ABSTRACT
Hepatocytic ballooning is a key histological feature in the diagnosis of non-alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems for diagnosing and staging non-alcoholic fatty liver disease (NAFLD) [namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system]. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in 'real life' situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter-observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory-Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Liver/pathology , Artificial Intelligence , Hedgehog Proteins , Severity of Illness Index , BiopsyABSTRACT
Non-alcoholic steatohepatitis (NASH) is emerging as a significant global health concern, characterized by hepatic lipid accumulation, inflammation, and hepatocellular injury. Hepatocytic ballooning, a histological feature of NASH, has gained prominence for its role in disease progression and potential as a therapeutic target. This review provides an overview of the current knowledge regarding hepatocytic ballooning in NASH, highlighting the key molecular and cellular mechanisms implicated in its development. We delve into the intricate interplay of metabolic dysregulation, oxidative stress, and lipid toxicity as drivers of hepatocytic ballooning, shedding light on the pathways responsible for its initiation and perpetuation. Furthermore, we explore the diagnostic challenges associated with hepatocytic ballooning and its significance as a prognostic indicator in NASH patients. While hepatocytic ballooning holds promise as a therapeutic target, this abstract discusses the various experimental and clinical approaches to ameliorate this histological hallmark. Potential interventions, including lifestyle modifications, pharmacological agents, and emerging therapies, are evaluated in terms of their efficacy and safety profiles. In conclusion, this review underscores the need to bridge the knowledge gap surrounding hepatocytic ballooning in NASH and emphasizes its importance in understanding disease pathogenesis and progression. By charting future research avenues and clinical strategies, we aspire to advance our comprehension of NASH and ultimately improve patient outcomes in this rapidly evolving field of hepatology.