SNPs of the IFNL favour spontaneous clearance of HCV infection in children

Mangone, Giusi; Serranti, Daniele; Bartolini, Elisa; Vigna, Veronica; Mastrangelo, G; Ricci, Silvia; Trapani, Sandra; Azzari, Chiara; Resti, Massimo; Indolfi, Giuseppe

doi:10.1038/s41390-021-01557-9

Cited by 3 publications

(4 citation statements)

References 32 publications

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“…The information on timing of clearance was not available for 10 children who were adopted or immigrated from other countries and were already HCV RNA negative (but anti‐HCV positive) at the time of first evaluation (median age: 8.5 years). The present results confirm previous findings of a spontaneous clearance rate after vertical transmission of 25%–40% in the first 4 years of life (4,5,13,18–20). Previous studies from our group demonstrated that raised aminotransferases levels in the first year of life, HCV genotype 3 infection, and some single nucleotide polymorphisms of IFNL3 and IFNL4 were associated with spontaneous clearance (19–21).…”

Section: Discussionsupporting

confidence: 92%

“…The present results confirm previous findings of a spontaneous clearance rate after vertical transmission of 25%–40% in the first 4 years of life (4,5,13,18–20). Previous studies from our group demonstrated that raised aminotransferases levels in the first year of life, HCV genotype 3 infection, and some single nucleotide polymorphisms of IFNL3 and IFNL4 were associated with spontaneous clearance (19–21). Describing and identifying risk factors for spontaneous clearance of HCV was beyond the scope of the present study aimed at collecting clinical information on the natural history of the infection.…”

Section: Discussionsupporting

confidence: 92%

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Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study

Stinco

Bartolini

Veronese

et al. 2022

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Objectives: To prospectively describe the epidemiology and long-term outcome of childhood-acquired hepatitis C virus (HCV) infection in a large cohort of children followed at a single center. Methods: All children with chronic HCV infection followed at the Liver Unit of our tertiary Hospital in Florence (Italy) from January 1, 1988, to September 30, 2021, were included in the analysis. Results: The final sample consisted of 163 children (median age at enrollment 4 years, interquartile range (IQR): 10; median age at last follow-up 14 years, IQR: 7). The median duration of follow-up was 86 months (IQR: 112). One hundred twenty-five children were vertically infected and 26 acquired the infection horizontally. Twenty-six of the 125 children who were vertically infected (20.8%) underwent spontaneous clearance of HCV RNA at a median age of 4 years (IQR: 2), whereas all the others remained persistently viremic. One patient was diagnosed with cirrhosis; 2 presented clinically detectable extrahepatic manifestations (chronic urticaria). Thirty-two children (19.6%) received antiviral therapy: 8 out of 32 (25%) were treated with pegylated-interferon alfa-2b [sustained virological response (SVR) 24 weeks after the end of treatment in 7/8]; 24 out of 32 (75%) were treated with direct-acting antivirals (SVR 12 weeks after the end of treatment in 23/24). Conclusions: The present study describes the largest cohort of children with chronic HCV infection prospectively evaluated with a long follow-up at a single center. HCV infection in children is often a chronic infection that can be cured with modern antiviral therapy. Early treatment could prevent the development of advanced liver disease.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study

Stinco

Bartolini

Veronese

et al. 2022

Journal of Pediatric Gastroenterology &Amp; Nutrition

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“…Following perinatal transmission, retrospective cohort data suggested spontaneous viral clearance (SVC) in 20%–40% of children by 4 years of age, associated with genetic polymorphisms in interferon-λ genes. 13 However, recent prospective data suggests higher rates of both perinatal transmission and SVC, the latter nearer to 66% (95% CI: 50.1–81.6), occurring at a median age of 12 months. 14 DAAs are available from 3 years, and while earlier therapy would result in significant overtreatment, it would have advantages in regions with high rates of loss to follow-up postpartum and potentially modifying neurocognitive deficits related to chronic HCV infection.…”

Section: Natural Historymentioning

confidence: 98%

Management of Hepatitis C in Children and Adolescents: An Update

Rubino,

Indolfi,

Foster

2024

Pediatric Infectious Disease Journal

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“…Additionally, while production of type I and II interferon is reduced during HCV infection and in advanced hepatic disease, IFN-λ receptor production is unaffected [24][25][26]. SNPs in the INFL3-INFL4 region, rs12979860, rs4803217 and rs368234815 were determined as a powerful foreteller of HCV clearance [27][28][29]. Several reports showed the genetic and functional association of these variants with liver fibrosis in different ethnicities [30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in INFL3-INFL4 region are associated with fibrosis and cirrhosis in Egyptian patients with chronic hepatitis C

Thabit,

Bkeet,

Abdelhalem

et al. 2023

Journal of advanced Biomedical and Pharmaceutical Sciences

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Genetic variables have a notable and polygenic impact on the incidence and development of hepatic fibrosis and cirrhosis in individuals with chronic hepatitis C (CHC). Genetic polymorphisms in interferon-λ3-interferon-λ4 (INFL3-INFL4) region, rs12979860 and its highly linked disequilibrium polymorphisms (rs368234815 and rs4803217) are linked to liver inflammation and fibrosis progression in CHC individuals from different ethnic groups. For Egyptian patients, no data available about the degree of linkage disequilibrium between these variants and their effect on liver fibrosis. In this study, 99 healthy controls and 176 CHC patients were genotyped for 3 variants in (INFL3-INFL4) region rs12979860, rs4803217, and rs368234815. We found that these variants are highly linked disequilibrium in Egyptian CHC cohort. Moreover, we found that the major alleles of these 3 polymorphisms (rs12979860, rs4803217, and rs368234815) significantly increase the risk of liver fibrosis (P = 0.015, 0.026, and 0.007 respectively). Additionally, these variants were linked to stage of hepatic fibrosis. This report shows that the 3 linked disequilibrium variants in INFL3-INFL4 region may be valuable foretellers of liver fibrosis and cirrhosis in CHC Egyptian patients.

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SNPs of the IFNL favour spontaneous clearance of HCV infection in children

Cited by 3 publications

References 32 publications

Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study

Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study

Management of Hepatitis C in Children and Adolescents: An Update

Single nucleotide polymorphisms in INFL3-INFL4 region are associated with fibrosis and cirrhosis in Egyptian patients with chronic hepatitis C

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