Liver Fibrosis Stage Research Articles

Noninvasive Models to Assess Liver Inflammation and Fibrosis in Chronic HBV Infected Patients with Normal or Mildly Elevated Alanine Transaminase Levels: Which One Is Most Suitable?

The prevalence of substantial inflammation or fibrosis in treatment-naïve patients with chronic hepatitis B (CHB) and normal alanine transaminase (ALT) levels is high. A retrospective analysis was conducted on 559 consecutive patients with hepatitis B virus infection, who underwent liver biopsy, to investigate the value of noninvasive models based on routine serum markers for evaluating liver histology in CHB patients with normal or mildly elevated ALT levels and to provide treatment guidance. After comparing 55 models, we identified the top three models that exhibited excellent performance. The APGA model, based on the area under the receiver operating characteristic curve (AUROC), demonstrated a superior ability to evaluate significant (AUROC = 0.750) and advanced fibrosis (AUROC = 0.832) and demonstrated a good performance in assessing liver inflammation (AUROCs = 0.779 and 0.874 for stages G ≥ 2 and G ≥ 3, respectively). APGA also exhibited significant correlations with liver inflammation and fibrosis stage (correlation coefficients, 0.452 and 0.405, respectively (p < 0.001)). When the patients were stratified into groups based on HBeAg status and ALT level, APGA consistently outperformed the other 54 models. The other top two models, GAPI and XIE, also outperformed models based on other chronic hepatitis diseases. APGA may be the most suitable option for detecting liver fibrosis and inflammation in Chinese patients with CHB.

Development and evaluation of a simple treatment eligibility score (HEPSANET) to decentralise hepatitis B care in Africa: a cross-sectional study

Hepatitis B virus (HBV) elimination requires expanding and decentralising HBV care services. However, peripheral health facilities lack access to diagnostic tools to assess eligibility for antiviral therapy. Through the Hepatitis B in Africa Collaborative Network (HEPSANET), we aimed to develop and evaluate a score using tests generally available at lower-level facilities, to simplify the evaluation of antiviral therapy eligibility in people living with HBV. We surveyed the availability of clinical and laboratory parameters across different health-care levels in sub-Saharan Africa. We used data from the HEPSANET dataset, the largest cross-sectional dataset of treatment-naive people living with HBV in sub-Saharan Africa, to derive and validate the score. Participants from this dataset were included in the analysis if they were aged 18 years or older and had liver fibrosis stages determined by a liver stiffness measurement or liver histopathology. Participants with co-infections or metabolic disorders were excluded. We allocated participants to the derivation and validation sets by geographical site. In the derivation set, we used stepwise logistic regression to identify the best performing parameters for identifying participants that met the 2017 European Association for the Study of the Liver (EASL) criteria. Regression coefficients were converted into integer points to construct simplified algorithms for different health-care levels. In the validation set, we estimated the area under the receiver operating characteristic, sensitivity, and specificity of the simplified algorithm for identifying antiviral therapy eligibility defined by the 2017 EASL criteria. At 11 sites from eight countries that returned surveys, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count were generally available at district hospital levels, and hepatitis B e antigen and point-of-care HBV DNA tests were available only at regional and provincial hospital levels or above. Among 2895 participants included from the HEPSANET database (1740 [60·1%] male, 1155 [39·9%] female), 409 (14·1%) met EASL antiviral therapy eligibility criteria. In the derivation set, the optimal district-level hospital score was: ALT (IU/L), less than 40 (0 points), 40-79 (+1), 80 or greater (+2); AST (IU/L), less than 40 (0), 40-79 (+1), 80 or greater (+2); and platelet counts (109/L), less than 100 (+2), 100-149 (+1), 150 or greater (0). When combined with family history and clinical data for decompensated cirrhosis that do not require any biological tests, a cut-off of 2 points or more had a sensitivity and specificity of 82% (95% CI 76-86) and 95% (93-96) to identify treatment-eligible individuals in the derivation set, and 78% (71-85) and 87% (86-89) in the validation set, respectively. Using a score incorporating platelet counts, AST, and ALT, the majority of people living with HBV requiring antiviral therapy can be identified. Our findings suggest that clinical staging can be decentralised down to district hospital level in sub-Saharan Africa. European Association for the Study of the Liver Foundation, John C Martin Foundation. For the French translation of the abstract see Supplementary Materials section.

Performance of continuous controlled attenuation parameter and liver stiffness measurement by the novel SmartExam in metabolic dysfunction-associated steatotic liver disease.

FibroScan® Expert 630 and FibroScan® Mini+430 are novel vibration-controlled transient elastography devices equipped with the same SmartExam software, which allows continuous measurement of controlled attenuation parameter (CAP) during the entire examination. This study aims to compare the CAP variabilities and the quantification for liver fibrosis and steatosis between the conventional FibroScan and the SmartExam-equipped machines in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This retrospective study included 118 patients with biopsy-proven MASLD who underwent liver biopsy at two tertiary centres between 2021 and 2023. Liver stiffness and steatosis measurements were performed using both FibroScan machines and M and XL probes for each individual. Liver histology was used as the reference standard for liver fibrosis and steatosis staging. Standard deviations of continuous CAP (cCAP) were significantly lower than those of CAP for all probes (p < .0001). CAP variability was significantly associated with body mass index (p < .01), probe selection (p < .001) as well as the random effect of centre. Only the effect of probe selection (p < .001) was significantly associated with cCAP variability. No significant difference was found in the performance of staging liver fibrosis and steatosis between two types of machines at the same cut-offs. The SmartExam-based VCTE reduces the variability of CAP measurement and achieves a similar accuracy as the FibroScan 502 device for the estimation of both hepatic steatosis and fibrosis. Future studies should determine if cCAP is a better tool to monitor changes in steatosis than the original CAP.

Liver Magnetic Resonance Elastography: Focus on Methodology, Technique, and Feasibility.

Magnetic resonance elastography (MRE) is an imaging technique that combines low-frequency mechanical vibrations with magnetic resonance imaging to create visual maps and quantify liver parenchyma stiffness. As in recent years, diffuse liver diseases have become highly prevalent worldwide and could lead to a chronic condition with different stages of fibrosis. There is a strong necessity for a non-invasive, highly accurate, and standardised quantitative assessment to evaluate and manage patients with different stages of fibrosis from diagnosis to follow-up, as the actual reference standard for the diagnosis and staging of liver fibrosis is biopsy, an invasive method with possible peri-procedural complications and sampling errors. MRE could quantitatively evaluate liver stiffness, as it is a rapid and repeatable method with high specificity and sensitivity. MRE is based on the propagation of mechanical shear waves through the liver tissue that are directly proportional to the organ's stiffness, expressed in kilopascals (kPa). To obtain a valid assessment of the real hepatic stiffness values, it is mandatory to obtain a high-quality examination. To understand the pearls and pitfalls of MRE, in this review, we describe our experience after one year of performing MRE from indications and patient preparation to acquisition, quality control, and image analysis.

Test characteristics for combining non-invasive liver fibrosis staging modalities in individuals with Hepatitis C virus.

Non-invasive methods have largely replaced biopsy to identify advanced fibrosis in hepatitis C virus (HCV). Guidelines vary regarding testing strategy to balance accuracy, costs and loss to follow-up. Although individual test characteristics are well-described, data comparing the accuracy of using two tests together are limited. We calculated combined test characteristics to determine the utility of combined strategies. This study synthesizes empirical data from fibrosis staging trials and the literature to estimate test characteristics for Fibrosis-4 (FIB4), APRI or a commercial serum panel (FibroSure®), followed by transient elastography (TE) or FibroSure®. We simulated two testing strategies: (1) second test only for those with intermediate first test results (staged approach), and (2) second test for all. We summarized empiric data with multinomial distributions and used this to estimate test characteristics of each strategy on a simulated population of 10,000 individuals with 4.2% cirrhosis prevalence. Negative predictive value (NPV) for cirrhosis from a single test ranged from 98.2% (95% CB 97.6-98.8%) for FIB-4 to 99.4% (95% CB 99.0-99.8%) for TE. Using a staged approach with TE second, sensitivity for cirrhosis rose to 93.3-96.9%, NPV to 99.7-99.8%, while PPV dropped to <32%. Using TE as a second test for all minimally changed estimated test characteristics compared with the staged approach. Combining two non-invasive fibrosis tests barely improves NPV and decreases or does not change PPV compared with a single test, challenging the utility of serial testing modalities. These calculated combined test characteristics can inform best methods to identify advanced fibrosis in various populations.

Automated classification of liver fibrosis stages using ultrasound imaging.

Ultrasound imaging is the most frequently performed for the patients with chronic hepatitis or liver cirrhosis. However, ultrasound imaging is highly operator dependent and interpretation of ultrasound images is subjective, thus well-trained radiologist is required for evaluation. Automated classification of liver fibrosis could alleviate the shortage of skilled radiologist especially in low-to-middle income countries. The purposed of this study is to evaluate deep convolutional neural networks (DCNNs) for classifying the degree of liver fibrosis according to the METAVIR score using US images. We used ultrasound (US) images from two tertiary university hospitals. A total of 7920 US images from 933 patients were used for training/validation of DCNNs. All patient were underwent liver biopsy or hepatectomy, and liver fibrosis was categorized based on pathology results using the METAVIR score. Five well-established DCNNs (VGGNet, ResNet, DenseNet, EfficientNet and ViT) was implemented to predict the METAVIR score. The performance of DCNNs for five-level (F0/F1/F2/F3/F4) classification was evaluated through area under the receiver operating characteristic curve (AUC) with 95% confidential interval, accuracy, sensitivity, specificity, positive and negative likelihood ratio. Similar mean AUC values were achieved for five models; VGGNet (0.96), ResNet (0.96), DenseNet (0.95), EfficientNet (0.96), and ViT (0.95). The same mean accuracy (0.94) and specificity values (0.96) were yielded for all models. In terms of sensitivity, EffcientNet achieved highest mean value (0.85) while the other models produced slightly lower values range from 0.82 to 0.84. In this study, we demonstrated that DCNNs can classify the staging of liver fibrosis according to METAVIR score with high performance using conventional B-mode images. Among them, EfficientNET that have fewer parameters and computation cost produced highest performance. From the results, we believe that DCNNs based classification of liver fibrosis may allow fast and accurate diagnosis of liver fibrosis without needs of additional equipment for add-on test and may be powerful tool for supporting radiologists in clinical practice.

Relationships between Cxcl12, Tweak, Notch1, and Yap mRNA Expression Levels in Molecular Mechanisms of Liver Fibrogenesis

Current data on the molecular mechanisms of liver fibrosis and cirrhosis fail to fully explain all stages of their development. Interactions between individual genes and signaling pathways are known to play an important role in their functions. However, data on their relationships are insufficient and often contradictory. For the first time, mRNA expression of Notch1, Notch2, Yap1, Tweak (Tnfsf12), Fn14 (Tnfrsf12a), Ang, Vegfa, Cxcl12 (Sdf), Nos2, and Mmp-9 was studied in detail at several stages of thioacetamide-induced liver fibrosis in Wistar rats. A factor analysis isolated three factors, which combined highly correlated target genes. The first factor included four genes: Cxcl12 (r = 0.829, p < 0.05), Tweak (r = 0.841, p < 0.05), Notch1 (r = 0.848, p < 0.05), and Yap1 (r = 0.921, p < 0.05). The second factor described the correlation between Mmp-9 (r = 0.791, p < 0.05) and Notch2 (r = 0.836, p < 0.05). The third factor included Ang (r = 0.748, p < 0.05) and Vegfa (r = 0.679, p < 0.05). The Nos2 and Fn14 genes were not included in any of the factors. The gene grouping by mRNA expression levels made it possible to assume a pathogenetic relationship between their products in the development of fibrotic changes due to liver toxicity.

Suboptimal reliability of FIB-4 and NAFLD-fibrosis scores for staging of liver fibrosis in general population.

The burden and incidence of liver cirrhosis are increasing worldwide. Early detection of liver fibrosis would help in early interventions and preventing the progression of fibrosis and cirrhosis. The accepted noninvasive markers for liver fibrosis staging, namely fibrosis-4 (FIB-4) and nonalcoholic fatty liver disease fibrosis score (NFS), have shown inconsistent performance for detecting the fibrosis stage. We aimed to evaluate the efficacy of FIB-4 score and NFS for the detection of liver fibrosis in the general population. From a general population referred from a single, community-based family-physician clinic, we included study participants between the ages of 45 and 65 years, with no knowledge of liver disease and no record of alcohol consumption. Liver fibrosis was evaluated by the FIB-4 score and NFS using shear wave elastography (SWE) or transient elastography (TE) measurements as a reference. A total of 76 participants (aged 61.5 ± 0.37 years, 33% females) were included in the study cohort. We observed a nonsignificant correlation between liver stiffness measurement (LSM) and FIB-4 and NFS (r = 0.1, P = 0.37; r = 0.16, P = 0.15, respectively). Our results showed that only 5.2% with FIB-4 >3.25 and 9.7% with NFS >0.675 had LSM >12 kPa. The compatibility of fibrosis staging was 55% between FIB-4 score and LSM and only 18% between NFS and LSM. We found that FIB-4 and NFS are unreliable tools for liver fibrosis estimation in the general population. There is a need for more reliable noninvasive methods for the early detection of liver fibrosis.

Analytical and Clinical Evaluation of a Chemiluminescent Immunoassay to Detect Serum Chitinase-3-like Protein 1 in HBV-Related Liver Diseases.

Serum chitinase-3-like protein 1 (CHI3L1) is a diagnostic marker for liver diseases, such as hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the analytical performance of a chemiluminescent immunoassay (CLIA) for the quantitative detection of CHI3L1 and its application in hepatitis B virus (HBV)-related liver diseases. The CLIA for CHI3L1 detection presented good analytical performance, with a linear range of 1.50-2000.00 ng/mL and a detection limit of 0.98 ng/mL. To evaluate its clinical application, serum CHI3L1 levels were detected in 82 patients with chronic hepatitis B (CHB) and in 21 healthy controls. The patients with CHB and HCC had higher CHI3L1 levels than the healthy controls and the patients with CHB without HCC. However, CHI3L1 levels did not change significantly with the increase in liver fibrosis stages. The area under the receiver operating characteristic curve for the diagnosis of HBV-related HCC was 0.808, representing a moderate diagnostic value. Correlation analysis revealed a significant association between CHI3L1 and alpha-fetoprotein (AFP) levels, the fibrosis-4 (FIB-4) index, and the aspartate aminotransferase-to-platelet ratio index (APRI). In conclusion, compared with currently reported methods for CHI3L1 detection, the CLIA has a high sensitivity, a wide linear range, and an acceptable accuracy, precision, and reference intervals, making it valuable in the diagnosis of HBV-related HCC.

Treatment of chronic viral hepatitis c in perm Krai

Objective. To analyze the effectiveness of etiotropic antiviral therapy with direct antiviral drugs against chronic viral hepatitis C in the adult population of the Perm Krai.&#x0D; Materials and methods. In the regional register of Perm Krai, 20095 patients with chronic viral hepatitis C were registered. In 2019–2021, antiviral therapy with direct antiviral drugs, registered in the Russian Federation, and included in the list of vital and essential medicines for medical use was prescribed to 282 patients with chronic hepatitis C. There were 137 men (48.6 %), 145 (51.4 %) – women. The age of the patients ranged from 26 to 82 years, the duration of the disease – from 3 to 25 years.&#x0D; Results. All the therapy regimes we used showed 100 % effectiveness in the population of patients suffering from chronic hepatitis C associated with mild liver fibrosis regardless of genotype, whereas in the population of patients with grade 3 fibrosis or liver cirrhosis, 100 % effectiveness was achieved only after the use of sofosbuvir-containing schemes. The pangenotypic schemes resulted in 100 % achievement of a stable virological response among patients with genotype 1 regardless of the stage of liver fibrosis and previous therapy experience. In the treatment of patients infected with genotype 3 of hepatitis C virus with severe fibrosis, the effectiveness of 100 % was noted after the use of sofosbuvir-containing regimes.&#x0D; Conclusions. Among the adult population of Perm Krai, the overall effectiveness of therapy in patients with chronic hepatitis C, who used direct antiviral drugs, was 97.8 %.

Tanshinone IIA regulates CCl4 induced liver fibrosis in C57BL/6J mice via the PI3K/Akt and Nrf2/HO-1 signaling pathways.

Chronic liver diseases caused by various factors may develop into liver fibrosis (LF). Early stage of LF could be reversible. Tanshinone IIA (Tan IIA), an extract from Salvia miltiorrhiza, has been reported to be hepatoprotective. However, the potential targets and mechanism of Tan IIA in the treatment of LF are still unclear. Our study aims at the anti-LF mechanism of Tan IIA through network pharmacological analysis combined with LF-related experiments. Serum biochemical indicators and histopathological examination showed that Tan IIA could ameliorate the process of LF in the CCl4 -induced mouse model. Western blot and immunohistochemical assays showed that Tan IIA decreased the expression of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt), and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1). Compared with the model group, the Tan IIA groups increased the decreased superoxide dismutase activity and glutathione content, while decreasing the increased malondialdehyde content. These results indicate that Tan IIA may play an antioxidant role by inhibiting the expression of KRAS, PI3K/Akt, and Nrf2/HO-1 to ameliorate the progression of LF, which to some extent explains the pharmacological mechanism of Tan IIA in LF. In conclusion, our study demonstrates that Tan IIA could regulate LF via PI3K/Akt and Nrf2/HO-1 signaling pathways. It may be an effective therapeutic compound for the treatment of LF.

Staging liver fibrosis: comparison of radiomics model and fusion model based on multiparametric MRI in patients with chronic liver disease.

To develop and compare radiomics model and fusion model based on multiple MR parameters for staging liver fibrosis in patients with chronic liver disease. Patients with chronic liver disease who underwent multiparametric abdominal MRI were included in this retrospective study. Multiparametric MR images were imported into 3D-Slicer software for drawing bounding boxes on MR images. By using a 3D-Slicer extension of SlicerRadiomics, radiomics features were extracted from these MR images. The z-score normalization method was used for post-processing radiomics features. The least absolute shrinkage and selection operator method (LASSO) was performed for selecting significant radiomics features. The logistic regression analysis was used for building the radiomics model. A fusion model was built by integrating serum fibrosis biomarkers of aspartate transaminase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4) with radiomics signatures. In the training cohort, AUCs of radiomics and fusion model were 0.707-0.842 and 0.718-0.854 for differentiating different groups. In the testing cohort, AUCs were 0.514-0.724 and 0.609-0.728. For the training cohort, there was no significantdifference of AUCs between radiomics and fusion model (p > 0.05). For the testing cohort, AUCs of fusion model were higher than those of radiomics model in differentiating F1-3 vs. F4 and F1-2 vs. F4 (p = 0.011 & 0.042). Radiomics model and fusion model based on multiparametric MRI exhibited the feasibility for staging liver fibrosis in patients with CLD, and APRI and FIB-4 could improve the diagnostic performance of radiomics model in differentiatingF1-3 vs. F4 and F1-2 vs. F4.

Serum level of proteins involved in apoptosis and autophagy in patients with type 2 diabetes and non-alcoholic fatty liver disease

Aim of the study was to estimate the blood serum level of microtubule-associated protein 1 light chain 3 alpha (MAP1LC3alpha), beclin-1 (BECN-1), Bcl-2 (BCL-2), caspase-3 (CASP3) and autophagy related 5 (ATG-5) protein as potential markers of liver fibrosis in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD).Material and methods. A single center cross-sectional observational study was performed. Seventy four patients with T2D and NAFLD were included, 23 men and 51 women, aged 18 to 74 years. Transient elastography was used for the assessment of liver fibrosis. The severity of fibrosis was estimated using the Metavir sсore. In addition, indirect liver fibrosis indices APRI and FIB-4 were calculated. Serum concentration of MAP1LC3alpha, BECN-1, BCL-2, CASP and ATG-5 was measured by ELISA. We applied ROC analysis to assess the value of studied indicators in diagnosis of liver fibrosis.Results. Liver fibrosis stage F1 was verified in 16 subjects, stage F2 in 12, stage F3 in 7, and stage F4 in 19 individuals. Patients with advanced liver fibrosis (stage 3-4) when compared to those without fibrosis (stage 0–2) had higher content of MAP1LC3alpha (p = 0.01) and BECN-1 (p = 0.01). There were no significant differences in the level of BCL-2, CASP3 and ATG-5 between patients with different severity of fibrosis. In the ROC analysis, MAP1LC3alpha and BECN-1 showed significance for the diagnosis of severe liver fibrosis, which, however, did not exceed that of the APRI index.Conclusions. In patients with T2D and NAFLD, serum levels of MAP1LC3alpha and BECN-1 are associated with severe liver fibrosis.

Alcohol-related cancer morbidity and mortality are stratified using modified albumin platelet product

Alcohol abuse is associated with several diseases, such as hepatocellular carcinoma, cirrhosis, and extrahepatic malignancies. Recently, we reported albumin platelet product (APP) and modified APP (mAPP) as novel indices of liver fibrosis staging and prognosis in patients without alcoholic liver diseases. This retrospective cohort study aimed to extend application of APP and mAPP in prognosis prediction of patients with alcoholic liver diseases. We enrolled 222 patients with alcoholic liver diseases based on their medical records. Cut-off values of APP = 4.349 and mAPP = 2.484 were adopted based on a past report. Hazard ratios of APP and mAPP were compared to those of albumin-bilirubin score and fibrosis-4 index. The primary and secondary endpoints were carcinogenesis and death, respectively. Thus, APP = 4.349 and mAPP = 2.484 significantly differentiated cancer-free survival and overall survival in univariate analysis. Hazard ratios of mAPP = 2.484 were greater than those of the albumin-bilirubin score of -2.270 and fibrosis-4 index of 3.25. Multivariate analysis revealed mAPP = 2.484 as an independent risk factor for carcinogenesis and overall death. In conclusion, mAPP is a simple index to stratify patient’s risk for carcinogenesis and death.

Intensive lifestyle intervention positively affects nonalcoholic fatty liver fibrosis score (NFS) and key metabolic parameters: A retrospective study

To date lifestyle intervention is the only proven therapy to treat nonalcoholic fatty liver disease (NAFLD). In this study, we retrospectively analyze the influence of a structured, multimodal 52-week lifestyle intervention program on NAFLD fibrosis score (NFS) as a marker for liver fibrosis. At baseline, 16/47 subjects (34.0%) in our cohort displayed elevated NFS levels suggestive for advanced stages of liver fibrosis. Already after the initial 12-week hypocaloric fasting phase with a formula diet, this number decreased significantly and continued to decrease until the end of the program to 10/47 (21.3%). At baseline, 48.9% of the participants had impaired glucose metabolism, as defined by impaired fasting glucose, elevated HbA1c, or overt type 2 diabetes mellitus. This proportion reduced markedly to 31.9% by the end of the program. The proportion of advanced stages of liver fibrosis was especially high in the subgroup of participants with impaired glucose metabolism. This group particularly benefited from the lifestyle intervention program in terms of their NFS. The present study demonstrates that participants of structured multimodal lifestyle intervention programs with formula diets can significantly improve their metabolic parameters, such as body weight, fasting glucose, HbA1c, and lipids, and substantially reduce their risk of advanced liver fibrosis. Primary care providers must be aware of the close link between impaired glucose metabolism and increased liver-related risk and refer their metabolically ill patients to effective programs.

Serum level of full-length connective tissue growth factor reflects liver fibrosis stage in patients with Fontan-associated liver disease.

Chronic liver disease leads to liver fibrosis, and an accurate diagnosis of the fibrosis stage is crucial for medical management. Connective tissue growth factor (CTGF) is produced by endothelial cells and platelets and plays a central role in inducing fibrosis in various organs. In the present study, we tested the validity of measuring the serum levels of two types of CTGF to estimate the biopsy-confirmed liver fibrosis stage. We used two detection antibodies targeting the N- and C-terminal of CTGF to measure the serum levels of two forms of CTGF consisting of its full length and its N-terminal fragment. We analyzed the level of CTGF (via enzyme-linked immunosorbent assay) and the liver fibrosis stage in 38 patients with Fontan-associated liver disease (FALD) (26 cases of which were diagnosed pathologically). Correlations were determined by multivariate analysis and the area under the receiver operating characteristic curve. The 65 patients with nonalcoholic fatty liver disease (NAFLD) were included as a disease control group for examination. Full-length CTGF was significantly inversely correlated with liver fibrosis in patients with FALD. Although the platelet count was also associated with the liver fibrosis stage, full-length CTGF was more closely correlated with the fibrosis stage. Furthermore, the level of full-length CTGF was inversely associated with high central venous pressure. Conversely, the serum level of CTGF was not correlated with the fibrosis stage in NAFLD. The serum level of full-length CTGF may be useful for estimating the liver fibrosis stage in patients with FALD.

Integrin-Targeted Theranostic Nanoparticles for Clinical MRI-Traceable Treatment of Liver Fibrosis.

Liver fibrosis is the critical stage in the development of chronic liver disease (CLD), from simple injury to irreversible cirrhosis. Timely detection and intervention of liver fibrosis are crucial for preventing CLD from progressing into a fatal condition. Herein, we developed iron oxide (Fe3O4) nanoparticles (IONPs) and ferulic acid (FA) coencapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), followed by surface modification with cRGD peptides (cRGD-PLGA/IOFA) for integrin-targeted clinical magnetic resonance imaging (MRI)-traceable treatment of liver fibrosis. The cRGD peptide linked on the surface of the PLGA/IOFA NPs could specifically bind to the overexpressed integrin αvβ3 on activated hepatic stellate cells (HSCs) in the fibrotic liver, enabling the high-sensitive clinical MR imaging (3 T) and precise staging of liver fibrosis. The FA encapsulated in cRGD-PLGA/IOFA showed excellent efficacy in reducing oxidative stress and inhibiting the activation of HSCs through the transforming growth factor-β (TGF-β)/Smad pathway. Notably, the IONPs encapsulated in cRGD-PLGA/IOFA NPs could alleviate liver fibrosis by regulating hepatic macrophages through the NF-κB pathway, lowering the proportion of Ly6Chigh/CD86+, and degrading collagen fibers. The FA and IONPs in the cRGD-PLGA/IOFA produced a synergistic enhancement effect on collagen degradation, which was more effective than the IONPs treatment alone. This study demonstrates that cRGD-PLGA/IOFA NPs could effectively relieve liver fibrosis by acting on macrophages and HSCs and provide a new strategy for the clinical MRI-traceable treatment of liver fibrosis.

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 &lt; 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 &lt;0.00001). The fucose concentration correlated with a number of laboratory parameters: erythrocytes (p &lt;0.001), hemoglobin (p &lt;0.01), platelets (p &lt;0.001), average hemoglobin concentration in erythrocyte (p &lt;0.01), alkaline phosphatase (p &lt;0.05), albumin (p &lt;0.001), LDH (p &lt;0.05), but not with ALT and AST levels (p&gt;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.

MR Elastography: Practical Questions, From the AJR Special Series on Imaging of Fibrosis.

MR elastography (MRE), first described in 1995 and FDA-cleared in 2009, has emerged as an important tool for noninvasively detecting and staging liver fibrosis in patients with known or suspected chronic liver disease. This review focuses on a series of practical questions about the clinical use of MRE. Most head-to-head comparison studies with other laboratory and imaging-based tests have concluded that MRE has the highest diagnostic performance among tests for staging liver fibrosis. Limitations in the accuracy of biopsy as a standard of truth in staging liver fibrosis are increasingly being recognized. MRE-based measurements show promise as quantitative surrogates of disease severity and predictors of important clinical outcomes. The appropriate role of MRE in the management of patients with chronic liver disease is being actively incorporated into recognized clinical guidelines. Growing evidence shows that MRI measurement of elevated liver fat is the most important single biomarker for detecting nonalcoholic steatohepatitis (NASH) and that MRE-based liver stiffness is the most important single biomarker for detecting at-risk NASH (i.e., NASH with stage ≥ F2 fibrosis). Advances in MRE technology are offering higher precision and new biomarkers, which have potential to allow independent assessment of inflammation and other histologic processes in addition to fibrosis.

Опыт лечения больных хронической ВГС‑инфекцией пангенотипной комбинацией препаратов прямого противовирусного действия (глекапревир/пибрентасвир) в Ставропольском крае

Objective. To analyze the results of usage of pangenotype combination glecaprevir/pibrentasvir (GLE/PIB) in real clinical practice in Stavropol Krai within the framework of the regional program on chronic hepatitis C (CHC) treatment. Materials and methods. In the framework of this study, a retrospective analysis of the use of GLE/PIB combination in the period from 2018 to 2022 within the framework of the regional program for the treatment of CHC in the Stavropol region was carried out. The drug was prescribed in accordance with the current label approved in Russia. Patients were observed during the entire period of GLE/PIB therapy and for 12 weeks after treatment completion. Data for analysis were collected from outpatient records and protocols of the “Regional Medical Commission on Diagnosis, Treatment and Drug Supply of Patients with Chronic Viral Hepatitis B and C in Stavropol Krai”. Results. The analysis included 405 patients treated within the framework of the regional program on drug supply of patients with chronic viral hepatitis B and C in the territory of the Stavropol region. The scope of the examination allowed to assess the sustained virologic response 12 weeks after the end of GLE/PIB therapy (SVR12). 92.6% (375/405) of patients had not previously received antiviral therapy. Absence or minimal manifestations of hepatic fibrosis (F0-1) were noted in 50.9% of patients, advanced stage of fibrosis (F3-4 by METAVIR scale) in 34.6%. The distribution by fibrosis stage was as follows: F0 – 21.98% (89/405), F1 – 28.9% (117/405), F2 – 14.6% (59/405), F3 – 13.1% (53/405), F4 (CP-A) – 21.5% (87/405). All patients with liver cirrhosis had compensated stage of the disease – class A according to Child-Pugh. In the study population, genotype (Gt) 3 prevailed, detected in 55.1% (223/405) of patients. Hepatitis C virus (HCV) Gt1 was diagnosed in 29.4% (119/405) of patients. Among them, 16.5% (67/405) of patients had Gt1b, 0.5% (2/405) had Gt1a, and 12.3% (50/405) of patients with Gt1 had no subtype identified. Gt2 was detected in 11.4% of patients (46/405), 3 (0.7%) patients had a genotype other than 1–3, and 14 (3.5%) patients had no HCV genotype determined. 14 (3.6%, 14/405) patients were co-infected with HCV and HIV. 23.5% (95/405) of patients belonged to the age group older than 60 years. The distribution of patients according to the duration of antiviral therapy was as follows: 8 weeks – 89.4% (362/405), 12 weeks – 6.4% (26/405) and 16 weeks – 4,2% (17/405). 405 (100,0%) out of 405 patients achieved SVR12. There were no cases of serious adverse events and treatment withdrawal during antiviral therapy. Conclusion. GLE/PIB has demonstrated high efficacy in patients with different HCV genotypes (including Gt3) and different stages of liver fibrosis (including compensated cirrhosis) in the real-world setting. The SVR12 rate obtained in this analysis is fully consistent with the data of clinical trials and real clinical practice published earlier. Key words: chronic hepatitis C, glecaprevir/pibrentasvir, pangenotypic, real clinical practice