• Cirrhosis
• Fibrosis
• Metabolic dysfunction-associated steatotic liver disease
• Noninvasive test

• interventional radiology
• liver biopsy
• percutaneous
• transjugular liver biopsy
• ultrasound

• Non-alcoholic fatty liver disease
• beta-D-galactosyl-specific lectin
• galactose-binding lectin
• hepatic cirrhosis.
• liver fibrosis
• liver steatosis

• Humans
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Galectin 3/metabolism
• Animals
• Hepatic Stellate Cells/metabolism
• Fatty Liver/metabolism
• Fatty Liver/pathology
• Galectins/metabolism
• Liver/metabolism
• Liver/pathology
• Blood Proteins

• National Natural Science Foundation of China
• Natural Science Foundation of Sichuan Province

• Artificial Intelligence
• U-Net
• cirrhosis
• convolutional neural network
• liver fibrosis
• segmentation

• fatty liver
• health check-up cohort
• hepatic fibrosis
• magnetic resonance elastography
• metabolic abnormality

• chronic hepatitis b
• dna
• hbv
• in situ hybridization
• intrahepatic

• Adult
• Biological Assay/methods
• Biological Assay/standards
• Biological Assay/statistics & numerical data
• China
• Cross-Sectional Studies
• Female
• Hepatitis B Core Antigens/analysis
• Hepatitis B Surface Antigens/analysis
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/physiopathology
• Humans
• Liver/pathology
• Liver/physiopathology
• Male
• Middle Aged

• Gossypin
• hepatic fibrosis
• methotrexate hepatotoxicity

• Cook needle
• Menghini needle
• TJLB
• Tru-cut needle

• biomarker
• cancer screening
• cirrhosis
• hepatocellular carcinoma
• precision medicine
• risk prediction

• DK099558, CA233794, CA226052 (to YH) NIH HHS
• R01 DK099558 NIDDK NIH HHS
• R01 CA233794 NCI NIH HHS

• Albi
• Fibrosis-4 index
• Hepatocellular carcinoma
• Liver stiffness measurement
• Non-invasive test
• Spleen stiffness measurement

• Carcinoma, Hepatocellular/diagnostic imaging
• Elasticity Imaging Techniques
• Humans
• Hypertension, Portal/diagnosis
• Hypertension, Portal/etiology
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Liver Neoplasms/diagnostic imaging
• Portal Pressure

To establish a novel nomogram for diagnosing liver fibrosis in patients with chronic hepatitis B virus (HBV) infection and verify the diagnostic performance of the established nomogram.

Patients with chronic HBV infection who met the inclusion and exclusion criteria were enrolled in this retrospective study; 70% and 30% of patients were randomly assigned to training dataset and validation dataset, respectively. The risk factors for liver fibrosis were screened using the univariate and multivariate logistic regression analyses. Based on the results, a nomogram was established and verified.

508 patients with chronic HBV infection were included in this study (n = 355 for training dataset and n = 153 for validation dataset). The logistic regression analysis showed that liver stiffness measurement (LSM), platelet (PLT) count, and prothrombin time (PT) were independent risk factors for liver fibrosis (P < 0.01), which were used to establish the nomogram. The consistency index (C-index) of the nomogram established for diagnosing liver fibrosis was 0.875. The calibration line and the ideal line were consistent, which indicated that diagnosis of liver fibrosis by the established model was accurate. The values of area under the receiver operator characteristic (ROC) curve (AUROC) for diagnosing liver fibrosis by the nomogram were 0.857 and 0.862 in the training dataset and validation dataset, respectively, which were noticeably higher than those in the well-known serological models, including the aspartate aminotransferase- (AST-) to-platelet ratio index (APRI) scoring model, fibrosis-4 (FIB-4) scoring model, APAG model (including age, PT, albumin, and γ-glutamyl transferase), and S-index model (all P < 0.05).

LSM, PT, and PLT were found as independent risk factors for liver fibrosis. The established nomogram exhibited an excellent diagnostic performance, and it can more visually and individually evaluate the probability of liver fibrosis in patients with chronic HBV infection.

The aim of this study was to compare the histopathological quality and physical features of the specimen of a full-core end-cut biopsy system with that of the standard side-notch system for liver biopsies.

A full-core end-cut 16G biopsy device and a standard side-notch 16G needle were used to take biopsies of unclear liver lesions. Patients were randomized in two groups of 16 patients each. The primary endpoint of this prospective study was the core length measured using a dedicated microscope imaging software. Secondary endpoints were the quality of the specimen rated by an independent pathologist unaware of the device (scale from 1 to 5; with 1 as best and 5 as worst), the core diameter (determined by the microscopic imaging software) and presence of fragmentation (evaluated by the pathologist).

For the full-core (FC) and side-notch (SN) groups, the mean core length was similar with 13,599 μm and 11,570 μm (p=0.131), respectively. The quality of the specimen was significantly better in the FC-group with an average rating of 1.68 vs 2.50 (p=0.009). The fragmentation rate in the FC-group was statistically significantly lower at 2/27 (7%) than in the SN-group at 13/33 (39%) (p=0.021). The diameter in the FC-group was 1042 μm vs 930 μm in SN-group (p=0.018).

• biopsy system
• full-core
• liver biopsy
• liver tumor
• side-notch

In this study, we aim to determine the hepatic pathological changes in HBV DNA-negative chronic Hepatitis B (CHB) patients after 12-month antiviral therapy.

Blood routine indicators including platelet count (PLT) and white blood cell (WBC) were determined. The coagulation function was evaluated by determining the prothrombin time (PT) and prothrombin time activity (PTA), together with the HBV DNA quantification and alpha fetoprotein (AFP). The virology data included hepatitis B surface antigen (HBsAg)/antibodies against hepatitis B surface antigen (anti-HBs), hepatitis B e antigen (HBeAg)/antibodies against hepatitis B e antigen (anti-HBe) and antibodies against hepatitis B core antigen (anti-HBc) were tested. Pathological assay was performed to the liver puncture tissues. Based on the HBV DNA data in the 12-month follow-up of the cases that received anti-viral therapy during this time, the experimental group was divided into group A (HBV DNA negative at the baseline level, HBV DNA negative after 12 months, N = 79) and group B (HBV DNA negative at the baseline level, HBV DNA turning to be positive after 12 months, N = 13). Statistical analysis was performed on the each test index of the two groups.

The inflammation grade of group A showed significant improvement after 12-month treatment (P < 0.05). The pathological inflammation grade of group B was increased after one year, and the liver function indices and the PTA (P < 0.05) levels were all increased. Pathological results indicated that the proportion of disease progression in group A was decreased after 12-month follow-up while that proportion was increased in group B. Significant differences were noticed in AFP levels between the patients with progression in group A and those with progression in group B.

Negative HBV DNA does not mean a controlled hepatitis B. Hepatitis B patients transferred to HBV DNA positivity during the anti-viral therapy are easily to show disease progression, and then special attention should be paid to the HBV DNA monitoring. Meanwhile, close monitoring to the changes of liver function, PTA and AFP levels may help to detect changes on the disease in a timely manner.

• Blood routine
• Coagulation function
• HBV DNA
• Hepatitis B
• Liver function
• Pathological analysis

• Adult
• Age Factors
• Antigens, Neoplasm/blood
• Area Under Curve
• Biomarkers
• Female
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/diagnosis
• Humans
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Male
• Membrane Glycoproteins/blood
• Middle Aged
• Plant Lectins/blood
• Platelet Count
• Receptors, N-Acetylglucosamine/blood

• Kaohsiung Medical University Chung-Ho Memorial Hospital
• Kaohsiung Medical University

To evaluate the influence of an active inflammatory process in the liver on Gd-EOB-DTPA-enhanced MR imaging in patients with different degrees of fibrosis/cirrhosis.

Overall, a number of 91 patients (61 men and 30 women; mean age 58 years) were included in this retrospective study. The inclusion criteria for this study were Gd-EOB-DTPA-enhanced MRI of the liver and histopathological evaluation of fibrotic and inflammatory changes. T1-weighted VIBE sequences of the liver with fat suppression were evaluated to determine the relative signal change (RE) between native and hepatobiliary phase (20min). In simple and multiple linear regression analyses, the influence of liver fibrosis/cirrhosis (Ishak score) and the histopathological degree of hepatitis (Modified Hepatic Activity Index, mHAI) on RE were evaluated.

RE decreased significantly with increasing liver fibrosis/cirrhosis (p < 0.001) and inflammation (mHAI, p = 0.004). In particular, a correlation between RE and periportal or periseptal boundary zone hepatitis (moth feeding necrosis, mHAI A, p = 0.001) and portal inflammation (mHAI D, p < 0.001) was observed. In multiple linear regression analysis, both the degree of inflammation and the degree of fibrosis were significant predictors for RE (p < 0.01).

The results of this study suggest that the MR-based hepatic enhancement index RE is not only influenced by the degree of fibrosis, but also by the degree of inflammation.

• Contrast Media
• Female
• Gadolinium DTPA
• Humans
• Inflammation/diagnostic imaging
• Inflammation/pathology
• Liver/diagnostic imaging
• Liver/pathology
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/pathology
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Regression Analysis
• Retrospective Studies

• Alcohol-related liver disease
• Fibrosis
• Histological staging
• Non-alcoholic fatty liver disease
• Pathogenesis
• Regression

• Budd-Chiari syndrome
• Fibrosis
• Hepatic vein
• Occlusion
• Thrombosis

• Hepatic myofibroblasts
• Hepatic stellate cells
• Liver biopsy
• Liver fibrosis
• Transient elestography

• Hepatocarcinogenesis
• Liver fibrosis
• M2BPGi

• chronic hepatitis B
• liver fibrosis
• liver histology
• longitudinal assessment
• quantitative fibrous collagen parameters

Strong correlations between the grade of fibrosis and cirrhosis, classified using the Ishak scoring system, and the uptake characteristics of Gd-EOB-DTPA with the relative enhancement (RE) of the liver parenchyma have been reported. To confirm the results of a retrospective analysis, patients undergoing liver surgery were prospectively examined with Gd-EOB-DTPA-enhanced liver 3 Tesla MRI to determine the degree of liver fibrosis. Correlations between the grade of fibrosis and cirrhosis, classified using the Ishak scoring system, and RE were investigated and compared with those derived from an initial retrospective study. After validating the cut-off values in the retrospective study (Ishak ≥ 1, RE-cut-off 0.90; Ishak ≥ 2, RE-cut-off 0.79; Ishak ≥ 4, RE-cut-off 0.60; and Ishak = 6, RE-cut-off 0.47), we showed that Gd-EOB-DTPA has a high sensitivity (≥86%) and a high positive predictive value (≥86%). These results support the use of Gd-EOB-DTPA-enhanced liver MRI as a non-invasive method for determining the degree of liver fibrosis and cirrhosis.

The aim of this study was to determine the diagnostic value of diffusion-weighted MRI of the liver at 3T to classify liver fibrosis/cirrhosis.

62 patients who underwent both histopathological examination and diffusion-weighted imaging of the liver via 3T MRI within a period of 3 months were included in the study. The Ishak score (1-6) was used to determine the degree of fibrosis: No liver fibrosis (NLF; Ishak 0, n = 16), mild liver fibrosis (MLF; Ishak 1-2, n = 23), advanced liver fibrosis (ALF; Ishak 3-5, n = 12), and liver cirrhosis (LC; Ishak 6, n = 11).

The corresponding ADC values for the individual patient groups were as follows: NLF: 1123 (SD 95.8); MLF: 1032 (SD 77.6); ALF: 962 (SD 68.8); LC: 1015 (SD 60.2) mm2/s. There is a significant difference between NLF and MLF (p = 0.004) and between MLF and ALF (p = 0.022). A significant difference between patients with ALF and LC (p = 0.117) could not be found.

Liver fibrosis/cirrhosis lowers the ADC values of the liver parenchyma in 3T MRI. However, the degree of fibrosis can only be conditionally determined on the basis of ADC values.

• abdomen
• fibrosis
• histology
• liver
• magnetic resonance imaging

• Cancer screening
• Chemoprevention
• Cirrhosis
• Hepatocellular carcinoma
• Precision medicine
• Risk prediction

• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/prevention & control
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/prevention & control
• Precision Medicine
• Prognosis
• Risk Factors

• 671231 European Research Council
• R01 DK099558 NIDDK NIH HHS

• Mac-2-binding protein
• Wisteria floribunda agglutinin
• hepatitis B virus
• hepatitis C virus
• liver biopsy

• animal model
• biopsy
• chronic hepatitis B
• fibrosis change
• liver cirrhosis
• liver fibrosis
• quantitative image analysis

• ATP Binding Cassette Transporter, Subfamily B/genetics
• ATP Binding Cassette Transporter, Subfamily B/metabolism
• Animals
• Carbon Tetrachloride Poisoning/diagnostic imaging
• Carbon Tetrachloride Poisoning/genetics
• Carbon Tetrachloride Poisoning/metabolism
• Disease Models, Animal
• Humans
• Liver/diagnostic imaging
• Liver/metabolism
• Liver Cirrhosis/chemically induced
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/genetics
• Liver Cirrhosis/metabolism
• Magnetic Resonance Imaging/methods
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• ATP-Binding Cassette Sub-Family B Member 4

• Abdominal Muscles/pathology
• Animals
• Bacteria/chemistry
• Biocompatible Materials/chemistry
• Cellulose/chemistry
• Hernia/therapy
• Hydrogels/chemistry
• Inflammation
• Male
• Peritoneum/pathology
• Polytetrafluoroethylene/chemistry
• Rats
• Rats, Wistar
• Stress, Mechanical
• Surgical Mesh
• Tissue Adhesions/prevention & control

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.

• Non-invasive
• digital
• hepatic fibrosis
• histology
• staging

• cirrhosis
• fibroscan
• fibrosis
• incremental cost-effectiveness ratio
• prognosis
• quality-adjusted-life-years

• Antiviral Agents/therapeutic use
• Cost-Benefit Analysis
• Diagnostic Errors/economics
• Diagnostic Errors/statistics & numerical data
• Diagnostic Tests, Routine/economics
• Health Care Costs
• Hepatitis B e Antigens/blood
• Hepatitis B, Chronic
• Humans
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/economics
• Quality-Adjusted Life Years
• United Kingdom
• Viral Load

• 09/114/02 Department of Health

• ductular reaction
• fibrosis
• hepatic myofibroblasts
• image analysis

Liver fibrosis is a public health problem worldwide. There is a need of noninvasive imaging based methods for better diagnosis of this disease. In the current study, we aim to evaluate the potential of T1ρ MRI technique in detecting and characterizing different grades of liver fibrosis in vivo in humans.

Healthy subjects and patients with liver fibrosis were prospectively recruited for T1ρ MRI of liver on a 1.5 T MR scanner. Single slice T1ρ weighted images were acquired at different spin lock duration (0, 10, 20 and 30 ms) with spin lock amplitude of 500 Hz in a single breath-hold. Additionally, liver’s T1ρ images were acquired from five healthy subjects on the same day (n = 2) and different day (n = 2) sessions for test–retest study. Liver biopsy samples from patients were obtained and used to calculate the METAVIR score to define the stage of fibrosis and inflammation grade. T1ρ maps were generated followed by computation of mean and standard deviation (SD) values. Coefficient of variation (COV) of T1ρ values between two MRI scans was computed to determine reproducibility in liver. T test was used to compare T1ρ values between healthy and fibrotic liver. Pearson correlation was performed between stages of liver fibrosis and T1ρ values.

The mean (SD) T1ρ value among subject with healthy liver was 51.04 (3.06) ms. The COV of T1ρ values between two repetitions in the same day session was 0.83 ± 0.8 % and in different day session was 5.4 ± 2.7 %. T1ρ values in fibrotic liver were significantly higher compared to those of healthy liver (p < 0.05). A statically significant correlation between stages of fibrosis and T1ρ values was observed (r = 0.99, p < 0.05). Inflammation score for one patient was 2 and for remaining patients it was 1.

Proposed T1ρ pulse sequence design and protocol enabled acquisition of a single slice T1ρ weighted images in a single breath-hold and hence mitigated breathing motion related artifacts. Preliminary results have shown the sensitivity of T1ρ values to changes induced by liver fibrosis, and may potentially be used as a clinical biomarker to delineate the stages of liver fibrosis. Further, studies on a large number of subjects are required to validate the observations of the current study. Nevertheless, T1ρ imaging can be easily setup on a clinical scanner to monitor the progression of liver fibrosis and to the evaluate efficacy of anti-fibrotic drugs.

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.

The present mini-review updated the progress in methodologies based on using liver biopsy.

Articles for study of liver fibrosis, liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014.

Key articles were selected mainly according to their levels of relevance to this topic and citations.

With the recently mounting progress in chronic liver disease therapeutics, comes by a pressing need for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients. Histopathological information is recognized as the most valuable data for fibrosis assessment. Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility. Morphometric assessment by computer assist digital image analysis, such as collagen proportionate area (CPA), detects change of fibrosis amount in tissue section in a continuous variable, and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort. Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.

With input from multidisciplinary innovation, liver biopsy assessment as a new “gold standard” is anticipated to substantially support the accelerated progress of Hepatology medicine.

• cholestasis
• fibrosis
• home parenteral nutrition
• intestinal failure
• liver
• transient elastography

• Adolescent
• Adult
• Aged
• Alkaline Phosphatase/metabolism
• Aspartate Aminotransferases/metabolism
• Bilirubin/blood
• Biopsy
• Body Mass Index
• Cholestasis/diagnosis
• Cholestasis/etiology
• Cohort Studies
• Cross-Sectional Studies
• Elasticity Imaging Techniques
• Female
• Hematocrit
• Humans
• Liver/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Male
• Middle Aged
• Parenteral Nutrition, Home/adverse effects
• Partial Thromboplastin Time
• Platelet Count
• Prospective Studies
• Serum Albumin/metabolism
• Young Adult
• gamma-Glutamyltransferase/metabolism