Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses….

Manon Allaire,Dominique Thabut,Marika Rudler

doi:10.1111/liv.14977

Manon Allaire, Dominique Thabut + Show 1 more

Open Access

https://doi.org/10.1111/liv.14977

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Abstract

Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients. Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021. Portal hypertension occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available. Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.

Highlights

Introduction: Portal hypertension (PHT) and Hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality
We aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, and the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients
PHT occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF)

Summary

Introduction

Portal hypertension (PHT) is a major complication of cirrhosis and is responsible for variceal bleeding, ascites and hepatorenal syndrome, which significantly contribute to morbidity and mortality. Angiogenesis mediated by VEGF promotes an extensive network of portosystemic collateral vessels, contribute to increased splanchnic and portal venous inflow that perpetuates and exacerbates PHT and favors liver fibrosis progression and inflammation (Figure 1). The use of Atezolizumab, which promotes cytotoxic lymphocytes, may contribute to increase production of proinflammatory cytokines that might activate innate immune cells, as well as HSCs and LSECs, and drive liver fibrosis, chronic inflammation and PHT [89], especially in NASH and alcoholic liver disease where chronic inflammation plays a major role in the progression of the liver disease. A better understanding of the crosstalk between these two complications of cirrhosis is mandatory to improve the outcome of these patients, especially in the era of Atezolizumab and Bevacizumab as a first line for advanced HCC

Human data No data No data No data

Findings

No specific exclusion criteria regarding bleeding history