Effect of pembrolizumab on viral hepatitis load and transaminases in advanced hepatocellular carcinoma

Stephen Lam Chan; Richard S Finn; Julien Edeline; Sadahisa Ogasawara; Jennifer J Knox; Bruno Daniele; Baek-Yeol Ryoo; Philippe Merle; Mohamed Bouattour; Ho-Yeong Lim; Yee Chao; Thomas Yau; Barbara Anne Haber; Usha Malhotra; Abby B Siegel; Chih-Chin Liu; Masatoshi Kudo; Ann-Lii Cheng

doi:10.1016/j.aohep.2025.102169

Effect of pembrolizumab on viral hepatitis load and transaminases in advanced hepatocellular carcinoma

Ann Hepatol. 2025 Dec 24;31(1):102169. doi: 10.1016/j.aohep.2025.102169. Online ahead of print.

Authors

Stephen Lam Chan¹, Richard S Finn², Julien Edeline³, Sadahisa Ogasawara⁴, Jennifer J Knox⁵, Bruno Daniele⁶, Baek-Yeol Ryoo⁷, Philippe Merle⁸, Mohamed Bouattour⁹, Ho-Yeong Lim¹⁰, Yee Chao¹¹, Thomas Yau¹², Barbara Anne Haber¹³, Usha Malhotra¹³, Abby B Siegel¹³, Chih-Chin Liu¹³, Masatoshi Kudo¹⁴, Ann-Lii Cheng¹⁵

Affiliations

¹ Department of Clinical Oncology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address: chanlam_stephen@cuhk.edu.hk.
² Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³ Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
⁴ Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁵ Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
⁶ Department of Oncology, Ospedale del Mare, Naples, Italy.
⁷ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁸ Department of Hepatology and Gastroenterology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
⁹ Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Liver Cancer and Innovative Therapy Unit Hôpital Beaujon, Clichy, France.
¹⁰ Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
¹¹ Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan.
¹² Department of Medicine, The University at Hong Kong, Pok Fu Lam, Hong Kong, China.
¹³ Clinical Research (Barbara Anne Haber, Usha Malhotra, Abby B. Siegel) and Biostatistics (Chih-Chin Liu), Merck & Co., Inc., Rahway, NJ, USA.
¹⁴ Department of Gastroenterology and Hepatology, School of Medicine, Kindai University, Osaka, Japan.
¹⁵ National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan.

PMID: 41453647
DOI: 10.1016/j.aohep.2025.102169

Abstract

Introduction and objectives: Prospective data are limited regarding viral hepatitis viral load and serology and immunotherapy in patients with hepatocellular carcinoma (HCC). This analysis evaluated hepatitis viral load and serology and transaminase levels in patients with sorafenib-treated advanced HCC who were receiving immunotherapy with pembrolizumab in the KEYNOTE-224 and KEYNOTE-240 studies.

Materials and methods: This was a post hoc analysis of the single-arm phase II KEYNOTE-224 (NCT02702414) and the placebo-controlled phase III KEYNOTE-240 (NCT02702401) studies. Patients positive for hepatitis B surface antigen (HBsAg) and/or with detectable hepatitis B virus (HBV), patients positive for isolated total hepatitis B core antibody (anti-HBc), and patients currently or previously infected with hepatitis C virus (HCV) were included. Viral-induced hepatitis flare was defined as >1 log increase from baseline and >1000 IU/ml viral load with concurrent alanine aminotransferase (ALT) elevation classified according to prespecified thresholds.

Results: No patient in the pembrolizumab arm who was positive for HBsAg and/or with detectable HBV or who was positive for isolated anti-HBc met the criteria for viral-induced hepatitis flare; 1 patient (3.4%) in the placebo arm met the criteria for viral-induced hepatitis flare. One patient (2.3%) in the pembrolizumab arm of KEYNOTE-240 who was infected with HCV met the criteria for viral-induced hepatitis flare, but the event was not attributed to pembrolizumab.

Conclusions: These results suggest that pembrolizumab does not cause viral-induced hepatitis flare in patients with advanced HCC.

Gov identifier: NCT02702414 and NCT02702401.

Keywords: Hepatitis B virus; Hepatitis C virus; Hepatitis viral load and serology; Immune checkpoint inhibitor; Liver cancer.

Associated data

ClinicalTrials.gov/NCT02702414
ClinicalTrials.gov/NCT02702401