Interferon lambda and hepatitis C virus core protein polymorphisms associated with liver cancer

Moreira, João; Malta, Fernanda de Mello; Diniz, Márcio A.; Kikuchi, Luciana; Chagas, Aline Lopes; Lima, Livia de Souza Botelho; Gomes‐Gouvêa, Michele Soares; Castro, Vanessa Fusco Duarte de; Santana, Rúbia Anita Ferraz; Sumita, Nairo Massakazu; Vezozzo, Denise Cerqueira Paranaguá; Carrilho, Flair José; Pinho, João Renato Rebello

doi:10.1016/j.virol.2016.03.008

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…Two studies were found to be eligible for inclusion in the process of hand search. Thus, 24 studies evaluating IL28B rs12979860 and rs8099917 were ultimately included in this meta-analysis, in which 18 studies evaluated the IL28B rs12979860 genotype CC vs CT/TT, [1,2,7,8,17–19,23,25–33] and 15 studies evaluated the IL28B rs8099917 genotype TT vs TG/GG [1,7,9,17,19,23,26,30,32,34–39] (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection

et al. 2019

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Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B) gene has proven to be associated with the clinical outcome of patients with chronic hepatitis virus B or C (HBV or HCV) infections. However, whether IL28B SNPs have an influence on the risk of hepatocellular carcinoma (HCC) among patients with HBV or HCV infection remains controversial. Therefore, this study aims to determine the association between IL28B polymorphisms and the risk of HCC in individuals with HBV or HCV infection.PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were used to identify studies meeting the selection requirements using the terms “interleukin 28B”, “IFN-lambda-3”, “IFNL3”, “single nucleotide polymorphisms”, “SNPs”, “hepatocellular carcinoma”, “HCC”, “liver cancer”.A total of 24 eligible original studies (1 cohort study and 23 case-control studies) involved 20238 individuals (HCC group = 8725 vs control group = 11,513) were included. Both IL28B rs12979860 CC and rs8099917 TT genotypes were significantly associated with a decreased risk of HCC among patients with HBV or HCV infection (OR = 0.71, 95% CI = 0.57–0.88; OR = 0.82, 95% CI = 0.72–0.94, respectively). Egger test and Begg test revealed no‘ publication bias (P > .05). Sensitivity analyses suggested the robustness of the results in this meta-analysis.Both IL28B rs12979860 CC and rs8099917 TT genotypes are protective factors for the development of HCC among patients with HBV or HCV infection. Future prospective studies examining the impact of IL28B polymorphisms on the risk of HCC and investigating the underlying mechanism for the protective role of IL28B polymorphisms in HCC development are warranted.

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Section: Resultsmentioning

confidence: 99%

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection

et al. 2019

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“…[1–3] In HCC endemic areas (e.g., Taiwan), several risk factors have been identified, such as chronic infections of hepatitis C virus (HCV) [4–6] and/or hepatitis B virus (HBV), [7–9] as well as long-term exposure of fine particle pollution (particulate matter ≤ 2.5 μm [PM2.5]). [10] At initial presentation, most HCC patients were diagnosed with locoregionally advanced disease, which prevents from curative managements, [11] such as surgical resection, percutaneous ethanol injection, and radiofrequency ablation (RFA), [12] resulting in persistent high death rates.…”

Section: Introductionmentioning

confidence: 99%

Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma

et al. 2016

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Background:Clinically, elderly patients with unresectable bulky hepatocellular carcinoma (HCC) are difficult to manage, especially in those with co-infections of hepatitis B and C virus. Herein, we reported such a case treated with radiotherapy (RT) by using combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy (SIEB-VMAT). After RT, significant symptoms alleviation and durable tumor control were observed.Case Summary:At presentation, an 85-year-old male patient complained abdominal distention/pain, poor appetite, and swelling over bilateral lower limbs for 1 month. On physical examination, a jaundice pattern was noted. Laboratory studies showed impaired liver and renal function. Abdominal computed tomography (CT) revealed a 12.5-cm bulky tumor over the caudate lobe of the liver. Biopsy was done, and hepatocellular carcinoma (HCC) was reported histopathologically. As a result, AJCC stage IIIA (cT3aN0M0) and BCLC stage C were classified. Surgery, radiofrequency ablation (RFA), trans-catheter arterial chemoembolization (TACE), and sorafenib were not recommended because of his old age, central bulky tumor, and a bleeding tendency. Thus, RT with SIEB-VMAT technique was given alternatively. RT was delivered in 26 fractions, with dose gradience as follows: 39 Gy on the outer Plan Target Volume (PTV), 52 Gy in the middle PTV, and 57.2 Gy in the inner PTV. Unexpectedly, cyproheptadine (a newly recognized potential anti-HCC agent) was retrospectively found to be prescribed for alleviating skin itching and allergic rhinitis since the last 2 weeks of the RT course (2 mg by mouth Q12h for 24 months).After RT, significant symptoms alleviation and tumor volume reduction were observed for 32 months till multiple bone metastases. Before and after RT, a large tumor volume reduction rate of 88.7% was observed (from 608.4 c.c. to 68.7 c.c.). No severe treatment toxicity was noted during and after RT. The patient died due to aspiration pneumonia with septic shock at 4 months after bone metastases identified.Conclusions:SIEB-VMAT physically demonstrated double benefits of intratumor dose escalation and extra-tumor dose attenuation. Significant tumor regression and symptoms alleviation were observed in this elderly patient with unresectable bulky HCC. Further prospective randomized trials are encouraged to demarcate effective size of SIEB-VMAT with or without cyproheptadine.

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“…In this study, we also evaluated SNPs in the IFNL3/4 region among Brazilians, an admixed population of three paternal lineages consisting of Native-American, European and African ancestries. Other studies with CHC patients treated with Peg-IFN-α/Ribavirin from different regions in Brazil focused on the SNPs rs12979860 and rs8099917, evidencing that CC and TT genotypes, respectively, presented favorable treatment outcomes ( Ge et al., 2009 ; Thomas et al., 2009 ; Cavalcante et al., 2012 ; Ramos et al., 2012 ; Moreira et al., 2016 ; Rizzo et al., 2016 ). Here, we confirmed the association of several SNPs with the responsiveness for treatment, highlighting the rs12979860 as the strongest predictor in obtaining SVR in patients treated with Peg-IFNα.…”

Section: Discussionmentioning

confidence: 99%

Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha

Silva

Alvarado-Arnez

Azamor

et al. 2021

Front. Cell. Infect. Microbiol.

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Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors’ genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).

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Interferon lambda and hepatitis C virus core protein polymorphisms associated with liver cancer

Abstract: the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development.

Cited by 11 publications

References 36 publications

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection

Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma

Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha

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