Time association between hepatitis C therapy and hepatocellular carcinoma emergence in cirrhosis: Relevance of non-characterized nodules
Por:
Marino, Z, Darne, A, Lens, S, Sapena, V, Diaz, A, Belmonte, E, Perello, C, Calleja, JL, Varela, M, Rodriguez, M, de Lope, CR, Llerena, S, Torras, X, Gallego, A, Sala, M, Morillas, RM, Minguez, B, Llaneras, J, Coll, S, Carrion, JA, Inarrairaegui, M, Sangro, B, Vilana, R, Sole, M, Ayuso, C, Rios, J, Forns, X, Bruix, J, Reig, M
Publicada:
1 may 2019
Resumen:
Background & Aims: Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC.
Methods: This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years.
Results: A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased.
Conclusion: These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation.
Lay summary: In this cohort of cirrhotic patients, interferonfree therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clearcut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased. (C) 2019 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
Filiaciones:
Marino, Z:
Univ Barcelona, Hosp Clin Barcelona, Liver Unit, IDIBAPS, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Darne, A:
Univ Barcelona, Hosp Clin Barcelona, Radiol Dept, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
Lens, S:
Univ Barcelona, Hosp Clin Barcelona, Liver Unit, IDIBAPS, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Sapena, V:
Univ Barcelona, Hosp Clin Barcelona, Liver Unit, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Diaz, A:
Univ Barcelona, Hosp Clin Barcelona, Pathol Dept, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
Belmonte, E:
Univ Barcelona, Hosp Clin Barcelona, Radiol Dept, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
Perello, C:
Univ Autonoma Madrid, Hosp Univ Puerta de Hierro IDIPHIM, Liver Unit, Madrid, Spain
Calleja, JL:
Univ Autonoma Madrid, Hosp Univ Puerta de Hierro IDIPHIM, Liver Unit, Madrid, Spain
Varela, M:
Univ Oviedo, Hosp Univ Cent Asturias, Gastroenterol Dept, Liver Unit, Oviedo, Spain
Rodriguez, M:
Univ Oviedo, Hosp Univ Cent Asturias, Gastroenterol Dept, Liver Unit, Oviedo, Spain
de Lope, CR:
Hosp Univ Marques de Valdecilla, Gastroenterol Dept, IDIVAL, Santander, Spain
Llerena, S:
Hosp Univ Marques de Valdecilla, Gastroenterol Dept, IDIVAL, Santander, Spain
Torras, X:
Hosp Santa Creu & Sant Pau, Gastroenterol & Hepatol Dept, CIBERehd, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Gallego, A:
Hosp Santa Creu & Sant Pau, Gastroenterol & Hepatol Dept, CIBERehd, Barcelona, Spain
Sala, M:
Hosp Badalona Germans Trias & Pujol, Gastroenterol Dept, Liver Unit, Badalona, Spain
CIBEREHD, Barcelona, Spain
Morillas, RM:
Hosp Badalona Germans Trias & Pujol, Gastroenterol Dept, Liver Unit, Badalona, Spain
CIBEREHD, Barcelona, Spain
Minguez, B:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron, VHIR, Liver Unit,Dept Internal Med, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Llaneras, J:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron, VHIR, Liver Unit,Dept Internal Med, Barcelona, Spain
Coll, S:
UAB, Hosp del Mar, Med Res Inst, Liver Sect,Gastroenterol Dept,IMIM, Barcelona, Spain
Carrion, JA:
UAB, Hosp del Mar, Med Res Inst, Liver Sect,Gastroenterol Dept,IMIM, Barcelona, Spain
Inarrairaegui, M:
Clin Univ Navarra, Liver Unit, IDISNA, Pamplona, Spain
CIBEREHD, Barcelona, Spain
Sangro, B:
Clin Univ Navarra, Liver Unit, IDISNA, Pamplona, Spain
CIBEREHD, Barcelona, Spain
Vilana, R:
Univ Barcelona, Hosp Clin Barcelona, Radiol Dept, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
Sole, M:
Univ Barcelona, Hosp Clin Barcelona, Pathol Dept, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
Ayuso, C:
Univ Barcelona, Hosp Clin Barcelona, Radiol Dept, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Rios, J:
Hosp Clin Barcelona, IDIBAPS, Med Stat Core Facil, Barcelona, Spain
Univ Autonoma Barcelona, Fac Med, Biostat Unit, Barcelona, Spain
Forns, X:
Univ Barcelona, Hosp Clin Barcelona, Liver Unit, IDIBAPS, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Bruix, J:
Univ Barcelona, Hosp Clin Barcelona, Liver Unit, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Reig, M:
Univ Barcelona, Hosp Clin Barcelona, Liver Unit, IDIBAPS,Barcelona Clin Liver Canc BCLC Grp, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Green Accepted
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