Liver Disease Of Various Etiologies Research Articles

New concept in fatty liver diseases.

In 2023, the nonalcoholic fatty liver disease (NAFLD) Nomenclature Consensus group proposed a new name and concept for NAFLD/nonalcoholic steatohepatitis. The Japanese Society of Gastroenterology and the Japanese Society of Hepatology have accepted these new names and concepts. It was reported that the terms "nonalcoholic" and "fatty" are misleading and inappropriate, because NAFLD does not reflect the etiology. Thus, appropriate disease names are discussed, and new concepts are published. First, the concept of steatotic liver disease (SLD) was proposed to encompass fatty liver diseases of various etiologies, which are classified into five categories. The diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) included fatty liver with at least one of the five cardiometabolic risk factors (body mass index or waist diameter, blood glucose or glycated hemoglobin, blood pressure, triglycerides, and high-density lipoprotein cholesterol) and the same restriction of alcohol consumption as NAFLD. A new fatty liver category was described, MetALD, to represent the intermediate drinker group (patients with MASLD with high weekly alcohol intake [140-350g/week in women and 210-420g/week in men]). The other five categories are alcohol-associated liver disease, fatty liver with an identifiable specific cause, and other fatty livers of unknown cause. Nonalcoholic steatohepatitis is an important pathological concept (metabolic dysfunction-associated steatohepatitis); however, its definition, including hepatocellular balloon-like degeneration, needs to be reassessed. In Japan, we should use these names and criteria to manage SLD, including hepatocellular carcinoma, which is markedly increasing.

Comparison between models for detecting hepatocellular carcinoma in patients with chronic liver diseases of various etiologies: ASAP score versus GALAD score

BackgroundDiagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). MethodsA multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. ResultsAmong 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. ConclusionsDespite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

Сhanges in the composition of gut microbiota in patients with chronic hepatitis С, non-alcoholic fatty liver disease at different stages of liver disease: a review

INTRODUCTION. The human gut microbiota is a set of microorganisms that are in symbiosis with the host organism. The predominance of bacteria of Bacteroidetes, Firmicutes, Actinobacteria types is a characteristic feature of human gut microbiota. However, the composition of the gut microbiota is subject to change under the influence of a number of factors. The influence of the gut-liver axis on the pathogenesis of many chronic liver diseases of various etiologies, both infectious and metabolic, has been proven. At the same time, in the analyzed literature, the data on the relationship between the nature of GM changes and the stage of liver damage are quite controversial.&#x0D; OBJECTIVE. Updating and systematization of ideas about the nature of changes in the composition of intestinal microbiota in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) at different stages of the disease.&#x0D; MATERIALS AND METHODS. We analyzed the scientific literature on GM changes in chronic liver diseases with regard to their etiology and disease stage, in particular in chronic viral hepatitis C and NAFLD. The search was conducted in PubMed, Google Scholar, and eLIBRARY databases for 2000-2023 using the following keywords: gut microbiota; microbiota in hepatitis C; microbiota in NAFLD; microbiota in liver fibrosis; liver fibrosis progression. Sixty scientific articles were analyzed and 42 sources were selected, of which more than 60% were published within the last five years.&#x0D; RESULTS. This review presents the results of original studies describing the main taxonomic differences between the microbiomes of healthy individuals and patients with CHC complicated by the formation of liver cirrhosis and hepatocellular carcinoma (HCC). Thus, patients with viral cirrhosis showed impoverishment of intestinal commensals Lachnospiraceae and Ruminococcaceae and significant enrichment of Streptococcaceae, Lactobacillaceae and Enterobacteriaceae. In patients with non-alcoholic steatohepatitis (NASH) and FII, enrichment of GM Phylum Bacteroides and Proteobacteria, Families Lachnospiraceae and Enterobacteriaceae, Genera Blautia and Escherichia, with a concomitant decrease of Prevotella was detected.&#x0D; DISCUSSION. The analysis of GM taxonomic units in the previously described studies did not reveal significant differences depending on the etiology of the underlying disease. However, a decrease in the representative of the phylum Firmicutes - Ruminococcaceae was observed in CHC in contrast to NAFLD. A more distinct relationship can be observed in the changes of intestinal microbiota in F(III-IV) irrespective of etiology. Thus, in advanced liver fibrosis and cirrhosis of both CHC and NAFLD etiologies, enrichment of GM has been described due to an increase in phylum Proteobacteria, in particular the genus Escherichia and phylum Firmicutes (Blautia, Veillonellaceae). In the studies analyzed, at F(III-IV), an enrichment of the microbiota is observed due to an increase in the phylum Bacteroidetes. Regarding the genus Prevotella, contradictory results were found. In addition, there are ambiguous data regarding the genera Lactobacillus, Ruminococcaceae and Bifidobacteria.&#x0D; CONCLUSION. Based on the results of the literature review, we obtained contradictory data on GM composition in patients with CHC and NAFLD. This may be due to the size of samples, heterogeneity of initial data during the selection of patients in the study. The relationship between the composition of microbiota and persistent inflammatory process, expressed liver fibrosis is observed. GM reflects not only functional disorders in chronic liver diseases of various etiologies, but can also serve as a diagnostic indicator of their progression.

Antifibrotic Efficacy of a New Phytocomposition of Essential Phospholipids with Glycyrrhizic Acid, Ecdysterone, Lycopene and Proanthacyanidin in Experimental Severe Chronic Hepatitis Compared with Phosphogliv

Since the prevalence of acute and especially severe chronic liver diseases of various etiologies increases from year to year, this pathology is recognized as the main burden on health worldwide. Currently, it has been established that the use of drugs based on essential phospholipids and plant origin with antioxidant and hepatoprotective activity is very effective in the prevention and treatment of liver diseases. In this regard, we studied under experimental conditions the effect of phytocomposition of soy lecithin, glycyrrhizic acid, lycopene and ecdysterone (conditional name hepalipin) and proanthacyanidin (conditional name yantacin) isolated from the plant Alhagi pseudalhagi on cytolytic-cholestatic liver damage, as well as on the development of fibrosis. In this study, we evaluated the hepatoprotective and antifibrotic effects of a new combination called Hepatocin obtained in a 1:1 ratio (100 mg/kg of Hepalipin and 100 mg/kg of Yantacin). All the studies conducted were conducted on adult nonlinear rats, while the experimental animals were divided into a control group infected with heliotrin, a substance with hepatotoxic action, a group receiving hepatocin, and an intact group that was not infected with heliotrin at the same time. In the conducted studies, hepatocin significantly inhibited the development of cytolytic-cholestatic liver damage, helped to maintain the functions of the liver synthesizing protein and glycogen, and when administered to experimental animals against the background of a chronic disease developing as a result of damage by heliotrin, it has an antioxidant effect. In addition, the use of hepatocin for more than two months in chronic liver damage or early stage fibrosis led to the restoration of serum enzymes of experimental animals, as well as regulators of cytochrome P450 and b5 fibrogenesis in liver tissues, PCNA, PDGF-BB to levels almost close to the initial (intact) values. Thus, in experimental conditions of chronic severe hepatitis or early stage fibrosis, hepatocin showed statistically significant advantages over Phosphogliv in terms of the intensity of hepatoprotective or antifibrotic action.

Validation of the albumin-bilirubin score for identifying decompensation risk in patients with compensated cirrhosis.

The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies. To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020. A total of 113 patients (91.9%) had Child A cirrhosis with a median model for end-stage liver disease (MELD) score of less than 9. Baseline clinical and laboratory variables and decompensation events were collected. The ALBI score was calculated and validated to classify decompensation risk into low-, middle-, and high-risk groups using three ALBI grade ranges (ALBI grade 1: ≤ -2.60; grade 2: > -2.60 but ≤ -1.39; grade 3: > -1.39). Decompensation events were defined as ascites development, variceal bleeding, or grade 3 or 4 hepatic encephalopathy. Among 123 cirrhotic patients enrolled, 13.8% (n = 17) developed decompensating events at a median time of 25 [95% confidence interval (CI): 17-31] mo. Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events [-2.768 (-2.956 to -2.453) vs -2.007 (-2.533 to -1.537); P = 0.01]. Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve (tAUC) of 0.86 (95%CI: 0.78-0.92), which was significantly better than that of ALBI-Fibrosis-4 (ALBI-FIB4) score (tAUC = 0.77), MELD score (tAUC = 0.66), Child-Pugh score (tAUC = 0.65), and FIB-4 score (tAUC = 0.48) (P < 0.05 for all). The 3-year cumulative incidence of decompensation was 3.1%, 22.6%, and 50% in the low-, middle-, and high-risk groups, respectively (P < 0.001). The odds ratio for decompensation in patients of the high-risk group was 23.33 (95%CI: 3.88-140.12, P = 0.001). The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.

Diagnostic accuracy of computer morphometry for steatosis and fibrosis assessment in patients with chronic liver disease of various etiologies

Background. Accurate assessment of the fibrosis stage is crucial for effective treatment. Histological examination, the primary method used for assessing liver fibrosis, has certain limitations due to variation within each stage. Computer morphometry offers an objective and quantitative approach to complement histological analysis, providing additional diagnostic information. The purpose of this study was to analyze the computer morphometry data in patients with chronic liver diseases (CLD) of different etiologies and determine their diagnostic accuracy for liver fibrosis diagnosis. Materials and methods. Seventy-five patients with CLD, namely 24 with non-alcoholic fatty liver disease (NAFLD), 8 with alcoholic liver disease (ALD), 1 with toxic hepatitis, and 42 with chronic hepatitis C (CHC), were included in the study. Percutaneous liver biopsy was performed under ultrasound guidance using a semi-automatic needle Colt Shot 16 G. The severity of fibrosis was assessed using the Metavir scale. For computer morphometry, biopsies were photographed and evaluated using the ImageJ 1.45S program (National Institutes of Health, USA). The computerized fibrosis index (CFI), steatosis index, and the number of apoptotic cells in 5 consecutive high-power fields were calculated. Receiver operating characteristic analysis was performed for CFI diagnostic accuracy assessment. Results. Advanced liver fibrosis (F3-F4) was diagnosed in 62.5 % of ALD cases and 31.0 % of CHC. The highest CFI was found in ALD, it exceeded the level of NAFLD and CHC patients by 3.3 (p &lt; 0.01) and 2 times (p &lt; 0.05), respectively. At the same time, people with NAFLD had the highest steatosis index (0.36 ± 0.11), which was 1.7 times higher (p &lt; 0.05) than in ALD and CHC. Moreover, CFI correlated with the fibrosis stage (r = 0.71, p &lt; 0.05). Stage I of liver fibrosis according to the Metavir scale is characterized by CFI up to 0.040, stage II — 0.041–0.130, stage III — 0.131–0.219, and stage IV — more than 0.220. CFI cut-off value was 0.017, which confirms the presence of liver fibrosis in patients with chronic liver diseases regardless of the etiology (sensitivity — 85.2 %, specificity — 100.0 %). Conclusions. Computer morphometry significantly improves the accuracy and reliability of histological examination, and allows to objectify morphological assessment of liver steatosis and fibrosis and to ensure long-term storage of the results.

Application of non-invasive methods of assessment of steatosis and fibrosis in chronic diffuse liver diseases of various etiologies

Background. The aim of the study is to analyze the parameters of liver steatosis and fibrosis based on shear wave elastography (SWE) and steatometry data in patients with chronic diffuse liver diseases, taking into account the etiological factor, and determine the diagnostic accuracy of SWE in the diagnosis of liver fibrosis. ­Materials and methods. Three hundred and sixty-four patients with chronic diffuse liver disease aged (48.00 ± 1.84) years were examined, 159 (43.7 %) were male, and 205 (56.3 %) female. The patients were divided into groups: 108 people with non-alcoholic fatty liver disease (NAFLD), 143 with chronic hepatitis C (HCV), 56 with alcoholic liver disease (ALD), and 57 with drug-induced toxic hepatitis. In all patients, SWE and steatometry were performed by Soneus P7 device (Kharkiv, Ukraine) with the liver stiffness and ultrasound attenuation coefficient measurement. Results. According to SWE data, 270 (74.2 %) patients with chronic liver disease had fibrotic changes in the liver. A significant increase in liver stiffness by 1.9 times (p &lt; 0.05) according to Young’s modulus was found in HCV patients and by 1.4 times (p &lt; 0.05) in ALD patients compared to the control group, by 1.7 (p &lt; 0.05) and 1.3 times (p &lt; 0.05), respectively, compared to the group of patients with NAFLD. According to steatometry data, an increase in ultrasound attenuation coefficient by 30.2 % (p &lt; 0.05) in patients with NAFLD, by 27.5 % (p &lt; 0.05) in those with ALD and by 22 % (p &lt; 0.05) in people with toxic hepatitis was found compared to the control group. In patients with liver fibrosis, the median liver stiffness was 6.70 kPa (6.35, 7.56), while in those without liver fibrosis, this parameter was 1.2 times lower (p &lt; 0.01). Histological evaluation of liver samples obtained through percutaneous biopsy in 75 patients with chronic liver disease demonstrated the absence of fibrosis in 14 (18.7 %) cases. According to the results of the ROC analysis, the cut-off value of the liver stiffness determined by SWE was 5.79 kPa, confirming the presence of liver fibrosis in patients with chronic liver disease regardless of etiology (AUC = 0.901, p &lt; 0.001). Conclusions. The liver stiffness determined by SWE in HCV and ALD patients was higher than in NAFLD patients (p &lt; 0.05), as well as the frequency of F3–4 stages of liver fibrosis (p &lt; 0.05). The threshold value of the liver stiffness for liver fibrosis diagnosis in chronic liver disease regardless of etiology was 5.79 kPa (sensitivity 100.0 %, specificity 85.7 %), which allows the family doctor to form a risk group of patients who needed dynamic monitoring with a further investigation of the etiological factor of liver fibrosis.

Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis

Fibroblast activation protein (FAP) is expressed on activated fibroblast. Its role in fibrosis and desmoplasia is controversial, and data on pharmacological FAP inhibition are lacking. We aimed to better define the role of FAP in liver fibrosis invivo and invitro. FAP expression was analyzed in mice and patients with fibrotic liver diseases of various etiologies. Fibrotic mice received a specific FAP inhibitor (FAPi) at 2 doses orally for 2 weeks during parenchymal fibrosis progression (6 weeks of carbon tetrachloride) and regression (2 weeks off carbon tetrachloride), and with biliary fibrosis (Mdr2-/-). Recombinant FAP was added to (co-)cultures of hepatic stellate cells (HSC), fibroblasts, and macrophages. Fibrosis- and inflammation-related parameters were determined biochemically, by quantitative immunohistochemistry, polymerase chain reaction, and transcriptomics. FAP+ fibroblasts/HSCs were α-smooth muscle actin (α-SMA)-negative and located at interfaces of fibrotic septa next to macrophages in murine and human livers. In parenchymal fibrosis, FAPi reduced collagen area, liver collagen content, α-SMA+ myofibroblasts, M2-type macrophages, serum alanine transaminase and aspartate aminotransferase, key fibrogenesis-related transcripts, and increased hepatocyte proliferation 10-fold. During regression, FAP was suppressed, and FAPi was ineffective. FAPi less potently inhibited biliary fibrosis. Invitro, FAP small interfering RNA reduced HSC α-SMA expression and collagen production, and FAPi suppressed their activation and proliferation. Compared with untreated macrophages, FAPi regulated macrophage profibrogenic activation and transcriptome, and their conditioned medium attenuated HSC activation, which was increased with addition of recombinant FAP. Pharmacological FAP inhibition attenuates inflammation-predominant liver fibrosis. FAP is expressed on subsets of activated fibroblasts/HSC and promotes both macrophage and HSC profibrogenic activity in liver fibrosis.

Gut-liver axis: physeology through the prism of the microbiome

This paper presents a brief historical description of the evolution of views on the development of the concept of the gut liver axis functioning and its physiological aspects. The “new virtual human organ” physiological fundamentals and their role in the pathogenesis of chronic liver diseases, including late post-transplant period, are described and discussed.Based on own experience, results of a new generation sequencing describing the characteristics of the microbiome palette in patients suffering from chronic liver diseases of various etiologies are presented. Personal study was based on 12 patients suffering chronic liver disease, who were examined before and after liver transplantation. The obtained results indicate the importance of the intestinal microbiome in the natural process of recovery after liver transplantation.

Comparison of Shearwave Elastography and Apri Score for Liver Fibrosis in Patients of Chronic Liver Disease

Chronic liver disease of various etiologies is the major causes of mortality and morbidity globally. Liver biopsy is the most accurate and oldest method to determine the chronic liver disease progression and for liver histology. Shear wave elastography (SWE) is a new non-invasive technique that applies localized mechanical compression to the soft tissue with focused ultrasonography and obtains tension images showing the tissue response. Aspartate aminotransferase to platelets ratio (APRI) on the other hand is relatively less expensive test and can be done on outpatient basis. Objective: To find the relation between APRI aspartate and SWE for detection of liver fibrosis in patients with chronic liver disease. Study Design: A Cross Sectional study Setting: Medical Unit-1 Lahore General Hospital Lahore and Department of Gastroenterology &amp; Hepatology, Doctors Hospital and Medical Centre, Lahore. Study Duration: From July 2019 to December 2021. Methods: 180 patients met the criteria of inclusion were included, the blood samples were obtained and sent to the hospital laboratory for valuation of AST and Platelets. Reports were evaluated, APRI was calculated and patients were labeled as negative or positive. Then all patients underwent SWE by a senior radiologist for assessment of liver fibrosis. Patients were labeled as negative or positive. Agreement was noted, all data was entered on a specifically designed proforma, and data were analyzed and entered in SPSS version 20 statistical method. Agreement was calculated by generating 2x2 tables between APRI and SWE findings. Kappa statistics was calculated to measure the strength and significance of agreement. P-value ≤0.05 was taken as significant. Results: In this study, the patients mean age was 46.39 ± 16.02years. There were 119 (66.11%) males and 61 (33.89%) females. The mean BMI of patients was 24.70 ± 5.23kg/m2. The mean duration of CLD was 5.50 ± 2.672 years. The mean AST of patients was 73.98 ± 60.23IU/L while mean platelet count was 200.65 ± 92.47/cm3. The mean APRI was 1.41 ± 1.20. The mean SWE was 18.32 ± 23.85kPa. The APRI and SWE agreed on 73 (54.9%) cases and showed 66.7% agreement between them for diagnosis of liver fibrosis (p&lt;0.05). Conclusion: Thus, APRI and SWE showed strong agreement but further trials are required to confirm the evidence. Keywords: Agreement, APRI, Aspartate aminotransferase to platelets ratio, SWE, Shear-wave elastography, Chronic liver disease and Liver fibrosis.

Клиническое значение определения уровня аммония в диагностике печеночной энцефалопатии у пациентов с заболеваниями печени

The paper presents the results of a survey of 35 patients with liver diseases of various etiologies hospitalized in Gastroenterology Department of Republic Clinical Hospital in Kazan. The patients were distributed according to etiology: liver cirrhosis — 28 (80%), acute hepatitis — 5 (14.3%), after liver transplantation — 2 (5.7%). The patients underwent a complete clinical examination, and psychometric tests were additionally used to assess the stage of hepatic encephalopathy. Blood ammonium level was determined in all patients using the PocketChem BA PA-4140 blood ammonia meter. Connect-the-Numbers Test revealed encephalopathy in 97.1% of patients with liver diseases, while latent hepatic encephalopathy was observed in 47% cases. According to the West-Haven criteria, hepatic encephalopathy was diagnosed in 80% patients. Hyperammonemia was determined in 80% of patients with liver diseases. There was some relationship between the ammonium level and the stage of hepatic encephalopathy.

Неселективные β-блокаторы при циррозе печени: эффект «терапевтического окна» и выживаемость пациентов

Objectives of the study: to analyze the survival rate of patients who received and did not receive various drugs of the class of non-selective beta-blockers (NSBB) while waiting for liver transplantation (LT) on the waiting list for liver transplantation (WLLT), depending on the presence or absence of a "therapeutic window" for the appointment of NSBB; to determine risk factors for death when prescribing various representatives of the NSBB class in patients with refractory ascites (RA). Material and methods. The retrospective case-control study was conducted. The "case" group included 278 adult patients with decompensated liver diseases of various etiologies included in the WLLT, who were treated with NSBB while waiting for LT. The "control" group consisted of 72 patients with decompensated liver diseases of various etiologies included in the WLLT, who did not receive NSBB therapy during the waiting period for LT. For the subsequent analysis, the group of patients receiving NSBB (n = 278) was divided into two subgroups: with the presence of a "therapeutic window" (n = 175), and without it (n = 103). The survival rate of patients was determined by the Kaplan - Mayer method. Predictors of mortality of patients receiving NSBB in the absence of a" therapeutic window "for NSBB were determined using the Cox proportional hazards model in the groups of patients with RA (n = 103) and non-RA (n = 175). Results. The survival rate of patients receiving NSBB in the presence of a" therapeutic window "for NSBB is significantly higher than in the group of patients receiving NSBB in WLLP while waiting for LT in the absence of a" therapeutic window " for NSBB (Log-Rank &lt; 0.0001). The risk of death in patients with RA treated with NSBB was significantly higher than in patients with non-RA (HR = 2.285; CI 1.237 4.220; p = 0.008). The risk of death for patients treated with propranol was significantly different from carvedilol (HR = 2,152 and HR = 0.765; p = 0.042, respectively). Conclusion. The results of the study confirmed the hypothesis that there is a "therapeutic window" for NSBB when they are prescribed to patients with decompensated cirrhosis of the liver and included in the WLLP. The use of NSBB contributes to an increase in the mortality of patients with RA, regardless of the type of drug, in the case when the "closed therapeutic window" phase develops. In order to reduce the mortality of patients waiting for LT for several years due to acute organ deficiency, doctors who lead patients to WLLT should assess the risk and benefit of using NSBB

Role of Ultrasonic Elastography in the Evaluation of Fibrosis in Children with Chronic Liver Disease in Comparison to Liver Biopsy

Background: Chronic liver illnesses can be caused by a variety of factors, including metabolic, genetic, drug-induced, inflammatory, structural, dietary, and immunological factors. Even with Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI), liver fibrosis makes diagnostic imaging difficult in chronic liver injury. Percutaneous liver biopsy is the gold standard for diagnosing, grading, and monitoring liver fibrosis in children, but it is painful, invasive, requires heavy sedation, and has numerous complications such as bleeding. Objectives: The aim of the current work was to assess and measure liver stiffness in children with chronic liver disease using real-time elastography (RTE), compare the results to histopathological findings obtained after performing a percutaneous liver biopsy, and investigate the availability of noninvasive safe liver elastography as a future replacement for this invasive tool in the evaluation and grading of liver fibrosis. Patients and methods: This hospital-based cross-sectional comparative study included a total of 30 individuals with chronic liver disease of various etiologies with age ranged from 4-16 years, attending at Department of Pediatric, Sohag University Hospitals. This study was conducted between January 2017 to December 2019. A control group of ten healthy people was also included in the investigation. Results: The degree of liver stiffness measured by the last ultrasonic elastography was greater in the patient group than in the control group, with a statistically significant difference between the two groups. Except for F0-F1 and F3-F4, there was a substantial relationship between fibrosis stage and liver stiffness assessment by sonoelastography, where the difference was significant between every two individual groups. There was a strong link between biopsy diagnosis and liver stiffness measurement. Conclusion: It could be concluded that in adults, ultrasonic elastography is a well-established approach for assessing liver fibrosis. The utility of elastography in the follow-up of children with chronic liver disease might be increased.

ИЗМЕНЕНИЯ СЫВОРОТОЧНЫХ КОНЦЕНТРАЦИЙ ПРЯМЫХ БИОМАРКЕРОВ ФИБРОЗИРОВАНИЯ ПРИ ХРОНИЧЕСКИХ БОЛЕЗНЯХ ПЕЧЕНИ У ДЕТЕЙ

It is assumed that serum concentrations of type I, III, IV collagen (Col I, Col III, Col IV) and hyaluronic acid (HA) can provide informative evidence for the diagnosis of liver fibrosis (LF) using non-invasive procedures, however, there is insufficient data on the subject in paediatrics. Objectives: to study characteristics of changes in concentrations of Col I, Col III, Col IV and HA in blood serum in accordance with the stages of liver fibrosis in children. Materials and methods of research: a prospective study was carried out, which included 80 patients aged 5 to 17 years with chronic liver diseases of various etiologies, who underwent marginal resection of liver tissue under laparoscopic control, then a morphological study of the obtained biopsy was performed with determination of the stage of fibrosis on the METAVIR scale and the content of Col I, Col III, Col IV and HA in blood serum by the method of enzyme immunoassay. Results: the assessment of the content of K-I in the blood serum allows differentiating the stage F1 and F3 from F4 (p=0,025, p=0,006), Col IV – F1 from F2 (p=0,011), F3 (p=0,002) and F4 (p&lt;0,001), HA – F1 from F3 (p=0,041), and also F4 from F1 (p&lt;0,001), F2 (p&lt;0,001) and F3 (p&lt;0,001). There were no statistically significant differences in the content of Col III at different stages of LF (p=0,061). Statistically significant correlations of the histological stage of LF with changes in serological levels of Col I (ρ=–0,267, p=0,023), Col IV (ρ=0,409, p&lt;0,001), and HA (ρ=0,575, p&lt;0,001), and also the relationship between the concentrations of Col IV and HA (ρ=0,265, p=0,023). Conclusions: the correlations found in the histological phase of LF with changes in serological levels of Col I, Col IV and HA lead to the conclusion that fibrosis direct biomarkers are of diagnostic importance in determining the stage of LF, which is of great importance for practical medicine, especially in pediatrics.

Complex ultrasonography in the assessment of intrarenal hemodynamic impairments in patients with portal hypertension

Rationale. Hepatorenal syndrome is a threatening complication in patients with liver cirrhosis and portal hypertension. The occurrence of renal dysfunction associated with hepatorenal syndrome manifestations significantly affects the condition severity, the disease duration, and the survival time during the waiting period for liver transplantation.The study purpose was to investigate the potential of a complex ultrasonography examination in the assessment of intrarenal hemodynamic impairments in patients with various diffuse liver diseases.Material and methods. The ultrasound examination results of 167 patients were analyzed. The 1st group included 28 patients with confirmed diffuse liver diseases of viral etiology who did not have signs of cirrhosis formation, the 2nd group included 139 patients with liver cirrhosis due to diffuse liver diseases of various etiologies, and the 3-rd group included 137 patients who had previously been in the 2nd group in whom orthotopic liver transplantation was performed.Results. The study revealed a statistically significant increase in the incidence of secondary hemodynamic impairments in kidney function in patients with liver cirrhosis and no relationship of their severity and incidence to the disease etiology, and also to such markers of the portal hypertension severity as splenomegaly, ascites, and portal vein thrombosis.Conclusions. The resistive index measured on the renal arterial branches by Doppler ultrasound, has a certain predictive value in relation to hepatorenal syndrome in patients with liver cirrhosis of various origins. This also makes it possible to timely identify a group of patients at a high risk of developing severe renal dysfunction and to assess the efficacy of the treatment that has been given.

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

BackgroundThe rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies.ObjectiveThe primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories.MethodsRADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit.ResultsThis trial is currently open for recruitment. The anticipated completion date for the study is December 2020.ConclusionsThis randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies.Trial RegistrationClinicalTrials.gov NCT03289897 https://clinicaltrials.gov/ct2/show/NCT03289897International Registered Report Identifier (IRRID)DERR1-10.2196/19189

Asphervon-related increase of bile secretion as a preventive measure and therapeutic agent for heliotrin induced hepatitis in rats

Background: Considering the significant increase in the number of patients suffering from liver diseases of various etiologies, for example, viral, toxic, medicinal, alcoholic, and others, today, improving the quality and safety of pharmacotherapy of the hepatobiliary system diseases is an urgent problem of modern pharmacology and clinical hepatology. Aim and Objectives: The purpose of this study was to investigate the Asfervon related increase of bile secretion activity in rats with heliotrin-induced hepatitis. Materials and Methods: The experiments were carried out on outbred white rats, males, weigh 160–210 g. For studying the preventive effect of drugs, animals were injected orally in doses of 25, 50, and 100 mg/kg Asfervon, and Legalon – 100 mg/kg, before the administration of heliotrin for 2 days, and after the administration of heliotrin for the next 5 days. A model of acute toxic hepatitis was reproduced by a single injection of a freshly prepared aqueous solution of heliotrin at a dose of 250 mg/kg subcutaneously. Results: Animals who received Asfervon preventively at doses of 25, 50, and 100 mg/kg bile secretion decrease were less significant of 49.2, 17.2, and 20.3%, respectively. The preliminary administration of Asfervon increased the amount of excreted bile in comparison with the untreated group of animals by 38.3, 125.5, and 117.0%, respectively, at the indicated doses. Conclusions: Asfervon is a drug with a pronounced hepatoprotective activity, not inferior to the classic hepatoprotective medication Legalon. Asfervon promotes bile secretion in preventive and treatment experiments.

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post-liver transplant patient.

Liver biopsy is considered the gold standard method for diagnosing and staging liver disease, particularly in the post-liver transplant setting. Given the invasive nature of biopsy, alternate means for accurately assessing liver fibrosis and steatosis are preferred especially as the number of patients with fatty liver disease is increasing. Transient elastography has been validated as a useful tool for evaluation of liver fibrosis, as has controlled attenuation parameter index as a tool for assessing steatosis. It is a non-invasive, rapid, and highly reproducible approach to demonstrate the presence of fibrosis among non-transplant patients with chronic liver disease of various etiologies. However, it has not yet found wide acceptance in liver transplant recipients. There are few published studies evaluating the merits and applicability of transient elastography to assess allografts after liver transplantation. We review the published data on the use of transient elastography with concurrent controlled attenuation parameter in liver transplant recipients and recommend its greater use to follow allograft function over time.

Relationships between ultrasonic, immunological changes in the progression of liver steatosis and fibrosis in patients with chronic diffusive liver diseases of various etiologies

Objective. To determine the relationships between ultrasound and immunological changes in the progression of steatosis and liver fibrosis in patients with chronic diffuse liver diseases (CLD) of various etiologies.Materials and methods. We examined 120 patients with CLD. Patients were distributed according to the etiological factor of the development of steatosis and liver fibrosis: Group I – 24 patients with non-alcoholic fatty liver disease (NAFLD), ІІ – 37 patients with non-alcoholic steatohepatitis (NASH); Group III – 21 people with chronic viral hepatitis associated with the C virus (HCV). Group IV consisted of 18 patients with alcoholic liver disease (ALD), group V – 20 patients with toxic hepatitis (TG). Sonographic abdominal examination, ultrasound attenuation coefficient (UAC) and shear wave elastography (SWE) of the liver / spleen were performed. The content of cellular immunity parameters, the level of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), insulin and HOMA-IR were determined. A correlation analysis was made between ultrasound and immunological parameters in the examined patients.Results. In patients with CLD, changes in liver structure in the form of heterogenety were detected in 97 (80.8 %) (P &lt; 0.001). The maximum values of SWE of the liver were observed in patients with ALD (18.10 ± 2.68) kPa, minimal – with NAFLD. The stiffness of the spleen was highest in patients with ALD 24.09 ± 3.68 kPa. TNF-α was significantly higher than the control values with NASH by 11.6 times (P &lt; 0.05), HCV by 13.9 times (P &lt; 0.05), ALD by 9.4 times (P &lt; 0.05) and TG by 9.5 times (P &lt; 0.05). The concentration of IL-6 was 2.1 times higher (P &lt; 0.05) in patients with NASH and CHC, 2.5 times higher (P &lt; 0.05) in patients with TG. The TNF-α / IL-10 ratio was increased by 7.1 times (P &lt; 0.05) in patients with NAFLD, by 19.3 times (P &lt; 0.05) in patients with NASH, by 14.4 times (P &lt; 0.05) in patients with chronic hepatitis C, by 14.0 times (P &lt; 0.05) in patients with ALD and by 8.4 times (P &lt; 0.05) in patients with TG.When conducting a correlation analysis, it was revealed that in patients with NAFLD, the level of TNF-α had a positive relationship with the spleen stiffness (r = +0.601, P &lt; 0.01). In patients with HCV, the level of IL-6 was associated with spleen stiffness (r = +0.680, P &lt; 0.05), liver stiffness (r = +0.618, P &lt; 0.05) and the degree of fibrosis (according to METAVIR) (r = +0.573, P &lt; 0.01). In patients with ALD, an increase in liver stiffness is accompanied by a significant increase in the NOMA index (r= +0.843). In patients with TG, a negative relationship was found between the level of T-helper cells and stiffness of spleen (r = - 0.577, P &lt; 0.05) and liver (r = -0.522, P &lt; 0.05).Conclusion. The progression of liver steatosis is accompanied by a lack of cellular immunity and an increase in the level of pro-inflammatory cytokines. An increase in structural changes of the liver and spleen, as well as the increase in the degree of steatosis, is accompanied by activation of pro-inflammatory cytokines, depletion of the anti-inflammatory response and increased insulin resistance.

Hepatic metabolic adaptation in a murine model of glutathione deficiency

Glutathione (GSH), the most abundant cellular non-protein thiol, plays a pivotal role in hepatic defense mechanisms against oxidative damage. Despite a strong association between disrupted GSH homeostasis and liver diseases of various etiologies, it was shown that GSH-deficient glutamate-cysteine ligase modifier subunit (Gclm)-null mice are protected against fatty liver development induced by a variety of dietary and environmental insults. The biochemical mechanisms underpinning this protective phenotype have not been clearly defined. The purpose of the current study was to characterize the intrinsic metabolic signature in the livers from GSH deficient Gclm-null mice. Global profiling of hepatic polar metabolites revealed a spectrum of changes in amino acids and metabolites derived from fatty acids, glucose and nucleic acids due to the loss of GCLM. Overall, the observed low GSH-driven metabolic changes represent metabolic adaptations, including elevations in glutamate, aspartate, acetyl-CoA and gluconate, which are beneficial for the maintenance of cellular redox and metabolic homeostasis.