Diffuse Liver Disease Research Articles

Features of management of patients with liver diseases in the conditions of the COVID-19 pandemic

Liver dysfunction is common with COVID-19 infection, and the prevalence is higher in men as well as in the elderly. Manifestations of liver damage such as high aspartate aminotransferase and alanine aminotransferase activity, increased bilirubin levels, low albumin levels, and prolonged prothrombin time are associated with severe COVID-19 infection. Mortality in patients with diffuse liver diseases without cirrhosis with COVID-19 infection was 12 %, in the presence of liver cirrhosis up to 40%, decompensated liver cirrhosis up to 4363%. The mechanisms of liver damage in COVID-19 include direct hepatotoxicity and indirect liver damage (due to systemic inflammation with impaired immunity, sepsis, hypoxia, ischemia, coagulopathy, endotheliitis, right ventricular failure, worsening of the course of existing liver diseases, drug liver damage). Treatment of patients with diffuse liver diseases includes lifestyle and nutritional modification, the use of hepatoprotective drugs, and means of correcting the intestinal barrier (bibliography: 30 refs).

MR elastography in patients with suspected diffuse liver disease at 1.5T: Intraindividual comparison of gradient-recalled echo versus spin-echo echo-planar imaging sequences and investigation of potential confounding factors

PurposeTo compare liver stiffness (LS) in patients with suspected diffuse liver disease between gradient-recalled-echo magnetic resonance elastography (GRE-MRE) and different spin-echo echo-planar imaging (SE-EPI-MRE) sequences and to investigate confounding factors including fat, iron, age, and sex. MethodLS was measured at 1.5T using GRE-MRE, SE-EPI-MRE and short-TE-SE-EPI-MRE (hiSE-EPI-MRE) sequences and compared using Bland-Altman-plots together with concordance correlation coefficients (CCC). Success gradings were evaluated considering possible confounding factors. Results305 patients (225 male, 80 females, mean age 51.12 years) were included. 109/305 showed hepatic iron overload, 183 hepatic steatosis. The mean difference (bias) in stiffness values between GRE-MRE and SE-EPI-MRE/hiSE-EPI-MRE was 0.15/0.2 kPa (LOA: −0.72,0.41 kPa/-0.94,0.55 kPa), between SE-EPI-MRE and hiSE-EPI-MRE 0.04 kPa (LOA: −0.62,0.53 kPa). The CCC for agreement between stiffness values for GRE-MRE and SE-EPI-MRE was 0.94 (0.92–0.95), 0.89 (0.86–0.91) for hiSE-EPI-MRE and GRE-MRE and 0.94 (0.92–0.95) for SE-EPI-MRE and hiSE-EPI-MRE. Using GRE-MRE, 72/305 showed unusable results whereby all these patients had high iron levels (mean R2*=209.7 1/s). For SE-EPI-MRE and hiSE-EPI-MRE only 10/305 and 8/305 were inconclusive respectively, corresponding to a significantly higher iron load (mean R2*= 549.2 1/s for SE-EPI-MRE and 570.7 1/s for hiSE-EPI-MRE). Concerning fat, age or sex no significant influence on success was observed for all sequences. ConclusionsGood agreement of LS values was observed between GRE-MRE and SE-EPI-MRE sequences. The number of successful exams, however, was considerably lower for GRE-MRE, mainly due to iron content.Study reference number: AN5093.

Non-Invasive Technique to Classify Cirrhotic Liver Using Texture Parameters

Texture analysis is an outstanding and fundamental task being used in many medical and computer vision applications. Malfunctioning of the human liver upsets almost all the other organs in the human body. Usually liver infections are difficult to analyze because of inconclusive side effects. More often, the liver could be confronting critically but it may not be significantly unveiled. The main objective of this research work is to provide some standard liver diagnostic measures to minimize the risk factors, as better diagnosis is essential requirement in radiology. The Computerized Tomography (CT) contributes important information to the clinical evaluation of diffuse liver diseases. Haralick texture parameters have been computed on the selected Regions of Interest. B11 is used for discrimination and interpretation of normal and cirrhotic liver diseases. Normal and diseased Liver CT images were collected from Bahawal Victoria Hospital. Normal and cirrhotic liver samples of clinically verified patients were obtained and total 900 Regions of Interest (ROIs) were taken from the selected data. Training of the classes was next step after texture parameter computation. In this work, supervised classification method was used to classify the selected images. In this way, the classes were trained in a supervised manner. The maximum accuracy obtained during this research work was 100%, linear dimensionality was 1 and the linear separability was 0.99%. Results of this research work suggested that texture parameters have high degree of reliability to automatically discriminate similar tissue textures, when regions are obvious. This framework separates benign from malignant liver tumors with moderately high precision and is therefore link up the psychophysics with machine vision to outline, recognize, categorize or discriminate textures.

Glutathione-S-transferases genes-promising predictors of hepatic dysfunction.

One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.

EUS-Guided versus Percutaneous Image-Guided Liver Biopsy: A Battle for Supremacy!

AbstractLiver biopsy has been the gold standard investigation for diagnosing and staging liver diseases. Image-guided percutaneous liver biopsy is a time-tested technique for obtaining the liver tissue in diffuse liver diseases. However, it is contraindicated in patients with ascites, altered mental status, skin infections, coagulopathy, and thrombocytopenia. It is associated with adverse events including postprocedure pain, bleeding, and pneumothorax. Transvenous liver biopsy can be performed in most cases with these contraindications, but it is an expensive technique and has its own inherent risks. Endoscopic ultrasound (EUS)-guided liver biopsy (EUS-LB) is a relatively new technique that has shown promising results and seems to have a potential of replacing percutaneous liver biopsy. In this news and views, we discuss the results of a randomized controlled trial (RCT) comparing EUS-guided and percutaneous techniques of liver biopsy. This RCT reported that percutaneous technique is superior in terms of diagnostic adequacy and total expenditure without any significant adverse effects compared with EUS-LB. EUS-LB is a promising technique that needs to be further explored in terms of appropriate situations in which it can be preferred over percutaneous or transvenous routes.

The Effect of Diffuse Liver Diseases on the Occurrence of Liver Metastases in Cancer Patients: A Systematic Review and Meta-Analysis.

Simple SummaryDiffuse liver diseases have a high incidence among the general population and even higher in patients with a solid cancer. Since many patients with a solid tumor die of liver metastases, the aim of this systematic review of the literature was to explore the correlation between diffuse liver diseases and the risk of having liver metastases at diagnosis or during follow-up. To summarize the results of included studies, a meta-analysis was also conducted. The results of our systematic review should encourage the research community to further investigate the complex relationship between the liver’s microscopic environment and metastases, which may also affect prognosis and response to therapy.This systematic review with meta-analysis aimed to assess the effect of diffuse liver diseases (DLD) on the risk of synchronous (S-) or metachronous (M-) liver metastases (LMs) in patients with solid neoplasms. Relevant databases were searched for systematic reviews and cross-sectional or cohort studies published since 1990 comparing the risk of LMs in patients with and without DLD (steatosis, viral hepatitis, cirrhosis, fibrosis) in non-liver solid cancer patients. Outcomes were prevalence of S-LMs, cumulative risk of M-LMs and LM-free survival. Risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale. We report the pooled relative risks (RR) for S-LMs and hazard ratios (HR) for M-LMs. Subgroup analyses included DLD, primary site and continent. Nineteen studies were included (n = 37,591 patients), the majority on colorectal cancer. ROB appraisal results were mixed. Patients with DLD had a lower risk of S-LMs (RR 0.50, 95% CI 0.34–0.76), with a higher effect for cirrhosis and a slightly higher risk of M-LMs (HR 1.11 95% CI, 1.03–1.19), despite a lower risk of M-LMs in patients with vs without viral hepatitis (HR 0.57, 95% CI 0.40–0.82). There may have been a publication bias in favor of studies reporting a lower risk for patients with DLD. DLD are protective against S-LMs and slightly protective against M-LMs for viral hepatitis only.

What does liver elastography measure? Technical aspects and methodology.

Elastography can be thought as an extension of the ancient technique of palpation. After giving a short introduction to the history of elastography, the different technologies that are nowadays available and the physics behind them, the article focuses on the assessment of liver stiffness in patients with diffuse liver disease using shear wave elastography (SWE). Practical advices on how to perform the SWE techniques and on the factors that should be considered for a correct interpretation of the results are given. This paper aimed to provide a practical guide for beginners and advanced clinical users to better understand technical aspects, methodologies and terminology.

Features Of Anemia In Patients With Chronic Liver Diseases

The features of the epidemiology, clinical picture, diagnosis and treatment of chronic diffuse liver diseases in combination with anemia are considered according to the literature on this problem. It has been shown that anemia aggravates the course, causes progression and worsens the prognosis of chronic diffuse liver diseases. The incidence of anemia in chronic diffuse liver diseases reaches 80%. Disclosure of the mechanisms of anemia in chronic diffuse liver diseases is necessary for timely correction and prevention of the progression of both pathological changes in red blood and underlying liver disease.

Role of inflammation and iron exchange disorders in progression of liver cirrosis

Objective. To assess the role of the main pathogenetically significant molecules, including tumor necrosis factor alpha (TNF-) and transferrin, as an inflammatory protein, in the progression of chronic diffuse liver diseases (CDLD).
 Material and methods. The study involved 86 patients with cirrhosis of the liver (LC) of viral, alcoholic and mixed etiology. Inflammatory parameters were studied, including tumor necrosis factor alpha (TNF-), indicators of iron metabolism, -fetoprotein (AFP), vasculoendothelial growth factor (VEGF), and functional liver biochemical tests. The control group consisted of 70 persons.
 Results. It was revealed that the LC severity class is interrelated with the clinical manifestations of the disease, the severity of biochemical syndromes as well as a significant increase in the concentration of -globulins, CRP, the amount of TNF- up to 3.5 (2.64.7) pg/ ml (p 0.001) and ferritin up to 325.8 (209; 401) ng / ml (p 0.001) compared to the control group. An increase in TNF- and ferritin as inflammatory protein in LC confirms the growth of the activity of inflammation in the liver and correlates with other parameters involved in the pathogenesis of LC: with VEGF, as a marker of endothelial dysfunction, which is involved in the activation of fibrosis and neoangiogenesis, and AFP, reflecting regeneration processes in the liver.
 Conclusions. The progression of liver damage in cirrhosis is based primarily on the secondary inflammation caused by portal hypertension with the entry of intestinal antigens and toxins into the central bloodstream. At the same time, the perverse circle of the development of the disease is closed.

Liver Fibrosis - Modern Methods of Diagnostics and Drug Correction

Liver fibrosis is a local or diffuse increase in the amount of connective tissue, extracellular matrix (collagen fibrous tissue in the perisinusoidal space) and the main pathway for the progression of chronic diffuse liver diseases. In the early stages of fibrosis, clinical manifestations are absent, and only a histological examination of a biopsy specimen reveals an excessive accumulation of connective tissue. In the future, fibrosis leads to the formation of nodes of regenerates, vascular anastomoses - to the formation of cirrhosis of the liver

Liver magnetic resonance imaging: how we do it.

Magnetic resonance imaging is used for evaluating focal liver lesions, hepatic vascular diseases, biliary diseases and diffuse liver diseases in children. MRI examinations take a long time, often requiring sedation or anesthesia in smaller children. This makes it essential to understand the concepts and technique necessary to obtain an optimal examination for answering the clinical question while minimizing the need for sedation/anesthesia. We discuss key concepts including appropriate sequence selection, choice of contrast media, dynamic imaging, phases of contrast enhancement and protocol organization.

Features of iron homeostasis in patients with steatohepatitis of alcoholic and non-alcoholic etiology and its correlation with the intensity of oxidative stress and apoptosis

Features of iron homeostasis in patients with steatohepatitis of alcoholic and non-alcoholic etiology and its correlation with the intensity of oxidative stress and apoptosis

Precise whole liver automatic segmentation and quantification of PDFF and R2* on MR images.

To automate the segmentation of whole liver parenchyma on multi-echo chemical shift encoded (MECSE) MR examinations using convolutional neural networks (CNNs) to seamlessly quantify precise organ-related imaging biomarkers such as the fat fraction and iron load. A retrospective multicenter collection of 183 MECSE liver MR examinations was conducted. An encoder-decoder CNN was trained (107 studies) following a 5-fold cross-validation strategy to improve the model performance and ensure lack of overfitting. Proton density fat fraction (PDFF) and R2* were quantified on both manual and CNN segmentation masks. Different metrics were used to evaluate the CNN performance over both unseen internal (46 studies) and external (29 studies) validation datasets to analyze reproducibility. The internal test showed excellent results for the automatic segmentation with a dice coefficient (DC) of 0.93 ± 0.03 and high correlation between the quantification done with the predicted mask and the manual segmentation (rPDFF = 1 and rR2* = 1; p values < 0.001). The external validation was also excellent with a different vendor but the same magnetic field strength, proving the generalization of the model to other manufacturers with DC of 0.94 ± 0.02. Results were lower for the 1.5-T MR same vendor scanner with DC of 0.87 ± 0.06. Both external validations showed high correlation in the quantification (rPDFF = 1 and rR2* = 1; p values < 0.001). In both internal and external validation datasets, the relative error for the PDFF and R2* quantification was below 4% and 1% respectively. Liver parenchyma can be accurately segmented with CNN in a vendor-neutral virtual approach, allowing to obtain reproducible automatic whole organ virtual biopsies. • Whole liver parenchyma can be automatically segmented using convolutional neural networks. • Deep learning allows the creation of automatic pipelines for the precise quantification of liver-related imaging biomarkers such as PDFF and R2*. • MR "virtual biopsy" can become a fast and automatic procedure for the assessment of chronic diffuse liver diseases in clinical practice.

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.

Pain assessment of ultrasound-guided liver biopsy for diffuse parenchymal diseases: a randomized trial comparing intercostal and subcostal techniques

Objectives: Percutaneous liver biopsy is widely used in diffuse liver parenchymal diseases. Comparison of the severity of pain is not properly studied. In this randomized study, pain intensity between the intercostal and subcostal techniques of US-guided Tru-Cut liver biopsy in diffuse liver diseases was compared. Methods: Between March 2016 and May 2017, all potential study participants referred to the interventional radiology department for ultrasound-guided liver biopsy (n = 245), were assessed for enrollment. The pain intensity at 0, 2, and 4 h post-procedure was compared in two groups using a Numeric Rating Scale (NRS). Premedication was not used. After applying local anesthesia under US-guidance, 18-G automatic biopsy needle free-hand US-guided biopsy was performed. Results: Immediately after the biopsy (p = 0.0024), and at the 2nd hour (p = 0.0298), NRS of the subcostal group was significantly less than the intercostal group. Furthermore, the need for oral (p = 0.0492) or intramuscular (p = 0.0094) analgesics after the biopsy in the subcostal group was significantly less than the intercostal group. At the evaluation of both groups together, 55.62% of the patients had a mild and 27.22% had a moderate pain score. NRS score decreased with time in each group. Conclusions: The pain intensity and the need for analgesics were less in the subcostal biopsies. Since intense pain and anxiety may be the cause of loss of the patients after the first biopsy, a subcostal biopsy could be preferred primarily.

Introduction to Imaging of Focal Liver Lesions and Diffuse Liver Disease

Introduction to Imaging of Focal Liver Lesions and Diffuse Liver Disease

Patterns of liver disease formation in victims of the Chornobyl nuclear power plant accident

The aim of the study is to determine the mechanisms for the formation and progressivity of chronic diffuse liver diseases in victims of the Chornobyl Nuclear Power Plant accident with the development of a diagnosis criteria for fibrous changes in this pathology. The materials were the results of examination and treatment in the clinic of the State Institution "NRCRM of the NAMS of Ukraine" of victims of the Chornobyl Nuclear Power Plant accident, 57 of which, according to the criteria for switching on and off, were assigned to the main group. The research methods were: general clinical examination, instrumental studies (ultrasound diagnostics of abdominal organs), biochemical, medical statistics, analytical. According to the results of the study, it was proved that in the victims of the Chornobyl Nuclear Power Plant accident, the main liver pathology was non-alcoholic fatty liver disease. It has been shown that in patients affected by the Chernobyl disaster, NAFLD develops a pronounced violation of fat metabolism with a reliable decrease in cholesterol and beta-lipoproteins in cirrhosis – a sign of a long-term course of the disease, accompanied not only by the development of fibrosis, but also by a fatty rebirth of liver tissue with low cholesterol and beta-lipoproteins; this can be considered a marker of cirrhosis in the Chornobyl accident clean-up personnel with NAFLD.

Contribution of changes in iron metabolism in pathogenesis of chronic diffuse liver diseases

Objective. To assess the role of iron metabolism changes in the pathogenesis of chronic diffuse liver diseases (CDLD). Assessment of the hepatic fibrosis progression and the most significant factors, influencing it, is still an actual target of modern medicine. A certain interest from the point of view of complex approach to studying the mechanism of development and progression of fibrosis is the determination of serum markers of iron metabolism.&#x0D; Materials and methods. The study included 170 patients with CDLD: 150 with chronic viral hepatitis C and 20 with alcohol hepatic cirrhosis (AHC). Iron metabolism indices and functional hepatic biochemical tests were studied. Expression of hepatic fibrosis in hepatitis was estimated by means of the liver density index with the scale METAVIR using the data of ultrasound elastography (Fibroscan 502, Echosens, France); fibrosis development rate was calculated with T. Poynard method. The control group enclosed 100 persons.&#x0D; Results. There was revealed a significant elevation of the blood ferritin concentration among patients with chronic hepatitis up to 107.9 [31; 250] ng/ml compared with the control (22.0 [11; 33] ng/ml) and to 325.8 [209; 401] ng/ml in patients with AHC.&#x0D; Conclusions. Progression of fibrosis into cirrhosis in patients with CDLD is interconnected with iron metabolism disorders in the form of increased ferritin concentration, which correlates with the parameters of liver lesion severity that confirms a direct involvement of iron metabolism disorders in CDLD pathogenesis.

Analysis of Point Shear Wave Elastography and Biochemical Markers for the Detection of Liver Fibrosis.

Background and Objectives: This work focuses on the possibility of using the point shear wave elastography (pSWE) method for detecting biochemical markers in diffuse liver diseases. Additionally, this study addresses the issue of the influence of ultrasound factors on the pSWE quality indicators of the obtained measurements. Materials and Methods: A pSWE examination was performed on 139 patients (69 female and 70 male) diagnosed with diffuse liver disease. The average age for all patients was 50.7 ± 15.0 years (female: 52.7 ± 15.2 years; male: 48.8 ± 14.6 years). Of these 139 patients, 65 met the inclusion criteria regarding biochemical parameters. The pSWE quality indicators were related to abnormalities found in B-mode ultrasound. Results: A strong positive correlation was found between the results of the pSWE and all biochemical indexes analysed, with the exception of age/platelet count (PLT), for which an average correlation was obtained. The greatest correlation was observed between the elastography and King’s Score index. There was no correlation observed between elastography and any of the analysed parameters or biochemical indexes considered. The pSWE measurements were impaired by factors such as thick soft tissue, uneven hepatic surface, hepatomegaly and female gender. No statistically significant difference in pSWE quality indicators parameters was found between disease entities. Conclusions: pSWE seems to be a complementary method for detecting biochemical indexes, but its results can be influenced by numerous factors.

Ultrasound in a differentiated treatment approach for liver diseases

Prospective assessment of the proposed diagnostic algorithm aimed at increasing the reliability of diagnosis of diffuse and focal liver diseases, reducing diagnostic invasiveness, economic costs, developing management strategy of patients with liver tumors and early diagnosis of hepatocellular carcinoma. A prospective case-control study included 336 patients with a preliminary diagnosis of diffuse focal liver damage for the period from January 2015 to April 2019. The authors described a diagnostic algorithm for focal liver lesions based on various ultrasound modes including gray-scale scanning (B-mode), Doppler ultrasound and pulse-wave Doppler. Moreover, 2D-SWE for assessing the liver stiffness and fibrosis grade (METAVIR grading system) and CEUS for differential diagnosis of liver neoplasms are applied.