NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options

Abstract

In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) represent an increasingly important underlying aetiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation are characterised by several unique features: in contrast to virally driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis and annual HCC incidence is comparatively low, complicating current surveillance strategies. On average, patients are older and are more frequently diagnosed at an advanced stage. While locoregional treatments are probably equally effective regardless of HCC aetiology, the picture is less clear for systemic therapy. Tyrosine kinase inhibitors are probably equally effective, while there have been initial signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC than in viral HCC. Current international clinical practice guidelines for HCC do not consider aetiology, as there are insufficient data to draw specific conclusions or to recommend aetiology-specific modifications to the current management of patients with HCC. However, in light of the growing relevance of NAFLD-HCC, future clinical trials should assess whether HCC aetiologyand NAFLD/NASH in particularinfluence the safety and efficacy of a given treatment.

Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis

“…8 The rising incidence of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) is projected to soon become the predominant underlying HCC etiology. [17][18][19] Although the number of HCV cured continues to rise, many of these patients still suffer from cirrhosis due to chronic inflammation, which may be further complicated by other risk factors including metabolic syndrome and excessive alcohol consumption. 20 Noninvasive biomarkers that can predict the natural course of chronic liver disease, cirrhosis outcome, early prediction of premalignant disease and HCC are still urgently needed.…”

Targeting Gut Microbiota With Natural Polysaccharides: Effective Interventions Against High-Fat Diet-Induced Metabolic Diseases

“…Non-alcoholic fatty liver disease remains a highly prevalent and largely underappreciated chronic liver disease that strongly affects about one-quarter of the global adults, and NAFLD is one of the most important risk factors of hepatocellular carcinoma ( Foerster et al, 2021 ; Lazarus et al, 2021 ). The majority of patients suffering from NAFLD are obese, and NAFLD is considered as a further manifestation of metabolic syndrome ( Tarantino and Finelli, 2015 ).…”

PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease

“…Since HCC is emerging as one of the leading causes for cancer-related mortality, great efforts have been performed to identify an efficient curative strategy. Currently, the only proposed strategies for HCC are loco-regional treatments (i.e., hepatic resection, ablation, transarterial chemoembolisation), inhibitors of tyrosin kinase/anti-angiogenetic agents, as Sorafenib, Regorafenib and ramucirumab, and ultimately liver transplantation [ 50 ]. Very recently also Lenvatinib, an oral multikinase inhibitor, was confirmed as non-inferior to Sorafenib in untreated advanced hepatocellular carcinoma [ 51 , 52 ].…”