Two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

We report two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral. He was diagnosed with HCC 8 years previously. He had undergone surgical resection 4 times, radio-frequency ablation (RFA) several times, and transcatheter arterial chemoembolization (TACE). However, HCC progressed and could not be controlled by locoregional treatment. Systemic chemotherapy was, therefore, selected. Atezolizumab-bevacizumab was administered after lenvatinib and sorafenib failure. Before starting treatment, his liver function was preserved (Child-Pugh score 5 and class A). His alpha fetoprotein and des-gamma-carboxyprothrombin levels were 3.6 ng/mL and 443 mAU/mL, respectively. Esophagogastroduodenoscopy showed no remarkable esophageal varices before atezolizumab-bevacizumab treatment. Nine months after the initiation of atezolizumab-bevacizumab, the patient was admitted for hematemesis from esophageal varices. The disease control of HCC was classified as stable disease (SD) for the liver and lung metastases, and partial response for the lymph node metastases. Neither AST nor ALT was markedly elevated in the clinical course. Endoscopic variceal ligation (EVL) for the spurting point of large esophageal varices with red wale signs was able to successfully achieve hemostasis. Atezolizumab-bevacizumab was stopped and additional EVL eradicated the esophageal varices. However, the post-banding ulcer was prolonged in comparison to usual cases. Case 2: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral therapy. He was diagnosed with HCC 6 years previously. He had received RFA 2 times and TACE 7 times. Atezolizumab-bevacizumab was administered after lenvatinib failure. The disease control of HCC was classified as SD; however, the esophageal varices ruptured after 15 courses of atezolizumab-bevacizumab. Neither AST nor ALT were markedly elevated in the clinical course. The esophageal varices of these patients did not require treatment before atezolizumab-bevacizumab; however, they rapidly worsened and ruptured during atezolizumab-bevacizumab treatment. Although rare, similar cases with rapid progression of portal hypertension after atezolizumab-bevacizumab have been reported. We should pay attention to the worsening of esophageal varices during atezolizumab-bevacizumab treatment and poor wound healing after EVL.
(© 2022. Japanese Society of Gastroenterology.)