Comparison and Evaluation of CTGF and P2/MS as Noninvasive Markers in Fibrosis Evaluation in Chronic Liver Disease (original) (raw)
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Journal of Hepatology, 2012
Background & Aims: Time-dependent statistics have been used to assess liver fibrosis progression (LFP) in liver diseases from birth to first biopsy, in a limited number of patients. Non-invasive biomarkers such as FibroTest (FT) should allow the estimation of LFP on larger populations. We aimed at validating this concept by comparing LFP using FT vs. biopsy (P1) and then at applying the non-invasive method to a large population (P2). Methods: In P1, LFP was assessed using biopsy and FT in 2472 untreated patients: 770 with chronic hepatitis C, 723 with hepatitis B, 761 with non-alcoholic fatty liver disease (NAFLD), and 218 with alcoholic fatty liver disease (ALD). In P2, 342,346 interpretable FT prospectively measured were used. LFP was estimated using transition rates (cumulative hazard rate) to cirrhosis (F4) or to minimal fibrosis (>F0). Results: In P1, there was a significant concordance between FT and biopsy estimates of hazards with intraclass correlation (ICC) = 0.961 (95% CI 0.948-0.970) and 0.899 (95% CI 0.135-0.969) for F4 and >F0, respectively. This concordance persisted according to the disease and the gender. The more rapid LFP to F4 (biopsy/FT) was observed for men with ALD (1.44/1.62), and the slower for women with NAFLD (0.09/0.02). In P2, the LFP started to increase for men at the age of 30 years. The cumulative fibrosis progression rate to minimal fibrosis in women crossed the ''man curve'' around the age of 80 years. The following factors were associated with LFP to F4 (all p <0.0001): male gender (Relative Risk = 3.29), HIV co-infection (2.33), and residency in Middle East (2.67) or Eastern Europe (2.15). Conclusions: Validated biomarkers such as FibroTest should allow powerful analysis of fibrosis progression in chronic liver diseases and better identification of risk factors.
Clinical and Experimental Gastroenterology, 2011
Background: Progressive hepatic fibrosis (HF) is a prominent feature of biliary atresia (BA), the most common indication for liver transplantation (LT) in children. Despite its importance in BA, HF is not evaluated in routine patient care because the invasiveness of liver biopsy makes histologic monitoring of fibrosis unfeasible. Therefore, the identification of noninvasive markers to assess HF is desirable especially in children. Purpose: The main goal of this pilot project was to establish an investigational framework correlating hepatic expression of fibrogenic markers with routine blood tests in BA. Methods: Using liver explants from patients with BA (n = 26), immune-expression of connective tissue growth factor (CTGF), a key fibrogenic cytokine was determined using horseradishlabeled antibodies. Expression intensities of lobular (L-CTGF) and portal (P-CTGF) CTGF were determined by using ImageJ software. These CTGF intensities were correlated with blood tests performed at the time of LT. Correlation coefficients were determined for each blood test variable versus mean L-CTGF and P-CTGF expression intensities. A P-value of less than 0.05 was considered statistically significant. Results: All patients had end-stage liver disease and persistent cholestasis at the time of LT. Kendall tau (τ) rank correlation coefficient for L-CTGF and white blood cell (WBC) was inversed (-0.52; P # 0.02). Similar but statistically nonsignificant inverse relationships were noted between L-CTGF and prothrombin time (PT) (-0.15; P # 0.4), international normalized ratio (INR) (-0.14; P # 0.5), and platelet count (-0.36; P # 0.09). Inversed (τ) rank correlation coefficients were also evident between P-CTGF expression and gamma-glutamyl transpeptidase (GGT), PT, INR, and platelet count. Pearson correlation coefficients for combinational analysis of standardized total bilirubin (TB), alkaline phosphatase, GGT, and platelet count with L-CTGF (0.33; P = 0.3) and P-CTGF (0.06; P = 0.8), were not significant. Similar analysis for alanine aminotransferase, TB, and GGT combination (L-CTGF, 0.16; P = 0.5; P-CTGF -0.3; P = 0.2) as well as WBC, platelet count, and TB (L-CTGF: -0.36; P = 0.09; P-CTGF -0.33; P = 0.13) also revealed nonsignificant results. Conclusion: Hepatic expression of fibrogenic markers can be correlated with routinely performed blood tests in patients with BA. We document that although a trend of inverse relationship is noted, hepatic CTGF expression does not correlate well with routinely performed blood tests in advanced BA. Further work is required to determine more reliable ways of noninvasive diagnosis of HF.
Future Science OA, 2018
Liver fibrosis occurs in response to different etiologies of chronic liver injury. Diagnosing degree of liver fibrosis is a crucial step in evaluation of severity of the disease. An invasive liver biopsy is the gold standard method associated with pain and complications. Biomarkers to detect liver fibrosis include direct markers of extracellular matrix turnover and indirect markers as a reflection of liver dysfunction. Although a single marker may not be useful for successful management, a mathematical equation combining tests might be effective. The main purpose of this review is to understand the diagnostic accuracy of biomarkers and scoring systems for liver fibrosis. Advances in-omics approach have generated clinically significant biomarker candidates for liver fibrosis that need further evaluation.
Evaluation of liver fibrosis: “Something old, something new…”
Annals of Gastroenterology, 2016
Hepatic fibrogenesis may gradually result to cirrhosis due to the accumulation of extracellular matrix components as a response to liver injury. Thus, therapeutic decisions in chronic liver disease, regardless of the cause, should first and foremost be guided by an accurate quantification of hepatic fibrosis. Detection and assessment of the extent of hepatic fibrosis represent a challenge in modern Hepatology. Although traditional histological staging systems remain the "best standard", they are not able to quantify liver fibrosis as a dynamic process and may not accurately substage cirrhosis. This review aims to compare the currently used non-invasive methods of measuring liver fibrosis and provide an update in current tissue-based digital techniques developed for this purpose that may prove of value in daily clinical practice.
From liver biopsy to non-invasive markers in evaluating fibrosis in chronic liver disease
2016
Chronic liver disease is a late stage of progressive hepatic fibrosis. It consists of functional and structural disruptions in most chronic liver diseases. An accurate diagnosis allows us to establish the degree of fibrosis and the stage of the disease, the prognosis of the patient and to predict a treatment response. Despite the fact that liver biopsy is considered a gold standard, noninvasive methods for diagnosing liver fibrosis have gained more and more importance. Whether we talk about serum biomarkers or imagistic methods from transient elastography to 3-D magnetic resonance elastography, the question remains: are these useful or useless? Serum biomarkers represent blood components that can reflect liver histological changes, thus they can monitor the continuous process of fibrosis. These can be subcategorized in direct (that show extracellular matrix turnover) and indirect markers (that reflect disturbances in the hepatic function). However these markers alone are not as accu...
Noninvasive Biomarkers for the Diagnosis of Liver Fibrosis and Cirrhosis
Liver Cirrhosis - Debates and Current Challenges, 2019
The clinical importance of monitoring liver fibrosis lies in the morbidity and mortality of the chronic liver diseases in relation to the stage and progression of fibrosis. Whether the fibrosis stabilizes or regresses depends on the specific treatment. Liver biopsy, the current standard for the diagnosis, has implicit limitations due to sampling heterogeneity. There are noninvasive imaging methods, such as transient elastography that measures the stiffness of the liver, but it has some limitations (feasibility and unreliability), particularly in obese patients. FibroTest is the most widely used noninvasive serological method worldwide which is efficacious in the extreme stages of fibrosis, but these methods cannot discern intermediate stages. Liver fibrosis is a dynamic response that involves multiple cellular and molecular events with an excessive deposit of extracellular matrix. Even though there is much information on the pathophysiology of fibrosis, that knowledge is still incomplete, greatly hindering the development of both an accurate treatment and a noninvasive diagnostic method with adequate sensitivity for all the stages of fibrosis. It is known that IGFBP participates in liver homeostasis, and thus these proteins can be used as serum biomarkers during the progression of liver fibrosis in chronic hepatitis C.