Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives

Abstract

The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as “hepatocellular carcinoma”, “immune checkpoint inhibitors”, “systemic therapy”, “portal hypertension”, “variceal bleeding” and “tyrosine kinase inhibitors”. Despite promising results of tyrosine kinase inhibitors in animal models for PH and fibrosis, only Sorafenib has demonstrated similar effects in human studies, whereas Lenvatinib appears to promote PH development. The impact of Atezolizumab/Bevacizumab on PH remains uncertain, with an increasing risk of bleeding related to Bevacizumab in patients with prior variceal hemorrhage. Given the absence of specific guidelines, endoscopic surveillance during treatment is advisable, and primary and secondary prophylaxis of variceal bleeding should adhere to the Baveno VII recommendations. Furthermore, in patients with advanced HCC, refinement of diagnostic criteria for CSPH and guidelines for its surveillance are warranted.

Insights in Molecular Therapies for Hepatocellular Carcinoma

“…For patients with esophageal varices or existing portal hypertension, an alternative therapy with durvlaumab/tremelimumab is also available. No evidence of an increased incidence of esophageal variceal bleeding has been reported to date for dual immune-checkpoint blockade [165].…”

“…Before starting treatment with atezolizumab/bevacizumab, the esophageal variceal status should be examined. Endoscopic monitoring throughout treatment is recommended, and adherence to primary and secondary prophylaxis of variceal bleeding is essential [165]. For patients with esophageal varices or existing portal hypertension, an alternative therapy with durvlaumab/tremelimumab is also available.…”