scholarly journals Noninvasive Biomarkers of Liver Fibrosis: An Overview

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Hind I. Fallatah

Chronic liver diseases of differing etiologies are among the leading causes of mortality and morbidity worldwide. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This paper will focus on the various noninvasive biochemical markers used to stage liver fibrosis.

Author(s):  
Enass A Abdel-hameed ◽  
Susan D Rouster ◽  
Shyam Kottilil ◽  
Kenneth E Sherman

Abstract Background Accurate noninvasive biomarkers of fibrotic progression are important for hepatitis C virus (HCV) management, but commonly used modalities may have decreased efficacy in human immunodeficiency virus (HIV)/HCV-coinfected persons. The enhanced liver fibrosis (ELF) index is a highly sensitive noninvasive marker of hepatic fibrosis that has had limited assessment in the HIV/HCV population. We compared ELF index performance to FIB4 and aspartate to platelet ratio index (APRI) at different stages of liver fibrosis as determined by liver histology, and validated the efficacy of the three noninvasive biomarkers in HIV/HCV-coinfected versus HCV-monoinfected. Methods The ELF index was determined in 147 HIV/HCV-coinfected and 98 HCV-monoinfected persons using commercial ELISA assays for the component elements of the index. Area under the receiver-operator curve was used to validate ELF and to compare its performance to liver histology as well as to other noninvasive biomarkers of liver fibrosis, FIB4, and APRI. Results The ELF index increased with histological stage of liver fibrosis and exhibited a linear relationship with Metavir score in all subjects. ELF performance was comparable between HIV/HCV and HCV with advanced liver fibrosis/cirrhosis. In the HIV/HCV cohort ELF cutoffs of 8.45 and 9.23 predicted mild and moderate fibrosis with 85% sensitivity, whereas the ELF cutoff of 9.8 had the highest specificity for advanced fibrosis and the cutoff of 10.4 was 99% specific for cirrhosis. ELF performance was superior to FIB4 and APRI in all subjects regardless of HIV status. Conclusions ELF index demonstrated excellent characteristics toward accurate prediction of liver fibrosis and cirrhosis with superior performance to APRI and FIB4 in HIV/HCV coinfection. Applying this noninvasive biomarker index for diagnosis of liver fibrosis and progression in HIV/HCV is warranted.


2014 ◽  
pp. 5-11
Author(s):  
Thi Khanh Tuong Tran ◽  
Trong Thang Hoang

Staging of hepatic fibrosis is crucial for prognosis, surveillance and treatment decision in patients with chronic liver diseases in clinical practice. Liver biopsy has still the gold standard for assessment of hepatic fibrosis, but it has some limitations. To overcome this, non-invasive methods were developed. The methods of noninvasive assessment of liver fibrosis were divided into two main groups: serum biomarkers and techniques measuring liver stiffness. Each method has its own advantages and limits. Some studies suggest that the effectiveness of noninvasive methods for assessing liver fibrosis may increase when they are combined. The aim of this article is to review and update the different non invasive methods for assessment of hepatic fibrosis, their advantages, disadvantages, diagnostic accuracy and their applications in clinical practice. Key words: hepatic fibrosis, liver stiffness, chronic liver disease


Author(s):  
Chenjun Huang ◽  
Lijuan Liu ◽  
Hao Wang ◽  
Meng Fang ◽  
Huijuan Feng ◽  
...  

Abstract Objectives Liver cirrhosis (LC) is the end-stage of fibrosis in chronic liver diseases, non-invasive early detection of liver fibrosis (LF) is particularly essential for therapeutic decision. Aberrant glycosylation of glycoproteins has been demonstrated to be closely related to liver abnormalities. Methods This study was designed to enroll a total of 1,565 participants with LC/LF, chronic hepatitis virus (CHB) and healthy controls. Fibrosis was confirmed by liver biopsy. Using capillary electrophoresis N-glycan fingerprint (NGFP) analysis, we developed a nomogram algorithm (FIB-G) to discriminate LC from non-cirrhotic subjects. Results The FIB-G demonstrated good diagnostic performances in identifying LC with the area under the curve (AUC) 0.895 (95%CI: 0.857–0.915). Furthermore, the diagnostic efficiencies of FIB-G were superior to that of log (P2/P8), procollagen III N-terminal (PIIINP), type IV collage (IV-C), laminin (LN), hyaluronic acid (HA), aspartate transaminase to platelets ratio index (APRI), and FIB-4 when detecting significant fibrosis (S0–1 vs. S2–4, AUC: 0.787, 95%CI: 0.701–0.873), severe fibrosis (S0–2 vs. S3–4, AUC: 0.844, 95%CI: 0.763–0.924), and LC (S0–3 vs. S4, AUC: 0.773, 95%CI: 0.667–0.880). Besides, changes of FIB-G were associated well with the regression of fibrosis and liver function Child–Pugh classification. Conclusions FIB-G is an accurate multivariant N-glycomic algorithm for LC prediction and fibrosis progression/regression monitoring. The high throughput feasible NGFP using only 2 μL of serum could help physicians make the more precise non-invasive staging of LF or cirrhosis and reduce the need for invasive liver biopsy.


2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Ola Galal Behairy ◽  
Ola Samir El-Shimi ◽  
Naglaa Hamed Shalan

Abstract Background Liver biopsy is the gold standard for detecting the degree of liver fibrosis; however, invasiveness constitutes its main limiting factor in clinical application, so we aimed to evaluate the non-invasive biomarker formulas (APRI and FIB-4) and their modified forms by BMI z-score (M-APRI, M-FIB-4, and B-AST) compared to liver biopsy in the assessment of liver fibrosis in children with chronic liver diseases. Two hundred children aged 6.3 ± 3.8 years (98 males, 102 females) with chronic liver diseases underwent liver biopsy. The stage of fibrosis was assessed according to the METAVIR system for all children, and the following non-invasive biomarker formulas were calculated: APRI, modified APRI (M-APRI: BMI z-score × APRI), Fibrosis-4 index (FIB-4), modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and B-AST (BMI z-score × AST). The best cutoff value was calculated to detect early fibrosis (F1–F2) from advanced liver fibrosis (F3–F4). Results There were positive correlations between all studied non-invasive biomarker models (APRI, FIB-4, M-APRI, M-FIB-4, B-AST) and fibrosis score as an increase in fibrosis score was associated with an increase in mean ± SD of all studied biomarker formulas. The best cutoff values of non-invasive biomarker models in the diagnosis of early fibrosis (F1–F2) were APRI > 0.96, M-APRI > 0.16, FIB-4 > 0.019, M-FIB-4 > 0.005, and B-AST > −8 with an area under the curve above 0.7 each, while the best cutoff values of non-invasive biomarker models (APRI, M-APRI, FIB-4, M-FIB-4, and B-AST) in the diagnosis of advanced liver fibrosis (F3–F4) were >1.96, >2.2, >0.045, and >0.015, >92.1, respectively, with an area under the curve above 0.8 each. Conclusion APRI, M-APRI, FIB-4, M-FIB-4, and B-AST are good non-invasive alternatives to liver biopsy in the detection of liver fibrosis in children with chronic liver diseases of different etiologies especially those that include BMI z-scores in their formulas.


2018 ◽  
Vol 13 (1) ◽  
pp. 44-46
Author(s):  
Hafizur Rahman

Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infection has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive technique and has been the standard of care of fibrosis assessment for years; however, it has several limitations and procedure related complications. Recently, several methods of noninvasive assessment of liver fibrosis have been developed which require either serologic testing or imaging of liver. Imaging based noninvasive techniques are reviewed here and their clinical use is described. Some of the imaging based tests are becoming widely available, and collectively they are shown to be superior to liver biopsy in important aspects. Clinical utilization of these methods requires understanding of performance and quality related parameters which can affect the results and provide wrong assessment of the extent of liver fibrosis. Familiarity with the strengths and weakness of each modality is needed to correctly interpret the results in appropriate clinical content. A new technique called Elast PQ uses ultrasound shear wave elastography to provide a noninvasive, reproducible, easily performed method of assessing liver fibrosis. It can easily combine a routine ultrasound imaging exam of the liver anatomy with targeted tissue stiffness values, assess liver fibrosis in patient with clinically suspected disease even before abnormalities are detected with ultrasound imaging, evaluate and obtain a baseline stiffness value in patients with chronic liver disease, follow up patients under treatment to monitor progression, stabilization or regression of liver disease and help avoid the need for liver biopsies when elastography results are consistent with other clinical findings. Both the prognosis and potential treatment of chronic liver diseases greatly depend on the progression of liver fibrosis, which is the ultimate outcome of chronic liver damage. Historically, liver biopsy has been instrumental in adequately assessing patients allows clinicians both to obtain diagnosis information and initiate adequate therapy. However, the technique is not exempt of deleterious effects. Multiple diagnostic tests have been developed for the staging of fibrosis using noninvasive methods, most of them in the setting of chronic hepatitis C. The goal of this paper is to review available data on the staging and assessment of liver fibrosis with two methods: serum markers & transient elastography (FibroScan).Faridpur Med. Coll. J. Jan 2018;13(1): 44-46


2018 ◽  
Vol 75 (4) ◽  
pp. 374-379
Author(s):  
Tamara Milovanovic ◽  
Ana Copertino ◽  
Ivan Boricic ◽  
Biljana Milicic ◽  
Aleksandra Pavlovic-Markovic ◽  
...  

Backgrund/Aim. In recent decades noninvasive methods for the assessment and monitoring of liver fibrosis have been developed and evaluated in numerous chronic liver diseases. The aim of this study was to evaluate the diagnostic accuracy of noninvasive markers for fibrosis assessment transient elastography (TE) and biochemical markers using liver biopsy as reference in patients with primary biliary cirrhosis (PBC). Methods. One hundred and twenty-two patients underwent both liver biopsy and blood tests on the same day and TE in a month following the biopsy and the tests. Liver biopsies were reviewed by a single pathologist using the METAVIR scoring system for assessment of liver fibrosis. Aspartate aminotransferase (AST), platelet ratio index (APRI), Forns scores, AST and alanine transaminase (ALT) ratio and TE were compared with liver fibrosis stage in order to determine the best noninvasive marker of liver fibrosis. Results. There was a statistically significant difference (p < 0.05) for the APRI score, Forns index and TE according to stages of liver fibrosis. TE showed superior diagnostic performance when compared to other surrogate markers of liver fibrosis that were investigated. Optimal cut-off for TE were 4.25 and 5.9 kPa for diagnosing the presence of fibrosis and distinguishing mild/moderate and advanced stages of fibrosis respectively. The areas under the receiver operating characteristic (AUROC) of TE were 0.963 and 0.865, respectively. Conclusion. Based on our investigation the APRI score, Forns index and TE adequately predict fibrosis stage in patients with primary biliary cirrhosis, but the most sensitive and specific parameter appears to be TE. Using noninvasive markers and methods in the evaluation of patients in daily clinical practice may reduce, but not eliminate, the need for invasive diagnostic procedures.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3204-3204
Author(s):  
Sean A. Fischer ◽  
Francis Carolyn ◽  
Kessler M. Craig

Abstract Background: Virtually all severe HEM exposed to plasma concentrates in the USA before 1985 are seropositive for HCVand HIV. HIV accelerates progression of HCV-induced chronic liver disease. HAART therapy has stabilized HIV in HEM so that end-stage liver disease is the predominant cause of death in HIV/HCV HEM. Pegylated interferon-alpha and ribavirin (IFN-R) produces significant remission in chronic HCV, and HEM with chronic HCV should benefit similarly. Liver histology is desirable to decide who should receive IFN-R since evidence of limited fibrosis with inflammation would be expected to derive the most benefit. Liver bx in HEM is fraught by significant costs of factor replacement and the small risk of significant bleeding. Thus, a surrogate marker for the information revealed by liver bx would be particularly advantageous for HEM with HCV. Diagnostic kits composed of specific and sensitive serum biochemical markers for the chronic complications of HCV are being validated as surrogates for liver bx, particularly prior to initiating IFN-R. The FibroSure assay (Labcorp, Burlington, USA) purportedly detects hepatic fibrosis and necrosis (necroinflammation) and in non-HEM cohorts appears predictive for either absent or minimal fibrosis or for advanced fibrosis/cirrhosis. The assay poorly predicts intermediate fibrosis. Patients and Methods: Histopathologic features of acute and chronic HCV and fibrosis observed from liver bx in 49 HEM were retrospectively correlated with the biochemical markers for liver fibrosis and necrosis. This was intended to determine if the FibroSure assay could substitute for liver bx in HEM. Impact of HIV/HCV co-infection on bx morphology and FibroSure results were also assessed. Trans-jugular liver bx was utilized in all HEM. Results: Of 49 HEM, 22 (44.9%) had HCV/HIV co-infection. Thirty one HEM underwent liver bx and 40 had FibroSure results. Twenty two had both liver bx and FibroSure. Only 18 had interpretable data from FibroSure. Seven of these 18 (38.9%) had morphological evidence of chronic HCV with significant fibrosis (Metavir score &gt;2) but only 3/7 (42.8%) had FibroSure results corroborative of significant fibrosis (score of 0.48 or higher correlating with a Meatier score&gt;2). All of these 7 HEM were co-infected. One of 18 (5.6%) HEM exhibited minimal fibrosis on liver bx but FibroSure results consistent with severe fibrosis. The 4 uninterpretable FibroSure results were from HIV/HCV HEM with opportunistic infections involving the liver but without marked fibrosis on bx. The median bx length was 1.7 cm for the entire cohort, which was adequate for representative morphological assessment. No bleeding complications occurred with transjugular liver bx. Conclusions: In this cohort of HEM, FibroSure results do not strongly correlate with the presence of severe liver fibrosis observed on bx. HIV co-infection may be responsible for this poor sensitivity since all 7 HEM with severe fibrosis on liver bx were infected with both. Trans-jugular liver bx was well tolerated and safe in HEM. In summary, our data do not support using the FibroSure assay as a sensitive or reliable surrogate marker for the extent of hepatic fibrosis in HCV/HIV co-infected HEM. Liver bx should still be considered the "gold standard" in co-infected HEM when assessing the suitability of IFN-R therapy.


2015 ◽  
Vol 156 (2) ◽  
pp. 43-52 ◽  
Author(s):  
Anna Egresi ◽  
Gabriella Lengyel ◽  
Krisztina Hagymási

Liver cirrhosis is one of the leading causes of death worldwide. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Studies have focused on non-invasive markers for liver fibrosis because of the dangers and complications of liver biopsy. The authors review the non-invasive direct as well as indirect methods for liver fibrosis assessment and present the positive and negative predictive value, sensitivity and specificity of those. Clinical utilities of transient elastography (Fibrsocan) is also reviewed. Non-invasive methods are useful in the assessment of liver fibrosis, monitoring disease progression and therapeutic response. Their accuracy can be increased by the combined or sequential use of non-invasive markers. Orv. Hetil., 2015, 156(2), 43–52.


2021 ◽  
Author(s):  
Shanshan Chen ◽  
Yuhan Gong ◽  
Jie Li ◽  
Xuan Dai ◽  
Yueyue Zhao ◽  
...  

Abstract Background: Many noninvasive models based on serum markers composition are used for the assessment of liver fibrosis, reducing the need for liver biopsy. However, most of the models have rarely been validated in Chinese hepatitis B patients. We aim to evaluate and validate chronic hepatitis B(CHB) patients with normal ALT, mildly and significantly elevated ALT levels.Methods: This single-center retrospective study enrolled 285 patients with CHB who underwent liver biopsy. There were 156 patients in normal ALT group, 85 patients in mildly elevated ALT group, and 44 patients in significantly elevated ALT group. The diagnostic accuracy of APRI and FIB-4 was evaluated by areas under the characteristic curves (AUROC) using the histological assessment of the fibrosis stages of the biopsy specimens as the standards.Results: Among 285 patients with CHB, 156 patients had normal ALT level, of which 65 (41.7%) had significant fibrosis(S2-4). The evaluation of significant fibrosis, AUROC in APRI and FIB-4 were 0.608, 0.634, 0.708 and 0.638, 0.679, 0.734 in normal ALT, mildly and significantly elevated ALT, respectively. The assessment of advanced fibrosis, AUROC in APRI and FIB-4 were 0.636, 0.751, 0.708 and 0.652, 0.763, 0.734 in normal ALT, mildly and significantly elevated ALT groups, respectively. Conclusions: APRI and FIB-4 may not be ideal noninvasive markers for evaluating liver fibrosis in Chinese HBV-infected patients with normal ALT levels. Compared with HBV-infected patients with normal ALT, APRI and FIB-4 had high accuracies in diagnosing liver fibrosis in patients with mildly and significantly elevated ALT.


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