{"doi":"10.1111/hepr.12867","title":"<i>ITPA</i> gene variation and ribavirin‐induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin","abstract":"<jats:sec><jats:title>Aim</jats:title><jats:p>Sofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV‐induced anemia is a troublesome side‐effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV‐induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment and <jats:italic>ITPA</jats:italic> gene variants.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Ninety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms of <jats:italic>ITPA</jats:italic> and the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall SVR at 12 weeks was 94.4% (85/90). Patients with the <jats:italic>ITPA</jats:italic> CA/AA genotypes had a lower degree of anemia throughout the therapy than those with the <jats:italic>ITPA</jats:italic> CC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with the <jats:italic>ITPA</jats:italic> CA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was &lt;12 g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Patients with the <jats:italic>ITPA</jats:italic> CA/AA genotype were less likely to develop anemia than those with the <jats:italic>ITPA</jats:italic> CC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug‐induced adverse events, particularly in patients with pre‐existing anemia.</jats:p></jats:sec>","journal":"Hepatology Research","year":2017,"id":675827,"datarank":1.2798611067002432,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.8381952598252771,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.8381952598252771,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":16,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1705981,"name":"Yasuhiro Asahina","orcid":null,"position":1,"is_corresponding":false},{"id":1765821,"name":"Hiroko Nagata","orcid":null,"position":2,"is_corresponding":false},{"id":1765822,"name":"Mina Nakagawa","orcid":null,"position":3,"is_corresponding":false},{"id":1765824,"name":"Sei Kakinuma","orcid":null,"position":4,"is_corresponding":false},{"id":1765826,"name":"Sayuri Nitta","orcid":null,"position":5,"is_corresponding":false},{"id":1765827,"name":"Fukiko Kawai‐Kitahata","orcid":null,"position":6,"is_corresponding":false},{"id":1765829,"name":"Satoshi Otani","orcid":null,"position":7,"is_corresponding":false},{"id":668859,"name":"Shun Kaneko","orcid":null,"position":8,"is_corresponding":false},{"id":1765832,"name":"Masato Miyoshi","orcid":null,"position":9,"is_corresponding":false},{"id":1765833,"name":"Tomoyuki Tsunoda","orcid":null,"position":10,"is_corresponding":false},{"id":1765834,"name":"Yu Asano","orcid":null,"position":11,"is_corresponding":false},{"id":1765835,"name":"Ayako Sato","orcid":null,"position":12,"is_corresponding":false},{"id":1765836,"name":"Yasuhiro Itsui","orcid":null,"position":13,"is_corresponding":false},{"id":1765837,"name":"Seishin Azuma","orcid":null,"position":14,"is_corresponding":false},{"id":1765838,"name":"Toshihiko Nouchi","orcid":null,"position":15,"is_corresponding":false},{"id":1765839,"name":"Yohei Furumoto","orcid":null,"position":16,"is_corresponding":false},{"id":1765840,"name":"Tooru Asano","orcid":null,"position":17,"is_corresponding":false},{"id":1765841,"name":"Yoshimichi Chuganji","orcid":null,"position":18,"is_corresponding":false},{"id":1765842,"name":"Shuji Tohda","orcid":null,"position":19,"is_corresponding":false},{"id":590374,"name":"Mamoru Watanabe","orcid":"0000-0002-5475-9544","position":20,"is_corresponding":false},{"id":1765820,"name":"Miyako Murakawa","orcid":"0000-0002-0468-4409","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>ITPA</i> gene variation and ribavirin‐induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin","abstract":"<jats:sec><jats:title>Aim</jats:title><jats:p>Sofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV‐induced anemia is a troublesome side‐effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV‐induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment and <jats:italic>ITPA</jats:italic> gene variants.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Ninety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms of <jats:italic>ITPA</jats:italic> and the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall SVR at 12 weeks was 94.4% (85/90). Patients with the <jats:italic>ITPA</jats:italic> CA/AA genotypes had a lower degree of anemia throughout the therapy than those with the <jats:italic>ITPA</jats:italic> CC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with the <jats:italic>ITPA</jats:italic> CA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was &lt;12 g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Patients with the <jats:italic>ITPA</jats:italic> CA/AA genotype were less likely to develop anemia than those with the <jats:italic>ITPA</jats:italic> CC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug‐induced adverse events, particularly in patients with pre‐existing anemia.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28128521","pmcid":null,"openalex_id":"https://openalex.org/W2582103643","authors":[],"funders":[],"total_grants":0,"fwci":2.1882,"citation_percentile":0.87433173,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":9},{"year":2019,"count":4},{"year":2020,"count":2},{"year":2021,"count":1},{"year":2022,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fhepr.12867","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/hepr.12867","host_type":"publisher"},{"url":"https://doi.org/10.1111/hepr.12867","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28128521","host_type":"repository"}],"fields_of_study":["Hepatitis C virus research","Biochemical and Molecular Research","Blood disorders and treatments"],"mesh_terms":[],"keywords":["ITPA","Ribavirin","Medicine","Anemia","Internal medicine","Gastroenterology","Sofosbuvir","Genotype","Hemolytic anemia","Hepatitis C","Hepatitis C virus","Immunology","Biology","Genetics","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T01:46:05.185290Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}