Higher Aminotransferase Levels Research Articles

Deep Contrast Clustering Analysis to Distinguish Diabetic Complications in Elderly Chinese Patients.

To establish an innovative clustering method for predicting variable categories of diabetic complications in Chinese ≥65 with diabetes. We selected and extracted data from elderly patients with diabetes (n=4980) from a medical examination group of 51,400 people followed up annually from 2014 to date in Kunshan, China. A deep contrast clustering approach was used to cluster and predict diabetic complications. The clustering approach was further validated using data from elderly patients with diabetes (n=397) from one medical examination cohort of 20,000 people followed up yearly from 2014 to date in Beijing Jiuhua Hospital. The patients were clustered into 6 categories by analysing 20 indicators. Cluster 1-Heavy smoking and a high cardiovascular disease (CVD) risk; Cluster 2-High alcohol consumption, high aminotransferase levels, the highest risk of stroke complications, and a high fatty liver disease (FLD) risk; Cluster 3-High blood lipid levels and a risk of FLD and stroke complications; Cluster 4-Good health indicators and a low risk of FLD, stroke, and CVD complications; Cluster 5-Older age, higher uric acid concentration and creatinine level, and the highest risk of CVD complications; Cluster 6-Large waist circumference, high BMI, high blood pressure, and the highest risk of FLD complications. The gene for nonalcoholic fatty liver disease in cluster 2 had the highest risk coefficient. This was consistent with cluster 2, which had a higher FLD prevalence. A new clustering method was developed from two large Chinese cohorts of older patients with diabetes, which may effectively predict complications by clustering into different categories.

Assessing the efficacy of tocotrienol-rich fraction vitamin E in obese children with non-alcoholic fatty liver disease: a single-blind, randomized clinical trial

BackgroundChildhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD.MethodsA total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored.ResultsAPO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045).ConclusionThe study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children.Trial registrationThe study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

Prevalence of Non-Alcoholic Fatty Liver Disease and Its Impact on Fibrosis Risk in Inactive Chronic Hepatitis B Patients: Insights from a Cross-Sectional Study.

Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are significant causes of chronic liver disease, potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, the coexistence of CHB and NAFLD is increasingly common, although the relationship between NAFLD and inactive CHB infection remains poorly understood. Objectives: This study aimed to investigate the prevalence of NAFLD among patients with inactive CHB, identify risk factors for NAFLD, and determine predictors of significant fibrosis in these patients. Methods: This single-center cross-sectional study targeted patients with inactive CHB at Sultan Qaboos University Hospital from January 2010 to November 2021. Results: A total of 425 patients with inactive CHB were identified, of which 53.1% were male and 62.6% were aged 40-60 years. The prevalence of NAFLD was 47.8%. Various independent factors were associated with NAFLD, including type 2 diabetes mellitus, elevated low-density lipoprotein levels, high hemoglobin levels, low platelet counts, and normal alpha-fetoprotein levels. Significant associations were noted between NAFLD and significant fibrosis, with 10.5% of CHB patients with NAFLD exhibiting significant fibrosis compared to 1.4% of those without NAFLD. Other significant parameters included male gender, increased age, high alanine transaminase levels, elevated hemoglobin, and decreased platelet levels. Conclusions: The high prevalence of NAFLD in patients with inactive CHB and its associations with increased fibrosis and cirrhosis risk underscore the need for comprehensive management strategies for these patients.

Autoimmune hepatitis – an increasingly common cause of hypertransaminasaemia among children. Case report and literature review

Autoimmune hepatitis is a chronic inflammatory process of unknown ethology, characterised by high levels of transaminases and IgG antibodies, the presence of tissue autoantibodies, and a typical histological picture. In the population of children, the paediatric form of autoimmune hepatitis and autoimmune sclerosing cholangitis are collectively classified as juvenile autoimmune liver disease. The condition often coexists with other autoimmune disorders. This paper aims to present the clinical profile of a paediatric patient with full-blown autoimmune hepatitis and describe the available therapies. The patient, a 13-year-old boy, was referred to a specialised hospital because of increasing hypertransaminasaemia. The patient was hospitalised for the first time at a district hospital for abdominal pain, and during his stay, elevated transaminases were found with a tendency to increase in follow-up tests. The picture suggested an inflammatory process of the liver and biliary tract. Upper gastrointestinal endoscopy revealed lesions consistent with chronic gastritis and portal gastropathy. Treatment included thiazolidinedioic acid, vitamin K, ursodeoxycholic acid, rifaximin, ciprofloxacin, and proton pump inhibitors. Therapy is aimed at maintaining immunosuppression and inhibiting the inflammatory response that leads to cirrhosis, and most commonly uses steroids alongside proton pump inhibitors for added protection or, alternatively, mycophenolate mofetil, cyclosporine A, tacrolimus, and biologic therapy. Ursodeoxycholic acid also exhibits immunomodulatory properties and makes it possible to reduce steroid doses and thus decrease the likelihood of adverse effects of therapy.

Histopathology and its clinical correlation of liver biopsy in patients with treated autoimmune hepatitis

The diagnosis of autoimmune hepatitis (AIH) relies on well-established criteria encompassing histological, serological, and clinical features. Diagnosing AIH may become challenging when encountering patients who have undergone steroid therapy for other co-existing diseases. Thirty-nine liver biopsies from 25 patients with treated and untreated AIH were classified into three groups: 1) Newly diagnosed untreated biopsies (n = 16); 2) Newly diagnosed partially treated biopsies from patients already on steroid treatment for other co-existing diseases (n = 9); 3) Previously diagnosed biopsies from patients who had undergone complete treatment (n = 14). In the untreated AIH group, at least 50 % of the cases exhibited the following features: at least moderate portal inflammation (81 %), at least moderate lobular inflammation (56 %), ductular reaction (94 %), inflammation gradient from bile duct to interface (88 %), unequivocal interface hepatitis (100 %), emperipolesis (56 %), plasma cell cluster (88 %), apoptosis or necrosis (63 %), pericentral inflammation (63 %), and periportal fibrosis (88 %). Although all these diagnostically sensitive histologic features were present in significantly fewer cases after treatment (p < 0.05), the features of ductular reaction, inflammation gradient from bile duct to interface, pericentral inflammation, and periportal fibrosis were likely to persist after treatment, especially in partially treated cases; these features did not show a significant association with higher transaminase levels (P > 0.05) and were considered as indirect features of hepatocytic injury. Our data suggest categorizing AIH histological features into direct and indirect hepatocytic injuries. Direct hepatocytic injury features significantly correlate with transaminase levels and respond well to treatment, while indirect ones show weaker transaminase correlation and relative treatment resistance.

Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide.

An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels. Patients were treated with TAF monotherapy for 96weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1logIU/mL from baseline) were evaluated. The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7logIU/mL. The median change in HBcrAg from baseline was -1.1logIU/mL at 96weeks after treatment. The HBcrAg response rate at 96weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96weeks of treatment (p=4.53×10-6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy. In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment.

Changing etiological spectrum of acute liver failure.

Acute liver failure (ALF) is an uncommon but potentially dramatic syndrome characterized by massive hepatic necrosis and has a very high mortality rate of 50% to75% without liver transplantation. This study is aimed at analyzing the etiological spectrum of ALF patients and compare these with ALF mimicssuch as malaria, dengue fever and other tropical infectious diseases. The study population included patients who presented with ALF and ALF mimics in a tertiary care center over two years. We retrospectively analyzed the patient case files and a comparison was made concerning the baseline demographic details, clinical profile, laboratory values and outcomes. Sixty-three patients were assessed, with 32 in ALF and 31 in ALF mimics group. The most common cause for ALF was hepatitis A virus (25%), followed by hepatitis B virus (18.7%), drug-induced liver injury (12.7%), autoimmune hepatitis (12.5%), hepatitis E virus (9.3%) and Wilson's disease (6.25%). In the ALF mimics group, malaria (58.06%) was the most common cause, followed by dengue fever (16.1%), leptospirosis (12.9%) and scrub typhus (12.9%). Patients in the ALF mimics group had significantly higher incidence of fever (p = 0.001), hepatosplenomegaly (p = 0.01), anemia (p = 0.02) and shorter jaundice to encephalopathy duration (p = 0.032) as compared to the ALF group, while higher transaminase levels (p = 0.03), bilirubin (p = 0.01), prothrombin time (p = 0.01), serum ammonia (p = 0.02) and mortality (p = 0.02) were observed in ALF patients. The most common cause for ALF was hepatitis A virus, followed by hepatitis B virus, while in ALF mimics it was malaria followed by dengue fever, in our study. Patients of ALF mimics can have similar presentation, but a high index of suspicion and awareness is required to identify the common infectious ALF mimics for early diagnosis.

Rapid in vivo evaluation system for cholestasis-related genes in mice with humanized bile acid profiles.

Pediatric cholestatic liver diseases (Ped-CLD) comprise many ultrarare disorders with a genetic basis. Pharmacologic therapy for severe cases of Ped-CLD has not been established. Species differences in bile acid (BA) metabolism between humans and rodents contribute to the lack of phenocopy of patients with Ped-CLD in rodents and hinder the development of therapeutic strategies. We aimed to establish an efficient in vivo system to understand BA-related pathogenesis, such as Ped-CLD. We generated mice that express spCas9 specifically in the liver (L-Cas9Tg/Tg [liver-specific Cas9Tg/Tg] mice) and designed recombinant adeno-associated virus serotype 8 encoding small-guide RNA (AAV8 sgRNA) targeting Abcc2, Abcb11, and Cyp2c70. In humans, ABCC2 and ABCB11 deficiencies cause constitutional hyperbilirubinemia and most severe Ped-CLD, respectively. Cyp2c70 encodes an enzyme responsible for the rodent-specific BA profile. Six-week-old L-Cas9Tg/Tg mice were injected with this AAV8 sgRNA and subjected to biochemical and histological analysis. Fourteen days after the injection with AAV8 sgRNA targeting Abcc2, L-Cas9Tg/Tg mice exhibited jaundice and phenocopied patients with ABCC2 deficiency. L-Cas9Tg/Tg mice injected with AAV8 sgRNA targeting Abcb11 showed hepatomegaly and cholestasis without histological evidence of liver injury. Compared to Abcb11 alone, simultaneous injection of AAV8 sgRNA for Abcb11 and Cyp2c70 humanized the BA profile and caused higher transaminase levels and parenchymal necrosis, resembling phenotypes with ABCB11 deficiency. This study provides proof of concept for efficient in vivo assessment of cholestasis-related genes in humanized bile acid profiles. Our platform offers a more time- and cost-effective alternative to conventional genetically engineered mice, increasing our understanding of BA-related pathogenesis such as Ped-CLD and expanding the potential for translational research.

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.

Managing Hepatotoxicity Caused by Anti-tuberculosis Drugs: A Comparative Study of Approaches.

Tuberculosis (TB) is one of the oldest and most well-known diseases that has been associated with humans for many years and remains a global health challenge today. Timely diagnosis and proper treatment are crucial for controlling and preventing the spread of the disease. While anti-TB drugs offer many benefits, inadequate monitoring can lead to a range of side effects, including hepatotoxicity, which is a major concern and can cause treatment discontinuation. The aim of this study was to determine the approach to the hepatotoxicity of anti-TB drugs and to investigate potential relationships between demographic factors, underlying medical conditions, and successful retreatment outcomes for hepatotoxicity induced by anti-TB drugs. For this study, we reviewed the medical records of patients who experienced hepatotoxicity due to anti-TB treatment and were admitted to the infectious ward of Imam Khomeini Hospital between April 2015 and February 2019. The data were collected using a questionnaire. The findings indicated that the female gender, weight loss at the beginning of hospitalization, hepatitis C virus, hepatitis B virus (HBV), heart disease, and high levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) at the beginning of hepatotoxicity are risk factors for failure to the retreatment of hepatotoxicity. There were two different approaches to the anti-TB retreatment regimen. The first approach involved gradually starting the drugs in full dose, while the second approach encompassed starting the drugs in the minimum dose and then increasing to the maximum dose. The results demonstrated no significant difference between the two approaches to managing hepatotoxicity induced by anti-TB drugs. Drug-induced hepatotoxicity is a common occurrence that often results in treatment discontinuation. Understanding the prevalence of this complication and identifying appropriate methods of rechallenge treatment is crucial to reducing complications and mortality rates.

Production, Nutritional Value and Toxicity of Kawal, a Fermented Product from the Leaves of Cassia obtusifolia (L.): A Review

Cassia obtusifolia is a plant of the Fabaceae family. Its leaves are eaten as a vegetable in several African countries. In some African countries like Chad and Sudan, the leaves are processed by fermentation in a solid state, called in arabic kawal, which is eaten with cereal couscous. The present study is a literature review on the production of kawal and similar products. The production of kawal remains made by craftsmen. After crushing, the leaves are incubated in a buried jar for a period that varies from 14 to 30 days, sun-dried for 3 to 5 days and are ready for consumption. Kawal has several nutritional benefits. Fermentation of C. obtusifolia leaves increases protein, calcium, magnesium and iron content by 38, 98, 75 and 47% respectively, and reduces the levels of secondary metabolites like polyphenols, tannins and phytic acid by 20, 6 and 47% respectively. Fermentation of C. obtusifolia leaves reduces the levels of secondary metabolites like polyphenols, tannins and phytic acid by 20, 6 and 47% respectively. However, some studies on the effect of kawal on albino rats and chicken’s growth have revealed signs of toxicity manifested through high level of serum transaminases and histopathology of the liver and kidneys. These data show that the fermentation of C. obtusifolia leaves improve nutritional value of this vegetable but does not considerably reduce secondary metabolites which could be considered as antinutrients and might be responsible of the toxicity in albino rats and chickens.

Hepatoprotective Efficacy of Phytochemically Screened &lt;i&gt;Nyctanthes arbor-tristis&lt;/i&gt;

The Oleaceae plant Nyctanthes arbor-tristis Linnaeus is used in Ayurveda medicine as a laxative, diuretic, and for the treatment of a variety of painful conditions including sciatica, arthritis, and fever. This study aimed to determine whether or not extracts of Nyctanthes arbor-tristis leaves, either in alcohol or water, might prevent liver damage caused by carbon tetrachloride in rats. Administration of alcoholic and aqueous extracts of the leaves of Nyctanthes arbor-tristis protects the liver against the toxicity of carbon tetrachloride by lowering the high levels of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, and serum bilirubin (total and direct). Both the alcoholic and aqueous extracts demonstrated hepatoprotective efficacy at a dosage of 500 mg/kg body weight by significantly reducing the high levels of biochemical markers. Liver histopathology studies corroborated the extracts’ potential to restore damaged hepatocytes.

An overlooked cause of hepatitis and thrombocytopenia with clinico-biochemical discrepancy: A case of infectious mononucleosis

A 22-year-old male was admitted to the outpatient clinic with fatigue, fever, and a sore throat. High transaminase levels, moderate thrombocytopenia, and elevated acute phase reactants were detected ten times. Ultrasound imaging revealed hepatosplenomegaly and a peripheral blood smear showed Downey cells. Epstein-Barr virus (EBV) infection was considered the definite diagnosis, and EBV serology was performed. His mild clinic improved to normal within days, but the patient's clinical progression and laboratory findings were incompatible. Laboratory results were on the extreme side, while the clinic was mildly deteriorating. EBV viral capsid antigen IgM was high, supporting the initial diagnosis. Biochemical normalization followed clinical improvement many days later. Clinicians should know that EBV infection may be mild, while laboratory results illustrate extreme findings.

Exploring the physiological plasticity of giant grouper (Epinephelus lanceolatus) to dietary sulfur amino acids and taurine to measure dietary requirements and essentiality.

Giant grouper (Epinephelus lanceolatus) is an economically important yet under-researched species, still reliant on 'trash fish' or generic aquafeeds. The transition toward sustainable formulations is contingent on establishing requirements of target species for limiting nutrients, among which the sulfur amino acids (methionine and cysteine) commonly limit fish growth. Further, there remains significant conjecture around the role of the sulfonic acid taurine in marine aquafeed formulation and its relationship to sulfur amino acids. To develop a species-specific feed formulation for giant grouper, dietary methionine was modulated in a dose-response experiment to achieve five graded levels from 9.5 to 21.5 g/kg, including an additional diet with methionine at 18.6 g/kg supplemented with 8 g/kg taurine. The mean (±SD) cysteine level of the diets was 4.5 ± 0.3 g/kg. Each diet was randomly allocated to triplicate tanks of 14 fish (83.9 ± 8.4 g). The best-fit regression for growth showed that the optimal dietary methionine content was 15.8 g/kg and the total sulfur amino acid content was 20.3 g/kg. Inadequate dietary methionine content triggered physiological responses, including hepatic hyperplasia and hypoplasia at 9.5 and 21.5 g/kg, respectively, and high aspartate transaminase levels at 18.9 g/kg. Moreover, inadequate dietary methionine contents resulted in higher densities of mixed goblet cell mucin and reduced absorptive surface area of posterior intestinal villi. Our results suggest that adequate levels of methionine, but not taurine, improved posterior intestinal conditions and liver homeostasis. These findings may aid informulating aquafeeds to optimize gastrointestinal and liver functions in juvenile giant grouper.

Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation

This research aimed to evaluate the preventing effects of naringin, naringenin, and their combination on liver injury induced by Taxol (paclitaxel) in Wistar rats. Male Wistar rats received 2 mg/kg Taxol intraperitoneal injections twice weekly on the second and fifth days of each week for 6 weeks. During the same period as Taxol administration, rats were given naringin, naringenin, or a combination of the two (10 mg/kg b.wt) every other day. Treatment with naringin and/or naringenin reduced the abnormally high serum levels of total bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase in Taxol-treated rats. It also significantly increased the level of serum albumin, indicating an improvement in the liver. The perturbed histological liver changes were markedly improved due to the naringin and/or naringenin treatment in Taxol-administered rats. Additionally, the treatments reduced high hepatic lipid peroxidation and increased liver glutathione content as well as the activities of superoxide dismutase and glutathione peroxidase. Furthermore, the treatments reduced the levels of alpha-fetoprotein and caspase-3, a pro-apoptotic mediator. The naringin and naringenin mixture appeared more effective in improving organ function and structural integrity. In conclusion, naringin and naringenin are suggested to employ their hepatoprotective benefits via boosting the body’s antioxidant defense system, reducing inflammation, and suppressing apoptosis.Graphical

β-arrestin2 deficiency ameliorates S-100-induced autoimmune hepatitis in mice by inhibiting infiltration of monocyte-derived macrophage and attenuating hepatocyte apoptosis.

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. β-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether β-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and β-arrestin2 knockout (Arrb2 KO) mice, and the experimentsidentified that liver β-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, β-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. β-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that β-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas β-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, β-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3β pathway. These results suggest that β-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, β-arrestin2 may act as an effective therapeutic target for AIH.

Novel radiological technique to recognize acute liver failure caused by yellow phosphorous containing rodenticides.

Yellow phosphorous rodenticide (YPR) poisoning is the commonest cause for acute liver failure (ALF) in southern and western India. Due to medicolegal issues, history of YPR ingestion may not be available. As early recognition of YPR poisoning is important and there are no specific biochemical assays, other early predictors to identify this entity is necessary. We evaluated the diagnostic role of plain computed tomography (CT) in identifying YPR-induced ALF. All patients admitted to the liver unit with a diagnosis of ALF underwent a plain CT scan abdomen. Demographic details, clinical history, laboratory parameters, liver attenuation index (LAI) calculated on CT scan, treatment details, need for liver transplantation and clinical outcome were analyzed. Parameters for YPR-induced ALF (ALF-YPR) and other causes (ALF-OTH) were compared. Ability of LAI to distinguish ALF-YPR and ALF-OTH was analyzed using receiver operating characteristic (ROC) curve analysis. Twenty-four patients (15 female [62.5%]) were included in the study. Thirteen patients (54%) had YPR poisoning, while the rest formed the ALF-OTH group (11,46%). ALF-YPR patients had higher transaminase levels, lower peak serum bilirubin levels. ALF-YPR livers had significantly lower LAI as compared to ALF-OTH (- 30 vs. - 8, p = 0.001). On ROC curve analysis, an LAI greater than - 18 ruled out YPR as the cause for ALF with 91% sensitivity and 85% specificity. On regression analysis, LAI was the only independent factor predicting ALF-YPR (odds ratio - 0.86, [0.76, 0.96] p = 0.008). Our data shows that LAI on plain abdominal CT scan can be used to quickly recognize ALF-YPR in unclear cases so that necessary treatment protocol can be activated, or patient transfer arranged. Our analysis shows that an LAI greater than - 18 can reliably rule out YPR ingestion as the cause for ALF.

Clinical Manifestations, Laboratory Markers and Their Association with Mortality in Patients with Severe Covid-19 Infection in Third Wave of Epidemics in Myanmar

Background Coronavirus disease 2019 (COVID-19) has been a major threat to health around the world as it causes significant morbidity and mortality. The clinical manifestations range from a common cold to more severe diseases such as pneumonia, severe acute respiratory distress syndrome (ARDS), multi-organ failure, and even death. It is important to identify red flag signs for mortality, helpful for prioritization of treatment especially in poor resource setting. The study aimed to assess association of clinical and laboratory markers and the outcome in patients with severe COVID-19 infection in Myanmar. Methods A descriptive study was conducted in COVID-19 treatment centers in Myanmar- Yangon and Nay Pyi Taw, from February 2020 to August 2021. Data were collected by using standardized case report forms and then, a total of 404 confirmed COVID-19 inpatients (&gt;18 years old) were included. The p value and odds ratio with a 95% confidence interval (CI) was used as a measure of association and the independent associated factors for severity of disease were investigated using logistic regression analysis. Results Among 404 patients, 258 (63.9%) were discharged; and 146 (36.1%) expired in hospital. Mortality was associated with clinical parameters such as age over 65 years (odds ratio 0.47, 95% CI 0.31– 0.72; p &lt; 0.001), low initial SpO2 less than 85% (95% CI -7.46 – -3.96; p &lt; 0.001), reduced Glasgow Coma Scale score less than ‘15’ (95% CI -0.70 – -0.20; p &lt; 0.001), high Quick Sequential Organ Failure Assessment Score “2 and 3”(qSOFA score) (95% CI 0.08 – 0.91; p = 0.025), high CXR Brixia Score more than ‘8’ (95% CI 3.42 – 4.89; p &lt; 0.001); and, laboratory criteria like total WBC count greater than 12 x 109/L (95% CI 1.81 – 4.33; p &lt; 0.001), CRP greater than 0.5mg/L (95% CI -61.37 – -23.26; p &lt; 0.001), ferritin greater than 400 ng/mL (95% CI -312.36 – -139.07; p &lt; 0.001), D-dimer greater than 0.5 μg/ml (95% CI -3340.65 – -2945.21; p &lt; 0.001), high serum creatinine greater than 1 mg% (95% CI 0.16 – 0.70; p = 0.002), LDH greater than 225 U/l (95% CI -166.53 – -46.66; p &lt; 0.001), ALT greater than 40 IU/L (95% CI 11.82 – 39.32; p &lt; 0.001) and AST greater than 37 IU/L (95% CI 21.26 – 55.16; p &lt; 0.001). Conclusions Clinical manifestations significantly associated with mortality were low Glasgow Coma Scale score, initial SpO2 less than 85%, qSOFA score ‘2’ and above, and severe chest radiographic involvement (CXR Brixia Score more than ‘8’). Laboratory markers like neutrophil leukocytosis, high level of inflammatory markers (CRP, ferritin, LDH), high levels of transaminase (ALT and AST), high D-dimer, high creatinine were significantly related with mortality. Awareness, identification of these predictors on admission was essential for early anti-viral therapy and timely anti-inflammatory treatments; hence, better outcome.

Abstract 6458: Maternal and paternal alcohol exposures program higher incidence of hepatocellular carcinoma in offspring

Abstract Environmental exposures during development are known to influence adult health and disease. Specifically, early developmental exposures have been shown to increase susceptibility to cancer in adults through epigenetic mechanisms. Alcohol is a potent environmental carcinogen and teratogen, causing a wide range of health problems across the life course of an individual. Current literature examining early life exposures solely focuses on maternal exposures despite recent efforts to recognize paternal epigenetic contributions. Thus, we investigated the influence of preconception paternal, maternal, and dual parental alcohol exposures on offspring’s predisposition to develop liver disease and hepatocellular carcinoma (HCC). We hypothesized that dual-parental alcohol exposure would exacerbate the incidence of liver cancer in adult offspring. Using an established mouse model, we exposed male and female adult C57BL/6J mice to control (0% EtOH) or alcohol (10% EtOH) preconception treatments. Next, we randomly assigned pups from each treatment to either a single injection of Diethylnitrosamine (DEN; 25mg/kg) to promote liver tumors, or saline control. Finally, we sacrificed offspring on postnatal day 182 and collected organs and blood for enzyme analysis. DEN-treated males display an increased liver-to-body weight ratio compared to saline males while also exhibiting lower body weight. The male progeny from the dual-parental treatment group exhibited a significant increase in tumor incidence and burden in DEN-treated males, exceeding those measured for the maternal and paternal treatments. Further, offspring from the dual-parental group had high levels of alanine transaminase (ALT) and aspartate transaminase (AST) compared to the other treatment groups. Oil Red-O and Sirius Red staining of liver sections revealed increased hepatic steatosis and fibrosis in DEN males compared to saline males. Again, the dual-parental exposed offspring exhibited the most aberrant phenotype. Blind scoring of H&amp;E-stained liver sections identified increases in steatosis, fibrosis, and HCC lesions, with the highest scores emerging in DEN-treated dual-parental offspring. These findings demonstrate that preconception paternal and gestational maternal alcohol exposures program a predisposition to adult-onset chronic diseases including alcoholic fatty liver disease, hepatic fibrosis, and HCC. These experiments not only confirm our hypothesis that dual-parental exposed offspring exhibit an exacerbated hepatic abnormality phenotype, but also highlight the importance of both maternal and paternal environmental exposures on disease risk in offspring. While the negative effects of maternal alcohol consumption have been well established, our novel finding that paternal alcohol exposure also promotes hepatocellular carcinoma in offspring has potentially profound clinical implications. Citation Format: Alison Basel, Sanat S. Bhadsavle, Kara N. Thomas, Katherine N. Zimmel, Alexis N. Roach, Matthew Gaytan, Grace Parkey, Michael C. Golding. Maternal and paternal alcohol exposures program higher incidence of hepatocellular carcinoma in offspring. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6458.

Predictive Factors for Recovery from Alcoholic Liver Failure.

Alcoholic liver disease is a risk factor for non-virus-related hepatocellular carcinoma (HCC), which is increasing in prevalence. This study aimed to identify the factors for recovery from alcoholic liver failure. Sixty-two consecutive patients hospitalized for alcoholic liver failure at Okayama City Hospital were enrolled. The characteristics of patients who survived to the 1-month follow-up and whose liver function improved to Child-Pugh A at 3 months (CPA3) and 12 months (CPA12) were compared with the rest of the patients. The survivors at 1 month (50 patients) were significantly younger than the deceased patients and had better liver and renal function with higher levels of γ-glutamyl transferase (GGT). The same factors, except renal function, were correlated with achieving CPA3. High AST, ALT, and GGT levels as well as short spleen length, total abstinence, and good Child-Pugh scores at admission were identified as factors for achieving CPA12. The extent of alcohol intake before admission was not identified as a risk factor in any analysis. In conclusion, baseline liver function is crucial for survival and achieving CPA3, whereas high transaminase and γ-GTP levels, the absence of splenomegaly, and total abstinence are significant factors for achieving CPA12.