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

Abstract

Recently, a combined regimen of atezolizumab and bevacizumab (AB) treatment has been approved as a first-line treatment in patients with advanced hepatocellular carcinoma (HCC), contributing to prolonged survival. However, we often encounter cases where treatment must be discontinued due to the occurrence of adverse events. One of these events, which is often fatal, is gastrointestinal bleeding. To clarify the clinical effects of gastrointestinal bleeding after AB treatment, we evaluated patients with HCC who were treated with AB at our institution. Of the 105 patients, five treated with AB developed gastrointestinal bleeding, necessitating treatment discontinuation. Additionally, we encountered two cases where exacerbation of varicose veins was observed, and AB therapy could be continued by preventive treatment of varices. In conclusion, an appropriate follow-up is required during treatment with AB to prevent possible exacerbation of varicose veins.

Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis

“… 28 Although both mechanisms impair hemostatic function, the specific inhibition of circulating VEGF leads to reduced capillary bed density in the liver and increased pressure in the reticuloendothelial system, resulting in exacerbated varicose veins. 28 , 29 Consequently, it is postulated that variceal bleeding is more prone to occur in patients receiving atezolizumab plus bevacizumab than in those receiving lenvatinib.…”

Efficacy and safety of atezolizumab plus bevacizumab in patients with portal hypertension for unresectable hepatocellular carcinoma

“… 31 Another study reported five cases of UGI bleeding and two cases of exacerbated varices during Atezo + Beva treatment. 32 AEs of bleeding, such as ruptured varices, require temporary interruption of Atezo + Beva therapy, and it has been reported that, once gastrointestinal bleeding occurs, continuation of Atezo + Beva is difficult in some cases for the following reasons: rapid deterioration of hepatic reserve, rapid growth of HCC, and acquired resistance against Atezo + Beva. 33 , 34 Therefore, the present study focused on PH, which can be associated with varices, and efficacy and safety were compared between PH(−) and PH(+) patients.…”

Massive bleeding from a gastric artery pseudoaneurysm in hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A case report

“…Therefore, these possibilities are unlikely. In a meta-analysis of the risk of high-grade bleeding in patients with various cancers treated with BVZ, the risk was significantly higher in those who received 5 mg/kg per wk than those who received 2.5 mg/kg per wk[ 21 ]. However, none of the studies included in the meta-analysis examined patients with HCC.…”