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Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, AustriaLiver Cancer (HCC) Study Group Vienna, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
Corresponding author. Address: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Tel.: +43 1 40400 47440, fax: +43 1 40400 47350.
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, AustriaLiver Cancer (HCC) Study Group Vienna, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
The last 5 years have witnessed relevant advances in the systemic treatment of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include 4 oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 4 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy).
Due to the lack of scientific evidence, the expert panel could not make a formal recommendation for the use of ICIs in HBV/HDV-coinfected individuals. Instead, they recommend an individualized approach that should take into account the lack of safety data as well as alternative treatment options.
Herein, we want to share the case of a 71-year-old female patient with advanced HCC and HBV/HDV coinfection who received systemic therapy with the ICI-based combination of atezolizumab and bevacizumab. The patient was referred to our outpatient clinic after developing early intrahepatic and extrahepatic recurrence after liver resection for HCC. She had compensated liver cirrhosis (Child-Pugh stage A5) without portal hypertension (hepatic venous pressure gradient: 3 mmHg), and an Eastern Cooperative Oncology Group performance status of 1. After interdisciplinary tumor board discussion, systemic treatment with atezolizumab/bevacizumab was initiated. The patient was under antiviral treatment with lamivudine at the time of presentation. Viral load at start of atezolizumab/bevacizumab was negative for HBV and 840 copies/ml for HDV.
So far, the patient received 9 cycles of immunotherapy and underwent 2 radiological follow-up scans, both showing partial response. HBV viral load remained negative throughout the course of treatment, and HDV viral load decreased to 290 copies/ml and 170 copies/ml at month 3 and month 6, respectively. The decrease of HDV viral load may result from enhanced T cell-mediated immunity, as previously suggested in patients with chronic hepatitis C treated with the ICI tremelimumab for HCC.
Transaminases remained stable over time (Fig. 1). The patient experienced no treatment-related adverse events. After pretty much 6 months of treatment, the patient is still alive, in partial remission, and continues receiving treatment with atezolizumab/bevacizumab.
In summary, atezolizumab/bevacizumab induced a partial response, and was well-tolerated with no signs of a hepatitis flare in a patient with HCC and HBV/HDV coinfection.
Financial support
The authors received no financial support for this manuscript.
Authors’ contributions
All authors contributed to the design, writing, and final review of the paper.
Conflict of interest
M.J. served as a speaker for Gilead. B.S. received travel support from AbbVie, Ipsen and Gilead. M.P. is an investigator for Bayer, BMS, Lilly, and Roche; he received speaker honoraria from Bayer, BMS, Eisai, Lilly, MSD, and Roche; he is a consultant for Bayer, BMS, Ipsen, Eisai, Lilly, MSD, and Roche; he received travel support from Bayer and BMS.
Please refer to the accompanying ICMJE disclosure forms for further details.
Supplementary data
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