AIM: To investigate the association between interleukin-28B (IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus (HCV) genotype 4.

METHODS: Two hundred and one HCV-genotype 4 patients were included. All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk. End of treatment response (ETR) was defined as loss of detectable serum HCV RNA at the end of treatment. Sustained viral response (SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up. Genotyping of IL28B rs12979860 was performed using the TaqMan assay. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95%CI.

RESULTS: The study included 201 HCV-genotype 4 patients. The majority of patients were men (89.6%), with a median age of 47 years, inter-quartile range (40-51). Approximately 62.5% of patients had ETR, and 49.6% had SVR. Individuals who achieved SVR were more likely to be younger (χ2 = 4.91, P = 0.027), and less likely to have fibrosis (χ2 = 15.54, P < 0.0001), or inflammation (χ2 = 7.58, P = 0.006). The genotype distribution of rs12979860 was 36.2%, 49.0% and 14.8% for genotypes CC, CT, and TT, respectively. In these participants, rs12979860 genotype distribution did not differ by gender (P = 0.466), pretreatment viral load (P = 0.600), inflammation (P = 0.435), or fibrosis (P = 0.291). The frequencies of IL28B rs12979860 genotypes were TT (14.8%), CT (49.0%), and CC (36.2%). Compared to rs12979860 genotype TT, aORs (95%CI) for ETR and SVR were: CC genotype, [17.55 (5.34-57.69) and 5.92 (2.09-16.76), respectively]; CT genotype, [5.15 (1.80-14.78) and 2.48 (0.94-6.52), respectively]. In the current study, the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC (17.4% and 23.3%, respectively) than individuals who had ETR or SVR (47.9% and 47.2%, respectively). Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype (aOR = 5.92; 95%CI: 2.09-16.76). Similarly, patients with CT genotype had SVR more often than patients with TT genotype (aOR = 2.48; 95%CI: 0.94-6.52). Carrying at least one copy of the C allele (genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT (aOR = 7.87; 95%CI: 2.84-21.82), and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT (aOR = 3.46; 95%CI: 1.37-8.74). In addition, data were consistent with a significant gene-dose relationship (aOR = 4.05/allele; 95%CI: 2.27-7.22). The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.

CONCLUSION: In HCV-genotype 4 patients, rs12979860 is a sensitive predictor of viral clearance, independent of viral load, age, gender or fibrosis, with no similar relation to severity of fibrosis.

Interleukin-28 and hepatitis C virus genotype-4: treatment-induced clearance and liver fibrosis.

Hepatitis C virus (HCV) infection is one of the most common chronic viral infections in the world. Approximately 80-90% of acutely infected individuals develop persistent infection, which is a major risk for liver cirrhosis and liver cancer. However, a small portion of patients (10-20%) clear the virus. Clinical outcomes of HCV infection are determined by the interplay between the host immune response, and viral and environmental factors. In regulating immune responses, cytokines play an indispensable role that controls the underlying pathogenesis and the resulting outcome of HCV infection. Cytokines themselves are manipulated by polymorphisms in their genes. In fact, the majority of genetic variants that apparently confer a significant risk for chronic HCV infection have been localized in genes involved in cytokine synthesis and the ultimate immune response. So far, treatment strategies for HCV infection have remained controversial. Genotyping of different polymorphisms will aid clinical decision making for both current standard and personalized care. Genotyping can potentially be useful for future integration of other agents, which provides an opportunity for clinicians to personalize treatment regimens for HCV patients. This review summarizes findings of different studies on host immune responses after HCV infection and the association between cytokine gene polymorphisms and the likelihood of HCV clearance.

Hepatitis C Virus Spontaneous Clearance: Immunology and Genetic Variance

Objective: To preliminarily explore the association of rs12979860 and rs8099917 SNPs with chronic HCV infection in Chinese Han children. Methods: Chronic HCV infection patients (n=277; 1-17 years old, 4.5 years old in average) and healthy subjects (n=150, children; 2-17 years old, 5.2 years old in average) were recruited and tested by PCR combining direct sequencing. The differences between the rs12979860 and rs8099917 genotypes in patients and healthy subjects were compared. Results: The genetic variations at rs12979860 and rs8099917 in chronic hepatitis C (CHC) children and healthy subjects did not differ significantly. The frequency of spontaneous clearance in CHC children was higher (47%), which is related to the genetic variations. The histological changes of patients were more significant compared to their clinical and biochemical indices, but they did not correlate with the genetic mutations at rs12979860 and rs8099917 significantly. Conclusion: The rs12979860 and rs8099917 SNPs are independent factors predicting the spontaneous clearance of Chinese CHC children patients. The correlation between diseases outcomes are in need of further study.

/pdf/association-of-hepatitis-c-virus-infection-and-interleukin-1hltefus33.pdf

Association of Hepatitis C Virus Infection and Interleukin-28B Gene Polymorphism in Chinese Children.

The three top single-nucleotide polymorphism (SNPs) rs12979860, rs12980275 and rs8099917 were recently related to treatment-induced hepatitis C virus (HCV) clearance. Thio and Thomas (1) elegantly reviewed that rs8099917 is likely irrelevant in the setting of African American patients. Furthermore, several studies confirmed that rs12979860 seems to be the most dominant SNP in Caucasian populations (2). In contrast, in an Asian population, rs8099917 has been superior to rs12979860 for predicting HCV treatment response or spontaneous clearance in some (3, 4) but not all studies (5).

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1478-3231.2011.02594.x

IL28B: relevance extended to hepatitis B virus or limited to interferon-based therapies in hepatitis C virus?

HCV infection will spontaneously resolve in 30% to 50% of patients. Patients with beneficial IL28B genotypes are more likely to clear spontaneously, while other are unlikely to, with less than 15% clearance rate. These patients would therefore be very likely to benefit from immediate treatment with pegylated interferon. In delayed treatment, ribavirin might be required to achieve similar results, making the delayed treatment also from the cost perspective only attractive in those likely to clear spontaneously: Patients with beneficial IL28B genotype and jaundiced patients with the intermediate IL28B genotype.

Acute HCV: Will IL28B Testing Change the Paradigm?

1339 il28b genetic variants and gender are associated with spontaneous clearance of hepatitis c virus infection

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1339 il28b genetic variants and gender are associated with spontaneous clearance of hepatitis c virus infection