Distribution of IL28B Genotypes in Iranian Patients with Chronic Hepatitis C and Healthy Individuals

Background

IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon.

Objectives

The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C.

Patients and Methods

In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46).

Conclusions

It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.     

Polymorphisms in the IFNL3/IL28B gene and hepatitis C: From adults to children

The purpose of the present review is to summarise the current knowledge on the association between single nucleotide polymorphisms (SNPs) in the interferon L3 (IFNL3) gene and hepatitis C virus (HCV) infection in children. Many studies in adults have demonstrated that genetic variation in IFNL3 is a strong predictor of the virological response in treatment-naive patients with HCV genotype 1 who were treated with Pegylated-IFN-α and ribavirin. Genetic variation in IFNL3 is also associated with the spontaneous clearance of HCV. Thus far, few paediatric studies have explored the association between variations in the IFNL3 gene and either spontaneous or treatment-induced clearance of HCV. The CC genotype of the rs12979860 SNP is associated with the spontaneous clearance of HCV in children independently of HCV genotype. Four paediatric studies have shown that both the CC genotype of the rs12979860 SNP and the TT genotype of the rs8099917 SNP are associated with the treatment-induced (IFN monotherapy and Pegylated-IFN-α and ribavirin association) clearance of HCV, while the rs12980275 SNP did not affect the virological response. The possible role of IFNL3 gene variation as a pre-treatment and on-treatment predictor of virological response in children is highly attractive but still undetermined. Further paediatric studies are needed to evaluate if testing for SNPs in IFNL3, either alone or together with other predictors of response to treatment, could be used to direct treatment strategies, including an avoidance of unnecessary protease inhibitor therapy and the duration of treatment.     

Mysterious Linkages Between Hepatitis C Virus Genotypes,Interleukin-28B Genotypes and Viral Clearance- A Meta-Analysis

Background:

Recent genome wide association studies (GWAS) have shown important roles of single nucleotide polymorphisms (SNP) near region of interleukin B 28 (IL28B) gene in spontaneous and drug-induced clearance of hepatitis C virus (HCV) in genotype 1 HCV infection.

Objectives:

This meta-analysis was designed to determine the world-wide distribution patterns of IL28B genotypes and alleles, and to find possible linkages between IL28B and HCV genotypes.

Patients and Methods:

Manual and electronic databases were searched. Critical appraisal was performed. According to the results of heterogeneity tests, we used fix/random model for the analysis. The data concerning patients’ ethnicity and HCV genotypes were analyzed by using statistical analysis software.

Results:

A total of 255 articles were found. After article review and quality assessment, 50 studies, including 18662 patients and 1313 healthy subjects, were analyzed. Presence of HCV genotype 3 versus genotype 1 was significantly associated with a higher frequency of CC genotype and C allele, with an odds ratio (OR) of 1.68 (95% CI: 1.44-1.99) and 1.49 (95% CI: 1.33-1.67), respectively. Prevalence of the rs12979860 CC genotype among genotype 1 HCV infected patients of Asian ethnicity was 69.48% (95% CI: 65.20-73.77), which was significantly higher than its prevalence [33.27% (95% CI: 28.88-37.67)] in the Caucasian genotype 1 HCV infected patients. Prevalence of rs12979860 TT genotype in the African-American genotype 1 HCV infected patients was the highest [36.20% (95% CI: 32.91-39.49)], and significantly different compared to all other ethnicities.

Conclusions:

There were significant linkages between HCV genotypes and IL28B genotypes/alleles. Patients with a favorable IL28B and genotypes 1 and 4 HCV infection stand a better chance to clear HCV in the acute phase.     

Role of Interleukin-28B Genetic Polymorphisms in Korean Patients with Hepatitis C Virus Infection

Background/Aims

This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea.

Methods

Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection.

Results

The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients.

Conclusions

The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.     

IFNL3 polymorphisms and HCV infection in patients with beta thalassemia

Background and relationale for the study. Genome-wide association studies have identified host genetic variation to be critical for spontaneous clearance and treatment response in patients infected with hepatitis C virus. Recently, the role of the IFNL3 polymorphisms in influencing the spontaneous clearance of HCV, the response to interferon and the progression of liver fibrosis, was also demonstrated in patients with thalassemia major infected by genotype 1b. In the present study we retrospectively analyzed 368 anti-HCV positive patients with beta-thalassemia at two Italian major centers in Cagliari and Torino.Results. C/C variant of polymorphism rs12979860 was related to response to interferon treatment and, above all, to spontaneous clearance of the virus. However, the positive predictive power was stronger for viral persistence than spontaneous clearance and in such respect the TT allele was more predictive than CC. The methylation associated polymorphism rs4803221 had independent effects with respect to rs12979860 and the haplotype tagged by SNP rs12979860 and rs4803221 significantly could improve the viral clearance prediction in infected patients. Neither necroinflammation or bilirubin values in the chronic phase of the hepatitis C were related to IFNL3 polymorphisms. No relation among IFNL3 polymorphisms and fibrosis stage directly shown by the liver biopsy was found.Conclusions. Also in thalassemia the SNPs on chromosome 19q13 closely associates with spontaneous and treatment-induced HCV clearance. The viral clearance prediction is significantly improved by the haplotype tagged by SNP rs12979860 and rs4803221. Neither necroinflammation, bilirubin values or fibrosis stage seem to be related to IFNL3 polymorphisms.     

Single nucleotide polymorphisms of the IL28B and sustained virologic response of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy: A meta-analysis: Meta-analysis of IL28B

Background

Hepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus (HCV) infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes.

Objectives

To assess the associations of single nucleotide polymorphisms (SNP) of the IL28B and sustained virologic response (SVR) of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy.

Materials and Methods

We searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate at SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied.

Results

The sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans (OR = 3.85, 95% CI: 3.06-4.83); the percentage of rs12979860 TT genotype was lower in Caucasians (OR = 0.25, 95% CI: 0.20-0.31) and the percentage of rs12979860 CC genotype was higher in Caucasians than that of Afro-Americans (OR = 3.45, 95% CI = 2.68-4.44). Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 (OR = 0.16, 95% CI: 0.11-0.24).

Conclusions

IL28B is significantly associated with response to PEG-interferon/ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes.     

IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

Background

Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection.

Design and Methods

We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 thalassemia major patients with hepatitis C virus infection.

Results

Ninety-eight patients (40%) had a spontaneous viral clearance while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; P=0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; P=0.001). During observation, 131 patients with chronic infection underwent a liver biopsy; age (OR 1.058; P=0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; P=0.001), and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; P=0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; P=0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; P=0.01), age (OR 0.902; P=0.001), female gender (OR 3.418; P=0.01) and 2 or 3 virus C genotypes (OR 4.700; P=0.007) were independently associated with sustained virological response in 114 patients treated with alpha-interferon.

Conclusions

Polymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in thalassemia major patients, and understanding allelic patterns has an important role in determining prognosis and therapeutic management.     

Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease

Background

IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.

Objectives

In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.

Patients and Methods

Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.

Results

A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.

Conclusions

Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.     

The Role of Interleukin-28b Gene Polymorphisms in Chinese Patients With Chronic Hepatitis C Treated With Pegylated Interferon and Ribavirin

Background:

Interleukin-28B (IL28B) single nucleotide polymorphism (SNP) rs8099917 has been described to be associated with response to treatment with pegylated interferon and ribavirin (PEG-IFN/RBV) in patients with chronic hepatitis C from the North America, Europe, Asia countries like Japan and Taiwan. Whether this holds true for Chinese patients remains unknown.

Objectives:

We aimed to study the effects of IL28B rs8099917 on antiviral therapy responses in Chinese patients with hepatitis C.

Patients and Methods:

IL28B rs8099917 was genotyped in 263 patients with hepatitis C virus (HCV) infection and 244 healthy controls in Tianjin, China using TaqMan SNP genotyping method. The roles of rs8099917 and clinical characteristics in antiviral treatment were analyzed by logistic regression.

Results:

Among 263 patients with chronic HCV infection, 223 had a TT genotype (84.8%). Frequencies of TG/GG genotypes in patients with hepatitis C were significantly different from those of healthy controls (15.2% vs. 9.0%; P = 0.033). Patients with HCV infection had a higher G allele frequency than healthy controls (7.8% vs. 4.7%; P = 0.044). Univariate analysis revealed no significant association between rs8099917 and sustained virological response (SVR) (P = 0.612). However, it was found that HCV genotypes 2a/3a, age, prothrombin time (PT), albumin (ALB) and cholesterol (CHO) were associated with SVR. In multivariate analysis, only ALB was significantly an independent predictor of SVR (OR = 1.223; 95%CI: 1.046−1.430; P = 0.011).

Conclusions:

In contrast with T, rs8099917 G is a susceptible allele to HCV in China. ALB can independently predict SVR. Rs8099917 may play a quiet role to predict treatment response of patients with hepatitis C who received PEG−IFN/RBV therapy in China.     

HLA-DPB1 Variant Effect on Hepatitis B Virus Clearance and Liver Cirrhosis Development Among Southwest Chinese Population

Background:

Previous studies have shown that genetic variants in HLA-DP genes affect disease progression in hepatitis B virus (HBV) infection.

Objectives:

We aimed to evaluate possible association between HLA-DPB1 rs9277534 polymorphism and different clinical complications of hepatitis B virus (HBV) infection.

Materials and Methods:

Snapshot assay was used to investigate the association of rs9277534 polymorphism in 342 patients with persistent HBV infection and 342 age and gender-matched HBV spontaneous clearance controls. Patients were categorized into asymptomatic HBV carriers (AsC, n = 104), chronic hepatitis B (CHB, n = 116), and liver cirrhosis (LC, n = 122) subgroups.

Results:

There was a significantly higher proportion of the rs9277534 minor allele A in HBV spontaneous clearance control than that in HBV persistent infection group (OR = 0.58, 95%CI = 0.46-0.73, P < 0.0001). Genotypic analysis showed that GA and AA genotypes were associated with HBV spontaneous clearance (GA: OR = 0.56, 95%CI = 0.40-0.79, P = 0.019; AA: OR = 0.24, 95%CI = 0.14-0.44, P < 0.0001). A significant difference was found between AsC and LC groups in the distribution of AA genotype (OR = 9.32, 95%CI = 1.293-67.14, P = 0.027).

Conclusions:

Variant at rs9277534 could affect both the spontaneous clearance of HBV infection and progression from asymptomatic HBV carriers to HBV-related liver cirrhosis in Southwest Han Chinese population.     

Association of IL28B Polymorphisms With the Response to Peginterferon Plus Ribavirin Combined Therapy in Polish Patients Infected With HCV Genotype 1 and 4

Background

Three single nucleotide polymorphisms (SNPs) near interleukin-28B (IL-28B) gene were shown to be highly associated with treatment response (SVR) in patients with chronic hepatitis C virus (HCV) infection. There is limited data about the role of single and combined IL-28B polymorphisms in HCV-infected Polish population.

Objectives

This study''s aim was to determine predictability of three IL-28B gene polymorphisms and other known prognostic factors on the treatment response in HCV genotype 1 and 4 infected Polish patients. The effect of IL-28B polymorphisms on therapy was also compared with other known prognostic factors.

Patients and Methods

We genotyped IL-28B polymorphisms (rs12979860, rs12980275 and rs8099917) by polymerase chain reaction-based restriction fragment length polymorphism assay in a group of 293 patients from which a selected cohort of 174 treatment-naiev patients underwent treatment.

Results

We showed that rs12979860 CC [odds ratio (OR) = 4.6, P < 0.001], rs12980275 AA (OR = 2.9, P = 0.002) and rs8099917 TT (OR = 2.2, P = 0.016) genotypes were associated with successful treatment compared to the rs12979860 CT-TT, rs12980275 AG-GG and rs8099917 TG-GG, respectively. Patients bearing of IL-28B profile including the three favourable genotypes do not have much chance of a recovery (OR = 3.4, P = 0.002). Except for IL-28B polymorphisms, there was no association of SVR with any other pretreatment clinical data in analyzed group. The correlation of SNPs with other host and viral factors revealed association of favorable genotypes of IL-28B markers with high levels of alanine aminotransferase and baseline HCV viral load.

Conclusions

IL-28B polymorphisms were the strongest pretreatment predictors of response to pegylated interferon and ribavirin in Polish patients chronically infected with HCV genotype 1 and 4. This study confirm the strongest impact of IL-28B rs12979860 on SVR, nevertheless rs12980275 AA seems to be more important than rs8099917 TT in predicting positive treatment response.     

Interferon Lambda 4 Polymorphism Predicts Sustained Viral Response in Hepatitis C Virus Patients Irrespective of Hepatitis C Virus Genotypes,Ethnicity or Treatment Regimen: Results From a Meta-Analysis

Context:

There is growing evidence that interferon lambda 4 (IFNL4) polymorphism is related to sustained virological response (SVR) in hepatitis C virus (HCV) infection. We analyzed the relationship between IFNL4 (rs368234815) polymorphism and SVR in dual- and triple- therapy in HCV genotype 1, 2, 3 and 4 infected Asian, Caucasian and African patients.

Evidence Acquisition:

We performed a systematic search of PubMed, Medline, Embase, EBSCO and Web of Science databases up to July 2015. Data of qualified studies were analyzed using the meta-analysis method in Stata 12.0 software.

Results:

Ten studies involving 4765 patients were included in the analysis. Of overall studies, SVR was more frequent in TT/TT genotype compared to TT /ΔG+ΔG /ΔG (OR = 4.439, 95% CI: 3.410 - 5.778). Genotype stratification analyses revealed rs368234815 TT/ TT was associated with higher SVR in G1, G2/3 and G4 HCV patients (ORG1 = 4.661, 95% CI: 3.937 - 5.518; ORG2/3 = 1.896, 95% CI: 1.265 - 2.841; ORG4 = 6.074; 95% CI: 3.129 - 11.788). Ethnicity stratification analyses of G1 patients showed that SVR was more frequent with TT/ TT genotype in Asians (OR= 8.245, 95% CI: 5.475 - 12.416), Caucasians (OR = 4.166, 95% CI: 3.441 - 5.042) and Africans (SVR: 37.5% vs 17.0%, P = 0.017). Moreover, similar results presented in therapy stratification analyses both in patients with dual-therapy (OR = 3.857; 95% CI: 3.288 - 4.524) or triple-therapy (OR = 8.119; 95% CI: 4.942 - 13.340).

Conclusions:

Favorable IFNL4 rs368234815 genotype is a strong predictor of SVR in HCV patients, irrespective of HCV genotypes, ethnicity or treatment regimen. Thus, detection for IFNL4 rs368234815 polymorphism may be beneficial to guide the clinician in the individualization of therapy and design.     

The IFN-λ Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients

Background

Polymorphisms in the interferon λ (INF λ) genes on chromosome 19 have been associated with clearance of hepatitis C virus (HCV) induced by interferon and ribavirin therapy however there is no such data available for Pakistani patients with HCV infection.

Objectives

In this study, the effects of single nucleotide polymorphisms (SNPs) have been investigated in response to treatment with interferon-α and ribavirin in a cohort of 75 HCV genotype 3a patients.

Patients and Methods

A total number of 50 SNPs from the Interferon λ region on chromosome 19 were genotyped to investigate allelic associations with the treatment response in HCV type 3a patients. Thirteen SNPs were associated with HCV clearance, with the most significant alleles being RS8109886 (Fisher’s P = 0.0001), RS8113007 (Fisher’s P = 0.0001) and RS12979860 (Fisher’s P = 0.0002).

Results

These SNPs were found to be the most suitable SNPs for predicting treatment response in the present study. These findings support those reported previously. This could be used to improve HCV treatment strategies and suggest that Pakistani patients should be genotyped for the relevant SNPs to identify the patients who are more likely to respond to interferon and ribavirin therapy.

Conclusions

This therapy is costly and can be accompanied by several adverse side-effects, hence pre-treatment prediction of patients who are most likely to benefit would have both economic and patient benefits in the long term.     

LRRFIP1 Inhibits Hepatitis C Virus Replication by Inducing Type I Interferon in Hepatocytes

Background:

Hepatitis C virus infection is one of the leading causes of end stage liver diseases. The innate immune response slows down viral replication by activating cytokines such as type I interferon (IFN-α/β), which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. Recently, leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) was reported contributing to the production of interferon-β in macrophages.

Objectives:

The aim of this study was to assess the role of LRRFIP1 in induction of IFN-β and inhibition of HCV infection in hepatocytes.

Materials and Methods:

Induction of IFN-β by LRRFIP1 in Huh7 and Huh7.5.1 was determined by real-time PCR and western blotting in vitro. Inhibition of HCV replication by LRRFIP1 overexpression in hepatocytes was assessed.

Results:

LRRFIP1 increased the expression of IFN-β in hepatocytes with or without HCV infection. Induction of IFN-β by LRRFIP1 was enhanced with the presence of hepatitis C virus. Overexpression of LRRFIP1 in hepatocytes inhibited HCV replication. However, HCV infection did not regulate intracellular expression of LRRFIP1.

Conclusions:

LRRFIP1 and its mediated production of type I interferon play a role in controlling HCV infection. The findings of this study provide new target for HCV treatment and contribute to development of anti-HCV drugs.     

Efficacy of 24-Week Pegylated Interferon Alpha and Ribavirin Combination Therapy in Highly Selected Patients Infected With Hepatitis C Virus Genotype 1

Background:

Previous studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate.

Objectives:

The current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR.

Patients and Methods:

In this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group.

Results:

The majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99).

Conclusions:

The current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients.     

The Reduced Predictive Value of Interleukin 28b Gene Polymorphisms in a Cohort of Patients With Thyroiditis Developed During Antiviral Therapy for Chronic Hepatitis C: A Preliminary Study

Background:

Single nucleotide polymorphism in the interleukin28B (IL28B) gene was recently shown to be associated with a significant increase in response to interferon-α and ribavirin treatment in patients with chronic hepatitis C. Similarly, thyroid disease (TD) occurring during treatment confer an improved sustained virologic response (SVR).

Objectives:

To determine the role of IL28B genotypes in a cohort of hepatitis C patients who develop TD during treatment and its relationship to SVR.

Patients and Methods:

IL28B gene profiles including rs12979860, rs12980275 and rs 8099917 and their genotypes were determined in a cohort of 23 hepatitis C patients who developed TD during treatment and their relationship to SVR.

Results:

Out of 23 studies cases, 19 has one or more favorable genotypes, of which 15 (78.9%) achieved SVR. Eleven has all three unfavorable genotypes and yet achieved 72.7 % SVR. The presence of more than one favorable genotype only correctly predicts SVR vs. non- SVR in ~50 % of cases, i.e. by chance.

Conclusions:

Despite the small number of subjects, the presence of one or more unfavorable IL28B genotype does not portend a poor SVR prognostic outcome. This suggests that TD in this clinical context may be a critical factor in the achievement of SVR, probably above that of the genetic predisposition.     

Development and Validation of a Simple, Rapid and Inexpensive PCR-RFLP Method for Genotyping of Common IL28B Polymorphisms: A Useful Pharmacogenetic Tool for Prediction of Hepatitis C Treatment Response

Background

In 2009, 3 genome-wide association studies implicated IL28B single-nucleotide polymorphisms (SNPs) as the strongest genetic pretreatment predictor of sustained virological response (SVR) in hepatitis C infection. Recently, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) included IL28B testing in their guidelines.

Objectives

The main aim of this study was to develop and validate a simple, rapid, and inexpensive polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for genotyping of common IL28B polymorphisms (rs12979860 and rs8099917).

Patients and Methods

Two methods were developed to genotype common IL28B polymorphisms: 1) PCR-sequencing as a reference method and 2) PCR-RFLP as a rapid and inexpensive method. Both polymorphisms were genotyped in 104 Iranian hepatitis C patients by both methods simultaneously. To validate the PCR-RFLP method, the PCR-RFLP genotyping results should be 100% concordant with the PCR-sequencing results.

Results

Genotyping of rs12979860 and rs8099917 by PCR-RFLP was concordant with PCR-sequencing in 104 (100%) individuals. The analytical sensitivity and specificity of the PCR-RFLP method for genotyping of both SNPs are 100%. Among these 104 patients with chronic hepatitis C, the frequency of the rs12979860 CC, CT and TT genotypes were 40.4%, 47.1% and 12.5% and the frequency of the rs8099917 TT, GT and GG genotypes were 59.6%, 35.6% and 4.8%, respectively. Also, three IL28B haplotypes (rs12979860-rs8099917) were found among our patients including C-T, T-G and T-T with 63.9%, 22.6% and 13.5% frequency, respectively. C-G haplotype was absent in all of our patients.

Conclusions

We have developed a validated, fast, and simple PCR-RFLP method for genotyping of common IL28B SNPs that is more cost-effective than sequencing.     

Predictors of Pegylated Interferon Alpha and Ribavirin Efficacy and Long-Term Assessment of Relapse in Patients With Chronic Hepatitis C: A One-Center Experience From China

Background:

Sustained virological response (SVR) and virological relapse maintain pivotal roles in the management of chronic hepatitis C (CHC); however, there is little data regarding the long-term outcomes of patients with CHC in China.

Objectives:

We aimed to investigate the predictive factors of therapeutic effect and viral relapse in patients who achieved end-of-treatment response (ETR).

Patients and Methods:

We retrospectively analyzed clinical, biochemical and virological data of 169 adult patients with CHC from China who were not treated with pegylated interferon-alpha (PEG IFN-α) and ribavirin, of which 142 achieved ETR and with a follow-up period ranging from six months to six years. Statistical analysis was performed by SPSS 20.0.

Results:

Of the 169 patients, 124 (73.4%) achieved SVR and 23 (16.2%) experienced relapses post-therapy in cases of ETR patients. We considered sex, age, alanine aminotransferase, aspartate transaminase, baseline hepatitis C virus RNA level, HCV genotypes, IL28B rs12979860 genotype, rapid virological response (RVR), and early virological response (EVR). For antiviral effect in patients with CHC, HCV genotypes (2, 3) (χ² = 11.285, P = 0.001), IL28B genotype (rs12979860 CC) (χ² = 16.552, P < 0.001), RVR (χ² = 37.339, P < 0.001), and EVR (χ² = 70.265, P < 0.001) were significantly correlated with achieving SVR. For ETR patients with long-term follow-up, the relapse rate within six months was significantly higher than within other periods during six-year follow-up (χ² = 7.792, P = 0.005). Relapse was virtually not observed after therapy ceased for 48 weeks. The IL28B genotype (rs12979860 CT/TT) (OR = 0.102; 95% CI, 0.031-0.339; P < 0.001), lower RVR (OR = 0.239; 95% CI, 0.078-0.738; P = 0.013), and EVR (OR = 0.102; 95% CI, 0.016-0.661; P = 0.017) were independent risk factors for relapse.

Conclusions:

Our study comprehensively explored the predictive factors of therapeutic effect of administered drugs and analyzed viral relapse during a six-months to six-year follow-up period from China. The SVR may not be the perfect endpoint of HCV therapy in Chinese people; we recommend 48 weeks after treatment withdrawal as the suitable time point.     

Hepatitis B,Hepatitis C and Human Immunodeficiency Virus Seropositivity Among Children in Kabul,Afghanistan: A Cross-Sectional Study

Background:

Hepatitis B virus (HBV), hepatitis C Virus (HCV), and human immunodeficiency virus (HIV) infections are significant causes of morbidity and mortality all over the world, especially in underdeveloped countries like Afghanistan. Limited data are available concerning the seroprevalence of HBV, HCV and HIV in the pediatric age group in Afghanistan .

Objectives:

The aim of the study was to assess HBV, HCV and HIV serology among children at an outpatient clinic in Kabul.

Patients and Methods:

A total number of 330 children were included to the study from outpatient clinics of Ataturk Kabul ISAF Role II Military Hospital from May to November 2012. Hepatitis B surface antigen (HBsAg), hepatitis C antibody (anti-HCV), and human immunodeficiency virus antibody (anti-HIV) were measured.

Results:

The mean age of children was 6.5 ± 4.2 years. The frequency of positive results for HBsAg, anti-HBs and anti-HCV in all age groups were 12 (3.6%), 47 (14.2%) and 2 (0.6%), respectively. Anti-HIV was not detected in any of the children''s serum samples. The frequency of positive results for HBsAg was significantly higher in children older than six years than in other age groups.

Conclusions:

Vaccination program including HBV has begun during the last five years in Afghanistan. The continuation of the vaccination program is of great importance. Vaccination program and implementation steps should be revised and the deficiencies, if any, should be overcome without delay.     

Treatment of chronic hepatitis C in a Canadian Aboriginal population: Results from the PRAIRIE study

BACKGROUND:

The Aboriginal population of Canada is at increased risk of exposure to the hepatitis C virus (HCV). Previous data indicate that spontaneous clearance of HCV occurs more often in Aboriginals than Caucasians. Whether this enhanced response extends to antiviral therapy for chronic HCV remains to be determined.

OBJECTIVES:

To document and compare the biochemical and virological responses to antiviral therapy in HCV-infected Canadian Aboriginals and Caucasians.

METHODS:

A total of 101 treatment-naive adult patients (46 Aboriginal, 55 Caucasian) with chronic HCV genotype 1 infections were prospectively treated with pegylated-interferon and ribavirin and followed as per national guidelines.

RESULTS:

Aboriginals had higher HCV-RNA loads at baseline (6.42log₁₀ versus 5.98log₁₀; P<0.03). Although normalization of serum aminotransferase levels, decreases in viral loads, and rapid, early and end-of-treatment virological responses were similar in the two cohorts, sustained virological responses were significantly lower in Aboriginals (35% versus 55%; P=0.047). Premature discontinuation of treatment and/or loss of patients to follow-up was common (Aboriginals 37%, Caucasians 27%). Treatment-related side effects were similar in the two cohorts.

CONCLUSION:

Despite higher rates of spontaneous HCV clearance, the response to antiviral therapy was similar, if not lower, in Aboriginals compared with Caucasians with chronic HCV genotype 1 infections. Compliance with treatment is an issue that needs to be addressed in the management of these patients.