IL28B Rs12979860 Research Articles

Association Between IL-28B Polymorphism and Clinical Laboratory Features in Patients with Chronic Hepatitis D

Objectives: We aimed to determine an association between IL-28B rs12989760 single nucleotide polymorphism (SNP) and clinical laboratory parameters in patients with chronic hepatitis D. Methods: A total of 59 patients who were chronically infected with HDV were had their serum tested for the presence of qHBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HCV, anti-HDV IgM, anti-HDV IgG, HDV RNA, HBV DNA and AFP. Liver function tests, coagulation tests and CBC were also performed. IL-28B polymorphism was performed using a TaqMan 5' allelic discrimination assay by real time PCR. Results: Of these 59 patients, 40 patients (67.8 %) carried the rs12979860CC homozygote genotype, 11 patients (18.6%) were rs12979860CC homozygote and 8 patients (13.6%) were rs12979860CT heterozygote. Alkaline phosphatase and direct bilirubin values were higher (p<0.05) and total protein levels were lower (p<0.05) in patients who were homozygotes for the T allele as opposed to the carriers of the C allele. AFP levels were significantly higher (p=0.02) in the rs12979860 TT genotype group. Liver enzymes including AST, ALT and GGT were significantly not higher in patients who carry C allele (p>.05). Conclusion: The most frequent genotype was IL-28B rs12979860CC among patients with chronic hepatitis D. The IL-28B rs12979860 polymorphism was associated with some abnormal liver function test parameters and AFP levels. Additional studies are necessary to understand the immune mechanisms of IL-28B polymorphism in HDV infection.

Multiple genetic variants associated with posttransplantation diabetes mellitus in Chinese Han populations.

Posttransplantation diabetes mellitus (PTDM) is a major complication after solid organ transplantation. This study is to investigate the association of nine genetic variant factors and PTDM in Chinese Han patients. HLA-DP (rs3077, rs9277535), HLA-DQ (rs7453920), signal transducer and activator of transcription 4 (STAT4) (rs7574865), IL-28B (rs12979860, rs8099917, and rs12980275), and IL-18 (rs1946518 and rs187238) were investigated in 260 liver transplant recipients (PTDM vs non-PTDM) by high-resolution melting curve analysis. Serum interleukin (IL)-1β, IL-6, IL-8, IL-17, interferon-γ, inducible protein-10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1b were analyzed by a Bio-Plex suspension array system (Bio-Plex Multiplex Immunoassays, Bio-Rad, Hercules, CA, USA). Signal transducer and activator of transcription 4 (rs7574865) T allele and IL-18 (rs1946518) A allele increase the risk for insulin resistance and PTDM. Recipients with STAT4 (rs7574865) T allele are associated with an increased concentration of IL-1β, interferon-γ, monocyte chemoattractant protein, and macrophage inflammatory protein-1b. The genetic variants of STAT4 (rs7574865) and IL-18 (rs1946518) may be new important markers for PTDM.

IL28B rs12979860 genotype as a predictor marker of progression to BKVirus Associated nephropathy, after kidney transplantation

BK virus (BKV) associated nephropathy (BKVAN) is still an important cause of allograft dysfunction after kidney transplantation (KT). Recent data have shown that the new interferon (IFN)-λ family has been ascribed antiviral properties similar to IFNα, and that the response to IFNλ in kidney is restricted to epithelial cells, suggesting that the IFNλ system evolves as specific protection of the epithelia. We aimed to test the hypothesis of correlation between a single nucleotide polymorphism (C/T dimorphism rs12979860) in the genomic region of IL28B and BKVAN, in patients after KT. Fifty kidney-transplanted patients were included as follow: Group 1 (BKV+/BKVAN+): 11 patients with active BKV− replication and biopsy-proven BKVAN; Group 2 (BKV+/BKVAN−): 22 patients with active BKV− replication but without evidence of BKVAN; Group 3 (BKV−/BKVAN−): 17 patients without evidence of BKV− replication (control group). Here we show that the C/C genotype was statistically higher in group 2 than in group 1 and BKVAN was detected significantly more frequently in patients with C/T and T/T genotypes than in patients with C/C genotype. We therefore propose IL28B polymorphism (rs12979860), as a predictor-marker to differentiate between patients with self-limited, even if persistent, BKV− reactivation and patients with a high risk of progression towards BKVAN, and to modulate the clinical management of these patients accordingly.

Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

IntroductionChronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients.MethodsNIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0–2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates.ResultsSeven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74).ConclusionThe identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.

Study of Interleukin IL-28B rs12979860 and rs8099917 Polymorphisms among HBV Infected Egyptian Patients

Background: HBV is a worldwide health problem as about 2 billion individuals have been infected with HBV and 350 million are the chronic carriers. The efficacy of anti-viral drugs used in treatment of HBV is high but these drugs are expensive, associated with many side effects and drug resistance was reported. Thus selection of patients with the highest probability of response is essential for clinical practice. Recent genome-wide association studies have revealed some polymorphisms near IL-28B region to be associated with HBV susceptibility, response to treatment or even spontaneous HBV clearance. Objective: This study aimed to investigate role of IL-28B single nucleotide polymorphisms among CHB Egyptian patients. Methodology: SNPs of IL-28B (rs12979860 and rs8099917) regions were genotyped using the MGB-TaqMan SNP genotyping assay in 60 HBV infected patients and 20 healthy volunteers. Results: IL-28B rs12979860 genotypes were expressed in similar proportions in all the studied groups and no statistical significant difference between them was found (MCP=0.272). Concerning IL-28B rs8099917 SNP; GG genotype was 90% expressed among healthy volunteers, while GT genotype was 80% expressed in naive HBV patients, and TT genotype was expressed in 10% non- responder HBV patients only. There was statistical significant difference between the studied groups as 80% of patients in the naive group were carrier to IL-28B rs8099917 GT allele (P=0.013). Conclusion: Genetic variations of IL-28B rs8099917 could be associated with HBV risk and resistance to treatment with nucleoside/ nucleotide analogues as G allele could be protective against HBV, GT genotypes could be risk factor for HBV infection while T allele may be predictive factors of treatment resistance.

Vitamin D receptor polymorphisms as predictors of response to interferon/ribavirin-based therapy in Egyptians with chronic hepatitis C infection

Objective The aim of the present study was to assess the influence of polymorphisms in vitamin D receptors (VDRs) Fok1 and Apa1 and interleukin 28B rs12979860 C/T on the response to interferon/ribavirin-based therapy in Egyptians with chronic hepatitis C. Background Vitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus. Genetic polymorphisms affecting the VDR gene have been implicated in several immune disorders. Patients and methods This retrospective study was conducted on 80 patients who were divided into two groups: group I – the nonresponders group – comprised 40 patients and group II – the sustained virological response (SVR) group – also comprised 40 patients. The present study also included 20 healthy volunteers as controls. Two single nucleotide polymorphisms in VDRs Fok1 and Apa1 and in IL28B rs12979860 C/T) were determined by real-time PCR and restriction fragment length polymorphisms. Results Genotypes of IL28B rs12979860 (CC/CT/TT) were found in 23 (57.5%), 15 (37.5%), and two (5%) patients and of Apa1 (CA/AA/CC) in 24 (60%), 14 (35%), and two (5%) patients. Genotypes of Fok1 (TT/CC/TC) were found in 23 (57.5%), nine (22.5%), and eight (20%) patients, respectively, in the SVR group. Regarding IL28B rs12979860 polymorphisms, patients with a T-allele carrier had higher frequency among nonresponders (87.5%) in comparison with SVR (42.5%). Regarding VDR (Fok1) polymorphisms, patients with a C-allele carrier had higher frequency among nonresponders (92.5%) in comparison with SVR (42.5%). Regarding VDR Apa1 polymorphisms, patients with a C-allele carrier had higher frequency among nonresponders (92.5%) in comparison with SVR (65%). Conclusion Pretreatment vitamin D level was significantly higher in responders, and this can be used as a predictor of response to combination therapy for hepatitis C virus. VDR gene polymorphisms (Fok1 and Apa1) and IL28B rs12979860 polymorphism are independently related to response to interferon/ribavirin-based therapy in chronic hepatitis C.

High frequencies of a favorable IL-28B rs8099917 polymorphism and the clinical implications in patients with HCV in one multiracial area of Taiwan

There is a strong association between hepatitis C virus (HCV) treatment efficacy and the interleukin (IL)-28B gene. However, the IL-28B variant's distribution and potential role in the therapeutic response are not well established in Taitung, a racially diverse county in Taiwan. Here, we investigated the distribution pattern of IL-28B rs8099917 and its influence on treatment efficacy. In this retrospective study, we enrolled 180 patients who had been treated with pegylated-interferon plus ribavirin. Patients' general information, virological characteristics, IL-28B status, laboratory results, treatment course, and outcome were analyzed. Of the patients enrolled, 56.7% were male, with a mean age of 54.11 years. A total of 24.4% of the population were indigenous people. The majority of patients had the favorable IL-28B polymorphism (rs8099917 TT/TG/GG: 94.4%/5.6%/0%). The proportion of patients with the TT genotype seemed to be higher in indigenous patients. The rate of sustained virological response (SVR) among included patients was 73.0%. Univariate analysis showed that genotype non-1, patients achieved rapid virological response (RVR), lower body mass index (BMI), and lower baseline HCV viral load were significantly associated with SVR. Multivariate analysis revealed that BMI <25 and RVR are the independent predictor of success treatment. In conclusion, the favorable IL-28B rs8099917 polymorphism occurs in high frequency in this multiracial area, which might be important to help guide physicians and patients in their future clinical decisions.

The relationship between ITPA rs1127354 polymorphisms and efficacy of antiviral treatment in Northeast Chinese CHC patients.

This prospective study investigated the relationship between 2 inosine triphosphatase (ITPA) polymorphisms (rs7270101 and rs1127354) and the efficacy of ribavirin-based antiviral therapy in hepatitis C virus (HCV)-infected Chinese patients.A total of 906 patients diagnosed with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin combination therapy between January 2011 and January 2014 from 5 hepatitis centers in Northeast China were enrolled. The patients were divided into genotype 1 and non-genotype 1 groups according to the genotype of infected HCV. ITPA single nucleotide polymorphism (SNP) genotyping was performed for all patients. Ribavirin-induced hemolytic anemia and virological response (VR) were monitored during treatment and follow-up. Multivariate regression analysis was used to analyze the predictors for sustained virological response (SVR).IPTA rs7270101 variants were not detected. IPTA rs1127354 variants were detected and showed no difference between the genotype 1 and non-genotype 1 groups. IPTA rs1127354 genotype CC was related to a higher incidence of ribavirin-induced hemolytic anemia. For patients who received >80% of the planned ribavirin dose, rs1127354 variants and related ITPase were related to better SVR. Multivariate analysis showed that IPTA rs1127354 non-genotype CC, HCV genotype, a baseline HCV RNA level <4 × 105 IU/mL, IL-28B rs12979860 genotype CC, and low liver fibrosis were independent predictors for SVR during the combination therapy.IPTA rs1127354 variants and related ITPase were not only related with ribavirin-induced hemolytic anemia but also directly affected the SVR to PEG-IFN plus ribavirin combination therapy in Chinese HCV-infected patients.

Role of IL28B genotype in the liver stiffness increase in untreated patients with chronic hepatitis C

The role of interleukin (IL)28B has been deepened in the treatment response to pegylated-interferon in patients affected by chronic hepatitis C (CHC). However, recently the IL28B genotypes were also related to hepatic fibrosis progression in untreated patients, using the liver biopsy. The aim of this prospective and longitudinal study was to assess the role of different IL28B genotypes in the liver stiffness progression in a cohort of untreated subjects affected by CHC.We included in this analysis all untreated patients affected by CHC and followed for at least 5years with the annual evaluation of liver stiffness using Fibroscan®. All enrolled subjects were genotyped for rs8099917 and rs12979860 IL28B polymorphisms.In the study period, 266 patients were considered. After 5years we observed the following median stiffness increases: 6.7kPa [5.1–7.8] in TT/CC, 4.9kPa [4.1–5.0] in TT/TC, 3.4kPa [3.2–3.8] in TG/TC and 1.7kPa [1.2–1.9] in GG/TT. These values were statistically significant in all groups (p<0.001). In the multivariate analysis resulted as predictive factors of liver stiffness progression the following: IL28B TT/CC genotype (OR=4.571; 95%IC=2.381–12.994; p<0.001) and IL28B GG/TT genotype (OR=0.510; 95%IC=0.289–0.712; p=0.007). In this study we evidenced that IL28B genotypes were associated with a different level of liver stiffness increase after 5years and could be used to select the patients who should be treated with priority.

Both Hepatitis C Virus-Specific T Cell Responses and IL28B rs12979860 Single-Nucleotide Polymorphism Genotype Influence Antihepatitis C Virus Treatment Outcome in Patients with Chronic Hepatitis C.

Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy. The interdependence and roles of T cell-mediated immune responses and IL28B rs12979860 single-nucleotide polymorphism genotype as predictors of virological response to anti-HCV treatment in patients with chronic hepatitis C were evaluated using nonparametric tests. Factors associated with rapid virological response (RVR) in univariate analysis were presence of CD4 T cell response against NS3 HCV protein, low baseline HCV-RNA, and IL28B CC genotype. Factors associated with sustained virological response (SVR) in univariate analysis were IL28B CC genotype, low baseline HCV-RNA, and presence of CD4 response against NS2. In the multivariate analysis, low baseline HCV-RNA and NS3-specific CD4 response showed a clear trend toward association with RVR (P = 0.09 and P = 0.07, respectively). Regarding SVR, IL28B CC genotype was the strongest predictor (P = 0.02), with presence of NS2-specific CD4 response showing a clear trend (P = 0.09). HCV-specific T cell response influences the outcome of pegIFNα/RBV therapy regardless of IL28B genotype. HCV-specific T cell responses (adaptive immunity) seem to influence viral clearance both in the short and long term during therapy (RVR and SVR), whereas the influence of the IL28B genotype (innate immunity) may be more relevant to the long-lasting therapeutic effect (SVR).

Association of Genotype and Haplotype of IL-28B Gene with Hepatitis C Infection Outcome in Iran: Spontaneous Clearance Versus Chronic Infection

Background: Spontaneous viral clearance occurs in 10% to 40% of individuals after hepatitis C virus infection. Some polymorphisms in IL-28B gene may influence the outcome of HCV infection. The present study aimed at investigating the genotype and allele frequency of IL-28B rs12979860 and rs8099917 SNPs in HCV infected patients in addition to determining their association with disease outcome. Methods: A total of 302 patients with chronic hepatic C infection and 36 individuals whose infection was spontaneously cleared were included in this case-control study. The presences of chronic or spontaneously cleared infection in participants were determined by serologic and molecular methods. Genomic DNA of the participants was extracted using salting out method. IL-28B/IFN-λ3 gene polymorphisms were conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of CC genotype (P = 0.001) and C allele (P = 0.0007) of IL-28B gene at rs12979860 SNP was significantly higher in participants with spontaneously cleared HCV infection compared to that of those who were chronically infected. In the case of rs8099917 SNP of IL-28B, no correlation was found between frequency of genotype (P = 0.17) or allele (P = 0.12) and HCV infection outcome. The results of haplotype analysis showed the association of CT (P = 0.012) and TT (P = 0.013) haplotypes with spontaneous clearance and chronic infection, respectively. Conclusions: The findings implied that individuals with CC or CT genotype at rs12979860 SNP but rs8099917 SNP was not in association with spontaneous clearance of HCV in an Iranian population with HCV infection.

The association of nonalcoholic fatty liver disease with genetic polymorphisms: a multicenter study.

Growing evidence suggests that multiple factors, such as insulin resistance, nutritional factors, gut microbiota, and hormones released from the adipose tissue, act together on genetically predisposed individuals. We aimed to investigate whether various single-nucleotide polymorphisms (SNPs) play a role in the development of nonalcoholic fatty liver disease (NAFLD) and severity of liver damage in the Anatolian population. Two hundred and sixteen patients with biopsy-proven NAFLD and 150 control participants, aged 18-70 years, were consecutively enrolled in this multicenter study. Blood samples were genotyped for the PNPLA3 (rs738409), IL28B (rs12979860, rs12980275, rs8099917), PPAR-α 227 ALA, PPAR-γ pro 12 ALA, SOD2 C47T, and LOX-1 IVS4-14 polymorphisms using the custom-made LightSNiP assays on a LightCycler 480 II instrument. Genotypic distributions of PNPLA3 rs738409 SNPs were different between NAFLD and control participants, but not for other SNPs. The PNPLA3 rs738409 GG polymorphism was associated with a 27-fold increased risk of development of NAFLD (odds ratio=27.8, 95% confidence interval: 3.5-218.4; P=0.002). Patients with the PNPLA3 GG genotype had higher nonalcoholic fatty liver disease activity score levels compared with patients with the PNPLA3 CC genotype (P<0.005). NAFLD patients without fibrosis had a higher frequency of IL28B rs12979860 TT and rs12980275 GG genotypes compared with NAFLD patients with fibrosis (P<0.005). The present study proposes that polymorphisms in the PNPLA3 gene have highly predictive value in the development of NAFLD and are independently associated with the severity of liver histology in patients with NAFLD. The results of this study suggest that IL28B rs12979860 TT or rs12980275 GG may play an important protective role against the development of advanced fibrosis and even cirrhosis.

SVR Rates of HCV-infected population under PEG-IFN-\u03b1/R treatment in Northwest China

BackgroundChronic HCV Patients taking PEG-IFN-α/R from different ethnic groups have different probabilities of reaching a sustained viral response (SVR). There are many influence factors, such as HCV genotype, IL-28B single-nucleotide polymorphisms (SNP), Fibrosis 4 index (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) score. But the baseline factors in relation to treatment outcome was still not much clear.MethodsWe evaluated data from 231 chronic HCV patients with or without liver fibrosis and their antiviral efficacy after treatment with pegylated interferon plus ribavirin (PEG-IFN-α/R) for 24–48 weeks. IL-28B SNP and HCV genotypes were analyzed with genome sequencing using pyrosequencing.ResultsSustained viral response (SVR) rates of patients with HCV 1b and 2a genotypes were 52.25% (58/111) and 75.28% (67/89) (P < 0.01). SVR rates of patients with IL-28B rs8099917 TT, rs12979860 CC and rs12980275 AA were 92.41% (25/27), 92.86% (26/28) and 88.89% (24/27) separately. We found that SVR rates in HCV 1b and 2a patients were only 31.0 and 39.4% if their FIB-4 > 3.25. In addition, when their APRI > 2, only 30.3% of HCV 1b patients and 50.2% of HCV 2a patients could obtain SVR.ConclusionsThere were high proportion of HCV genotype 1b and 2a in Northwest China. In both HCV 1b and 2a genotypes, patients with protective-genotype of IL-28B were more likely to obtain SVR. However, those with significant fibrosis or cirrhosis were less likely, no matter their genotype. Combined factors of HCV genotype, IL-28B genotype, FIB-4 and ARPI may indicate high prediction and clinical value regarding treatment with PEG-IFN-α/R and prognostic evaluation of chronic hepatitis C patients.

Impact of interleukin 28B rs12979860 C/T polymorphism on severity of disease and response to treatment in hepatitis delta.

Pegylated-interferon alpha (Peg-IFN α) is the therapy most commonly used to treat chronic hepatitis delta virus (HDV) infection. In the present study, we planned to investigate effect of IL28B polymorphism on response to Peg-IFN α therapy and disease progression in patients with chronic HDV. A total of 47 patients who received Peg-IFNα therapy for at least one year were investigated. The patients were divided into three groups based on their response to treatment: sustained viral response (SVR) (32%), unresponsive (53%), and relapse (15%). The groups were compared in terms of age, gender, blood biochemistry (albumin, total bilirubin, lactic acid dehydrogenase, ALT, AST, ALP, GGT), complete blood count, HBeAg, HBsAg, HBV-DNA, HDV-RNA, IL28B genotypes (CC, CT, TT), and results of liver biopsy. Regarding the investigation of IL28B genotype, the prevalence of CC, CT, and TT showed no difference among the three groups. In the SVR group, the prevalence of CC was 53%, CT was 47%, but there was no patient with TT. In the unresponsive group, prevalence of CC was 52%, CT was 32%, and TT was 16%. In the relapse group, prevalence of CC was 43%, CT was 57%, but there was no patient with TT genotype. No significant difference was found among the groups with sustained response, no response, and relapse in terms of CC and CT polymorphisms (p>0.05). No relationship was found between IL28B rs12979860 polymorphism and response to treatment and disease severity in patients with chronic HDV infection.

Interleukin-28B Polymorphism is a Pharmacogenetic Predictor during Sofosbuvir Plus Pegylated Interferon and Ribavirin Therapy for Chronic Hepatitis C Egyptian Patients

Background and Aim: Interleukin-28B (IL-28B) polymorphism is a predictor of sustained virologic response (SVR), spontaneous clearance and personalizing therapy of hepatitis C virus (HCV). This study aimed to determine IL28B rs12979860 polymorphism among chronic hepatitis C (CHC) Egyptian patients as a step in personalized HCV therapy and pharmacogenomics. Methods: CHC Egyptian patients were received sofosbuvir (SOF) plus pegylated interferon (PEG-IFN) and ribavirin (RBV) for 12 weeks. A total of 82 HCV infected Egyptian patients and 27 healthy individuals were included in the present study. CHC Patients were classified as achieving SVR if plasma HCV-RNA was undetectable (group A) and non-responders if plasma HCV-RNA was detectable (group B). IL28B genotypes were analyzed and their associations with SVR were selected. Results: The end of treatment response (ETR) rate was 100%. However, SVR12 was 76.8% (group A) and 23.2% relapsed (group B). Among studied CHC patients, 50% were IL-28B TT, 40.2% CT, and 9.8% CC. while the percentage of their frequencies in the healthy persons were 18.5%, 51.8%, and 29.6%, respectively. These results showed that the frequencies of TT genotypes were more prevalent in HCV patients. The genotype CC (n=8) achieved higher rates of SVR in group A (87.5%) than relapsed patients in group B (12.5%) and it had the least prevalence in group B compared with the frequencies of CT (21.2%) and TT (26.9%) genotypes. These results showed that CC genotype was associated with SVR. Conclusions: It can be concluded that the individuals with IL28B TT genotype are more susceptible to HCV infection in Egyptian patients and relapse. Moreover, IL-28B CC is useful for pretreatment prediction of the outcome of HCV treatment. Hence, IL28B polymorphism could be considered as a pharmacogenetic predictor in personalized HCV therapy and pharmacogenomics during SOF plus PEG-IFN and RBV therapy for chronic hepatitis C Egyptian patients.

NS5A-P32欠失を検出したC型慢性肝疾患Genotype 1bにおける治療効果の検討

1,516 patients with chronic HCV genotype 1b infection, who were treated with all-oral combinations of direct-acting antivirals (DAAs), were evaluated NS5A resistance-associated variants. 6 of 110 patients (5.45%), who could not achieve sustained virological response after Asunaprevir plus Daclatasvir for 24 weeks, were detected NS5A-P32 deletion. 4 of 6 patients with P32 deletion received retreatment of DAAs, and could not achieve sustained virological response. All of 6 patients with P32 deletion, were with three treatment-resistant host-factors of IL28B rs8099917 TG, FIB-4 index ≥3.25, and non-response for prior interferon-related therapy. Further understanding of the complex interaction between virus- and host-related factors might facilitate the development of more effective therapeutic regimens for HCV patients with P32 deletion.

Assessment of IL-28: rs12979860 and rs8099917 Polymorphisms in a Cohort of Cuban Chronic HCV Genotype 1b Patients.

Hepatitis C virus (HCV) is a significant global public health problem with >185 million infections worldwide. A series of genome-wide association studies (GWAS) has identified IL-28B polymorphisms as a predictor of sustained virologic response (SVR), as well as spontaneous clearance in chronic HCV genotype 1 patients. The objective of this work was to evaluate the prevalence of IL-28B rs12979860 and rs8099917 polymorphisms in Cuban chronic HCV patients. The study cohort included 73 chronic HCV patients treated with concomitant administration of CIGB-230 and nonpegylated IFN-α plus ribavirin (non-pegIFN-α/R) antiviral therapy. The genotype distribution of IL-28B rs12979860CC, -CT, and -TT was 29, 41, and 30%, respectively, and the distribution for rs8099917TT, -TG, and -GG was 63, 31, and 5%, respectively. The allele frequencies for rs12979860C and -T alleles were 51 and 49%, respectively, and for rs8099917G and -T alleles, the values were 21 and 79%, respectively. SVR rates were 55, 42, and 35% for rs12979860CC, -CT, and -TT, respectively, and 52, 30, and 25% for rs8099917TT, -GT, and -GG, respectively. The combined assessment of both single nucleotide polymorphisms (SNPs) resulted in 3 major genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TT, and rs12979860CT/rs8099917GG) with a frequency of 30.1, 21.9, and 20.5%, respectively. In patients with heterozygous variant rs12979860CT, the additional genotyping of rs8099917 contributed to increase the SVR rate. It is concluded that in Cuban HCV-infected patients, the responder homogeneous variant rs8099917TT is the most frequent genotype. The simultaneous genotyping of 2 IL-28B SNPs could improve the prediction of SVR contributing to better therapeutic decisions and treatment management.

HBV/HCV co-infection is associated with a high level of HCV spontaneous clearance among drug users and blood donors in China.

Understanding the biology of spontaneous clearance of hepatitis C virus (HCV) infection could lead to improved strategies to prevent the sequelae associated with chronic HCV infection. Chronic infections with hepatitis virus are very common in China, but the factors associated with spontaneous clearance of HCV have not been adequately studied. We evaluated the spontaneous clearance of HCV among 1918 drug users and 1526 HCV-seropositive blood donors in Guangzhou, China. Among participants who were co-infected with hepatitis B virus (HBV), 41.38% of drug users and 39.47% of blood donors had cleared their HCV infection without antiviral therapy compared to 9.41% of drug users and 16.73% of blood donors who were mono-infected with a single virus (P<.01). The proportion of subjects who had cleared their HCV infection was significantly greater in the co-infected subjects whose serum HBV DNA was greater than 2000IU/mL than those with lower levels. A multiple logistic regression analysis found female gender, IL28B rs8099917 TT genotype, HBV co-infection and blood donors (vs drug users) associated with increased spontaneous clearance of HCV infection. Although acute HCV infections are common in China, the incidence of chronic HCV may be reduced among the high prevalence of chronic HBV and IL28B genotypes associated with spontaneous clearance of HCV in Chinese populations.

Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort.

BackgroundNatural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans.ObjectivesWe aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy.MethodsSocio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All subjects were treated with Ursodeoxycholic acid at a dose of 15 mg/kg. HLA class II DRB1 alleles were compared with those of 237 healthy control subjects. IL28B genotyping for IL28B rs12979860 C/T and rs80899917 G/T was performed in a sub-group of patients.ResultsHLA-DRB1*07 (RR 5.3, P = 0.0008) and HLA-DRB1*08 (RR n.c. P = 0.0005) were significantly associated with the risk of PBC development. Patients younger than 45 years had significantly higher alanine aminotransferase (P = 0.038) and alkaline phosphatase levels (P = 0.047) than older cases. In comparison to non-CC rs12979860, patients with CC rs12979860 genotype showed an early histological stage at onset (93.8% vs. 62.5%, P = 0.03). After a mean follow-up of 61 months, three patients died, one underwent liver transplantation and sixteen (21.9%) had progression of the disease. At multivariate analysis, extrahepatic autoimmune disease (P = 0.04), pruritus (P = 0.008) and advanced histological stage (P < 0.0001) were independent risk factors for disease progression.ConclusionsHLA-DRB1*07 and HLA-DRB1*08 alleles increase susceptibility to disease development. At onset, higher biochemical activity was observed in younger patients, whereas rs12979860 CC genotype was associated with milder histological stage. Pruritus and coexistence of extrahepatic autoimmune diseases were significantly associated with poorer prognosis.

Prevalence and clinical implications of IL28B genotypes in Taiwanese patients with chronic hepatitis C.

Clinical implications of IL28B gene in Taiwanese chronic hepatitis C (CHC) patients remain unknown. We thus investigated the prevalence and clinical implications of IL28B rs8099917 genotypes in CHC patients with different hepatitis C virus (HCV) genotypes and healthy controls. A total of 200 HCV genotype 1 patients and 200 HCV genotype 2 patients who received liver biopsy, as well as 197 healthy controls were enrolled to determine the frequencies of IL28B rs8099917 genotypes. In addition, the association of IL28B rs8099917 genotype with baseline data, including HCV RNA level, HCV genotype, histological activity grade, fibrosis stage, and body mass index, were evaluated and further stratified by covariant factors. Compared with healthy controls, CHC patients had a lower prevalence rate of favorable IL28B rs8099917 TT genotype (81.0% vs. 89.3%, p=0.025). In addition, the prevalence rates of favorable TT genotype in patients with HCV genotypes 1 and 2 were 76.0% and 86.0%, respectively (p=0.007). Using ordered logistic regression analysis, higher fibrosis stages were found to be associated with a lower prevalence of TT genotype (p=0.033), but not histological activity grades (p=0.748). The association with fibrosis stages was more pronounced in female patients (p=0.024). In Taiwan, CHC patients have a lower frequency of favorable IL28B TT genotype than healthy controls. Among patients with CHC, the frequency of TT genotype is higher in HCV genotype 2 patients than in HCV genotype 1 patients. In addition, CHC patients with TT genotype, particularly females, have a lower likelihood of advanced fibrosis.