The mutation profiles of HBV or HCV infected hepatocellular carcinoma patients underlie the varied responses to second-line immunotherapy.

Abstract

e16629 Background: HBV and HCV infections facilitate the development of hepatocellular carcinoma (HCC) via different mechanisms, given that the DNA sequence of HBV but not HCV can integrate into the host genome. However, it remains unclear that whether the altered genomic landscape of HCC patients caused by HBV or HCV infection may result in different responses to treatments. Methods: The MSK panel sequencing results and treatment data of 127 HCC patients were downloaded from the TCGA database (MSK, Clin Cancer Res 2018). Profiles of HBV positive and HCV positive patients were extracted. Based on the treatment received, those patients were classified to sorafenib treated groups and sorafenib + immunotherapy (IT) groups. The progression-free survival (PFS, months) and overall survival (OS, months) were compared, and the mutational profiles of patients were analyzed. Results: Among patients who received sorafenib treatment alone, the mean PFS of HBV positive patients (n = 12, 4.9 ±1.1) is similar to that of the HCV positive patients (n = 21, 5.1±1.8). However, the mean OS of HBV positive patients (n = 12, 18.3 ±6.6) was longer than the mean OS of HCV positive patients (n = 21, 10.0 ±1.9). Among the patients who received immunotherapy following sorafenib treatment, the mean IT PFS of HBV positive patients was (n = 5, 4.4 ±1.8), which was longer than the mean IT PFS of HCV positive patients (n = 5, 2.5 ±0.5). Consistently, the mean IT OS of HBV positive patients (n = 5, 10.9 ±4.4) was longer than the mean IO PFS of HCV positive patients (n = 5, 4.6 ±1.0). Overall it seems that the HBV positive patients responded better to second-line immunotherapy, despite the fact that these comparisons did not reach statistical difference due to the limited sample size. By comparing the MSK panel sequencing results, mutations exclusive to the HBV or HCV infected groups were identified. Enrichment analysis showed that 7/35 mutations exclusively found in the HBV positive group are responsible for lymphocyte activation (p < 0.00001), which may underlie the better IT treatment outcome. Among the mutations restricted to the HCV infected group, 9/50 were involved in histone modification, 7/50 were involved in Hepatitis B pathways (p < 0.0001), suggesting that HCV infection may interfere with diverse molecular processes. Conclusions: HBV and HCV infected HCC patients may respond differently to second-line immunotherapy. This difference is perhaps related to the altered genetic landscape of the patients resulted from virus infections by HBV or HCV.