CHRONIC HEPATITIS C

Journal of Hepatology ◽

10.1016/s0168-8278(10)60399-6 ◽

2010 ◽

Vol 52 ◽

pp. S163

Author(s):

C.G. Fierbinteanu-Braticevici ◽

L. Tribus ◽

A. Petrisor ◽

R. Usvat ◽

C. Busegeanu ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Liver Fibrosis ◽

Chronic Hepatitis C ◽

Acoustic Radiation ◽

Radiation Force ◽

Acoustic Radiation Force ◽

Acoustic Radiation Force Impulse ◽

Arfi Elastography

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Significance of serum WFA+-M2BP level as a marker of liver fibrosis in patients with chronic hepatitis C

Infekcionnye bolezni ◽

10.20953/1729-9225-2020-4-80-84 ◽

2020 ◽

Vol 18 (4) ◽

pp. 80-84

Author(s):

N.N. Volkova ◽

◽

N.S. Ibadullaeva ◽

M.U. Asilova ◽

E.I. Musabaev ◽

...

Keyword(s):

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Liver Fibrosis ◽

Antiviral Therapy ◽

Chronic Hepatitis C ◽

Treatment Initiation ◽

Serum Levels ◽

Serum Marker

Objective. To evaluate the role of dynamics of WFA+-M2BP, a serum marker of liver fibrosis, in patients with chronic hepatitis C (CHC). Patients and methods. We examined 56 CHC patients who received antiviral therapy. The severity of liver fibrosis was assessed using indirect elastometry. There were 8 patients with F0 fibrosis, 17 patients with F1 fibrosis, 6 patients with F2 fibrosis, 12 patients with F3 fibrosis, and 13 patients with F4 fibrosis. The level of WFA+-M2BP was measured prior to treatment initiation, then 1 month after treatment initiation, and 3 months after treatment completion. Results. We found that both CHC patients and patients with HCV-induced liver cirrhosis demonstrated a decrease in the serum level of WFA+-M2BP in response to antiviral therapy. Mean levels of WFA+-M2BP in individuals with F3 and F4 fibrosis were significantly higher than those in patients with F0 fibrosis (p < 0.01). Conclusion. Higher grades of liver cirrhosis were associated with higher serum levels of WFA+-M2BP, while antiviral therapy led to a decrease in the concentration of this biomarker. The assessment of WFA+-M2BP dynamics will help to detect early stages of liver fibrosis and also to monitor it in patients receiving antiviral therapy. Key words: chronic hepatitis C, liver cirrhosis caused by HCV, biomarker, WFA+-M2BP, liver fibrosis, antiviral therapy

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Role of polymorphic markers for the genes of hemostasis and platelet receptors in liver fibrosis progression in patients with chronic hepatitis C

Terapevticheskii arkhiv ◽

10.17116/terarkh201688893-98 ◽

2016 ◽

Vol 88 (8) ◽

pp. 93-98

Author(s):

E E Starostina ◽

L M Samokhodskaya ◽

T P Rozina ◽

T N Krasnova ◽

E B Yarovaya ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Liver Fibrosis ◽

Chronic Hepatitis C ◽

Melting Curve ◽

Integral Model ◽

Melting Curve Analysis ◽

Progression Rate ◽

Platelet Receptors ◽

Fibrosis Progression

Aim. To estimate the clinical and prognostic value of the carriage of different allele variants of the gene polymorphisms of the coagulation system and platelet receptors in the progression of liver fibrosis (LF) in patient with chronic hepatitis C (CHC). Subjects and methods. The investigation enrolled 177 patients with CHC and liver cirrhosis at its outcome who were divided into 2 groups according to the rate of LF progression: 1) 89 patients with rapid (rapid fibrosis) and 2) 88 patients with slow (slow fibrosis) progression. The polymorphism of the study genes was studied using a real-time polymerase chain reaction and a melting curve analysis. Results. In CHC patients, the FV 1691G/A genotype was more often in the rapid progressors than that in the slow progressors (10.11% vs 1.14%; p=0.011). The A allele of the 1691 G/A FV gene was more common in the rapid fibrosis group than that in the slow fibrosis group (1.7% vs 5.56%, odd ratio 9.787; p=0.139). In our investigation, the polymorphic marker GA in the FII 20210 G/A gene, as well as the 4G allele (5G4G + 4G4G genotypes) and the 4G allele of PAI-I -675 5G/4G were more often seen in the rapid fibrosis group than that in the slow fibrosis group; the detection rate was only at the trend level (p=0.118, p=0.112, and p=0.117 respectively). There were no significant differences between the groups in the spread of variant genotypes and alleles of other study genes. Integral model construction by coding «profibrogenic» genotypes (FV 1691 G/A, FII 20210 G/A, PAI-I -675 5G/4G) showed that the fibrosis progression rate expressed as fibrosis units annually also increased with higher total scores (p=0.039), indicating the combined effect of these genes. Conclusion. The carriage of mutant genotypes of FV 1691 G/A, FII 20210 G/A, and PAI-I -675 5G/4G genes is a prognostic factor for rapid CHC progression.

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