Liver Fibrosis Stage Research Articles

Bile duct matrix metalloproteinase-7 expression: a new modality for diagnosis of biliary atresia

BackgroundBiliary atresia (BA) is an obliterative cholangiopathy of infancy that results in cholestasis and liver fibrosis. This fibrosis is due to an imbalance in extracellular matrix (ECM) breakdown and deposition. The mechanism by which the progressive injury occurs is not fully elucidated. Matrix metalloproteinases (MMPs) are involved in ECM turnover but also have non-ECM-related functions. Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing BA.ObjectiveThe aim of this study was to assess the hepatic expression of MMP-7 in infants with BA.Patients and methodsThe study was a retrospective-prospective case–control study that included 50 patients who were categorized into two groups, BA group (25 patients) and non-BA cholestatic patients as a control group (25 patients). Liver biochemistry, liver biopsy, histopathology, and immunohistochemical staining for primary antibody MMP-7 were performed for all studied patients.ResultsBile duct MMP7 expression was significantly higher in infants with BA than in non-BA cholestasis (P = 0.003), While the hepatic MMP-7 intensity did not differ significantly between both groups (P > 0.05). Bile duct expression of MMP-7 had a significant positive correlation with the BA Score (P = 0.017), while hepatic MMP-7 intensity had a significant positive correlation with alanine transaminase levels (P = 0.007) and a significant negative correlation with γ glutamyl transferase in the BA group (P = 0. 038). There was no statistically significant difference among different stages of fibrosis as regards the median of the hepatic MMP-7 intensity score and MMP-7 bile duct expression in infants with BA. There was no statistically significant difference between infants with successful and failed Kasai as regard the hepatic MMP-7 intensity and its bile duct expression.ConclusionBile duct expression of MMP-7 measured by immunohistochemistry is useful for the diagnosis of BA, but it is limited in predicting the stage of liver fibrosis and the outcome of Kasai portoenterostomy (KPE).

EUS-guided liver palpation as a screening tool for advanced fibrosis and cirrhosis in patients with suspected metabolic dysfunction—associated steatotic liver disease: a pilot study

Background and AimsEndoscopic liver “palpation” can be performed by indenting the liver surface under endoscopic ultrasound (EUS). Indentation depth is measured with sonographic calipers. We hypothesize that fibrotic livers are more difficult to indent, and indentation can accurately predict liver fibrosis staging. We compared EUS-guided liver palpation to conventional screening modalities in patients with suspected metabolic dysfunction-associated steatotic liver disease (MASLD). MethodsThis was a cross-sectional pilot study. Consecutive patients at three hospitals between 2021-2023 underwent EUS-guided palpation with liver biopsy. Liver palpation was compared to Fibrosis-4 index (FIB-4), AST to Platelet Ratio Index (APRI), NAFLD Fibrosis Score (NFS), and transient elastography in predicting fibrosis staging on histology. Area under the receiver operator characteristic (AUROC) curve analysis was performed. Results73 patients were included. Mean age was 49.1 and 71.2% were female. Mean body mass index was 41.1. Indentation depth was negatively correlated with fibrosis stage (Kruskal-Willis test, p<0.0001). EUS palpation demonstrated c-statistic of 0.79 and 0.95 discriminating advanced fibrosis and cirrhosis respectively. EUS-liver palpation was superior to NFS in predicting advanced fibrosis (p=0.0057) and superior to APRI and NFS predicting cirrhosis (p=0.0099 and 0.045 respectively). EUS palpation was not significantly different versus FIB-4. EUS palpation was superior to transient elastography in predicting cirrhosis (p=0.045). Using optimal cut-offs, indentation measurement ≤3.5mm yielded 100% predictive value ruling in advanced fibrosis, and ≥4.0mm yielded 100% predictive value ruling out cirrhosis. ConclusionsEUS liver palpation is a novel, accurate, and easy-to-use screening tool for advanced fibrosis and cirrhosis in patients with MASLD.

Erken Evre Karaciğer Fibrozisini Öngörmede Shear Wave Elastografinin Rolü

Aim: We examined the relationship between shear wave elastography (SWE) values and histopathological results in our study. Thus, we found the sensitivity of SWE in demonstrating early fibrosis. Materials and Methods: A total of consecutive 70 patients with chronic hepatitis B were prospectively evaluated. The patients included in fibrosis stages (F) 0, 1, 2, 3 and 4 according to Ishak scoring were examined with SWE. SWE measurements of F2, F3 and F4 patients who were found to have early stage fibrosis were compared with those of F0 and F1 patients. Results: The velocity+SD, and kPa+SD values in the group requiring treatment (F2, F3 and F4) were significantly higher than the group not requiring treatment (F0 and F1 )(p &amp;lt; 0.05). The sensitivity rate of the 1.85 cut-off value for velocity+SD was 53.8%, the positive prediction rate was 80.8%, the specificity rate was 83.3%, and the negative prediction rate was 58.1%. For kPa+SD, the cut-off value of 10.8 had a sensitivity rate of 51.3%, a positive prediction rate of 95.2%, a specificity of 96.7%, and a negative predictive rate of 60.4%. A significant correlation was observed between the fibrosis score and the kPa+SD distribution. Conclusion: SWE can differentiate the patients requiring treatment (F2, F3 and F4) from the patients not requiring treatment.

Effects of HCV Clearance with Direct-Acting Antivirals (DAAs) on Liver Stiffness, Liver Fibrosis Stage and Metabolic/Cellular Parameters.

Chronic hepatitis C (CHC) is a clinical and pathological syndrome with various causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. It is a significant cause of liver transplantation and liver-related death worldwide. The hepatic manifestations of CHC are typically characterized by slowly progressing liver fibrosis, which is a non-specific and often disproportionate response to tissue damage. A large majority of HCV patients have extrahepatic manifestations with varying degrees of severity. HCV infection is a risk factor for cardiovascular disease and diabetes mellitus, which increases insulin resistance, oxidative stress, and iron overload and causes chronic systemic inflammation. HCV infection is treated using direct-acting antivirals (DAAs) with cure rates of over 95 percent, minimal side effects, and shorter therapeutic courses. Despite the effective elimination of the virus, it seemed pertinent to understand to what extent HCV clearance eliminates or attenuates all the systemic alterations already induced by the virus during infection and chronicity. Our study aimed to determine whether eliminating HCV with DAAs alters the severity of liver disease (liver stiffness and liver fibrosis stage by TE) and the metabolic/cellular profile of patients with CHC. A group of 329 CHC patients from a Gastroenterology and Hepatology outpatient department were prospectively studied. Of these, 134 were also studied with DAAs. The liver fibrosis stage was evaluated by transient elastography (TE) using a FibroScan® device, and two groups were established for the analysis of liver stiffness (LS): mild and moderate stiffness (fibrosis F1 and F2; F1/2) and severe stiffness (fibrosis and cirrhosis F3 and F4; F3/4). Metabolic/cellular parameters were evaluated before and after antiviral treatment using standard methods: alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl-transpeptidase (γ-GT), haptoglobin (Hp), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), free iron (Fe), transferrin saturation (TS), total iron binding capacity (TIBC), ferritin (Ft), glycemia, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and platelets count. The results were statistically analyzed using SPSS 24.0 for Windows. Comparing the fibrosis stage before and after DAAs treatment, we verify a reduction in LS in 85.7% of patients and an improvement in liver fibrosis stage in 22.2% of them after DAAs treatment. Before DAAs treatment, patients showed a 2.410 risk for higher fibrosis stages (F3/4). Comparing metabolic/cellular parameters before and after DAAs treatment, patients showed lower ALP, AST, ALT, γGT, TG, Fe, TIBC, and Ft values and higher TC, LDL, and Hp values after treatment. As such, HCV elimination reduces iron overload and insulin resistance. On the other hand, it caused dyslipidemia, raising total cholesterol and LDL to levels outside the reference values. The improvement in the liver fibrosis stage by TE was mainly associated with higher baseline platelet count and HDL values and lower insulin resistance. With this study, we were able to contribute to the knowledge of the effects of HCV elimination with DAAs on liver disease and metabolic profile to improve the quality of treatment and follow-up of these patients after HCV elimination.

Preliminary Study on the Evaluation of Liver Fibrosis Using Endoscopic Ultrasound Elastography and Transabdominal Ultrasound Transient Elastography Combined with Strain Ratio

Background: This study aimed to explore the effectiveness of endoscopic ultrasound elastography (EUS-EG) in evaluating liver fibrosis. Methods: The present study involved 11 patients with chronic liver disease who met study criteria and underwent EUS-EG, transabdominal ultrasound transient elastography (TUS-TE), and liver biopsy (LB) examinations at the same time. The Batts-Ludwig scoring system for liver fibrosis was used as the gold standard to analyze the correlation between the EUS-EG strain ratio (SR) and TUS-TE liver stiffness measurement with the pathological stage of liver fibrosis. The optimal cut-off value and area under the receiver operating characteristic curve (AUROC) of EUS-EG and TUS-TE for diagnosing liver fibrosis were calculated by drawing an ROC curve, and the corresponding sensitivity, specificity, and accuracy were also calculated. Results: Endoscopic ultrasound elastography was highly positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.759, P = 0.01), and TUS-TE was positively correlated with the pathological stage of liver fibrosis (S ≥ 2, r = 0.857, P = 0.003). The optimal diagnostic cut-off value of cirrhosis undergoing EUS-EG and TUS-TE was 0.84 and 14.2 Kpa, respectively. When the pathological stage was S0-S1, the sensitivity, specificity, accuracy, and AUROC value of TUS-TE in the diagnosis of liver fibrosis were higher than those of EUS-EG (96.2%, 83.3%, 81.8%, and 0.96 vs. 94.6%, 75%, 72.7%, and 0.8958). When the pathological stage was ≥ S2, the sensitivity, specificity, accuracy, and AUROC values of EUS-EG were higher than those of TUS-TE (100%, 87.5%, 88.9%, and 0.97 vs. 100%, 83.3%, 88.9%, and 0.94). Conclusions: There is a superior correlation between EUS-EG combined with SR and the pathological stage of liver fibrosis, compared to TUS-TE, and it has the same or even higher diagnostic efficacy as TUS-TE. Larger prospective studies are needed to evaluate the clinical utility of this approach in the assessment of liver fibrosis.

Association of Blood NK Cell Phenotype with the Severity of Liver Fibrosis in Patients with Chronic Viral Hepatitis C with Genotype 1 or 3.

NK cells phenotype and functional state in different genotypes of chronic viral hepatitis C (CVHC), depending on liver fibrosis severity, have not been sufficiently studied, which limits the possibilities for the development of pathology therapy. The CVHC diagnosis was based on the EASL recommendations (2018). Clinical examination with liver elastometry was performed in 297 patients with genotype 1 and in 231 patients with genotype 3 CVHC. The blood NK cells phenotype was determined by flow cytometry in 74 individuals with genotype 1 and in 69 individuals with genotype 3 CVHC. The frequency of METAVIR liver fibrosis stages F3-F4 was 32.5% in individuals with genotype 3, and 20.5% in individuals with genotype 1 CVHC (p = 0.003). In patients with both genotype 1 and genotype 3 CVHC, a decrease in the total number of blood NK cells, CD56brightCD16+ NK cells and an increase in the proportion of CD56dimCD16+ NK cells, CD94+ and CD38 + CD73+ NK cells were registered in patients with fibrosis stage F3-F4 by METAVIR in comparison with persons with METAVIR fibrosis stage F0-F1. In patients with both genotype 1 and genotype 3 CVHC, an imbalance in the ratio between cytokine-producing and cytotoxic NK cells and an increase in the content of NK cells that express inhibitory molecules were determined in patients with severe liver fibrosis.

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.