Hepatocellular carcinoma recurrence in hepatitis C virus-related cirrhosis treated with direct-acting antivirals: a case–control study

Adhoute, Xavier; Pénaranda, Guillaume; Raoul, Jean‐Luc; Sellier, Floriane; Castellani, Paul; Oulès, Valérie; Perrier, H.; Lefolgoc, G.; Pol, Bernard; Campanile, M.; Bayle, Olivier; Beaurain, Patrick; Monnet, O.; Bourlière, Marc

doi:10.1097/meg.0000000000001082

Cited by 24 publications

(34 citation statements)

References 54 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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“…Overall, 24 papers (with 25 cohorts of patients) [6,7, reporting on HCC recurrence after DAAs treatment in patients with previously and successfully treated HCC (liver resection, ablation or trans-catheter arterial chemoembolization -TACE) were identified. Two papers only considered patients with HCC recurrence [25,27], two included also patients who underwent liver transplantation before starting DAAs [16,29], and one focused on radiological features of…”

Section: Literature Selectionmentioning

confidence: 99%

“…Most patients had limited disease burden at baseline, i.e. single HCC (67-94% of cases) [10, 13-15, 23, 26, 27, 29] < 5 cm in size (range of median size 1.8-4.7 cm) [10, 13-16, 23, 26, 27, 29] and Barcelona-Clinic Liver Cancer (BCLC) stage 0/A (61-100% of cases) [6,7,10,11,16,20,23,24,26,29].…”

Section: Recurrence Riskmentioning

confidence: 99%

“…Twelve study groups performed a Kaplan-Meyer analysis [6, 9-11, 13-15, 17, 18, 20, 23, 24, 31], and one paper performed a Poisson regression [26]. The time to recurrence was calculated in different ways: from the last HCC treatment in 8 papers [6,9,14,17,18,20,23,29], from the initiation of DAAs therapy in 9 papers [9-11, 13, 15, 17, 20, 26, 31] and from the end of DAAs therapy in one study [24]. In the last two groups, the mean/median time between the last HCC treatment and DAAs start ranged from 8 to 21 months.…”

Section: Time-to-event Analysesmentioning

confidence: 99%

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Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

Galati

Muley

Viganò

et al. 2018

Digestive and Liver Disease

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Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid growth and vascular invasion) of tumor recurrence after DAAs still remains to be confirmed. Several limitations of the available studies were highlighted, and should drive future researches. The time-to-recurrence should be computed since the last HCC treatment and results stratified for cirrhosis and sustained viral response. Any comparison with historical series is of limited interest because of a number of biases affecting these studies and differences between enrolled patients. Prospective intention-to-treat analyses will be probably the best contribution to drive clinical practice, provided that a randomized trial can be difficult to design.

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“…( 7‐10 ) Other authors described a higher incidence of tumor recurrence after curative therapies for HCC, particularly with more aggressive tumor patterns, ( 6,11 ) whereas other groups reported no association. ( 12‐17 ) Consequently, whether rapid viral eradication with DAAs leads to an abrupt withdrawal of antineoplastic immunological surveillance is still under discussion. ( 18 )…”

mentioning

confidence: 99%

Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence

et al. 2020

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The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre-or post-LT DAA effect). From 994 included patients, 50.6% were HCV−, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alphafetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre-or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT. LiverTransplantation 26 640-650 2020 AASLD. PiñerO et al. liver transPlantatiOn, vol. 26, no. 5, 2020 PiñerO et al.

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Hepatocellular carcinoma recurrence in hepatitis C virus-related cirrhosis treated with direct-acting antivirals: a case–control study

Cited by 24 publications

References 54 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

Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence

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