Viral selection pressure and CD4+T cell epitope in HLA-DRB1 * 11:01 of HCV infected patients / 中国输血杂志

【Objective】 HLA-DRB1 * 11:01, as a class HLA-Ⅱ gene, was reported to be associated with spontaneous clearance of HCV in Han and Li population. Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1 * 11:01 positive infected patients. 【Methods】 The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1 * 11:01 positive and negative groups in Guangdong were respectively analyzed. The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method. Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups. 【Results】 The positive selection sites (PSSs) of E1E2 and NS3 of common HCV 6a in HLA-DRB1 * 11:01 negative group were greater than those in HLA-DRB1 * 11:01 positive group. Furthermore, the number of PPSs in CD4+T cell peptide in HLA-DRB1 * 11:01 negative group were also greater than those in HLA-DRB1 * 11:01 positive group; Both groups of HCV 6a had a population growth in Guangdong, and the expansion trend of HLA-DRB1 * 11:01 negative group was significantly higher than that of HLA-DRB1 * 11 :01 positive group. Compared to HCV chronic infection group, the response rate of HCV spontaneous clearance group to five peptides (C-52 E2691-707, C-119 NS31545-1560, C-134 NS4A1669-1684, C-154 NS4B1912-1927, C-159 NS4B1929-1944) was higher. However, the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS31497-1512, C-130 NS31650-1665). When HLA-DRB1 * 11:01 typing was considered, there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1 * 11:01 positive and HLA-DRB1 * 11:01 negative groups. 【Conclusion】 This study revealed the relationship between viral selection pressure of HLA-DRB1 * 11:01 HCV infected persons and CD4+T cell antigen epitopes. At the same time, CD4+ T cell antigen epitopes of HCV pan-genotype were obtained, providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.

Hepatitis C: A Review on Current and Emerging Genotyping Assays

@#Hepatitis C is a global public health concern that infects millions of people worldwide. The continual discovery of new genotypes and subtypes of hepatitis C virus (HCV) is an indication of a persistent molecular evolution of the virus. This remains a concern in the efforts towards hepatitis C elimination, as effective management of the disease is, in part, dependent on the HCV genotype responsible for the infection. Accurate HCV screening and quantification using rapid but highly sensitive and reliable methods are crucial for the diagnosis and subsequent management of HCV-related diseases. Thus, this article discusses HCV and the common methods employed for HCV detection and genotyping. While nucleotide sequencing and phylogenetic analysis of core/E1 and NS5B region are regarded as the gold standard and the most recommended method used for HCV genotyping, electrochemical sensors are being explored for their rapidity.

Status of clinical research in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts / 器官移植

Antiviral therapy for chronic hepatitis C virus (HCV) infection has entered the era of direct antiviral agent (DAA), and up to 95% of patients could be clinically cured. Under this circumstance, HCV infection has gradually changed from relative contraindication to surgical indication for kidney transplantation. However, at present, the number of kidney transplantation from HCV-infected donors or recipients has been rarely reported in China. The short-term follow-up data of HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts in other countries have confirmed that DAA yields high cure rate and safety in the treatment of HCV infection, and recipients could obtain favorable short-term survival and allograft outcome. However, the long-term safety of HCV-infected kidney transplantation remains to be validated by clinical trials with large sample size and long-term follow-up. In this article, the virological clearance, allograft outcome and safety of DAA use in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts under the intervention of DAA were investigated, aiming to evaluate clinical safety and efficacy of this pattern of kidney transplantation and deepen the understanding of safe use of HCV-positive organs.

Prevalence of Hepatitis B and Hepatitis C Virus Infection in Patients with Advanced Renal Failure: A Tertiary Care Centre Study from North Indian Population

Abstract: Viral hepatitis (Hepatitis B Virus (HBV) & Hepatitis C Virus (HCV)) related liver disease is a leading cause of morbidity and mortality especially in the patients with advanced renal failure who are treated with dialysis, and this is due to high number of blood transfusion sessions and/or cross contamination from the dialysis circuits. Aims & Objectives: This study aimed to determine the prevalence of HBV and HCV infections in patients with advanced renal failure (ARF). Materials & Methods: A cross-sectional study was done in joint collaboration of Department of Nephrology and Department of Gastroenterology, KGMU, Lucknow, from June 2018 to June 2020 among, CRF patients. Clinical data such as age, gender, duration of dialysis; number of transfusions, Serum sample was collected from each patient. Serological markers for HBV and HCV were determined with ELISA by using commercial diagnostic kits. HCV-RNA and HBV-DNA were determined quantitatively by polymerase chain reaction (PCR) assay. Results: A total 934 patients with advanced renal failure attended the nephrology OPD. Out of 934 patients, 65 (6.96%) patients screened positive for HBV/HCV infection. The results of this study also showed that the prevalence of viral hepatitis infection in the haemodialysis (HD) and without HD patients is 8.25% and 6.3% respectively. Conclusion: It has been found that viral infections, particularly HBV and HCV infections are common in advanced renal failure patients who are on HD.

Virucidal activity of oriental hornet Vespa orientalis venom against hepatitis C virus

Abstract Background Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). Results The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. Conclusion WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.

Virucidal activity of oriental hornet Vespa orientalis venom against hepatitis C virus

Background Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). Results The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. Conclusion WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.(AU)

Research progress on the application of liver transplantation in HIV combined with HCV positive patients / 器官移植

With the advent of highly active antiretroviral therapy (HAART), acquired immune deficiency syndrome (AIDS) has gradually evolved from an incurable terminal disease to a controllable chronic disease. Due to the extended survival of AIDS patients, chronic renal failure and (or) chronic liver failure have become the main cause of death, and AIDS patients with chronic liver failure are constantly complicated with hepatitis C virus (HCV) infection. Human immunodeficiency virus (HIV) infection was previously considered as a contraindication for liver transplantation. With the deepening of medical cognition and improvement of surgical management experience, the quantity of HIV positive liver transplantation recipients has been steadily elevated and high long-term survival rate has been achieved. Nevertheless, the 3-, 5-, and 10-year survival rates after liver transplantation of HIV combined with HCV positive patients remain extremely low. In this article, the development of liver transplantation in HIV positive patients, the disease progression of HIV combined with HCV positive patients, and the treatment for the recurrence of viral hepatitis C after the operation were summarized.

Direct-acting antivirals response in hepatocellular carcinoma: Does the presence of hepatocellular carcinoma matter?

During the clinical trial development of directly acting antivirals (DAAs), evidence regarding the treatment efficacy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) was scarce because these patients have always been excluded. Apart from the clinical trials, more HCC patients are currently being treated in daily practice, given that these treatments are highly effective and involve well-tolerated regimens. Large scale, real-world studies have demonstrated potentially suboptimal antiviral treatment efficacy in HCC patients who received DAAs. It is postulated that the impairment of the bioavailability of DAAs may account for the inferior treatment response. However, the results could not be generalized across all studies. The differing results were attributed to diverse patient characteristics, suboptimal regimens or imprecise definitions of active cancer statuses at the time of treatment initiation. Additional large-scale studies that utilize the treatment of choice in clearly defined HCC patients with different disease severities are warranted to clarify the issue.

DNA sequences homologous to hepatitis C virus (HCV) in the extrachromosomal circular DNA in peripheral blood mononuclear cells of HCV-negative subjects / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: This study aimed to investigate DNA sequences that are substantially homologous to the corresponding RNA sequence sections of the hepatitis C virus (HCV). These DNA sequences are present in the whole DNA extracted from peripheral blood mononuclear cells (PBMCs) of HCV-negative subjects. We presumed that these experimentally proven 5′-noncoding region (5′-NCR) homologous DNA sequences could be contained in the extrachromosomal circular DNA (eccDNA) fraction as part of the whole cellular DNA. Methods: Home-made polymerase chain reaction (PCR) with whole cellular and isolated eccDNA, nucleotide basic local alignment search tool (BLASTn) alignments, and tests for patterns of methylation in selected sequence sections were performed. Results: The PCR tests revealed DNA sequences of up to 320 bp that broadly matched the corresponding sequence sections of known HCV genotypes. In contrast, BLASTn alignment searches of published HCV 5′-NCR sequences with human genome databases revealed only sequence segments of up to 36 bp of the 5′-NCR. The composition of these sequences shows missing base pairs, base pair mismatches as well as complete homology with HCV reference sequences. These short sequence sections are present in numerous copies on both the same and different chromosomes. The selected sequence region within the DNA sequences of the 5′-NCR revealed a broad diversity of individual patterns of methylation. Conclusions: The experimental results confirm our assumption that parts of the HCV 5′-NCR genomic RNA sequences are present at the DNA level in the eccDNA fraction of PBMCs. The tests for methylation patterns therein revealed individual methylomes which could represent an epigenetic feature. The respective sequence section might be subject to genetic regulation.

Upcoming direct acting antivirals for hepatitis C patients with a prior treatment failure

Despite the high efficacy of direct acting antivirals (DAAs) not all patients successfully clear hepatitis C virus infection, in fact, approximately 1–3% fail to reach a sustained virological response 12 weeks after end of treatment. DAA failures are characterized by advanced liver disease, specific genotypes/subtypes and resistance associated substitutions to the DAA class they have been treated with. Current European Association for the Study of the Liver guidelines recommend three therapeutic options for such patients. The first is a 12 week course of sofosbuvir (SOF), velpatasvir (VEL) and voxilaprevir (VOX), which has shown to be effective in 90–99% of patients and was granted A1 level recommendation. The second option, reserved for patients who have predictors of failure consists in 12 weeks regimen with glecaprevir (GLE) and pibrentasvir (PIB), effective in 90–97%. Finally, although not supported by published data, for especially difficult to treat patients there should theoretically be a benefit in prolonged combinations of SOF+GLE/PIB or SOF/VEL/VOX±ribavirin. This review presents the latest evidence from both clinical trials and real-life on such therapeutic strategies.

Assessment of prevalence of sexually transmissible infections among voluntary blood donors and its comparison with replacement donors at Hassan Institute of Medical Science, Hassan, Karnataka, India

Background: Hepatitis B virus, Hepatitis C virus and Human immunodeficiency virus (HIV) are important STDs which can be transmissible to the recipients of blood transfusion. The aim of the present study is to study the seroprevalence of HIV, HBV and HCV infection in the blood among voluntary and replacement donors in HIMS Hassan during 2010 to 2012.Methods: A retrospective study was conducted at blood bank of HIMS, Hassan for the years 2010 to 2012. The donors with Hemoglobin>12gm% for both sexes, weight >50 kg, no history of chronic illness, hepatitis, high risk behaviours were included in the study. All the blood samples collected were screened for HIV, HBV and HCV using ELISA kits. All the blood samples were sent to NACO (national AIDS control organization) and subjected to NAT (nucleic acid test) for detection of antigens. Results compared for both voluntary and replacement donors.Results: Total of 10938 blood donors screened. Majority of the donors were males 95.8% (10484) and belonged to voluntary group 72.8% (7971). The total prevalence of STDS were 0.61% (67). The prevalence of HBV, HCV and HIV was 0.47% (51), 0.04% (4) and 0.11% (12) respectively. Prevalence of STDs was higher among voluntary donors 0.57% (62) compared to replacement donors 0.05 % (5). Statistically significant difference was observed in HBV prevalence in voluntary and replacement donors.Conclusions: Most common STDs in blood donors was HBV followed by HIV and HCV. STDs were mainly seen in voluntary donors compared to replacement donors. Majority of the donors were males.

The long-term efficacy of PEG-IFN in treatment of chronic hepatitis C with IL28B rs12979860 C/C genotype / 西安交通大学学报(医学版)

Objective To investigate the long-term efficacy of PEG-IFN alpha-2a (PEG-IFNα-2a)plus ribavirin (RBV)in treatment of chronic hepatitis C (CHC)patients with IL28B single nucleotide polymorphisms (SNPs)rs12979860 C/C type in different HCV genotypes.Methods A prospective study was conducted on 38 CHC patients from our hospital's Infection Department from March 2011 to September 2015.The patients were treated with PEG-IFNα-2a/RBV for 48 weeks.A 42-month follow-up of patients was performed after withdrawal of treatment.The main paramenters to value the efficacy were liver function,blood lipids,and sustained virological response (SVR).Results In the CHC patients with IL28B SNP rs12979860 C/C type,the rate of SVR in patients with antiviral therapy had no significant difference between groups 1b and 2a (73.33% and 95.65%,respectively, P＞0.05).After anti-HCV therapy,liver function indices such as ALT,AST,TBIL,TC,TG and HDL all significantly improved in the two groups (all P＜0.05).However,there was no difference in biochemical indices (ALT,GGT,bilirubin,blood lipids)between the two groups (all P＞0.05).Conclusion In CHC patients with IL28B SNP rs12979860 C/C type,the long-term efficacy of PEG-IFNα-2a/RBV is good.IFN-based antiviral therapy has a higher SVR rate,and liver function and lipid metabolism can be significantly improved.

Evaluation of neutralizing antibodies in serum immunized with virus-like particle chimerized HCV series of neutralizing epitopes / 中国免疫学杂志

Objective:New Zealand rabbits were immunized with VLPs-MEpS,VLPs-E2S,and the levels of neutralizing antibodies in serum were determined.Methods: New Zealand rabbits were immunized with 10 μg VLPs-MEpS and VLPs-E2S,serum was collected at diffferent time with a two-weeks interval.The neutralizing antibodies were determined by ELISA.HCV(type 1b) had been prepared and mixed with serum from immunized rabbit before infected Huh7.5 cell.The protection of neutralizing antibodies in serum was assessed.Results: Neutralizing antibodies had been induced in rabbit after immunized with VLPs-MEpS and VLPs-E2S.VLPs-MEpS group had higher titer of antibodies than that of VLPs-E2S group(P<0.05),both group had higher titer of antibodies than that of control groups significantly(P<0.01).VLPs-MEpS group had higher neutralization than that of VLPs-E2S group(P<0.05),the highest neutralization rate was 61.49%.Both groups were higher than control group notably(P<0.01).Conclusion: Protective neutralizing antibodies have been induced in New Zealand rabbit after immunized with VLPs-MEpS and VLPs-E2S.It′s the basement for development of neutralizing antibodies vaccine.

Comparative evaluation of Immunochromatographic Assay for screening Hepatitis C among blood donors in a rural teaching hospital, Sangareddy

Background: HCV is a blood borne virus. Mainly HCV infection attacks the liver and can cause chronic Hepatitis, liver cirrhosis (27%) and liver cancer (25%) and shows significant mortality and morbidity. Aim: The present study was to assess ICT kit used in the preliminary screening process of HCV infection among blood donors in a rural teaching hospital, Sangareddy. Nagababu Pyadala, Prudhvi Chand Mallepaddi, Rajaneesh Borugadda, Soumendra Nath Maity, Rohit C. P., Rathnagiri Polavarapu. Comparative evaluation of Immunochromatographic Assay for screening Hepatitis C among blood donors in a rural teaching hospital, Sangareddy. IAIM, 2016; 3(6): 152-156. Page 153 Materials and methods: In this study, 1050 number of blood units were collected from donors containing both voluntary and replacement donors for a period of one year from January 2015 to December 2015. 1050 donors were tested for HCV by using ICT kit and ELISA method. Results: We found 4 out of 1050 subjects tested positive for HCV by using ICT kit and conformed by ELISA method. Conclusion: The present study concluded that the overall performance of the rapid ICT kit for HCV was equally sensitive to ELISA and yet they were cheap and quicker. It can be recommended that ELISA comparable rapid devices may be allowed to be used for preliminary screening of Hepatitis C especially, in remote areas or where cost is an issue.

Hepatitis C virus (HCV) infection & risk factors for HCV positivity in injecting & non-injecting drug users attending a de-addiction centre in northern India.

Background & objectives: Injecting drug use is a major route of hepatitis C virus (HCV) infection in India, but there may be other risk factors also. this study was carried out to determine the seroprevalence of anti-HCV antibody in injecting drug users (IDUs) vs. non-IDUs (NIDUs), and to study the risk estimates for HCV seropositivity in the total sample of substance users with regard to various demographic, clinical, behavioural and personality factors. Methods: the IDUs (n = 201) and NIDUs (n = 219) were assessed for demographic, clinical and behavioural information, and were rated on instruments for severity of dependence, risk behaviour and personality profiles. Anti-HCV antibody was tested by ELISA and confirmed by recombinant immunoblot assay (RIBA) test. Results: Almost one-third of the IDUs (64 of 201; 31.8%) were positive for anti-HCV antibody, as opposed to only seven (3.2%) of the NIDUs. The four risk factors strongly associated with HCV positivity in multivariate analysis were sharing syringe [Exp(B) 75.04; 95%CI 18.28-307.96; P<0.001], reuse of injection accessories (16.39; 3.51-76.92; P<0.001), blood transfusion (5.88; 1.63-21.23; P=0.007) and IDU status (3.60; 1.26-10.31; P=0.017). Other variables less strongly but significantly associated with HCV positivity were multiple sex partners, opioid dependence, risk behaviour scores, impulsivity, and lower age of onset of drug use. Interpretation & conclusions: Our study showed a high seroprevalence of anti-HCV antibody in IDUs. In the substance users, HCV positivity was significantly and independently associated with several clinical, behavioural, and personality risk factors.

Seroprevalence of hepatitis B surface antigen and antibody to hepatitis C virus at a tertiary care centre in Telangana.

Background: Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are serious public health problem worldwide and major causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The purpose of this study was to estimate the prevalence rates of HBV and HCV infections in this part of country. Methods: Serum samples of inpatients and outpatients were collected over a period of one and a half year. HBsAg was determined using the HBsAg one step (HEPACARD) hepatitis B surface antigen test device. Antibody detection of HCV was done using HCV TRI-DOT. Results: A total of 4369 serum samples were tested for HBsAg detection and 736 serum samples were tested for hepatitis C virus antibodies. Seropositivity for HBsAg was 1.69% whereas HCV seropositivity was 0.4%. A higher seroprevalence of HBsAg and HCV was found in males as compared with females. Conclusion: Attempts should be made to reduce the incidence of HCV and HBV and their unregulated spread which can be done by increasing public awareness of simple preventive measures.

Residual Risk of Transfusion-Transmitted Infection with Hepatitis C Virus since the Introduction of Nucleic Acid Testing in Korea / 대한수혈학회지

BACKGROUND: In 2005, the Korean Red cross introduced mini-pool nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), which upgraded to individual donation (ID) NAT including HBV in 2012. In this study, we analyzed the trend of HCV infection among blood donors after introduction of NAT by estimating the residual risk (RR) of transfusion transmitted infection (TTI) of HCV. METHODS: Donation data from 2003 to 2014 were analyzed using the Blood Information Management System (BIMS). Each donation was tested for antibodies and viral RNA for HCV. Prevalence and incidence rate (IR) among repeat donors were determined. RR was determined using the incidence rate/window period model. RESULTS: During the 12-year period, a total of 29,058,436 donations were screened with 34 HCV NAT yield donations. Calculated RR per million donations for HCV was significantly reduced from 13.41 in the pre-NAT period (2003~2004) to 0.52 in the post NAT period (2006~2007) (P<0.001). Most recently (2013~2014), RR for HCV with TTI was estimated by 0.16 per million donations (1:6,289,308). CONCLUSION: RR of TTI with HCV was remarkably decreased since introduction of NAT. However, the prevalence and IR of HCV RNA among first time donors was still high and yield cases were more frequent among repeat donors. Therefore, establishment of a sensitive and accurate screening system and measures for maintaining healthy donors should be considered in order to ensure blood safety.

Thrombocytopenia in Egyptian Patients with Hepatitis C Virus Treated with Standard of Care Therapy: A Cohort Study.

Background and Study Aims: Thrombocytopenia (TP) in chronic hepatitis C virus (HCV) is a common finding either directly due to viral infection of platelets or indirectly due to immune alteration triggered by the virus, the consequences of HCV- induced cirrhosis and portal hypertension, or induced by Interferon (IFN), the corner element of the standard of care (SOC) therapy for HCV. This study aimed to evaluate TP in patients with chronic HCV, and to evaluate the mutual effect between SOC and TP. Methods: The study was conducted on 209 patients with chronic HCV from Railway Hospital, Cairo. Patients were divided into two groups, Group (I): 144 patients who received SOC therapy, and Group (II): 65 patients who did not receive therapy. All patients were subjected to clinical examination, laboratory investigations, abdominal ultrasonography, and liver biopsy. Results: TP was a common finding (60/209; 28.7%), more in group I (33/ 60; 55%, mean= 124.8±16.2/ml), and was significantly worse in group II (mean= 99.7±36.3/ml, p=0.008). Along the course of treatment, 2 significant drops of platelet count took place, nadirs at W8 and W24. TP was significantly related to hepatitis activity and hepatic synthetic function, and not related to the viral load. Four cases developed severe TP, only 1 of them continued therapy on IFN dose reduction. Conclusions: TP is a common complication among HCV patients and along its SOC therapy, particularly influenced significantly by splenomegaly and advanced fibrosis.

Evaluation of IL-10 and IL-12B Gene Polymorphisms on the Response to the Standard of Care Therapy in Chronic Hepatitis C Patients: An Egyptian Cohort Study.

Background: Interleukin-10 (IL-10) and IL–12B single nucleotide polymorphisms (SNPs) are confirmed to influence the natural history of hepatitis C virus (HCV) infection, and the response to treatment. This work aimed at evaluating the impact of SNPs in IL-10 gene at positions _1082, _819, and_592 and IL-12B gene on the response to the standard of care (SOC) treatment in Egyptian patients with chronic HCV. Methods: Eighty seven patients with chronic HCV treated by SOC therapy and 20 healthy controls were tested for SNPs in IL-10 at _1082 G/A, _819 C/T and_592 C/A and in IL- 12B (30-UTR 1188-A/C) by polymerase chain reaction (PCR). Patients were divided according to their virologic response into 2 groups; group Ι=patients who achieved sustained virologic response (SVR) and group Π = non responder (NR) patients. Results: SNPs of IL-10 at _1082 G/A and_819 C/T showed that; GA and TT genotypes were significantly related to SVR (P=0.001 and 0.007 respectively). IL-12 genepolymorphisms showed that; CC genotype was significantly related to SVR group (P=0.01) while AA genotype was significantly related to NR (P=0.01). Conclusions: Studying SNPs of IL-10_1082 G/A, IL-10_819 C/T and IL-12B (30-UTR 1188-C/A) proved GA, TT and CC genotypes, respectively, to be good predictors for SVR. Conversely, SNPs of IL-12 C/A proved AA genotype to be good predictor for NR.

Naturally Occurring Mutations of Hepatitis B virus and Hepatitis C Virus in Korean Chronic Patients by Distinct CD4 T Cell Responses

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most common causes of chronic liver disease worldwide. The host immune pressure against hepatitis viruses during the chronic infection has led to mutations in their coding genes, which could play a pivotal role in the clinical outcomes of chronic patients. Our recent molecular epidemiologic studies regarding the HBV precore/core (preC/C) regions and HCV nonstructural 5B (NS5B) protein suggest the presence of distinct CD4 T cell immune pressure against HBV and HCV in Korean chronic patients. However, induced HBV and HCV mutations seem to exert an opposite effect on Korean chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients, respectively. On the basis of two of our recent papers, we focused in this review on the relationships between the mutation patterns of HBV preC/C and HCV NS5B, which were presumed to be caused by distinct CD4 T cell pressure in the Korean population and their effect on the clinical outcomes and liver disease progression of CHB and CHC patients.