Portal hypertension, advanced hepatocellular carcinoma and therapy by atezolizumab-bevacizumab: A “menage à trois” !

Campion, Bertille; Larrey, Edouard; Wagner, Mathilde; Rudler, Marika; Thabut, Dominique; Allaire, Manon

doi:10.1016/j.clinre.2021.101785

Cited by 10 publications

(11 citation statements)

References 5 publications

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“…Median time of occurrence from previous AVB and atezolizumab–bevacizumab initiation was 6.5 months. None of them died within 6 weeks of AVB and one patient presented AVB recurrence after the second EBL 15 . AVB incidence was 21% at 12 months, was not influenced by EV size ( p = .44), but was significantly more frequent in case of a history of AVB ( p < .001) (Figure 2A–C).…”

Section: Resultsmentioning

confidence: 94%

“…None of them died within 6 weeks of AVB and one patient presented AVB recurrence after the second EBL. 15 AVB incidence was 21% at 12 months, was not influenced by EV size (p = .44), but was significantly more frequent in case of 3).…”

Section: Variceal Bleeding Occurrence Under Atezolizumab-bevacizumabmentioning

confidence: 84%

“…One of them had progressive disease which may explain the AVB episode. However, the second patient had a stable HCC disease with stable vascular invasion 15 . None of them died from AVB.…”

Section: Discussionmentioning

confidence: 95%

“…However, the second patient had a stable HCC disease with stable vascular invasion. 15 None of them died from AVB. Hepatic sinusoidal obstruction syndrome leading to PHT was already noticed after nivolumab treatment, as well as a rapid progression to liver fibrosis after atezolizumab.…”

Section: Discussionmentioning

confidence: 95%

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A history of variceal bleeding is associated with further bleeding under atezolizumab–bevacizumab in patients with HCC

Larrey

Campion

Evain

et al. 2022

Liver International

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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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Section: Resultsmentioning

confidence: 94%

Section: Variceal Bleeding Occurrence Under Atezolizumab-bevacizumabmentioning

confidence: 84%

“…One of them had progressive disease which may explain the AVB episode. However, the second patient had a stable HCC disease with stable vascular invasion 15 . None of them died from AVB.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

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A history of variceal bleeding is associated with further bleeding under atezolizumab–bevacizumab in patients with HCC

Larrey

Campion

Evain

et al. 2022

Liver International

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“…[3][4][5] Moreover, some HCC treatment might worsen PHT level as it was described under Atezolizumab-Bevacizumab treatment for advanced HCC, within short delay, thus strengthening the need for OHT-lowering therapies in those patients. 23,24 Last, a meta-analysis of randomised trials on the effect of NSBBs for prevention of AVB indicates that NSBBs may reduce incidence of HCC. In conclusion, favourable Baveno VI criteria are not appropriate to rule out the presence of high-risk EV in patients with HCC patients and endoscopy should be performed to rule out patients with high-risk EV.…”

Section: Discussionmentioning

confidence: 99%

Baveno VI and VII criteria are not suitable for screening for large varices or clinically significant portal hypertension in patients with hepatocellular carcinoma

Allaire

Campion²,

Demory

et al. 2023

Aliment Pharmacol Ther

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

Furusawa

Naganuma

Suzuki

et al. 2022

Clin J Gastroenterol

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Portal hypertension, advanced hepatocellular carcinoma and therapy by atezolizumab-bevacizumab: A “menage à trois” !

Cited by 10 publications

References 5 publications

A history of variceal bleeding is associated with further bleeding under atezolizumab–bevacizumab in patients with HCC

A history of variceal bleeding is associated with further bleeding under atezolizumab–bevacizumab in patients with HCC

Baveno VI and VII criteria are not suitable for screening for large varices or clinically significant portal hypertension in patients with hepatocellular carcinoma

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

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