• Humans
• Biomarkers/blood
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Practice Guidelines as Topic
• Severity of Illness Index
• Platelet Count
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/pathology
• Aspartate Aminotransferases/blood
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/pathology

• LC-MS/MS
• apo A-I
• fibrinogen alpha chain
• haptoglobin
• liver cirrhosis
• mass spectrometry
• proteoforms
• top-down proteomics

• Humans
• Liver Cirrhosis/blood
• Proteomics/methods
• Disease Progression
• Male
• Female
• Middle Aged
• Biomarkers/blood
• Aged
• Proteome/metabolism
• Blood Proteins/metabolism
• Blood Proteins/analysis
• Adult
• Pilot Projects

• P41 GM108569 NIGMS NIH HHS
• T32 DK077662 NIDDK NIH HHS

• Carcinoma, Hepatocellular
• Hepatitis B, Chronic/complications
• Humans
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/etiology
• Risk Assessment

• hepatocellular carcinoma
• liver disease
• one-carbon metabolism
• proteomics

• B2017/BMD-3817 Comunidad de Madrid
• SEV 2017-0712 Severo Ochoa Project. CNB-CSIC
• 202020E079 Spanish National Research Council
• 202020E108 Spanish National Research Council
• EU 2020/2094 European Commission-NextGenerationEU

• NASH
• morbid obesity
• noninvasive diagnosis

Our group has recently developed the GlycoTyper assay which is a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins including immunoglobulin G (IgG). This method needs only a few microliters of serum and utilizes a simplified processing protocol that requires no purification or sugar modifications prior to analysis. In this method, antibody captured glycoproteins are treated with peptide N-glycosidase F (PNGase F) to release N-glycans for detection by MALDI imaging mass spectrometry (IMS). As alterations in N-linked glycans have been reported for IgG from large patient cohorts with fibrosis and cirrhosis, we utilized this novel method to examine the glycosylation of total IgG, as well as IgG1, IgG2, IgG3 and IgG4, which have never been examined before, in a cohort of 106 patients with biopsy confirmed liver fibrosis. Patients were classified as either having no evidence of fibrosis (41 patients with no liver disease or stage 0 fibrosis), early stage fibrosis (10 METAVIR stage 1 and 18 METAVIR stage 2) or late stage fibrosis (6 patients with METAVIR stage 3 fibrosis and 37 patients with METAVIR stage 4 fibrosis (cirrhosis)). Several major alterations in glycosylation were observed that classify patients as having no fibrosis (sensitivity of 92% and a specificity of 90%), early fibrosis (sensitivity of 84% with 90% specificity) or significant fibrosis (sensitivity of 94% with 90% specificity).

• Biomarkers
• Female
• Glycoproteins/metabolism
• Glycosylation
• Humans
• Immunoglobulin G/immunology
• Liver Cirrhosis
• Male
• Middle Aged
• Polysaccharides/blood
• Research Design
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods

• R01 CA237659 NCI NIH HHS
• R41 DK124058 NIDDK NIH HHS
• U01 CA242096 NCI NIH HHS
• P30 DK123704 NIDDK NIH HHS
• U01 CA226052 NCI NIH HHS
• National Institute of Diabetes and Digestive and Kidney Diseases
• Division of Cancer Prevention, National Cancer Institute

• NMR
• cardiovascular risk
• glycoproteins
• metabolic-associated fatty liver disease
• triglyceride-rich lipoproteins

• Aged
• Alanine Transaminase/metabolism
• Aspartate Aminotransferases/metabolism
• Diabetes Mellitus, Type 2/metabolism
• Female
• Glycoproteins/metabolism
• Humans
• Lipoproteins/metabolism
• Male
• Metabolic Syndrome/metabolism
• Middle Aged
• Non-alcoholic Fatty Liver Disease/diagnostic imaging
• Non-alcoholic Fatty Liver Disease/metabolism
• Obesity/metabolism
• Proton Magnetic Resonance Spectroscopy
• Triglycerides/metabolism
• Ultrasonography

• Instituto de Salud Carlos III

A case of severe jaundice in a patient with a long history of alcohol abuse led to a questionable diagnosis of liver cirrhosis. To determine its diagnostic utility in the setting of liver disease, elastography was utilized on our patient to confirm the clinically suspected diagnosis of cirrhosis.

A 59-year-old male presented to our emergency department (ED) with two days of progressive jaundice and right upper quadrant (RUQ) pain. The patient admitted to drinking > 500 mL of vodka daily for the last seven years, with his last drink on the morning of admission. Physical exam revealed a man in mild acute distress with severe jaundice and an abdomen diffusely tender to palpation. Two spider angiomas were present on the torso along with caput medusae and mild asterixis. Labs revealed aspartate aminotransferase (AST) 408, alanine aminotransferase (ALT) 69, prothrombin time (PT) 16.3, partial thromboplastin time (PTT) 36, total bilirubin 22.6, and direct bilirubin 19.9 mg/dL. While admitted, total bilirubin rose as high as 31.5 mg/dL. Examination showed a Model for End-Stage Liver Disease (MELD) score of 22 and a Maddrey score of 37. Ultrasound revealed moderate hepatosplenomegaly with no signs of pancreatitis.

Based on the patient’s history of alcohol abuse paired with physical exam findings and elevated laboratory markers, we were able to diagnose with a high level of suspicion that this patient was suffering from chronic alcoholic liver disease, exacerbated by an acute episode of alcoholic hepatitis, which led to hepatic encephalopathy. Based on these findings, a diagnosis of liver cirrhosis was suspected; however, this diagnosis required further confirmation. We utilized ultrasound elastography to measure the velocity of shear wave transmission in the liver of our patient. A literature review was conducted on the use of elastography for the diagnosis of liver disease, and a significant correlation between the velocity of shear wave transmission and hepatic histological findings was identified. Elastography revealed a mean velocity of shear wave transmission of 1.77 m/s in our patient. This finding is consistent with a Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) score of F = 4, indicating significant fibrosis and confirming the suspected diagnosis of alcohol-induced liver cirrhosis.

As a non-invasive and inexpensive diagnostic tool, elastography demonstrates significant potential for clinical utility in patients with liver disease. Clinicians may benefit from the use of elastography in diagnosis, while patients may receive both therapeutic and prognostic benefits secondary to its use. In similar cases with clinical uncertainty, elastography can reliably identify the presence of fibrous tissue in the liver without tissue biopsy, thus aiding in clinical diagnoses and enabling the use of optimal therapeutic regimens for future patients.

• alcoholic cirrhosis
• cirrhosis diagnosis
• elastography
• jaundice
• liver cirrhosis
• maddrey's discriminant function
• meld score
• severe alcoholic hepatitis

• Chronic hepatitis C
• Diagnostic
• IGFBPs
• Liver fibrosis

• Adult
• Cross-Sectional Studies
• Female
• Hepatitis C, Chronic/blood
• Humans
• Insulin-Like Growth Factor Binding Protein 1/blood
• Insulin-Like Growth Factor Binding Protein 2/blood
• Insulin-Like Growth Factor Binding Protein 3/blood
• Insulin-Like Growth Factor Binding Protein 4/blood
• Insulin-Like Growth Factor Binding Protein 5/blood
• Insulin-Like Growth Factor Binding Protein 6/blood
• Insulin-Like Growth Factor Binding Proteins/blood
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Logistic Models
• Male
• Middle Aged
• Odds Ratio
• Prospective Studies
• ROC Curve

• SALUD-2016-272579 Consejo Nacional de Ciencia y Tecnología

The course of hepatitis C infection (HCV) in patients with thalassemia has not been adequately studied, and management has not been optimized. The current prospective longitudinal study assessed the clinical course, outcome, progression, and management of recently acquired HCV in patients with transfusion-dependent thalassemia major versus acute HCV without thalassemia.

A well-characterized cohort of patients with thalassemia and recent HCV infection or recent HCV without thalassemia were enrolled and prospectively followed. The blood transfusion needs and chelating agents were determined. Liver functions tests, HCV-RNA, iron, and ferritin levels were measured. Patients with chronic HCV evolution received treatment for HCV. The fibrosis progression rate was determined in chronic HCV patients with or without thalassemia by paired liver biopsies or serial transient elastography (TE), or serum markers of liver fibrosis. Liver iron content (LIC) was assessed by R2 MRI.

Self-limited acute HCV was observed in 17% of patients with acute HCV and thalassemia versus 35% of patients without thalassemia (P=0.031). The fibrosis progression rates were significantly higher in patients with chronic HCV and thalassemia compared to those with chronic HCV alone (1.14±0.48) and (0.35±0.14) (P<0.0001), respectively. A direct linear correlation was observed between the fibrosis progression rate and each of LIC (R=+0.67; P=0.01) and ferritin (R=0.77; P<0.01). In patients with chronic HCV and thalassemia, the sustained virologic response (SVR) to pegylated interferon-based therapy and direct antiviral agents (DAAS) were 33% and 82% respectively (P<0.0001), while in chronic HCV patients without thalassemia, the SVR rates to PEG-IFN/RBV and DAAs were 51% and 92% respectively. Five patients with concomitant HCV and thalassemia died during the study due to cardiac causes (n=3) and liver cancer (n=2).

Patients with acute HCV and thalassemia have low rates of spontaneous resolution of HCV infection, and the majority develop chronic HCV. Direct-acting antiviral combinations are associated with high SVR rates and low adverse event in treatment naïve and experienced patients with chronic HCV and thalassemia. Liver fibrosis is accelerated in thalassemia patients with chronic HCV; therefore, early diagnosis, treatment with DAAs, adequate iron chelation, and non-invasive monitoring liver status are recommended to prevent cirrhosis and hepatocellular carcinoma.

• Hepatitis C
• Liver fibrosis progression
• Serum fibrosis markers
• Thalassemia
• Transient elastography

Liver fibrosis consists in the accumulation of extracellular matrix components mainly derived from activated hepatic stellate cells. This is commonly the result of chronic liver injury repair and represents an important health concern. As liver biopsy is burdened with many drawbacks, not surprisingly there is great interest to find new reliable noninvasive methods. Among the many are new potential fibrosis biomarkers under study, some of the most promising represented by the growth arrest-specific gene 6 (Gas6) serum protein and its family of tyrosine kinase receptors, namely, Tyro3, Axl, and MERTK (TAM). Gas6/TAM system (mainly, Axl and MERTK) has in fact recently emerged as an important player in the progression of liver fibrosis. This review is aimed at giving an overall perspective of the roles played by these molecules in major chronic liver diseases. The most promising findings up to date acknowledge that both Gas6 and its receptor serum levels (such as sAxl and, probably, sMERTK) have been shown to potentially allow for easy and accurate measurement of hepatic fibrosis progression, also providing indicative parameters of hepatic dysfunction. Although most of the current scientific evidence is still preliminary and there are no in vivo validation studies on large patient series, it still looks very promising to imagine a possible future prognostic role for these biomarkers in the multidimensional assessment of a liver patient. One may also speculate on a potential role for this system targeting (e.g., with small molecule inhibitors against Axl) as a therapeutic strategy for liver fibrosis management, always bearing in mind that any such therapeutic approach might face toxicity.

• aspirin
• embolization
• hepatocellular carcinoma
• hepatoprotective
• liver function

• Biomarkers
• Gas6
• HGF
• Liver fibrosis
• PlGF
• Staging

• Biomarkers
• HIV non-alcoholic fatty liver disease
• HIV-hepatitis B
• HIV-hepatitis C
• Liver fibrosis
• Transient elastography

Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic hepatitis (CH). The development of fibrosis is a crucial event in the progression of hepatic disease that is of prognostic value. The pathophysiology of hepatic fibrosis in human patients and rodent models has been studied extensively. Although less is known about this process in dogs, evidence suggests that fibrogenic mechanisms are similar between species and that activation of hepatic stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs requires histopathological examination of a liver biopsy specimen. However, performing a liver biopsy is invasive and assessment of fibrotic stage is complicated by the absence of a universally accepted staging scheme in veterinary medicine. Serum biomarkers that can discriminate among different fibrosis stages are used in human patients, but such markers must be more completely evaluated in dogs before clinical use. When successful treatment of its underlying cause is feasible, reversal of hepatic fibrosis has been shown to be possible in rodent models and human patients. Reversal of fibrosis has not been well documented in dogs, but successful treatment of CH is possible. In human medicine, better understanding of the pathomechanisms of hepatic fibrosis is leading to the development of novel treatment strategies. In time, these may be applied to dogs. This article comparatively reviews the pathogenesis of hepatic fibrosis, its diagnosis, and its treatment in dogs.

• Antifibrotic
• Chronic hepatitis
• Fibrogenesis
• Hepatic stellate cell

Detection of advanced fibrosis (F3-F4) in nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis. Serum markers have been proposed as alternatives to biopsy. We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms.

We included 158 patients with biopsy-proven NAFLD. Of these, 38 had advanced fibrosis. The following fibrosis algorithms were calculated: NAFLD fibrosis score, BARD, NIKEI, NASH-CRN regression score, APRI, FIB-4, King´s score, GUCI, Lok index, Forns score, and ELF. Study population was randomly divided in a training and a validation group. A multiple logistic regression analysis using bootstrapping methods was applied to the training group. Among many variables analyzed age, fasting glucose, hyaluronic acid and AST were included, and a model (LINKI-1) for predicting advanced fibrosis was created. Moreover, these variables were combined with platelet count in a mathematical way exaggerating the opposing effects, and alternative models (LINKI-2) were also created. Models were compared using area under the receiver operator characteristic curves (AUROC).

Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83, respectively. Higher accuracy was achieved with the novel LINKI algorithms. AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89.

The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts.

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Alanine Transaminase/blood
• Algorithms
• Area Under Curve
• Aspartate Aminotransferases/blood
• Biomarkers/blood
• Blood Glucose/analysis
• Female
• Humans
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Logistic Models
• Male
• Middle Aged
• Models, Biological
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/complications
• Prognosis
• Prospective Studies
• ROC Curve
• Young Adult

• Royal Swedish Academy of Sciences
• Medical Research Council of Southeast Sweden

Chronic hepatitis B (CHB)-related cirrhosis is a major threat to public health, and about 23% of patients with CHB progress naturally to liver cirrhosis. Worldwide, about 650000 people die each year from various complications caused by CHB. liver cirrhosis has become a global concern. Progressive hepatic fibrosis can lead to cirrhosis, and early diagnosis of liver fibrosis is fundamental. Staging fibrosis is critical for the prognosis evaluation and management of patients with liver diseases. Liver biopsy is the reference standard for assessment of liver fibrosis. However, this method is invasive, and is associated with pain and complications that can be fatal, which leads to the progress of non-invasive assessment based on serological and imaging techniques. These non-invasive assessments have been shown to be effective in the diagnosis of liver fibrosis. This article mainly introduces the principle, clinical application, diagnostic efficacy, and limitations of non-invasive assessments for hepatitis B virus-related fibrosis.

• Chronic liver disease
• Chronic hepatitis B
• Cirrhosis
• Non-invasive diagnosis

Purpose. To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis. Materials and Methods. In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). Using L₁ regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses. Results. The texture-based predicted fibrosis score significantly correlated with qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001) histology. The prediction model for qualitative histology had 0.814–0.976 areas under the curve (AUC), 0.659–1.000 sensitivity, 0.778–0.930 specificity, and 0.674–0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742–0.950 AUC, 0.688–1.000 sensitivity, 0.679–0.857 specificity, and 0.696–0.848 accuracy, depending on the binary classification threshold. Conclusion. CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.

• Benzimidazoles/therapeutic use
• DNA, Viral/blood
• Female
• Fluorenes/therapeutic use
• Hepacivirus/genetics
• Hepatitis C, Chronic/drug therapy
• Humans
• Male
• Sofosbuvir/therapeutic use

• Adipokines/blood
• Adipokines/genetics
• Adipokines/metabolism
• Biomarkers/blood
• Biomarkers/metabolism
• Chitinase-3-Like Protein 1
• Enzyme-Linked Immunosorbent Assay
• Humans
• Lectins/blood
• Lectins/genetics
• Lectins/metabolism
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/genetics

• Biomarkers
• Hepatitis C
• Hepatocellular carcinoma
• Liver fibrosis
• MicroRNAs

• Animals
• Antiviral Agents/therapeutic use
• Biomarkers
• Genomics/methods
• Hepacivirus/genetics
• Hepacivirus/isolation & purification
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/virology
• Humans
• Liver/drug effects
• Liver/pathology
• Liver/virology
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/virology
• Prognosis

• Antiviral Agents/economics
• Antiviral Agents/therapeutic use
• Biomarkers
• Chronic Disease
• Cost-Benefit Analysis
• Diagnostic Techniques and Procedures/economics
• Diagnostic Techniques and Procedures/instrumentation
• Elasticity Imaging Techniques
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/pathology
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/pathology
• Humans
• Liver Cirrhosis/diagnosis
• Liver Diseases/pathology
• Markov Chains
• Models, Econometric
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/pathology
• Quality-Adjusted Life Years
• Sensitivity and Specificity
• Sex Factors

• 09/114/02 Department of Health

• Alpha-1 antitrypsin
• Chronic hepatitis B
• Liver cirrhosis
• Transferrin

• Adolescent
• Adult
• Aged
• Area Under Curve
• Biomarkers/blood
• Female
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/pathology
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Male
• Middle Aged
• Multivariate Analysis
• ROC Curve
• Retrospective Studies
• Transferrins/blood
• Young Adult
• alpha 1-Antitrypsin/blood

Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

• Cirrhosis
• Death
• Fibroscan
• Hepatic events
• Hepatocellular carcinoma
• Liver stiffness measurement

Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules) specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1) known biochemical pathways associated with liver injuries and 2) clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20%) genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects.

• Algorithms
• Animals
• Biomarkers
• Chemical and Drug Induced Liver Injury/diagnosis
• Chemical and Drug Induced Liver Injury/genetics
• Chemical and Drug Induced Liver Injury/metabolism
• Cluster Analysis
• Computational Biology/methods
• Databases, Genetic
• Gene Expression
• Gene Expression Profiling
• Gene Regulatory Networks
• Humans
• Rats
• Reproducibility of Results
• Signal Transduction
• Transcriptome

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

• Liver fibrosis markers
• Alcoholic liver disease

• Biomarkers/blood
• Biopsy
• Disease Progression
• Humans
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis, Alcoholic/blood
• Liver Cirrhosis, Alcoholic/diagnosis
• Liver Cirrhosis, Alcoholic/mortality
• Liver Cirrhosis, Alcoholic/pathology
• Liver Function Tests
• Predictive Value of Tests
• Prognosis
• Severity of Illness Index

Noninvasive markers of liver fibrosis have not been extensively studied in patients with chronic hepatitis B virus (HBV) infection. Our aim was to evaluate the capacity of FibroSURE, one of the two noninvasive fibrosis indices commercially available in the United States, to identify HBV infected patients with moderate to severe fibrosis.

Forty-five patients who underwent liver biopsy at a single tertiary care center were prospectively enrolled and had FibroSURE performed within an average interval of 11 days of the biopsy.

Of the 45 patients, 40% were Asian, 40% were African American, and 13% were Caucasian; 27% were co-infected with HIV and 67% had no or mild fibrosis. We found FibroSURE to have moderate capacity to discriminate between patients with moderate to high fibrosis and those with no to mild fibrosis (area under receiver operating characteristic [AUROC] curve = 0.77; 95% confidence interval [CI] [0.61, 0.92]). When we combined the fibrosis score determined by FibroSURE with aspartate aminotransferase (AST) measurements and HIV co-infection status, the discriminatory ability significantly improved reaching an AUROC of 0.90 (95% CI [0.80, 1.00]). FibroSURE also had a good ability to differentiate patients with no or mild from those with moderate to high inflammation (AUROC = 0.83; 95% CI [0.71, 0.95]).

FibroSURE in combination with AST levels has an excellent capacity to identify moderate to high fibrosis stages in chronic HBV-infected patients. These data suggest that FibroSURE may be a useful substitute for liver biopsy in chronic HBV infection.

• Area Under Curve
• Biomarkers/blood
• Biopsy
• Chronic Disease
• Collagen/blood
• Decision Trees
• Disease Progression
• Elasticity Imaging Techniques
• Humans
• Hypertension, Portal
• Laminin/blood
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Liver Function Tests
• Magnetic Resonance Imaging
• Matrix Metalloproteinases/blood
• Models, Statistical
• Prognosis

• Biomarkers/blood
• Clinical Laboratory Techniques/economics
• Diagnosis
• Humans
• Liver Cirrhosis/diagnosis

• Antiviral Agents/therapeutic use
• Biomarkers/blood
• Biopsy
• Elasticity Imaging Techniques
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/pathology
• Humans
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/pathology
• Liver Cirrhosis/virology
• Magnetic Resonance Imaging
• Severity of Illness Index

• Adult
• Aspartate Aminotransferases/blood
• Biomarkers
• Biopsy, Large-Core Needle
• Discriminant Analysis
• Extracellular Matrix/metabolism
• Extracellular Matrix/pathology
• Female
• Fibronectins/blood
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/diagnostic imaging
• Hepatitis C, Chronic/pathology
• Humans
• Liver/diagnostic imaging
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/pathology
• Logistic Models
• Male
• Middle Aged
• Platelet Count
• Predictive Value of Tests
• Prospective Studies
• ROC Curve
• Reproducibility of Results
• Serum Albumin/analysis
• Severity of Illness Index
• Ultrasonography

• Disease Progression
• Humans
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/physiopathology
• Recovery of Function
• Severity of Illness Index

• extracellular matrix
• liver fibrosis
• neo-epitope
• serum marker

Liver biopsy is the reference standard for assessing liver fibrosis and no reliable non-invasive diagnostic approach is available to discriminate between the intermediate stages of fibrosis. Therefore suitable serological biomarkers of liver fibrosis are urgently needed. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.

Proteins in plasma samples from healthy control individuals and patients with hepatitis C virus (HCV) induced cirrhosis were analysed using a proteomics technique: two dimensional gel electrophoresis (2-DE). This technique separated the proteins in plasma samples of control and cirrhotic patients and by visualizing the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by Western blotting. Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect. These markers will be further validated using a large clinical cohort.

This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.

• Adult
• Aged
• Apolipoprotein L1
• Apolipoproteins/blood
• Biomarkers/blood
• Clusterin/blood
• Complement C3d/metabolism
• Female
• Hepatitis C/blood
• Hepatitis C/pathology
• Humans
• Lipoproteins, HDL/blood
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Male
• Middle Aged
• Severity of Illness Index
• Transcortin/metabolism

• Wellcome Trust
• 091663 Wellcome Trust
• G108/601 Medical Research Council

• APRI
• APRI, AST/platelet ratio index
• AST, aspartate aminotransferase
• AUC, area under the curve
• CAPRI
• CAPRI, CEC with APRI
• CEC, circulating endothelial cell
• CTP, Child–Turcotte–Pugh
• EGD, esophagogastroduodenoscopy
• ELF, enhanced liver fibrosis
• IQR, interquartile range
• MELD, model for end-stage liver disease
• PC, platelet count
• ROC, receiver operator characteristic
• circulating endothelial cells
• cirrhosis
• non-invasive markers
• portal hypertension

AIM: To verify the usefulness of FibroQ for predicting fibrosis in patients with chronic hepatitis C, compared with other noninvasive tests.

METHODS: This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ, aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to platelet ratio index, cirrhosis discriminant score, age-platelet index (API), Pohl score, FIB-4 index, and Lok’s model were calculated and compared.

RESULTS: FibroQ, FIB-4, AAR, API and Lok’s model results increased significantly as fibrosis advanced (analysis of variance test: P < 0.001). FibroQ trended to be superior in predicting significant fibrosis score in chronic hepatitis C compared with other noninvasive tests.

CONCLUSION: FibroQ is a simple and useful test for predicting significant fibrosis in patients with chronic hepatitis C.

• Liver fibrosis
• Noninvasive test
• FibroQ
• Aspartate aminotransferase
• Alanine aminotransferase
• FIB-4 index
• Aspartate aminotransferase to platelet ratio index
• Lok’s model
• Cirrhosis discriminant score
• Pohl score