Disadvantages of peginterferon and ribavirin treatment in older patients with chronic hepatitis C: an analysis using the propensity score

Ebinuma, Hirotoshi; Saito, Hidetsugu; Tada, Shinichiro; Nakamoto, Nobuhiro; Ohishi, Tazuko; Tsunematsu, Satoshi; Kumagai, Naoya; Tsuchimoto, Kanji; Tsukada, Nobuhiro; Inagaki, Yasutaka; Horie, Yoshinori; Takahashi, Masahīko; Atsukawa, Kazuhiro; Okamura, Yukishige; Kanai, Takanori; Hibi, Toshifumi

doi:10.1007/s12072-011-9312-9

Cited by 8 publications

(2 citation statements)

References 29 publications

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“…The issues of IFN-based treatment were the high rate of adverse events and long duration of treatment. Hence, it was difficult for elderly patients to achieve sustained virologic response (SVR) due to dropout from treatment 3,4) . As a result, 1-1.5 million patients still have HCV infection in Japan 5) despite the nationwide campaign to promote the treatment of chronic HCV infection.…”

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confidence: 99%

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection

et al. 2020

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Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in "rural" regions. Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan. Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events. Conclusion: G/P therapy is effective and safe for old-aged patients.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection

et al. 2020

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“…Treatment of HCV infection has been progressed with introduction of protease inhibitors. Although the combination therapy with pegylated interferon (PEG-IFN), ribavirin, and protease inhibitors has shown a higher sustained virological response (SVR) rate, the SVR rate of patients with genotype 1b and a high viral load has not been satisfactory [Ikeda et al, 2006;Ebinuma et al, 2012;Takayama et al, 2011]. Effective drugs without severe side effects are needed for treatment of chronic infection with HCV genotype 1b.…”

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Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication

Sato

Saito

Sugiyama

et al. 2013

J of Cellular Biochemistry

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The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) has a clinical promise for treatment of cancer including hepatocellular carcinoma (HCC). To investigate effect of SAHA on hepatitis C virus (HCV) replication, we treated the HCV replicon cell OR6 with SAHA. HCV replication was significantly inhibited by SAHA at concentrations below 1 μM with no cellular toxicity. Another HDAC inhibitor, tricostatin A, also showed reduction of HCV replication. The microarray analysis and quantitative RT-PCR demonstrated up-regulation of osteopontin (OPN) and down-regulation of apolipoprotein-A1 (Apo-A1) after SAHA treatment. Direct gene induction of OPN and knockdown of Apo-A1 also showed reduction of HCV replication. The liver specific microRNA-122, which is involved in HCV replication, was not affected by SAHA treatment. These results suggest that SAHA has suppressive effect on HCV replication through alterations of gene expression such as OPN and Apo-A1 in host cells. Epigenetic treatment with HDAC inhibitors may be a novel therapeutic approach for diseases associated with HCV infection such as chronic hepatitis, liver cirrhosis, and HCC.

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Assessment of efficacy and safety of PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C

Wen

Cheng

Hsu

et al. 2018

Adv in Digestive Medicine

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Patients with chronic hepatitis C‐associated liver disease are of an older age in southern Taiwan. PEGylated interferon‐based therapy could reduce the risk of cirrhosis and hepatocellular carcinoma and improve survival. We assessed the efficacy and safety of combination therapy with PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C. A total of 88 consecutive patients with chronic hepatitis C treated with combination therapy were analyzed retrospectively to identify factors associated with a sustained virological response (SVR). These patients were divided into two groups according to age: elderly patients ≧ 60 years (n = 43) and patients 50 to 59 years (n = 45). We compared baseline characteristics, adherence 80/80/80, dose modification, discontinuation, and adverse events profiles between these two groups. We further compared virological response rates stratified by genotype. The factors associated with an SVR were determined by total patients and different age groups. In the intent‐to‐treat analysis, the SVR rate was 61.8%. The SVR rate of elderly patients tended to be superior to that of total patients. Patients aged ≧ 60 years had a higher proportion of concomitant chronic disease, dose modification, clinical events with anorexia, depression, leucopenia, and anemia than those aged 50 to 59 years. Total patients with genotype 1 tended to have a lower SVR rate than nongenotype 1 (P = 0.067). Total patients with nongenotype 1 had a significantly higher rapid virological response (RVR) rate than genotype 1 (P = 0.009). In patients aged ≧ 60 years, the relapse rate of genotype 1 was higher than that of nongenotype 1 (P = 0.034). After stratification by HCV genotype 1, high viral load, and achievement of an RVR, the SVR rates remained similar between the two groups. The most strongly predictive factors of an SVR of total patients were the achievement of an RVR (OR: 49.744; 95% CI: 6.979‐354.574; P < 0.001), followed by breakthrough (OR: 0.018; 95% CI: 0.002‐0.195; P = 0.001). The factor mostly predictive of an SVR in age ≧ 60 years group was achievement of an RVR (OR: 12.779; 1.430‐114.180; P = 0.023). Elderly patients had a greater frequency of adverse events. Genotype 1 is independently associated with lower SVR and RVR rates and high relapse rates. Attainment of an RVR is the most powerful predictor of SVR in elderly patients.

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Disadvantages of peginterferon and ribavirin treatment in older patients with chronic hepatitis C: an analysis using the propensity score

Abstract: The analysis using PS indicated that RBV adherence in the older patients decreased even if they did not have lower pretreatment RBC and Hgb levels.

Cited by 8 publications

References 29 publications

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection

Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication

Assessment of efficacy and safety of PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C

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