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Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

ABSTRACT: In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3?±?2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ?24?kg/m² was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p?=?0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

SUBMITTER: Hsu WF

PROVIDER: S-EPMC7096452 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

Hsu Wei-Fan WF Chen Chi-Yi CY Tseng Kuo-Chih KC Lai Hsueh-Chou HC Kuo Hsing-Tao HT Hung Chao-Hung CH Tung Shui-Yi SY Wang Jing-Houng JH Chen Jyh-Jou JJ Lee Pei-Lun PL Chien Rong-Nan RN Lin Chun-Yen CY Yang Chi-Chieh CC Lo Gin-Ho GH Tai Chi-Ming CM Lin Chih-Wen CW Kao Jia-Horng JH Liu Chun-Jen CJ Liu Chen-Hua CH Yan Sheng-Lei SL Bair Ming-Jong MJ Su Wei-Wen WW Chu Cheng-Hsin CH Chen Chih-Jen CJ Lo Ching-Chu CC Cheng Pin-Nan PN Chiu Yen-Cheng YC Wang Chia-Chi CC Cheng Jin-Shiung JS Tsai Wei-Lun WL Lin Han-Chieh HC Huang Yi-Hsiang YH Tsai Pei-Chien PC Huang Jee-Fu JF Dai Chia-Yen CY Chuang Wan-Long WL Yu Ming-Lung ML Peng Cheng-Yuan CY

Scientific reports 20200325 1

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the ...[more]

PMID: 32214132

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Project description:BackgroundRheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q.MethodsWe tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus.ResultsA SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis.ConclusionsA haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses.

Project description:BackgroundClinical and epidemiological studies have suggested systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are comorbidities and common genetic etiologies can partly explain such coexistence. However, shared genetic determinations underlying the two diseases remain largely unknown.MethodsOur analysis relied on summary statistics available from genome-wide association studies of SLE (N = 23,210) and RA (N = 58,284). We first evaluated the genetic correlation between RA and SLE through the linkage disequilibrium score regression (LDSC). Then, we performed a multiple-tissue eQTL (expression quantitative trait loci) weighted integrative analysis for each of the two diseases and aggregated association evidence across these tissues via the recently proposed harmonic mean P-value (HMP) combination strategy, which can produce a single well-calibrated P-value for correlated test statistics. Afterwards, we conducted the pleiotropy-informed association using conjunction conditional FDR (ccFDR) to identify potential pleiotropic genes associated with both RA and SLE.ResultsWe found there existed a significant positive genetic correlation (r g = 0.404, P = 6.01E-10) via LDSC between RA and SLE. Based on the multiple-tissue eQTL weighted integrative analysis and the HMP combination across various tissues, we discovered 14 potential pleiotropic genes by ccFDR, among which four were likely newly novel genes (i.e., INPP5B, OR5K2, RP11-2C24.5, and CTD-3105H18.4). The SNP effect sizes of these pleiotropic genes were typically positively dependent, with an average correlation of 0.579. Functionally, these genes were implicated in multiple auto-immune relevant pathways such as inositol phosphate metabolic process, membrane and glucagon signaling pathway.ConclusionThis study reveals common genetic components between RA and SLE and provides candidate associated loci for understanding of molecular mechanism underlying the comorbidity of the two diseases.

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Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

Publications

Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

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