Effectiveness and Safety of Immunotherapy for Hepatocellular Carcinoma in Clinical Practice A Brazilian Multicenter Study summary

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Britany: Welcome to PACULit, your daily literature update for acute and critical care clinicians. Today, we’re discussing a multicenter Brazilian study on immunotherapy for hepatocellular carcinoma, or HCC. Seth, great to have you here. How are you?

Seth: Thanks, Britany. I’m well and excited to discuss this. HCC is challenging, especially advanced stages. Immunotherapy has changed the landscape.

Britany: Absolutely. HCC remains a leading cause of cancer deaths worldwide, with rising incidence due to chronic liver diseases like viral hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD). Brazil has a unique population with diverse etiologies and liver function profiles not extensively studied in real-world immunotherapy.

Seth: Right. Landmark trials like IMbrave150 have strict criteria, often excluding patients with poorer liver function or comorbidities. This Brazilian cohort fills a gap by evaluating immunotherapy effectiveness and safety in a more heterogeneous, real-world population.

Britany: Exactly. Da Fonseca et al. included 163 patients with unresectable or metastatic HCC treated mainly with atezolizumab plus bevacizumab from 2019 to 2024. They assessed overall survival and adverse events, identifying prognostic factors like ALBI grade, variceal status, and MASLD presence.

Seth: The retrospective, multicenter design across Brazilian oncology centers captured a broad patient spectrum. Inclusion was adults with advanced HCC not amenable to curative therapies who received at least one immunotherapy dose. They excluded incomplete data or early loss to follow-up.

Britany: Although no formal comparator arm existed, the observational nature provided valuable real-world insights. The primary endpoint was overall survival; secondary endpoints included immune-related adverse events and bevacizumab-related complications like variceal bleeding.

Seth: Median overall survival was 14.7 months, with 12- and 24-month survival rates of 57% and 41.4%. Patients with Child-Pugh A liver function and ECOG 0-1 had median OS of 20.6 months, which is encouraging.

Britany: That aligns with IMbrave150’s median OS of 19.2 months for atezolizumab plus bevacizumab. It’s reassuring that real-world Brazilian outcomes mirror controlled trials despite a more diverse population.

Seth: Key prognostic factors were ALBI grade 2-3, MASLD etiology, and esophagogastric varices, all predicting worse survival. This highlights baseline liver function and disease characteristics’ role in guiding treatment.

Britany: The ALBI grade, based on albumin and bilirubin, is a more objective hepatic reserve tool than Child-Pugh in some settings. These findings echo Tomonari et al., emphasizing hepatic reserve’s importance in immunotherapy outcomes.

Seth: MASLD’s impact is notable. Chon et al. reported poorer outcomes in metabolic liver disease patients receiving atezolizumab plus bevacizumab, suggesting non-viral etiologies may influence immunotherapy efficacy and need closer monitoring.

Britany: On safety, immune-related adverse events occurred in 19.6%, mainly thyroid dysfunction and skin disorders. Bevacizumab-related variceal bleeding was low at 3.7% but remains a critical concern given cirrhotic bleeding risk.

Seth: Managing varices before bevacizumab is essential. Prophylactic band ligation or beta-blockers may reduce bleeding risk. Acute care pharmacists and intensivists should watch for bleeding and immune toxicities.

Britany: The retrospective design and lack of standardized radiologic response are limitations, but the large, diverse cohort strengthens generalizability to Latin American populations.

Seth: Also, lack of prospective data on Child-Pugh B patients leaves a gap. These patients are a grey zone clinically; future studies should focus on their immunotherapy safety and efficacy.

Britany: The study underscores the need for tailored strategies in MASLD and variceal disease patients. Personalized management could improve survival and reduce complications.

Seth: Regarding drug interactions, bevacizumab’s anti-angiogenic effects impair wound healing and increase bleeding risk, especially with anticoagulants or antiplatelets. Careful medication reconciliation is vital.

Britany: Immune checkpoint inhibitors like atezolizumab can cause diverse irAEs affecting multiple organs. Early recognition and management with corticosteroids or immunosuppressants prevent severe toxicity.

Seth: Consider a clinical case: a 62-year-old male with unresectable HCC, Child-Pugh A, ECOG 1, MASLD etiology, and small esophageal varices without prior bleeding. How would you approach immunotherapy?

Britany: First, optimize variceal management—likely prophylactic band ligation or beta-blockers to reduce bleeding risk. Baseline labs including liver function and thyroid panels are essential. Starting atezolizumab plus bevacizumab is appropriate with close monitoring for irAEs and bleeding.

Seth: Regular imaging and clinical follow-up are necessary. If immune-related hypothyroidism develops, start thyroid hormone replacement promptly without necessarily stopping immunotherapy.

Britany: This highlights the multidisciplinary approach—oncologists, pharmacists, hepatologists, and critical care teams collaborating to optimize outcomes.

Seth: Gao et al.’s meta-analysis of real-world studies confirmed atezolizumab plus bevacizumab’s efficacy and safety, reinforcing the Brazilian study’s findings across diverse populations.

Britany: Hatanaka et al. compared viral versus non-viral HCC patients, finding similar safety but survival differences, again emphasizing etiology’s role. This may influence future trials and treatment algorithms.

Seth: Performance status is another clinical pearl. Patients with ECOG 0-1 had better survival, underscoring careful functional assessment before immunotherapy.

Britany: In poor performance or advanced liver dysfunction, risk-benefit may shift, making alternative therapies or supportive care more appropriate.

Seth: To sum up, this Brazilian multicenter study provides real-world evidence supporting atezolizumab plus bevacizumab’s effectiveness and manageable safety in advanced HCC. It highlights prognostic factors like ALBI grade, MASLD, and variceal status clinicians must consider.

Britany: For acute and critical care pharmacists and physicians, understanding these nuances helps tailor therapy, anticipate complications, and improve outcomes. It also points to research needs like prospective Child-Pugh B studies and variceal bleeding mitigation strategies.

Seth: Agreed. This study enriches our clinical toolkit and reminds us that personalized medicine is essential in managing complex diseases like HCC.

Britany: Thanks for the insightful discussion, Seth. And thank you to our listeners for joining PACULit. Stay tuned for more clinical literature updates.

Seth: Thanks, Britany. Looking forward to our next deep dive. Take care!

Britany: Take care!