Past history of hepatocellular carcinoma is an independent risk factor of treatment failure in patients with chronic hepatitis C virus infection receiving direct‐acting antivirals

Sugiura, Ayumi; Joshita, Satoru; Umemura, Takeji; Yamazaki, Tomoo; Fujimori, Naoyuki; Kimura, Takefumi; Matsumoto, Akihiro; Igarashi, Koji; Usami, Yoko; Wada, Shinpei; Mori, Hiromitsu; Shibata, Soichiro; Yoshizawa, Kaname; Morita, S.; Furuta, Kiyoshi; Kamijo, Atsushi; Iijima, Akihiro; Kako, Satoko; Maruyama, Atsushi; Kobayashi, Masakazu; Komatsu, Michiharu; Matsumura, Makiko; Miyabayashi, Chiharu; Ichijo, Tetsuya; Takeuchi, A; Koike, Yuriko; Gibo, Yukio; Tsukadaira, Toshihisa; Inada, Haruhiko; Kiyosawa, Kendo; Tanaka, Eiji

doi:10.1111/jvh.12973

Cited by 21 publications

(16 citation statements)

References 40 publications

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“…Most recently, history of HCC was reported to be an independent factor of treatment failure in patients receiving DAAs . However, the present study failed to find significant independence: the SVR rate in patients who previously received treatment for HCC (91.1% [214/235]) was numerically lower than in patients without any treatment for HCC (93.2% [1767/1896]), although not with statistical significance ( P = 0.224).…”

Section: Discussioncontrasting

confidence: 90%

Efficacy of direct‐acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study

Itokawa

Atsukawa

Tsubota

et al. 2018

Hepatology Research

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Aim Although the development of new direct‐acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection has markedly advanced, the effects of cirrhosis on DAA treatment remain unclear. We aimed to clarify the impact of cirrhosis on DAA treatment of patients infected with HCV. Methods This large‐scale, multicenter, retrospective study consisted of 2130 HCV genotype 1b‐infected patients who were treated with one of the following DAA combination therapies: asunaprevir/daclatasvir (ASV/DCV), ledipasvir/sofosbuvir (LDV/SOF), or paritaprevir/ombitasvir/ritonavir (PTV/OBV/r). Ninety‐two patients (4.3%) previously received DAA‐based treatment. Seven hundred and forty‐five patients (34.9%) had cirrhosis. Results Overall, the sustained virologic response (SVR) rate was 93.0%. The SVR rates in patients who received ASV/DCV, LDV/SOF, or PTV/OBV/r were 90.0%, 96.9%, and 97.6%, respectively. The SVR rate in patients with cirrhosis (89.1%) was significantly lower than that in patients without cirrhosis (95.1%, P = 6.94 × 10–7). In the multivariate analysis for the overall cohort, absence of cirrhosis (P = 1.26 × 10–3), no previous DAA‐based treatment (P = 2.54 × 10–14), low HCV‐RNA levels (P = 1.64 × 10–6), wild‐type non‐structural protein 5A L31/Y93 (P = 7.33 × 10–13), and DAA regimen (LDV/SOF or PTV/OBV/r) (P = 1.92 × 10–14) were independent factors contributing to SVR. Except for patients with DAA‐based treatment history, absence of cirrhosis (P = 2.15 × 10–3; odds ratio, 2.51) was an independent factor contributing to SVR in 2038 DAA‐naïve patients. Conclusion This study suggests that the presence of cirrhosis reduces the SVR rate of DAA treatment, regardless of the type of DAA treatment.

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Section: Discussioncontrasting

confidence: 90%

Efficacy of direct‐acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study

Itokawa

Atsukawa

Tsubota

et al. 2018

Hepatology Research

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“…It was noteworthy that eight patients receiving hemodialysis achieved an SVR under G/P, which supported previous reports that even individuals with accompanying conditions could achieve an SVR safely and effectively by a G/P regimen [17]. We very recently described that a history of HCC was an independent risk factor of DAA treatment failure [18]. However, all 10 patients (6.2%) with prior HCC in our cohort achieved an SVR to further highlight the broad utility of G/P.…”

Section: Discussionsupporting

confidence: 82%

“…The P32 deletion has also been strongly linked to G/P therapy ineffectiveness by previous clinical reports [23,24], but we were unable to conclude a relationship with G/P failure as there was only one P32 deletion patient in our cohort who had acquired the mutation after DCV/ASV failure and did not receive G/P due to prior identification of the deletion. Regarding the administration of DCV + ASV, if patients harbored the NS5A-Y93H RAS and could no longer postpone treatment due to age, disease progression, or other clinical reasons, they commenced the regimen instead of waiting for next-generation DAAs, which could achieve a high SVR rate of 91.7% as reported previously [18]. The relatively low frequency of the P32 deletion in our cohort was presumably due to the above strategy.…”

Section: Discussionmentioning

confidence: 60%

Effectiveness of Glecaprevir/Pibrentasvir for Hepatitis C: Real-World Experience and Clinical Features of Retreatment Cases

et al. 2020

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Glecaprevir/pibrentasvir (G/P) are direct-acting antivirals (DAAs) that achieve a high sustained virological response (SVR) rate for hepatitis C virus (HCV) infection. We investigated G/P effectiveness for HCV patients based on real-world experience and the clinical features of retreatment cases. HCV patients (n = 182) were compared for clinical features and outcomes between first treatment (n = 159) and retreatment (n = 23) G/P groups. Overall, 77 patients (42.3%) were male, the median age was 68 years, and 86/66/1/4 cases had genotype 1/2/1 + 2/3, respectively. An SVR was achieved in 97.8% (178/182) of cases by intention-to-treat analysis and 99.4% (178/179) of cases by per-protocol analysis. There were no remarkable differences between the first treatment and retreatment groups for male (42.8% vs. 39.1%, p = 0.70), median age (68 vs. 68 years, p = 0.36), prior hepatocellular carcinoma (5.8% vs. 8.7%, p = 0.59), or the fibrosis markers AST-to-platelet ratio index (APRI) (0.5 vs. 0.5, p = 0.80) and fibrosis-4 (FIB-4) index (2.2 vs. 2.6, p = 0.59). The retreatment group had a significantly more frequent history of interferon treatment (12.3% vs. 52.2%, p < 0.01) and the Y93H mutation (25.0% vs. 64.7%, p = 0.02). The number of retreatment patients who had experienced 3, 2, and 1 DAA treatment failures was 1, 3, and 19, respectively, all of whom ultimately achieved an SVR by G/P treatment. In conclusion, G/P was effective and safe for both HCV first treatment and retreatment cases despite the retreatment group having specific resistance mutations for other prior DAAs. As G/P treatment failure has been reported for P32 deletions, clinicians should consider resistance mutations during DAA selection.

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“…Study characteristics were summarised in Tables and . Fifty‐six studies were included, with a total of 5522 patients with HCC, while 27 studies enrolled non‐HCC patients as control groups. Fifty‐three (95%) studies were observational cohorts (45 retrospective and eight prospective) and three studies were clinical trials.…”

Section: Resultsmentioning

confidence: 99%

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

Lockart

Alavi

et al. 2019

Aliment Pharmacol Ther

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Summary Background Direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision‐making. Aim To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC. Methods Bibliographic databases and conference abstracts were searched. Meta‐analysis was conducted to pool sustained virologic response (SVR) estimates. Results Fifty‐six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1‐90.4). Twenty‐seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0‐91.4) and 92.4% (95% CI 91.1‐93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43‐0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3‐92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3‐99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1‐95.6). Conclusion Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.

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Past history of hepatocellular carcinoma is an independent risk factor of treatment failure in patients with chronic hepatitis C virus infection receiving direct‐acting antivirals

Cited by 21 publications

References 40 publications

Efficacy of direct‐acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study

Efficacy of direct‐acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study

Effectiveness of Glecaprevir/Pibrentasvir for Hepatitis C: Real-World Experience and Clinical Features of Retreatment Cases

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

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