miRNA Expression and HCC Occurrence in HCV Cirrhotic Patients Treated with Direct Acting Antivirals
Antonietta Romano,
Alessandra Brocca,
Zoe Mariño,
Sofía Pérez-del-Pulgar,
Sabela Lens,
Loreto Boix,
María Reig,
Jordi Bruix,
Giulio Ceolotto,
Valeria Calvino,
Gianluca Zilio,
Paula Piñero Romero,
Ranka Vukotic,
Valeria Guarneri,
Pietro Andreone,
Saverio Giuseppe Parisi,
Francesco Paolo Russo,
Salvatore Piano,
Umberto Cillo,
Paolo Angeli
Affiliations
Antonietta Romano
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
Alessandra Brocca
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
Zoe Mariño
Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
Sofía Pérez-del-Pulgar
Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
Sabela Lens
Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
Loreto Boix
Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
María Reig
Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
Jordi Bruix
Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, Spain
Giulio Ceolotto
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
Valeria Calvino
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
Gianluca Zilio
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
Paula Piñero Romero
CIBER-ehd, General University Hospital of Alicante, 03010 Alicante, Spain
Ranka Vukotic
Department of Medical and Surgical Sciences, DIMEC, University of Bologna, 40138 Bologna, Italy
Valeria Guarneri
Department of Medical and Surgical Sciences, DIMEC, University of Bologna, 40138 Bologna, Italy
Pietro Andreone
Internal and Metabolic Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
Saverio Giuseppe Parisi
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
Francesco Paolo Russo
Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, University of Padova, 35121 Padova, Italy
Salvatore Piano
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
Umberto Cillo
Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
Paolo Angeli
Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, 35128 Padova, Italy
Background: The risk of hepatocarcinoma in HCV cirrhotic patient responders after treatment with DAAs decrease, but HCC still occurs. A correlation between specific miRNAs and the development of hepatocarcinoma have been highlighted. Aim: To investigate miRNA expression in HCV-infected cirrhotic patients treated with DAAs, regarding whether or not they developed HCC at follow-up. Methods: A total of 73 outpatients with HCV-related cirrhosis treated with DAAs were enrolled, 28 of which had HCC. Samples were collected at the start and at the end of treatment. In the screening phase, 172 miRNAs were analyzed at baseline. Differentially expressed miRNAs were validated in the entire cohort. Results: In the validation phase, at baseline and in patients treated for 12 weeks, miR-28-5p was confirmed to be more highly expressed in the HCC group compared to the non-HCC group. In all of the patients treated for 12 weeks, at end of the treatment we found a significant downregulation in miR-132-3p, miR-133b-3p, miR-221-3p and miR-324-3p. In the HCC group, miR-28-5p was significantly downregulated after DAA therapy as well as in HCC patients treated for 24 weeks. Conclusion: In the HCC group, miR28-5p was differently expressed both at baseline and at the end of therapy with DAAs. This difference in expression should suggest its involvement in HCC development.
