PREDICTIVE SCORES FOR HEPATOCELLULAR CARCINOMA OCCURRENCE AFTER HEPATITIS C VIRUS CURE WITH DIRECT ANTIVIRALS

Authors

  • Cristina MUZICA “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • C. STANCIU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Laura HUIBAN “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Irina GIRLEANU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Oana PETREA “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Ramona CADAR “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • S. ZENOVIA “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • T. CUCIUREANU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • R. NASTASA “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Ermina STRATINA “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • R. STAFIE “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • A. ROTARU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • H. MINEA “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Ana-Maria SINGEAP “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • C. SFARTI “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • S. CHIRIAC “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Camelia COJOCARIU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Anca TRIFAN “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Abstract

Hepatitis C virus (HCV) chronic infection has an important tumorigenic propensity and represents a major cause of hepatocellular carcinoma (HCC). Although the therapy of chronic HCV infection has been revolutionized with the introduction of direct acting antivirals (DAAs) resulting in sustained virological response (SVR) in up to 98% of patients, viral clearance does not totally alleviate the risk of liver-related complications, including HCC. The aim of our study was to assess the performance of predictive scores for HCC occurrence in patients with chronic HCV infection who obtained SVR with DAAs. Material and methods: We conducted a prospective study in which we included 992 patients diagnosed with chronic HCV infection and treated with DAAs, between 1st  November 2015 and 31st  December 2020. HCC risk scoring systems were applied to each patient enrolled in the study before starting DAA treatment. HCC was diagnosed by imaging methods such as computed tomography and magnetic resonance imaging. Results: Of the 992 patients included in the study, 59 (5.9%) were diagnosed with HCC during the follow-up period, mostly women (55.9%) with a mean age of 60-69 years. The mean time to HCC onset was 19.53 ± 11.553 months, with a median of 17 months, with a cumulative incidence at 1, 3, and 5 years of 1.1%, 2.1%, and 2.9%, respectively. The General Evaluation Score (GES),  aMAP and ADRESS score had statistically significant higher values in patients with HCC than in those without HCC. GES demonstrated a good  discriminating power with an AUC coefficient of 0.804 at a cut-off value of 6.25 which has good sensitivity and specificity (0.746 and 0.799, respectively). Conclusions: GES score has a very good predictive power for the risk of HCC after obtaining SVR and could be recommended in clinical practice. Future development and validation of other individualized predictive scores score is needed for a correct and cost-efficient selection of patients with high risk of HCC.

Author Biographies

  • Cristina MUZICA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • C. STANCIU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Laura HUIBAN, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Irina GIRLEANU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Oana PETREA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Ramona CADAR, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Surgery (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    1st Surgical Unit

  • S. ZENOVIA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • T. CUCIUREANU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • R. NASTASA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Ermina STRATINA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • R. STAFIE, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • A. ROTARU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • H. MINEA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Ana-Maria SINGEAP, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • C. SFARTI, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • S. CHIRIAC, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Camelia COJOCARIU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

  • Anca TRIFAN, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

    Faculty of Medicine
    Department of Medical Specialties (I)
    “Sf. Spiridon” County Clinical Emergency Hospital, Iasi, Romania
    Institute of Gastroenterology and Hepatology

References

1. Cheng TS, Liang PC, Huang CF, et al. Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C patients with genotype-2 infection after completed treatment. Kaohsiung J Med Sci 2021; 37: 334-345.
2. Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol 2017; 5: S0168-8278(17)32273-0.
3. Akuta N, Sezaki H, Fujiyama S, et al. Simple Predictive Markers and Clinicopathological Features of Primary Liver Cancer following HCV Clearance with Direct-Acting Antivirals. Oncology 2023; 101(2): 79-88.
4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 2018; 69: 182-236.
5. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carci-noma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatol-ogy 2018; 68: 723-750.
6. Kanda T, Lau GK, Wei L, et al. APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation. Hepatol Int 2019; 13: 649-661.
7. Luna-Cuadros MA, Chen HW, Hanif H, Ali MJ, Khan MM, Lau DT. Risk of hepatocellular carcinoma after hepatitis C virus cure. World J Gastroenterol 2022; 28: 96-107.
8. Yamashita Y, Joshita S, Sugiura A, et al. aMAP score prediction of hepatocellular carcinoma occur-rence and incidencefree rate after a sustained virologic response in chronic hepatitis C. Hepatol Res 2021; 51: 933-942.
9. Shiha G, Waked I, Soliman R, et al. GES: A validated simple score to predict the risk of HCC in patients with HCV-GT4-associated advanced liver fibrosis after oral antivirals. Liver Int 2020; 40(11): 2828-2833.
10. Bergna I, Degasperi E, D’Ambrosio R. Suboptimal accuracy of GES score to stratify post-SVR HCC risk in a single center cohort of European cirrhotics infected with any HCV genotype. Liver Int 2021; 41: 1152-1153.
11. Flemming JA, Yang JD, Vittinghoff E, Kim WR, Terrault N. Risk prediction of hepatocellular carci-noma in patients with cirrhosis: the ADRESS-HCC risk model. Cancer 2014; 120(22): 3485-3493.
12. Fan R, Papatheodoridis G, Sun J, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol 2020; 73(6): 1368-1378.
13. Shiha G, Mikhail N, Soliman R. External validation of aMAP risk score in chronic hepatitis C genotype 4 patients with liver cirrhosis who achieved SVR following DAAs. J Hepatol 2021; 74: 994-996.
14. Abe K, Wakabayashi H, Nakayama H, et al. Factors associated with hepatocellular carcinoma occur-rence after HCV eradication in patients without cirrhosis or with compensated cirrhosis. PLoS One 2020;15(12):e0243473.
15. Alonso Lopez S, Manzano ML, Gea F, et al. A model based on non-invasive markers predicts very low hepatocellular carcinoma risk after viral response in hepatitis C virus - advanced fibrosis. Hepatology 2020; 72: 1924-1934.

Additional Files

Published

2023-09-30

Issue

Section

INTERNAL MEDICINE - PEDIATRICS