S Duarte, BSc

Currently, the most effective treatment for non-alcoholic fatty liver disease (NAFLD) is diet and exercise. Weight loss of 5% achieved through lifestyle interventions has been associated with the reversal of steatosis, and a 10% weight reduction has been linked to the reversal of fibrosis. Physical activity (PA) has been hypothesised to reduce the accumulation of intrahepatic triglycerides contributing to NAFLD progression.

Lipid droplets (LDs) are lipid-rich and dynamic organelles which undergo cycles of biogenesis (triacylglycerol synthesis, as well as LD growth, budding, and expansion) and degradation (lipophagy). Many studies have highlighted the causative role of abnormal LD accumulation in the development of non-alcoholic fatty liver disease (NAFLD). Furthermore, while the positive impact of physical activity on NAFLD has been widely studied, its effect on LD dynamics remains unclarified.

Research in recent years has documented the rise of quantitative ultrasound-based examinations (qnUS) for the assessment of liver steatosis. qnUS of interest include continuous attenuation parameters (CAP), backscatter coefficients, and ultrasound envelope statistic parametric imaging. Despite the clear financial and patient-centric benefits of such non-invasive tools, their reliability in defining both the presence and degree of liver steatosis remains unclear.

The term metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been
suggested as an alternative to non-alcoholic fatty liver disease (NAFLD). Unlike NAFLD,
MAFLD’s diagnosis is based on the active identification of NAFLD-associated metabolic abnormalities. Many researchers agree that MAFLD adequately captures the systemic factors and upstream drivers of the disease, with a significant proportion concluding that it does so better than the original NAFLD definition.

Non-alcoholic fatty liver disease (NAFLD) has become the fastest growing cause of hepatocellular carcinoma (HCC) in the United States, Europe, and South-East Asia. HCC related to non-alcoholic steatohepatitis (NASH), the inflammatory subtype of NAFLD, may soon become as prominent worldwide as viral HCC.

Recent evidence has highlighted non-alcoholic steatohepatitis’ (NASH) predisposing role in the development of hepatocellular carcinoma (HCC). Despite this, the mechanisms underlying NASH-related HCC remain unknown. Identifying the molecular pathways contributing to the development of NASH-HCC is crucial to addressing this knowledge gap, and the determination of novel therapeutic targets for NASH-HCC remains a clinical priority.

A recent pilot study found that elderly individuals (over 65 years of age) with type 2 diabetes mellitus (T2DM) are at a significantly higher risk of developing NAFLD and advanced fibrosis. However, this finding requires further validation before systematic screening of this patient population can be recommended by practice guidelines. 

Dysfunctional visceral adipose tissue is one of the major drivers and determinants of non-alcoholic fatty liver disease (NAFLD). Due to an inability to store excess energy in adipose tissue compartments, the body resorts to storing it in ectopic fat compartments. Compared with lean individuals, people who are overweight or obese are thus at a higher risk of developing NAFLD.

While liver biopsy is the current golden standard for the diagnosis and staging of fibrosis, many studies have highlighted the usefulness of non-invasive tests (NITs) for fibrosis screening and risk stratification. Despite this, pertinent NIT thresholds for these applications have yet to be defined.

Myeloid immune cells, e.g. macrophages, play a crucial role in the progression of non-alcoholic fatty liver disease (NAFLD), and thus significantly contribute to the development of non-alcoholic steatohepatitis (NASH). However, due to its complex phenotype and high heterogeneity, this cell type is particularly difficult to isolate and analyse.

The term metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been suggested as an alternative to non-alcoholic fatty liver disease (NAFLD). Unlike NAFLD, MAFLD’s diagnosis is based on the active identification of NAFLD-associated metabolic abnormalities. While MAFLD is commonly associated with obesity, recent evidence has affirmed that a significant proportion of MAFLD patients in fact possess normal body mass indexes (BMI).

The current gold standard for the diagnosis and assessment of non-alcoholic fatty liver disease (NAFLD) progression is liver biopsy, which is then followed by microscopic analysis by a pathologist.To assess disease progression, the Kleiner and Brunt scoring system is typically used. In short, this approach assesses three histological features of liver injury (ballooning, inflammation, and steatosis). Analyses of these features are then combined to generate a NAFLD activity score.