Hepatic Manifestations Research Articles

DETECTION OF CLINICAL BIOMARKERS ASSOCIATED WITH HEPATO AND RENAL MANIFESTATIONS IN COVID-19 PATIENTS

The COVID-19 pandemic has spread in many countries worldwide, surpassing one million confirmed cases and resulting in deaths globally. Developing nations such as Pakistan face heightened vulnerability to such outbreaks due to limited healthcare infrastructure and resources. This study examines clinical biomarkers linked to hepatic and renal manifestations in COVID-19 patients in North Waziristan, recognizing the vulnerability of developing countries like Pakistan to such pandemics due to limited healthcare resources. Nasopharyngeal swabs were collected from 110 suspected COVID-19 patients visiting Dr. Azim Ullah clinic and DHQ Hospital North Waziristan, Miran Shah. Hematological, hepatic, renal, C-reactive protein (CRP), and ferritin markers were assessed. Most patients were male (75%), with varying age distributions. Abnormalities were observed in hematological parameters, liver enzymes, renal function markers, CRP, and ferritin levels. Significant correlations (p<0.001) were found among these markers. The study concludes that inflammatory, hematological, renal, and liver markers are associated with COVID-19 infection, with higher levels indicating severe disease. Continuous monitoring of these biomarkers may enhance patient outcomes and aid in predicting disease progression

Mixed cryoglobulinemia as a potential indicator of clinically silent Hepatitis C infection

Hepatitis C virus (HCV) is one of the major causes of chronic liver disease and its prevalence is increasing worldwide. There are many extra hepatic manifestations of Hepatitis C infection including B –cell lymphoproliferative disorders. Mixed cryoglobulinemia (MC) is the most common prototype of B-cell lymphoproliferative disorders. Cryoglobulinemia is an immune complex mediated disease causing multi organ damage with vasculitis being the primary manifestation. We report a case of 50 years old Asian lady having clinically silent chronic liver disease secondary to hepatitis C who presented to us with a purpuric skin rash, joint pains and fatigue. She was confirmed to be a case of mixed cryoglobulinemia. Patient was prescribed direct antiviral agents and prednisolone which improved her condition to a great extent. Heightened awareness of cutaneous manifestations of MC associated with HCV might improve the detection rate of clinically silent HCV infection.

Measles-Clinical and Biological Manifestations in Adult Patients, Including a Focus on the Hepatic Involvement: Results from a Single-Center Observational Cohort Study from Romania.

Background: Hepatic involvement in measles, particularly among adolescents and adults, has been recognized since 1960. This involvement typically manifests during the eruptive phase of the disease and is primarily characterized by hepatocellular dysfunction, with jaundice being a less common occurrence. Studies have reported hepatic involvement in 80-86% of measles cases among young adults associated with severe forms of the disease with intra-infectious hepatitis. Recent data from Romania indicated 20,035 confirmed measles cases between January and June 2024, including 17 fatalities and significant hepatic alterations. These findings underscore the need for the further investigation of the hepatic manifestations of measles. The primary objective of our study was to evaluate the clinical and baseline characteristics of the enrolled patients with a brief assessment of liver impairment. Methods: In light of these observations, we conducted a retrospective analysis between 1 November 2023 and 15 June 2024 in patients aged >16 years who were confirmed, by the detection of measles IgM in serum samples, to have acute measles infection and hospitalization. Results: During the study period, 71 hospitalized patients were diagnosed with measles, of whom 37 were female (52.1%), with ages ranging from 16 to 64 years (mean age 34.21 years). Most cases (77.5%) exhibited moderate clinical forms of measles, while 22.5% had severe forms. Respiratory failure requiring oxygen therapy was uncommon (25.4% of severe pneumonia cases). Although a Pearson chi-square test indicated no significant association between the presence of pneumonia and clinical form (p = 0.066), the likelihood ratio test suggested a potential link (p = 0.018). Hepatic involvement was common with elevated AST (87.3%) and ALT (76%) levels. Jaundice was observed in 12.7% of patients. GGT changes were noted in 35.2% of cases, with significant correlations between GGT levels and disease severity (p = 0.001). Analysis of various symptoms revealed significant associations between nausea, dyspnea, and severe clinical forms. Anorexia, diarrhea, and nausea were the most frequently reported symptoms. Thrombocytopenia was observed in 11 patients, with no significant correlation with disease severity. Comorbidities, such as COPD, were significantly associated with disease severity (p = 0.010). Conclusions: Our findings highlight that, while cytolytic hepatic damage is a typical response to measles infection, cholestatic involvement may serve as an indicator of more severe disease progression.

Clinical and laboratory profile and outcome in children with Wilson disease: an observational study in South India

ABSTRACT Background Wilson disease is an autosomal recessive disorder owing to defective copper metabolism which causes abnormal accumulation of copper and damage to the liver, brain, kidneys and other organs. Aim To describe the clinical features, laboratory investigations and outcome of Wilson disease in children. Methods A retrospective observational study was conducted in the paediatric department of a tertiary- care hospital in South India by reviewing medical records between January 2018 and March 2023. The diagnosis of Wilson disease was confirmed by the presence of low serum ceruloplasmin and/or high urine copper excretion in combination with clinical and ophthalmological features. Results A total of 32 cases were analysed. The mean (SD) age at presentation was 110 (36) months with a M:F ratio of 1.6:1. Isolated hepatic involvement was seen in 19 (60%) patients while 13 (40%) patients had a neurological presentation, either as an isolated entity or in combination with hepatic manifestations. Low serum ceruloplasmin levels were detected in 31 (96%) patients. Urine copper levels were elevated in all patients. Twenty-one patients were commenced on D penicillamine while 11 patients were treated with a combination chelation therapy with zinc. Eighteen patients (56%) were on regular follow-up. Conclusion The clinical presentation of Wilson disease in children is diverse, varying from the more common hepatic or neurological manifestations to the less common atypical forms of the disease. Diagnosis is based on clinical and ophthalmological features in combination with biochemical abnormalities in the form of low ceruloplasmin and high urinary copper. The majority of patients can be medically managed with chelation therapy.

Abstract P307: A Review Of The Burden, Management And Outcomes Of Patients With Aldosterone Dysregulation

Introduction: Aldosterone dysregulation (excess aldosterone production) is a complex physiological driver of uncontrolled hypertension as well as cardiovascular (CV) and kidney outcomes. Understanding the clinical and economic burden of excess aldosterone in routine practice is critical to optimizing treatment and improving long-term outcomes. This review examines the burden of excess aldosterone production as a driver of disease and its impact on clinical and economic outcomes. Hypothesis: Excess aldosterone production has a broad impact on long-term outcomes, and left untreated, contributes to worsened patient outcomes. Methods: A targeted literature review was conducted to identify articles on the burden, management and outcomes of patients with excess aldosterone production (2013 – 2024) with 27 manuscripts included. Results: More studies document the impact of excess aldosterone on organ function in the cardiovascular system and kidney (10, 8 manuscripts) compared to liver (1 manuscript). Excess aldosterone levels and aldosterone-induced oxidative stress and inflammation are associated with increased risk of CV events including myocardial infarction, heart failure, stroke, and increased morbidity and mortality. For example, Framingham Offspring Study showed increased CV disease risk with each rise in serum aldosterone levels (HR, 1.11; 95% CI, 1.02–1.21). Kidney, hepatic and metabolic manifestations are also well-documented, with implications for progression to chronic kidney disease, liver disease and metabolic syndrome. Another study reported an 11% increased risk of CKD progression associated with each doubling of serum aldosterone. Current pharmacological interventions for hypertension, including mineralocorticoid receptor antagonists, were not reported to restore normal aldosterone levels. No literature was found on the economic burden of excess aldosterone or the association between excess aldosterone production and clinical outcomes independent of blood pressure control. Conclusions: Currently available literature emphasizes the broad impact of excess aldosterone production on CV, kidney, hepatic, and metabolic outcomes. The impact on outcomes indicates that excess aldosterone production is underappreciated, with prognostic implications beyond primary aldosteronism. Current hypertension treatments do not address excess aldosterone production. These findings underscore the unmet need for novel management strategies that target excess aldosterone production.

Hepatic manifestations of hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia is a genetic condition of abnormal blood vessel formation resulting from an imbalance of pro- and anti-angiogenic products of the transforming growth factor β/bone morphogenetic protein signalling pathway which contributes to vascular remodelling and maintenance. Hepatic vascular malformations are common although less frequently symptomatic, but may result in high-output cardiac failure, portal hypertension and biliary ischaemia. Whilst the understanding of the genetic and cell signalling pathways that are the hallmark of hereditary haemorrhagic telangiectasia have been clarified, there remain challenges in therapy for these patients. Only patients with symptomatic hepatic vascular malformations require treatment, with most (63%) responding to first-line medical therapy. For non-responders, bevacizumab is effective in reducing cardiac output in those with heart failure secondary to hepatic vascular malformations as well as other manifestations of the disease. Although liver transplantation is the only curative option, optimal timing is critical. Novel anti-angiogenetic drugs and those that target aberrant cell signalling pathway are being explored.

Hepatic Manifestations in Systemic Lupus Erythematosus (SLE) and Cholestatic Hepatitis as Rare Initial Presentation: A Diagnostic Challenge

Hepatic Manifestations in Systemic Lupus Erythematosus (SLE) and Cholestatic Hepatitis as Rare Initial Presentation: A Diagnostic Challenge

Preoperative nonalcoholic steatohepatitis and resolution of metabolic comorbidities after bariatric surgery

BackgroundMost patients undergoing bariatric surgery demonstrate elements of the metabolic syndrome (MetS) and can therefore be diagnosed with metabolically unhealthy obesity (MUO). Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) as hepatic manifestations of the MetS occur in many patients with obesity, but their leverage on postoperative improvement to Metabolic Health (MH), defined as absence of any metabolic comorbidity, remains unclear. ObjectivesThe aim of this study was to assess the influence of liver health status, operative procedure, and sex on postoperative switch from a MUO to an MH phenotype. Secondary objective was weight loss to MH. SettingUniversity Hospital, Germany. MethodsPatients who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at our obesity surgery center were included in this retrospective study. Liver biopsy was taken and evaluated for presence of NAFLD/NASH. For diagnosis of MH, blood pressure and laboratory values referring to the MetS were assessed preoperatively and at 3, 6, 12, and 24 months’ postoperatively. ResultsOne hundred thirty-three patients (73% female) with a mean body mass index of 52.0 kg/m2 and mean age of 43 years were included in this study. A total of 55.6% underwent RYGB and 44.4% underwent SG. NAFLD was found in 51.1% of patients and NASH in 33.8%. All patients were diagnosed MUO at baseline. Postoperatively, 38.3% patients (n = 51) switched to a MH condition. Mean time to MH was 321 days and mean excess body mass index loss to MH was 63.8%. There were no differences regarding liver health status, operative procedure, or sex. ConclusionsBariatric surgery can resolve MUO independent of liver health status, operative procedure, and sex. However, patients should be closely monitored to ensure sustainable long-term outcomes following the switch to the MH condition.

Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome

BackgroundAlagille syndrome (ALGS) is a multisystem genetic disorder frequently characterized by hepatic manifestations. This study analyzed the clinical, pathological, and molecular genetic features of ALGS to improve the efficiency of clinical diagnosis.MethodsWe retrospectively analyzed the clinical manifestations, pathological examination findings, and genetic testing results of 17 children diagnosed with ALGS based on the revised criteria and hospitalized at our center from January 2012 to January 2022.ResultsThe clinical manifestations are as follows: Cholestasis (16/17, 94%), characteristic facies (15/17, 88%), heart disease (12/16, 75%), butterfly vertebrae (12/17, 71%) and posterior embryotoxon (7/12, 58%). Among the 15 patients who underwent liver pathology examination, 13 (87%) were found to have varying degrees of bile duct paucity. Genetic testing was performed on 15 children, and pathogenic variants of the jagged canonical Notch ligand 1 (JAG1) gene were identified in 13 individuals, including 4 novel variants. No pathogenic variant in the notch homolog 2 (NOTCH2) gene were identified, and 2 children exhibited none of the aforementioned gene pathogenic variants. The median follow-up duration was 7 years. Of the remaining 15 patients (excluding 2 lost to follow-up), 11 remained stable, 4 deteriorated, and no patient died during the follow-up period.ConclusionsAmong children diagnosed with ALGS, cholestasis stands as the most common feature. To minimize the risk of misdiagnosis, genetic testing should be performed on children exhibiting cholestasis, followed by the application of the revised diagnostic criteria for ALGS. While pharmacological therapy has shown effectiveness for ALGS patients, liver transplantation may be considered in instances of severe pruritus.

The Interplay of Chronic Hepatitis C and COVID-19: Implications for Prognosis and Treatment.

Introduction Chronic hepatitis C (CHC) remains a significant public health concern due to both hepatic and extrahepatic manifestations associated with substantial morbidity and mortality. The emergence of SARS-CoV-2 has raised concerns about the outcomes of COVID-19 in CHC patients. Method We conducted a retrospective analysis of patients with CHC and SARS-CoV-2 infection admitted to a tertiary care hospital between 2020 and 2023. We performed a global analysis of the entire batch of patients and, later, we evaluated the patients according to the severity of the SARS-CoV-2 infection Results The cohort included 89 patients (63 females, 26 males) with a median age of 65 years. Most patients were hospitalized in 2021. Common clinical manifestations included fever, cough, digestive symptoms, and headache. The most frequent comorbidities were renal disease, thyroid disorders, and cancer. Univariate logistic regression analysis identified older age, hospitalization in 2021, and respiratory failure as risk factors for severe COVID-19. Elevated lactate dehydrogenaselevels were also associated with an increased risk of severe COVID-19. Regarding CHC, detectablehepatitis C virus viremia was associated with more severe liver disease (p<0.01). Conclusion Patients with CHC and SARS-CoV-2 infection have a substantial risk of severe outcomes. Early identification and management of these patients are crucial to improve their prognosis.

Monogenic lupus with neuroregression in an infant due to rare compound heterozygous variants in C1QA gene: Case based review.

Monogenic lupus is a rare variant of systemic lupus erythematosus (SLE) that develops in patients with a single gene disorder. Early complement component deficiencies were the first forms of monogenic lupus to be described and C1Q gene mutations are one of the most common forms. C1QA complement deficiency has been reported to occur usually due to biallelic variants in C1QA gene and compound heterozygous variants in C1QA gene have rarely been reported. Majority of the monogenic lupus patients with C1Q deficiency present with mucocutaneous, renal, and musculoskeletal manifestations. Our patient is an unusual case of monogenic lupus with severe neurological manifestations along with cutaneous, haematological, and hepatic manifestations secondary to rare compound heterozygous variants in C1QA gene and anti-ribosomal P autoantibody positivity. She was treated with glucocorticoids, rituximab and fresh frozen plasma with partial neurological recovery. Thus, we present a unique case of monogenic lupus due to a rare compound heterozygous variant in C1QA gene with a brief review of literature.

COVID-19 and Digestive Diseases: A Comprehensive Review on Pathophysiology and Clinical Management

Abstract: A serious pandemic has been presented by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a coronavirus that causes the severe acute respiratory infection known as Coronavirus disease 2019 (COVID-19). It has become a major health hazard that affects people all around the world. Although the respiratory symptoms are the main manifestations of COVID-19, several extrapulmonary manifestations have been observed, including cardiovascular, renal, and gastrointestinal symptoms. The digestive system may be an additional or non-traditional pathway for COVID-19 to spread and manifest as Angiotensin-Converting Enzyme 2 (ACE2), the entry point of SARS-CoV-2 into the cells is present in the gastrointestinal tract and liver. Gastrointestinal symptoms, such as vomiting, anorexia, nausea, and diarrhea, are infrequent in COVID-19 patients; however, some of these symptoms may manifest independently of other respiratory symptoms. Also, SARS-CoV-2 virus can cause liver and pancreatic damage. Studying the pathogenic mechanisms of COVID-19 in the digestive system could aid in improving patient diagnosis and treatment. The review aims to provide an overview of the mechanisms, symptoms, and management of SARS-CoV- 2's effects on the digestive system. Hence, medical professionals would be aware of the digestive symptoms associated with COVID-19 and would promptly alter treatment regimens for patients exhibiting abnormal hepatic and gastrointestinal manifestations.

Syndromic genetic causes of pulmonary fibrosis.

The identification of extra-pulmonary symptoms plays a crucial role in diagnosing interstitial lung disease (ILD). These symptoms not only indicate autoimmune diseases but also hint at potential genetic disorders, suggesting a potential overlap between genetic and autoimmune origins. Genetic factors contributing to ILD are predominantly associated with telomere (TRG) and surfactant-related genes. While surfactant-related gene mutations typically manifest with pulmonary involvement alone, TRG mutations were initially linked to syndromic forms of pulmonary fibrosis, known as telomeropathies, which may involve hematological and hepatic manifestations with variable penetrance. Recognizing extra-pulmonary signs indicative of telomeropathy should prompt the analysis of TRG mutations, the most common genetic cause of familial pulmonary fibrosis. Additionally, various genetic diseases causing ILD, such as alveolar proteinosis, alveolar hemorrhage, or unclassifiable pulmonary fibrosis, often present as part of syndromes that include hepatic, hematological, or skin disorders. This review explores the main genetic conditions identified over the past two decades.

Intracerebroventricular 2-hydroxypropyl-γ-cyclodextrin alleviates hepatic manifestations without distributing to the liver in a murine model of Niemann–Pick disease type C

Niemann–Pick disease type C (NPC) is a lysosomal lipid storage disorder characterized by progressive neurodegeneration and hepatic dysfunction. A cyclic heptasaccharide, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), is currently under clinical investigation for NPC, but its adverse events remain problematic. We previously identified that a cyclic octasaccharide, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), also ameliorated NPC manifestations with higher biocompatibility than HP-β-CD. However, preclinical studies describing the associations between the biodistribution and pharmacodynamics of these compounds, which are essential for clinical application, are still lacking. Here, we investigated these properties of HP-γ-CD by measuring its organ biodistribution and therapeutic effect after systemic and central administration. The effect of HP-γ-CD on disturbed cholesterol homeostasis appeared within several hours after exposure and persisted for several days in NPC model cells and mice. Tissue distribution indicated that only a small fraction of subcutaneously administered HP-γ-CD rapidly distributed to peripheral organs and contributed to disease amelioration. We found that a subcutaneous dose of HP-γ-CD negligibly ameliorated neurological characteristics because it has limited penetration of the blood–brain barrier; however, an intracerebroventricular microdose unexpectedly attenuated hepatic dysfunction without the detection of HP-γ-CD in the liver. These results demonstrate that central administration of HP-γ-CD can indirectly attenuate peripheral manifestations of NPC.

Paradoxical tuberculous reaction to anti-tnfα discontinuation: a complex case of miliary tuberculosis and macrophagic activation syndrome with hepatic manifestations

Tuberculosis reactivation during anti-TNF-alpha therapy paradoxically worsened following reconstitution of pathogen-specific immune responses after cessation of TNFα antagonist treatment and initiation of anti-bacillary therapy. We report the case of a 46-year-old woman who was prescribed a tumor necrosis factor blocker (anti-TNF) for a relapse of Behçet's disease. The patient developed pulmonary miliary tuberculosis following the reactivation of latent tuberculosis, despite a normal pre-therapeutic work-up. Discontinuation of anti-TNF and initiation of anti-bacillary drugs triggered a paradoxical tubercular reaction (PTR). The diagnosis of paradoxical reaction to anti-tuberculosis drugs was evoked by the clinical and biological deterioration and the appearance of miliary cerebral tuberculosis and cerebral venous thrombosis after a period of clinical improvement. Although this phenomenon has been documented, it represents a major challenge for clinicians. The peculiarity of this case lies in its association with a macrophagic activation syndrome (MAS) with hepatic involvement, retained on clinical-biological and histological criteria. The overlap between MAS and PTR makes it difficult to diagnose these two entities with certainty. The patient responded favorably to moderate-dose systemic corticosteroid therapy with progressive degression, and the reintroduction of anti-tuberculosis drugs.This work aims to highlight the importance of close monitoring of TB patients on anti-TNFα therapy for early diagnosis and management of complications to improve the prognosis of these complex patients.

LEMD2-associated progeroid syndrome: Expanding the phenotype of the nuclear envelopathy caused by a defect in LEMD2 gene.

Nuclear envelopathies are rare genetic diseases that compromise the integrity of the nuclear envelope. Patients with a defect in LEM domain nuclear envelope protein 2 (LEMD2) leading to LEMD2-associated progeroid syndrome are exceedingly scarce in number, yet they exhibit shared clinical features including skeletal abnormalities and a prematurely-aged appearance. Our study broadens the understanding of LEMD2-associated progeroid syndrome by detailing its phenotypic and molecular characteristics in the first female and fourth reported case, highlighting a distinct impact on metabolic functions. The patient's history revealed growth delay, facial and skeletal abnormalities, and recurrent abdominal pain crises caused by hepatomegaly. Comparisons with the previously documented cases emphasized similarities in skeletal and facial features while showcasing unique variations, notably in cardiac and hepatic manifestations. Invitro experiments conducted on patient-derived peripheral blood and urinary epithelial cells and LEMD2-downregulated HepG2 cells confirmed abnormalities in the structure of the nuclear envelope in all three tissue-types. Overall, our work offers a comprehensive profile of a patient with LEMD2-related syndrome, emphasizing the hepatic involvement in the disease and broadening our understanding of clinical and molecular implications. This study not only contributes specific insights into LEMD2-related conditions but also underscores potential therapeutic paths for disorders affecting nuclear envelope dynamics.

Multidisciplinary Management Strategies for Long COVID: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness,skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategiesfor the most common long COVID conditions.

Gastrointestinal and Hepatic Manifestations of COVID-19 in Children: A Systematic Review and Meta-analysis.

Children with COVID-19 may present with gastrointestinal (GI) symptoms and liver dysfunction. To determine the type and prevalence of gastrointestinal (GI) and hepatic manifestations of COVID-19 in children and its association with severity of illness. A systematic literature search was done from inception until January 4, 2021 using PubMed, Cochrane Library, Google Scholar and prepublication repositories with no language restrictions. Studies that reported the demographic and clinical features of children with COVID-19 and provided data on their GI and hepatic signs and symptoms were included. Prevalence of GI and hepatic manifestations were pooled using Stata14. We included 58 studies with total of 4497 participants. Overall, one-third of children with COVID-19 presented with at least one GI symptom (33.8%; 95% confidence interval (CI) 23.0, 45.4; I2 97.5%; 42 studies, 3327 participants) with abdominal pain, nausea or vomiting, and diarrhea each occurring in approximately 20%. Children with severe COVID-19 were more likely to present with GI symptoms (odds ratio 2.59; 95% CI 1.35, 4.99; I2 24%; 4 studies, 773 participants). The pooled prevalence of elevated transaminases was 11% for both AST (11.3%, 95% CI 4.9, 19.3; I2 74.7%; 11 studies, 447 participants) and ALT (11.2%, 95% CI 7.1, 16.0; I2 40.8%; 15 studies, 513 participants). Hepatic findings such as jaundice (2-17%), hepatomegaly (2%) or behavioral changes (2%) from hepatic encephalopathy were variably reported by a few studies.The degree of heterogeneity was not improved on exclusion of studies with poor quality, but markedly improved on subgroup analysis according to geographical region and presence of MIS-C. Studies from China showed that children with COVID-19 had significantly lower pooled prevalence for any of the GI symptoms with low degree of heterogeneity, particularly for diarrhea, nausea/vomiting, and abdominal pain, all of which had I2 of 0%. Those with multisystem inflammatory syndrome in children (MIS-C) had significantly more common GI symptoms and increased transaminases than those without. One-third of children with COVID-19 exhibit at least one GI symptom and more likely present in those with severe disease. Elevated transaminases were present in 10%. Prevalence of GI and hepatic manifestations were higher among children with MIS-C.

Redesigning the kinetics of lysozyme amyloid aggregation by cephalosporin molecules.

In lysozyme amyloidosis, fibrillar aggregates of lysozyme are associated with severe renal, hepatic, and gastrointestinal manifestations, with no definite therapy. Current drugs are now being tested in amyloidosis clinical trials as aggregation inhibitors to mitigate disease progression. The tetracycline group among antimicrobials in use is in phase II of clinical trials, whereas some macrolides and cephalosporins have shown neuroprotection. In the present study, two cephalosporins, ceftazidime (CZD) and cefotaxime (CXM), and a glycopeptide, vancomycin (VNC), are evaluated for inhibition of amyloid aggregation of hen egg white lysozyme (HEWL) under two conditions (i) 4 M guanidine hydrochloride (GuHCl) at pH 6.5 and 37° C, (ii) At pH 1.5 and 65 °C. Fluorescence quench titration and molecular docking methods report that CZD, CXM, and VNC interact more strongly with the partially folded intermediates (PFI) in comparison to the protein's natural state (N). However, only CZD and CXM proficiently inhibit the aggregation. Transmission electron microscopy, tinctorial assessments, and aggregation kinetics all support oligomer-level inhibition. Transition structures in CZD-HEWL and CXM-HEWL aggregation are shown by circular dichroism (CD). On the other hand, kinetic variables and soluble fraction assays point to a localized association of monomers. Intrinsic fluorescence (IF),1-Anilino 8-naphthalene sulphonic acid, and CD demonstrate structural and conformational modifications redesigning the PFI. GuHCl-induced unfolding and differential scanning fluorimetry suggested that the PFI monomers bound to CZD and CXM exhibited partial stability. Our results present two mechanisms that function in both solution conditions, creating a novel avenue for the screening of putative inhibitors for drug repurposing. We extend our proposed mechanisms in the designing of physical inhibitors of amyloid aggregation considering shorter time frames and foolproof methods.Communicated by Ramaswamy H. Sarma.

НАСЛЕДСТВЕННЫЕ ЗАБОЛЕВАНИЯ, ПРОТЕКАЮЩИЕ С ПОРАЖЕНИЕМ ПЕЧЕНИ (ЛЕКЦИЯ)

Background. Hereditary liver diseases are a serious problem in all age groups. Diagnosis of the hereditary liver disor-ders in many cases turns out to be difficult, and before final diagnosis, the patient can change more than one doctor and lose time, which can lead to a worsening of the disease. Therefore, the issue of timely diagnosis of hereditary liver diseases remains relevant. The lecture discusses the issues of diagnosing hereditary diseases occurring with liver damage. Both monogenic syndromes and multifactorial diseases are reviewed. Urea cycle disorders, aminoacidopathias and organic acidurias, lysosomal storage diseases, mitochondrial and peroxisomal diseases, disorders of fatty acids β-oxidation, carbohy-drate, lipid and cholesterol metabolism disorders and other diseases are described. The article describes the syndromes of liver disorders that occur in hereditary diseases; presents the combinations of individual syndromes having diagnostic significance. The pathogenetic aspects of the development of hepatic manifestations of hereditary diseases are considered. Conclusion. Symptoms of liver damage are often in the practice of any physician. Most of them are the manifesta-tions of somatic pathology. However, certain combinations of symptoms of liver damage (syndromes) indicate heredi-tary pathology. Therefore, it is extremely important to know the main liver syndromes in specific hereditary diseases, to understand the etiopathogenesis of such disorders and to carry out proper differential diagnosis.