Immunotherapy for NAFLD and NAFLD-related hepatocellular carcinoma

Abstract

The progression of non-alcoholic fatty liver disease (NAFLD), the most common liver disease, leads to non-alcoholic steatohepatitis and hepatocellular carcinoma. Despite the increasing incidence and prevalence of NAFLD, its therapeutic and preventive strategies to lower the disease burden is limited. In recent years, immunotherapy, including anti-programmed cell death 1/programmed cell death 1 ligand 1 treatment, has emerged as a potential approach to reach satisfactory modulation for the progression of NAFLD and treatment of NAFLD-related hepatocellular carcinoma. However, the effectiveness of immunotherapy against NAFLD and NAFLD-related hepatocellular carcinoma is in the early phase and it is yet not advanced. In addition, conflicting results are being reported regarding the prognosis of patients with NAFLD-related hepatocellular carcinoma and high expression of programmed cell death 1/programmed cell death 1 ligand 1. Herein, this review will discuss and elucidate the attempts and underlying mechanisms of immunotherapy against NAFLD and NAFLD-related hepatocellular carcinoma.

Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments

“…Several pharmaceutical agents have been developed to target PD-1 receptors. Pembrolizumab has shown significant enhancement in overall survival and progression-free survival although statistical significance was not met[ 176 ]. However, it is also thought that NASH-derived HCC may be less responsive to immune modulated therapy due to NASH-related aberrant T cell activation, causing damage to tissues[ 175 , 177 , 178 ].…”

Interleukins: Pathogenesis in Non-Alcoholic Fatty Liver Disease

“…Given the tight relationship between IR, type 2 diabetes, and NAFLD, several antihyperglycemics were used as a treatment option for NAFLD/NASH, especially for patients who are overweight/obese [ 69 , 70 ]. Despite weak evidence related to the beneficial effect on liver fat and fibrosis, metformin is the first treatment option for type 2 diabetes and NAFLD [ 70 ].…”

“…Despite weak evidence related to the beneficial effect on liver fat and fibrosis, metformin is the first treatment option for type 2 diabetes and NAFLD [ 70 ]. If the glycemic control is not achieved with metformin, other treatment options are as follows: thiazolidinediones, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP1) receptor antagonists [ 69 , 70 ].…”

“…Thiazolidinediones (e.g., rosiglitazone and pioglitazone) are peroxisome proliferator-activated receptor (PPARγ) agonists acting to enhance insulin sensitivity and diminish hepatic steatosis [ 69 ]. Pioglitazone was shown to reduce lobular inflammation and hepatic steatosis and even improved liver fibrosis, as confirmed by a recent meta-analysis that included five randomized controlled trials with pioglitazone in patients with NAFLD, thus being regarded as the current treatment option for patients with T2DM and NAFLD [ 70 ].…”

“…GLP1 receptor antagonists (e.g., liraglutide, semaglutide, exenatide, dulaglutide) act as inducers of pancreatic β cells to secrete insulin, have beneficial effects on NAFLD, mostly due to systemic alterations in the metabolism rather than a direct effect on the liver itself [ 69 ]. NAFLD patients exhibit insufficient GLP-1 secretion.…”