Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics
Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/6/1351 |
| _version_ | 1797567037778690048 |
|---|---|
| author | Luca Rinaldi Riccardo Nevola Gianluigi Franci Alessandro Perrella Giusy Corvino Aldo Marrone Massimiliano Berretta Maria Vittoria Morone Marilena Galdiero Mauro Giordano Luigi Elio Adinolfi Ferdinando Carlo Sasso |
| author_facet | Luca Rinaldi Riccardo Nevola Gianluigi Franci Alessandro Perrella Giusy Corvino Aldo Marrone Massimiliano Berretta Maria Vittoria Morone Marilena Galdiero Mauro Giordano Luigi Elio Adinolfi Ferdinando Carlo Sasso |
| author_sort | Luca Rinaldi |
| collection | DOAJ |
| description | Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management. |
| first_indexed | 2024-03-10T19:35:55Z |
| format | Article |
| id | doaj.art-af78dcbca41e4cff9c7cf55a3bc60853 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:35:55Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-af78dcbca41e4cff9c7cf55a3bc608532023-11-20T01:45:03ZengMDPI AGCancers2072-66942020-05-01126135110.3390/cancers12061351Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of EpigeneticsLuca Rinaldi0Riccardo Nevola1Gianluigi Franci2Alessandro Perrella3Giusy Corvino4Aldo Marrone5Massimiliano Berretta6Maria Vittoria Morone7Marilena Galdiero8Mauro Giordano9Luigi Elio Adinolfi10Ferdinando Carlo Sasso11Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Medicine, Surgery, Dentistry, University of Salerno “Scuola Medica Salernitana”, 84100 Salerno, ItalyImmunological and Neurological Infectious Diseases, Cotugno Hospital, 80100 Naples, ItalyDepartment of Experimental Medicine, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Medical Oncology, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, 33081 Aviano, ItalyDepartment of Experimental Medicine, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Experimental Medicine, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, ItalyDirect-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.https://www.mdpi.com/2072-6694/12/6/1351hepatocellular carcinomadirect acting antiviralsHCVcytokinessustained virological responseepigenetic modulation |
| spellingShingle | Luca Rinaldi Riccardo Nevola Gianluigi Franci Alessandro Perrella Giusy Corvino Aldo Marrone Massimiliano Berretta Maria Vittoria Morone Marilena Galdiero Mauro Giordano Luigi Elio Adinolfi Ferdinando Carlo Sasso Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics Cancers hepatocellular carcinoma direct acting antivirals HCV cytokines sustained virological response epigenetic modulation |
| title | Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics |
| title_full | Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics |
| title_fullStr | Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics |
| title_full_unstemmed | Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics |
| title_short | Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics |
| title_sort | risk of hepatocellular carcinoma after hcv clearance by direct acting antivirals treatment predictive factors and role of epigenetics |
| topic | hepatocellular carcinoma direct acting antivirals HCV cytokines sustained virological response epigenetic modulation |
| url | https://www.mdpi.com/2072-6694/12/6/1351 |
| work_keys_str_mv | AT lucarinaldi riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT riccardonevola riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT gianluigifranci riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT alessandroperrella riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT giusycorvino riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT aldomarrone riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT massimilianoberretta riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT mariavittoriamorone riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT marilenagaldiero riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT maurogiordano riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT luigielioadinolfi riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics AT ferdinandocarlosasso riskofhepatocellularcarcinomaafterhcvclearancebydirectactingantiviralstreatmentpredictivefactorsandroleofepigenetics |