Abstract A036: Comparison of immunotherapies response in hepatocellular carcinoma HCC with viral hepatitis vs non-viral hepatitis

Abstract Background: Hepatocellular carcinoma (HCC), the most common liver cancer, accounts for 80% of diagnosed cases. Immunotherapy is increasingly used for advanced HCC and other solid tumors. Approximately 13% of cancers are associated with infections. HCC etiology varies by regionally, with 54% of cases in Asia and sub-Saharan Africa due to hepatitis B, while hepatitis C is more common in Italy and Japan. Hepatitis infections disrupt liver signaling, causing inflammation and abnormal cell regeneration. In HCC progression, inflammation serves as a “double-edged sword.” While chronic inflammation is a significant driver of tumor development and immune evasion, it can also promote tumor cell death, either directly through ferroptosis or indirectly by enhancing anticancer immune responses, thereby potentially inhibiting HCC progression. This study aimed to evaluate immunotherapy response in HCC associated with viral hepatitis compared to non-viral hepatitis. Methods: HCC patients were analyzed using data from the cBioPortal database, from a cohort study of hepatobiliary cancers. Only HCC patients who received nivolumab, pembrolizumab, atezolizumab, bevacizumab, durvalumab, tremelimumab, ipilimumab, ramucirumab, or daratumumab, either as monotherapy or in combination were included. We excluded all cases of cholangiocarcinoma (CCA), HCC with CCA, and those not treated with immunotherapy. We calculated median overall survival (OS) for immunotherapy-treated HCC patients with viral hepatitis compared to those with non-viral hepatitis. Survival analysis was conducted using the Kaplan–Meier (KM) method. Results: Among 1,370 hepatobiliary cancer cases, 289 were identified as HCC. After excluding patients who did not receive immunotherapy, a total of 101 cases remained, of which 56 (55.4%) had viral HCC, and 45 (44.6%) had non-viral HCC. Most patients were white 62 (61%), and 27 (26%) had cirrhosis. Additionally, 66 (65%) had TERT mutations, 45 (43%) had TP53 mutations. Of the total, 52 (51%) had died, while 49 (48%) were still alive. All patients received at least one immunotherapy cycle, with 65 (64.4%) receiving it as a palliative setting. Viral HCC was associated with a median OS of 60 months (95% CI,38.24-NA), while non-viral HCC showed median OS of 40 months (95% CI,25.34-NA) (p=0.106). Conclusion: Our study highlighted that HCC patients with underlying viral infections achieve better outcomes from immunotherapy, evidenced by a longer OS compared to patients with non-viral HCC. This suggests that viral HCC may have a unique tumor biology or immune environment that enhances the response to immunotherapy, leading to improved survival outcomes relative to non-viral cases. Citation Format: Saifudeen Abdelrahim, Ebtesam Al-Najjar, Bayan Khasawneh, Abdullah Esmail, Ala Abudayyeh. Comparison of immunotherapies response in hepatocellular carcinoma HCC with viral hepatitis vs non-viral hepatitis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A036.