Abstract

The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology. It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. Our aim was to investigate whether immunohistochemistry and multiplexing for collagen type (I & III) and elastic fibres and a modified Victoria blue method could be helpful. We studied 43 livers removed at transplantation for acute liver failure (ALF, 20 cases) or cirrhosis (23) plus 8 normal controls. In ALF the periportal ECM was normal in 2 cases, contained mainly collagen I associated with a ductular reaction in 6 cases, and delicate elastic strands in 11 cases. Periportal deposition of mainly collagen I and mature elastic fibres was observed in cirrhosis. In ALF the perisinusoidal ECM was intact in 4 cases, collapsed or condensed but of normal composition (predominantly collagen III) in 2 cases, and collapsed and condensed containing mostly collagen I in 17 cases (7 including delicate immature elastic strands). In contrast, bridging fibrous septa of cirrhosis contained abundant collagen 1 and bundles of mature elastin. We propose the use of a scale and the use of immunohistochemistry and multiplexing in additional to histochemical stains to characterise the ECM changes in acute and chronic liver injury.

Highlights

  • The double stain for collagen I and collagen III failed to reach standard in four cases and the elastin stain failed in one case, in likelihood due to defective fixation

  • Our study cohort of cases of acute liver failure (ALF) was based on 12 cases of submassive necrosis, 6 cases of massive necrosis and 5 cases of confluent necrosis due to paracetamol overdose (POD) related injury

  • The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology

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Summary

Introduction

The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. A challenging aspect in liver pathology is the interpretation of changes occurring in areas of hepatocyte loss when differentiating between acute and chronic liver injury This is often characterised by a distinction between an active profibrogenic deposition of connective tissue fibres and pre-existing connective tissue fibres collapsed and condensed from hepatocyte ­dropout[1]. Our aim was to describe the changes to the composition of the extracellular matrix (ECM) in terms of collagen types (I & III) using multiplex IHC and elastic fibres (Oxytalan vs Elaunin and mature elastin) using VB and elastin IHC in areas of hepatocyte loss occurring in acute and chronic liver injury. We have studied a retrospective cohort of livers removed at transplantation for acute liver failure (ALF) or cirrhosis and a control group of Scientific Reports | (2021) 11:14569

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