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Rituximab occasionally induces reactivation of hepatitis C virus (HCV) in patients with resolved HCV infection, sometimes with fatal consequences. As rituximab has become one of the first-line therapies for the treatment of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) and is more widely used, there is a lack of studies reporting the effectiveness and safety of rituximab in patients with PLA2R-associated MN and resolved HCV infection. A single-center retrospective study was conducted on PLA2R-associated membranous nephropathy (MN) patients who were HCVAb positive but HCV-RNA negative and treated with rituximab. A total of 598 adult patients with PLA2R-associated MN who underwent rituximab therapy were screened. General clinical information, including gender, age, pathological data, and previous treatment plans, was collected from medical records. Routine blood tests, liver and kidney function assessments, blood lipid profiles, 24-h urine protein levels, anti-PLA2R antibody titers, circulating B-cell counts, and HCV viral loads were measured at the time of rituximab infusion and repeated at intervals of 1–3 months post-rituximab administration. A total of 8 patients were enrolled, with a median follow-up period of 19.00 (range: 16.00–25.25) months. Among the 8 patients, 5 were male, and the mean age was 50.13 ± 4.29 years. Histological findings indicated that tubuloreticular inclusions, mesangial deposits, intramembranous deposits, and subendothelial deposits were not observed in any of the 8 patients. The overall 1-year remission rate for these patients was 75%, accompanied by a significant reduction in proteinuria. Additionally, blood albumin levels increased significantly, and renal function remained stable. No increase in HCV viral load and stable liver function tests were observed throughout the entire follow-up period. This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and resolved HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials. [ABSTRACT FROM AUTHOR]

Background Methods Results: Conclusion: There is limited literature describing the real‐world practice of delayed initiation and shortened duration direct‐acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1‐week post‐transplant.Retrospective study of HCV‐negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections.102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups. Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects. [ABSTRACT FROM AUTHOR]

INTRODUCTION : Mifepristone (RU 486) is a progesterone receptor modulator with antagonistic properties. It binds strongly to endometrial progesterone receptors, minimally to estrogen receptors, and upregulates androgen receptors. In a placebo-controlled trial low dose mifepristone (RU 486) has been shown to decrease myoma size as well as symptoms. An increase in androgen receptors also contributes to antiproliferative effects. Mifepristone also delays or inhibits ovulation, which may produce amenorrhoea. Direct suppressive effects on endometrial vasculature as well as on reducing stromal vascular endothelial growth factor (VEGF) have also been suggested for reducing menstrual blood loss. OBJECTIVES : To determine the efficacy and safety of mifepristone for the management of uterine fibroids in premenopausal women. MATERIAL AND METHODS : The study was conducted in the tertiary care center. This hospital-based study was conducted between September 2023 and February 2024 for 6 months. 30 consecutive cases were studied based on inclusion criteria. All patients were treated with mifepristone 25mg once daily for 3 months. A pictorial blood loss assessment chart (PBAC) score was used to assess menstrual blood loss. A haemogram, liver function test, and ultrasound were performed. RESULTS: In this study, we observed there was a significant improvement in the hemoglobin (Hb)level, a significant reduction in uterine volume, fibroid size, and heavy menstrual bleeding. CONCLUSION : Mifepristone was able to significantly improve the patient outcome by reducing the amount of blood flow during menstruation increasing the Hb levels and significantly reducing the size of myoma. [ABSTRACT FROM AUTHOR]

Background: Hepatitis A is a common self-limiting infection of the liver. In recent times, there is a change in the pattern of hepatitis A infection producing extrahepatic manifestations. Aims and Objective: Our aim of the study is to find the profile of extrahepatic manifestations of hepatitis A. The secondary objective is to find a correlation of liver function test values with extrahepatic manifestations. Materials and Methods: A retrospective study was conducted over 3 years. 169 seropositive school-going cases were presented with signs and symptoms of hepatitis A and were clinically assessed. Results: Among 169 immunoglobulin M (+)ve hepatitis A, 36% of patients (61 cases) presented with extrahepatic features. Among the 61 patients, 41 patients presented with aspartate transaminase (AST):alanine transaminase (ALT) >2:1 and 20 patients presented with AST:ALT <2:1. Conclusion: In recent times, there has been a changing pattern in the presentation of hepatitis A producing extrahepatic manifestations in the pediatric age group. [ABSTRACT FROM AUTHOR]

Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disorder with variable global incidence. Genetic susceptibility, combined with hormonal and environmental influences, contributes to ICP aetiology. Adverse pregnancy outcomes linked to elevated serum bile acids highlight the importance of comprehensive risk assessment. ABCB4 and ABCB11 gene variants play a significant role in about 20% of severe ICP cases. Several other genes including ATP8B1, NR1H4, ABCC2, TJP2, SERPINA1, GCKR and HNF4A have also been implicated with ICP. Additionally, ABCB4 variants elevate the risk of drug-induced intrahepatic cholestasis, gallstone disease, gallbladder and bile duct carcinoma, liver cirrhosis and abnormal liver function tests. Genetic variations, both rare and common, intricately contribute to ICP susceptibility. Leveraging genetic insights holds promise for personalised management and intervention strategies. Further research is needed to elucidate variant-specific phenotypic expressions and therapeutic implications, advancing precision medicine in ICP management. [ABSTRACT FROM AUTHOR]

Background Serum level of microRNA-122 (miR-122) has been reported as a sensitive diagnostic biomarker for detecting liver injury, comparable to the aminotransferases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities are increased in other conditions, such as acute skeletal muscle injury (ASMI). We determined whether miR-122 is nonspecifically increased in patients suffering from ASMI. Methods We measured ALT, AST, creatine kinase (CK), and miR-122 in 3 groups: healthy controls (n = 24), patients with ASMI (total n = 29, 11 with recreational drug use and 18 without recreational drug use), and patients with acute liver injury (ALI; n = 14). Results Levels of ALT, AST, and CK increased 83%, 97%, and 100% for patients with ASMI and 100% for all 3 enzymes in ALI patients. In contrast, miR-122 increased in 34% of patients with ASMI (44.4% with recreational drug use and 18.2% without recreational drug use) and 100% of ALI patients. In 2 drug-induced liver injury cases, miR-122 increased about 12-24 hours before ALT and AST. Conclusion Recreational drug misuse is associated with both rhabdomyolysis and drug-induced liver injury (DILI). The traditional liver function markers AST and ALT were nonspecifically increased in the majority of patients with ASMI. miR-122 is only increased in patients at risk for DILI and demonstrates superior specificity for liver injury. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the ameliorative potential of Nigella sativa oil (N.s) against the adverse effects induced by atrazine (ATZ) in mice. Four groups were divided into: Control group (untreated); N.s group (N. sativa oil, 2 mL/kg/BW); ATZ group (atrazine 200 mg/kg/BW); ATZ+N.s group (atrazine 200 mL/kg/BW; and N. sativa oil, 2 mL/kg/BW). All doses were administered by gavage once daily for 4 weeks. The atrazine-administered group showed a significant increase in total leukocytes, granulocytes, and agranulocytes and a decrease in red blood cells, hemoglobin, mean corpuscular volume, and packed cell volume. Serum concentrations of aspartate aminotransferase, alanine transaminase, and alkaline phosphatase were high in the ATZ group. Atrazine exposure reduced serum albumin and total protein levels in the blood. A significantly higher concentration of bilirubin, urea, and creatinine was also found in the ATZ group. The simultaneous administration of atrazine and N. sativa led to improvements in all the parameters studied above. Thus, this study revealed that atrazine exposure has toxic effects on hematological parameters, liver, and kidney function, and that N. sativa oil reduces these toxic effects of atrazine in male mice. [ABSTRACT FROM AUTHOR]

Adipocyte fatty acid-binding protein (A-FABP; FABP4) plays a significant role in the pathogenesis and progression of metabolically driven low-grade inflammation and organ damage. This study aimed to evaluate the performance of circulating FABP4 as a predictive and diagnostic biomarker for thalassemia-associated cardiometabolic events. This case-control study enrolled 50 adults with β-thalassemia and 30 age-, sex-, and body mass index-matched controls. Participants underwent a comprehensive evaluation, including complete blood count, liver and kidney function tests, serum blood glucose, lipid profile, and ferritin levels, pelviabdominal ultrasound, ECG, and echocardiography after taking a full medical history and conducting a clinical examination. Serum levels of FABP4 were measured using an Enzyme-Linked-Immunosorbent-Assay. The diagnostic performance of FABP4 was assessed using receiver operator characteristic (ROC) curve analysis to determine optimal values for excluding and confirming cardiometabolic metflammation. The thalassemia cohort exhibited a statistically significant higher concentration of FABP4 compared to the control group (p-value < 0.001). Positive correlations were found between FABP4 and ferritin serum levels above 800 or 1000 ug/L, as well as with ALT, TGS, and LDL (p-value < 0.05). Circulating FABP4 was identified as a statistically significant risk factor for thalassemia-associated cardiometabolic comorbidities (OR = 84.00, 95%CI:18.6–378.6, p-value < 0.001). ROC analysis determined that the FABP4 exclusionary cut-off value > 2.30 ng/ml could effectively discriminate between thalassemia-associated adverse metaflammation and controls, while the FABP4 confirmatory cut-off value was > 2.58 ng/ml. In conclusion, circulating FABP4 appears to be a potential risk factor for predicting progression to cardiometabolic events in thalassemia-associated adverse metaflammation. FABP4 holds promise as a diagnostic and prognostic biomarker for disease monitoring and risk stratification. Further validation through large-scale, multicenter, prospective studies is warranted. [ABSTRACT FROM AUTHOR]

Background: Immune thrombocytopenia (ITP) is an immune-mediated disease that results in low platelet counts. Despite appropriate treatment, many patients continue to experience refractory disease. Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, has emerged as a promising option for refractory ITP. Objective: This meta-analysis aims to evaluate the efficacy and safety of fostamatinib compared to conventional therapy in adults aged ≥ 18 years with refractory ITP. Materials and methods: Literature search was conducted in PubMed, Scopus, Embase, and clinicaltrials.gov databases from inception to March 31, 2024. Randomized controlled trials (RCTs) assessing the safety and efficacy of fostamatinib in adults with refractory ITP were included. Data extraction, risk of bias assessment, and statistical analysis were performed following PRISMA guideline. Results: A total of 495 articles were screened, with three RCTs meeting the inclusion criteria. Fostamatinib therapy demonstrated superior efficacy in achieving stable platelet response by week 24 (ORR 0.80; 95%CI 0.72–0.88), platelet count ≥ 50,000/µL at weeks 12 (ORR 0.80; 95%CI 0.72–0.90) and week 24 (ORR 0.82; 95%CI 0.72–0.90). Additionally, fostamatinib improves platelet counts in subjects with a baseline count of < 15,000/µL. The Number Needed to Treat (NNT) was calculated as 10. Adverse effects include diarrhea (RR 2.32; 95%CI 1.11–4.84), hypertension (RR 2.33; 95%CI 1.00-5.43), and abnormal liver function tests (RR 4.18; 95% CI 1.00-17.48). Interestingly, the occurrences of nausea (RR 1.77; 95% CI 0.33–9.67) and rash (RR 2.28; 95% CI 0.50-10.29) did not achieve statistical significance. Conclusion: This meta-analysis provides robust evidence supporting the efficacy of fostamatinib in improving platelet counts and achieving therapeutic goals in adults with refractory ITP. However, fostamatinib's safety profile warrants consideration due to higher rates of diarrhea, hypertension, and abnormal liver function tests. [ABSTRACT FROM AUTHOR]

Purpose: Liver abscesses concomitant with acute prostatitis are rare and potentially fatal. We analyzed the occurrence of this condition and clinical characteristics of the affected patients. Materials and Methods: The medical records of 474 patients diagnosed with acute prostatitis between June 2006 and July 2022 were retrospectively reviewed. Patients in whom pathogens were not detected in serum or urine cultures were excluded. A total of 271 patients were included in the analysis. Patient characteristics and laboratory test results were compared between patients with acute prostatitis with and without liver abscesses. Results: Fifteen patients (5.5%) were identified with simultaneous liver abscesses and acute prostatitis. The liver abscess group was younger than the non-liver abscess group in terms of mean age. In the univariate analysis, a high proportion of patients had diabetes mellitus, whereas a low proportion had hypertension. None of the underlying diseases, including benign prostatic hyperplasia, malignancy, or alcoholism, demonstrated a significant association with liver abscess in multivariate analysis; however, an association was observed in liver function test results. All patients with liver abscesses tested positive for Klebsiella pneumoniae. Conclusions: When K. pneumoniae is identified in patients with acute prostatitis and abnormal liver function tests, considering the possibility of metastatic infection in other organs, including the liver, and performing an active evaluation is essential. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: There are different situations in which an extrahepatic bile duct replacement or substitute is needed, such as initial and localized stages of bile duct cancer, agenesis, stenosis, or bile duct disruption. Materials and Methods: A prosthesis obtained by electrospinning composed of Poly (D,L-lactide-co-glycolide) (PGLA) - Polycaprolactone (PCL) - Gelatin (Gel) was developed, mechanical and biological tests were carried out to evaluate resistance to tension, biocompatibility, biodegradability, cytotoxicity, morphological analysis and cell culture. The obtained prosthesis was placed in the extrahepatic bile duct of 15 pigs with a 2-year follow-up. Liver function tests and cholangioscopy were evaluated during follow-up. Results: Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable. The prosthesis implanted in the experimental model allowed cell adhesion, migration, and proliferation, maintaining bile duct permeability without altering liver function tests. Immunohistochemical analysis indicates the presence of biliary epithelium. Conclusions: A tubular scaffold composed of electrospun PGLA-PCL-Gel nanofibers was used for the first time to replace the extrahepatic bile duct in pigs. Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable, making it an excellent candidate for use in bile ducts and potentially in other tissue engineering applications. [ABSTRACT FROM AUTHOR]

Featured Application: The methodology and findings can be used as a basis for further research into other predictive models for various diseases, contributing to the advancement of predictive analytics in healthcare. Chronic atrophic gastritis is a serious health issue beyond the stomach health problems that affect normal life. This study aimed to explore the influencing factors related to chronic atrophic gastritis (CAG) using non-invasive indicators and establish an optimal prediction model to aid in the clinical diagnosis of CAG. Electronic medical record data from 20,615 patients with CAG were analyzed, including routine blood tests, liver function tests, and coagulation tests. The logistic regression algorithm revealed that age, hematocrit, and platelet distribution width were significant influences suggesting chronic atrophic gastritis in the Chongqing population (p < 0.05), with an area under the curve (AUC) of 0.879. The predictive model constructed based on the Random Forest algorithm exhibited an accuracy of 83.15%, precision of 97.38%, recall of 77.36%, and an F1-score of 70.86%, outperforming the models constructed using XGBoost, KNN, and SVC algorithms in a comprehensive comparison. The prediction model derived from this study serves as a valuable tool for future studies and can aid in the prediction and screening of chronic atrophic gastritis. [ABSTRACT FROM AUTHOR]

This case report describes a patient with major depressive disorder (MDD) who developed acute hepatocellular liver injury after being treated with sertraline, a selective serotonin reuptake inhibitor (SSRI). The diagnosis of MDD was made two years prior, and the patient had previously responded partially to escitalopram and cognitive-behavioral therapy (CBT). Upon switching to sertraline 50 mg daily, the patient presented with severe symptoms indicative of acute liver injury, including elevated liver enzymes, jaundice, and gastrointestinal distress. Following the discontinuation of sertraline, the patient's liver function tests gradually normalized over a 90-day period, confirming the diagnosis of sertraline-induced hepatotoxicity. This case underscores the importance of continuous monitoring for potential liver injury in patients treated with sertraline. The findings contribute to the existing body of evidence on the hepatotoxic risks associated with SSRIs and highlight the need for personalized treatment strategies to mitigate adverse effects and enhance patient safety. Further research is needed to explore the long-term safety and efficacy of sertraline, particularly in vulnerable populations. [ABSTRACT FROM AUTHOR]

Parenteral nutrition (PN) is a life-sustaining method to provide adequate nutrients to patients unable to receive oral or enteral nutrition. PN typically contains a mixture of macro- and micro-nutrients, although the lipid composition has been identified as a concern for liver disease. Therefore, the study of the intravenous lipid emulsion (ILE) prescribing practices in home-based PN (HPN) patients and whether differing lipid PN alters liver function tests (LFTs) is needed. Methods: A retrospective study of monthly LFTs from a random sample of 105 adult HPN patients in the U.S. over a 6-month period was conducted. Patients were receiving olive oil/soy oil (n = 53, Clinolipid), mixed ILE (n = 39, SMOF Lipid), soy oil (SO; n = 4, Intralipid), or none (n = 7). LFTs monitored were alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (T Bili). Results: No differences were observed in baseline LFTs across groups (all, p > 0.25, η2 < 0.04), nor were there differences in age, body mass index, days of PN, or mean PN volume (all, p > 0.36, η2 < 0.05). There were no significant interactions between ILE type and time (all p > 0.64, ηp2 < 0.03), no effect of ILE type (all p > 0.60, ηp2 < 0.03), and no effect of time (all p > 0.69, ηp2 < 0.01) in terms of LFTs. Average LFTs over six months were also not different between ILE types (all p > 0.30, η2 < 0.04). Conclusion: These findings suggested that patients were mostly prescribed mixed or ILE PN containing more than one lipid source and that differing ILEs in long-term HPN patients did not alter LFTs over a six-month period. [ABSTRACT FROM AUTHOR]

Background: Dengue, an important cause of fever, spread by bite of infected Aedes mosquito. Sometimes changes of platelet parameters, haematocrit and liver function tests are found in dengue fever. The aims of this study are to find out the prevalence of liver function tests abnormalities in patients with dengue and to find out the abnormalities in platelet parameters in patients with dengue. Methods: Total 300 patients with NS1 antigen and IgM positive or dengue IgG or IgM positive, having no preexisting liver diseases or other superadded infection i.e. hepatitis, malaria, enteric fever causing hepatitis (according to bed head tickets) from January’22 to December’23, admitted in the Sishu-o- Matrimongal Kendra hospital are included in this study. Results: In this study, most of the patients are adults (>18 years to 60 years) male (56.67%). Majority (85.33%) have platelet count >1,00,000/cumm, 8.67% have platelet count <50,000/cumm. Majority of them (92%) have normal mean platelet volume, platelet distribution width and haematocrit. Most of them have plateletcrit lower than normal. Most of the males have aspartate aminotransferase level and alanine aminotransferase level between 40U/L -250U/L. Majority of the females have both aspartate aminotrasferase and alanine aminotransferase level <40U/L. Most of the patients (both males and females) have alkaline phosphatase level less than 128 IU/L. Majority of them (both males and females) have more than normal level of gammaglutamyl transferase level. Most of the patients (both males and females) have total serum bilirubin level 20μmol/L or less. Majority of the patients ( both males and females) have total serum protein level 64 gm/L or less and serum albumin level less than 35gm/L. Conclusion: Dengue, a mosquito borne viral fever, is a condition very commonly encountered in all over India. Along with haematological changes, some liver function tests are also found deranged in dengue patients. Liver involvement in the form of elevated transaminases, GGT, bilirubin, low protein, albumin were found in this study population. The spectrum of hepatic involvement in dengue can vary from asymptomatic biochemical changes to severe liver damage. The haematocrit level of dengue patients are increased significantly indicating the haemoconcentration of the patients. Platelet parameters give information about ongoing destruction of platelets in dengue patients. Limitation of this study is that no differentiation is examined between dengue fever and dengue haemorrhagic fever and coagulation profile is not assessed. [ABSTRACT FROM AUTHOR]

To investigate the effects of methadone maintenance therapy on body mass index (BMI) and some biochemical parameters, including fasting blood glucose, lipid profile, and liver function indices as indicators of the biochemical function of the body for 3 years. This interventional study was performed on 43 opioid use disorder patients who had been selected for methadone maintenance therapy from 2016 to 2020. The morphine test on blood samples was carried out monthly for all patients. Fasting blood glucose, lipid profile including triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and liver function tests including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and body mass index (BMI) were measured over 3 years. Data analysis was performed using SPSS software. FBS in second and third year of therapy increased by 15.57 mg/dL (p-value 0.01) and 21.87 mg/dL (p-value 0.009), respectively; none of lipid profile variables was significantly different over time (p-value > 0.05). Only mean ALP levels significantly decreased 21.51 IU/L (p-value 0.04), 21.02 IU/L (p-value 0.04), and 26.07 IU/L (p-value 0.01) in liver function tests. The mean BMI increases each years but not significantly. Methadone treatment affects some biochemical parameters such as blood sugar and liver activity, so changes in biochemical parameters should be considered. [ABSTRACT FROM AUTHOR]

Background: Obesity and its associated complications raise significant public concern, revealing gender disparities in the susceptibility to metabolic disorders, with females often displaying greater resistance to obesity-related metabolic disorder than males. Sestrin2 is a crucial protein involved in metabolism and energy balance. This study seeks to explore whether Sesn2 knockout (KO) exacerbates high-fat diet (HFD) induced obesity in female mice. Methods: Female mice with wild-type (WT) and Sesn2 KO were subjected to a 12-week regimen of normal diet or HFD. Using a Body Composition Analyzer, body composition was gauged. Biochemical assays encompassed glucose, lipid, and liver function measurements, alongside 24-hour urine albumin excretion. Echocardiographic evaluation assessed cardiac function. Histopathological analysis of key metabolic tissues (liver, kidney, and heart tissues) were conducted. Western blotting or qRT-PCR evaluated key proteins and genes linked to inflammation, mitochondrial, and lipid metabolism in adipose tissues. Results: In comparison to mice fed a regular diet, those on a HFD exhibited significant increases in body weight and fat mass. Notably, Sesn2 KO further aggravated obesity, showcasing the most pronounced metabolic anomalies: elevated body weight, fat mass, impaired glucose tolerance, and insulin sensitivity, alongside heightened levels of free fatty acids and triglycerides. Additionally, KO-HFD mice displayed exacerbated multi-tissue impairments, including elevated hepatic enzymes, increased urinary albumin excretion, compromised cardiac function, and accumulation of lipids in the liver, kidney, and heart. Moreover, adipose tissue showcased altered lipid dynamics and function, characterized by enhanced triglyceride breakdown and modified adipokine levels. Browning was diminished, along with decreased Pgc1α and Sirt1 in KO-HFD mice. Conclusion: Sesn2 KO exacerbates HFD-induced obesity and metabolic disorders in female mice. These findings underscore Sestrin2's novel role as a regulator of obesity in female mice. [ABSTRACT FROM AUTHOR]

Approximately 2.2% of Libyans have chronic hepatitis B (CHB) and are at the highest risk of developing end-stage disease complications. Several resource-limited countries, including Libya, may be far from achieving the WHO goal of hepatitis B elimination by 2030 as a result of several testing and linkage to care (LTC) barriers. In Libya, data about the current HBV infection situation is scarce. Therefore, our study aimed to evaluate the trends of HBV in eastern Libya, Tobruk region, and try to identify the region-specific gaps and barriers that could potentially delay the WHO goal of HBV elimination. An eighteen-year retrospective review of records of the main district medical center in the region was done to estimate the trends of HBV infection and qualitative interviews with the clinical staff of the CHB registry in the region were conducted to investigate the current status of HBV management. Out of 392,952 records, 371 (0.09%) HBV-positive were recorded and declining trends of the infection were noticed over the study period. Until late 2019, there was no linkage to care or follow-up for people with HBV infection. However, a CHB registry was established in late 2019 to manage HBV infections in the region, yet there are several barriers such as the lack of diagnostic infrastructure for liver function assessment and antiviral treatment. Despite the significant decline observed in the occurrence of HBV infection and introduction of important HBV management steps such as establishment of the CHB registry, there are still several barriers that could delay the elimination of the infection. [ABSTRACT FROM AUTHOR]

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This study's gaol is to ascertain the impact of diazinon about the condition of common carp, a significant fish species used for food in aquaculture (Cyprinus carpio). The LC50 of diazinon after 96 h was 9.5 mg/L in C. carpio (78.8 ± 5 g in weight). The fish were divided into six tanks as two treatments in order to ascertain the long-term effects of diazinon (three tanks per treatment). They were subjected to diazinon (2.37 mg/L; 25% LC50-96 h concentration) and 0 (control) for 4 days, 14 days, and 28 days before blood biochemical assays were performed on samples taken. Dry-chemistry analyzer was used to determination the Liver Function enzyme, also SOD and CAT was estimated by use spectrophotometer. At day four and day fourteen, the plasma SOD activity of the diazinonexposed fish did not significantly decrease in comparison to the control group; however, after day twenty-eight, the plasma SOD activity of the diazinon-exposed fish significantly increased in comparison to the control group. Diazinon exposure and control report a significant increase in serum CAT activity. Diazinon exposure increased significantly in serum ALT, AST and ALP activity compared to the control group. [ABSTRACT FROM AUTHOR]

Background: Ethylene oxide, a reactive epoxy compound, has been widely used in various industries for many years. However, evidence of the combined toxic effects of ethylene oxide exposure on the liver is still lacking. Methods: We analyzed the merged data from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016. Ultimately, 4141 adults aged 18 and over were selected as the sample. We used linear regression to explore the association between blood ethylene oxide and LFT indicators. Results: The weighted linear regression model showed that HbEO is positively correlated with ALP (β = 2.61, 95% CI 1.97, 3.24, p < 0.0001), GGT (β = 5.75, 95% CI 4.46, 7/05, p < 0.0001), ALT (β = 0.50, 95% CI 0.09, 0.90, p = 0.0158), and AST (β = 0.71, 95% CI 0.44, 0.98, p < 0.0001) and negatively correlated with TBIL (β = −0.30, 95% CI −0.43, −0.16, p < 0.0001). Conclusions: Ethylene oxide exposure is significantly associated with changes in liver function indicators among adults in the United States. Future work should further examine these relationships. [ABSTRACT FROM AUTHOR]

Background: Antitubercular drugs are commonly associated with drug-induced liver injury (DILI), which can present as asymptomatic alterations in liver function test (LFT) to symptomatic hepatic injury and failure. Regular and frequent monitoring of LFT during intensive phase of therapy helps to identify early DILI and its complication. Aims and Objectives: The main objective was to evaluate the effects of antitubercular drugs on liver functions by early monitoring. Materials and Methods: A prospective observational study was conducted for 1 year among 97 newly diagnosed tuberculosis patients in tertiary care hospital. LFT was performed during baseline, at the end of 2nd week, and at end of intensive phase of treatment. Diagnosis of liver injury was based on DILI criteria and assessment of the clinical pattern of liver damage was done using "R value". Results: Among 97 patients, 16 had experienced DILI and incidence was higher during the first visit. Aspartate aminotransferase (AST) and alanine aminotransferase were significantly altered during the first visit while AST and total bilirubin during the second visit. The number of parameters deranged was higher at the end of intensive phase than during the end of 2nd week. Cholestatic pattern (81.25 %) of liver injury was the most common type as per "R value". According to DILI network severity index, the majority were categorized as "moderately-severe" and "moderate" during the first and second follow-up, respectively. Conclusion: The incidence of antitubercular drugs-induced liver injury was higher during the initial 2 weeks of treatment, but the derangement was more evident at the end of the intensive phase. Frequent and regular monitoring during the initial phase of treatment helps to detect early DILI which prevents the impending liver failure. [ABSTRACT FROM AUTHOR]

Introduction and importance: Choledochal cysts are congenital conditions that affect the biliary tree, typically identified during childhood. These cysts present as dilations in the biliary system, occurring either in the extrahepatic or intrahepatic regions or in some cases, in both areas. Occasionally, it may have associated chronic pancreatitis posing a challenge to the management of both conditions. In the case reported, a female child was diagnosed with a choledochal cyst along with chronic pancreatitis. She had an excision of cyst and lateral pancreaticojejunostomy simultaneously for both conditions resulting in favorable outcomes. Case presentation: An 8-year-old child visited the clinic with a complaint of upper abdominal pain accompanied by intermittent vomiting. An ultrasound was performed which showed a dilated common bile duct. To confirm the diagnosis, an MRCP and baseline labs including liver function tests were ordered. The findings were suggestive of a type IA choledochal cyst with concomitant chronic pancreatitis. Subsequently, she had choledochal cyst excision with Roux-en-Y hepaticojejunostomy reconstruction plus lateral pancreaticojejunostomy using the classical Puestow's technique. The patient's recovery post-surgery was uneventful, resulting in discharge on the fifth post-operative day for routine outpatient follow-up. Clinical discussion: Patients afflicted with choledochal cysts are prone to recurrent pancreatitis, though the precise underlying mechanism is unknown. Certain studies propose an association between abnormal pancreatico-biliary junction and recurrent pancreatitis, often defined as a common channel surpassing 15 mm in length. However, this aberration could not be definitively established in the current case. Diagnosis of choledochal cysts can be confirmed through either ERCP or MRCP, with the latter preferred due to its non-invasive nature. The optimal management strategy for choledochal cysts necessitates cyst resection and Roux-en-Y hepaticojejunostomy reconstruction Moreover, in cases associated with chronic pancreatitis, longitudinal pancreatojejunostomy may be undertaken. Conclusion: Thus, it is concluded that although rare choledochal cysts may have associated chronic pancreatitis. Surgical excision of the cyst and lateral pancreaticojejunostomy can be performed simultaneously resulting in favorable post-operative outcomes. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B infection has been associated with the development of gestational diabetes but the underlying mechanism is not known. Objective: To examine associations between viral activity, gestational diabetes mellitus (GDM), and insulin resistance in pregnant people with chronic hepatitis B infection (HBV). Design: Prospective cohort study across three tertiary maternity centres in Melbourne, Australia, between May 2021 and April 2023. Methods: Participants were followed prospectively through pregnancy to evaluate subsequent GDM diagnosis. Demographics, pregnancy outcomes, and markers of viral activity were compared between those with GDM versus those without. Logistic regression analysis was performed pre- and post-adjustment for known confounders. Sub-group analysis of participants from South East Asia (SEA) was performed. Outcome measures included GDM diagnosis, insulin resistance (Homeostatic Model Assessment Insulin Resistance score (HOMA-IR) score), HBV activity as measured by liver function tests, HBV viral load, hepatitis B e antigen, and quantitative hepatitis B surface antigen (quantHBsAg). Results: A total of 113 women were recruited. One third (38/112, 33.9%) developed GDM, mostly diagnosed on isolated postprandial hyperglycaemia (25/38, 65.8%). Over half were born in SEA (66/113, 58.4%). Mean quantHBsAg was significantly lower in those with GDM (p = 0.044). No other associations were identified between GDM or HOMA-IR and markers of hepatic activity on multivariate logistic regression analysis and on sub-group analysis of those born in SEA. Conclusions: QuantHBsAg was significantly lower in those with GDM; otherwise, no association between GDM and measures of HBV viral activity was found. QuantHBsAg may be useful as an early pregnancy marker for GDM risk and warrants further research. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is an immunological disease that is depicted by high prevalence and eminent burden for patients and society that is attributable to the arbitrary nature of symptoms and inconsistent tools for assessment of activity and severity. Transglutaminase-2 (TG2) is a posttranslational enzyme that is pervasively expressed in many cells and tissue types including mast cells. It has various biological functions, and its role in allergic disorders has been highlighted and delineated through several postulated mechanisms. This case–control study aimed at determining the relationship between serum levels TG2 and severity of CSU. To the best of our knowledge, this is the first study in Egypt to determine the relationship between serum TG2 and severity of CSU. We enrolled 60 adult patients with confirmed diagnosis of CSU. According to urticaria activity score (UAS), patients were categorized into three groups [20 with mild disease; UAS = 0, 20 with moderate disease; UAS = 1–3, 20 with severe disease; UAS = 4–6]. Another 20 healthy individuals (age and gender matched) served as a control group. All patients were subjected to detailed medical history, clinical examination, complete blood count with differential, serum total IgE, CRP, ESR, TSH, ANA, liver and renal function tests. Serum level of TG2 was done by quantitative ELISA for all enrolled patients and controls. Serum TG2 is significantly higher in patients group compared to control group (P value < 0.001). Serum TG2 levels were significantly higher in patients with severe disease compared to patients with moderate or mild disease. This is illustrated by the significant positive correlation between serum TG2 and UAS (r 0.814 and P value 0.000). Moreover, serum TG2 accurately classified CSU patients into mild, moderate and severe subgroups: as regards differentiation between mild and moderate cases (sensitivity 70%, specificity 80%, PPV 77.8, NPV 72.7) and as for the differentiation between moderate and severe cases (sensitivity 95%, specificity 90%, PPV 90.5, NPV 94.7). Serum TG2 may have a pivotal role as a marker of severity in patients with CSU. [ABSTRACT FROM AUTHOR]

Summary: Background: The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min. Aims: Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests. Methods: This study combined the data from two prospectively conducted US studies: HALT‐C and SHUNT‐V. A total of 455 subjects underwent both the SHUNT test and esophagogastroduodenoscopy (EGD). Results: DSI scores correlated with the probability of LEVs (p < 0.001) and demonstrated a stepwise increase from healthy lean controls without liver disease to subjects with chronic liver disease and no, small or large varices. Furthermore, a cutoff of DSI ≤ 18.3 from DuO had a sensitivity of 0.98 (missing only one case) and, if applied to the endoscopy (EGD) decision, would have prevented 188 EGDs (41.3%). The AUROC for DSI from DuO did not differ from that of the reference SHUNT test method (0.82 versus 0.81, p = 0.3500). Conclusions: DSI from HepQuant DuO links liver function and physiology to the risk of LEVs across a wide spectrum of patient characteristics, disease aetiologies and liver disease severity. DuO is minimally invasive, easy to administer, quantitative and may aid the decision to avoid or perform EGD for LEVs. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen (APAP) is commonly used as an antipyretic analgesic. However, acetaminophen overdose may contribute to liver injury and even liver failure. Acetaminophen-induced liver injury (AILI) is closely related to mitochondrial oxidative stress and dysfunction, which play critical roles in cuproptosis. Here, we explored the potential role of cuproptosis-related genes (CRGs) in AILI. Methods: The gene expression profiles were obtained from the Gene Expression Omnibus database. The differential expression of CRGs was determined between the AILI and control samples. Protein protein interaction, correlation, and functional enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was evaluated. The AILI mouse model was established by intraperitoneal injection of APAP solution. Quantitative real-time PCR and western blotting were used to validate hub gene expression in the AILI mouse model. The copper content in the mouse liver samples and AML12 cells were quantified using a colorimetric assay kit. Ammonium tetrathiomolybdate (ATTM), was administered to mouse models and AML12 cells in order to investigate the effects of copper chelator on AILI. Results: The analysis identified 7,809 differentially expressed genes, 4,245 of which were downregulated and 3,564 of which were upregulated. Four optimal feature genes (OFGs; SDHB, PDHA1, NDUFB2, and NDUFB6) were identified through the intersection of two machine learning algorithms. Further nomogram, decision curve, and calibration curve analyses confirmed the diagnostic predictive efficacy of the four OFGs. Enrichment analysis indicated that the OFGs were involved in multiple pathways, such as IL-17 pathway and chemokine signaling pathway, that are related to AILI progression. Immune infiltration analysis revealed that macrophages were more abundant in AILI than in control samples, whereas eosinophils and endothelial cells were less abundant. Subsequently, the AILI mouse model was successfully established, and histopathological analysis using hematoxylin–eosin staining along with liver function tests revealed a significant induction of liver injury in the APAP group. Consistent with expectations, both mRNA and protein levels of the four OFGs exhibited a substantial decrease. The administration of ATTAM effectively mitigates copper elevation induced by APAP in both mouse model and AML12 cells. However, systemic administration of ATTM did not significantly alleviate AILI in the mouse model. Conclusion: This study first revealed the potential role of CRGs in the pathological process of AILI and offered novel insights into its underlying pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusion 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. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its tissues and organs. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme released in response to the drop in cholesterol level occurring in sepsis. Our study aimed to evaluate the prognostic role of serum Proprotein convertase subtilisin/kexin type 9 (PCSK9) level in children with sepsis and severe sepsis. Sixty children were included in this study. They were divided into two groups: 30 children in the sepsis group and 30 in the severe sepsis group. Another 30 apparently healthy children were included as a control group. Blood samples were withdrawn from all included children for complete blood count (CBC), renal function tests (RFT), liver function tests (LFT), LDL-cholesterol (LDL-C), blood culture, and serum PCSK9. In this study, PCSK9 and LDL-C were higher in the two sepsis groups than in the control group (p < 0.05). They were also higher in the severe sepsis group than the sepsis group and in the non-survivors than in the survivors (p < 0.05). PCSK9 was positively correlated with length of hospital stay in surviving children (r = 0.67, p = 0.001) and had predicted significant hematological dysfunction (adjusted B = − 96.95, p = 0.03). In conclusion, the PCSK9 assay can be used as a biomarker for bad prognosis in children suffering from clinical sepsis. [ABSTRACT FROM AUTHOR]

Objective: Betatrophin is a hepatokine that modulates hepatic glucose and lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis. Therefore, this study aimed to investigate the relationship between NAFLD and betatrophin levels in hypogonadal males. Methods: The study included 56 newly diagnosed hypogonadal males aged 18-60 and 60 eugonadal males of similar age and body mass index. All participants were assessed for anthropometric and metabolic parameters, liver function tests, and betatrophin levels. Transient elastography was used to evaluate liver steatosis [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)]. Accordingly, hypogonadal and control groups were divided into NAFLD (n = 64) and non-NAFLD (n = 52). Results: Controlled attenuation parameter, LSM, waist circumference (WC), triglycerides (TG), IR index homeostasis model assessment (HOMA-IR), and betatrophin were significantly higher in the hypogonadal group than controls. Hepatic steatosis and fibrosis (67.9%-43.3%) were higher in hypogonadal males. Triglycerides, HOMA-IR, and betatrophin were higher, and total testosterone was significantly lower in the NAFLD group. Serum betatrophin was also significantly higher in patients with fibrosis than without. There was a significant positive correlation between WC, TG, HOMA-IR, betatrophin, and LSM and CAP. The predictive factors were TG (ß = 0.329, P < .001), betatrophin (ß = 0.221, P = .029), HOMA-IR (ß = 0.213, P = .019) for CAP, and betatrophin for LSM (ß = 0.466, P < .001). Conclusion: Non-alcoholic fatty liver disease is more common in hypogonadal males than in eugonadal males. Betatrophin is an independent risk factor for developing and progressing NAFLD. However, more research is needed to explain the causal relationship between betatrophin and NAFLD. [ABSTRACT FROM AUTHOR]

Background: To assess the impact of orally given itopride and levosulpride on non-ulcer dyspepsia. Materials and Methods: A total of 120 patients were divided equally into two groups, with 60 patients in each group. Group A consists of 60 patients. Subjects were randomly allocated to receive a 50 mg dose of itopride hydrochloride, administered three times per day prior to meals. Contrarily, Group B received a 75 mg dose of Levosulpiride, which was likewise administered three times daily prior to meals. The therapy regimen was adhered to for a duration of two weeks, and then continued for a total of three months. This study included individuals between the ages of 18 and 60 (both males and females) who had symptoms of non-ulcer dyspepsia, such as bloating or pain in the upper abdomen, nausea, and heartburn, lasting for a minimum of 12 weeks. Results: After two weeks of therapy, the Itopride group had 46.66% of patients experiencing remarkable or full reduction of symptoms, 30% experiencing moderate relief, 16.67% experiencing little relief, and 6.67% experiencing no improvement. Within the Levosulpiride group, 40% of participants saw significant or total alleviation, 36.67% experienced moderate alleviation, 15% experienced little alleviation, and 8.33% experienced no alleviation. Both medications demonstrated efficacy, however, the Itopride group had a greater proportion of significant or full alleviation. Incidents with negative consequences were documented and compared between the two groups. Within the Itopride group, 13.33% of patients had minor gastrointestinal discomfort, 8.33% experienced headaches, and 3.33% experienced dizziness. Within the Levosulpiride group, 15% of participants had minor gastrointestinal distress, 5% reported headaches, and 8.33% reported dizziness. Both groups saw a comparable occurrence of minor negative effects, while the Levosulpiride group had a significantly greater occurrence of dizziness. Before and after therapy, a series of biochemical tests were performed, including a hemogram, blood urea nitrogen (BUN), serum creatinine, liver function tests (AST, ALT, γ-GT, Alk. Phos), bilirubin, total cholesterol, fasting blood sugar (FBS), and QT-interval. Conclusion: Our investigation showed that both Itopride and Levosulpiride are effective in relieving symptoms of non-ulcer dyspepsia, and they have a comparable safety profile. However, Itopride shown a much higher incidence of persons achieving substantial or complete relief from symptoms. [ABSTRACT FROM AUTHOR]

Background: Several factors contribute to post-anesthetic hepatic dysfunction, including a decrease in oxygen supply to the liver, direct physical compression of the liver, viral hepatitis, blood transfusions, preexisting hepatic dysfunction, and the use of hepatotoxic drugs. Diagnosing volatile anesthetic drug-induced liver injury (VA-DILI) involves excluding these causes. Case: The patient underwent total mastectomy under anesthesia using sevoflurane. He had diabetes, and no abnormal results were found on preoperative laboratory examinations, and surgery was uneventful. Abnormal laboratory findings were observed after surgery, including an aspartate aminotransferase level of 1,417 IU/L, an alanine aminotransferase level of 2,176 IU/L, and a total bilirubin level of 3.8 mg/dl. He presented with symptoms of mild icteric sclera, fatigue, and pruritus. After ruling out other causes of liver injury, we concluded that these results indicated VA-DILI. Conclusions: VA-DILI, though rare, we should be aware of the association between the disease and the use of halogenated anesthetics. [ABSTRACT FROM AUTHOR]

Background: β-Thalassemia major patients require lifelong blood transfusions, leading to iron overload and liver injury. This study examines the longitudinal association between serum ferritin and liver function over 5 years in pediatric patients. Methods: This retrospective study included 582 transfusion-dependent thalassemia patients aged 1-18 years. Serum ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin were measured annually. Correlation and linear regression analyses assessed associations between ferritin trajectories and liver enzymes. Results: Mean ferritin rose from 1820 ± 960 ng/mL at baseline to 4500 ± 1900 ng/mL at year 5, indicating worsening iron overload. AST and ALT levels also steadily climbed over follow-up, whereas albumin declined slightly. Ferritin correlated positively with AST (r = 0.675, P < 0.01) and ALT (r = 0.607, P < 0.01), but not with albumin (r = -0.143, P = 0.153) annually. The regression interaction term showed within-patient ferritin increases over time were independently associated with escalating AST and ALT (P < 0.05), after adjusting for confounders. Conclusion: Rising ferritin levels predict progressive liver injury in regularly transfused pediatric thalassemia patients. Tighter control of iron overload may help preserve hepatic function. [ABSTRACT FROM AUTHOR]

BACKGROUND: Salvia officinalis (Common Sage) plant, is used as herbal medicine. The study was aimed at investigating the antimalarial potential and liver function profiles of the Methanol Extract of Salvia officinalis. METHODS: Mice infected with Plasmodium berghei were treated (p.o) with the extract in the curative, suppressive, and prophylactic antimalarial models at doses of 250mg/kg, 500mg/kg, and 1000mg/kg. The positive control drug used was artemether/ lumefantrine (7mg/kg A/L) while the negative control was 10mk/kg of Tween 80. RESULTS: The curative stage showed a significant (p < 0.001) dose-dependent antiplasmodial effect (of the methanol extract of S. officinalis leaf) compared with the negative control (Group 1). At doses of 250, 500, and 1000mg/kg, the Salvia officinalis extract produced parasite suppression of 37.13%, 57.18% and 66.80% respectively. While the positive control group produced parasite percentage suppression of 74.38%. There was a significant chemosuppressive effect (p < 0.001) at all doses of the methanol extract of Salvia officinalis leaf.The leaf extracts demonstrated a prophylactic significant (p < 0.001) activity. There was no significant effect (p > 0.05) on packed cell volume at doses of 250 and 500mg/kg while 1000mg/kg body weight showed a significant (p < 0.05) effect. There was a reduction in the level of activity of the enzymes and other parameters in the liver function tests with an increase in the dosage of the leaf extract. CONCLUSION: The methanol extract of Salvia officinalis possesses in vivo antiplasmodial activities and could be a lead plant in the development of antiplasmodial agents. [ABSTRACT FROM AUTHOR]

Nowadays, drug-induced liver toxicity (DILT) is one of the main contributing factors to severe liver disease. In the United States (US) alone, DILT is the cause of more than 50% of instances of acute liver failure. Prescription or over-the-counter drugs, xenobiotics, and herbal and nutritional supplements can cause DILT and could produce anomalies in hepatic function tests. Some drugs induce hepatotoxicity directly, and others induce it indirectly (i. e. through their toxic or reactive metabolites). Currently, the United States Food and Drug Administration (US FDA) has issued black box warnings for about 1279 drugs due to their hepatotoxicity. When we analyzed their mechanism in inducing hepatotoxicity, we found nearly 18 drugs causing hepatotoxicity by their toxic metabolites. In this review, we attempted to highlight the well-known drugs that induce hepatotoxicity indirectly through their toxic metabolites including the enzymes involved in the formation of these metabolites. The Cytochrome P-450 (CYP), Hypoxanthine phosphoribosyltransferase 1, Alcohol oxidase, Uridine diphosphate (UDP)-glucuronosyltransferases, Xanthine dehydrogenase, Purine-nucleoside phosphorylase, Xanthine oxidase, Thiopurine S-methyltransferase, Inosine-5'-monophosphate dehydrogenase, and aldehyde dehydrogenase are involving in the formation of toxic metabolites. The metabolic reactions and enzymes discussed in this review help toxicologists, pharmacologists, and chemists to design and develop hepatotoxicity-free pharmaceutical products containing the inhibitors of these enzymes to reduce hepatotoxicity and improve human health. [ABSTRACT FROM AUTHOR]

The article explores the growing prevalence of metabolic liver disease, specifically focusing on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Associated Steatotic Hepatitis (MASH), and Metabolic Alcohol-Related Liver Disease (MetALD). It highlights that metabolic risks such as central obesity, high blood pressure, and hyperglycemia significantly contribute to liver disease, which has become the third leading cause of death in the UK.

Objective Low-density lipoprotein cholesterol (LDL-C) has been commonly calculated by equations, but their performance has not been entirely satisfactory. This study aimed to develop a more accurate LDL-C prediction model using machine learning methods. Methods The study involved predicting directly measured LDL-C, using individual characteristics, lipid profiles, and other laboratory results as predictors. The models applied to predict LDL-C values were multiple regression, penalized regression, random forest, and XGBoost. Additionally, a novel 2-step prediction model was developed and introduced. The machine learning methods were evaluated against the Friedewald, Martin, and Sampson equations. Results The Friedewald, Martin, and Sampson equations had root mean squared error (RMSE) values of 12.112, 8.084, and 8.492, respectively, whereas the 2-step prediction model showed the highest accuracy, with an RMSE of 7.015. The LDL-C levels were also classified as a categorical variable according to the diagnostic criteria of the dyslipidemia treatment guideline, and concordance rates were calculated between the predictive values obtained from each method and the directly measured ones. The 2-step prediction model had the highest concordance rate (85.1%). Conclusion The machine learning method can calculate LDL-C more accurately than existing equations. The proposed 2-step prediction model, in particular, outperformed the other machine learning methods. [ABSTRACT FROM AUTHOR]

Purpose: Patients who receive frequent blood transfusions are at an elevated risk of developing hepatic fibrosis due to iron overload in the liver. In this study, we evaluated the effectiveness of transient elastography (TE) (FibroScan®) for assessing liver fibrosis in patients with pediatric cancer. Methods: We enrolled 106 consecutive cases of acute leukemia in individuals under 21 years of age. The participants were followed for 2 years. Based on their serum ferritin (SF) levels, the patients were divided into two groups: group 1 (SF≥300 ng/mL) and group 2 (SF<300 ng/mL). A liver FibroScan® was performed, and a p-value of less than 0.05 was considered statistically significant. Results: Among the various parameters in the liver function test (LFT), alkaline phosphatase was significantly higher in a subgroup of patients aged 5--8 years in group 2 compared to those in group 1. The indices of liver fibrosis determined by TE, including the FibroScan score, controlled attenuation parameter score, steatosis percentage, and meta-analysis of histological data in viral hepatitis score, as well as indirect serum markers of liver fibrosis such as the aminotransferase (AST)/alanine aminotransferase (ALT) ratio, Fibrosis 4 score, and AST to platelet ratio index, did not differ significantly between the two groups. The association between the TE results and LFT parameters was only significant for ALT. Conclusion: Transfusion-associated iron overload does not have a significant correlation with severe liver fibrosis. FibroScan® is not a sensitive tool for detecting early stages of fibrosis in survivors of pediatric leukemia. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic cholecystectomy (LC) requires the creation of pneumoperitoneum via insufflations of carbon dioxide; resulting in increased partial pressure of carbon dioxide (Co2) and intraperitoneal pressure which leads to changes in pulmonary functions and hemodynamic measurements. Liver function indicators were observed to be disrupted after a laparoscopic cholecystectomy (LC) in numerous studies. Pneumoperitoneum induced by carbon dioxide modifies splanchnic microcirculation and can affect lung, liver, kidney and heart physiology. The purpose of the study was to determine how liver function tests in LC were affected by carbon dioxide pneumoperitoneum. The studies objective was to determine the impact of changes to liver function test and the safety of the surgery. Methods of study: Pre operative and post operative ( day 1 and day 3 ) serum bilirubin, albumin, AST and ALT will be estimated ( Method used for serum Bilirubin and albumin is Colorimetric and for serum AST and ALT is multiple -- point rate ) followed by Comparison of preoperative and postoperative liver enzymes changes in laparascopic cholecystectomy with CO2 as pneumoperitoneum . Results : There is statistically insignificant changes of serum bilirubin and albumin on post operative 3 rd day in both open and laparoscopic cholecystectomy but in case of laparoscopic cholecystectomy there is statistically significant change of serum ALT in post operative day 1 and 3 with p value <0.001 and statistically significant elevation of serum AST on post operative day 1 whereas on post operative day 3 it is statistically insignificant with p value <0.001. In terms of duration of hospital stay and duration of surgery longer duration is found in open cholecystectomy as compared to laparoscopic cholecystectomy .Discussion: Current study shows no change in serum bilirubin and albumin but shows statistically significant increase of serum AST and ALT in post operative status of laparoscopic cholecystectomy. [ABSTRACT FROM AUTHOR]

Background: Budd–Chiari syndrome (BCS) is a rare condition, usually associated with hematological disorders such as thrombotic diathesis and hypercoagulability. Serum CA-125 level is an established tumor marker of ovarian malignancy; however, cases of primary BCS may also show raised CA-125 levels. BCS in a case of ovarian carcinoma is usually primary in nature due to hypercoagulable state, and raised CA-125 levels with tender hepatomegaly in a treated case of ovarian carcinoma usually imply metastatic recurrence in the liver. However, our case demonstrates an atypical secondary cause of BCS in such a patient caused by extrinsic compression of IVC due to recurrent disease. Case presentation: We report an unusual case of a 69-year-old female who presented with nausea and abdominal pain. She had a 7-year-old history of endometrioid carcinoma of the right ovary for which she underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic lymph node dissection along with adjuvant chemotherapy. Currently, she had right hypochondrium tenderness, deranged liver function tests (LFT) and raised CA-125 levels, which raised suspicion of hepatic metastasis. However, CECT abdomen revealed peripheral mottled enhancement of liver with multifocal extrahepatic tumor deposits, one of them causing compression of inferior vena cava (IVC) implying a diagnosis of secondary Budd–Chiari syndrome. Conclusions: In a background of treated ovarian malignancy with raised CA-125 levels and deranged LFT, primary suspicion is of hepatic tumor recurrence. However, in our case, radiological investigation revealed diagnosis of secondary Budd–Chiari syndrome due to perihepatic metastatic recurrence with the absence of frank intrahepatic lesions. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) imposes a substantial symptom burden that adversely impacts patients' quality of life. Current anti-fibrotic treatments for IPF provide limited symptomatic relief, necessitating the implementation of complementary disease management strategies to enhance health-related quality of life (HRQOL). Serracor-NK® and Serra Rx260, systemic enzyme supplements, improved symptoms and HRQOL with favorable safety profiles in a proof-of-concept study in PF patients. This prospective, double-blind randomized placebo-controlled trial enrolled 100 IPF patients from six institutions. The supplement group (n = 50) received the oral systemic enzyme supplements Serracor-NK® and Serra Rx260 in addition to standard care for 6 months, while the placebo group (n = 50) received standard care alone. The primary objective was to evaluate the regimen's impact on symptoms, QOL, and well-being using the UCSD shortness of breath (UCSD-SOB) questionnaire, St. George's respiratory questionnaire (SGRQ), and WHO well-being index (WHO-5). Safety evaluation was a secondary objective. A significantly higher proportion of patients in the supplement group demonstrated meaningful improvement in symptoms as compared to the placebo group, as assessed by the UCSD-SOB (p < 0.05) and SGRQ questionnaires (p < 0.05). Additionally, a significantly greater proportion of patients in the supplement group showed improved QOL and well-being (p < 0.05) and reduced health impairment (p < 0.05), as assessed by SGRQ. Mental well-being (WHO-5) and physical activity (SGRQ activity domain) did not differ significantly between the groups. Safety assessments, including liver function tests and vital signs, indicated that the supplement regimen was well tolerated. To conclude, Serracor-NK® and Serra Rx260 alleviate symptoms and enhance HRQOL in IPF patients with a favorable safety profile (Clinical Trials Registry India registration number: CTRI/2020/05/025374). [ABSTRACT FROM AUTHOR]

Globally, 300 million people worldwide are exposed to groundwater arsenic poisoning in the recent time, while an estimated 10 million population are exposed to arsenic poisoning in Bihar (India). The arsenic contamination in ground water has caused serious health hazards in the exposed population. The typical symptoms of arsenicosis are observed in the exposed population mostly skin manifestations such as hyperkeratosis, melanosis, loss of appetite, neuro-behavioral disorders etc. Hence, the present study aims to develop novel drug discovery against arsenic induced toxicity in rat models. In the present study treatment groups received sodium arsenite orally at the dose of 8 mg/kg body weight daily for 90 days followed by administration of Ocimum sanctum (Tulsi) seed extract at the dose of 500 mg/ kg body weight daily by gavage method for 60 days. Their biochemical levels like liver and kidney function tests were assayed and were found with elevated levels. Furthermore, their free radical assessment such as lipid peroxidation levels were assayed which was also found to be many folds higher. Furthermore, the arsenic concentration in the tissue of liver and kidney was significantly very high. But, after the administration of ethanolic seed extract of Ocimum sanctum, there was significant restoration in the biochemical and lipid peroxidation levels. Moreover, there was also reduction in the arsenic content in the liver and kidney tissues of rats. The phytoremedial effect of this novel plant (Ocimum sanctum) denotes that it possesses antidote effect against arsenic induced toxicity. [ABSTRACT FROM AUTHOR]

Background: The general practice out-of-hours (GPOOH) service is under pressure to treat more patients in less time, while reducing referrals and minimising diagnostic errors. Point-of-care (POC) testing involves rapid clinical tests that can be used to generate results during the consultation, and has the potential to facilitate managing these competing demands safely. Aim: To describe current availability of POC tests in GPOOH in Scotland, and identify barriers, enablers, benefits, and drawbacks to its use. Design & setting: Cross-sectional mixed-methods study, which surveyed opinions of clinicians working in the GPOOH service in NHS Scotland. Method: An electronic questionnaire was developed, designed, piloted, and distributed to clinicians, which had closed questions and areas for free text. Results: In total, 142 responses were received. Urine dipstick testing (99.2%), pregnancy tests (98.5%), oxygen saturation (97.7%), and blood glucose testing (93.9%), were the only POC tests commonly available in GPOOH in NHS Scotland. There was strongest support for the provision of POC tests, particularly C-reactive protein (CRP; 79.4%), strep A (76.0%), and D-dimer (75.2%). Responders felt that POC tests would improve confidence (92.3%) and safety (89.8%) surrounding clinical decision making, improve patient satisfaction (80.6%), and reduce hospital and secondary care referrals (77.5%). Barriers to POC test use were availability of the test kits and machines (94.5%), training requirements on how to use the machine (71.1%) and interpret results (56.3%), and time to do the test (62.0%). Conclusion: Few POC tests are in regular use in GPOOH in Scotland. GPOOH clinicians are supportive of using POC testing. They identified a number of benefits to its use, with very few drawbacks. Increased provision of POC testing in GPOOH in NHS Scotland should be considered urgently. [ABSTRACT FROM AUTHOR]

In Mexico, hepatitis B and C infections are a significant burden on the health system. The aim of this narrative review was to analyze the state of the art on hepatitis B and C in Mexico by searching and studying available data in academic articles and government reports and statements on epidemiology, prevention, treatment, and elimination strategies undertaken by the Mexican government. Even where the government has implemented a hepatitis B vaccination strategy to reduce its incidence, a very low proportion of people complete the vaccination schedule. Regarding hepatitis C, there is a National Elimination Program that emphasizes the importance of screening, diagnosis, and treatment focused on the population at risk. With the implementation of this program, more than a million fast tests have been carried out and the positive cases have been verified by viral load. Infected patients are tested to determine liver function, fibrosis stage, and coinfection with HBV and/or HIV. Patients without cirrhosis and/or coinfections are treated in first-level care centers, while those with cirrhosis and/or comorbidities are referred to specialists. The possibility of hepatitis C eradication in Mexico seems more likely than eradication of hepatitis B; however, major challenges remain to be overcome to reach both infections' elimination. [ABSTRACT FROM AUTHOR]

HepQuant tests quantify liver function from clearance of deuterium‐ and 13C‐labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child‐Pugh classification to categorize the degree of hepatic dysfunction. We compared HepQuant tests with Child‐Pugh classification in predicting the pharmacokinetics of ampreloxetine. Twenty‐one subjects with hepatic impairment (8 Child‐Pugh A, 7 Child‐Pugh B, and 6 Child‐Pugh C), and 10 age‐ and sex‐matched controls were studied. The pharmacokinetics of ampreloxetine were measured after oral administration of a single dose of 10 mg. Disease severity index (DSI), portal‐systemic shunting (SHUNT%), hepatic reserve, and hepatic filtration rates (HFRs) were measured from serum samples obtained after intravenous administration of [24‐13C]‐cholate and oral administration of [2,2,4,4‐2H]cholate. Ampreloxetine plasma exposure (AUC0‐inf) was similar to controls in Child‐Pugh A, increased 1.7‐fold in subjects with Child‐Pugh B, and 2.5‐fold in subjects with Child‐Pugh C and correlated with both Child‐Pugh score and HepQuant parameters. The variability observed in ampreloxetine exposure (AUC0‐inf) in subjects with moderate (Child‐Pugh B) and severe hepatic impairment (Child‐Pugh C) was explained by HepQuant parameters. Multivariable regression models demonstrated that DSI, SHUNT%, and Hepatic Reserve from SHUNT and DuO were superior predictors of ampreloxetine exposure (AUC0‐inf) compared to Child‐Pugh score. HepQuant DSI, SHUNT%, and hepatic reserve were more useful predictors of drug exposure than Child‐Pugh class for ampreloxetine and thus may better optimize dose recommendations in patients with liver disease. The simple‐to‐administer, oral‐only DuO version of the HepQuant test could enhance clinical utility. [ABSTRACT FROM AUTHOR]

Abdifatah Abdullahi Jalei,1 Abdifetah Ibrahim Omar,1,2 Shafie Abdulkadir Hassan,1 Yahye Sheikh Abdulle Hassan,1 Nur Rashid Ahmed1,2 1Faculty of Medicine and Health Sciences, Jamhuriya University of Science and Technology, Mogadishu, Somalia; 2Jamhuriya Research Center, Jamhuriya University of Science and Technology, Mogadishu, SomaliaCorrespondence: Abdifatah Abdullahi Jalei, Faculty of Medicine and Health Sciences, Jamhuriya University of Science and Technology, Mogadishu, Somalia, Tel +252617000684, Email Jeele301@gmail.comIntroduction: Reference intervals (RIs) are crucial for the accurate interpretating of laboratory test results in clinical settings, serving as benchmarks for evaluating individual health status. This study investigates the influence of sex and age on common liver function tests (LFTs) and renal function tests (RFTs) in healthy adults in Mogadishu, Somalia.Methods: A community-based cross-sectional study was carried out from October 2022 to January 2023 on a randomly selected sample of 255 healthy participants from Mogadishu, Somalia. Approximately 5 mL of whole blood was collected from each participant and processed screening of hepatitis B and C, and human immunodeficiency virus, and then biochemical analyses were conducted for common liver and kidney parameters.Results: The study found significant sex and age-related differences in the measured LFTs and RFTs parameters. For LFTs, males had higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to females (ALT: 11.5 vs 7.5 U/L; AST: 25.5 vs 19.1 U/L; both p < 0.001). Age-related differences were also observed, with individuals aged 30 and above had higher levels of ALT and AST compared to those aged 18– 29 (ALT: 10.9 vs 8.5 U/L; AST: 24.3 U/L vs 21.0 U/L, both p < 0.001). For RFTs, males had higher levels of creatinine (0.9 vs 0.7 mg/dL), urea (23.1 vs 16.1 mg/dL), and uric acid (5.2 vs 4.2 mg/dL) than females, all with p < 0.001.Conclusion: The study established population specific RIs for common liver and renal function parameters and revealed significant variations across sex and age groups. These findings underscore the importance of developing and using local RIs to ensure accurate clinical interpretation and effective patient management. Further research with larger sample sizes and in diverse regions of Somalia is highly recommended.Keywords: reference intervals, liver function tests, renal function tests, Mogadishu, Somalia

Introduction Despite strong and consistent epidemiological evidence linking cigarette smoking to several cardiovascular diseases (CVDs), the association between smoking intensity and CVD risk factors remains unclear. This study aimed to explore the possible effects of cigarette smoking on cardiometabolic risk in healthy individuals. Methods This cross-sectional study was conducted between November 2022 and June 2023. Consecutive sampling was performed to include 160 healthy participants: 100 smokers with 60 males and 40 females; and 60 age- and sexmatched non-smokers with 36 males and 24 females. Blood samples were taken from each participant to assess their cardiometabolic function: lipid profile, von Willebrand factor (vWF), high-sensitivity cardiac troponin I (hs-cTnI), and fibrinogen levels; and liver function using an automated enzymatic method. In addition, blood sugar level, body mass index (BMI), and blood pressure were recorded. Results Smokers had significantly higher vWF functional activity and hs-cTnI but significantly lower albumin and total bilirubin levels than non-smokers (65.87 ± 19.07 vs 56.45 ± 6.59, respectively, p

Arsenic catastrophe has caused serious health hazards to the exposed population. An estimated 10 million people are exposed to arsenic poisoning through groundwater. The arsenic contamination through ground water has caused health diseases such as skin manifestations, loss of appetite, nausea, bowel disorders, neurological disorders etc. Therefore, there is need for search for proper therapeutic drug against arsenic induced toxicity in rats. In the present study, arsenic induced toxic model was developed by treating Charles Foster rats (n=18) with sodium arsenite orally at the dose of 8 mg/kg body weight daily for 60 days followed by administration of Bacopa moneri (Brahmi) leaf extract at the dose of 30mg/kg body weight daily by gavage method for 60 days. After the completion of the experiment, all the animals were sacrificed and their blood samples were collected along with their vital tissues. Following parameters were assayed such as haematological assay, biochemical assay and histopathological evaluation in the present study. The haematological study comprised of RBC counts, WBC counts, platelets counts and heamoglobin percentage. For biochemical evaluation, the liver function test and the kidney function test parameters along with free radical assay were carried out. The histopathological study also showed very high degree of degeneration in the hepatocytes and the nephrocytes in the vital organ's liver and kidney. But, after the administration of ethanolic leaf extract of Bacopa moneri, there was marked restoration in the studied parameters. The haematological parameters, the biochemical parameters as well as the histopathological study showed very significant outcomes. Therefore, the present studied medicinal plant Bacopa moneri possesses antidote effect against arsenic induced toxicity in Charles Foster rats which can be used as therapeutic drug in the future after clinical approval. [ABSTRACT FROM AUTHOR]