Abnormal Liver Research Articles

The health effects of non-prescribed anabolic-androgenic steroid use: Findings from The Performance and image-enhancing drugs UseRS' Health (PUSH) audit.

To ascertain the adverse health outcomes experienced by those using prescribed testosterone and non-prescribed anabolic-androgenic steroids presenting to general practitioner (GP) clinics. Retrospective clinical audit from nine GP clinics in major metropolitan areas across three Australian states. Data included demographic and individual characteristics (age, sexuality, body mass index, smoking status and HIV status); performance and image-enhancing drug use (type, reasons for use, patient-reported adverse effects); and blood biochemistry measurements (lipid profiles, liver function tests and red blood cell tests). Adverse health outcomes included evidence of polycythaemia, hypertension, liver abnormalities and hypercholesterolemia. Three hundred men were identified as either using prescribed testosterone (66%; n = 197) or non-prescribed anabolic-androgenic steroids (AAS) (34%; n = 103). Individuals in the prescribed group were more likely to be older (p < 0.001), gay or bisexual (p < 0.001) and living with diagnosed HIV (p < 0.001) compared to individuals in the non-prescribed group. Abnormal liver function, polycythemia and gynecomastia were the top three adverse events experienced. When adjusting for age, sexuality, HIV status and smoking status, those who used non-prescribed AAS were more likely to experience any adverse event (aPR = 1.28; 95% CI 1.01-1.60; p = 0.038), hypertension (aPR = 1.86; 95% CI 1.19-2.91; p = 0.006) and liver abnormalities (aPR = 1.51; 95% CI 1.04-2.20; p = 0.030) compared to those using prescribed testosterone. For GPs who have clients who may be using, or who they suspect of using, AAS, these findings highlight the importance of not only exploring a patient's history of the adverse effects they have experienced, but that measuring for these other conditions may provide a more accurate clinical picture.

Therapeutic effect of San Bi Tang combined with glucosamine sulfate capsules in cold-dampness-type knee osteoarthritis.

Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease, but its pathogenesis is not fully understood, and its clinical treatment has limitations. Glucosamine sulfate capsules are commonly used for treating arthritis, and San Bi Tang is a classic formula of traditional Chinese medicine (TCM) that has the effects of warming yang, dispelling dampness, relaxing muscles, and activating collaterals. This research hypothesized that the combination of modified San Bi Tang and glucosamine sulfate capsules could enhance the clinical efficacy of treating cold-dampness-type knee osteoarthritis through complementary effects. To analyze the clinical efficacy of San Bi Tang combined with glucosamine sulfate capsules when treating cold-dampness-type knee osteoarthritis. A total of 110 patients with cold-dampness-type knee osteoarthritis were selected as research subjects and randomly divided into a control group and an experimental group of 55 cases each. The control group received only treatment with glucosamine sulfate capsules, while the experimental group received additional treatment with modified San Bi Tang for a duration of 5 wk. The patients' knee joint functions, liver and kidney function indicators, adverse reactions, and vital signs were evaluated and analyzed using SPSS 26.0 software. Before treatment, the two groups' genders, ages, and scores were not significantly different, indicating comparability. Both groups' scores improved after treatment, which could indicate pain and knee joint function improvement, but the test group had better scores. The TCM-specific symptoms and the clinical efficacy of the treatment in the test group were higher. Before and after treatment, there were no abnormalities in the patients' liver and kidney function indicators. The combination of modified San Bi Tang and glucosamine sulfate capsules is superior to treatment with sulfated glucosamine alone and has high safety.

Association between COVID-19 severity with liver abnormalities: A retrospective study in a referral hospital in Indonesia.

Coronavirus disease 2019 (COVID-19) is characterized by an acute respiratory infection with multisystem involvement and the association of its severity to liver function abnormalities is not well characterized. The aim of this study was to assess the association between the severity of COVID-19 patients and liver function abnormalities. This retrospective study included adult patients with confirmed COVID-19, which were classified as non-severe or severe according to World Health Organization guidelines. Liver function test results were compared between the severity groups. A total of 339 patients were included of which 150 (44.25%) were severe cases. The male-to-female ratio was 0.9:1 and 3:2 in the non-severe and severe groups, respectively (p=0.031). Aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels and acute liver injury (ALI) incidence were significantly higher in the severe group compared to non-severe group (p<0.001, p<0.001, p=0.025, p=0.014, respectively). In contrast, albumin levels were significantly lower (p=0.001). Multivariate analysis showed that ALI was significantly associated with human immunodeficiency virus (HIV) infection (odds ratio (OR): 5.275; 95% confidence interval (CI): 1.165-23.890, p=0.031), hemoglobin level (OR: 1.214; 95%CI: 1.083-1.361, p=0.001), and hypoalbuminemia (OR: 2.627; 95%CI: 1.283-5.379, p=0.008). Pre-existing liver diseases were present in 6.5% of patients. No significant differences were observed between the groups based on COVID-19 severity and ALI presence. Liver function test abnormalities, including ALI, are more prevalent in patients with severe COVID-19 infection. HIV infection, high hemoglobin levels, and hypoalbuminemia may be potential risk factors for ALI.

Abnormal Liver Biopsies of Donor Grafts in Pediatric Liver Transplantation: How Do They Fare?

BACKGROUND Little is known about outcomes of pediatric patients transplanted using donor liver grafts with abnormal biopsy results. We assessed donor liver biopsy data to report characteristics and outcomes of abnormal livers transplanted in pediatric patients. MATERIAL AND METHODS We identified pediatric patients who received a liver transplant from a biopsied deceased donor between 2015 and 2022 using the national database UNOS Standard Transplant Analysis and Research files. Recipients were excluded if they received multi-organ transplants or were lost to follow-up. Livers with ≤5% macrosteatosis, no fibrosis, and no inflammation were classified as normal livers (NL). Allografts with >5% macrosteatosis, any fibrosis, or any inflammation were considered abnormal livers (AL). Donor and recipient demographic data and outcomes were examined. RESULTS Of the 3808 total pediatric liver transplants in the study period, there were 213 biopsied donor liver allografts transplanted into pediatric recipients. Of those, 114 were NL and 99 were AL. 35.4% (35/99) of the AL had >5% macrosteatosis with a mean of 7.6±11.4%, 64.6% (64/99) had any inflammation, and 18.2% (18/99) had any fibrosis. AL donors were significantly older than NL donors. AL recipients had higher PELD scores. There were no significant differences in length of stay, rejection rates and causes, or allograft survival between AL and NL. Multivariable analysis revealed that inflammation was independently associated with a significantly greater risk for graft failure. CONCLUSIONS Outcomes of abnormal livers are excellent. Inflammation was an independent risk factor for poor graft prognosis. Donor biopsies in pediatric liver transplantation can be a useful adjunct to assess outcomes.

Exploitation of Bio-Inspired Classifiers for Performance Enhancement in Liver Cirrhosis Detection from Ultrasonic Images.

In the current scenario, liver abnormalities are one of the most serious public health concerns. Cirrhosis of the liver is one of the foremost causes of demise from liver diseases. To accurately predict the status of liver cirrhosis, physicians frequently use automated computer-aided approaches. In this paper, through clustering techniques like fuzzy c-means (FCM), possibilistic fuzzy c-means (PFCM), and possibilistic c means (PCM) and sample entropy features are extracted from normal and cirrhotic liver ultrasonic images. The extracted features are classified as normal and cirrhotic through the Gaussian mixture model (GMM), Softmax discriminant classifier (SDC), harmonic search algorithm (HSA), SVM (linear), SVM (RBF), SVM (polynomial), artificial algae optimization (AAO), and hybrid classifier artificial algae optimization (AAO) with Gaussian mixture mode (GMM). The classifiers' performances are compared based on accuracy, F1 Score, MCC, F measure, error rate, and Jaccard metric (JM). The hybrid classifier AAO-GMM, with the PFCM feature, outperforms the other classifiers and attained an accuracy of 99.03% with an MCC of 0.90.

Oral β-RA induces metabolic rewiring leading to the rescue of diet-induced obesity

Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as β-resorcylic acid (β-RA). Here, we show that oral supplementation with β-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of β-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of β-RA. Consequently, β-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of β-RA supports its translational potential. Thus, β-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD).

Alpha-1-Antitrypsin Deficiency in Children-Unmet Needs Concerning the Liver Manifestation.

This study aimed to analyse the clinical course of 45 children with severe alpha-1-antitrypsin deficiency (AATD) registered in our clinic to detect possible predictors of poor outcomes. The clinical and biological data of 45 patients with homozygous or compound heterozygous AATD were analysed. The data were collected retrospectively going back to 2005 and prospectively from May 2020 until October 2021. It was based on questionnaires, laboratory values, sonography, and biopsy findings. Liver disease was classified into four grades depending on the grade of liver disease: mild or no liver disease, moderate disease, severe disease, and liver transplantation. Thirty-nine patients (86.7%) had a Pi*ZZ and five (11.1%) a Pi*SZ genotype. One patient showed a new, not-yet-described compound heterozygous genotype (Pi*Z + Asp95Asn). A total of 66.7% of the cohort showed mild or no liver disease, 20% moderate, and 13.3% severe. AATD was diagnosed in most cases because of liver abnormalities, such as the elevation of transaminases (42.2%). A total of 29.4% of the patients with neonatal icterus prolongatus developed severe liver disease, and 25.7% were born small for their gestational age (SGA). Diseases of the atopic type were reported in 47.4% of the cases. The presence of neonatal icterus prolongatus in the first weeks of life was significantly more likely in severe courses of liver disease (r = 0.371, p = 0.012). A tendency toward atopic comorbidity in AAT-deficient children needs to be further evaluated.

A High-Fat and High-Fructose Diet Exacerbates Liver Dysfunction by Regulating Sirtuins in a Murine Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the most prevalent chronic liver disease, closely linked to the escalating rates of diabesity. The Western diet's abundance of fat and fructose significantly contributes to MASLD, disrupting hepatic glucose metabolism. We previously demonstrated that a high-fat and high-fructose diet (HFHFD) led to increased body and liver weight compared to the low-fat diet (LFD) group, accompanied by glucose intolerance and liver abnormalities, indicating an intermediate state between fatty liver and liver fibrosis in the HFHFD group. Sirtuins are crucial epigenetic regulators associated with energy homeostasis and play a pivotal role in these hepatic dysregulations. Our investigation revealed that HFHFD significantly decreased Sirt1 and Sirt7 gene and protein expression levels, while other sirtuins remained unchanged. Additionally, glucose 6-phosphatase (G6Pase) gene expression was reduced in the HFHFD group, suggesting a potential pathway contributing to fibrosis progression. Chromatin immunoprecipitation analysis demonstrated a significant increase in histone H3 lysine 18 acetylation within the G6Pase promoter in HFHFD livers, potentially inhibiting G6Pase transcription. In summary, HFHFD may inhibit liver gluconeogenesis, potentially promoting liver fibrosis by regulating Sirt7 expression. This study offers an epigenetic perspective on the detrimental impact of fructose on MASLD progression.

Factors Influencing Liver Abnormalities in Psoriatic Arthritis Patients: A Comprehensive Study.

The aim of this study was to establish the incidence of liver abnormalities in psoriatic arthritis patients and identify the factors that contributed to this condition. This is a longitudinal cohort study. Psoriatic arthritis (PsA) patients with liver enzymes abnormalities were identified. Our control group consisted of PsA patient from the same cohort who had no history of liver abnormalities. Factors associated with liver abnormalities were identified using univariate and multivariate analysis. A total of 247 of PsA patients were included and out of those, 99 developed liver enzymes abnormalities. The mean age of the patients was 56 years old (±13.5) with 56.1% female and 39.4% Indian descendants. The univariate logistic regression demonstrated that disease duration of PsA (OR=1.06, 95% CI=1.01 - 1.10, p=0.012), diabetes mellitus (OR=2.16, 95% CI=1.26 - 3.70, 0.005) and non-alcoholic fatty liver disease (NAFLD) (OR=3.90, 95% CI = 1.44 - 10.53, p=0.007) were associated with abnormal liver function in PsA patients. No association was found with both conventional synthetic disease-modifying antirheumatic drugs or biologics. Liver enzymes abnormalities in PsA patients were linked to disease duration, diabetes mellitus and NAFLD. For these high-risk populations, vigilant monitoring of liver function tests is vital for early detection and intervention.

Association of liver-abscess presence and severity with trim loss, slaughter yield, carcass grading performance, lung lesions, and value of fed-Holsteins*

ObjectiveOur objective was to evaluate the effects of liver abscesses on carcass characteristics and value of Holstein carcasses. Materials and MethodsFed-Holsteins were evalu- ated at 2 commercial processing facilities in Texas (n = 1,073) and Kansas (n = 1,070) from fall of 2016 through spring of 2017. Liver abscesses were visually assessed and scored; simultaneously, lungs were manually palpated to assess degree of consolidation and fibrin tag formation, to assess their association with liver abnormality. Finally, carcass trim was weighed from carcasses moved off line for zero tolerance trimming. Carcass and viscera values were assigned using USDA market reports and adjusted based on viscera condemnations along with premiums and dis- counts for quality and yield outcomes. Data were analyzed using the MIXED and GENMOD procedures of SAS v9.4 (SAS Institute Inc., Cary, NC) with carcass as the experi- mental unit. Results and DiscussionHot carcass weight was re- duced (−25.1 kg, −6.6%) in carcasses that had an ad- hered and open liver abscess as compared with carcasses without abscessed livers. Carcasses with adhered, open, or adhered and open liver scores had increased carcass trim (0.72, 3.92, and 3.39 kg, respectively) when compared with carcasses without abscessed livers (0.38 kg). Similarly, carcasses with adhered, open, or adhered and open liver scores returned gross carcass revenues that were 5.0% to 6.4% less (–$97.69, –$93.86, and –$121.22/carcass, re- spectively) than carcasses without abscessed livers. Liver abscesses reduced gross offal values of individual animals by 20% to 84% depending upon severity. Implications and ApplicationsFed-Holsteins have been a significant portion of the beef industry, even though Holsteins have increased rates of severe liver ab- scesses compared with their non-dairy-reared equivalents. Therefore, methods to control liver abscesses should be employed, to mitigate the greater financial risk that Hol- steins and dairy-reared animals incur to both cattle feeders and beef processors.

Relationship of liver abnormalities with carcass performance and value*

Relationship of liver abnormalities with carcass performance and value*

Morphological and Histopathological Liver Abnormalities Caused by Carbamazepine-Induced Injury in Female Albino Mice

Background: The adverse effects of drugs can damage various organs, especially the liver, leading to a hepatic injury known as hepatotoxicity. Drug-induced liver injury (DILI) is challenging nowadays because of the large number of different drugs used, one of the offending medications that cause DILI is carbamazepine (CBZ), since the liver has an array of functions including detoxification, it will deal with several damages caused by exposure to the drugs. Objective: investigate the effect of (CBZ) 20mg/kg/day on female mice liver after 14 and 30 days of treatment on morphological and histopathological levels. Materials and methods: 20mg/kg/day of CBZ was administered orally for (14) days to (10) female mice, another (10) mice were taking the same concentration for 30 days, and control groups were administered tap water. Results: The findings showed that CBZ can cause liver enlargement, changes in liver appearance, distortion in Glisson’s capsule, cytologic alterations, hepatocyte hypertrophy, ballooning degeneration, pyknosis, karyolysis, karyomegaly, sinusoids dilation, increase in the number and sizes of Kupffer cells, fibrosis, glycogen depletion, and cirrhosis. Conclusion: These findings have shown that carbamazepine (CBZ) can cause hepatotoxicity that can manifest into morphological and histopathological changes.

Subacute cadmium exposure changes different metabolic functions, leading to type 1 and 2 diabetes mellitus features in female rats.

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd-exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd-exposed rats had increased liver cholesterol levels, insulin receptor beta (IRβ) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats.

Characterization of liver abnormalities in a population of adult turner women: results from an observational study

Characterization of liver abnormalities in a population of adult turner women: results from an observational study

Randomized,double-blind,parallel controlled,multicenter clinical trial of effectiveness and safety of Shexiang Zhuifeng Zhitong Ointment in alleviating pain in knee osteoarthritis(syndrome of cold-dampness obstruction)

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P&lt;0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P&lt;0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P&lt;0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P&lt;0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.

Customized m-RCNN and hybrid deep classifier for liver cancer segmentation and classification

Diagnosing liver disease presents a significant medical challenge in impoverished countries, with over 30 billion individuals succumbing to it each year. Existing models for detecting liver abnormalities suffer from lower accuracy and higher constraint metrics. As a result, there is a pressing need for improved, efficient, and effective liver disease detection methods. To address the limitations of current models, this method introduces a deep liver segmentation and classification system based on a Customized Mask-Region Convolutional Neural Network (cm-RCNN). The process begins with preprocessing the input liver image, which includes Adaptive Histogram Equalization (AHE). AHE helps dehaze the input image, remove color distortion, and apply linear transformations to obtain the preprocessed image. Next, a precise region of interest is segmented from the preprocessed image using a novel deep strategy called cm-RCNN. To enhance segmentation accuracy, the architecture incorporates the ReLU activation function and the modified sigmoid activation function. Subsequently, a variety of features are extracted from the segmented image, including ResNet features, shape features (area, perimeter, approximation, and convex hull), and enhanced median binary pattern. These extracted features are then used to train a hybrid classification model, which incorporates classifiers like SqueezeNet and DeepMaxout models. The final classification outcome is determined by averaging the scores obtained from both classifiers.

Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population

Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

P008 High response rate to Janus Kinase inhibitors after multiple biologic drug failures, across disease indications, in a District General Hospital: results from an audit of the prescribing, safety and efficacy of Janus Kinase inhibitor

Abstract Background/Aims This audit aimed to improve the standard of prescribing JAK inhibitors and to determine the sustainability of response in Rheumatology patients at Royal Berkshire hospital (RBH) in Reading. During the last decade Janus kinase (JAK) inhibitors have had a dramatic uptake across multiple conditions in Rheumatology to control inflammation, reduce damage, pain and fatigue. Emerging data provides insight into their safety and effectiveness. These medications are contraindicated in patients with serious infections, cancer, blood clots, pregnancy and abnormal liver or renal function. Prescribing these medications needs careful consideration. We want to ensure we are taking appropriate precautions to minimize them and to review their efficacy in a real world District General Hospital setting. Methods Data was collected retrospectively from 100 patients who started treatment with JAK inhibitors in the last five years. We reviewed the indication, stage of disease, risk factors, whether patient information was provided and the response to treatment. We included patients with Rheumatoid arthritis (RA), Ankylosing Spondylitis, Psoriatic Arthritis. Our data collection template covered demographic information, medical history and disease activity at baseline as well as after starting JAK inhibitors; concomitant use of other DMARDs, safety and efficacy. Results A cohort of 100 patients (69 female and 31 male, average age 51.4 years) diagnosed with rheumatic conditions. The largest group were started on Baricitinib 64%, the smallest group on Upadacitinib. Baricitinib was the first JAK inhibitor approved for use in Rheumatology. Most RA patients were seropositive and had active disease at baseline. Comorbidities such as hypertension and diabetes were noted in 24 % and 14% of the patients respectively. 31% had a past history of smoking history, 9% had a history of malignancy. 22% of patients were on JAK monotherapy, the majority required an additional disease modifying antirheumatic drug (DMARDs). 43% of patients had tried two to three different biologics before starting JAK inhibitors. The average time from diagnosis to the first use of JAK inhibitors was 11 years. 2% of patients developed MACE and 3% herpes zoster on JAK. Only one of the deceased patients was on JAK inhibitors at the time of death and no causality was found. In &amp;lt; 10% of patients discussion on potential side effects was documented at baseline. 36% have discontinued the medication. Conclusion JAK inhibitors are highly effective in a real world population even when started after two to three biologic failures. A significant reduction in disease activity and sustainable remission was obtained in 64% of our patients. 43% of patients had previously failed to two or three biologics before starting a JAK inhibitor. We could improve patient education before starting treatment. Disclosure A. Escudero: None. S. Jain: None. N. Nisoe: None. J. McNally: None. H. Wardak: None.

Synergistic developmental effects of zebrafish exposed to combined perfluorooctanoic acid and atrazine

Perfluorooctanoic acid (PFOA) and atrazine are two endocrine disruptors that are widely found in waters. Negative effects of PFOA and atrazine have been studied individually, but few data have focused on their combined effects. Here, zebrafish embryos were used as model to investigate the combined toxicity of PFOA and atrazine. The acute toxicity of atrazine (11.9 mg/L) to zebrafish embryos was much higher than that of perfluorooctanoic acid (224.6 mg/L) as shown by the 120h-LC50 value. Developmental effects, including delayed yolk sac absorption, spinal curvature, and liver abnormalities, were observed in both one- and two-component exposures. Notably, the rate of embryonic malformations in the co-exposure group was more than twice as high as that of single component exposure in the concentration range of 1/8-1/2 EC50, which indicated a synergistic effect of the binary mixture. The synergistic effect of PFOA-atrazine was further validated by combinatorial index (CI) modeling. In addition, changes of amino acid metabolites, reactive oxygen species and superoxide dismutase indicated that oxidative stress might be the main pathway for enhanced toxicity under co-exposure condition. Overall, co-exposure of PFOA and atrazine resulted in stronger developmental effects and more complicated amino acid metabolic response toward zebrafish, compared with single component exposure.

A retrospective study of morbidity and mortality of chronic acid sphingomyelinase deficiency in Germany

BackgroundAcid sphingomyelinase deficiency (ASMD) is a rare, progressive, potentially fatal lysosomal storage disease that exhibits a broad spectrum of clinical phenotypes. There is a need to expand the knowledge of disease mortality and morbidity in Germany because of limited information on survival analysis in patients with chronic ASMD (type B or type A/B).MethodsThis observational, multicentre, retrospective cohort study was conducted using medical records of patients with the first symptom onset/diagnosis of ASMD type B or type A/B between 1st January 1990 and 31st July 2021 from four German medical centres. Eligible medical records were abstracted to collect data on demographic characteristics, medical history, hospitalisation, mortality, and causes of death from disease onset to the last follow-up/death. Survival outcomes were estimated using the Kaplan–Meier analysis. Standardised mortality ratio (SMR) was also explored.ResultsThis study included 33 chart records of patients with ASMD type B (n = 24) and type A/B (n = 9), with a median (interquartile range [IQR]) age of 8.0 [3.0–20.0] years and 1.0 [1.0–2.0] years, respectively, at diagnosis. The commonly reported manifestations were related to spleen (100.0%), liver (93.9%), and respiratory (77.4%) abnormalities. Nine deaths were reported at a median [IQR] age of 17.0 [5.0–25.0] years, with 66.7% of overall patients deceased at less than 18 years of age; the median [IQR] age at death for patients with ASMD type B (n = 4) and type A/B (n = 5) was 31.0 [11.0–55.0] and 9.0 [4.0–18.0] years, respectively. All deaths were ASMD-related and primarily caused by liver or respiratory failures or severe progressive neurodegeneration (two patients with ASMD type A/B). The median (95% confidence interval [CI]) overall survival age since birth was 45.4 (17.5–65.0) years. Additionally, an SMR [95% CI] analysis (21.6 [9.8–38.0]) showed that age-specific deaths in the ASMD population were 21.6 times more frequent than that in the general German population.ConclusionsThis study highlights considerable morbidity and mortality associated with ASMD type B and type A/B in Germany. It further emphasises the importance of effective therapy for chronic ASMD to reduce disease complications.