Atezolizumab/Bevacizumab Shows Benefit in Selected Child-Pugh B HCC Patients, ALBEX Score Identifies Best Candidates
Key Insights
A large multicenter analysis of 1,499 patients found that Child-Pugh B HCC patients had median overall survival of 8.1 months versus 16.8 months in Child-Pugh A, yet a subset derived meaningful benefit from atezolizumab/bevacizumab.
The novel ALBEX score, combining ALBI grade and metastatic status, stratified Child-Pugh B patients into three distinct prognostic groups with median survival ranging from 10.3 to 4.2 months.
Atezolizumab/bevacizumab outperformed sorafenib in Child-Pugh B patients with median OS of 8.3 versus 6.4 months (p=0.002), supporting immunotherapy use in selected patients with impaired liver function.
A large international multicenter study has demonstrated that while patients with Child-Pugh B hepatocellular carcinoma (search) (HCC) face significantly poorer outcomes than those with compensated liver disease, a clinically meaningful subset may still benefit from first-line atezolizumab/bevacizumab combination therapy. The findings, published in JHEP Reports, provide some of the strongest real-world evidence to date supporting immunotherapy use in this traditionally underrepresented population.
The analysis, led by Anne Victoire Odent and colleagues, evaluated 1,499 patients with unresectable HCC treated with first-line atezolizumab plus bevacizumab across 12 academic centers in Europe and South Korea between 2020 and 2024. Among the cohort, 246 patients (16.4%) had Child-Pugh B cirrhosis (search), representing one of the largest real-world analyses of immunotherapy in this population.
Survival Outcomes Reveal Stark Disparities
The survival gap between Child-Pugh classes was substantial. Median overall survival reached only 8.1 months in Child-Pugh B patients compared with 16.8 months in Child-Pugh A patients. Progression-free survival similarly diverged at 5.2 versus 8.6 months. Two-year overall survival stood at 20.4% for Child-Pugh B versus 38.4% for Child-Pugh A, while three-year survival was 11.7% versus 25%, respectively.
Despite these sobering figures, the data revealed that Child-Pugh B disease is far from homogeneous. Some patients achieved durable benefit and survived for years after treatment initiation, underscoring the need for refined patient selection rather than blanket exclusion from immunotherapy.
ALBEX Score Stratifies Prognosis
A key innovation emerging from the study was the ALBEX score, a practical clinical tool integrating ALBI (Albumin–Bilirubin) grade and extrahepatic metastatic status. Using only two readily available clinical variables, the investigators separated Child-Pugh B patients into three distinct prognostic categories.
Patients with ALBI grade 1–2 and no extrahepatic metastases formed a favorable-risk group with median overall survival of 10.3 months. Those with either ALBI grade 3 or metastatic disease were classified as intermediate risk, achieving median survival of 7.9 months. Patients with both adverse factors—ALBI grade 3 and metastatic spread—represented a poor-prognosis population with median survival of just 4.2 months. Notably, all patients in the poor-risk category had either progressed or died within one year.
Immunotherapy Outperforms Sorafenib in Child-Pugh B
The study included a comparative analysis with a historical cohort of Child-Pugh B patients treated with sorafenib. After adjustment for baseline differences using inverse probability weighting, atezolizumab plus bevacizumab demonstrated superior efficacy. Median overall survival was 8.3 months with the immunotherapy combination versus 6.4 months with sorafenib (p=0.002), and median progression-free survival was 5.5 versus 3.1 months. The radiologic response rate was also higher with atezolizumab plus bevacizumab.
These findings reinforce the potential benefit of immunotherapy-based treatment over tyrosine kinase inhibitors even in selected patients with impaired liver function, despite the retrospective and non-randomized nature of the comparison.
Liver Function Is Dynamic, Not Static
Perhaps the most clinically instructive finding was the demonstration that liver function can improve during systemic therapy. Among evaluable patients, 31% improved from Child-Pugh B to Child-Pugh A during treatment, while 50% remained Child-Pugh B and 19% worsened to Child-Pugh C.
Improvement in liver function was independently associated with reduced mortality, with a hazard ratio for death of 0.59. In contrast, progressive disease carried a hazard ratio for death of 2.38. Patients who had recently initiated antiviral therapy for hepatitis B or hepatitis C, or who had achieved alcohol abstinence, were more likely to demonstrate improvements in Child-Pugh status during treatment.
Safety and Treatment Exposure
The safety profile of atezolizumab plus bevacizumab was generally comparable between Child-Pugh A and Child-Pugh B patients, with no significant increase in grade 3–4 adverse events among those with impaired liver function. However, treatment duration was considerably shorter in Child-Pugh B patients (median 70 days versus 187 days), and early discontinuation occurred more frequently (54% versus 31%), likely reflecting both disease progression and liver-related complications rather than excessive treatment toxicity alone.
Toward Individualized Treatment Selection
The findings suggest that Child-Pugh B status alone should not automatically exclude patients from combination immunotherapy. Instead, integrating ALBI grade, metastatic burden, and dynamic liver function changes may better identify patients who can meaningfully benefit. The study points toward a more individualized approach in advanced HCC, where optimization of liver health alongside systemic therapy could become an important therapeutic strategy. Prospective validation of the ALBEX framework is needed to confirm its utility in routine clinical practice.