Evaluation of potential serum biomarkers of hepatic fibrosis and necroinflammatory activity in dogs with liver disease

Abstract

BackgroundSerum interleukin 6 (IL‐6), chemokine ligand 2 (CCL2), C‐reactive protein (CRP), and the ratio of aspartate transaminase to alanine transaminase (AST:ALT) have been correlated with fibrosis and necroinflammatory activity in humans with various hepatopathies.Hypothesis/ObjectivesTo determine whether increases in serum IL‐6, CCL2, CRP, or AST:ALT were associated with moderate to severe fibrosis or necroinflammatory activity in dogs with various hepatopathies.AnimalsForty‐four client‐owned dogs with clinical evidence of liver disease and 10 healthy purpose‐bred dogs, all undergoing liver biopsies by laparoscopy or laparotomy.MethodsMeasurement of serum IL‐6, CCL2, CRP, AST, and ALT before scheduled liver biopsy and evaluation of liver histopathology using the METAVIR scoring system used in human medicine, blinded to clinical presentation.ResultsMedian serum IL‐6 was approximately twice as high in dogs with high fibrosis scores (15.5 pg/mL; range, 1.4 to 235 pg/mL) compared to dogs with low fibrosis scores (7.6 pg/mL; range, 1.4 to 148.1 pg/mL), with marginal significance (P = .05). Median serum CCL2 was significantly higher in dogs with active necroinflammation (444 pg/mL; range, 144 to 896 pg/mL) compared to dogs without detectable necroinflammation (326 pg/mL; range, 59 to 1692 pg/mL; P = .008), but with considerable overlap between groups. Neither serum CRP nor AST:ALT ratios were significantly different based on fibrosis or necroinflammatory scores.Conclusions and Clinical ImportanceBecause of substantial variability among dogs, single measurements of IL‐6 and CCL2 have limited diagnostic utility for identifying fibrosis or necroinflammation, respectively, in dogs with various chronic liver diseases. The value of these biomarkers should be explored further in monitoring response to treatment in individual dogs with chronic hepatopathies.

Liver and spleen elastography of dogs affected by brachycephalic obstructive airway syndrome and its correlation with clinical biomarkers

“…In contrast, patients affected by severe OSA had different levels of liver serum biomarkers 11 and elastography studies has shown excellent correlation between the SWV values and biochemical predictors of liver fibrosis (ratio AST/ALT) and between levels of liver biomarkers individually (ALT, AST, GGT and total bilirubin) 30,58 . Whereas, the ratio AST/ALT has no significant correlation to liver fibrosis in dogs and actually has an overlap of values between healthy and affected dogs 24 and, therefore, the ALT and AST enzymatic activities were evaluated individually in this study.…”

“…the most important prognostic factor related to NAFLD 19 . The liver injury and fibrosis are also associated with concomitant portal hypertension 20 that can lead to spleen alterations 21,22 and changes in serum biomarkers 23,24 .…”

Ammonium tetrathiomolybdate treatment of copper‐associated hepatopathy in dogs

“…The H&E‐stained slides were scored for necroinflammatory activity and fibrosis (Table ). A validated scoring system for hepatopathology in dogs does not exist, and the scoring system used herein was derived from the same sources used in previous veterinary publications . It closely resembles a scoring system proposed by the World Small Animal Veterinary Association Liver Standardization Group with the exception that centrilobular inflammation was treated as a distinct category, given the classic pattern of copper accumulation and inflammation in CAH .…”

“…A validated scoring system for hepatopathology in dogs does not exist, and the scoring system used herein was derived from the same sources used in previous veterinary publications. 22,[34][35][36] It closely resembles a scoring system proposed by the World Small Animal Veterinary Association Liver Standardization Group with the exception that centrilobular inflammation was treated as a distinct category, given the classic pattern of copper accumulation and inflammation in CAH. 31 Briefly, scores were assigned for the severity of fibrosis (range, F0-F4), centrilobular inflammation (range, C0-C3), portal inflammation (range, P0-P3), lobular necrosis (range, LN0-LN2), and piecemeal necrosis (range, PMN0-PMN3).…”

Neutrophilia is associated with a poorer clinical outcome in dogs with chronic hepatitis

“…Inflammatory markers such as C-reactive protein12 and haptoglobin13 have previously been investigated in chronic hepatopathies. However, there is a paucity of data evaluating the utilisation of routinely available haematological variables in prognosticating dogs with chronic hepatitis.…”