Spontaneous Clearance Group Research Articles

Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population.

Hepatocellular carcinoma associated with chronic hepatitis B virus infection seriously affects human health. Present studies suggest that genetic susceptibility plays an important role in the mechanism of cancer development. Therefore, this study focused on single nucleotide polymorphisms (SNPs) of MMR genes associated with HBV-HCC. Five groups of participants were included in this study, which were healthy control group (HC), spontaneous clearance (SC), chronic hepatitis B group (CHB), HBV-related liver cirrhosis group (LC) and HBV-related hepatocellular carcinoma group (HBV-HCC). A total of 3128 participants met the inclusion and exclusion criteria for this study. 20 polymorphic loci on MSH2, MSH3 and MSH6 were selected for genotyping. There were four case-control studies, which were HC vs. HCC, SC vs. HCC, CHB vs. HCC and LC vs. HCC. We used Hardy-Weinberg equilibrium test, unconditional logistic regression, haplotype analysis, and gene-gene interaction for genetic analysis. Ultimately, after excluding confounding factors such as age, gender, smoking and drinking, 12 polymorphisms were found to be associated with genetic susceptibility to HCC. Haplotype analysis showed the risk haplotype GTTT (rs1805355_G, rs3776968_T, rs1428030_C, rs181747_C) was more frequent in the HCC group compared with the HC group. The GMDR analysis showed that the best interaction model was the three-factor model of MSH2-rs1981928, MSH3-rs26779 and MSH6-rs2348244 in SC vs. HCC group (P=0.001). In addition, we found multiplicative or additive interactions between genes in our selected SNPs. These findings provide new ideas to further explore the etiology and pathogenesis of HCC. We have attempted to explain the molecular mechanisms by which certain SNPs (MSH2-rs4952887, MSH3-rs26779, MSH3-rs181747 and MSH3-rs32950) affect genetic susceptibility to HCC from the perspectives of eQTL, TFBS, cell cycle and so on. We also explained the results of haplotypes and gene-gene interactions. These findings provide new ideas to further explore the etiology and pathogenesis of HCC.

Reversibility of some oxidative stress markers in chronic hepatitis C patients after receiving direct-acting antiviral agents

IntroductionHepatitis C (HCV) is associated with extra-hepatic involvment, morbidity as well as metabolic changes. Whether these might be reversible if sustained virologic response (SVR) is achieved by direct-acting antiviral (DAA) therapy remains unknown. MethodsChronic hepatitis C (CHC) individuals receiving DAA treatment with SVR were compared to those who underwent spontaneous clearance (SC) of HCV infection at the 2-year follow-up. Plasma oxidative stress markers (oxidized low-density lipoprotein (oxLDL), 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA) and ischemia-modified albumin (IMA)) as well as progression of liver fibrosis were evaluated. ResultsCompared to SC individuals, those in the CHC group exhibited at baseline higher levels of oxLDL, 8-OHdG and IMA but not of MDA. In the SC group, 8-OHdG levels were elevated at 2-year post-SVR (p = 0.0409), while the DAA-treated CHC group showed decrease in oxLDL (p < 0.0001) and 8-OHdG (p = 0.0255) levels, approaching those of the SC group, but increased MDA (p = 0.0055) levels. Additionally, oxLDL levels were positively correlated with liver stiffness measurements at SVR (p = 0.017) and at 1 year post- SVR (p = 0.002). ConclusionsPlasma oxLDL showed post-SVR normalization after clearance of HCV viremia with DAAs and was associated with levels of hepatic fibrosis.

Comprehensive investigating of mismatch repair genes (MMR) polymorphisms in participants with chronic hepatitis B virus infection.

Background and aim: In this study, we focused on the relationship between single nucleotide polymorphisms in MMR genes and the occurrence and development of HBV infection. Materials and methods: A total of 3,128 participants were divided into five groups: negative control group (NeC), spontaneous clearance group (SC), chronic hepatitis B group (CHB), liver cirrhosis group (LC) and hepatocellular carcinoma group (HCC), CHB, liver cirrhosis and hepatocellular carcinoma constitute HLD. We conducted three case-control studies: NeC (840 cases) vs. HLD (1792 cases), SC (486 cases) vs. HLD (1792 cases) and CHB + LC (1,371 cases) vs. HCC (421 cases). 11 polymorphic loci in MLH1, MLH3, MSH5, PMS1 and PMS2 were involved in genotyping by Sequenom MassArray. The SNPStats performed Hardy-Weinberg equilibrium test. Linkage disequilibrium patterns were visualized using Haploview4.2. The GMDR (v0.9) was conducted to generalized multifactor dimension reduction analysis. The correlation, multiplicative interaction and additive interaction analyses were calculated by Logistic Regression through SPSS21.0. Matrix and programmed excel were also involved in the calculation of additive interaction. Results: In NeC vs. HLD group, MSH5-rs1150793(G) was a risk base to HBV susceptibility (nominal p = 0.002, OR = 1.346). We found multiplicative interaction between MLH1-rs1540354 (AA + AT) and PMS1-rs1233255 (AA) (nominal p = 0.024, OR = 1.240). There was additive interaction between PMS1-rs1233255 (AA) and PMS1-rs256554(CA + CC). In SC vs. HLD group, MLH1-rs1540354 (TT) was a risk genotype (nominal p < 0.05, OR>1). Through haplotype analysis, we found the linkage disequilibrium of three loci in MLH1. The results of GMDR showed the optimal five-locus model about the spontaneous clearance of HBV. In CHB + LC vs. HCC group, PMS2-rs12112229(A) was related to the cancerization of liver. Conclusion: We found rs1150793(G), rs1540354(T) and rs12112229(A) were significantly related to HBV susceptibility, spontaneous clearance of HBV and cancerization after infection, respectively.

The potential effect of HBV vaccination on off-treatment HBsAg reversion after interferon-induced HBsAg clearance

ABSTRACT Off-treatment HBsAg reversion occurs in a considerable number of chronic hepatitis B(CHB) patients after IFN(interferon)-induced HBsAg clearance. HBV vaccination protects the general population against HBV infection. However, it remains unclear whether HBV vaccination could prevent off-treatment HBsAg reversion in CHB patients with HBsAg clearance. CHB patients (n = 199) with HBsAg clearance were included in the current study, comprising spontaneous HBsAg clearance group (n = 51), NA (nucleoside/nucleotide analogues)-induced group (n = 36) and IFN-induced group (n = 112). Log-rank test was performed to compare the cumulative incidences of HBsAg reversion between groups. Cox regression model was used to identify the factors associated with off-treatment HBsAg reversion. The 5-year cumulative incidence of HBsAg reversion in IFN-induced group was significantly higher than that in NA-induced group or spontaneous group (27.6% vs. 3.3% vs. 8.1%, both p < .05). In IFN-induced group, 66.7% of CHB patients received HBV vaccination. The cumulative incidence of HBsAg reversion in individuals with strong responses to HBV vaccination (HBsAb level >100mIU/ml) was significantly lower than that in those with weak responses to HBV vaccination (HBsAb level ≤100mIU/ml) or without HBV vaccination in IFN-induced group (7.7% vs. 58.5% vs. 31.9%, both p < .05). Multivariate Cox regression analysis confirmed strong responses to HBV vaccination were independently associated with a lower cumulative incidence of HBsAg reversion after IFN-induced HBsAg clearance (HR = 0.246, 95%CI: 0.066–0.907, p = .035). HBV vaccination has potential to prevent off-treatment HBsAg reversion in CHB patients after IFN-induced HBsAg clearance via a sufficiently high level of HBsAb, helping clinicians optimize the clinical management of such patients.

Relationships between IL-1β, TNF-α genetic polymorphisms and HBV infection: A meta-analytical study.

IL-1β and TNF-α have been demonstrated as pro-inflammatory cytokines to participate in the innate immune response and suppression of HBV infection. However, the exact relationship between IL-1β, TNF-α gene polymorphisms and HBV infection remains unknown. Our study aims to assess the associations between IL-1β, TNF-α gene polymorphisms and HBV infection. A systematic literature search of PubMed and Embase databases was conducted through February 2020, and studies that were included in the present meta-analysis should fulfil the following conditions: (1) case-control studies focusing on the associations between IL-1β, TNF-α polymorphisms and HBV infection; (2) patients in the case group should be tested positive for the HBsAg and/or HBV-DNA without liver cirrhosis or hepatocellular carcinoma; (3) the control group including healthy population or HBV spontaneous clearance population; (4) odds ratios (ORs) and their 95% confidence intervals (CIs) could be calculated based on the allele and genotype frequencies provided in articles. The quality of included studies was assessed according to the Newcastle-Ottawa scale (NOS) assessment system. Pooled ORs and 95% CIs were used to analyze the strength of associations. Subgroup analysis was performed according to ethnicity and control type. In the present meta-analysis, 49 articles including 10,218 cases and 9,557 controls were enrolled and seven polymorphisms (IL-1β rs16944, rs1143634, TNF-α rs1799724, rs1799964, rs1800629, rs1800630, rs361525) were studied. In overall meta-analysis, significant associations were found in IL-1β rs1143634, TNF-α rs1799724 and TNF-α rs1799964. For subgroup analysis under ethnicity, TNF-α rs1799724 and rs1800630 were markedly related to HBV infection in both Asian and Caucasian populations. In terms of control type subgroup, TNF-α rs1799724, rs1799964, rs1800630 were significantly associated with HBV persistence in HBV spontaneous clearance group. In the present study, we identified that three polymorphisms (IL-1β rs1143634, TNF-α rs1799724, rs1799964) might serve as potential genetic biomarkers in HBV infection.

Influence of HLA-C environment on the spontaneous clearance of hepatitis C in European HIV–HCV co-infected individuals

Natural killer (NK) cell functions are regulated by diverse inhibitory and activating receptors, including killer cell immunoglobulin-like receptors (KIR), which interact with human leukocyte antigen (HLA) class I molecules. Some KIR/HLA genetic combinations were reported associated with spontaneous clearance (SC) of hepatitis C virus (HCV) but with discordant results, possibly reflecting KIR and/or HLA gene polymorphism according to populations. KIR/HLA genetic combinations associated with both an exhaustive NK and T cell repertoire were investigated in a cohort of HIV-HCV co-infected individuals with either SC (n=68) or chronic infection (CI, n=163) compared to uninfected blood donors [controls (Ctrl), n=100]. Multivariate analysis showed that the HLA C2C2 environment was associated with SC only in European HIV-HCV co-infected individuals [odds ratio (OR)=4·30, 95% confidence interval=1·57-12·25, P=0·005]. KIR2D+ NK cell repertoire and potential of degranulation of KIR2DL1/S1+ NK cells were similar in the SC European cohort compared to uninfected individuals. In contrast, decreased frequencies of KIR2DS1+ and KIR2DL2+ NK cells were detected in the CI group of Europeans compared to SC and a decreased frequency of KIR2DL1/S1+ NK cells compared to controls. Regarding T cells, higher frequencies of DNAX accessory molecule-1 (DNAM-1)+ and CD57+ T cells were observed in SC in comparison to controls. Interestingly, SC subjects emphasized increased frequencies of KIR2DL2/L3/S2+ T cells compared to CI subjects. Our study underlines that the C2 environment may activate efficient KIR2DL1+ NK cells in a viral context and maintain a KIR2DL2/L3/S2+ mature T cell response in the absence of KIR2DL2 engagement with its cognate ligands in SC group of HCV-HIV co-infected European patients.

Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae: data from GToG

ObjectivesNeisseria gonorrhoeae (NG) infection can resolve without antibiotic treatment, however the literature describing the frequency of clearance at individual sites, how rapidly it occurs and potential predictive factors is limited....

Association between Signal Transducer and Activator of Transcription 4 Genetic Polymorphisms and the Spontaneous Clearance of Hepatitis B Surface Antigen: A Large Population Case Control Study in China

Aim: Several host factors mediating immune response influence susceptibility to Hepatitis B Virus (HBV) infection, ability to clear the virus, and maintenance of a chronic state. Signal Transducer and Activator of Transcription 4 (STAT4) variations are correlated with the risk of developing autoimmune diseases. However, there have been few studies to assess the relationship between STAT4 variations and Hepatitis B surface Antigen (HBsAg) clearance in adults infected with HBV. Our aim was to evaluate the association between genetic variants in STAT4 and HBsAg clearance in a large sample size population. Methods: This case control study included Chronic Hepatitis B (CHB) (n = 1.688), HBsAg Clearance after Treatment (TC) (n = 170), HBV Uninfected (HC) (n = 1.012), and HBsAg Spontaneous Clearance (SC) (n = 1,052) patients. In the CHB group, patients were categorized into four subgroups: the Immune Tolerant (IT), Immune Active (IA), Inactive (IC), and Immune Reactivation (IR) phases, with 97, 855, 198, and 538 patients in each subgroup, respectively. Results: We found that the G allele in STAT4 rs7574865 was more frequent in the CHB and TC groups, compared with the SC group, whereas the STAT4 rs7574865 GG genotype was more frequent in the CHB and TC group, compared with the SC group in the dominant model. However, there was no statistical significance in genotype between TC and CHB, nor between the IT, IA, IC, and IR groups. Conclusions: The prevalence of the minor allele rs7574865 T was higher in subjects with spontaneously cleared HBV infections than in CHB patients.

Spontaneous Clearance After Relapse Following Direct-Acting Antiviral Treatment for Chronic HCV Infection

Direct-acting antivirals (DAAs) cure most cases of chronic hepatitis C virus (HCV) infection. However, a small percentage of patients relapse with reappearance of viremia after a full course of therapy. Although most who relapse require retreatment, some patients spontaneously clear HCV without additional therapy. We studied patients who relapsed with detectable HCV RNA after a full course of DAA therapy and then spontaneously cleared the HCV infection without retreatment. We performed a case-control study of patients who spontaneously cleared chronic HCV infection following a documented relapse after DAA therapy at the Toronto Centre for Liver Disease, from January 2014 through December 2017. We collected clinical information at baseline, 12 weeks after treatment, and 6 months after relapse and compared data among spontaneous clearers, patients with persistent relapse, and patients who achieved a sustained virologic response to therapy 12 weeks after treatment (SVR12). The strength and breadth of interferon gamma cytokine secretion by HCV-specific T cells from peripheral blood were quantified using the ELISPOT assay. Of the 1032 individuals with chronic HCV infection who were treated with DAAs, 93 patients had a documented relapse. Of these patients, 12 patients (13%) spontaneously cleared HCV within 6 months after the documented relapse without additional therapy. The spontaneous clearers had low levels of HCV RNA (<4 log IU/mL in 11 of 12) and normal levels of alanine aminotransferase at the time of relapse, much like patients with an SVR12. There was no significant difference between the spontaneous clearance group and the SVR12 group in magnitude and breadth of HCV-specific T cell responses. In a case-control study of patients who spontaneously cleared chronic HCV infection following a relapse after DAA therapy, we found that it is important to confirm viremia prior to retreatment after the relapse-particularly for individuals with low levels of HCV RNA and normal or near-normal levels of alanine aminotransferase after treatment.

Correlation of CpG methylation of the Pdcd1 gene with PD-1 expression on CD8+ T cells and medical laboratory indicators in chronic hepatitis B infection.

The negative signal provided by some co-inhibitory factors such as programmed cell death-1 (PD-1) has been associated with chronic hepatitis B (CHB) infection induced-T cell exhaustion, although the correlation of CpG methylation of the Pdcd1 gene with PD-1 expression and medical laboratory indicators in CHB infection has not yet been elucidated. Blood samples from 20 CHB infection patients and 20 spontaneous clearance (SC) patients were collected. Percentages of PD-1-positive CD8+ T cells were analyzed by flow cytometry. The percentage of CpG methylation at the Pdcd1 locus was analyzed by bisulfite sequencing. Student's t test, Pearson and Spearman's correlation, and Mann-Whitney tests were used in the statistical analysis. Percentages of PD-1-positive CD8+ T cells in peripheral blood T cells were significantly higher in CHB patients than in the SC group (p < 0.001). The methylation level of Pdcd1 was significantly lower in CHB patients (p < 0.001) and the methylation level of Pdcd1 was negatively correlated with PD-1 expression level in CD8+ T cells (p < 0.001) and hepatitis-B surface antigen (HBsAg) (p < 0.001). The results of the present study suggest that Pdcd1 methylation is correlated with PD-1 expression on CD8+ T cells and correlated with HBsAg and alanine aminotransferase. The results may provide new ideas regarding anti-PD-1 inhibitors, and epigenetic regulators such as demethylation inhibitors could represent more successful therapeutic strategies in hepatitis B infection patients.

Can Direct-Acting Antiviral Treatment Change the Immunologic Risk Profile in Patients Infected with Hepatitis C Virus Who Are on the Cadaveric Waiting List?

BackgroundIn patients with hepatitis C virus (HCV) infection, the activation of the immune system by the virus or viral proteins leads to the production of numerous autoantibodies and clinical manifestations. The objectives of this study were to investigate the relationship between HCV and anti-HLA antibodies, as well as the effect of viremia on the antibody response and of direct-acting antivirals (DAAs) on anti-HLA antibody persistence in patients on the waiting list for a cadaveric kidney transplant. MethodsA total of 395 patients from the cadaveric renal transplant waiting list were included in the study. The patients were grouped according to the presence of HCV infection, and patients with HCV positivity were further divided into a spontaneous clearance group and a persistent group. Anti-HLA antibodies were examined before and after treatment of the patients in the persistent group. The One Lambda Luminex method (Thermo Fisher Scientific, Waltham, MA, United States) was used to assess both HLA class I and II alleles and the anti-HLA antibody profile. ResultsAnti-HLA class I and II antibodies were detected in 48.2% and 55.1%, respectively, of the patients infected with HCV and in 21.8% and 20.4%, respectively, of the patients who were not infected. The level of anti-HLA A3, A11, B72, B52, Cw6, Cw16, DR3, and DQ4 antibodies was significantly higher in the patients infected with HCV. There was no statistically significant difference in class I and II antibody titration between the HCV-infected spontaneous clearance group and the persistent group (class I mean fluorescence intensity [MFI] ± SD: 13,583 ± 6224, 13,450 ± 9540, P = .808; Class II MFI ± SD: 13,000 ± 8673, 8440 ± 8302, P = .317, respectively). There was no significant difference in the class I and class II anti-HLA antibody profile and titration in the persistent group after treatment with DAAs (P > .05). ConclusionsThe results of this study demonstrated that hepatitis C DAA treatment did not change the anti-HLA antibody profile and titration.

HCV genotype 6 prevalence, spontaneous clearance and diversity among elderly members of the Li ethnic minority in Baisha County, China.

The epidemiology of hepatitis C virus varies widely across geographical regions and ethnic groups. Our previous study showed that 6 strains isolated from Baisha County, Hainan Island, China, were all new genotype 6 (gt6) subtypes which differed significantly from subtypes of other regions. In the current study, we conducted a comprehensive epidemiological survey of HCV in the Li ethnic group, native to Baisha County. Anti-HCV antibodies were detected by 2 independent ELISAs in all participants, and positive results confirmed by the recombinant immunoblot assay (RIBA) and HCV RNA viral loads were measured. Univariate chi-square test and multivariable logistic regression analyses were used to determine the risk factors for HCV infection and spontaneous clearance rates. Indeterminate RIBA results were excluded or included in analyses; consequently, findings were expressed as a range. Direct sequencing of partial regions within NS5B and E1 was employed for genotyping. Among 1682 participants, 117 to 153 were anti-HCV positive (7.0%-9.1%), with 42.7%-52.6% confirmed to have cleared infection. Anti-HCV positivity was associated with older age (≥60years) (OR=0.02, 95% CI 0.01-0.05, P<0.01) and surgery (OR=2.75, 95% CI 1.36-5.57, P<0.01), with no significant difference found between the HCV infection group and the HCV spontaneous clearance group. The gt6 subtype distribution characteristics of Baisha County were unique, complex and diverse. The sequences did not cluster with known gt6 subtypes but formed 4 Baisha community-specific groups. HCV infection in members of the Li minority ethnic group is characterized by high prevalence rates in the elderly, high spontaneous clearance rates and broad gt6 diversity.

Association between Interleukin-21 and Interleukin-21 receptor gene polymorphisms with susceptibility to chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population

Hepatitis B virus (HBV) infection is a major public health concern due to the infection often leads to chronic infection, liver cirrhosis and also liver cancer. The host immune response to HBV infection and also genetic background play significant role in outcome of infection. Single nucleotide polymorphisms (SNPs) are the most important kind of variation in genetic sequences that caused by point mutations. As cytokines have major roles in viral infections, it seems that cytokine gene polymorphisms are independently associated with response to viral infections. Interleukin 21 (IL-21) plays an influential role in both innate and adaptive immune responses. Its specific receptor, IL-21R, produced and located on the surface of T, B and natural killer (NK) cells and is critical for the proliferation and differentiation of these immune effector cells. Many studies confirmed that the IL-21 involved in response to viral infections.We aimed to investigate the association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population. MethodsIn this study, blood samples were gathered from 320 patients with chronic HBV and 310 healthy controls and also 120 HBV spontaneous clearance individuals. Following genomic DNA extraction, genotypes of the selected SNPs determined by PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using Chi-square, Logistic Regression, ANOVA and Independent Samples t-Test. ResultsAccording to our results, in IL-21R (rs3093390 C/T) gene polymorphism, allele frequency of T is statistically different in the HBV spontaneous clearance group compared to chronic HBV cases. But there is no significant difference between G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) genotypes distribution in three groups.Also we found that higher serum aspartate transaminase (AST) level in HBV spontaneous clearance group is significantly associated with TT genotype of IL-21 (rs2055979) compared to GG genotype (P value = 0.006). DiscussionOur results showed that T allele frequency in IL-21R (rs3093390 C/T) gene polymorphism could consider as a host genetic factor for HBV spontaneous clearance. Probably we can serve it as a potential prognostic genetic marker for spontaneous clearance of HBV infection.

Correlation of IL28Brs12979860 genotype and gender with spontaneous clearance of HCV infection: a Pakistani cross-section study.

There is a strong correlation of IL28B rs12979860 genetic variations and gender with spontaneous clearance of hepatitis C virus (HCV) infection. HCV-infected subjects were categorized into HCV spontaneous clearance (SC) group and chronic hepatitis C (CHC) group on the basis of anti-HCV antibodies and HCV RNA level and follow-up of 6 months. 35 subjects were classified in SC group and 165 subjects were classified in CHC group. IL28B rs12979860 genotypes were determined by allele-specific PCR. Multinominal logistic regression analyses revealed that both genders favor IL28B rs12979860 CT genotype (OR: 4.80; CI: 2.22-10.35; p =0.0005) and (OR: 3.47; CI: 1.63-7.43; p =0.001) for male and female, respectively, are significant in spontaneous clearance of HCV infection.

Accelerated decline in anti-HCV antibody levels in spontaneous HCV seroconverters with HIV co-infection

Objective To investigate the influence on anti-HCV antibody levels in spontaneous HCV seroconverters co-infected with HIV. Methods A retrospective study was conducted on people with a history of blood donation in Wangying Village, Shangcai County, Henan Province in 2009 and 2017.According to the infection status in 2009, patients who were positive for anti-HCV antibody were divided into four groups: HIV-negative chronic HCV infection group (HCVc), HIV-negative spontaneous HCV clearance group (HCVr), HIV-positive chronic HCV infection group (HIV+ HCVc), HIV-positive spontaneous HCV clearance group (HIV+ HCVr). All patients were followed up in 2017 and those who were lost to follow-up, received HCV treatment or were reinfected with HCV (only for those of HCV seroconverters) were excluded from this study.Altogether 167 patients met the inclusion criteria (HCVc: n=65; HCVr: n=34; HIV+ HCVc: n=44; HIV+ HCVr: n=24). A horizontal comparison of anti-HCV antibody levels among the above four groups in 2009 and a longitudinal comparison of changes in anti-HCV antibody in each group from 2009 to 2017 were respectively conducted. Results The horizontal comparison indicated that the levels of anti-HCV antibody were higher in chronic HCV-infected patients than in HCV seroconverters no matter whether they were co-infected with HIV or not (both P<0.000 1). After comparison of anti-HCV antibody titers in 2017 and 2009, no significant changes were found in HCVc or HIV+ HCVc group.The levels of anti-HCV antibody in HCVr and HIV+ HCVr groups decreased significantly from 2009 to 2017 (both P<0.000 1). HIV+ HCVr group showed a faster decline in anti-HCV antibody level than HCVr group (P=0.003 9). Significant negative correlations between the decline speed in anti-HCV antibody sample/cut-off (S/CO) values and the initial anti-HCV antibody S/CO values (in 2009) were found in both HCVr (r=-0.517 7, P=0.001 7) and HIV+ HCVr groups (r=-0.753 2, P<0.000 1). The decline speed in anti-HCV antibody in HIV+ HCVr patients was found to be negatively correlated with their CD4+ T cell counts in 2009 (r=-0.563 8, P=0.004 1). Moreover, the seroreversion rate of anti-HCV antibody in patients of the HIV+ HCVr group was higher than that of HCVr group (P=0.027 5). Conclusion HIV co-infection can accelerate the decline of anti-HCV antibody in spontaneous HCV seroconverters.This study indicates that in a large-scale retrospective epidemiological investigation especially for HIV-infected populations, the prevalence of anti-HCV antibody may be underestimated. Key words: Anti-HCV antibody; Spontaneous HCV clearance; HIV co-infection; Decline in anti-HCV antibody; Correlation

Association of HLA-DQ and IFNL4 polymorphisms with hepatitis B virus infection and clearance

Objective: To confirmed the polymorphisms of HLA-DQ and IFNL4 were associated with HBV infection and clearance in a Chinese population. Methods: The Sequenom MassARRAY MALDI-TOF system was used to genotype the HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917. A binary logistic regression test was conducted to estimate the relative risk of these SNPs with HBV infection and clearance. Haploview4.2 software and PHASE software (v2.0.2) were employed to analyze linkage disequilibrium (LD) and haplotype frequencies. The MDR program was applied to analyze interactions between SNP and SNP.Statistical analysis was performed using SPSS 19.0 and P-values were corrected by Bonferroni's corrections. Results: A total of 1,069 subjects were recruited and divided into three groups: 238 healthy controls(HC), 397 with HBV-related chronic liver disease (CLD), 434 with spontaneous clearance (SC). The rs9275319TT was most frequently identified among all groups(86.2% in the CLD group, 77.6% in the SC group, and 75.9% in the HC group).Carriage of the rs9275319 C allele was a protective factor for chronic HBV infection (the allele model: P = 0.000 3, OR,0.514; 95% CI, 0.359-0.738) and clearance (the allele model: P = 0.002, OR, 1.659; 95% CI, 1.197-2.300). HLA-DQ rs9275319 showed a significant association with HBV infection (allele model, OR, 0.514; 95% CI, 0.359-0.738, adjusted P = 0.000 3) and spontaneous clearance (allele model, OR, 1.659; 95% CI, 1.197-2.300, adjusted P = 0.002). However, there was no association between IFNL4 polymorphism and HBV infection((allele model: P = 0.082 for rs368234815; P = 0.063 for rs12971396; P = 0.517 for rs12979860; P =0.695 for rs8099917) or spontaneous clearance ((allele model: P = 0.358 for rs368234815; P = 0.105 for rs12971396; P = 0.640 for rs12979860; P = 0.640 for rs8099917;all P > 0.05). The multifactor dimensionality reduction (MDR) test showed there was a three-way interaction (rs12971396, rs12979860, and rs9275319) between IFNL4 and HLA-DQ polymorphisms for HBV infection (permutation P = 0.009 for the best factor model) and clearance (permutation P = 0.014 for the best factor model). Conclusion: The SNP-SNP interaction between HLA-DQ and IFNL4 is associated with the regulation of HBV infection and natural clearance.

Circulating microRNAs as potential biomarkers of HBV infection persistence

ObjectivesTo investigate different microRNA (miRNA) expression profile in patients of hepatitis B virus (HBV) infection compared with virus spontaneous clearance ones, and try to find new biomarker for diagnosis and treatment assessment. MethodsmiRNA expression profiling was analyzed in patients with HBV infection and patients with virus spontaneous clearance by Affymetrix Gene Chip miRNA 4.0 Arrays. The differently expressed miRNAs, as verified by RT-PCR, were analyzed and compared with each other in the two groups of patients. ResultsSignificant difference was found in the expression of miR-29b, miR-34, miR-4485, miR-3180, miR-125, miR-330-3p, miR-1468 in spontaneous clearance group and CHB group. miR-29b, miR-34, miR-4485 was significantly increased in CHB group, while miR-125, miR-330-3p, miR-1468, miR-3180 was significantly decreased. Correlation analysis indicate only miR-29b was positive correlation with HBsAg. ConclusionsThese results indicated above miRNAs may be associated with HBV infection persistence, and provided us new ideas for finding potential biomarkers.

Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study

People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID). 5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9-8·7), and the median time to reinfection was 3·0 years (1·5-5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15-1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44-1·76) than in the SVR group (0·48, 0·36-0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00-3·68), individuals co-infected with HIV (2·25, 1·78-2·85), and PWID (1·53, 1·21-1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54-0·98), as was engagement with mental health counselling services (0·71, 0·54-0·92). The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission. The British Columbia Centre for Disease Control and the Canadian Institutes of Health Research.

Hepatitis C virus infection in patients with hemophilia in Korea: Is antiviral therapy effective and safe?

Hepatitis C virus infection in patients with hemophilia in Korea: Is antiviral therapy effective and safe?

Correlation Analysis Between Protein Phosphatase-1 Regulatory Inhibitor Subunit-11 Polymorphism and Hepatitis C Virus Spontaneous Clearance

Objective To explore the association of protein phosphatase-1 regulatory inhibitor subunit-11 (PPP1R11) polymorphism and hepatitis C virus (HCV) spontaneous clearance.Methods From January 2009 to May 2013,a total of 328 blood donors whose blood samples were anti-HCV positive with enzyme-linked immunosorbent assay (ELISA) were included into this study.According to follow-up results,they were divided into spontaneous clearance group whose HCV RNA were negative but anti-HCV recombinant immunoblot assay results were positive (n =134),and chronic infection group whose HCV RNA were positive (n=198).Polymerase chain reaction with sequence specific primer(PCR-SSP) was performed to determine the genotype of rs3807031 of PPP1R11.Statistical software SPSS was used to analyze the association between genotype of rs3807031 and HCV spontaneous clearance.Results The average age of donors in spontaneous clearance group was (28.8± 10.2) years old,which was significantly lower than that of chronic infection group whose average age was (31.0±9.0) years old (t=2.135,P =0.034).Higher percentage of female was observed in spontaneous clearance group compared to chronic infection group (35.8％ vs 21.6％ ; x2 =7.994,P=0.005).Importantly,rs3807031 A allele composed 30.6％ and 22.4％,while C allele composed 69.4％ and 77.6％ in spontaneous clearance and chronic infection group,respectively.The frequencies of rs3807031 alleles were statistically different between these two groups (x2 =5.538,P =0.023).Multivariate unconditional logistic regression analysis showed that gender (OR=1.957,95％CI:1.118-3.224,P=0.008) and genotype of rs3807031 (OR=0.650,95％CI:0.450-0.973,P =0.021) are independent factors associated with HCV spontaneous clearance.Conclusions PPP1R11 rs3807031 is associated with HCV spontaneous clearance,which has the potential to predict the spontaneous clearance of HCV infection.Our results provide information to the research on the mechanism and molecular marker of HCV spontaneous clearance. Key words: Hepatitis C, chronic; Hepacivirus; Genotype; Polymorphism, single nucleotide