MASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges

Abstract

Metabolic-dysfunction-associated steatotic liver disease (MASLD, previously known as non-alcoholic fatty liver disease (NAFLD)) represents a rapidly increasing cause of chronic liver disease and hepatocellular carcinoma (HCC), mirroring increasing rates of obesity and metabolic syndrome in the Western world. MASLD-HCC can develop at an earlier stage of fibrosis compared to other causes of chronic liver disease, presenting challenges in how to risk-stratify patients to set up effective screening programmes. Therapeutic decision making for MASLD-HCC is also complicated by medical comorbidities and disease presentation at a later stage. The response to treatment, particularly immune checkpoint inhibitors, may vary by the aetiology of the disease, and, in the future, patient stratification will be key to optimizing the therapeutic pathways.

Keywords: cancer; hepatocellular carcinoma (HCC); immunotherapy; liver; metabolic-dysfunction-associated steatotic liver disease (MASLD); non-alcoholic fatty liver disease (NAFLD).

Figure 1

Pathogenesis of MASLD-HCC.

Figure 2

Updated Barcelona Clinic Liver Cancer Staging System 2022. Abbreviations: AFP, alpha fetoprotein; ALBI, albumin–bilirubin; BSC, best supportive care; ECOG-PS, Eastern Cooperative Oncology Group performance status; HCC, hepatocellular carcinoma; LT, liver transplant; MELD, Model for End-Stage Liver Disease; TACE, transarterial chemoembolisation. Reprinted with permission from Reig et al. [110].