Effect of immune checkpoint inhibitor (ICI) treatment in hepatocellular carcinoma (HCC) based on underlying liver disease.

396 Background: While treatment of unresectable HCC remains challenging, ICI either alone or in combination with bevacizumab, has become a standard therapy. Overall, HCC outcomes are improved with the use of ICI, but only a small percentage of patients respond. As a result, there remains a need for biomarker discovery for optimal patient selection. Emerging evidence suggests that patients with non-viral causes of HCC, including nonalcoholic steatohepatitis (NASH) and alcohol use, may not derive the same benefit from ICI as patients with viral causes of HCC. A recent study by Pfister et al. (2021) demonstrated in preclinical models that NASH-related aberrant T cell activation and impaired immune surveillance play a role in reducing responsiveness to ICI. Our study aimed to use real-world data to evaluate whether there is a difference in overall survival (OS) following treatment with ICI in patients with viral-induced compared to those with non-viral-induced HCC. Methods: We conducted a retrospective chart review of all patients with unresectable HCC at Mount Sinai Health System who received ICI from 1/2017 to 6/2021. The primary outcome investigated was OS of patients with viral etiologies compared to non-viral etiologies of HCC. Results: A total of 349 patients were included. The cohort was predominantly male (84%), with median age of 63 years. 86% of patients were cirrhotic. 246 (70%) patients had HCC with a viral etiology, with the majority (67.5%) due to hepatitis C infection. 103 patients (30%) had non-viral causes of HCC, with 47% due to NASH and 39% due to alcohol. At the time of ICI initiation, most patients (66%) had Child Pugh (CP) class A liver disease and performance status (PS) ECOG 0 (71%). Nivolumab was the most common ICI given (87%) and 79% of patients received ICI as first-line therapy. The viral and non-viral HCC groups were evenly matched in terms of sex, age, cirrhosis, ECOG PS, type of ICI, and line of therapy. With a median duration of follow-up of 10.5 months (range: 1.4-62.4 months), the median OS (mOS) of patients with viral HCC was 19.3 months (95% CI: 14.2-26.6) and mOS of patients with non-viral HCC was 11.4 months (95% CI: 9.3-17.7; P = 0.08). The hazard ratio, adjusted for CP class and stage, for viral HCC treated with ICI was 0.81 (95% CI: 0.583-1.127; P = 0.21). Conclusions: Patients with viral-induced HCC appear to have improved OS when treated with ICI compared to patients with non-viral-induced HCC, but the difference is not statistically significant. Further studies are required to better understand the mechanisms underlying response to ICI in HCC.