Hepatocellular carcinoma (HCC) is the most rapidly expanding cause of cancer-related mortality in the United States. Recent in vitro and animal research suggests that PD-1 targeted immunotherapy drugs do not cause tumor regression in HCC if underlying nonalcoholic steatohepatitis (NASH) is present. The effects of immunotherapy on individuals with NASH-related HCC remain unclear, but more clinical trials are needed to shed light on the topic. Individuals with HCC and cirrhosis owing to NASH to determine which patients had the best responses to immunotherapy. Patients were classified as having HCC associated with NASH cirrhosis or not having HCC associated with NASH cirrhosis. 

All patients were treated with immunotherapy, either as monotherapy or in conjunction with other cancer-targeted therapies, with response evaluations taking place throughout treatment. The end result is that 79 people participated in the study. Fifteen people were diagnosed with HCC because of their NASH cirrhosis, while 64 people were diagnosed with HCC but did not have cirrhosis caused by NASH. Best disease responses to immunotherapy showed that disease progression occurred in 7 of the 14 patients (46.7%, P=0.004) with HCC with NASH cirrhosis but only in 1 of the 14 patients (10.9%, P=0.004) with HCC without NASH cirrhosis. Moreover, immunotherapy was more effective at bringing about disease management (stable disease, partial response, or complete response) in the group without NASH cirrhosis (89.1%) than in the group with NASH cirrhosis-related HCC (8 patients, 53.3%; risk ratio 1.67, P=0.004). Although there were no statistically significant differences in age, gender, or the immunotherapy drugs used, there was a substantially higher number of patients of Hispanic origin in the HCC group with NASH cirrhosis (P=0.006). 

While non-Hispanic patients had a higher risk of disease advancement than Hispanic patients (P=0.07), Hispanic patients did not have a significantly higher risk of disease progression than all other research participants. Individuals with HCC and NASH cirrhosis had a considerably greater rate of disease progression as the best response to immunotherapy compared to patients without NASH cirrhosis. Further prospective studies are required to establish the impact of underlying liver disease etiology on the response to immunotherapy as it relates to the rising usage of immunotherapy in HCC patients.

Source – ASCO GI 2023