Direct-Acting Antivirals Decreased Tumor Recurrence After Initial Treatment of Hepatitis C Virus-Related Hepatocellular Carcinoma

Ikeda, Kenji; Kawamura, Yusuke; Kobayashi, Masahiro; Kominami, Yoko; Fujiyama, Shunichiro; Sezaki, Hitomi; Hosaka, Tetsuya; Akuta, Norio; Saitoh, Satoshi; Suzuki, Fumitaka; Suzuki, Yoshiyuki; Arase, Yasuji; Kumada, Hiromitsu

doi:10.1007/s10620-017-4739-z

Cited by 89 publications

(111 citation statements)

References 23 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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“…Direct‐acting antivirals (DAAs) have been considered to represent a long‐awaited solution in the treatment of hepatitis C. Thus, recent reports of the increased incidence of recurrent and de novo hepatocellular carcinoma (HCC) after DAA use have raised great concern. Following the publication of these reports, several other studies have confirmed the increased occurrence of HCC after DAA use, whereas others have refuted these findings . In a recent meta‐analysis of 41 DAA‐ and interferon (IFN)‐based studies (26 of HCC occurrence and 17 of HCC recurrence) including a total of 13,875 patients (90% with liver cirrhosis [LC]), DAA therapy was not associated with increased HCC occurrence or recurrence .…”

mentioning

confidence: 99%

“…use, (3,4) whereas others have refuted these findings. (5)(6)(7) In a recent meta-analysis of 41 DAA-and interferon (IFN)-based studies (26 of HCC occurrence and 17 of HCC recurrence) including a total of 13,875 patients (90% with liver cirrhosis [LC]), DAA therapy was not associated with increased HCC occurrence or recurrence. (8) In general, these studies show that the rate of recurrence is more variable than that of de novo HCC.…”

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confidence: 99%

Liver Angiopoietin‐2 Is a Key Predictor of D e N ovo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct‐Acting Antivirals

et al. 2018

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Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA‐treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin‐2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C‐reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echo‐Doppler work‐up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = –0.412, P = 0.037 and r = –0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3‐month follow‐up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044‐1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080‐2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395‐16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127‐13.203; P = 0.032) were independent predictors of de novo HCC. Conclusion: Our study indicates that DAA‐mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo‐angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 00:000‐000).

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“…In Japan report, the recurrence rate increased in accordance with treatment times in the past [11]. One-year recurrence rates were 18.1, 28.2, and 60.2%, and 2-year rates were 22.…”

Section: Hcc Recurrence After Daa Treatmentmentioning

confidence: 87%

9th Asia-Pacific Primary Liver Cancer Expert Meeting, Seoul, South Korea, July 6-8, 2018

2018

Liver Cancer

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Direct-Acting Antivirals Decreased Tumor Recurrence After Initial Treatment of Hepatitis C Virus-Related Hepatocellular Carcinoma

Abstract: DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.

Cited by 89 publications

References 23 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

Liver Angiopoietin‐2 Is a Key Predictor of D e N ovo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct‐Acting Antivirals

9th Asia-Pacific Primary Liver Cancer Expert Meeting, Seoul, South Korea, July 6-8, 2018

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