Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis

Chiara Masetti, Raffaella Lionetti, Marinella Lupo, Massimo Siciliano, Valerio Giannelli, Francesca Romana Ponziani, Elisabetta Teti, Chiara Dell'Unto, Simona Francioso, Arianna Brega, Marzia Montalbano, Ubaldo Visco-Comandini, Chiara Taibi, Giovanni Galati, Umberto Vespasiani Gentilucci, Antonio Picardi, Massimo Andreoni, Maurizio Pompili, Adriano M. Pellicelli, Gianpiero D'OffiziAntonio Gasbarrini, Adriano De Santis, Mario Angelico

Research output: Contribution to journalArticle

Abstract

Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment.

Original languageEnglish
Pages (from-to)1493-1500
Number of pages8
JournalJournal of Viral Hepatitis
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

Keywords

  • alpha-fetoprotein
  • direct-acting antiviral agents
  • hepatitis C
  • hepatocellular carcinoma

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

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    Masetti, C., Lionetti, R., Lupo, M., Siciliano, M., Giannelli, V., Ponziani, F. R., Teti, E., Dell'Unto, C., Francioso, S., Brega, A., Montalbano, M., Visco-Comandini, U., Taibi, C., Galati, G., Vespasiani Gentilucci, U., Picardi, A., Andreoni, M., Pompili, M., Pellicelli, A. M., ... Angelico, M. (2018). Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis. Journal of Viral Hepatitis, 25(12), 1493-1500. https://doi.org/10.1111/jvh.12982