Hepatocytic ballooning in non‐alcoholic steatohepatitis: Dilemmas and future directions

Li, Yangyang; Zheng, Tian‐Lei; Xiao, Shu‐Yuan; Wang, Peng; Yang, Wenjun; Jiang, Li-Lin; Chen, Lili; Sha, Jun‐Cheng; Jin, Yi; Chen, Sui‐Dan; Byrne, Christopher D.; Targher, Giovanni; Li, Jianmin; Zheng, Ming‐Hua

doi:10.1111/liv.15571

Cited by 19 publications

(19 citation statements)

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“…The demonstration of pronounced glycogenotic and steatotic metabolic aberrations in BH comparable to those emerging early during hepatocarcinogenesis under a variety of conditions strongly suggests a preneoplastic or early neoplastic nature. Pronounced glycogenosis may serve as an appropriate biomarker for BH, particularly solving the dilemma recently emphasized by Li et al 39 to distinguish BH from hepatocellular edema.…”

Section: Discussionmentioning

confidence: 99%

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Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming

Ribback,

Peters,

Yasser

et al. 2023

J Clin Transl Hepatol

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Background and Aims Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development. Methods Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections. Results BH were present in 43.8% of cirrhotic livers. Particularly pronounced excess glycogen storage of (glycogenosis) and/or lipids (steatosis) were characteristic, ground glass features and MDB were often observed. Decreased glucose-6-phosphatase, increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis, lipid metabolism, and cholesterol biosynthesis were discovered. Furthermore, components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis. Conclusions BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis, many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases. Hence, BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming, indicative of a preneoplastic nature.

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Section: Discussionmentioning

confidence: 99%

“… 8 , 30 – 33 The complexity of BH feature recognition due to a lack of appropriate biomarkers has been emphasized in recent considerations on the application of artificial intelligence-based imaging for diagnosis of NAFLD. 38 , 39 …”

Section: Introductionmentioning

confidence: 99%

Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming

Ribback,

Peters,

Yasser

et al. 2023

J Clin Transl Hepatol

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“…At present, the histological nonalcoholic fatty liver disease activity score (NAS), the Matteoni score, the K score, or other semi‐quantitative histological scoring systems are commonly used in clinical practice to diagnose HB 17,26,56,59–61 . However, these scoring systems are often subject to the diagnosing pathologist's subjectivity, which may affect diagnostic results.…”

Section: Analysis Limitations Of Existing Hb Recognition Algorithmsmentioning

confidence: 99%

“…Among these methods, liver histological examination is considered the reference method for diagnosing MASH 24,25 . Hepatocyte ballooning (HB) is an essential histological feature of MASH, indicating hepatocyte degeneration associated with enlargement, swelling, rounding, characteristic reticulated cytoplasm, 26 and playing a critical role in its pathological diagnosis 27,28 . HB is one of the four key histological features for the diagnosis of MASH, along with hepatic steatosis, fibrosis, and lobular inflammation 24,29 .…”

Section: Introductionmentioning

confidence: 99%

Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning

Zheng,

Sha,

Deng

et al. 2023

Liver International

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Metabolic dysfunction‐associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time‐consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.

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“…As hepatocytic ballooning worsens, the delicate balance between cell survival and apoptosis becomes disrupted, tilting toward heightened cellular injury and subsequent inflammation. This concept of a tipping point underscores the clinical significance of hepatocytic ballooning as an indicator of disease severity and progression [ 27 ].…”

Section: Reviewmentioning

confidence: 99%

Hepatocytic Ballooning in Non-alcoholic Steatohepatitis: Bridging the Knowledge Gap and Charting Future Avenues

Singla,

Muneshwar,

Pathade

et al. 2023

Cureus

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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.

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Hepatocytic ballooning in non‐alcoholic steatohepatitis: Dilemmas and future directions

Cited by 19 publications

References 50 publications

Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming

Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming

Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning

Hepatocytic Ballooning in Non-alcoholic Steatohepatitis: Bridging the Knowledge Gap and Charting Future Avenues

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