Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses…

Abstract

Background and Aims 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. Methods Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021. Results 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. Conslusions Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.

Haemostatic alterations in patients with cirrhosis and hepatocellular carcinoma: laboratory evidence and clinical implications

“…113 In particular, the effect of antiangiogenic drugs may be compounded on the progressive weakening of variceal walls by CPSH, 114 thus ultimately leading to VH. 111,115 Data from Phase III trials on treatments for advanced HCC such as sorafenib, 116 ramucirumab 117 and pembrolizumab 118 demonstrated a relatively low risk of portal-hypertensive related bleeding (<3%). However, patients were well selected and those with a recent history of bleeding 116,118 or presence of varices at risk 117,118 were not eligible for recruitment.…”

“…119,120 More recently, the combination of bevacizumab (antiangiogenic drug) and atezolizumab (immune checkpoint inhibitor anti-PDL1) has been evaluated for the treatment of advanced HCC. 121 Although both molecules may have the potential to reduce or prevent CPSH, 111 and patients with history of recent bleeding or untreated/ incompletely treated varices were not eligible, bleeding events were significantly more frequent in patients treated with bevacizumab and atezolizumab than in those with sorafenib (25.2% vs 17.3%), including 7% vs 4.5% of gastrointestinal bleeding, and 2.4% vs 0.6% of VH respectively. 121 These findings confirm the earlier observations by phase II trials on bevacizumab in which the rate of portal hypertensive bleeding was around 10%.…”

“…Therefore, in patients with cirrhosis and HCC treated with antiangiogenic drugs, the alterations in endothelial cells due to inhibition of VEGF may determine an increased risk of bleeding 113 . In particular, the effect of antiangiogenic drugs may be compounded on the progressive weakening of variceal walls by CPSH, 114 thus ultimately leading to VH 111,115 …”

“…In this context, inhibition of vascular endothelial growth factor (VEGF)‐driven angiogenesis by antiangiogenic drugs such as sorafenib has not only been associated with reduced liver fibrosis and portosystemic collaterals in animal models of chronic liver disease 111 but also with lower severity of portal pressure in patients with cirrhosis, 112 which could theoretically protect from development of varices and VH.…”

Case Report: Exacerbation of varices following atezolizumab plus bevacizumab treatment of hepatocellular carcinoma: A case series and literature review

“…In the past few years, immune checkpoint inhibitors (ICIs), which target tumor immunity, have caused a paradigm shift in the treatment of advanced HCC (3). Patients with HCC having liver cirrhosis, particularly decompensated liver cirrhosis, often experience complications, such as varicose veins, associated with portal hypertension, hepatic encephalopathy, and hepatorenal syndrome (5,6). Treatment of advanced stages of HCC involving MTAs and ICIs, often aggravates these complications, rendering treatment continuation difficult (3).…”