Stage Of Chronic Liver Disease Research Articles

Dietary total antioxidant capacity in relation to disease severity and risk of mortality in cirrhosis; results from a cohort study

Liver Cirrhosis, defined as the final stage of chronic liver disease, may become more prevalent in the lower level of body defense against oxidation and inflammation. Therefore, we assessed the association of dietary total antioxidant capacity (DTAC) with the severity and mortality of cirrhosis in a cohort study. 120 newly diagnosed cirrhosis patients from Tehran, Iran, participated in this study. The patients’ habitual diet was assessed using a 168-item validated food frequency questionnaire. Both ferric-reducing antioxidant potential (FRAP) and oxygen radical scavenging capacity (ORAC) methods were computed to achieve DTAC scores. The association between DTAC with disease severity and mortality was estimated by multivariate linear regression and cox proportional hazards regression models. Dietary total antioxidant capacity-ORAC had a significant inverse association with disease severity in both crude and adjusted models (P for trend: <0.001 and 0.016 respectively). The risk of mortality in the first and second tertiles of ORAC was 5.56 (95 % CI: 2.25–13.75; P = 0.002) and 3.20 (95 % CI: 1.25–8.19; P = 0.015) higher than those in the third category, respectively. In conclusion, a higher antioxidant capacity of diet is associated with less disease severity and mortality risk in cirrhosis.

FoxD1 expression identifies a distinct subset of hepatic stellate cells involved in liver fibrosis

Hepatic stellate cells (HSCs) are pericytes of the liver responsible for liver fibrosis and cirrhosis, which are the end stages of chronic liver diseases. TGF-β activates HSCs, leading to the differentiation of myofibroblasts in the process of liver fibrosis. While the heterogeneity of HSCs is appreciated in the fibrotic liver, it remains elusive which HSC subsets mainly contribute to fibrosis. Here, we show that the expression of the pericyte marker FoxD1 specifically marks a subset of HSCs in FoxD1-fate tracer mice. HSCs fate-mapped by FoxD1 were preferentially localized in the portal and peripheral areas of both the homeostatic and fibrotic liver induced by carbon tetrachloride. Furthermore, the deletion of Cbfβ, which is necessary for TGF-β signaling, in FoxD1-expressing cells ameliorated liver fibrosis. Thus, we identified an HSC subset that preferentially responds to liver injuries.

Case Report : Hepatic Cirrhosis and Nephrolithiasis

Liver cirrhosis and nephrolithiasis are significant health problems with different pathophysiological mechanisms. Liver cirrhosis, the final stage of chronic liver disease, is characterized by fibrosis and regenerative nodules, leading to severe complications, including portal hypertension and liver failure. Nephrolithiasis, commonly known as kidney stones, is a common urological condition characterized by the formation of stones in the renal system. Although these conditions are distinct, metabolic and physiological changes in cirrhotic patients may predispose to nephrolithiasis. It was reported that a man came to the emergency room of RSUD Dr. Suhatman MARS with complaints of left-sided low back pain that had been felt for 1 week. The complaint was accompanied by shortness of breath which was getting worse over time. The patient also felt cough, headache, nausea, fatigue, urine slightly coloured like tea, weight loss. The patient has a history of untreated kidney stones. The patient has a history of hepatitis 31 years ago. The main objective of investigating the coexistence of liver cirrhosis and nephrolithiasis is to understand the relationship between these two conditions and to develop effective management strategies that can address their combined impact on patients.

Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes. Our findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC. MDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

Free-breathing, fat-corrected T1 mapping of the liver with stack-of-stars MRI, and joint estimation of T1, PDFF, , and .

Quantitative T1 mapping has the potential to replace biopsy for noninvasive diagnosis and quantitative staging of chronic liver disease. Conventional T1 mapping methods are confounded by fat and inhomogeneities, resulting in unreliable T1 estimations. Furthermore, these methods trade off spatial resolution and volumetric coverage for shorter acquisitions with only a few images obtained within a breath-hold. This work proposes a novel, volumetric (3D), free-breathing T1 mapping method to account for multiple confounding factors in a single acquisition. Free-breathing, confounder-corrected T1 mapping was achieved through the combination of non-Cartesian imaging, magnetization preparation, chemical shift encoding, and a variable flip angle acquisition. A subspace-constrained, locally low-rank image reconstruction algorithm was employed for image reconstruction. The accuracy of the proposed method was evaluated through numerical simulations and phantom experiments with a T1/proton density fat fraction phantom at 3.0 T. Further, the feasibility of the proposed method was investigated through contrast-enhanced imaging in healthy volunteers, also at 3.0 T. The method showed excellent agreement with reference measurements in phantoms across a wide range of T1 values (200 to 1000 ms, slope = 0.998 (95% confidence interval (CI) [0.963 to 1.035]), intercept = 27.1 ms (95% CI [0.4 54.6]), r2 = 0.996), and a high level of repeatability. In vivo imaging studies demonstrated moderate agreement (slope = 1.099 (95% CI [1.067 to 1.132]), intercept = -96.3 ms (95% CI [-82.1 to -110.5]), r2 = 0.981) compared to saturation recovery-based T1 maps. The proposed method produces whole-liver, confounder-corrected T1 maps through simultaneous estimation of T1, proton density fat fraction, and in a single, free-breathing acquisition and has excellent agreement with reference measurements in phantoms.

AYURVEDIC MANAGEMENT OF CIRRHOSIS OF LIVER WITH PORTAL HYPERTENSION - A CASE REPORT

Cirrhosis is characterized by severe liver scarring and impaired liver function, typically marks the advanced stage of chronic liver disease. Prolonged exposure to toxins such as alcohol or viral infections primarily causes scarring. Initially, it may progress slowly without noticeable symptoms. However, as liver function deteriorates, serious complications can arise. In classical Ayurvedic texts, it is mentioned as Yakritdalludara.In this case report, a male patient of 40 years of age cameas a diagnosed case of cirrhosis of liver with portal Hypertension with complaints of indigestion, constipation, weakness, nausea and acidity in the OPD of kayachiktsa,drugs such as Kayakalp kwath, Sarvakalp kwath ,Livogrit, Arogyavardhini vati, Livamrit Advance , Punarnavadi mandoor, Haritaki churna , aloe vera juice was given which are effective in pacifying the pitta dosha and purifying the blood and exhibiting immunomodulatory and hepatoprotective action, results into ultimately alleviate underlying symptoms of the patient and liver functioning.

The contribution of imaging to non-invasive fibrosis biomarkers in the diagnosis and staging of chronic liver disease

Aims: Gold standard technique for determining the stage of fibrosis in cirrhosis is a biopsy. Non-invasive tests are used when a biopsy is contraindicated. However, their specificity and sensitivity still fall short of expectations. Aim of the study is to develop a model capable of determining fibrosis using serum biomarkers and liver ultrasonography. Methods: A retrospective study was designed including patients with chronic hepatitis B and C underwenting liver biopsies between the time frame of 2015 to 2020 years at Trakya University School of Medicine. Epidemilogical data, ltrasonography and pathology reports were noted. Blood values were recorded and used to calculate AST / Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), Gothenburg University Cirrhosis Index (GUCI) noninvasive fibrosis indices. The fibrosis stages of the patients were assessed accoridng to pathology reports into three categories: advanced (F5-F6), moderate (F3-F4), and lower Ishak scores. Results: A total of 259 patients were included in the study. The median age of the patients was 54 (19-90), and 40.9% (106) were female. The median values of APRI, GUCI and FIB-4 scores were respectively: 0.6 (0-21.8), 0.6 (0-26.2) and 1.6 (0.2-8.5). The effects of ultrasonography findings were examined to improve the diagnostic performance of APRI, GUCI and FIB-4 indices. Accompanied by statistical analysis, it was observed that the FIB-4 index and the presence of hepatosteatosis in the liver had a significant effect on the detection of F?3 (respectively; p&lt;0.001, p=0.033). A new model named FIB4u (ultrasonography) was developed. The AUC values of indices for differentiation of intermediate and advanced stages of fibrosis (?3) were respectively:FIB4u 0.760; FIB-4 0.753; GUCI 0.676; APRI 0.667 (p&lt;0.001). The FIB4u index demonstrated considerably better performance compared to both APRI and GUCI. Conclusion: The FIB4u index, developed by combining ultrasonography and laboratory data, can be used as a new index for fibrosis assessment in the absence of advanced elastography techniques. It needs to be validated in larger patient cohorts to be used safely in the long term.

Acute and non-acute decompensation of liver cirrhosis (47/130).

In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding.

Liver segmentation using Mnet for cirrhosis

Liver biopsies for diagnosing cirrhosis, the last stage of chronic liver disease was analysed using imaging and it could able to determine the severity level of the disease. Liver lesions can be segmented for evaluation of tumor burden, therapeutic strategy, prognosis, and follow-up on the efficacy of therapy. Automatic technologies for malignancy identification and segmentation are preferable because manual segmentation is a laborious process that is prone to error. We thus propose an M-Net approach to cirrhosis of the liver segmentation. The liver datasets are collected initially as raw data, which, due to the existence of noise, must be normalized before the investigation can begin. With the help of the Bilateral Filter and the Wavelet Transform, we can get rid of the noise and improve the de-noised image. The Gabor Filter is used for feature extraction. Hybrid Genetic Algorithm (HGA) is used to pick the best feature subsets for classification. Ensemble Deep Convolutional Neural Network (EDCNN) method is applied to the classification process. MATLAB, a simulation program, is used to conduct the entire inquiry. In terms of accuracy, our system has outperformed the most sophisticated automatic techniques.

MELD-Na score may underestimate disease severity and risk of death in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)

Portal hypertension often precedes the development of advanced fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) and may accelerate disease progression to cirrhosis. We aimed to evaluate whether prioritization tools accurately predict survival in patients with MASLD and clinically significant portal hypertension (CSPH). We retrospectively identified patients diagnosed with esophageal or gastric varices (EGV). Laboratory results, endoscopy reports and outcomes of patients with MASLD were compared to patients with advanced stage chronic liver disease (CLD) of other etiologies. During the study period 326 patients were diagnosed with EGV. 88 (26.9%) had MASLD, 113 (34.6%) viral hepatitis (VH), 63 (19.3%) alcoholic liver disease (ALD) and 62 (19%) both VH and ALD (VHALD). EGV bleeding events were significantly more frequent in patients with MASLD (36.3%), compared to VH (28.3%), ALD (30.1%) and VHALD (25.8%), respectively (p < 0.01). Mean Model for End-Stage Liver Disease (MELD)-Na score surrounding 1 year of first event of EGV bleeding was significantly lower in MASLD patients compared to all other etiologies (p = 0.02). At a MELD-Na score of 11–20, cumulative survival rate was significantly lower in MASLD patients compared to all other etiologies (log rank p < 0.01). MASLD patients present with EGV bleeding at lower MELD-Na scores compared to other etiologies of CLD. MELD-Na score may therefore underestimate disease severity and risk of death in patients with MASLD and CSPH.

Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.

Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.

Thyroid hormone receptor alpha modulates fibrogenesis in hepatic stellate cells.

Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells(HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly affect development, growth, cell differentiation and metabolism through activation of TH receptor α and/or β (TRα/β). Here, we evaluated the influence of TH in hepatic fibrogenesis. Human liver tissue was obtained from explanted livers following transplantation. TRα-deficient (TRα-KO) and wild-type (WT) mice were fed a control or a profibrogenic methionine-choline deficient (MCD) diet. Liver tissue was assessed by qRT-PCR for fibrogenic gene expression. In vitro, HSC were treated with TGFβ in the presence or absence of T3. HSC with stable TRα knockdown and TRα deficient mouse embryonic fibroblasts (MEF) were used to determine receptor-specific function. Activation of HSC and MEF was assessed using the wound healing assay, Western blotting, and qRT-PCR. TRα and TRβ expression is downregulated in the liver during hepatic fibrogenesis in humans and mice. TRα represents the dominant isoform in HSC. In vitro, T3 blunted TGFβ-induced expression of fibrogenic genes in HSC and abrogated wound healing by modulating TGFβ signalling, which depended on TRα presence. In vivo, TRα-KO enhanced MCD diet-induced liver fibrogenesis. These observations indicate that TH action in non-parenchymal cells is highly relevant. The interaction of TRα with TH regulates the phenotype of HSC via the TGFβ signalling pathway. Thus, the TH-TR axis may be a valuable target for future therapy of liver fibrosis.

Therapeutic Effect of Hydrodynamics-Based Delivery of Matrix Metalloproteinase-13 Gene on Thioacetamide-Induced Liver Fibrosis in Rats

Liver cirrhosis is the final stage of chronic liver disease and can be life-threatening. Despite extensive studies on its treatment, a standard therapy is yet to be developed. Considering the complex mechanism of fibrogenic and fibrolytic processes in liver cirrhosis, combined therapy may have clinically significant effects on cirrhotic livers. In this study, we used thioacetamide (TAA) administration and matrix metalloproteinase-13 (MMP13) gene delivery to induce extracellular matrix generation and degradation in rats. The aim of this study was to determine whether hydrodynamics-based gene delivery of MMP13 to cirrhotic liver has regressive and suppressive effects on fibrogenesis. MMP13-encoding plasmids were hydrodynamically delivered to TAA-induced cirrhotic livers, and intravascular pressure was monitored. Therapeutic effect with and without continuous TAA exposure was assessed 8 weeks after the gene delivery. Test results indicated successful gene delivery and gene expression in the cirrhotic livers. Furthermore, microscopic imaging showed that MMP13 delivery resulted in significant degradation of fibrotic areas. Quantitative analysis of hydroxyproline content supported the microscopic findings. These results suggest that transgene delivery of MMP13 can be a promising candidate to treat liver fibrosis and that hydrodynamics-based gene delivery can be a good option for delivery of MMP13 to cirrhotic livers.

Identification of oxidative stress-related biomarkers associated with the development of acute-on-chronic liver failure using bioinformatics

Acute-on-chronic liver failure (ACLF) is a serious stage of chronic liver disease with high short-term mortality and no definitely effective treatment. Oxidative stress (OS) is involved in the development of ACLF. OS-related genes targeted therapy may provide additional assistance for the treatment of ACLF. ACLF related gene sets and oxidative stress-related genes (OSGs) were respectively downloaded from gene expression omnibus (GEO) database and GeneCards database for integrated bioinformatics analyses (functional enrichment, weighted gene co-expression network and immune cells infiltration). Immune-related differentially expressed oxidative stress-related genes (DEOSGs) in ACLF were used for construction of protein–protein interaction (PPI) network in which hub genes were screened out. Hub genes with consistently good diagnostic or prognostic value for ACLF in four gene sets were named as key genes. DEOSGs were significantly enriched in biological process and signaling pathways related to inflammation, immune response and oxidative stress. Six key genes (MPO, CCL5, ITGAM, TLR2, TLR4, and TIMP1) were identified and found to be highly correlated with immune response and metabolic process. This study deepened our understanding of the impact of oxidative stress on the pathogenesis and prognosis of ACLF and provided more insights into the prediction of prognosis and molecular targeted therapy in ACLF.

The Intensity and Pattern of Syndecan-1 (CD138) Expression in Normal and Diseased Livers.

Introduction Heparan sulfate proteoglycans (HSPGs) belongto the syndecan family, and syndecan-1 (CD138) is a heparan sulfate proteoglycan. Syndecan-1 has a potential role in cell-matrix and cell-cell communications as they are present in cell epithelium. Its expression is different in an extensive range of benign, inflammatory, and neoplastic diseases. In routine histopathology, it is used as a marker for plasma cells. However, it is expressed in a large variety of normal and neoplastic epithelia including squamous epithelium and gastric glandular epithelium expressed in other tissues, i.e., the liver. In the liver, variable expression is seen in cirrhosis, hepatitis, and carcinoma. The objective of this study was to investigatethe expression of this marker in normal, inflammatory, and neoplastic lesions of the liver. This in turn may help clinicians to select patients whomay benefit from anti-CD138 therapy. It is currently used in the diagnosis and management of plasma cell proliferations. Material and methods This is a retrospective study in which weretrieved 53 formalin-fixed paraffin-embedded (FFPE) liver specimen blocks and selected one block from each case by reviewing the hematoxylin and eosin (H&E) slides of each case. Syndecan-1 (CD138), pancytokeratin, and CD68 expression were analyzed immunohistochemically (IHC) to evaluate the percentage and intensity of CD138 expression in various hepatic entities and identify those entities where syndecan-1 can be consistently used to make a definitive diagnosis. Results The expression of pancytokeratin and CD68 was analyzed in hepatocytes and Kupffer cells, respectively. For syndecan-1 (CD138), 15.4% of cases showed basolateral membranous positivity, 44.6% of cases showed complete membranous positivity, and 40% of cases showed no positivity in hepatocytes. Cytokeratin (CK) was positive as expected in hepatocytes, and CD68 was expressed in Kupffer cells. Conclusion CD138 does not appear to be a reliablesurrogate marker for liver disease. However, it may be included with other ancillary markers as a predictor of the stage of chronic liver disease and metastatic potential. The response to anti-CD138 therapy needs to be further studied.

Prognostic assessment of liver cirrhosis and its complications: current concepts and future perspectives.

Liver cirrhosis is an irreversible stage of chronic liver disease with varying clinical course. Acute decompensation of liver cirrhosis represents a watershed in prognosis and is characterized by the occurrence of clinical complications such as ascites, jaundice, hepatic encephalopathy, infections, or portal-hypertensive hemorrhages. Emergent data indicate that an acute decompensation can be subdivided into stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on chronic liver failure (pre-ACLF) and acute-on chronic liver failure (ACLF), while the mortality risk varies greatly between the respective subgroups. ACLF is the most severe form of acutely decompensated cirrhosis and characterized by the development of organ failure(s) and a high short-term mortality. Due to the dynamic disease course of acute decompensation, it is paramount to detect patients at particular risk for severe complications those at high risk for developing ACLF as early as possible in order to initiate optimal management. This review describes new concepts and perspectives in the definition and classification of decompensated cirrhosis and provides on overview on emerging predictive scoring systems, non-invasive measurement methods and new biomarkers, which allow an early identification of patients with acute decompensation at risk.

ALBUMIN VERSUS STANDARD MEDICAL TREATMENT IN BRAZILIAN PUBLIC AND PRIVATE HEALTHCARE SYSTEMS.

•To assess the economic impact of implementing long-term albumin infusions in patients with cirrhosis and ascites in Brazil •Incremental cost per cirrhotic patient treated with long-term albumin was estimated based on the rates of complications and healthcare resource utilization from the ANSWER trial and local costs from the public and private healthcare system perspective in Brazil. •Implementation of long-term albumin could save up to 118,759 BRL and 189,675 BRL per patient treated in the public and private healthcare system setting, respectively. •Should results from the ANSWER trial translate into real-world effectiveness, addition of albumin to standard medical treatment could lead to improved clinical outcomes and reduced costs. Background - Cirrhosis is one of the final stages of chronic liver disease. Common causes of cirrhosis include alcoholism and viral hepatitis infections. Cirrhosis can progress from an asymptomatic, compensated phase to decompensation and the appearance of overt symptoms. There is no specific treatment for decompensated cirrhosis. The ANSWER trial positioned long-term albumin infusions as a potential treatment for patients with cirrhosis and uncomplicated ascites. Objective - This study assesses the economic impact of albumin infusions following the ANSWER trial regimen in Brazilian patients with decompensated cirrhosis from the public and private healthcare systems perspectives. Methods - The incremental cost per patient per year was calculated for standard medical treatment (SMT) plus long-term albumin infusions versus SMT alone. Costs of diuretics and albumin were obtained from Banco de Preços em Saúde and the Drug Market Regulation Chamber. Costs for complication and procedures were gathered from the published literature. Costs were transformed to 2021 Brazilian reals (BRL). Incidences of clinical complications and treatments were gathered from the ANSWER trial. Univariate sensitivity analysis was performed by increasing and decreasing all inputs by 20%. Results - The cost per patient per year was 118,759 BRL and 189,675 BRL lower for patients treated with SMT and albumin (compared to SMT only) for the public and private healthcare systems, respectively. The additional cost of albumin was offset by reduced complications and treatments (149,526 BRL and 249,572 BRL, respectively). The univariate sensitivity analysis showed cost savings for both healthcare systems in all the scenarios assessed. Conclusion - This economic analysis suggests that, if the ANSWER trial clinical outcomes translate into real-world effectiveness, addition of albumin infusions to SMT in patients with decompensated cirrhosis may lead to cost savings for the public and private healthcare systems in Brazil.

Imaging Findings in Cirrhotic Liver: Pearls and Pitfalls for Diagnosis of Focal Benign and Malignant Lesions.

Cirrhosis is the end stage of chronic liver disease and causes architectural distortion and perfusional anomalies. It is a major risk factor for developing hepatocellular carcinoma (HCC). Common disease entities in noncirrhotic livers, such as hemangiomas, can be rare in cirrhotic livers, and benign entities such as confluent hepatic fibrosis and focal nodular hyperplasia-like lesions may mimic the appearance of malignancies,. HCC usually has typical imaging characteristics, such as the major features established by the Liver Imaging Reporting and Data System. However, HCC can also have a spectrum of atypical or uncommon appearances, such as cystic HCC, hypovascular HCC, or macroscopic fat-containing HCC. HCCs with certain genetic mutations such as CTNNB-1-mutated HCC can harbor unique imaging features not seen in other types of HCC. In addition, malignancies that are less common than HCC, such as cholangiocarcinoma and metastases, which can be difficult to differentiate, can still occur in cirrhotic livers. Atypical imaging features of benign and malignant lesions can be challenging to accurately diagnose. Therefore, familiarity with these features and an understanding of the prevalence of disease entities in cirrhotic livers are key in the daily practice of radiologists for evaluation of cirrhotic livers. The authors illustrate the typical and atypical features of benign and malignant lesions in cirrhosis and discuss the technical pitfalls and unique advantages associated with various imaging modalities in assessing cirrhotic livers, including noncontrast and contrast-enhanced US, CT, and MRI. Work of the U.S. Government published under an exclusive license with the RSNA. Quiz questions for this article are available in the supplemental material.

The effect and mechanism of Qingre Huashi formula in the treatment of chronic hepatitis B with Gan-dan-shi-Re syndrome: An integrated transcriptomic and targeted metabolomic analysis

Ethnopharmacological relevanceQingre Huashi (QRHS) formula is an empirical prescription for the treatment of Gan-Dan-Shi-Re syndrome (GDSR) syndrome in traditional Chinese medicine (TCM). GDSR is one of the typical TCM syndromes in chronic hepatitis B (CHB). However, little is known about the mechanism of the QRHS formula in treating CHB patients with GDSR. The biological basis of GDSR also remains largely unknown.Aim of the study: GDSR mostly occurs in the acute and early stages of chronic liver disease. Effectively alleviating GDSR stalls disease development and benefits patients. The purpose of this study was to explore the molecular basis of GDSR in CHB and then study the mechanism of the QRHS formula treating GDSR using transcriptomics and metabolomics. Materials and methodsThe transcriptome and metabolome of CHB patients with GDSR syndrome were detected using RNA microarray combined with ultra-high performance liquid chromatography/mass spectrometry and information mining. The potential biomarkers were identified from differentially expressed genes and metabolites, and the metabolic pathway was analyzed. We also investigated the callback of metabolic biomarkers after treatment with the QRHS formula, an empirical prescription for the treatment of GDSR syndrome. RT-PCR analysis was carried out in an independent patient cohort of CHB for validation. ResultsFour candidate genes—GPT2, HK2, DDIT3, and HIF1A—and 14 candidate metabolic biomarkers, including L-alpha-aminobutyric acid, selenomethionine, and fructose 1,6-bisphosphate, were identified and validated. All four transcripts of GPT2, HK2, DDIT3, and HIF1A were significantly differentially expressed between the GDSR and non-GDSR groups through independent microarray data and RT-PCR. After treatment with the QRHS formula, the clinical indexes and TCM syndrome were significantly improved, and the 14 disturbed biomarkers were obviously corrected. Three metabolic pathways were confirmed to be perturbed in CHB GDSR patients: alanine, aspartate, and glutamate metabolism, arginine biosynthesis, and aminoacyl-tRNA biosynthesis. ConclusionUsing integrated transcriptomic and targeted metabolomic methods, we identified the potential biomarkers and dysregulated metabolic pathways in CHB patients with GDSR syndrome, which was alleviated by the QRHS formula treatment. These results may provide the mechanism of metabolic dysregulation in GDSR syndrome as well as that underlying the curative effect of the QRHS formula.

Association of Serum Vitamin D and Calcium with Different Stages of Chronic Liver Diseases

Introduction: Chronic liver disease (CLD) is a progressive condition characterized by liver tissue destruction, leading to complications such as cirrhosis. Vitamin D deficiency is highly prevalent in patients with CLD and is associated with skeletal and immune system impairments. This brief focuses on the impact of vitamin D deficiency in CLD and the significance of assessing vitamin D status and calcium levels for effective interventions and improved patient outcomes. Aim of the Study: The aim of this study was to investigate the association between the serum vitamin D and calcium with different stages of chronic liver diseases. Methods: This observational cross-sectional study was conducted in the Department of Gastroenterology at BSMMU in Dhaka, Bangladesh, over a period from April 2019 to March 2020. The study included 60 patients, of them 30 patients had chronic liver disease and a comparison group comprising 30 healthy attendants from the same department. Data were collected without interventions, cleaned, and analyzed using SPSS version 22.0. Ethical clearance of this study was obtained from the Institutional Review Board (IRB) of BSMMU, Dhaka, Bangladesh. Results: The study examined the association between serum vitamin D and calcium levels with different stages of chronic liver disease (CLD). Among the CLD patients, a significant proportion (63.4%) had deficient vitamin D levels compared to the healthy individuals (23.3%), and only 3.3% had sufficient levels (p = 0.007). Serum calcium levels were significantly lower in CLD patients (8.05 ± 0.76 mg/dl) compared to healthy individuals (8.81 ± 0.49 mg/dl) (p &lt; 0.001). Furthermore, vitamin D levels were associated with the severity of liver cirrhosis, as higher Child-Turcotte-Pugh (CTP) classes had lower vitamin D levels (p = 0.009). These results indicate a potential link between vitamin D deficiency and advanced stages of chronic liver disease, emphasizing the importance of monitoring vitamin D and ......