Various Stages Of Liver Fibrosis Research Articles

РОЛЬ ФУКОЗЫ КРОВИ КАК ДОПОЛНИТЕЛЬНОГО ПРЕДИКТОРА ФИБРОЗА ПЕЧЕНИ У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ ВГС ИНФЕКЦИЕЙ

Introduction. Chronic hepatitis C is a widespread condition and poses severe burden on public health. Given the high relevance of chronic hepatitis C, the search for new prognostic markers of liver fibrosis progression is an important area of research. Aim. To evaluate the clinical significance of fucose in patients with chronic HCV infection with various stages of liver fibrosis. Methods. The study included 77 patients with chronic HCV infection (chronic hepatitis with various stages of liver fibrosis, cirrhosis of the liver). The study evaluated parameters of complete blood count, coagulation tests, biochemical blood analysis (including fucose) according to the stages of fibrosis (or cirrhosis). The statistical analysis was performed in R 4.3.2. P-values < 0.05 were considered statistically significant. Results. Blood fucose in patients with severe stages of liver fibrosis (or cirrhosis) – 18.3 (14.7; 20.7) mg/dl (compared to stages F0-F2 – 7.5 (6.7; 10.3) mg/dl, p <0.00001). The fucose concentration correlated with a number of laboratory parameters: erythrocytes (p <0.001), hemoglobin (p <0.01), platelets (p <0.001), average hemoglobin concentration in erythrocyte (p <0.01), alkaline phosphatase (p <0.05), albumin (p <0.001), LDH (p <0.05), but not with ALT and AST levels (p>0.05). Conclusion. Fucose concentration in blood was significantly higher in patients with severe stages of fibrosis or liver cirrhosis. Absence of correlation between blood fucose and cytolytic syndrome allows to use it as a potential additional predictor of liver fibrosis, especially in cases where the results of liver elastography may be questioned.

Identification of key genes and functional enrichment analysis of liver fibrosis in nonalcoholic fatty liver disease through weighted gene co-expression network analysis.

Nonalcoholic fatty liver disease (NAFLD) is a common type of chronic liver disease, with severity levels ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). The extent of liver fibrosis indicates the severity of NASH and the risk of liver cancer. However, the mechanism underlying NASH development, which is important for early screening and intervention, remains unclear. Weighted gene co-expression network analysis (WGCNA) is a useful method for identifying hub genes and screening specific targets for diseases. In this study, we utilized an mRNA dataset of the liver tissues of patients with NASH and conducted WGCNA for various stages of liver fibrosis. Subsequently, we employed two additional mRNA datasets for validation purposes. Gene set enrichment analysis (GSEA) was conducted to analyze gene function enrichment. Through WGCNA and subsequent analyses, complemented by validation using two additional datasets, we identified five genes (BICC1, C7, EFEMP1, LUM, and STMN2) as hub genes. GSEA analysis indicated that gene sets associated with liver metabolism and cholesterol homeostasis were uniformly downregulated. BICC1, C7, EFEMP1, LUM, and STMN2 were identified as hub genes of NASH, and were all related to liver metabolism, NAFLD, NASH, and related diseases. These hub genes might serve as potential targets for the early screening and treatment of NASH.

Interleukin-24 protects against liver injury in mouse models.

BackgroundInterleukin-24 (IL-24) binds to two kinds of receptor complexes, namely IL-20R1/IL-20R2 and IL-20R2/IL-22R1, which are also bound by IL-20. IL-20 plays a detrimental role in liver fibrosis. Due to the sharing of receptor complexes, we aimed to determine whether IL-24 also participates in liver fibrosis.MethodsClinical biopsy specimens from various stages of liver fibrosis were used to analyze IL-24 expression. IL-24 protein was administered to mice with thioacetamide (TAA)-induced liver injury. The direct effects of IL-24 on mouse primary hepatocytes or hepatic stellate cells (HSCs) were analyzed. Wild-type, IL-20R1-, and IL20R2-deficient mice were used to establish a model of acute TAA-induced liver injury.FindingsAmong patients with more severe liver fibrosis, there was a reduced IL-24/IL-20 ratio. Administration of IL-24 protein protected mice from TAA-induced liver injury and reduction of liver inflammation by antioxidant effects. IL-24 protected hepatocytes from TAA-induced apoptosis and prevented liver fibrosis through the inhibition of the HSCs activation. The protective role of IL-24 acted on liver cells were mainly IL-20R1-independent. IL-20R2-deficient mice exhibited more severe liver injury upon TAA treatment, thus confirming the protective role of IL-24.InterpretationIL-24 plays a key protective role in the progression of liver injury and has therapeutic potential for treating liver injuries.FundingThis work was supported by the Ministry of Science and Technology of Taiwan (MOST 106–2320-B-006–024) and Taiwan Liver Disease Prevention & Treatment Research Foundation.

Prognostic value of computed tomographic perfusion in the diagnosis of liver fibrosis and cirrhosis. Pilot study

Relevance: Most diffuse liver diseases lead to fibrosis over time with the risk of cirrhosis. With progressive fibrosis and cirrhosis of the liver both physical properties of the hepatic parenchyma and its hemodynamics change. The only reliable method for determining the stage of the disease is puncture biopsy and subsequent histological examination, but this method is invasive and associated with complications. Currently, the determination of the severity of cirrhosis is based on clinical data (the Child-Pugh scale) and elastography is considered to be the main non-invasive instrumental method. It lets reliably differentiate the initial fibrosis and cirrhosis of the liver, while the F2 and F3 stages according to the conventional METAVIR scale remain a "gray zone", as well as the differentiation of degrees of the severity of cirrhosis. In addition elastography has a number of limitations. The main ones of which are operator dependence, apparatus dependence and the inability to determine functional changes in the liver. With the use of perfusion computed tomography (CT perfusion) it is possible to assess the functionality of the liver by quantifying changes in hemodynamics. The method applied measures the characteristics of blood flow in the tissue at a given scanning level by computed-tomographic data on the dynamics of the distribution of the contrast agent in the area of interest is collected, besides the type of liver perfusion is determined. This parameter is needed to assess the dynamics of treatment against the background of drug therapy.Objective: To identify statistically significant parameters of CT perfusion to determine the severity of hemodynamic disturbances in patients with various stages of liver fibrosis and cirrhosis and to compare the values of parameters of liver CT perfusion with fibrosis according to the METAVIR conditional scale determined using elastography.Materials and methods: 18 patients were included in this parallel pilot study. On the basis of clinical and laboratory data and the results of elastography, 10 of them were diagnosed with fibrosis and cirrhosis. The stages of fibrosis F1, F2 were determined in 3 patients; stages F3, F4 – in 7. In the group of patients with F3, F4, according to the METAVIR conditional scale, subgroups were distinguished depending on the severity of cirrhosis: compensated – 3 patients, subcompensated – 2, decompensated – 2. The control group consisted of 8 patients with organ diseases abdominal cavity not associated with liver damage. All patients underwent CT perfusion of the liver on a Philips iCT 256 using the following scan parameters: 80 KVp, 120 mAc, total scan time 56 s, and slice thickness 5.0 mm. Intravenously, bolus was administered to all patients with 50 ml of ioversol 350 mg/ml, the rate of administration was 3.8–4.0 ml/s, the time from the moment of administration of the contrast medium to the start of scanning was 6 s. After receiving a series of images, the data was processed on a Philips workstation. Quantitative analysis was carried out according to the following indicators: TTP (time to peak, s), BV (blood volume, ml/100 g), AP (arterial perfusion, ml/min/100 ml), PP (portal perfusion, ml/min/100 ml), TP (total perfusion, ml/min/100 ml) and HPI (hepatic perfusion index, %).Results: In the control group of 8 patients, the perfusion values were: TTP 37.4±5.2 s, BV 16.1±5.0 ml/100 g, AP 25.0±7.5 ml/min/100 ml, PP 44.5±14.5 ml/min/100 ml, TP 70.1±14.9 ml/min/100 ml, HPI 70.1±14.9%. In 3 patients with F1, F2, according to the METAVIR conditional scale, the following statistically significant values (p<0.039) of perfusion indices were determined: BV 27.2±8.6 ml/100 g, AP 20.0±3.8 ml/min/100 ml; with compensated liver cirrhosis (n=3): TTP 46.2±1.7 s, BV 12.4±1.9 ml/100 g, AP 10.7±2.8 ml/min/100 ml, PP 37.3±5.2 ml/min/100 ml, TP 48.1±3.5 ml/min/100 ml, HPI 22.4±5.5%; subcompensated (n=2): TTP 43.0±3.2 s, BV 8.9±2.6 ml/100 g, AP 12.8±3.0 ml/min/100 ml, PP 27.7±9.0 ml/min/100 ml, TP 40.5±7.3 ml/min/100 ml; decompensated (n=2): BV 30.5±1.8 ml/100 g, PP 8.5±1.5 ml/min/100 ml, HPI 81.3±1.8%.Conclusion: The preliminary results obtained confirm that CT perfusion can be used to predict and assess the severity of hemodynamic disturbances in patients with varying degrees of severity of cirrhosis and supplements clinical, laboratory and elastography data.

CT and MR perfusion techniques to assess diffuse liver disease.

Perfusion imaging allows for the quantitative extraction of physiological perfusion parameters of the liver microcirculation at levels far below the spatial the resolution of CT and MR imaging. Because of its peculiar structure and architecture, perfusion imaging is more challenging in the liver than in other organs. Indeed, the liver is a mobile organ and significantly deforms with respiratory motion. Moreover, it has a dual vascular supply and the sinusoidal capillaries are fenestrated in the normal liver. Using extracellular contrast agents, perfusion imaging has shown its ability to discriminate patients with various stages of liver fibrosis. The recent introduction of hepatobiliary contrast agents enables quantification of both the liver perfusion and the hepatocyte transport function using advanced perfusion models. The purpose of this review article is to describe the characteristics of liver perfusion imaging to assess chronic liver disease, with a special focus on CT and MR imaging.

NONINVASIVE PARAMETERS AND STAGING OF LIVER FIBROSIS IN CHRONIC HEPATITIS C PATIENTS

OBJECTIVES: To use biochemical parameters and FibroScan as noninvasive tool in determination of various stages of liver fibrosis in chronic hepatitis C virus (HCV) patients. METHODS: Total 759 participants (609 chronic HCV patients and 150 normal healthy controls) were recruited from Lady Reading Hospital and Al-Hayat Medical Center, Dabgri garden, Peshawar, Pakistan and analyzed for biochemical markers from February 2015 to January 2017. On the basis of liver stiffness, 609 HCV patients were categorized in 05 groups as per FibroScan findings that include patients with no fibrosis, mild fibrosis, moderate fibrosis, severe fibrosis and cirrhosis. Only those HCV patients who showed presence of HCV RNA (PCR assay) in serum were included in this study. HCV patients who were co-infected with Hepatitis B virus and HIV were excluded from this study.RESULTS: Advance staged disease patients with severe liver fibrosis and cirrhosis showed elevated level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), AST/ALT, total bilirubin and lower level of albumin and haptoglobinas compared to controls and were found statistically significant (P<0.01). Patients group with cirrhosis showed elevated level of AST, GGT, ALP, AST/ALT and total bilirubin when compared to patients group with no liver complications and were statistically significant (P<0.01). Albumin and haptoglobin were significantly lower (P<0.05) in cirrhotic patients compared to those without liver complications. CONCLUSION: Combination of FibroScan and routinely available biochemical parameters are helpful in identifying liver fibrosis and cirrhosis in chronic HCV patients.

Automated detection and classification of liver fibrosis stages using contourlet transform and nonlinear features

Background and objectiveLiver fibrosis is a type of chronic liver injury that is characterized by an excessive deposition of extracellular matrix protein. Early detection of liver fibrosis may prevent further growth toward liver cirrhosis and hepatocellular carcinoma. In the past, the only method to assess liver fibrosis was through biopsy, but this examination is invasive, expensive, prone to sampling errors, and may cause complications such as bleeding. Ultrasound-based elastography is a promising tool to measure tissue elasticity in real time; however, this technology requires an upgrade of the ultrasound system and software. In this study, a novel computer-aided diagnosis tool is proposed to automatically detect and classify the various stages of liver fibrosis based upon conventional B-mode ultrasound images. MethodsThe proposed method uses a 2D contourlet transform and a set of texture features that are efficiently extracted from the transformed image. Then, the combination of a kernel discriminant analysis (KDA)-based feature reduction technique and analysis of variance (ANOVA)-based feature ranking technique was used, and the images were then classified into various stages of liver fibrosis. ResultsOur 2D contourlet transform and texture feature analysis approach achieved a 91.46% accuracy using only four features input to the probabilistic neural network classifier, to classify the five stages of liver fibrosis. It also achieved a 92.16% sensitivity and 88.92% specificity for the same model. The evaluation was done on a database of 762 ultrasound images belonging to five different stages of liver fibrosis. ConclusionsThe findings suggest that the proposed method can be useful to automatically detect and classify liver fibrosis, which would greatly assist clinicians in making an accurate diagnosis.

Correlation of the Stiffness of Hepatocellular Carcinoma and Surrounding Liver Parenchyma by Point Shear Wave Elastography

The purpose of this study was to assess the correlation between hepatocellular carcinoma (HCC) and surrounding liver parenchyma stiffness using point shear wave elastography (pSWE). HCC was diagnosed using the criteria of the American Association for the Study of Liver Diseases. Liver fibrosis was classified into three groups (nonsignificant fibrosis, significant fibrosis, and cirrhosis). pSWE was performed on the HCC and the adjacent hepatic parenchyma and was expressed as kilopascal (kPa). A total of 59 HCC patients with 64 tumors were included in the study. The mean stiffnesses of HCC and liver background were 9.25 ± 3.76 and 10.84 ± 4.81 kPa, respectively. There was no statistical significance in HCC stiffness in any stage of liver fibrosis. Low HCC/liver background stiffness ratio was noted in the cirrhotic group and statistically significant in two comparison groups (cirrhosis vs significant fibrosis and cirrhosis vs nonsignificant fibrosis), with P &lt; .001. In this cohort, HCC stiffness alone demonstrated no statistically significant difference in various stages of liver fibrosis.

15. Transient elastography for diagnosis of stages of hepatic fibrosis in people with alcohol dependence syndrome

Background and Aims: The presence and progression of hepatic (liver) fibrosis into cirrhosis is a prognostic variable having impact on survival in people with alcohol dependence. Liver biopsy is generally considered the gold standard for assessing hepatic fibrosis; however, this protocol frequently carries a risk of severe complications and false-negative results. Transient elastography is a non-invasive method for assessing and staging hepatic fibrosis. The aim of this study was thus to determine the prevalence of various stages of liver fibrosis using Fibroscan in patients with alcohol dependence syndrome. Methods: We enrolled 100 patients with alcohol dependence syndrome according to International Classification of Disease, 10th revision, diagnostic criteria for research (ICD-10 DCR) were included in the study using a cross sectional descriptive design. The evaluation was conducted using a specially designed intake proforma and tools such as Severity of Alcohol Dependence Questionnaire, and ICD-10 DCR. Fibroscan and abdominal ultrasonography were performed on all patients. Fibrosis stage was assessed using the Brunt scoring system Results: Sixty-nine percent had severe alcohol dependence as per the SADQ scores. Majority of the patients (50%) did not have any liver fibrosis. The stage of fibrosis (F1–F4) was distributed among the cohort as follows: 26 patients at F1, 14 patients at F2, 7 patients at F3, and 3 patients at F4. Liver stiffness differed significantly between each fibrosis stage (P < 0.001). Conclusions: Transient elastography is a useful method for assessing liver fibrosis in patients with alcohol dependence syndrome. The authors have none to declare.

Staging of rat liver fibrosis using monoexponential, stretched exponential and diffusion kurtosis models with diffusion weighted imaging- magnetic resonance.

Early diagnosis of liver fibrosis is important. The objective of this study was to explore the characteristics and to assess the accuracy of monoexponential, stretched exponential models (SEM), and diffusion kurtosis imaging (DKI) with diffusion-weighted imaging (DWI)-magnetic resonance imaging (MRI) in various stages of liver fibrosis in two standard rat models induced by carbon tetrachloride (CCl4) and biliary duct ligation (BDL). Parameters (ADC, Dapp, Kapp, DDC, α) were measured with a 3.0T MRI. Liver fibrosis stages (F0–F4) were defined by METAVIR scoring. Parameters (ADC, Dapp, DDC) were found to be negatively associated (r: -0.675~-0.789; P<0.05) with advancement of fibrosis stage. The analysis of receiver operating characteristic (ROC) curves illustrated that the areas under the curves (AUC) for ADC, Dapp, and DDC were 0.687~0.957, 0.805~0.938 and 0.876~1.000, respectively. The study showed that (ADC, Dapp, Kapp, DDC, α) from various diffusion models reflected pathological and physiological tissue changes. We conclude that SEM and DKI may provide more accurate information about diffusion, and non-Gaussian diffusion analysis may be a complementary tool for the assessment of liver fibrosis.

Diagnostic value of γ-glutamyl transpeptidase-to-platelet ratio index for hepatic fibrosis in patients with chronic hepatitis B

Objective To compare the diagnostic values of γ-glutamyl transpeptidase-to-platelet ratio index (GPRI), aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (Fib-4) for chronic hepatitis B(CHB) fibrosis and cirrhosis. Methods According to the Metavir score, 262 CHB patients were divided into F0—F1 group (n=131), F2—F3 group (n=102) and F4 group (n=29). The age, gender, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidas (γ-GT) and platelet count were recorded. GPRI, APRI, Fib-4 scores were calculated separately. Statistical analysis was performed by t test, Kruskal-Wallis H test, and χ2 test. The correlations between serum models and liver fibrosis stages were analyzed using the Spearman test. Results The scores of GPRI in F0—F1 group, F2—F3 group and F4 group were 0.39 (0.21, 0.95), 1.05 (0.38, 2.39) and 2.11 (1.12, 3.33), respectively. The difference was statistically significant (χ2=40.645, P<0.01). APRI scores in the three groups were 0.49 (0.32, 0.97), 0.77 (0.52, 1.52) and 1.12 (0.77, 2.50), respectively. The difference was statistically significant (χ2=32.636, P<0.01). Fib-4 scores in the three groups were 1.36 (0.92, 2.05), 2.34 (1.28, 4.35) and 3.86 (3.03, 8.99), respectively. The difference was statistically significant (χ2=48.943, P<0.01). Age, γ-GT, AST and liver fibrosis were all positively correlated with liver fibrosis (r=0.322, 0.301 and 0.199, respectively, all P<0.05). Platelet was negatively correlated with liver fibrosis (r=—0.455, P<0.05), while ALT was not significantly associated with hepatic fibrosis (r=0.111, P=0.073). GPRI, APRI and Fib-4 were positively correlated with liver fibrosis (r=0.625, 0.417 and 0.399, respectively, all P<0.05). The areas under the operating characteristic curve of GPRI for significant hepatic fibrosis, advanced liver fibrosis and cirrhosis were 0.818, 0.864 and 0.837, respectively. APRI for significant hepatic fibrosis, advanced liver fibrosis and cirrhosis were 0.694, 0.766 and 0.722, respectively, while Fib-4 were 0.696, 0.770 and 0.724, respectively. The low cutoff values of GPRI for various stages of liver fibrosis were 0.99, 1.04 and 1.06, respectively, and the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were all higher than those of APRI and Fib-4. The high cutoff values of GPRI for liver fibrosis at each stage were 2.49, 3.69 and 6.77, respectively, and the sensitivity, specificity, PPV and NPV of the diagnosis were all higher than those of APRI and Fib-4. Conclusion The diagnostic value of GPRI for CHB liver fibrosis is higher than those of APRI and Fib-4. Key words: Hepatitis B, chronic; Liver fibrosis; γ-glutamyl transpeptidase; Platelets; Prognosis

Dynamic Changes in Liver Stiffness Measured by Transient Elastography Predict Clinical Outcomes Among Patients With Chronic Hepatitis B.

We aimed to evaluate the validity of transient elastography in monitoring the antiviral outcomes in patients with chronic hepatitis B. This study included 108 patients treated with nucleos(t)ide analogues and 67 patients treated with interferon (IFN). Liver biopsies were evaluated by the METAVIR score. Transient elastography was performed initially at baseline, 48 weeks, and 96 weeks. Liver tissue was obtained before and after 96 weeks of treatment. The area under the receiver operating characteristic curve was used to examine the diagnostic value of transient elastography in predicting and monitoring outcomes of antiviral treatment. The liver stiffness value correlated well with the baseline alanine aminotransferase level (r = 0.33; P < .001) and was significantly different among various stages of liver fibrosis (P < .001). In the nucleos(t)ide analogue group, the mean pretreatment and posttreatment liver stiffness values ± SD were 8.7 ± 3.1 and 5.9 ± 1.6 kPa, respectively (P < .001), and they were 9.2 ± 3.7 and 7.2 ± 1.9 kPa (P < .001) in the IFN group. Although the liver stiffness values at baseline between the groups were similar (P = .45), they were 5.9 ± 1.6 kPa in the nucleos(t)ide analogue group and 7.2 ± 1.9 kPa in the IFN group after 48 weeks of treatment (P < .001). With the decreased magnitude liver stiffness for predicting the improvement in liver fibrosis, the area under the receiver operating characteristic curve was 0.68 (P = .029). When the decreased magnitude of liver stiffness was 4.1 kPa or higher, the sensitivity and specificity for predicting a histologic response were 88.2% and 50.0%. Our findings suggest that transient elastography is an effective measurement tool for diagnosing and monitoring the histologic response in patients with chronic hepatitis B during antiviral treatment and can help avoid multiple liver biopsies.

Modeling the mechanical properties of liver fibrosis in rats

The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading.

CHI3L1 Is a Liver-Enriched, Noninvasive Biomarker That Can Be Used to Stage and Diagnose Substantial Hepatic Fibrosis.

Liver fibrosis is a major disease that is primarily caused by hepatitis virus infections, toxins, and alcohol abuse. Diagnosing and staging liver fibrosis are critical in guiding the treatment of chronic liver diseases, according to several international and Chinese guidelines. Liver biopsy is the gold standard for diagnosing and staging liver fibrosis, but it is invasive and suffers from several limitations. Consequently, much research has focused on the search for a noninvasive serum biomarker of fibrosis. In this study, we determined that Chitinase 3-like 1 (CHI3L1) is an abundantly expressed liver gene whose expression is highly enriched in the liver. We then compared serum levels of CHI3L1 among patients with various stages of liver fibrosis, as determined by liver biopsies, and found that the CHI3L1 levels were able to differentiate early stages of liver fibrosis (S0-S2) from late stages of liver fibrosis (S3-S4). We further showed that CHI3L1 is a good marker of substantial fibrosis, with areas under the ROC curves (AUCs) of 0.94 for substantial (S2, S3, S4) fibrosis and 0.96 for advanced (S3, S4) fibrosis. Finally, we showed that CHI3L1 is superior to hyaluronic acid (HA), type III procollagen (PCIII), laminin (LN), and type IV collagen (CIV), which are also serum biomarkers of liver fibrosis, in identifying advanced liver fibrosis in patients with HBV-related liver fibrosis in China.

Intravoxel incoherent motion MRI evaluation for the staging of liver fibrosis in a rat model.

To explore the characteristics of intravoxel incoherent motion (IVIM) in various stages of liver fibrosis, and their relationships with fibrotic stages in rats. Fifty rats were given various doses of carbon tetrachloride (CCl4 ) to induce various fibrotic stages in rats; 15 untreated rats served as controls. Diffusion-weighted magnetic resonance imaging (MRI) was performed and eight b-values (0-800 s/mm(2) ) were applied to obtain IVIM parameters (D, pure molecular diffusion; f, perfusion fraction; D*, pseudodiffusion). The stages of liver fibrosis (stages F0-F4) were evaluated histologically using METAVIR scores. Fifty-seven rats (15 controls and 42 with fibrosis) were analyzed by nonparametric methods and receiver operating characteristic curves to determine diagnostic accuracy. Significant differences (P < 0.001) were found between stages (stages F0-F4) by D, f, D*, and apparent diffusion coefficient (ADC). There were inverse correlations between fibrosis stages and D, f, D*, ADC (r = -0.657, r = -0.631, r = -0.711 r = -0.719, respectively). Multivariate analysis showed that the combination models (D, f, D*) were better than the individual parameter (ADC) for the evaluation fibrosis stages (area under the curve [AUC]: 0.821-1.000 vs. AUC: 0.753-0.918) CONCLUSION: IVIM-derived parameters showed significant correlations with stages of liver fibrosis in a rat model.

Proteome analysis of hepatic non-parenchymal cells of immune liver fibrosis rats

Elucidation of the mechanisms of liver fibrogenesis is important to treat liver fibrosis. In this study, we established rat models of liver fibrosis with stages from 0-1, 2, and 3-4 to 4 at 2, 4, 6, and 8 weeks, respectively, by injection of pig serum. Liver fibrogenesis was detected by Masson's trichrome staining. Rat non-parenchymal cells (NPCs) were enriched 4-fold by Percoll density gradient centrifugation. Protein extracts from NPCs were prepared at 4 and 8 weeks, separated by two-dimensional electrophoresis, and then stained with Coomassie Blue G-250. At 4 weeks, we identified 18 non-redundant differentially expressed proteins of which protein disulfide-isomerase associated protein 3 (PDIA3) and NDUV showed consistent expression at protein and mRNA levels from 4 to 8 weeks. PDIA3 was found to be down-regulated by Western blotting in the rat model and immunohistochemically in human liver. Our results revealed important aspects of the pathogenesis/progression of liver fibrosis and demonstrated important changes in protein expression levels of NPCs at various stages of liver fibrosis.

Baseline Liver Fibrosis Stage and ART Use Predict Clinical Outcomes in HIV/HCV-Coinfected Patients

Patients coinfected with HIV and hepatitis C virus (HCV) are at greater risk for premature death than HCV-monoinfected patients, in part because they tend to have more rapidly progressive liver disease. In the present study, researchers quantified the mortality risk associated with various stages of liver fibrosis in HIV/HCV-coinfected patients and also evaluated the effects of HIV and HCV …

Spatial and temporal patterns of gene expression for the proteoglycans biglycan and decorin and for transforming growth factor-β1 revealed byin situ hybridization during experimentally induced liver fibrosis in the rat

Expression of the proteoglycans biglycan and decorin and of transforming growth factor-beta 1 at various stages of liver fibrosis induced experimentally in rats by oral administration of thioacetamide was examined. Using in situ hybridization combined with immunocytochemical staining for cell-type characteristic markers, we demonstrate spatial and temporal expression patterns specific for each of the genes. Biglycan gene expression levels coincided tightly with the activity and extent of fibrosis, fat-storing cells and their transformed form, the myofibroblast-like cells, being the major contributors. Decorin messenger RNA was detectable only after the transition to the chronic inflammatory stage in nonparenchymal cells of periportal fields and, transiently, in the forming septa. In the cirrhotic stage, expression was detected solely in periportal fields with enhanced bile duct proliferation. Transforming growth factor-beta 1 expression was undetectable in normal liver. During the subacute inflammatory stage, a hepatocyte subpopulation expressing low levels of transforming growth factor-beta 1 occurred at the limiting plate. With the progression of fibrosis, transforming growth factor-beta 1 expression levels increased considerably but remained restricted to the mesenchymal cells of the fibrotic septa.