Form Of Liver Disease Research Articles

Case of Fatal Hepatitis Related to HEV-3 Infection in Central Italy

Hepatitis E virus (HEV) is a global health problem, causing an estimated 20 million infections annually. Thus, the management of HEV requires special consideration. In developed countries, hepatitis E is mainly recognized as a foodborne disease (mainly transmitted via undercooked meat consumption) that is generally caused by genotype 3 and 4 circulating in various animals, including pigs and wild boars. The current absence of officially recognized protocols for the analysis of HEV in foods and the lack of awareness of this disease among healthcare workers, together with the high percentage of asymptomatic cases, make HEV infection highly underestimated. Most HEV-3 infections in immunocompetent individuals are self-limited. Nevertheless, the possibility of serious forms of liver disease, especially in patients with co-morbidities, should be considered because it can lead to a fatal outcome. Here, we report a case of fatal hepatitis related to HEV-3 infection in a 67-year-old male patient with underlying chronic liver disease (CLD) and living in a region where a high prevalence and genetic heterogeneity of HEV-3 in wild boar has been recently demonstrated. Our case report describes the interdisciplinary approach used (from the diagnosis to the virus phylogenetic characterization) in order to improve epidemiologic HEV surveillance in central Italy.

Faecal microbiota transplantation associated adverse events

Abstract Faecal microbiota transplantation (FMT) aims to restore intestinal microbiota balance with the objective of normalising its composition and achieve therapeutic benefits. The procedure involves the administration of fresh or frozen faecal microbes from a healthy donor into the recipient’s gastrointestinal tract with the intent to restore the proper structure and functionality of the recipient’s intestinal microbial community. Evidence showing the positive effects of FMT is abundant, however, less attention has been devoted to FMT-associated adverse events, especially in relation to liver diseases. Based on literature review, studies and reports regarding FMT-associated adverse events since the beginning of FMT use, have been analysed. The review covering the period 2010-2022 was undertaken in accordance with the PRISMA guidelines. Studies conducted on the patient population suffering from various types and forms of liver disease have proven the possible effectiveness of the FMT method and reported moderate adverse events (nausea, constipation, flatulence). Severe adverse events occurring in relation to FMT were also noted. No safety issues or infection signals associated with FMT were observed in studies performed within the population suffering from cirrhosis. The present review of scientific reports, publications and literature reviews describes the adverse events reported in the literature. Faecal microbiota transplants are associated with adverse events classified as mild, moderate and severe, among others, diarrhoea, fever, infections or death. There is a need to implement a donor screening programme and personalised transplantation methods. Further research is recommended to assess and monitor FMT efficacy, benefits and risks.

Association between Autoimmune Hepatitis and Celiac Disease among Egyptian Children and Adolescents

Abstract Background Celiac disease (CD) is an immune-mediated intolerance to gluten .CD has been recognized as a multisystem disorder which may affect other extra intestinal organs, such as the skin, thyroid, heart, nervous system, pancreas and liver. Individuals with CD are at increased risk of liver disease namely cryptogenic liver disorder and autoimmune liver disorder. However, until now, it remains unknown whether these two forms of liver disease are really different entities or only different severities of the same disorder. Objective To evaluate the association of CD with autoimmune hepatitis in pediatrics. Subjects and Methods This was a cross-sectional study that was conducted at the Pediatric Hepatology Clinic and Pediatric Gastroenterology Clinic, Children’s Hospital, Ain Shams University. The study included 2 groups of patients each comprised 20 children and adolescents as follow: Group I: Patients with established diagnosis of autoimmune hepatitis (AIH). All patients were receiving corticosteroids and azathioprine Group II: Patients with established diagnosis of CD. In group I patients with AIH, CD was screened for using anti-tissue transglutaminase (tTG) IgA in addition to measuring serum IgA to determine the need to measure anti-tTG IgG. Immunological markers (ANA, anti-smooth muscle antibody (ASMA) and liver and kidney microsomal (LKM) antibodies in addition to protein electrophoresis were done for group II patients with CD to screen for AIH. Results All patients in group I with AIH had normal serum IgA levels and were found negative for anti-tTG IgA. Also, group II patients with CD were negative for ANA, ASMA and LKM antibodies with normal protein electrophoresis. Conclusion The current study showed that CD does not seem to have significant association with AIH, however, the small sample size is a study limitation. Further wider scale studies are needed to evaluate the risk of AIH in CD.

FAdV-4-induced ferroptosis affects fat metabolism in LMH cells

Ferroptosis is a form of controlled cell death that was first described relatively recently and that is dependent on the formation and accumulation of lipid free radicals through an iron-mediated mechanism. A growing body of evidence supports the close relationship between pathogenic infections and ferroptotic cell death, particularly for viral infections. Ferroptosis is also closely tied to the pathogenic development of hepatic steatosis and other forms of liver disease. Fowl adenovirus serotype 4 (FAdV-4) is a hepatotropic aviadenovirus causing hydropericardium syndrome (HPS) that is capable of impacting fat metabolism. However, it remains uncertain as to what role, if any, ferroptotic death plays in the context of FAdV-4 infection. Here, FAdV-4 was found to promote ferroptosis via the p53-SLC7A11-GPX4 axis, while ferrostain-1 was capable of inhibiting this FAdV-4-mediated ferroptotic death through marked reductions in lipid peroxidation. The incidence of FAdV-4-induced fatty liver was also found to be associated with the activation of ferroptotic activity. Together, these results offer novel insights regarding potential approaches to treating HPS.

ONBLR: An effective optimized ensemble ML approach for classifying liver cirrhosis disease

Liver cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. Early diagnosis and management can help slow the progression of the disease and improve quality of life. Developing more accurate and non-invasive methods for the early detection of liver cirrhosis to enhance timely intervention and improve patient outcomes. Effective prediction reduces overall cirrhosis patients' mortality due to various bleeding, making further study in this field a significant task. Therefore, we propose a novel ensemble machine learning based approach for classification. Label encoding and data normalization using the min-max approach are performed in preprocessing. Then, characteristics such as age, gender, Liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and Medical history and comorbidities are retrieved using the ConvNeXt approach. Using the Improved Grasshopper optimization algorithm (IGOA), the essential features that increase the accuracy even more were selected. Finally, the optimized ensemble machine learning approach naïve Bayes and logistic regression (ONBLR) is employed to classify the liver cirrhosis disease. Harris Hawks optimization algorithm is employed to optimize the hyperparameters. The proposed approach is compared with the existing state-of-the-art machine learning approaches. While compared with existing approaches, the proposed model yields 99.18 % accuracy, 99.12 % of Sensitivity and 98.92 % of specificity which is greater among other approaches.

Acetaminophen: A Liver Killer or Thriller.

Acetaminophen, or paracetamol, ranks among the most extensively utilized analgesic and antipyretic medications globally. The administration of acetaminophen to individuals with underlying liver disease has long sparked concerns regarding the potential risk of hepatotoxicity. However, the available literature and recommendations consider it a safe option in all forms of liver diseases and is deemed safe when used at recommended doses. This article aims to offer a concise review of the pharmacokinetics, toxicity profile, and the intricate considerations surrounding the safety of acetaminophen in patients with liver disease. By delving into the liver-acetaminophen interactions, we seek to provide a nuanced perspective on the use of acetaminophen in this critical patient population.

Correlation between Severity of Liver Disease According to CHILD & MELD Scores and Degree of Cardiac Impairment

Abstract Background Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. The prevalence of cirrhosis has nearly doubled over the last decade, and the number of hospitalizations has similarly increased. Objective To detect correlation between severity of liver disease according to Child and MELD scores and degree of cardiac impairment such as systolic and diastolic functions and ECG changes. To elucidate this aim 60 cases were included in the current study. Patients and Methods Type of Study: Cross-sectional Study. Study Setting: This study was carried out in El-Demerdash Hospital-Ain Shams University and El-Qabbary Hospital - Alexandria. Study Period 6 months Results In the current study, there was statistically significant increase in age of positive ECG cases than negative ECG cases; also the percentage of males in positive ECG cases was found higher than those of negative ECG cases. There was statistically significant increase in child B and C in positive ECG group than negative ECG group. There was statistically significant increase in the level of Meld score, T. bilirubin and D. bilirubin in positive ECG group than negative ECG group; and statistically significant decrease in the level of albumin and NA in positive ECG group than negative ECG group. That there was statistically significant positive correlation found between MELD score and AST, ALT, total biliruibn, direct bilirubin, PT, INR and creatinine and also negative correlation found between meld score and albumin and NA levels. Conclusion There was statistically significant relation found between child score, MELD.S (the severity of cirrhosis) and ECG results. There was a high statistically significant difference in between ECHO and MELD.S but no statistically significant difference in between ECHO and CHILD.S, therefore, in order to prepare the best post-procedural management of cirrhotic patients, echocardiography is required for all patients before any interventional procedure or liver transplantation regardless of the stage of cirrhosis. The mechanism of cardiac involvement in patients with cirrhosis seems to be complex and multifactorial.

Evaluation of Left Ventricular Diastolic Function Using a Tissue-Doppler Imaging Based Algorithm According to 2016 Ase/Eacvi Guidelines in Patients with Decompensated Liver Cirrhosis: A Prospective Observational Study

Abstract Background Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. The prevalence of cirrhosis has nearly doubled over the last decade, and the number of hospitalizations has similarly increased. Aim of the Work We aimed to correlate between the severity of liver cirrhosis using new MELD score and left ventricle diastolic dysfunction using tissue doppler imaging. Patients and Methods A prospective observational study in ICU of Theodor Bilharz Research Institute Hospital and Ain Shams University Hospitals for 6 months from June 2021 till end of November 2021 on hepatic patients who were admitted to ICU of Theodor Bilharz Research Institute Hospital and Ain Shams University Hospitals. Results In the studied group, the mean age was 53.13±9.44 years with males constituting more than half of them (57.8%). The mean MELD score was 24.08±6.01, and the mean left ventricular ejection fraction (LVEF %) was 60.43±5.49%. There were 5 patients (5.6%) with normal LV diastolic function and 85 patients (94.4%) with abnormal LV diastolic dysfunction. Out of the 90 patients, 5 patients were normal, 44 patients (48.9%) had a grade I LVDD, 28 patients (31.1%) had a grade II LVDD and 13 patients (14.4%) had a grade III LVDD. There was a highly statistically significant positive association between the grades of left ventricular diastolic dysfunction according to ALT, AST, T.Bilirubin, D.Bilirubin, INR and Creatinine. Additionally, there was a highly statistically significant negative association between grading of left ventricular diastolic dysfunction according to platelet count and sodium levels. Conclusion There was a statistically significant correlation found between the severity of liver cirrhosis represented by the new MELD score and the grade of left ventricular diastolic dysfunction. Therefore, in order to prepare the best post-procedural management of cirrhotic patients, echocardiography is required for all patients before any interventional procedure or liver transplantation regardless of the stage of cirrhosis. The mechanism of cardiac involvement in patients with cirrhosis seems to be complex and multifactorial.

Every ED Visit is an Opportunity to Talk about Contraception

Every ED Visit is an Opportunity to Talk about Contraception

Recent advances in NAFLD: current areas of contention.

This brief review focuses on two contentious issues within the field of non-alcoholic fatty liver disease (NAFLD); the first is the recent effort to redefine NAFLD as metabolic (dysfunction)-associated fatty liver disease (MAFLD). The modification of "NAFLD" to "MAFLD" is expected to highlight the role of metabolic factors in the disease aetiology, which is hoped to improve patient understanding of the disease, facilitate patient-physician communication and highlight the importance of public health interventions in prevention and management. The diagnostic criteria for MAFLD allow it to coexist with other forms of liver disease, which recognises that metabolic dysfunction contributes towards disease progression in other liver pathologies, such as alcoholic liver disease. However, there remain concerns that renaming NAFLD may be premature without fully considering the broader implications, from diagnostic criteria to trial endpoints; therefore, the new definition has not yet been accepted by major societies. Another contentious issue within the field is the gap in our understanding of how patients undergoing therapeutic interventions should be monitored to assess amelioration/attenuation or the worsening of their liver disease. Biomarker scoring systems (such as the ELF test and FIB-4 test) and imaging techniques (such as transient elastography [TE] and magnetic resonance imaging [MRI] techniques) are proven to be reasonably accurate, and comparable with histology, in the diagnosis of NAFLD and evaluation of disease severity; however, their use in monitoring the response of disease to therapeutic interventions is not well established. Whilst biomarker scoring systems and TE are limited by poor diagnostic accuracy in detecting moderate fibrosis (e.g. F2 liver fibrosis defined by histology), more accurate MRI techniques are not practical for routine patient follow-up due to their expense and limited availability. More work is required to determine the most appropriate method by which therapeutic interventions for NAFLD should be monitored in clinical practice.

Noninvasive identification of probable fibrotic nonalcoholic steatohepatitis across the spectrum of glucose tolerance in the United States

AimIdentifying patients with fibrotic nonalcoholic steatohepatitis (NASH) is crucial in order to refer them to specialist care as fibrotic NASH represents one of the major inclusion criteria for clinical trials. The aim of this study is to report the prevalence of fibrotic NASH in the general US population across the spectrum of glucose tolerance and evaluate the performance of the recently proposed Fibrotic NASH Index (FNI). MethodsThis is a cross-sectional study of US adults participating in the 2017–2020 cycles of the National Health and Nutrition Examination Survey. Participants with available data to calculate FNI (which is based on AST, HbA1c and HDL-cholesterol) and with a reliable vibration controlled transient elastography examination were included. We excluded participants with chronic viral hepatitis, significant alcohol consumption or other forms of liver disease. Probable fibrotic NASH was defined as a Fibroscan-AST (FAST) score ≥ 0.35. ResultsWe included a total of 6268 participants. The overall prevalence of probable fibrotic NASH was 5.9 % (95 % CI 5.2–6.7) and it increased progressively from participants with normal glucose tolerance (3.7 %, 95 % CI 2–9-4.7) to those with diabetes (14.7 %, 95 % CI 12.1–17.8). The performance of FNI for probable fibrotic NASH was satisfactory in the overall population (area under the receiver operating characteristic curve (AUROC): 0.93, 95 % CI 0.92–0.94) and it maintained a good accuracy also in participants with diabetes (n = 1113, AUROC 0.89, 95 % CI 0.86–0.92). In all groups it outperformed Fibrosis-4. ConclusionsFNI is an easy and reliable test to screen for NASH and its performance is maintained in patients with diabetes, a condition that was shown to negatively influence the performance of several non-invasive scores.

Preparation and Characterization of Silymarin Gel: A Novel Topical Mucoadhesive Formulation for Potential Applicability in Oral Pathologies.

Silybum marianum has been used for centuries by herbalists and physicians to treat different forms of liver diseases. It contains flavonoid, which has antioxidant, anti-inflammatory, antifibrotic and anticancer properties. The objective of this research was to develop a silymarin-based mucoadhesive gel for prolonged release in oral mucosa and to evaluate the same by using in vitro drug release kinetic models and ex vivo methods for drug permeation using chicken buccal mucosa. The mucoadhesive gel was formulated in different trials by varying the concentration of silymarin and polymer. Out of 10 formulation trials, the F10 optimized trial was characterized for in vitro physicochemical parameters such as pH, homogeneity, viscosity, stability, drug content, in vitro drug release, in vitro antioxidant assay and ex vivo permeation study. Trial 10 was chosen as the best trial formulation among the other trials and was marked as an optimal trial. The physicochemical properties observed were pH to be 6.4 ± 0.01, the gel free of lumps, spreadability of 23.75 ± 0.03 and drug content of 32.77 ± 0.20 mg/g. It had no physiological changes such as color shift or fluid exudate segregation after 6 months of storage at room temperature. In vitro drug release established the presence of a non-fickian mechanism and demonstrated dose-dependent antioxidant activity. Ex vivo findings indicated 21.97 ± 0.18% release, proving that the gel can permeate through the oral mucosal membrane. Our future research will concentrate on expanding the therapeutic scope by developing the formulation trial F10 to a nanoformulation and conducting clinical trials for its potential use in various oral diseases.

Prediction of Liver Disease using Machine Learning

Healthcare system is becoming a significant factor of every human being. So in this paper we are discussing about the vital organ of the human body i.e. Liver. Early analysis of liver disease prediction is highly challenging. As a result, liver disease has become more common which is gradually improved, enhancing people's troubles. To recognize the causes and the identification phases are more important. For this, we applied a machine learning technique that was highly promising for studies with regard to healthcare and health. To uncover hidden data for precise diagnosis and decision-making, ML can also be used. Any form of liver disease is hazardous to your health. Poisons, narcotics, and excessive drinking are the main causes of this condition. In this study, we will use several associated features and KNN technology to enhance liver disease prediction. The accuracy forecast is provided by this algorithm.

Phytochemical Characterization, Hepatoprotective Activity on Alcohol-Induced Toxicity of the Aqueous Extract of Curcuma longa (Zingiberaceae) in Wistar Rats

Introduction: Liver or hepatic disease refers to different conditions that affect the liver. Chronic alcohol consumption is one of the most frequent causes of liver disease and accounts for about 55% of liver cirrhosis deaths recorded in Cameroon in 2020. Standard accessible treatments focus on end-stage liver disease with safety and efficacy obstacles. We have a research gap in Cameroon to understand the alternative use of natural products as treatment with a long traditional history of safe use. Curcuma longa has long been a source of traditional and modern medicine. It is commonly used in Cameroon as a spice and herbal product with some level of activity against various forms of liver disease.
 Objective: To phytochemically screen for bioactive metabolites and evaluate the hepatoprotective activity of the aqueous extract of Curcuma longaon alcohol-induced toxicity in Wistar rats.
 Methods: Phytochemical screening was carried out on the aqueous extract obtainedfrom maceration of plant rhizomes. Three doses (125, 250 and 500mg/Kg) of the plant extract and the reference (Silymarin 50mg/Kg) were administered daily (p.o) to rats 30 min before administration of 40% alcohol (2mL/100g p.o) for 21 days. Biochemical parameters such as ALAT, ASAT, GGT, Bilirubin and Lipid profile were quantified and histological studies of the liverwas carried out using standard procedures.
 Results: Phytochemical screening of the aqueous extract of C. longa revealed polyphenols such as flavonoids, tannins, quinones, saponins and phlobatanins. The plant showed hepatoprotective activity by decreasing liver toxicity markers such as ASAT, ALAT, GGT and Bilirubin. Histology revealed dose-dependent protection with 500 mg/Kg showing the most cellular integrity, no central vein occlusion and minimal fibrosis.
 Conclusion: This study indicated the presence of polyphenols like flavonoids and tannins in the aqueous extract of C. longa. The presence of these secondary metabolites in the studied extract justifies its antioxidant and anti-inflammatory properties confirmed by its hepatoprotective effects on alcohol-induced toxicity. This was clearly shown by biochemical and histological parameters. More sensitive and specific methods are required to test for these secondary metabolites in serum.

Abstract 10784: Circulating Obesity Associated Pro-Fibrotic Protein Promotes Fibrosis in Liver and Heart

Introduction: Non-alcoholic steatohepatitis (NASH), driven by the obesity epidemic, has become the most common form of liver disease. Obesity contributes inflamed visceral adipose tissue secretes pro-inflammatory adipokines that is causal for systemic metabolic disorders. Despite its importance, the mechanism of NASH in the presence of morbid obesity related adipokines from BAT remains unclear. Hypothesis: Various kinds of white adipokines are known in obesity. However, brown adipokines still remain to be explored. Methods: To identify the function of obesity associated pro-fibrotic protein (OAFP), we generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and murine systemic OAFP knockout (KO) model. We also conducted functional in vitro studies with differentiated brown adipocytes. Results: Analyzing two sets of DNA microarray data with bioinformatics, we identified a secreted form OAFP expressed in dysfunctional brown adipose tissue (BAT) in mice. Testing our biobank samples, we found this protein increased in plasma of NASH patients or aged individuals. We generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and found that OAFP is produced predominantly by BAT. In this model, we also found that OAFP increased in plasma. For this reason, we generated a murine systemic OAFP knockout (KO) model and found that liver fibrosis ameliorated in OAFP-KO model. In addition, vaccination therapy also inhibited liver fibrosis. In contrast, liver fibrosis augmented in OAFP gain of function (GOF) model, and these results suggested that OAFP has causal role for the progression of fibrotic response in liver. In the obese NASH model, we found that cardiac fibrosis also developed and this ameliorated in OAFP-KO model, indicating that OAFP may have pathological roles for heart failure with preserved ejection fraction (HFpEF) related with age-related disorders. In vitro studies with differentiated brown adipocytes showed that OAFP was upregulated through by PERK/JNK/c-fos/AP1 pathways. Conclusions: Our results suggest that OAFP contributes for the progression of fibrotic responses in obese or aged models. Inhibition of OAFP may become a therapy for NASH or HFpEF.

Endo-hepatology: An emerging field.

Gastroenterologists have long been spearheading the care of patients with various forms of liver disease. The diagnosis and management of liver disease has traditionally been a combination of clinical, laboratory, and imaging findings coupled with percutaneous and intravascular procedures with endoscopy largely limited to screening for and therapy of esophageal and gastric varices. As the applications of diagnostic and therapeutic endoscopic ultrasound (EUS) have evolved, it has found a particular niche within hepatology now coined endo-hepatology. Here we discuss several EUS-guided procedures such as liver biopsy, shear wave elastography, direct portal pressure measurement, paracentesis, as well as EUS-guided therapies for variceal hemorrhage.

NAFLD and its link with diabetes: Why we should be worried

Louise Cremonesini and Emma Harkin look at this increasingly common form of liver disease

Myeloid DJ-1 deficiency protects acetaminophen-induced acute liver injury through decreasing inflammatory response.

Background: DJ-1 (also known as PARK7), a noted protein implicated in modulating ROS production and immune response, has been observed to play critical roles in the pathogenesis of many forms of liver disease through multiple mechanisms. However, its role and specific mechanism in acetaminophen (APAP) -induced liver injury have not been explored.Results: In this present study, by employing an acute liver injury induced by APAP overdose mouse model, we demonstrated that DJ-1 knockout (DJ-1−/−) mice showed reduced liver injury and lower mortality. In accordance with these changes, there were also alleviating inflammatory responses in both the serum and the liver of the DJ-1−/− mice compared to those of the wild-type (WT) mice. Functional experiments showed that APAP metabolism did not affected by DJ-1 deficiency. In addition, to investigate DJ-1 modulates which kind of cell types during APAP-overdose-induced acute liver injury, hepatocyte-specific DJ-1-knockout (Alb-DJ-1−/−) and myeloid-specific DJ-1-knockout (Lysm-DJ-1−/−) mice were generated. Interestingly, hepatic deletion of DJ-1 did not protect APAP-overdose induced hepatotoxicity and inflammation, whereas Lysm-DJ-1−/− mice showed similar protective effects as DJ-1−/− mice which suggest that the protective effects of deletion of DJ-1 was through modulating myeloid cell function. Consistently, there were alleviated pro-inflammatory cells infiltration and reduced reactive oxygen species (ROS) production in the liver of Lysm-DJ-1−/− mice relative to control mice.Conclusion: our findings clearly defined that deletion of DJ-1 protects APAP-induced acute liver injury through decreasing inflammatory response, and suggest DJ-1 as a potential therapeutic and/or prophylactic target of APAP-induced acute liver injury.

Melatonin as a Potential Multitherapeutic Agent.

Melatonin (N-acetyl-5-methoxytryptamine, MEL) is a hormone produced by the pineal gland that was discovered many years ago. The physiological roles of this hormone in the body are varied. The beneficial effects of MEL administration may be related to its influence on mitochondrial physiology. Mitochondrial dysfunction is considered an important factor in various physiological and pathological processes, such as the development of neurodegenerative and cardiovascular diseases, diabetes, various forms of liver disease, skeletal muscle disorders, and aging. Mitochondrial dysfunction induces an increase in the permeability of the inner membrane, which leads to the formation of a permeability transition pore (mPTP) in the mitochondria. The long-term administration of MEL has been shown to improve the functional state of mitochondria and inhibit the opening of the mPTP during aging. It is known that MEL is able to suppress the initiation, progression, angiogenesis, and metastasis of cancer as well as the sensitization of malignant cells to conventional chemotherapy and radiation therapy. This review summarizes the studies carried out by our group on the combined effect of MEL with chemotherapeutic agents (retinoic acid, cytarabine, and navitoclax) on the HL-60 cells used as a model of acute promyelocytic leukemia. Data on the effects of MEL on oxidative stress, aging, and heart failure are also reported.

SARS-CoV-2 infection in patients with autoimmune hepatitis

Background & AimsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continues to have a devastating impact across the globe. However, little is known about the disease course in patients with autoimmune hepatitis (AIH).MethodsData for patients with AIH and SARS-CoV-2 infection were combined from 3 international reporting registries and outcomes were compared to those in patients with chronic liver disease of other aetiology (non-AIH CLD) and to patients without liver disease (non-CLD).ResultsBetween 25th March and 24th October 2020, data were collected for 932 patients with CLD and SARS-CoV-2 infection including 70 with autoimmune hepatitis (AIH). Fifty-eight (83%) patients with AIH were taking ≥1 immunosuppressive drug. There were no differences in rates of major outcomes between patients with AIH and non-AIH CLD, including hospitalization (76% vs. 85%; p = 0.06), intensive care unit admission (29% vs. 23%; p = 0.240), and death (23% vs. 20%; p = 0.643). Factors associated with death within the AIH cohort included age (odds ratio [OR] 2.16/10 years; 1.07–3.81), and Child-Pugh class B (OR 42.48; 4.40–409.53), and C (OR 69.30; 2.83–1694.50) cirrhosis, but not use of immunosuppression. Propensity score matched (PSM) analysis comparing patients with AIH with non-AIH CLD demonstrated no increased risk of adverse outcomes including death (+3.2%; -9.2%–15.7%). PSM analysis of patients with AIH vs. non-CLD (n = 769) demonstrated increased risk of hospitalization with AIH (+18.4%; 5.6–31.2%), but equivalent risk of all other outcomes including death (+3.2%; -9.1%–15.6%).ConclusionPatients with AIH were not at increased risk of adverse outcomes despite immunosuppressive treatment compared to other causes of CLD and to matched cases without liver disease.Lay summaryLittle is known about the outcomes of COVID-19 in patients with autoimmune hepatitis (AIH), a rare chronic inflammatory liver disease. This study combines data from 3 large registries to describe the course of COVID-19 in this patient group. We show that AIH patients do not appear to have an increased risk of death from COVID-19 compared to patients with other forms of liver disease and compared to patients without liver disease, despite the use of medications which suppress the immune system.