Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B

George V Papatheodoridis; George N Dalekos; Ramazan Idilman; Vana Sypsa; Florian Van Boemmel; Maria Buti; Jose Luis Calleja; John Goulis; Spilios Manolakopoulos; Alessandro Loglio; Margarita Papatheodoridi; Nikolaos Gatselis; Rhea Veelken; Marta Lopez-Gomez; Bettina E Hansen; Savvoula Savvidou; Anastasia Kourikou; John Vlachogiannakos; Kostas Galanis; Cihan Yurdaydin; Rafael Esteban; Harry L A Janssen; Thomas Berg; Pietro Lampertico

doi:10.1016/j.jhepr.2021.100290

Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B

JHEP Rep. 2021 Apr 20;3(3):100290. doi: 10.1016/j.jhepr.2021.100290. eCollection 2021 Jun.

Authors

George V Papatheodoridis¹, George N Dalekos², Ramazan Idilman³, Vana Sypsa⁴, Florian Van Boemmel⁵, Maria Buti⁶, Jose Luis Calleja⁷, John Goulis⁸, Spilios Manolakopoulos^{1

9}, Alessandro Loglio¹⁰, Margarita Papatheodoridi¹, Nikolaos Gatselis², Rhea Veelken⁵, Marta Lopez-Gomez⁷, Bettina E Hansen^{11

12}, Savvoula Savvidou⁸, Anastasia Kourikou⁹, John Vlachogiannakos¹, Kostas Galanis², Cihan Yurdaydin¹³, Rafael Esteban⁶, Harry L A Janssen¹², Thomas Berg⁵, Pietro Lampertico^{10

14}

Affiliations

¹ Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
² Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
³ Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey.
⁴ Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece.
⁵ Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
⁶ Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain.
⁷ Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain.
⁸ 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
⁹ 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Hippokratio", Athens, Greece.
¹⁰ Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹¹ Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
¹² Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.
¹³ Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey.
¹⁴ Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Abstract

Background & aims: Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC.

Methods: We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively.

Results: HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78-0.82). NPVs were always >99% (99.3-100%), whereas PPV ranged between 13% and 24%.

Conclusions: In NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease.

Lay summary: Several risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.

Keywords: ALT, alanine aminotransferase; AUROC, area under receiver operating characteristic; CHB, chronic hepatitis B; Cirrhosis; ETV, entecavir; Entecavir; HCC, hepatocellular carcinoma; HR, hazard ratio; NA, nucleos(t)ide analogue; NPV, negative predictive value; PPV, positive predictive value; Prediction; TDF, tenofovir disoproxil fumarate; Tenofovir; ULN, upper limit of normal.