Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B.

Abstract

BACKGROUND & AIMS:

Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting.

METHODS:

Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5.

RESULTS:

In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups.

CONCLUSIONS:

In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy.

LAY SUMMARY:

In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.

• Authors: George V Papatheodoridis, Vana Sypsa, George N Dalekos, Cihan Yurdaydin, Florian Van Boemmel, Maria Buti, Jose Luis Calleja, Heng Chi, John Goulis, Spilios Manolakopoulos, Alessandro Loglio, Theodoros Voulgaris, Nikolaos Gatselis, Onur Keskin, Rhea Veelken, Marta Lopez-Gomez, Bettina E Hansen, Savvoula Savvidou, Anastasia Kourikou, John Vlachogiannakos, Kostas Galanis, Ramazan Idilman, Rafael Esteban, Harry L A Janssen, Thomas Berg, Pietro Lampertico
• Journal: Journal of hepatology (J Hepatol) Vol. 72 Issue 6 Pg. 1088-1096 (06 2020) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 31981727 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B Surface Antigens
• entecavir
• Guanine
• Tenofovir

Topics

• Administration, Oral
• Adult
• Aged
• Antiviral Agents (administration & dosage)
• Carcinoma, Hepatocellular (epidemiology, etiology)
• DNA, Viral (blood, genetics)
• Female
• Follow-Up Studies
• Guanine (administration & dosage, analogs & derivatives)
• Hepatitis B Surface Antigens (blood)
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (complications, drug therapy, ethnology, virology)
• Humans
• Incidence
• Liver Cirrhosis (complications)
• Liver Neoplasms (epidemiology, etiology)
• Male
• Middle Aged
• Risk Factors
• Tenofovir (administration & dosage)
• Treatment Outcome
• White People
• Young Adult