Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents

Calvaruso, Vincenza; Cabibbo, Giuseppe; Cacciola, Irene; Petta, Salvatore; Scalisi, I.; Barbàra, Marco; Squadrito, Giovanni; Cammà, Calogero; Marco, V. Di; Cabbibbo, G.; Colletti, Pietro; Mazzola, Giovanni; Cascio, Antonio; Montalto, Giuseppe; Licata, Anna; Giannitrapani, Lydia; Prestileo, Tullio; Lorenzo, Francesco Di; Sanfilippo, Adriana; Ficalora, A.; Madonia, Salvatore; Tinè, Fabio; Malizia, Giuseppe; Latteri, Federica; Maida, Marcello; Cartabellotta, F.; Vassallo, Roberto; Caccamo, Gaia; Maimone, S.; Saitta, Carlo; Raimondo, Giovanni; Mondello, L.; Smedile, A.; DʼAndrea, Samantha; Bertino, Gaetano; Ardiri, A.L.; Frazzetto, Evelise; Rigano, Giuseppe; Montineri, Arturo; Larocca, Licia; Cacopardo, Bruno; Benanti, F.; Russello, Maurizio; Benigno, R.; Bellia, Adriano; Iacobello, Carmelo; Davì, A.; Rosolini, Maria Antonietta Di; Digiacomo, A.; Fuduli, G.; Scifo, G.; Distefano, Marco; Portelli, V.; Savalli, F.; Scalici, I.; Gioia, Giuseppe Di; Magro, A.; Alaimo, Giuseppe; Alinovi, M.R.; Salvo, A.; Averna, A.; Lomonaco, F; Guarneri, L.; Maffeo, F.; Falzone, É.; Pulvirenti, Federica

doi:10.1053/j.gastro.2018.04.008

Cited by 313 publications

(301 citation statements)

References 37 publications

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“…We plotted the incidence of HCC in subgroups based on the presence or absence of cirrhosis at baseline, given previous data demonstrating cirrhosis as the single most important risk factor for HCC following SVR . The HCC incidence rates ranged from 1.3 to 2.3 per 100 PY in patients with cirrhosis (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although successful treatment resulting in SVR represents a cure from the standpoint of chronic infection, studies suggest that subsequent risk of hepatocellular carcinoma (HCC), while considerably reduced compared with active HCV infection, persists after treatment with DAAs. The absolute risk of HCC ranged from 1.8%‐3.5% in the first 12 months following SVR in published studies . However, these studies were limited by short‐term follow up.…”

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confidence: 99%

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Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

et al. 2019

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Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long‐term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow‐up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB‐4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow‐up. The cumulative 1, 2, and 3‐year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio = 4.13, 95% confidence interval = 3.34‐5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person‐years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB‐4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB‐4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion: Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow‐up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.

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Section: Resultsmentioning

confidence: 99%

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Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

et al. 2019

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“…A prospective Italian cohort study of 2,249 DAA-treated patients with cirrhosis required that all patients have a baseline ultrasound (US) before antiviral therapy and excluded patients who did not have an US after DAA initiation (11). The 1-year cumulative incidence of HCC was 2.6% in patients who achieved SVR versus 8.0% in patients who failed to achieve SVR.…”

Section: Daa Treatment and De Novo Hccmentioning

confidence: 99%

The Impact of Direct-acting Antiviral Therapy for Hepatitis C on Hepatocellular Carcinoma Risk

Ioannou

2018

Curr Hepatology Rep

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Purpose of review Direct-acting antiviral agents (DAAs) eradicate hepatitis C virus (HCV) infection in the majority of patients. We critically evaluated the impact of DAAs on hepatocellular carcinoma (HCC) risk, a major complication of HCV infection. Recent findings Large cohort studies show that patients who achieve sustained virologic response (SVR) with DAAs have a significantly lower risk of developing de novo HCC than patients who fail treatment or remain untreated. Furthermore, reduction in HCC risk is similar whether SVR is achieved with DAAs or interferon (IFN). However, DAA-induced SVR does not eliminate HCC risk entirely. Therefore, patients with pre-existing cirrhosis require ongoing surveillance even after SVR is achieved. Early, descriptive, uncontrolled reports suggested that DAAs may increase the risk of recurrent HCC. While studying HCC recurrence presents major methodologic challenges, larger studies containing appropriate comparison control groups largely refuted these concerns. Summary Recent studies provide evidence that DAA-induced SVR reduces HCC risk.

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“…Among those treated with IFN‐based treatments, the cumulative rate of hepatocellular carcinoma (HCC) occurrence is higher in non‐SVR patients than in SVR patients . Furthermore, among those treated with IFN‐free treatment, the cumulative rate of HCC occurrence is higher in non‐SVR patients than in SVR patients . However, regarding IFN‐free DAA treatment, Conti et al .…”

Section: Introductionmentioning

confidence: 99%

Hepatocellular carcinoma occurrence does not differ between interferon‐based and interferon‐free treatment with liver histological assessment

Tahata

Sakamori

Urabe

et al. 2020

Hepatology Research

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Aim Several studies have recently reported that hepatocellular carcinoma (HCC) occurrence does not differ between hepatitis C virus patients receiving interferon (IFN)‐based and IFN‐free treatments considering the patients’ backgrounds. However, liver fibrosis was not directly considered in these studies. Methods In total, 3972 patients without a history of HCC who started IFN‐based or IFN‐free treatment between August 2002 and April 2017 at 30 Japanese hospitals and achieved a sustained virologic response were included. Propensity score matching considering liver histology was performed. Results The median age and percentage of patients with advanced liver fibrosis (F3/4) were 58 years and 11.4% in the IFN‐based group, and 68 years and 18.9% in the IFN‐free group, respectively. The HCC occurrence rates at 1 year and 2 years were 0.4% and 1.1% in the IFN‐based group, and 1.6% and 4.1% in the IFN‐free group, respectively, and HCC occurrence in the IFN‐free group was significantly higher than that in the IFN‐based group (P < 0.001). The characteristics of the HCC occurrence patterns did not differ between the two groups. After propensity score matching, among 764 patients, the HCC occurrence rates at 1 year and 2 years were 0.5% and 1.9% in the IFN‐based group and 1.1% and 3.0% in the IFN‐free group, respectively, and no significant difference was observed between the two groups (P = 0.489). Conclusions HCC occurrence in sustained virologic response patients does not differ between IFN‐based and IFN‐free treatment considering liver fibrosis stage. The degree of its progress at diagnosis does not differ between the two groups.

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Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents

Cited by 313 publications

References 37 publications

Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

The Impact of Direct-acting Antiviral Therapy for Hepatitis C on Hepatocellular Carcinoma Risk

Hepatocellular carcinoma occurrence does not differ between interferon‐based and interferon‐free treatment with liver histological assessment

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