Restoration of CD4+ T Cells during NAFLD without Modulation of the Hepatic Immunological Pattern Is Not Sufficient to Prevent HCC

Simple Summary Global incidence of hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease (NAFLD) is projected to increase over the next ten years. This is thought to be due to an increased consumption of an inflammatory Western diet (WD) which is a high fat and high sugar diet that alters the hepatic immune system, particularly CD4(+) T cells. The aim of this study is to determine if an anti-inflammatory drug, SP16, could protect CD4(+) T cells during WD, and potentially prevent NAFLD-associated HCC. Although SP16 treatment restored the depleted CD4(+) T cells, the drug was administered late in the course of NAFLD and was therefore unable to fully modulate the hepatic immunological patterns, which appears to be critical in preventing NAFLD-associated HCC. Predominant inflammatory immunological patterns as well as the depletion of CD4(+) T cells during nonalcoholic fatty liver disease (NAFLD) are reported to be associated with the progression of hepatocellular carcinoma (HCC). Here, we report that an LRP-1 agonistic peptide, SP16, when administered during advanced NAFLD progression, restored the depleted CD4(+) T cell population but did not significantly affect the inflammatory immunological pattern. This data suggests that restoration of CD4(+) T cells without modulation of the hepatic immunological pattern is not sufficient to prevent HCC. However, SP16 administered early during NAFLD progression modulated the inflammatory profile. Future studies will determine if regulation of the inflammatory immune response by SP16 early in NAFLD progression will prevent HCC.

Automated summary

The study investigated the potential protective effect of an anti-inflammatory drug, SP16, on CD4(+) T cells in the context of western diet-associated NAFLD and its progression to HCC. The results showed that although SP16 treatment restored depleted CD4(+) T cells, it was not able to fully modulate the hepatic immunological patterns, indicating the importance of early administration for HCC prevention. Future studies will explore the regulation of inflammatory immune response by SP16 in early NAFLD progression to prevent HCC.