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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2021; 27(26): 4104-4142
Published online Jul 14, 2021. doi: 10.3748/wjg.v27.i26.4104
Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges
Hsuan Yeh, Chun-Cheng Chiang, Tzung-Hai Yen
Hsuan Yeh, Tzung-Hai Yen, Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
Chun-Cheng Chiang, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Author contributions: Yeh H and Chiang CC contributed equally to this study, and both contributed to data collection and manuscript writing; Yen TH contributed to study design and supervision.
Supported by Chang Gung Memorial Hospital, No. CORPG3K0191, No. CMRPG3G0871, and No. CMRPG3G0872.
Conflict-of-interest statement: The authors declare no competing financial interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tzung-Hai Yen, MD, PhD, Doctor, Professor, Department of Nephrology, Chang Gung Memorial Hospital, No. 199 Tung Hwa North Road, Taipei 105, Taiwan. m19570@adm.cgmh.org.tw
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: March 6, 2021
Revised: March 17, 2021
Accepted: June 16, 2021
Article in press: June 16, 2021
Published online: July 14, 2021
Processing time: 164 Days and 16.7 Hours
Abstract

The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.

Keywords: Hepatocellular carcinoma; Chronic kidney disease; End-stage renal disease; Hemodialysis; Cancer prognosis; Cancer therapeutics

Core Tip: The varying degrees of renal dysfunction, from the various stages of chronic kidney disease to dialysis-dependent end-stage renal disease, often affect the choice of treatment and prognosis of patients with hepatocellular carcinoma (HCC). This complicates HCC treatment. This review encompasses the presumptive causes of the high degree of comorbidity of HCC and renal dysfunction, the impact of renal dysfunction on HCC prognosis, and the concerns that are specific to patients with pre-existing renal dysfunction for each stage of HCC treatment.