Etiology–histomorphology–entity correlation in liver pathology: a narrative review

Abstract

Objective: The liver is the central metabolic organ for many biochemical reactions and is involved in the organ-crosstalk via several inter-organ axes. Liver morphology, in particular histomorphology, depends on diverse hepatocellular metabolic activities as well as liver-harmful substances with etiological and clinical relevance (e.g., infection, immune-mediated injury, hepatotoxicity). Intensity, distribution, and composition of the different histomorphological features are variable and result in stereotypic patterns, which show overlaps concerning their etiology and entity. Background: The purpose of the narrative review was to summarize the current knowledge about the correlation of etiology with histomorphology and entity in liver pathology to assist clinical procedures in diagnostic and therapy. In particular, the histomorphological distribution of inflammatory infiltrates, hepatocellular damage, cell loss, fattening and fibrosis in liver tissues is important to derive safe reliable statements concerning etiology and entity of any liver disease. An immediate link between etiology, histomorphology, and entity is possible, but not the rule. Methods: In this narrative review, the different stereotypical reaction patterns of the liver histomorphology are characterized and the key morphology for the respective entity and etiology is shown in the clinical context. In July 2021, the bibliographic database PubMed was searched for publications satisfying the key words: [liver pathology], [entity], [etiology], [review]. In this sorting 572 publications were identified and further studied in detail. Conclusions: The morphological classification of liver injury comprises the important features inflammation, injury of living hepatocytes, cell death, fibrosis, regeneration, vascular remodeling, and neoplasia. The histomorphological estimation of these features in routine pathology is assisted by well-designed sets of scoring systems. In the majority, these rated and validated histomorphological patterns are sufficient to correlate and connect both parameters of clinical relevance, etiology and entity. The importance of tissue-based diagnostic for clinical procedures is evident. However, depending on the weighting and distribution of histomorphological changes and findings, the clear definition of disease entity and/or etiology can be hampered. In particular, the inflammation-related liver morphology is diverse, but the inflammation related patterns show strong overlaps. For that reason the definitive assignment of the histomorphological changes to a clear etiology and/or entity can be problematic. In such instance, the clinical data, e.g., serological parameters and imaging findings, are necessary for the final interpretation of the etiology– histomorphology–entity correlation.