Impact of direct-acting antivirals on early recurrence of HCV-related HCC: Comparison with interferon-based therapy

Kinoshita, Mizuki Nishibatake; Minami, Tatsuya; Tateishi, Ryosuke; Wake, Taijiro; Nakagomi, Ryo; Fujiwara, Naoto; Sato, Masaya; Uchino, Katsuyoshi; Enooku, Kenichiro; Nakagawa, Hayato; Asaoka, Yoshinari; Shiina, Shuichiro; Koike, Kazuhiko

doi:10.1016/j.jhep.2018.09.029

Cited by 76 publications

(56 citation statements)

References 29 publications

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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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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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“…23 In addition, debate is ongoing as to whether or not DAA use increases HCC recurrence rates. 18,20,27,28,29, 30…”

Section: Discussionmentioning

confidence: 99%

Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma

Kamp

Sellers

Stein

et al. 2019

Preprint

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26Direct-acting antiviral use is associated with increased survival in hepatitis C-related 27 hepatocellular carcinoma patients. Patients treated with direct-acting antiviral who achieved 28 hepatitis C cure had additionally increased survival versus those treated with direct-acting 29 antiviral who did not achieve hepatitis C cure. This study supports the use of direct-acting 30 antiviral for hepatitis C treatment in hepatocellular carcinoma patients. Abbreviations 53 DAA: Direct-acting antivirals; SVR12: 12-week sustained virologic response; HCC: 54 hepatocellular carcinoma; HCV: hepatitis c virus; OS: median overall survival; AJCC: American 55 Joint Committee on Cancer stage; MELD: Model for end stage liver disease; HR: hazard ratio 4 56 Abstract: 57 Background: To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained 58 viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C 59 virus (HCV) infection. Methods: Retrospective analysis of HCC patients diagnosed from 2005 60 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox 61 proportional hazards models were used to assess survival. Results: 969 patients met inclusion 62 criteria. 478 patients received interventional oncology treatment (catheter-based therapies, 63 ablation or combination locoregional therapies), 141 received supportive care (palliative or no 64 treatment), 125 underwent liver transplantation, 112 had tumor resection and 94 received 65 chemotherapy or radiation as their primary treatment. Median overall survival of the cohort was 66 24.2 months (95% CI: 20.9-27.9). 470 patients had HCV (56%). 123 patients received DAA 67 therapies for HCV (26.2%), 83 of whom achieved SVR12 (68%). HCV-positive and HCV-68 negative patients had similar survival (20.7 months vs 17.4 months, p=0.22). Patients receiving 69 DAA therapy had an overall survival of 71.8 months (CI: 39.5-not reached) vs 11.6 months (CI: 70 9.8-14.5) for patients without DAA therapy (p<0.0001). DAA patients who achieved SVR12 had 71 an overall survival of 75.6 months (CI: 49.2-not reached) vs the non-SVR12 group (26.7 months, 72 CI: 13.7-31.1, p<0.0001). Multivariable analysis revealed AJCC, Child-Pugh Score, MELD, 73 tumor size, tumor location and treatment type had independent influence on survival (p<0.05). 74 In HCV-positive patients, AJCC, MELD, tumor location, treatment allocation and DAA were 75 significant (p<0.05). In patients receiving DAA therapy, only MELD and SVR12 were predictive 76 of overall survival (p<0.05). Conclusions: DAA therapy and achieving SVR12 is associated 77 with increased overall survival in HCV patients with HCC. 78 5 79

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“…Tertiary prevention by IFN-based therapy has been proved to reduce tumor recurrence and prolong survival in postsurgical resection HCC patients [4,32,33]. However, conflicting reports have shown uncertainty of the tertiary prevention effects of DAA treatment in HCC recurrence prevention [11,12,15,27,[34][35][36]. These inconsistent results might come from a selection bias, since patients eligible for IFN-based therapy were younger and with better liver reserve, which are protective factors for HCC development, than those treated with the DAA regimen [37,38].…”

Section: Discussionmentioning

confidence: 99%

“…However, a recent meta-analysis concluded that the HCC occurrence and recurrence rates were comparable between DAA-and IFN-treated patients regardless of the higher SVR rate of the DAA regimen [10]. Moreover, several reports with single-arm DAA-treated HCV-HCC patients declared abruptly increased HCC recurrence rate after antiviral treatment [11][12][13][14], while conflicting results have been reported in other studies comparing to the untreated [15][16][17][18][19][20][21][22][23][24][25] or IFN-treated groups [10,21,[26][27][28][29][30]. Concerns have been raised about the benefit and the timing of adjuvant DAA-based therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Some of these studies consisted of an IFN-containing DAA regimen [27,28] and did not adjust for baseline characteristics before comparison [26,30]. The definition of follow-up duration varies across these studies [10,21,[23][24][25][26][27][28][29][30] and may lead to inconsistent or conflicting comparison results [31]. We therefore conducted this nested case-control study, using propensity score matching (PSM) to adjust for the confounders, and with application of different follow-up time frames to investigate if the tertiary prevention effect is different between the DAA and PegIFN/RBV regimens in curative CHC-HCC patients.…”

Section: Introductionmentioning

confidence: 99%

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Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

Teng

Jeng

Yang

et al. 2019

Cancers

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The elimination of chronic hepatitis C infection (CHC) by pegylated interferon plus ribavirin (Peg-IFN/RBV) decreases hepatocellular carcinoma (HCC) recurrence rate. However, the tertiary prevention of HCC recurrence by direct acting antiviral agents (DAA) remains controversial. This study aims to compare the tertiary prevention effect between DAA and Peg-IFN/RBV in CHC-HCC patients. Three hundred and one patients who received curative HCC treatment were retrospectively recruited. The recurrence incidence rate (IR) was compared among patients either receiving Peg-IFN/RBV or DAA regimen or untreated by three timeframes (I: from HCC treatment to antiviral therapy; II: during antiviral therapy; III: after antiviral therapy). The prevention effect between Peg-IFN/RBV and DAA were compared in frame II and III after propensity score matching (PSM) with age, tumor staging, HCC treatment modality, and cirrhotic status. Before PSM, the recurrence IRs in three arms were comparable in frame I, while being lower in the Peg-IFN/RBV and DAA arm compared to the untreated arm in frame II. In frame III, the tertiary prevention effect lasted in the Peg-IFN/RBV arm (p < 0.001), but diminished in the DAA arm (p = 0.135) compared to untreated patients. After PSM, the HCC recurrence IR was higher in the DAA arm than the Peg-IFN/RBV arm in frame II (2724 vs. 666 per 10 4 person-years, log-rank p = 0.042) and III (5259 vs. 3278 per 10 4 person-years, log-rank p = 0.048). Preantiviral ALBI grade therapy is the only predictor for postantiviral therapy HCC recurrence. In conclusion, the tertiary prevention effect of HCC recurrence was not durable in DAA-treated patients, but persisted in Peg-IFN/RBV treatment patients.

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Impact of direct-acting antivirals on early recurrence of HCV-related HCC: Comparison with interferon-based therapy

Cited by 76 publications

References 29 publications

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

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

Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma

Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

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