<i>ITPA</i> gene variation and ribavirin‐induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin

Murakawa, Miyako; Asahina, Yasuhiro; Nagata, Hiroko; Nakagawa, Mina; Kakinuma, Sei; Nitta, Sayuri; Kawai‐Kitahata, Fukiko; Otani, Satoshi; Kaneko, Shun; Miyoshi, Masato; Tsunoda, Tomoyuki; Asano, Yoshihiro; Sato, Ayako; Itsui, Yasuhiro; Azuma, Seishin; Nouchi, Toshihiko; Furumoto, Yohei; Asano, Tooru; Chuganji, Yoshimichi; Tohda, Shuji; Watanabe, Mamoru

doi:10.1111/hepr.12867

Cited by 17 publications

(19 citation statements)

References 25 publications

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“…The role of RBV adherence might affect SVR. Japanese real‐world data on the efficacy of SOF + RBV for genotype 2 infections have been reported, and there is disagreement on the impact of RBV dose reduction on SVR …”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] The role of RBV adherence might affect SVR. Japanese real-world data on the efficacy of SOF + RBV for genotype 2 infections have been reported, [12][13][14][15] and there is disagreement on the impact of RBV dose reduction on SVR. 12,13 The goal of antiviral treatment is to avoid fibrosis progression by HCV eradication and to prevent hepatic decompensation or hepatocellular carcinoma (HCC).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Real‐world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group

Akahane¹,

Kurosaki

Itakura

et al. 2018

Hepatology Research

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real‐world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group

Akahane¹,

Kurosaki

Itakura

et al. 2018

Hepatology Research

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“…However, there are still few reports on patients treated with IFN‐free DAA therapy, and factors associated with RBV‐induced hemolytic anemia have not been examined in detail. A previous report suggested that ITPA was associated with RBV‐induced anemia in patients during treatment with SOF/RBV therapy, but other factors were unknown . This study identified groups that did not develop anemia with SOF and RBV combination treatment in HCV genotype 2‐infected patients.…”

Section: Discussionmentioning

confidence: 76%

“…Japanese patients with the rs1127354 CC genotype are prone to developing severe anemia during treatment with a combination of PEG‐IFN plus RBV . The ITPA SNPs have also been shown to be among significant factors associated with anemia in patients during treatment with PEG‐IFN/RBV plus telaprevir or simeprevir triple therapy and SOF/RBV . However, factors associated with RBV‐induced hemolytic anemia other than ITPA in patients with SOF/RBV therapy have not been examined in detail.…”

Section: Introductionmentioning

confidence: 99%

Predictive factors of anemia during sofosbuvir and ribavirin therapy for genotype 2 chronic hepatitis C patients

Urabe

Sakamori

Tahata

et al. 2019

Hepatology Research

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Aim Sofosbuvir (SOF) and ribavirin (RBV) combination therapy has improved the sustained virologic response (SVR) rate and shortened the treatment duration for patients with chronic hepatitis C virus (HCV) genotype 2 infection. Ribavirin‐induced hemolytic anemia is one of the most troublesome side‐effects of SOF/RBV therapy; however, factors associated with this condition have not been fully elucidated. We aimed to identify a safer way to complete treatment with SOF/RBV therapy by examining factors related to RBV‐induced hemolytic anemia and identifying patients who did not develop anemia. Methods Two hundred and one patients with genotype 2 chronic hepatitis C treated with SOF/RBV therapy were studied. Significant factors associated with the decline in hemoglobin (Hb) levels from the baseline were analyzed. Results The SVR rate was 96.5% (194 out of 201 patients) based on intent‐to‐treat analysis. In multivariate analysis, inosine triphosphatase (ITPA) gene variation (P < 0.0001) and estimated glomerular filtration rate (eGFR) (0.001) were significantly associated with a decrease in Hb levels less than 2 g/dL. All patients were divided into four groups by ITPA and eGFR at baseline, and we identified patients with ITPA CA/AA and eGFR >75 as a group that did not develop anemia. Conclusions The results presented here suggest that patients with ITPA CA/AA and eGFR >75 had no reduction in Hb levels during the treatment with SOF/RBV in HCV genotype 2‐infected patients. Adding RBV to direct‐acting antiviral therapy might not be problematic in certain patients, at least in terms of the occurrence of anemia.

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“…Insofar as IFNL3 (IL28B) influences the responsiveness to PEG‐IFN and RBV, polymorphisms in ITPA gene—the most studied gene in our data mining—influence anaemia induced by RBV and strongly correlated to RBV‐induced haemolytic anaemia (RIHA) . The development of RIHA during anti‐HCV treatment is responsible for treatment discontinuation, dose reduction, and consequently decreased SVR.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

Sghaier

Brochot

Yacoubi-Loueslati

et al. 2019

Reviews in Medical Virology

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Summary HCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.

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ITPA gene variation and ribavirin‐induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin

Cited by 17 publications

References 25 publications

Real‐world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group

Real‐world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group

Predictive factors of anemia during sofosbuvir and ribavirin therapy for genotype 2 chronic hepatitis C patients

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

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