Background The combination of atezolizumab and bevacizumab (AtezoBev) is the current first‐line treatment for patients with hepatocellular carcinoma (HCC). Our aim was to evaluate the prognostic role of alpha‐foetoprotein (AFP) early response and its combination with albumin–bilirubin (ALBI) in these patients. Methods Patients with HCC under AtezoBev with AFP > 20 ng/ml were included in three centres. The optimal threshold of AFP variation after 3 weeks of treatment was identified for overall survival (OS) and radiological response (RR) using RECIST 1.1 and mRECIST and its ability to predict progression‐free survival (PFS) and OS was tested using univariate and multivariate analysis in derivation and validation cohorts. Results Seventy‐five patients with AFP values >20 ng/ml were included. Fifty‐eight patients were male with a median age of 63.5 years; 73% had cirrhosis and HCC stage was classified as BCLC B (18.7%) or C (81.3%). In the derivation cohort (n = 38), a decline in AFP ≥ 20% at 3 weeks (AFP early response) was associated with RR using mRECIST criteria (OR: 13.09 95% CI: 1.44–19.34 p = .02), PFS (HR: 0.42; 95% CI: 0.19–0.93, p = .03) and OS (HR: 0.35; 95% CI: 0.15–0.83, p = .01). AFP early response was confirmed as predictor of RR (p = .02 for mRECIST) and OS (p = .03) in the validation cohort (n= 37). In the whole cohort, the combination of ALBI and AFP early response was significantly associated with OS (p = .046) and PFS (p = .012) with a poor prognosis in patients belonging to the ALBI2‐AFP non‐responders class. Conclusion AFP early response at 3 weeks predicts oncological outcomes in HCC patients treated with AtezoBev and combination with ALBI grade refines prognostic discrimination.

Background Atezolizumab–bevacizumab is the new standard for advanced hepatocellular carcinoma (HCC) but its impact on portal hypertension (PHT) is unknown. We aimed to identify predictive factors of acute variceal bleeding (AVB) and to monitor PHT parameters under treatment. Methods We conducted a prospective study including all cirrhotic patients treated with atezolizumab–bevacizumab since 2020. We performed monitoring of PHT using upper endoscopy at inclusion and at 6 months and hepatic venous pressure gradient (HVPG) at inclusion, 3 and 6 months after the beginning of treatment. We also included a retrospective series of patients treated with sorafenib. Time‐to‐events data were estimated by Kaplan–Meier with the log‐rank test, along with Cox models. Results Forty‐three patients treated with atezolizumab–bevacizumab were included (male 79.1%, Child‐Pugh A 86%). At baseline, 48.8% were treated with curative anticoagulation, 16.3% already experienced AVB and 25.6% had large oesophageal varices (EV). Sorafenib group characteristics were similar. Vascular invasion was present in 60.5% and median was HVPG 8.5 mm Hg. No significant modification in HVPG and EV size was observed at 6 months in the whole cohort but also when considering vascular invasion and radiological response. 14% presented AVB within a median time of occurrence of 3 months, without bleeding‐related death. In multivariate analysis, history of AVB (HR = 10.58, p = .03) was associated with AVB. AVB incidence was higher in atezolizumab–bevacizumab compared to sorafenib group (21% vs. 5% at 1 year, p = .02). Conclusions Atezolizumab–bevacizumab treatment was associated with a higher risk of AVB compared to sorafenib. A history of AVB was associated with AVB during follow‐up, which questions the use of bevacizumab in this setting.

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Summary Background Baveno VI and VII criteria are used in patients with cirrhosis to rule out large size oesophageal varices (EV) and rule in/out clinically significant portal hypertension (CSPH). Aim To evaluate their diagnostic performance in these patients. Methods We retrospectively included all patients with Child‐Pugh A cirrhosis and HCC who had endoscopy, liver stiffness measurement (LSM) and platelet count within 6 months. They were classified according to the BCLC stage. Favourable Baveno VI criteria were defined by LSM < 20 kPa and platelets > 150 G/L (to rule out large EV), favourable Baveno VII criteria if LSM ≤ 15 kPa and platelets ≥ 150 G/L (to rule out CSPH, which was defined by a HVPG ≥ 10 mm Hg. Results We included 185 patients; 46% were BCLC‐0/A, 28% BCLC‐B and 26% BCLC‐C. EV were present in 44% (23% large), and HVPG ≥ 10 mm Hg in 42% (mean 8 mm Hg). In patients with favourable Baveno VI criteria, 8% of the whole cohort (Se 93%, NPV 92%), 11% of BCLC‐0‐A (Se 89%, NPV 89%) and 10.0% of BCLC‐C patients (Se 91%, NPV 90%) had large EV. Among patients with HVPG < 10 mm Hg, 6% had large EV and 17% small. CSPH was present in 23% of patients with favourable Baveno VII criteria among the whole cohort, and in 25% of those with BCLC‐0/A. The specificity of LSM ≥ 25 kPa to rule in CSPH was 48%. Conclusions Favourable Baveno VI criteria are not appropriate to rule out the presence of high‐risk EV, or Baveno VII criteria to rule CSPH in/out in patients with HCC.

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