Non-invasive serum fibrosis markers: A study in chronic hepatitis

Abstract

Introduction: Chronic hepatitis is specified as inflammatory disease of the liver lasting for more than six months. Role of noninvasive fibrosis markers as prognostication factors of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis is the aim of this study. Methods: Two hundred twenty-one patients with chronic hepatitis involved in the study between 2011 and 2013. Routine biochemical indices and serum fibrosis markers such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were evaluated, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Diagnostic accuracies of these markers for prediction of significant fibrosis were assessed by Receiver Operating Characteristic (ROC) curve analysis. Results: Contemporaneous laboratory indices for imputing AAR, APRI, and FIB-4 were identified with liver biopsies. From all, 135 males (61.1%) and 86 females (38.9%), with mean age of 39.6±14.4 were studied. Significant correlation between stages of fibrosis and FIB-4, APRI and AAR were detected, with a correlation coefficient higher than that of other markers in the patients with Hepatitis B (r = 0.46), C (r = 0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) were superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy. Conclusion: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.

Liver Biopsy is the Gold Standard at Present, How about Tomorrow?

“…However, although rare, apart from severe complications such as bleeding, biliary perforation and peritonitis, pneumothorax or death, it has some other drawbacks including inaccurate staging due to sampling errors (needle biopsy samples only 1/50.000 of the liver), lack of standardization of staining, observer-dependent diagnostic variations (inter or intra observer), and financial burden (1,2,3,4). Moreover, patients undergoing liver biopsy may require hospitalization, thus, more than 90% of complications are likely to happen during the first 24 hours after biopsy (3). Also, in patients with chronic viral hepatitis, repeated biopsies for defining the therapy response or predicting prognosis in the posttreatment follow-up period may be another problem (4).…”

“…Also, in patients with chronic viral hepatitis, repeated biopsies for defining the therapy response or predicting prognosis in the posttreatment follow-up period may be another problem (4). For these reasons, there are attempts searching non-invasive predictive models to substitute liver biopsy (2,3,4).…”

“…Indeed, certain non-invasive modalities, including direct or indirect serum markers and imaging tools are available for determining fibrosis degree in patients with viral hepatitis, particularly hepatitis C virus infection (2,3,4).…”

“…Aside from imaging tools, serum markers, indirect or direct, may be the other options to evaluate liver fibrosis (2,3,4). Indirect serum markers, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio, γ-glutamyltranspeptidase, total bilirubin, γ2-macroglobulin, apolipoprotein A1, haptoglobin, cholesterol and platelet count or indices, singly or especially in a combination including age-platelet index, AST-to-ALT ratio, AST-to-platelet ratio index (APRI), Forns' index, fibrosis index based on four factors, Fibrotest, Fibroindex, Lok index, King's score and Goteborg University Cirrhosis Index have been evaluated in many studies with questionable results (2,3,4).…”

“…Furthermore, hepatic matrix metabolism markers, reflecting matrix accumulation (fibrogenesis) or degradation (fibrolysis), as direct markers including type IV collagen, hyaluronic acid, laminin, transforming growth factor beta 1, YKL-40, metalloproteinases or tissue inhibitors of metalloproteinases have been found to be useful in predicting fibrogenesis (2,3,4).…”