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

Furusawa, Ai; Naganuma, Akira; Suzuki, Yuhei; Hoshino, Takashi; Yasuoka, Hidetoshi; Tamura, Yukie; Naruse, Hiroaki; Hatanaka, Takeshi; Kakizaki, Satoru

doi:10.1007/s12328-022-01605-9

Cited by 17 publications

(18 citation statements)

References 20 publications

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“…The prevalence of gastrointestinal bleeding in the current study (4.8%) was similar to that in a previous clinical trial (7). To the best of our knowledge, two cases of rapid growth of esophageal varices following AB have been reported (13). Table 1 shows the characteristics of those patients and that of the patients in the present study.…”

Section: Discussionsupporting

confidence: 88%

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

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 88%

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

et al. 2022

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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%

“…Unfortunately, no data of NSBBs and its potential impact on the outcome are available in these series 3–5 . 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 25 .…”

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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“…However, the mechanisms underlying the exacerbation of varices during Atez/Bev remain unclear. We reported two cases with the rupture of esophageal varices during Atez/Bev treatment in spite of pre-treatment esophagogastroduodenoscopy screening [5]. In these two cases, the spleen volume was observed to gradually increase on CT imaging [5].…”

Section: Introductionmentioning

confidence: 95%

“…We reported two cases with the rupture of esophageal varices during Atez/Bev treatment in spite of pre-treatment esophagogastroduodenoscopy screening [5]. In these two cases, the spleen volume was observed to gradually increase on CT imaging [5]. While an increase in spleen volume resulted in the aggravation of portal hypertension, whether it was caused by the progression of underlying chronic liver diseases or by Atez/Bev remains unknown.…”

Section: Introductionmentioning

confidence: 97%

Increased Spleen Volume in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab in Comparison to Lenvatinib: A Retrospective Analysis

et al. 2023

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Introduction: We previously reported 2 cases of esophageal varices rupture during atezolizumab and bevacizumab (Atez/Bev) treatment, in which the spleen volume gradually increased. The aim of this retrospective study is to compare the chronological change in spleen volume of patients treated with Atez/Bev and lenvatinib (LEN). Methods: Seventy-two patients (Atez/Bev group, n = 26; LEN group, n = 46) were included in this retrospective study. The splenic parenchyma area was measured based on CT imaging. We used mixed-effect regression models with random intercepts to test the difference in the rate of change in spleen volume between the Atez/Bev and LEN groups. Results: The median age of the Atez/Bev and LEN groups was 74.0 (71.0–82.0) and 72.0 (67.5–76.0), respectively. About 80% patients were male. The mALBI grade was classified as 1, 2a, 2b, and 3 in 10 (38.5%), 6 (23.1%), 10 (38.5%), and zero (0.0%) patients, respectively, in the Atez/Bev group and 21 (45.7%), 9 (19.6%), 15 (32.6%), and 1 (2.2%) patient in the LEN group (p = 0.9). The median baseline neutrophil-to-lymphocyte ratio (NLR) was 2.61 (1.80–3.41) in the Atez/Bev group and 2.71 (1.76–3.67) in the LEN group (p = 1.0). The median baseline spleen volume was 185 (132–246) cm3 in the Atez/Bev group and 231 (150–355) cm3 in the LEN group. The spleen volume gradually increased during Atez/Bev treatment (2.41 cm3 per week), while it was mostly consistent during LEN treatment (0.32 cm3 per week). Among patients with mALBI grade 2b or 3, the spleen volume increased in the Atez/Bev group (2.99 cm3 per week) and slightly decreased in the LEN group (0.82 cm3 per week), without statistical significance (p = 0.07). Among patients with a baseline NLR of >2.68, the spleen volume increased at a rate of 2.57 cm3 per week in the Atez/Bev group and decreased at a rate of 1.18 cm3 per week in the LEN group. The difference in the slope of the two groups was statistically significant (p = 0.04). Discussion/Conclusion: Atez/Bev treatment could result in an increased spleen volume. Caution is required when managing patients treated with Atez/Bev, especially those with a high NLR.

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

Cited by 17 publications

References 20 publications

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

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

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

Increased Spleen Volume in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab in Comparison to Lenvatinib: A Retrospective Analysis

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