Liver cancer risk after HCV cure in patients with advanced liver disease without non-characterized nodules.


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
Apr 2022
Historique:
received: 30 05 2021
revised: 14 11 2021
accepted: 15 11 2021
pubmed: 3 12 2021
medline: 26 4 2022
entrez: 2 12 2021
Statut: ppublish

Résumé

Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population. We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months. A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified. Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs. Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population.
METHODS METHODS
We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months.
RESULTS RESULTS
A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified.
CONCLUSIONS CONCLUSIONS
Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs.
LAY SUMMARY BACKGROUND
Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.

Identifiants

pubmed: 34856322
pii: S0168-8278(21)02228-5
doi: 10.1016/j.jhep.2021.11.023
pii:
doi:

Substances chimiques

Antiviral Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

874-882

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Conflict of interest MSZ: received speaker fees from Bayer and travel grants from Bayer, BTG and Eisai; ZM: received consultancy fees from Gilead, Abbvie, Alexion, Orphalan and Deep Genomics; speaker fees from Gilead and Abbvie and research grants from Gilead; SL: received consultancy and speaker fees from Gilead and Abbvie and grants from Gilead, VS: received travel grants from Bayer; GI: received ravel grants from Bayer; NG: congress inscriptions: Eisai; NLL: Bayer, AstraZeneca, Travel funding: Bayer Congress inscriptions: Eisai; AD: speaker fees and travel grants from Bayer; AGC: Speaker fees from BTG and Terumo; AD: speaker fees from Bayer and travel grants from Bayer; SMM: received speaker fees from Bayer and travel grants from Bayer and Eisai; CA: Speaker fees, travel and research grants from Bayer, BTG and Terumo. Consultancy from ROCHE; JR: has consulted for Roche and received speaker fees from Bayer and Roche and travel grants from Bayer; AF: Lecture fees from Bayer, Gilead and MSD; consultancy fees from Bayer, AstraZeneca, Roche and Guerbert; FT: DSMB fees from Archivel Farma, S.L., Daiichi-Sankyo Pharma Development, ArQule and Rovi; speaker fees from Bayer; lecture fees from Janssen; JB: has consulted for Arqule, Bayer-Shering Pharma, Novartis, BMS, BTG- Biocompatibles, Eisai, Kowa, Terumo, Gilead, Bio-Alliance, Roche, AbbVie, MSD, Sirtex, Ipsen, Astra-Medimmune, Incyte, Quirem, Adaptimmune, Lilly, Basilea, Nerviano, Sanofi; and received research/educational grants from Bayer, and lecture fees from Bayer-Shering Pharma, BTG-Biocompatibles, Eisai, Terumo, Sirtex, Ipsen; XF: acted as advisor for Gilead and Abbvie; MR: received consultancy fees and/or travel support from Bayer, BMS, Roche, Ipsen, AstraZeneca, UniversalDX, Boston Scientific and Lilly, lecture fees from Bayer, BMS, Gilead, and Lilly and research grants from Bayer and Ipsen. Please refer to the accompanying ICMJE disclosure forms for further details.

Auteurs

Marco Sanduzzi-Zamparelli (M)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Zoe Mariño (Z)

Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.

Sabela Lens (S)

Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.

Victor Sapena (V)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Gemma Iserte (G)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Anna Pla (A)

Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.

Núria Granel (N)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Concepció Bartres (C)

Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.

Neus Llarch (N)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Ramón Vilana (R)

BCLC Group. Radiology Department Hospital Clinic of Barcelona, University of Barcelona, Spain.

Isabel Nuñez (I)

Radiology Department, Hospital Clinic of Barcelona, Spain.

Anna Darnell (A)

BCLC Group. Radiology Department Hospital Clinic of Barcelona, University of Barcelona, Spain.

Ernest Belmonte (E)

BCLC Group. Radiology Department Hospital Clinic of Barcelona, University of Barcelona, Spain.

Angeles García-Criado (A)

BCLC Group. Radiology Department Hospital Clinic of Barcelona, University of Barcelona, Spain.

Alba Díaz (A)

BCLC Group. Department of Pathology, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.

Sergio Muñoz-Martinez (S)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Carmen Ayuso (C)

BCLC Group. Radiology Department Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.

Luis Bianchi (L)

BCLC Group. Radiology Department Hospital Clinic of Barcelona, University of Barcelona, Spain.

Carla Fuster-Anglada (C)

BCLC Group. Department of Pathology, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.

Jordi Rimola (J)

BCLC Group. Radiology Department Hospital Clinic of Barcelona, CIBERehd, University of Barcelona, Spain.

Alejandro Forner (A)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Ferran Torres (F)

Medical Statistics Core Facility, IDIBAPS, Hospital Clinic of Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma of Barcelona, Barcelona, Spain.

Jordi Bruix (J)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.

Xavier Forns (X)

Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain. Electronic address: XFORNS@clinic.cat.

Maria Reig (M)

BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain. Electronic address: mreig1@clinic.cat.

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