Different Stages Of Liver Fibrosis Research Articles

Characteristics of liver volume and pathological changes with different stages of liver fibrosis in chronic liver disease

Objective: To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease. Methods: 53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes. Results: As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased (P<0.05), while the spleen volume gradually increased (P<0.05). The expression of CD31 and GS gradually increased (P<0.05), and the expression of Ki67 first increased and then decreased (P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume (r=-0.609, P<0.001) and the total liver volume (r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume (r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume (r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume (r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV (r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area(r=-0.511, P=0.009). Conclusion: As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.

Feasibility of ultrasound radiomics based models for classification of liver fibrosis due to Schistosoma japonicum infection.

Schistosomiasis japonica represents a significant public health concern in South Asia. There is an urgent need to optimize existing schistosomiasis diagnostic techniques. This study aims to develop models for the different stages of liver fibrosis caused by Schistosoma infection utilizing ultrasound radiomics and machine learning techniques. From 2018 to 2022, we retrospectively collected data on 1,531 patients and 5,671 B-mode ultrasound images from the Second People's Hospital of Duchang City, Jiangxi Province, China. The datasets were screened based on inclusion and exclusion criteria suitable for radiomics models. Liver fibrosis due to Schistosoma infection (LFSI) was categorized into four stages: grade 0, grade 1, grade 2, and grade 3. The data were divided into six binary classification problems, such as group 1 (grade 0 vs. grade 1) and group 2 (grade 0 vs. grade 2). Key radiomic features were extracted using Pyradiomics, the Mann-Whitney U test, and the Least Absolute Shrinkage and Selection Operator (LASSO). Machine learning models were constructed using Support Vector Machine (SVM), and the contribution of different features in the model was described by applying Shapley Additive Explanations (SHAP). This study ultimately included 1,388 patients and their corresponding images. A total of 851 radiomics features were extracted for each binary classification problems. Following feature selection, 18 to 76 features were retained from each groups. The area under the receiver operating characteristic curve (AUC) for the validation cohorts was 0.834 (95% CI: 0.779-0.885) for the LFSI grade 0 vs. LFSI grade 1, 0.771 (95% CI: 0.713-0.835) for LFSI grade 1 vs. LFSI grade 2, and 0.830 (95% CI: 0.762-0.885) for LFSI grade 2 vs. LFSI grade 3. Machine learning models based on ultrasound radiomics are feasible for classifying different stages of liver fibrosis caused by Schistosoma infection.

Electron Microscopic Studying the Impact of Ozone on Chronic Hepatitis C Patients as Antifibrotic

We aimed to evaluate the histopathological and ultrastructural changes detected by light and electron microscopy, induced in patients having chronic hepatitis C receiving ozone/oxygen gas treatment. Twenty six patients with chronic hepatitis C who were at different stages of liver fibrosis, non-responders to interferon plus ribavirin therapy (n = 9), had contraindications (n = 2), or were not compliant (n = 15) were included. At baseline and 12 weeks after administering the ozone/oxygen gas mixture, liver biopsies were carried out utilizing both the major rectal insufflations and auto-hemotherapy along with clinical evaluation, kidney and liver function assessments, liver biopsies and abdominal ultrasonography. Before and 12 weeks after the treatment of ozone, quantitative PCR was performed. Two pathologists evaluated the histological activity index (HAI) using Ishak's score while working in blind settings, taking into account the degree of inflammation and the stage of fibrosis. Electron microscopy was done for all cases before and after treatment. Significant improvements in liver enzymes in hepatic fibrosis and inflammatory activity based on Ishak scoring system were detected. The mean grade of inflammation dropped from 10.3 to 8.4 and the mean stage of fibrosis dropped from 2.3 to 2.0 both with P value &lt; 0.001 and &lt; 0.05 respectively. Mean PCR values showed significant increase after 12 weeks of treatment from 17059 to 218736 with P value &lt;0.05. As regards electron microscopy findings, the ultra-structural manifestations of HCV infection were disclosed in liver specimens exposed or not to ozone treatment. Stellate cells were often encountered in unexposed samples to ozone, meanwhile they disappeared after ozone exposure. Apoptotic hepatocytes which were frequently encountered before treatment are rarely seen in specimens after treatment with ozone. Signs of cellular regeneration in the form of binucleated cells, RER enveloping mitochondria, hepatocyte progenitors insinuating between the cells at the sinusoid pole are seen after treatment. Circulating inflammatory cells in the sinusoids and infilterating the lobule were decreased after treatment. Peroxisomes were increased after exposure to ozone with longitudinal orientation of mitochondrial cristae thus increasing the antioxidative activity of hepatocytes. No single significant complication was recorded in a total of &gt;1000 settings of ozone therapy. In conclusion, ozone oxygen gas mixture is a direct anti-fibrotic and anti-inflammatory agent in treatment of chronic hepatitis C patients without improving viral PCR as evidenced by histopathology, electron microscopy and quantitative PCR.

Clinical study of standard residual liver volume and transient elastography in predicting poor prognosis of patients after hemihepatectomy.

Liver cancer resection, especially in patients with hemihepatectomy or extended hemihepatectomy, often leads to poor prognosis, such as liver insufficiency and even liver failure and death, because the standard residual liver volume (SRLV) cannot be fully compensated after surgery. To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches. The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed. The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy. It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation. The liver stiffness measure (LSM) value and SRLV were associated with liver dysfunction after hemihepatectomy. Logistic regression analysis showed that an LSM value ≥ 25 kPa [odds ratio (OR) = 6.254, P < 0.05] and SRLV ≤ 0.290 L/m2 (OR = 5.686, P < 0.05) were independent risk factors for postoperative liver dysfunction. The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score (P < 0.05). SRLV and LSM values can be used to evaluate the safety of hemihepatectomy. The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.

Assessment of body mass index in patients with chronic hepatitis C who received an effective antiviral therapy

To evaluate the body mass index (BMI) in patients with chronic hepatitis C (CHC) with different stages of liver fibrosis and steatosis who received effective antiviral therapy (AVT). The study included 278 CHC patients with a sustained virologic response (SVR) at the end of treatment. In addition to assessing the investigational data to determine the clinical status of the patient, we calculated BMI (following the World Health Organization guidelines) and determined the severity of liver fibrosis (F) and steatosis (S) using transient elastography. The patients were assessed at the start of antiviral therapy, after ≥6 months from the moment SVR was confirmed, and then every 12 to 24 months. By the end of the study, the mean patient age was 49 years, 53% of them were men, and 34% of the patients were obese. Excessive weight gain was registered in 17% (n=48) of the cases, with 60% newly diagnosed with Class 1 to 2 obesity. Both before the start of AVT and years after reaching SVR, the mean BMI corresponded to the reference pre-obesity values, the liver steatosis was significantly more often absent in normal BMI; on the contrary, fatty liver (predominantly S2 to S3) was registered in individuals with elevated BMI (p<0.0001). After the long-term period following a successful therapy, Stage F4 liver fibrosis patients were mainly diagnosed with obesity (80% versus 44% before AVT; p=0.0010). The high proportion of patients with elevated BMI and liver steatosis seen years after a successful CHC therapy indicates a continued risk of progression of chronic liver disease. Such patients should be advised on how important it is to change their lifestyle to reduce overweight and prevent weight gain. We also need long-term assessments of how liver steatosis changes over time and what are the outcomes associated with post-SVR increase in BMI.

Diagnostic Accuracy of Indocyanine Green Clearance Test for Different Stages of Liver Fibrosis and Cirrhosis.

(1) Background: This study aimed to correlate the indocyanine green clearance (ICG) test with histopathological grades of liver fibrosis and liver cirrhosis to assess its diagnostic accuracy in differentiating normal liver parenchyma from liver fibrosis and liver cirrhosis. (2) Methods: A total of 82 patients who received a histopathological liver examination, imaging, and ICG test within three months were included in this retrospective study. The histopathological level of fibrosis was graded using the Ishak scoring system, and the patients were divided into five categories: no liver fibrosis (NLF), mild liver fibrosis (MLF), advanced liver fibrosis (ALF), severe liver fibrosis (SLF), and liver cirrhosis (LC). The non-parametric Kruskal-Wallis test with post hoc pairwise comparison utilizing Mann-Whitney U tests and Bonferroni adjustment was used to analyze differences in the ICG test results between the patient groups. Cross correlation between the individual fibrosis/cirrhosis stages and the score of the ICG test was performed, and the sensitivity, specificity, and positive and negative predictive values were calculated for each model predicting liver fibrosis/cirrhosis. (3) Results: A significant difference (p ≤ 0.001) between stages of NLF, LF, and LC was found for the ICG parameters (ICG plasma disappearance rate (ICG-PDR) and ICG retention percentage at 15 min (ICG-R15)). The post hoc analysis revealed that NLF significantly differed from SLF (ICG-PDR: p = 0.001; ICG-R15: p = 0.001) and LC (ICG-PDR: p = 0.001; ICG-R15: p = 0.001). ALF also significantly differed from SLF (ICG-PDR: p = 0.033; ICG-R15: p = 0.034) and LC (ICG-PDR: p = 0.014; ICG-R15: p = 0.014). The sensitivity for detection of an initial stage of liver fibrosis compared to no liver fibrosis (Ishak ≥ 1) was 0.40; the corresponding specificity was 0.80. The differentiation of advanced liver fibrosis or cirrhosis (Ishak ≥ 4) compared to other stages of liver fibrosis was 0.75, with a specificity of 0.81. (4) Conclusions: This study shows that the ICG test, as a non-invasive diagnostic test, is able to differentiate patients with no liver fibrosis from patients with advanced liver fibrosis and liver cirrhosis. The ICG test seems to be helpful in monitoring patients with liver fibrosis regarding compensation levels, thus potentially enabling physicians to both detect progression from compensated liver fibrosis to advanced liver fibrosis and cirrhosis and to initiate antifibrotic treatment at an earlier stage.

Extracellular matrix turnover: phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis.

Extracellular matrix (ECM) resolution by matrix metalloproteinases (MMPs) is a well-documented mechanism. MMPs play a dual and complex role in modulating ECM degradation at different stages of liver fibrosis, depending on the timing and levels of their expression. Increased MMP-1 combats disease progression by cleaving the fibrillar ECM. Activated hepatic stellate cells (HSCs) increase expression of MMP-2, -9, and -13 in different chemicals-induced animal models, which may alleviate or worsen disease progression based on animal models and the stage of liver fibrosis. In the early stage, elevated expression of certain MMPs may damage surrounding tissue and activate HSCs, promoting fibrosis progression. At the later stage, downregulation of MMPs can facilitate ECM accumulation and disease progression. A number of phytochemicals modulate MMP activity and ECM turnover, alleviating disease progression. However, the effects of phytochemicals on the expression of different MMPs are variable and may depend on the disease models and stage, and the dosage, timing and duration of phytochemicals used in each study. Here, we review the most recent advances in the role of MMPs in the effects of phytochemicals on liver fibrogenesis, which indicates that further studies are warranted to confirm and define the potential clinical efficacy of these phytochemicals.

The early diagnosis of hepatobiliary lesions in children with cystic fibrosis

Background. An increase in life expectancy of patients with cystic fibrosis contributes to the formation of severe patho­logy of the hepatobiliary system, leading to the development of fatal biliary cirrhosis. The purpose was to prospectively assess the predictive value of a combination of serum liver enzymes, ultrasound liver parameters and transient elastography for diagnosis of clinically significant liver fibrosis. Materials and methods. We enrolled 108 children aged 0–17 years with cystic fibrosis. The fibrosis stage was determined using transient elastography on FibroScan® 502 (Echosens, France). The activity of enzymes (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase-5), ultrasound parameters of the liver at different stages of liver fibrosis have been investigated. Results. Liver fibrosis of varying severity was detected in 29.6 % of patients with cystic fibrosis (liver elasticity ranged from 5.9 to 49.0 kPa). Li­ver cirrhosis was observed in 14.8 % of children with cystic fibrosis. The dependence of an increase in the activity of alkaline phosphatase, gamma-glutamyl transpeptidase, lactate dehydrogenase-5 and an enlargement of the left lobe of the liver, a reduction in the k ratio of the sizes of the right and left lobes of the liver on the degree of fibrosis F1-F4 (р &lt; 0.05) was found. Conclusions. The combined use of transient elastography FibroScan with increased activity of the alkaline phosphatase, gamma-glutamyl transpeptidase, lactatе dehydrogenase-5 and changing of ultrasound liver parameters could be used for early diagnosis of hepatobiliary lesions in cystic fibrosis. The age of a patient with cystic fibrosis over 6 years old, male gender and the presence of ΔF508 deletion in the genotype have a high positive predictive value for liver fibrosis and cirrhosis.

FRI-251 - Extracellular vesicle-derived microRNA signature in chronic hepatitis C patients with different stages of liver fibrosis

FRI-251 - Extracellular vesicle-derived microRNA signature in chronic hepatitis C patients with different stages of liver fibrosis

Evaluating Variability of Commercial Liver Fibrosis Elastography Phantoms.

Liver fibrosis has been found to increase the mechanical stiffness of the liver. To mimic different stages of liver fibrosis, commercially available phantoms (Model 039, CIRS, Inc.) have been produced for clinical quality assurance and research purposes. The purpose of this study was to investigate the mechanical property variability of the phantoms in two lots of CIRS Model 039 phantoms. Each lot consisted of phantoms of four stiffness types, and there were 8-10 phantoms of each type. Shear wave elastography measurements were conducted on each phantom at 10 different angles. Group velocity measurements and phase velocity curves were calculated for every SWE acquisition. Multilevel functional principal component analysis (MFPCA) was performed on phase velocity data, which decomposes each phase velocity curve into the sum of eigenfunctions of two levels. The variance of the component scores of levels 1 and 2 were used to represent inter-phantom and intra-phantom variability, respectively. The 95% confidence intervals of phase velocity in a phantom type were calculated to reflect curve variability. The standard deviations of the group velocity for phantoms of any type were less than 0.04 and 0.02 m/s for lots 1 and 2, respectively. For both lots, in every type, the phase velocity curves of most individual phantoms fall within the 95% confidence interval. MFPCA is an effective tool for analyzing the inter- and intra-phantom variability of phase velocity curves. Given the known variability of a fully tested lot, estimation of the variability of a new lot can be performed with a reduced number of phantoms tested.

Features of immune status in children with Wilson–Konovalov disease at different stages of liver fibrosis

The pathology in WilsonConovalov disease (WCD) results from impaired excretion of copper, thus leading to its excessive accumulation in tissues. Hypercupreniluria is characteristic to the WCD. Toxic effects of copper on liver tissue can manifest as fatty degeneration of hepatocytes, hepatitis, fibrosis and cirrhosis. Purpose of the present work was as follows: estimation of immune status in children with WD depending on the stage of liver fibrosis. Fifty-three patients with WCD aged 6 to 18 years, were examined. The stage of liver fibrosis was assessed by transient liver elastography using FibroScan F502 (EchoSence, France). The immune status of peripheral blood lymphocytes was examined using CYTOMICS FC500 flow cytofluorimeter (Beckman Coulter, USA). The relative numbers of B lymphocytes (B1 and B2 populations), NK cells, T helper cells, cytotoxic T lymphocytes, Th17 lymphocytes, regulatory T cells, activated T helper cells were assessed in the lymphoid area. All indices of the patients immune status were recalculated for percentage of deviation from the age-dependent reference values. Mass concentration of copper in daily urine was determined by atomic absorption method using AAnalyst 800 spectrometer. Statistical processing was performed by Statistica10.0 program. The WCD patients are characterized by an increase of Т helpers, regulatory Т cells, Th17 lymphocytes and activated Т helpers, along with decrease of cytotoxic Т lymphocytes and NK cells against normal levels. The number of B cells did not depend on the stage of liver fibrosis and was at the lower limit of normal range, or decreased. Upon increase of the liver fibrosis stage, the number of B1 lymphocytes increases and B2 lymphocytes become decreased. The urinary copper content in the examined patients varied from 19 to 835 g/day, being higher than the reference values in 88% of children, with median value of 175 g/day (71-330). A correlation between urinary copper concentration and degree of immune status deviation was revealed (R = 0.63): urinary copper concentration was increased when the number of Th17 lymphocytes, B1 lymphocytes and regulatory T cells became higher, and when the number of B2 lymphocytes decreased. A significant decrease in the population of cytotoxic T lymphocytes (p = 0.034) was observed in children with WCD in the presence of KaiserFleischer ring. Indexes of cellular immunity in children with WCD are an informative tool to assess the severity of liver damage.

Quantitative Assessment of Liver Impairment in Chronic Viral Hepatitis with [99mTc]Tc-Mebrofenin: A Noninvasive Attempt to Stage Viral Hepatitis-Associated Liver Fibrosis.

Background and objectives—Chronic viral hepatitis B and C infections are one of the leading causes of chronic liver impairment, resulting in liver fibrosis and liver cirrhosis. An early diagnosis with accurate liver fibrosis staging leads to a proper diagnosis, thus tailoring correct treatment. Both invasive and noninvasive techniques are used in the diagnosis and staging of chronic liver impairment. Those techniques include liver biopsy, multiple serological markers (as either single tests or combined panels), and imaging examinations, such as ultrasound or magnetic resonance elastography. Nuclear medicine probes may also be employed in staging liver fibrosis, although the literature scarcely reports this. The purpose of our study was to investigate whether a dynamic liver scintigraphy with [99mTc]Tc-mebrofenin has any value in staging or grading chronic liver damage. Materials and Methods—We prospectively enrolled patients with chronic viral hepatitis B and C infection referred for liver biopsy. All patient underwent dynamic liver scintigraphy with 99mTc-mebrofenin prior to liver biopsy. Dynamic liver scintigraphy was performed immediately after intravenous tracer injection for 30 min scanning time. Multiple scintigraphy parameters were calculated (whole liver lobe and focal area time to peak (TTP), 30 min to peak ratio (30/peak), whole lobe and focal area slope index in 350 s (slope_350). Liver biopsy took place shortly after imaging. Results—We found that many dynamic scintigraphic parameters are positively or negatively associated with different stages of liver fibrosis. The main parameters that showed most value are the ratio between 30 min and the peak of the dynamic curve (30/peak_dex (ratio)), and liver clearance corrected for body surface area and liver area (LCL_m2_dm2 (%/min/m2/dm2)). Conclusions—Our present study proves that conducting dynamic liver scintigraphies with [99mTc]Tc-mebrofenin has potential value in staging liver fibrosis. The benefits of this method, including whole liver imaging and direct imaging of the liver function, provide an advantage over presently used quantitative imaging modalities.

Comparison of the diagnostic performance of shear wave elastography with shear wave dispersion for pre-operative staging of hepatic fibrosis in patients with hepatocellular carcinoma

PurposeThis prospective study aimed to compare the diagnostic accuracy of shear wave elastography (SWE) with that of shear wave dispersion (SWD) in evaluation of hepatic fibrosis in patients with hepatocellular carcinoma before resection. MethodA total of 210 consecutive patients with hepatocellular carcinoma (HCC) who were scheduled to undergo hepatectomy were prospectively enrolled, pre-operative SWE and SWD examinations were performed. Fibrosis staging and necroinflammatory activity were determined histopathologically according to the Scheuer standard. Multivariate linear regression analysis was used to identify factors associated with SWE and SWD values. The performance of SWE and SWD were determined by receiver operating characteristic (ROC) analysis. ResultsBoth SWE and SWD values of liver were highly correlated with liver fibrosis stage and necroinflammatory activity (p < 0.05). Both SWE and SWD values were significantly different among the patients with different stages of liver fibrosis (p < 0.001). ROC analysis revealed that SWE that predicted substantial fibrosis (S ≥ 2), severe fibrosis (S ≥ 3) and cirrhosis (S = 4) were 0.895, 0.877 and 0.854, the SWD that predicted substantial fibrosis (S ≥ 2), severe fibrosis (S ≥ 3) and cirrhosis (S = 4) were 0.857, 0.815 and 0.791. SWE had better diagnostic performance than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S = 4). ConclusionsBoth SWE and SWD are useful, accurate and non-invasive methods for evaluating hepatic fibrosis in patients with hepatocellular carcinoma adapted to hepatectomy, SWE is a more accurate imaging modality than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S = 4).

Clinical Application of Shear Wave Elastography With Shear Wave Dispersion Imaging in the Preoperative Evaluation of Hepatic Parenchyma in Patients With Liver Tumors.

This study aimed to compare the diagnostic accuracy of shear wave elastography (SWE) with that of shear wave dispersion (SWD) in evaluation of hepatic parenchyma in patients with liver tumors before resection. A total of 174 patients with liver tumors were prospectively enrolled. SWE and SWD examinations were performed. Fibrosis stage and necroinflammatory activity were determined histopathologically according to the Scheuer standard. We compared the diagnostic accuracy of SWE and SWD. Both SWE and SWD values of the liver were highly correlated with liver fibrosis stage (P < .05, respectively). Both SWE and SWD values of the liver were moderately correlated with necroinflammatory activity (P < .05, respectively). Both SWE and SWD values of the liver were not correlated with steatosis (P > .05, respectively). Both SWE and SWD values were significantly different among the patients with different stages of liver fibrosis (P < .001, respectively). The area under the receiver operating characteristic (ROC) curve of SWE value was 0.982, 0.977, 0.969, and 0.984 for predicting S ≥ 1, S ≥ 2, S ≥ 3, and S=4, respectively. The optimal cutoff SWE values were 6.9, 7.9, 8.7, and 10.6kPa for S ≥ 1, S ≥ 2, S ≥ 3, and S=4, respectively. The area under the ROC curve of SWD value was 0.967, 0.960, 0.925, and 0.954 for predicting S ≥ 1, S ≥ 2, S ≥ 3, and S=4, respectively. The optimal cutoff SWD values were 11.2, 12.0, 13.2, and 16.0 m/s/kHz for S ≥ 1, S ≥ 2, S ≥ 3, and S=4, respectively. SWE and SWD could be noninvasive and accurate for predicting the stage of liver fibrosis in patients with liver tumors before surgery. SWE was more accurate than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S=4).

ВЗАИМОСВЯЗЬ РЕТИНОЛА И РЕТИНОЛ-СВЯЗЫВАЮЩЕГО БЕЛКА С НЕИНВАЗИВНЫМИ МАРКЕРАМИ ФИБРОЗА (PDGF-BB,TGF-β1) ПРИ ХРОНИЧЕСКИХ ПОРАЖЕНИЯХ ПЕЧЕНИ

Background. Perisinusoidal lipocytes (HSC) and retinol (R) metabolism play an important role in liver fibrosis. Objective. To estimate R and retinol-binding protein type 4 (RBP4) correlation with non-invasive fibrosis markers in patients with chronic liver diseases. Material and methods. The subjects of the study were 129 adult patients with chronic diffuse liver diseases, who were divided into 2 groups: those with chronic hepatitis - 104 patients, and those with liver cirrhosis - 25 patients. In addition, 48 patients were further subdivided according to liver fibrosis stages. Blood levels of R, RBP4, platelet growth factor BB, and transforming growth factor β1 (TGF-β1) were determined in the patients. Results. Differences in R and RBP4 content were established in the patients with different stages of liver fibrosis, the most informative values and coefficients for liver fibrosis staging were found. High blood levels of retinol and TGF-β1 are indicative of transformation of HSC into myofibroblasts, increased synthesis of profibrogenic factors, including TGF-β1, and the progression of liver fibrosis. Conclusions. Laboratory monitoring of R, RBP4 and TGF-β1 levels as well as of RBP4/R and PDGF-BB/R coefficients is an additional test for the diagnosis of liver fibrosis in chronic liver diseases.

Comparison of NAFLD Fibrosis Score with Shear Wave Elastograpghy to Identify Liver Fibrosis in Patients with NAFLD

Introduction: NAFLD is diagnosed by non-invasive and invasive methods. Non-invasive methods include NAFLD fibrosis score, AST/Platelets ratio index (APRI), FIB-4 score, BARD score, USG abdomen, Fibro-scan liver, transient elastography, MRI and MRI with elastography (MRE). Objectives: To determine the frequency of different grades of fibrosis on shear wave elastography in patients with NAFLD and to compare mean NAFLD fibrosis score in different stages of liver fibrosis. Study design: Cross-sectional study. Study duration: 26th February 2021 to 25th August 2021. Settings: Department of Gastroenterology SZH, Lahore. Materials &amp; Methods: A total of 197 patients with NAFLD of age 18-70 years were included. Patients with hepatitis B and/or C infection, hemochromatosis, Wilson’s disease, Alpha 1 antitrypsin deficiency, celiac disease, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis were excluded. Hepatic ultrasonographic examination was performed. Blood samples were taken in a 10cc BD syringe and were sent for assessment of PT/INR, LFTs including albumin, platelets count and fasting or random glucose level. Reports were assessed and the NAFLD fibrosis scores were calculated. Shearwave elastography was used as gold standard test for the detection and confirmation of liver fibrosis; and results were compared. Results: Age range in this study was from 18 to 70 years with mean age of 49.30 ± 12.05 years. Majority of the patients 145 (73.60%) were between 41 to 70 years of age. Out of these 197 patients, 80 (40.61%) were males and 117 (59.39%) were females with male to female ratio of 1:1.5. In this study, frequency of different grades of fibrosis on shear wave elastography in patients with NAFLD was as follows; F0 in 44 (22.34%), F1 in 89 (45.18%), F2 in 31 (15.74%), F3 in 22 (11.17%) and F4 in 11 (5.58%) patients. Conclusion: This study concluded that non-invasive NAFLD fibrosis score should be used to rule out the presence or absence of liver fibrosis by using simple clinical and biochemical variables and thus avoid the need of liver biopsy. Keywords: Non-Alcoholic Fatty Liver Disease, Fibrosis Score, Shearwave Elastography

Abdominal Ultrasound Combined with Laboratory Tests as a Reliable, Easily Accessible and Cost-Effective Way of Assessing the Stages of Liver Fibrosis and Cirrhosis.

In the last two decades, the simple low-cost abdominal ultrasound (US) examination for the diagnosis of advanced fibrosis and cirrhosis was displaced by very expensive and not readily available modern imaging systems like magnetic resonance imaging (MRI), computed tomography (CT) scan and transient elastography. The aim of this study is to evaluate and emphasize the potential of US for diagnosis of advanced liver fibrosis and cirrhosis. US, laboratory tests (blood counts, transaminases, aspartate platelet ratio index [APRI], international normalized ratio [INR], serum albumin and bilirubin) and liver biopsy were performed on 197 patients with chronic liver diseases. Development of liver fibrosis was categorized in six stages, with stages 1-3 considered as mild to moderate and stages 4-6 as advanced fibrosis. Sonographic parameters (interrupted liver surface line, nodularity of liver surface, biconvexity of liver edges, grade of liver angle, caudate lobe diameter, parenchyma echotexture and spleen size) were obtained. All variables were dichotomized into zero and one and compared with respect to the different stages of liver fibrosis. The sensitivity, specificity, and positive and negative predictive values of all variables as well as their summations scores through receiver operating characteristic (ROC) curve analysis were calculated for the correct histologic diagnosis. Totally, 39 cases had severe fibrosis and cirrhosis and 158 had mild to moderate fibrosis. The area under the curve by ROC curve analysis of sonographic variables (surface nodularity, angle of left lobe, echotexture of liver and spleen size) was 85%, that of laboratory data (APRI, serum albumin and INR combined) was 83.8%, that of APRI alone was 81.8% and all combined (sonography and lab data together) was 92.4% for the correct diagnosis. The simple US examination, alone or combined with lab data, is able to diagnose advanced fibrosis and cirrhosis with excellent accuracy, making the use of other modern imaging modalities unnecessary.

Study on the diagnostic value of transient elastography, APRI and FIB-4 for liver fibrosis in children with non-alcoholic fatty liver disease

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.

Proteomic Analysis of Human Serum for Patients at Different Pathological Stages of Hepatic Fibrosis.

Background Hepatic fibrosis is a severe liver disease that has threatened human health for a long time. In order to undergo timely and adequate therapy, it is important for patients to obtain an accurate diagnosis of fibrosis. Laboratory inspection methods have been efficient in distinguishing between advanced hepatic fibrosis stages (F3, F4), but the identification of early stages of fibrosis has not been achieved. The development of proteomics may provide us with a new direction to identify the stages of fibrosis. Methods We established serum proteomic maps for patients with hepatic fibrosis at different stages and identified differential expression of proteins between fibrosis stages through ultra-high-performance liquid chromatography tandem mass spectrometry proteomic analysis. Results From the proteomic profiles of the serum of patients with different stages of liver fibrosis, a total of 1,338 proteins were identified. Among three early fibrosis stages (control, F1, and F2), 55 differential proteins were identified, but no proteins simultaneously exhibited differential expression between control, F1, and F2. Differential proteins were detected in the comparison between different fibrosis stages. Significant differences were found between advanced fibrosis stages (F2-vs.-F3 and F3-vs.-F4) through a series of statistical analysis, including hierarchical clustering, Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. The differential proteins identified by GO annotation were associated with biological processes (mainly platelet degranulation and cell adhesion), molecular functions, and cellular components. Conclusions All potential biomarkers identified between the stages of fibrosis could be key points in determining the fibrosis staging. The differences between early stages may provide a useful reference in addressing the challenge of early fibrosis staging.

Role of serum M2BPGi levels in diagnosing significant liver fibrosis and cirrhosis in patients with chronic hepatitis B

Abstract Background and aim Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum diagnostic marker for liver fibrosis in various liver diseases. We aimed to evaluate its role in assessment of liver fibrosis in chronic hepatitis B infection (CHB) with reference to liver stiffness measurement (LSM) by transient elastography (Fibroscan). Design and Methods A case control study. 50 CHB patients with LSM by transient elastography technology and retrievable serum samples and 20 normal volunteers as a control group were recruited. Results 50 CHB patients (M: F = 30:20; mean age 43years ± 10.58) and 20 normal control volunteers (M: F = 12:8; mean age 37years ± 14.5) were recruited. The mean M2BPGi values for control group, F0-F1, F2, F3 and F4 progressively increased with more advanced stages of liver fibrosis: 0.282, 0.719, 1.322, 1.65 and 1.904 COI, respectively (p &amp;lt; 0.001). M2BPGi levels correlated well with liver stiffness (r = 0.911) and moderately with FIB-4 (r = 0.682), and with APRI (r = 0.536) (all p &amp;lt; 0.001). Using cut-off values of 0.455, 1.02, 1.16, 1.66 and 1.71COI for control, F0-F1, F2, F3 and F4 groups, respectively, the AUROCs were 0.996, 0.996, 0.691, 0.794 and 1.00 for control, F0-F1, F2, F3 and F4 groups, respectively. There was a statistically significant but with weak positive correlation between M2BPGi serum level and INR (r = 0.333, p = 0.018). And there was a statistically significant but with weak negative correlation between M2BPGi serum level and platelet count (r = -0.41, p = 0.003) and HBV DNA (r = -0.373, p = 0.008).There was a statistically significance between M2BPGi serum level and the history of varices (p = 0.023) Conclusions WFA+-M2BP is an accurate serum indicator for assessing different stages of liver fibrosis. WFA+-M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan.