The interleukin-10 receptor 1 (IL-10R1) G330R allele is associated with advanced fibrosis in chronic HCV-1 infection

ABSTRACT Elevated levels of interleukin 10 (IL-10) were previously described for chronically hepatitis C virus (HCV)-infected patients. We determined by a sequence-specific oligonucleotide probing technique the IL-10 promoter genotypes in 286 Argentinean HCV patients grouped according to disease outcome. The GG genotype (position −1082) is known to be associated with high IL-10 production, GA is considered an intermediate producer, and AA is associated with low IL-10 production. We found an increase in frequency of the GG genotype in female patients who do not eliminate the virus (RNA+). In these patients, the GG frequency was 0.19, versus 0.10 in controls (P = 0.03). This association became more significant in those RNA+ female patients with elevated hepatic transaminases (GG frequency of 0.25; P = 0.0013). Additionally, this genotype frequency was higher in noncirrhotic female patients than in controls (GG frequency for noncirrhotic female patients was 0.31; P = 0.009). In RNA− patients, the GA frequency was elevated compared with that in controls (GA frequency of 0.76 in RNA− patients versus 0.48 in controls; P = 0.01), that in all HCV patients (GA frequency of 0.43; P = 0.001), and that in RNA+ patients (GA frequency of 0.40; P = 0.0005). We conclude that a gender effect is observed with women carrying the GG high IL-10 producer genotype. The higher levels of IL-10 present in those individuals are associated with a higher risk of an inefficient clearance of the HCV and the development of a chronic HCV infection together with a lower risk of progression to cirrhosis in female patients.

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Incidence and Predictors of Advanced Liver Fibrosis by a Validated Serum Biomarker in Liver Transplant Recipients

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2017/4381864 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8

Author(s):

Mamatha Bhat ◽

Kathleen C. Rollet-Kurhajec ◽

Aparna Bhat ◽

Amanda Farag ◽

Marc Deschenes ◽

...

Keyword(s):

Liver Fibrosis ◽

Liver Transplant ◽

Hcv Infection ◽

Serum Biomarker ◽

Advanced Fibrosis ◽

Advanced Liver Fibrosis ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Liver Transplant Recipients

Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the liver transplant (LT) population. We employed a simple serum biomarker to elucidate incidence and predictors of advanced fibrosis after LT over a long follow-up period.Methods. We included 440 consecutive patients who underwent LT between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond 12 months after LT.Results. Over 2030.5 person-years (PY) of follow-up, 189 (43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95% confidence interval [CI], 8.1–10.7). Advanced fibrosis was predicted by chronic HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92–5.36,p< 0.001), hypoalbuminemia (aHR = 2.31, 95% CI 1.72–3.09;p< 0.001), and hyponatremia (aHR = 1.48, 95% CI 1.09–2.01;p= 0.01). LT recipients with more than 1 predictor had a higher incidence of advanced fibrosis, the highest being when all 3 predictors coexisted (log-rank:p< 0.001).Conclusions. Chronic HCV infection, hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis following LT. Patients with these risk factors should be serially monitored using noninvasive fibrosis biomarkers and prioritized for interventions.

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Intrahepatic interleukin 10 expression modulates fibrinogenesis during chronic HCV infection

PLoS ONE ◽

10.1371/journal.pone.0241199 ◽

2020 ◽

Vol 15 (10) ◽

pp. e0241199

Author(s):

Ednelza da Silva Graça Amoras ◽

Samara Tatielle Monteiro Gomes ◽

Maria Alice Freitas Queiroz ◽

Mauro Sergio Moura de Araújo ◽

Marialva Tereza Ferreira de Araújo ◽

...

Keyword(s):

Interleukin 10 ◽

Hcv Infection ◽

Chronic Hcv Infection ◽

Chronic Hcv

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Regulatory T Cells Suppress In Vitro Proliferation of Virus-Specific CD8+ T Cells during Persistent Hepatitis C Virus Infection

Journal of Virology ◽

10.1128/jvi.79.12.7852-7859.2005 ◽

2005 ◽

Vol 79 (12) ◽

pp. 7852-7859 ◽

Cited By ~ 207

Author(s):

Simon M. Rushbrook ◽

Scott M. Ward ◽

Esther Unitt ◽

Sarah L. Vowler ◽

Michaela Lucas ◽

...

Keyword(s):

Cell Proliferation ◽

T Cells ◽

T Cell ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Interleukin 10 ◽

Hcv Infection ◽

T Cell Proliferation ◽

Chronic Hcv

ABSTRACT The basis of chronic infection following exposure to hepatitis C virus (HCV) infection is unexplained. One factor may be the low frequency and immature phenotype of virus-specific CD8+ T cells. The role of CD4+CD25+ T regulatory (Treg) cells in priming and expanding virus-specific CD8+ T cells was investigated. Twenty HLA-A2-positive patients with persistent HCV infection and 46 healthy controls were studied. Virus-specific CD8+ T-cell proliferation and gamma interferon (IFN-γ) frequency were analyzed with/without depletion of Treg cells, using peptides derived from HCV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CD4+CD25+ Treg cells inhibited anti-CD3/CD28 CD8+ T-cell proliferation and perforin expression. Depletion of CD4+CD25+ Treg cells from chronic HCV patients in vitro increased HCV and EBV peptide-driven expansion (P = 0.0005 and P = 0.002, respectively) and also the number of HCV- and EBV-specific IFN-γ-expressing CD8+ T cells. Although stimulated CD8+ T cells expressed receptors for transforming growth factor beta and interleukin-10, the presence of antibody to transforming growth factor beta and interleukin-10 had no effect on the suppressive effect of CD4+CD25+ regulatory T cells on CD8+ T-cell proliferation. In conclusion, marked CD4+CD25+ regulatory T-cell activity is present in patients with chronic HCV infection, which may contribute to weak HCV-specific CD8+ T-cell responses and viral persistence.

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A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease

Clinical Science ◽

10.1042/cs20100246 ◽

2010 ◽

Vol 120 (7) ◽

pp. 287-296 ◽

Cited By ~ 32

Author(s):

Rika Iwata ◽

Katharina Baur ◽

Bruno Stieger ◽

Joachim C. Mertens ◽

Ann K. Daly ◽

...

Keyword(s):

Liver Disease ◽

Bile Acid ◽

Hepatitis C ◽

Fatty Liver ◽

Bile Acids ◽

Fatty Liver Disease ◽

Advanced Fibrosis ◽

Alcoholic Fatty Liver ◽

Chronic Hcv ◽

Alcoholic Fatty Liver Disease

Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member II) 1331T>C and NR1H4 (nuclear receptor) −1G>T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol >40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012–1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1–110) μmol/l compared with 3.5 (1–61) μmol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P=0.047) was observed in the χ2 test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F≥2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.

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Exploring the Diagnostic Potential of Serum Golgi Protein 73 for Hepatic Necroinflammation and Fibrosis in Chronic HCV Infection with Different Stages of Liver Injuries

Disease Markers ◽

10.1155/2019/3862024 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Xiangjun Qian ◽

Sujun Zheng ◽

Leijie Wang ◽

Mingjie Yao ◽

Guiwen Guan ◽

...

Keyword(s):

Disease Progression ◽

Hcv Infection ◽

Diagnostic Efficiency ◽

Advanced Fibrosis ◽

Promising Alternative ◽

Diagnostic Potential ◽

Liver Injuries ◽

Chronic Hcv Infection ◽

Golgi Protein ◽

Chronic Hcv

Background and Aim. Serum Golgi protein 73 (GP73) is a promising alternative biomarker of chronic liver diseases, but most data are from patients with HBV infection rather than HCV. Materials and Methods. Two independent cohorts of chronic hepatitis C (CHC) patients from the 5th Medical Centre of the Chinese PLA General Hospital (n=174) and Beijing Youan Hospital (n=120) with different histories of HCV infection were enrolled. The correlations between serum GP73 and other biochemical indices, as well as its correlations with different stages of liver disease progression, were investigated. The receiver operating characteristic (ROC) curve was employed to evaluate the diagnostic potential of serum GP73 for liver necroinflammation and fibrosis, and comparisons of the diagnostic efficiency with traditional indices of hepatic liver injuries were further investigated. Results. Levels of serum GP73 were found significantly elevated in patients with moderate to severe inflammatory grade (G≥2) and/or with advanced fibrotic stages (F≥3) in both cohorts (P<0.05, respectively), as compared to those with a normal or mild liver lesion. Further ROC analysis demonstrated that serum GP73 was comparable to serum ALT and AST in diagnosing the liver necroinflammation grade at G≥2, but its diagnostic values for advanced fibrosis (F≥3) and cirrhosis (F=4) were limited when compared to APRI and FIB-4, and FIB-4 exhibited the best performance. Notably, an obvious elevation of serum GP73 was observed after patients received PEG-IFN and ribavirin treatment. Conclusions. Serum GP73 is an important biomarker in evaluating and monitoring the disease progression including liver necroinflammation and fibrosis in patients with chronic HCV infection, but the value is limited for diagnosing advanced fibrosis and cirrhosis in comparison with APRI and FIB-4.

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A multivariable model with BMI predicts advanced fibrosis in patients with chronic HCV infection

Gastroenterology ◽

10.1016/s0016-5085(03)83806-4 ◽

2003 ◽

Vol 124 (4) ◽

pp. A753

Author(s):

Joel Gingerich ◽

Tom Imperiale ◽

Rong Qi ◽

George Eckert ◽

Paul Kwo

Keyword(s):

Hcv Infection ◽

Advanced Fibrosis ◽

Multivariable Model ◽

Chronic Hcv Infection ◽

Chronic Hcv

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Association of interleukin-10 polymorphisms with chronic hepatitis C virus infection in a case-control study and its effect on the response to combined pegylated interferon/ribavirin therapy

Epidemiology and Infection ◽

10.1017/s0950268814000466 ◽

2014 ◽

Vol 143 (1) ◽

pp. 71-80 ◽

Cited By ~ 4

Author(s):

A. J. KHAN ◽

V. A. SARASWAT ◽

G. CHOUDHURI ◽

D. PARMAR ◽

T. S. NEGI ◽

...

Keyword(s):

Case Control Study ◽

Pegylated Interferon ◽

Interleukin 10 ◽

Case Control ◽

Genotype 3 ◽

Chronic Hepatitis C Virus ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Control Study ◽

Increase In Risk

SUMMARYWe conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 –1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 –1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 –592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 –1082A/G and CC genotype of IL-10 –592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.

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Effect of Direct-Acting Antiviral Therapy on Thrombocytopenic Patients with Hepatitis C Virus-Related Chronic Liver Disease

Gastroenterology Research and Practice ◽

10.1155/2021/8811203 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Mahmoud Saif-Al-Islam ◽

Usama M. Abdelaal ◽

Mustafa Adel Younis ◽

Hisham A. Alghany Algahlan ◽

Safaa Khalaf

Keyword(s):

Platelet Count ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatic Fibrosis ◽

White Blood Cells ◽

Advanced Fibrosis ◽

Direct Acting Antiviral ◽

Chronic Hcv ◽

Direct Acting ◽

A Prospective Study

Background and Aims. Thrombocytopenia is a common complication in patients with chronic hepatitis C virus (HCV) that increases the risk of bleeding. We aimed to analyze the hematologic effects of the new direct-acting antiviral (DAA) therapy, particularly on the platelet count in chronic HCV-infected patients with thrombocytopenia. Patients and Methods. One hundred thrombocytopenic patients chronically infected with HCV were included in a prospective study. All patients were eligible for receiving anti-HCV treatment with sofosbuvir-based regimens for 12 weeks, according to the protocol of the National Program for treatment of HCV in Egypt sponsored by the Ministry of Health. Results. At the end of treatment (EOT), there was a highly significant increase in platelet count ( p < 0.001 ), a significant increase in white blood cells (WBCs) count ( p ≤ 0.032 ), and a highly significant decrease in hemoglobin level ( p < 0.001 ) as compared to pretreatment levels. Patients with mild to moderate hepatic fibrosis had significantly higher median and interquartile range (IQR) platelet count at baseline and EOT than those with advanced fibrosis and cirrhosis ( p ≤ 0.023 and p < 0.001 , respectively). There was more elevation in platelet count at EOT in patients with mild to moderate fibrosis than those with advanced fibrosis and cirrhosis. Out of the hundred patients, 73% showed improvement of platelet count, while 27% showed no improvement or even decrease in the platelet count. Conclusion. Sofosbuvir-based DAA therapy is a highly effective and safe treatment regimen that results in the improvement of platelet count in thrombocytopenic patients, particularly in mild to moderate stages of hepatic fibrosis.

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