Serum Biomarkers for Noninvasive Diagnosis of Liver Diseases: How laudable are these tools?

Abstract:: Innumerable reasons have been reported to affect and infect the liver and cause liver diseases. The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, it has become evident that this once defined as “gold-standard” is now not the best method as it involves many limitations. Attempts to reveal non-invasive diagnostic tools have generated serum biomarkers, multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and are less expensive than liver biopsy. Biomarkers have various advantages like minimal invasive, easy to apply with great availability and easier reproducibility, useful for monitoring therapy and less expensive. But then, direct biomarkers involved in extra cellular matrix turnover, need further validation in different geographic population and indirect biomarkers may not predict early pathophysiological changes in liver parenchyma. The accuracy and diagnostic value of most, if not all, of these biomarkers remains controversial. Hence, there is a need for biomarker which is specific for liver and can identify magnitude of clinical outcome of the disease. In this review, we discuss the clinical utility, limitations, and development of noninvasive biomarkers in their use as diagnostic and prognostic tests and analyze whether the present known serum biomarkers are laudable and accurate tools for diagnosis of liver diseases.

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Magnetic resonance cholangiopancreatography as a diagnostic tools to diagnose biliary atresia at Dr.Soetomo hospital

Qanun Medika - Medical Journal Faculty of Medicine Muhammadiyah Surabaya ◽

10.30651/jqm.v3i2.2131 ◽

2019 ◽

Vol 3 (2) ◽

pp. 137

Author(s):

Gina Noor Djalilah ◽

Reny Widayanti ◽

Bagus Setyoboedi ◽

Sjamsul Arief

Keyword(s):

Magnetic Resonance ◽

Liver Biopsy ◽

Biliary Atresia ◽

Sensitivity And Specificity ◽

Predictive Value ◽

Magnetic Resonance Cholangiopancreatography ◽

Diagnostic Value ◽

Diagnostic Tools ◽

Diagnostic Study ◽

Cross Sectional

ABSTRACT Cholestasis jaundice results from diminished bile flow and/or excretion, and caused by a number of disorders such as biliary atresia (BA). Magnetic resonance cholangiopancreatography (MRCP) is widely accepted as one of the modalities for biliary system imaging; however, liver biopsy still generally used for BA diagnosis, especially in developing countries. This aim study was to evaluate the diagnostic value of biliary atresia from MRCP compared to the result of a liver biopsy. A cross-sectional for diagnostic study documented of hospitalized patients from June 2014 to June 2015. All patients had MRCP and liver biopsy examination. The collection of data including age, gender, clinical manifestation and the result of MRCP and liver biopsy with ROC to evaluate the sensitivity and specificity was done. Liver biopsy revealed of biliary atresia was made based on proliferation, degeneration, and fibrosis of bile ducts. ROC to evaluate the sensitivity and specificity was done. The sensitivity, specificity, negative predictive value, positive predictive value of MRCP in diagnosing BA were calculated. There were 16 patients enrolled in this study with a median age of diagnosis was 6 months old (range 3-11). There were nine female patients out of the 16 patient. The median age of jaundice onset was 5 days (range 2-14 days). All patients had hepatomegaly and splenomegaly. Histopathology from liver biopsy revealed biliary atresia in 12 patients. From the ROC curve, the sensitivity of MRCP was 87.5% and specificity 62.5% with PPV 70% and NPV 80%. Five patients underwent a Kasai procedure and revealed biliary atresia. MRCP is sensitive but not specific for diagnosing BA, and MRCP has moderate sensitivity and specificity for BA diagnosis.Keyword: biliary atresia, magnetic resonance cholangiopancreatography, liver biopsy, diagnostic test.Correspondence: [email protected] ABSTRAKIkterus dikarenakan kolestasis terjadi akibat berkurangnya aliran empedu dan/ atau ekskresi, dan dapat disebabkan oleh sejumlah gangguan seperti atresia biliaris (BA). Magnetic resonance cholangiopancreatography (MRCP) secara luas diterima sebagai salah satu modalitas untuk pencitraan sistem empedu, namun biopsi hati masih secara umum digunakan untuk diagnosis BA, terutama di negara berkembang. Studi ini bertujuan untuk mengevaluasi nilai diagnostik atresia biliaris dari MRCP ke hasil biopsi hati. Sebuah cross sectional untuk studi diagnostik didokumentasikan pasien rawat inap dari Juni 2014 hingga Juni 2015. Semua pasien menjalani MRCP dan pemeriksaan biopsi hati. Data usia, jenis kelamin, manifestasi klinis dan hasil MRCP dan biopsi hati dengan ROC untuk mengevaluasi sensitivitas dan spesifisitas dilakukan. Biopsi hati mengungkapkan atresia biliar dibuat berdasarkan proliferasi, degenerasi dan fibrosis saluran empedu. ROC untuk mengevaluasi sensitivitas dan spesifisitas yang dilakukan. Dilakukan perhitungan sensitivitas, spesifisitas, nilai prediktif negatif, nilai prediksi positif MRCP dalam mendiagnosis BA. Terdapat 16 pasien yang terdaftar dalam penelitian ini dengan median usia diagnosis adalah 6 (kisaran 3-11) bulan. Terdapat 9 perempuan dari 16 pasien tersebut. Usia rata-rata onset penyakit kuning adalah 5 (kisaran 2-14) hari. Semua pasien mengalami hepatomegali dan splenomegali. Histopatologi dari biopsi hati mengungkapkan atresia bilier pada 12 dari 16 pasien. Dari kurva ROC, sensitivitas MRCP adalah 87,5% dan spesifisitas 62,5% dengan PPV 70% dan NPV 80%. Lima pasien menjalani prosedur Kasai dan mengungkapkan atresia bilier. MRCP sensitif namun tidak spesifik untuk mendiagnosis BA dan MRCP memiliki sensitivitas dan spesifisitas sedang untuk diagnosis BA.Kata kunci: biliary atresia, magnetic resonance cholangiopancreatography, liver biopsy, diagnostic test.Korespondensi: [email protected]

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559 An overview of biochemical markers (fibrotest-actitest) diagnostic value in chronic liver diseases: A non-invasive alternative to liver biopsy

Hepatology ◽

10.1016/s0270-9139(03)80601-8 ◽

2003 ◽

Vol 38 ◽

pp. 430-430 ◽

Cited By ~ 1

Author(s):

T POYNARD ◽

F IMBERTBISMUT ◽

V RATZIU ◽

S NAVEAU ◽

D THABUT ◽

...

Keyword(s):

Liver Biopsy ◽

Biochemical Markers ◽

Liver Diseases ◽

Diagnostic Value ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Non Invasive

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Basis of using ultrasound elastography in diffuse and focal liver diseases

Medical Visualization ◽

10.24835/1607-0763-2018-6-69-75 ◽

2019 ◽

Vol 22 (6) ◽

pp. 69-75 ◽

Cited By ~ 1

Author(s):

T. G. Morozova ◽

A. V. Borsukov

Keyword(s):

Liver Biopsy ◽

Liver Diseases ◽

Prognostic Value ◽

Clinical Laboratory ◽

Ultrasound Elastography ◽

Diagnostic Tools ◽

Diffuse Liver Disease ◽

Clinical Forms ◽

Dynamic Observation ◽

Diagnostic And Prognostic Value

Objective:to develop the basics of ultrasound elastography for diffuse and focal liver diseases.Material and methods.180 patients were examined, including 102 (56.7%) men and 78 (43.3%) women. Patients were hospitalized in the gastroenterological and surgical departments: 100 (55.6%) patients with diffuse liver disease (DLD), 80 (44.4%) with focal liver pathology (FLP). All elastographic techniques were used; The liver biopsy served as the reference method (n = 169 (93.8%)).Results.If a patient has steatohepatitis, it is recommended to begin research with transient elastography (TE), in hepatitis – with compression elastography (CE), according to the study, it is determined that shear wave elastography (SWE) is informative in all clinical forms of DLD. The terms of elastographic monitoring have been developed: upon admission, after 6, 9, 12 months. With dynamic observation of patients, elastographic techniques have a high diagnostic and prognostic value with stable and positive clinical laboratory and instrumental dynamics (liver biopsy – AUROC 0,882, DI 0.741–0.699, elastography – AUROC 0,991, DI 0.779–0.997). At FLP the results of SWE help in determining the “zone of interest” for the subsequent conduct of a morphological study, with the aim of establishing a diagnosis.Conclusions.1. In the presence of a patient with steatohepatitis, it is recommended to begin research with TE, in hepatitis with CE, according to the results of the study, it is determined that SWE is informative in all clinical forms of DLD. 2. Dynamic elastographic monitoring in case of DLD should be performed at admission, after 6, 9 and 12 months, and then individually for each patient. 3. With dynamic observation of patients with DLD, elastographic techniques have a high diagnostic and prognostic value with stable and positive clinical laboratory and instrumental dynamics (liver biopsy – AUROC 0.882, DI 0.741–0.66, elastography – AUROC 0.991, DI 0.779–0.997). 4. It has been established that the results of all elastographic techniques can not be used as differential diagnostic tools, SWE helps in choosing a “zone of interest” for biopsy with subsequent verification of the diagnosis (AUROC 0.907 (95% DI 0.889–0.933)).

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Matrix metalloproteinase-1 as a non-invasive biomarker to assess liver fibrosis in children with chronic liver disease

Egyptian Liver Journal ◽

10.1186/s43066-021-00148-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ola Galal Behairy ◽

Mohamed Mostafa El-Bakry ◽

Amira Ibrahim Mansour ◽

Amira M. N. Abdelrahman ◽

Ghada Mansour Emam

Keyword(s):

Liver Fibrosis ◽

Liver Biopsy ◽

Liver Diseases ◽

Serum Biomarkers ◽

Chronic Liver ◽

Control Group ◽

Chronic Liver Diseases ◽

Non Invasive ◽

Matrix Metalloproteinase 1 ◽

The Mean

Abstract Background Abnormal extracellular matrix (ECM) turnover is linked to liver fibrosis as it reflects an imbalance between repair and progressive substitution of the liver parenchyma by scar tissue. Matrix metalloproteinases (MMPs) are the primary enzymes involved in ECM breakdown. So, this study aims to measure the value of serum matrix metalloproteinase-1 (MMP-1) in children with chronic liver diseases (CLD) in comparison with liver biopsy and serum biomarkers. A hundred twenty children with chronic liver diseases and sixty healthy children as a control group were included in this study. Both groups were evaluated via medical history, clinical, radiological, laboratory investigations, and serum MMP-1 level was measured by ELISA. Liver biopsy was performed for studied patients only. Results The mean MMP-1 was 15.2 ± 5.1 ng/ml in children with CLD, and 64.7 ± 27.4 ng/ml in the control group. MMP-1 was statistically lower in the children with CLD than controls (p < 0.001). The mean ± SD of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores in all studied cases showed a significant trend of increase with progressive fibrosis stage evident with histological METAVIR scoring system, while serum MMP-1 concentration was decreased significantly with increasing the degree of fibrosis in CLD group (P 0.001). Serum MMP-1 was indirectly correlated with serum biomarkers and the degree of fibrosis in patients. Conclusions MMP-1 is a useful non-invasive marker for detection of the stage of liver fibrosis in children with chronic liver diseases.

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Diagnostic Performance of Noninvasive Methods for Liver Biopsy by Fibroscan in Pediatric

Journal of Child Science ◽

10.1055/s-0041-1725079 ◽

2021 ◽

Vol 11 (01) ◽

pp. e55-e59

Author(s):

Farzaneh Motamed ◽

Ghobad Heidari ◽

Bita Heirati ◽

Parisa Rahmani

Keyword(s):

Liver Biopsy ◽

Liver Diseases ◽

Storage Disease ◽

Sampling Error ◽

Medical Center ◽

Glycogen Storage ◽

Chronic Liver ◽

Noninvasive Methods ◽

Function Test ◽

Diagnostic Modalities

AbstractLiver biopsy is the gold standard for the diagnosis and management of various liver diseases; however, noninvasive diagnostic modalities may help prevent adverse effects of anesthesia, prolonged hospitalization, sampling error, and other serious complications, particularly in pediatric patients. The aim of this study is to compare the results of liver biopsy and fibroscan in children with chronic liver diseases. All patients presenting chronic liver disease admitted in the ward or clinic of Tehran's Children Medical Center were enrolled in the study. Required laboratory tests were performed to diagnose the disease, followed by elastography using fibroscan 402 (M-probe) Echosens machine and liver biopsy using Menghini technique. Samples were scored by using METAVIR scoring system. Thirty-two patients were reported (68.8%, female) with autoimmune hepatitis (18.8%), Wilson disease (12.5%), and glycogen storage disease (12.5%). The most common pathologic stage and fibroscan result was stage III and F0 (46.9%), respectively. Association between pathology and fibroscan results was not significant. Nonetheless, age and diagnosis, age and Fibroscan score, and pathology and liver function test were significantly associated with each other. Fibroscan cannot be used as an alternative to liver biopsy; however, it can be a useful accessory tool.

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Diagnostic work up of anemic patients: role of iron deficiency

LaboratoriumsMedizin ◽

10.1515/labmed-2020-0060 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Daniela Meiser ◽

Lale Kayikci ◽

Matthias Orth

Keyword(s):

Iron Deficiency ◽

Complete Blood Count ◽

Iron Status ◽

Area Under The Curve ◽

Diagnostic Value ◽

Diagnostic Tools ◽

Operating Characteristics ◽

Inflammatory Conditions ◽

Reliable Parameter ◽

Work Up

AbstractObjectivesDiagnosing disturbances in iron metabolism can be challenging when accompanied by inflammation. New diagnostic tools such as the “Thomas-plot” (TP) (relation of soluble transferrin receptor [sTfR]/log ferritin to reticulocyte hemoglobin content [RET-He]) were established to improve classification of anemias. Aim of this retrospective study was to assess the added diagnostic value of the TP in anemia work up.MethodsPatients from December 2016 to September 2018 with a complete blood count, iron status, RET-He and sTfR were manually classified into the four quadrants of the TP on basis of conventional iron markers. Manual and algorithm-based classifications were compared using cross tabulations, Box–Whisker-Plots as well as Receiver-Operating-Characteristics (ROC) to calculate the diagnostic accuracy using Area under the Curve (AUC) analysis.ResultsA total of 3,745 patients with a conventional iron status, including 1,721 TPs, could be evaluated. In 70% of the cases the manual classification was identical to the TP, in 10% it was deviant. 20% could not clearly be classified, mostly due to inflammatory conditions. In the absence of an inflammatory condition, ferritin was a reliable parameter to define iron deficiency (ID) (AUC 0.958). In the presence of inflammation, the significance of the ferritin index (AUC 0.917) and of the RET-He (AUC 0.957) increased.ConclusionsThe TP can be useful for narrowing down the causes of anemia in complex cases. Further studies with focus on special patient groups, e.g., oncological or rheumatic patients, are desirable.

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Novel Laboratory Tests in Assessment of Liver Function in Acute and Chronic Liver Diseases

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/v10046-009-0035-4 ◽

2009 ◽

Vol 63 (4-5) ◽

pp. 228-233

Author(s):

Ludmila Vīksna ◽

Jāzeps Keišs ◽

Artūrs Sočņevs ◽

Baiba Rozentāle ◽

Māra Pilmane ◽

...

Keyword(s):

Liver Function ◽

Liver Biopsy ◽

Liver Diseases ◽

Laboratory Tests ◽

Serum Markers ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Noninvasive Methods ◽

Disease Evolution ◽

Prognostic Accuracy

Novel Laboratory Tests in Assessment of Liver Function in Acute and Chronic Liver Diseases Liver biopsy in clinical practice has been widely used for the diagnosis and management of patients with liver diseases, particularly, with chronic liver diseases. However, liver biopsy is an invasive method with potential complications, sampling and interpretation errors. Therefore, noninvasive tests are being developed and introduced to replace liver biopsy. The aim of the present study was to identify the new noninvasive methods to be used for the assessment of liver structure and function, by use of the appropriate serum surrogate markers and to evaluate the clinical diagnostic and prognostic accuracy of these methods, including immunogenetic methods, in cases of acute and chronic liver diseases. The obtained data showed that serum markers of apoptosis (cytokeratin-18 neoepitope and citochrome c) and fibrosis (hyaluronic acid) should be included in viral and toxic liver damage management algorithms. The punctual identification of immunogenetic factors (HLA class II antigens) may prove to be useful in predicting disease evolution, and in guiding the appropriate therapy for patients with poor prognosis.

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