OBJECTIVE: Coexisting chronic hepatitis C can be problematic when treating rheumatoid arthritis (RA). This study examined the changes in the transaminase and viral load in hepatitis C virus (HCV)-infected RA patients after initiating biologic agents. METHODS: A multicenter retrospective study was conducted at 12 University Hospitals in Korea between November 2014 and November 2015, and 78 RA patients, who met the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA and were concomitantly infected with HCV, were identified. The baseline and longitudinal clinical data, changes in liver function, and viral RNA titers were evaluated. RESULTS: Seventeen (21.8%) patients were treated with biologic agents, including etanercept (n=8), adalimumab (n=8), infliximab (n=2), tocilizumab (n=2), abatacept (n=1), and golimumab (n=1) (median 1.5 patient-years). Four patients experienced marked increases in transaminase during treatment with adalimumab (n=2) and tocilizumab (n=2). Two patients (one using adalimumab, the other using tocilizumab) were treated with anti-viral agents and showed dramatic improvement in both the viral RNA and transaminase. One patient discontinued adalimumab due to the repeated elevated transaminase levels along with a twofold increase in the viral RNA titer, and the transaminase level subsequently normalized. No case of overt viral reactivation was identified. CONCLUSION: The data support that changes in transaminase and/or viral load associated with biologic agents in HCV-infected RA patients are possible. Therefore, the liver function and viral RNA titer should be followed regularly during biologic therapy.
Abatacept ; Adalimumab ; Antirheumatic Agents ; Arthritis, Rheumatoid* ; Biological Factors ; Biological Therapy* ; Classification ; Etanercept ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic* ; Hepatitis, Chronic* ; Hospitals, University ; Humans ; Infliximab ; Korea ; Liver ; Retrospective Studies ; Rheumatic Diseases ; Rheumatology ; RNA, Viral ; Viral Load

No abstract available.
Antiviral Agents/*therapeutic use ; Benzimidazoles/*therapeutic use ; Female ; Fluorenes/*therapeutic use ; Hepacivirus/*classification ; Hepatitis C, Chronic/*drug therapy ; Humans ; Liver Cirrhosis/*drug therapy ; Male ; Ribavirin/*therapeutic use ; Uridine Monophosphate/*analogs & derivatives

OBJECTIVETo investigate the prevalence and distribution of hepatitis C virus (HCV) genotypes in Henan province in 2012.

METHODSA total of 32 203 permanent residents (1 to 74 years old) in Henan were recruited using multi-stage random samping method from March to June 2012. All participants were asked to complete a questionnaire to collect demographic information, past medical history and the exposure history of risk factors. A blood sample of 5 ml was collected at the same time. The condition of anti-HCV and HCV RNA was determined through the ELISA test and nested RT-PCR. HCV RNA positive samples were further subject to the nonstructural protein 5 region (NS5B) gene amplification and sequencing. The sequence was amplified for the phylogenetic tree and genetic analysis. The differences of the positive rate of anti-HCV and HCV RNA and the HCV genetic subtype distribution in different respondents'characteristics were analyzed.

RESULTSAmong 32 203 subjects, the overall positive rate of anti-HCV and HCV RNA were 0.48% (153/32 203) and 0.24% (78/32 203), in which men were 0.42% (65/15 634), and 0.23% (36/15 634), and women were 0.53% (88/16 569) and 0.25% (42/16 596). The differences between men and women were not statistically significant (χ(2) values were 2.26, 0.18, respectively, both P values > 0.05). The results of NS5B genotyping and molecular evolution analysis showed that there were six subtypes in the 71 HCV RNA positive samples.In those six subtypes, the proportion of genotypes 1b, 6a, 3a, 2a, 3b and 1a were 56.3% (40/71), 19.7% (14/71), 11.3% (8/71), 8.5% (6/71), 2.8% (2/71) and 1.4% (1/71), respectively. The HCV genetic subtypes of infestor were mainly present with two branches of 1b and 6a, and the two subtypes Bootstrap values were 0.95.

CONCLUSIONThe prevalence of HCV infection was high in Henan. The major HCV genotypes in patients with HCV infection were 1b and 6a.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Genotype ; Hepacivirus ; classification ; genetics ; Hepatitis C ; epidemiology ; virology ; Humans ; Infant ; Male ; Middle Aged ; Phylogeny ; RNA, Viral ; genetics ; Sequence Analysis, DNA ; Young Adult

OBJECTIVETo generate hepatitis C virus pseudo-particles (HCVpp) containing the complete E1-E2 envelope glycoprotein, in order to establish a HCVpp database covering the six major genotypes of HCV (1b, 2a, 3b, 4, 5, and 6) and to develop a simple and effective method for detection of neutralizing antibodies in HCV patients.

METHODSHCVpp were generated for the six genotypes by co-transfecting 293T cells with a plasmid expressing the respective E1-E2 (p HR, CMVA 8.2 construct) and a MLV-GFP plasmid. Titration of each HCVpp was carried out by p24 ELISA. Infectivity of each HCVpp was assessed by mixing the harvested supernatant of producer cells with sera from HCV patients, adding the mixture to Huh-7 cells, and detecting the subsequent titers of neutralizing antibodies against HCVpp.

RESULTSAll six types of HCVpp were able to infect Huh-7 cells in vitro. For healthy HCV carriers, only two genotypes of HCVpp (1b and 2a) produced neutralizing antibody titers more than 1:40. For cured HCV patients, only the 1b genotype produced neutralizing antibody titers more than 1:40. One patient showed titer of 1:200 for genotype 4. A healthy spouse of a chronic hepatitis C patient showed titers more than 1:40 for four genotypes of HCVpp (3a, 4, 5, 6).

CONCLUSIONWe generated six different genotypes of HCVpp successfully, established the in vitro neutralizing antibody detection method, and provided an effective model for screening antiviral drugs.

Adolescent ; Adult ; Antibodies, Neutralizing ; blood ; Antibodies, Viral ; blood ; Female ; Genotype ; Hepacivirus ; classification ; Hepatitis C ; blood ; immunology ; Humans ; Male ; Middle Aged ; RNA, Viral ; blood ; Viral Envelope Proteins ; immunology ; Young Adult

OBJECTIVETo investigate the effect of hepatitis C virus (HCV) strain JFH1 on expression of the human gene, growth arrest and DNA damage-inducible gene 45 alpha (GADD45a), in infected hepatoma cells.

METHODSHCV JFH1 RNA-containing supernatants were used to infect the human hepatoma cell line, Huh7.5.1; infection was confirmed by Western blot detection of the HCV-encoded non-structural 5A (NS5A) protein and core protein. Infection-induced changes in GADD45a mRNA and protein expressions were measured by real time PCR using SYBR Green and Western blotting, respectively. Significance of differences between the levels detected in JFH1-infected or uninfected Huh7.5.1 cells was analyzed by single factor analysis of variance testing.

RESULTSThe HCV infection system was successfully established, as evidenced by expression of NS5A protein and core protein. The GADD45a mRNA and protein levels were significantly down-regulated in JFH1-infected Huh7.5.1 cells, by 0.57+/-0.09 and 0.28+/-0.03, respectively, as compared to levels in uninfected Huh7.5.1 cells (F values were 75.407 and 560.04, respectively; P less than 0.01).

CONCLUSIONHCV inhibits the mRNA transcription and protein expression of host GADD45a, which may contribute to the pathogenesis of hepatocellular carcinoma caused by HCV infection.

Cell Line, Tumor ; DNA Damage ; Hepacivirus ; classification ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Transcription, Genetic

BACKGROUNDAn epidemiologic link between hepatitis C virus (HCV) and abnormal glycometabolism had been established. This study was designed to investigate the prevalence of type 2 diabetes mellitus and insulin resistance, and to explore the relation between insulin resistance and hepatitis C virus genotype, serum hepatitis C virus-RNA level in chronic hepatitis C (CHC) patients.

METHODSThree hundred and fifty-nine consecutive patients (CHC, n = 296; chronic hepatitis B (CHB), n = 63) were evaluated. HCV genotyping was performed by restriction fragment method and serum hepatitis C virus-RNA quantified PCR for all CHC patients in the baseline serum. Fasting levels of insulin and glucose were measured in all patients and the homeostatic assessment of insulin resistance was calculated in the baseline serum.

RESULTSType 2 diabetes mellitus was diagnosed in 15.5% of 296 CHC patients. Insulin resistance was present in 23.8% of the 235 nondiabetic CHC patients, in 23.1% of the 182 nondiabetic and noncirrhotic CHC patients, and associated with high serum HCV RNA level (OR: 1.754; 95%CI: 1.207 - 2.548, P = 0.003) and age > 40 years (OR: 3.542; 95%CI: 1.257 - 9.978, P = 0.017). Insulin resistance was less frequent in CHB than in matched CHC (7.9% vs. 21.4% respectively, P < 0.0001).

CONCLUSIONThe incidence of insulin resistance in CHC was significantly higher than that in CHB patients, associated with high serum HCV RNA level and age > 40 years.

Adult ; Aged ; Blood Glucose ; metabolism ; China ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; virology ; Female ; Genotype ; Hepacivirus ; classification ; genetics ; pathogenicity ; Hepatitis C, Chronic ; blood ; metabolism ; virology ; Humans ; Insulin ; blood ; Insulin Resistance ; genetics ; physiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; RNA, Viral ; genetics ; Risk Factors

OBJECTIVETo explore the transmission routes, genotypes/subtypes distribution and genetic character of HCV in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province.

METHODSReverse transcription (RT) nested PCR was performed to amplify the HCV NS5B gene region from 95 HIV/HCV co-infected and 99 HCV mono-infected individuals lived in Guangdong province. The PCR products were then sequenced for HCV subtyping. Genetic analysis was done by MEGA4 software.

RESULTS(1) HIV/HCV co-infected individuals infected HCV mostly through injection drug use (IDU, 78.9%), the HCV subtypes were identified as 6a (53.7%), 3a (17.9%), 1b (15.8%), 3b (11.6%) and 1a (1.0%) respectively, the genetic distance within subtype 1b was longer than those within other subtypes, the predominant HCV subtype in HIV/HCV co-infected individuals infected through IDU was 6a (60.0%). (2) HCV mono-infected individuals infected HCV mostly through blood or blood products transfusions (80.8%), the HCV subtypes were identified as 1b (67.7%), 6a (17.2%), 3a (6.1%), 2a (5.0%), 3b (2.0%), 4a (1.0%) and 5a (1.0%) respectively, the genetic distance within subtype 1b was also longer than those within other subtypes, the predominant HCV subtype in HCV mono-infected individuals infected through blood or blood products transfusions was 1b (76.2%).

CONCLUSIONThe diversity of HCV subtypes in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province was high, both the major transmission route and HCV subtype between HIV/HCV co-infected individuals and HCV mono-infected individuals were different.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Coinfection ; virology ; Female ; Genotype ; HIV ; HIV Infections ; epidemiology ; virology ; Hepacivirus ; classification ; genetics ; Hepatitis C ; epidemiology ; virology ; Humans ; Male ; Middle Aged ; Phylogeny ; Young Adult

OBJECTIVETo determine the distribution of HCV genotypes among volunteer blood donors in Guangzhou.

METHODSSix-nine HCV RNA-positive samples were collected from volunteer blood donors in Guangzhou. NS5B fragments of HCV were amplified followed by DNA sequencing and phylogenetic analysis.

RESULTSHCV genotypes were determined for 67 samples. Among them, the subtypes 1b, 2a, 3a, 3b, 6a and 6n were detected at the frequencies of 37.31%, 4.48%, 7.46%, 4.48%, 44.78% and 1.49%, respectively.

CONCLUSIONHCV 1b and 6a are the most predominant two subtypes among volunteer blood donors in Guangzhou.

Blood Donors ; China ; Genotype ; Hepacivirus ; classification ; genetics ; isolation & purification ; Humans ; Phylogeny ; RNA, Viral ; genetics ; Sequence Analysis, DNA

OBJECTIVETo develop a rapid and specific method for hepatitis C virus ( HCV) genotyping using reverse dot blot hybridization technique and investigate the distribution of HCV genotypes and subtypes in Guangdong.

METHODSThe primers and the probes targeting the 5'untranslated region (5'UTR) and core region of HCV genotypes 1b, 2a, 3a, 3b and 6a were designed, and the RT-PCR reverse dot blot hybridization (PCR-RDH) method for HCV genotyping was established. A total of 115 patients with hepatitis C were genotyped using this method, and 38 of them were also genotyped by sequencing and phylogenetic analysis to evaluate the accuracy and specificity of the method.

RESULTSOf the 115 patients, 111 were successfully genotyped to be 1b, 2a, 3a, 3b, 6a and mix-infection of 1b/2a at frequencies of 56.8%, 8.1 %, 3.6%, 5.4%, 25.2% and 0.9% respectively, and all the 15 healthy control samples showed negative results. The accuracy and reliability of the genotyping method of PCR-RDH was confirmed in 38 cases by amplification of HCV core and NS5B regions followed by DNA sequencing and phylogenetic analysis.

CONCLUSIONThis method for HCV genotyping, with high reliability and specificity, is suitable for clinical and epidemiological investigations. The prevalence of HCV genotypes 1b and 2a decreases while 1b remains the dominant genotype in Guangdong, where the prevalence of 6a significantly increases as compared with that 10 years ago.

Genes, Viral ; Genotype ; Genotyping Techniques ; methods ; Hepacivirus ; classification ; genetics ; Hepatitis C ; virology ; Humans ; Immunoblotting ; Nucleic Acid Hybridization ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo perform a Meta-analysis on peginterferon with interferon in treatment of HIV patients coinfected with refractory genotype HCV.

METHODSA literature search of Medline was conducted to identify eligible randomized controlled trials. Meta analysis was conducted to evaluate peginterferon and interferon in treatment of coinfected HCV genotype 1 or 4 in HIV patients.

RESULTSix trials of 88 matched the selection criteria. Total 1,131 patients with coinfection of HCV genotype 1 or 4 and HIV were included. Sustain viral response was higher in patients treated with peginterferon plus ribavirin compared with that of interferon plus ribavirin (26 % compared with 8 %) or peginterferon alone (26 % compared with 13 %). Severe adverse effects and withdrawal rates were similar for patients treated with peginterferon and patients treated with interferon.

CONCLUSIONPeginterferon plus ribavirin in treatment of patients with coinfection of genotype 1 or 4 HCV and HIV can achieve higher sustain viral response and the likelihoods of serious adverse effects and withdrawal rates are similar to other therapies.

Adult ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Female ; Genotype ; HIV Infections ; complications ; drug therapy ; immunology ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; complications ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Polyethylene Glycols ; administration & dosage ; Randomized Controlled Trials as Topic ; Recombinant Proteins ; Ribavirin ; administration & dosage