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The severity of COVID‐19's outcomes has been positively correlated with an increased risk of respiratory failure and death, especially in patients with chronic illnesses. This case–control design study aims to examine the correlation in the Palestinian population in light of its impact on diabetic patients. The study was conducted from March 2020 to June 2021 on 417 patients admitted to the Palestinian National Center for Rehabilitation. Of them, 198 cases were tested positive for COVID‐19 and had diabetes, whereas the remaining 219 were those who tested positive for COVID‐19 but were not diagnosed with diabetes and acted as controls. Data from patient files were collected to address the study questions. Patients' ages ranged from 17 to 98 years, with a mean age of 58. Male participants represented 53.5% of the total. The results of the current study indicated that the case fatality rate (CFR) was 14.2% for all participants and 19.7% for patients with diabetes. In regard to patients' health conditions, 5.7% had cardiovascular diseases (CVD), 33.6% had hypertension, 6.5% had kidney diseases, and 47.4% had diabetes. According to the multivariate analysis, diabetic patients had a 1.63 times higher risk for COVID‐19 infection compared to nondiabetic patients (adjustment of odds ratio of 1.63 and confidence interval [CI] = 0.354–1.856). This is the first study to investigate the relationship between the severity of COVID‐19 outcomes in Palestine and the diabetes status, and the majority of its findings are consistent with other research studies that assessed the impact of COVID‐19 on diabetic patients (with minor variations in the number and percentage). The study confirms that along with diabetes, age, hypertension, kidney diseases, shortness of breath, requirement of oxygen, D‐dimer, C‐reactive protein (CRP), kidney function test (KFT), and days of hospitalization were also associated with severe COVID‐19 outcomes, whereas gender, CVDs, and liver function test (LFT) were not associated with severe COVID‐19 outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH.In the US multicentre SHUNT‐V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy.Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut‐off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%.SHUNT‐V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child–Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%–100% for LEV and 97.3%–100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%–35% of EGDs could have been avoided with 0%–3.7% of LEV and 0%–2.7% of all significant PH lesions missed.HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal‐systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child–Pugh A cirrhosis.Trial Registration: The SHUNT‐V study was registered at ClinicalTrials.gov (NCT03583996) [ABSTRACT FROM AUTHOR]

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin are well-established liver biomarkers with significant physiological functions. Alterations in these liver function tests can be indicative of the presence and progression of acute and chronic liver conditions such as liver cirrhosis, non-alcoholic fatty liver disease, biliary disease, and liver failure. Therefore, accurate and quantitative detection of these biomarkers is crucial for diagnosing and monitoring liver disease. There are several commercially available chemistry analyzers capable of simultaneously detecting all these biomarkers, as well as numerous biosensors designed for individual detection. Various techniques have been employed, including colorimetry, surface-enhanced Raman spectroscopy (SERS), electrochemiluminescence (ECL), fluorescence-based techniques, and electrochemical methods. Among these, electrochemical detection stands out due to its simplicity, cost-effectiveness, low sample volume requirement, label-free detection, high sensitivity, fast response times, miniaturization, and portability. Information on recently developed electrochemical biosensors is summarized through detailed tables and is intended to guide future research and development efforts in this area. [ABSTRACT FROM AUTHOR]

Introduction: To ascertain the adverse health outcomes experienced by those using prescribed testosterone and non‐prescribed anabolic–androgenic steroids presenting to general practitioner (GP) clinics. Methods: 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. Results: 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. Discussion and Conclusion: 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]

We have previously shown that body mass index attenuates a positive association of platelet count (PLT) and inverse of mean platelet volume (MPV) with lung cancer risk in men. It is unclear whether fat mass, lean mass, or liver function tests (LFTs) show similar attenuations. Using bioelectrical impedance measurements (UK Biobank cohort) and multivariable Cox proportional hazards models, we examined the associations of allometric fat-mass index (AFI, fat mass adjusted for height), allometric lean-mass index (ALI, fat-free mass adjusted for height and fat mass), and LFTs with lung cancer risk and their multiplicative and additive interactions with platelet parameters. Based on 1573 lung cancer cases in men and 1473 in women with body composition measurements (1541 in men; 1428 in women with biomarker measurements), AFI in women, ALI in both sexes, alanine aminotransferase (ALT) and total bilirubin in men were inversely associated, while gamma-glutamyl transferase in men and alkaline phosphatase in both sexes were positively associated with lung cancer risk. Only AFI and ALT interacted inversely with PLT and positively with MPV in men. The attenuation of the associations of platelet parameters with lung cancer risk by high-AFI and high-ALT in men suggests that adiposity-related factors hinder lung-cancer-related platelet associations. [ABSTRACT FROM AUTHOR]

Accumulating evidence has shown that adipose-derived stem cells (ADSCs) have the potential to differentiate into hepatic lineages, which are ideal engraftments for tissue-engineered repair. In this study, we investigated the potential of transplanted induced hepatocyte-like cells (iHEPs) in treating hepatic alveolar echinococcosis and describe an efficient three-step protocol for the generation of iHEPs in vitro from ADSCs. The expression of hepatocyte lineage markers was assessed and iHEPs function was evaluated by Periodic acid-Schiff staining. iHEPs were intravenously transplanted into mice infected with Echinococcus multilocularis. Histopathological analysis and liver function tests were used to assess therapeutic effects. The iHEPs exhibit morphological features and a glycogen storage function similar to those of mature hepatocytes and demonstrate an upregulation in hepatic gene programs with increasing induction time. Following transplantation, iHEPs were observed surrounding the metacestode lesions in the liver parenchyma of E. multilocularis-infected mice. iHEPs transplantation effectively restored liver function and improved liver injury in the infected mice. Additionally, we observed significant activation of the Wnt/β-catenin signaling pathway in the livers of infected mice transplanted with iHEPs. Our results provide evidence that iHEPs transplantation can alleviate E. multilocularis-induced liver injury, potentially creating new avenues for treating liver injury in end-stage hepatic alveolar echinococcosis. [ABSTRACT FROM AUTHOR]

Background: As one of the most requested profiles of blood tests, there is a need for standardization among liver function tests (LFT). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are key markers of hepatocellular injury. ALT and AST are used to calculate a Fibrosis-4 (FIB-4) score for assessing liver fibrosis. Despite recommendations by the International Federation of Clinical Chemistry (IFCC) to include pyridoxal-5-phosphate in ALT and AST assay methodologies, most laboratories continue to omit this. Methods: Data from the UK NEQAS for Clinical Chemistry Scheme, Distribution 1160 (November 2023), was reviewed to investigate variation in practice regarding liver blood tests in relation to ALT, AST and FIB-4. In addition, a series of questions audited laboratory practice in relation to liver enzymes. Results: Wide variation was seen in LFT profiles offered by laboratories, with 32 different combinations of tests used. The IFCC-recommended methods for ALT and AST are used by one-third of laboratories and give significantly higher results than non-IFCC methods. Laboratories using IFCC methods also reported significantly higher FIB-4 scores. Reference ranges and cut-offs for these tests also varied, and did not account for method-related differences in results. Conclusions: The lack of standardization of LFTs can have a significant impact on patient care. The difference in results for ALT, AST and FIB-4 in laboratories not using IFCC-recommended methods may lead to misdiagnosis. This issue should be addressed by laboratories using methods including pyridoxal-5-phosphate. Until then, method-related reference ranges and cut-offs for ALT, AST and FIB-4 are required. [ABSTRACT FROM AUTHOR]

Background Atezolizumab plus bevacizumab is the standard of care for advanced hepatocellular carcinoma (HCC) in the first-line setting, although was only evaluated in patients with Child-Pugh (CP) A liver function in the IMbrave150 trial. We sought to determine the outcomes of these patients based on CP score and ALBI grade in the US population. Methods This multicenter cohort study included patients with HCC who received atezolizumab with bevacizumab as first-line systemic therapy between March 2018 and November 2023. Overall survival (OS) was determined using the Kaplan-Meier method and multivariate analyses were performed using Cox proportional hazard regression method. Results Among 322 patients, 226, 86, and 10 patients had CP-A, CP-B, and CP-C liver function, respectively. Median age was 66.5 years, 78.6% were male, and 82.6% were White. Median OS (mOS) was 21.6 months for those with CP-A, 9.1 months for those with CP-B7, and 4.7 months for those with CP-B8-C12 (P  < .0001). Among patients with CP-A, those with ALBI grade 1 had an mOS of 34.9 months versus 14.2 months in those with grade 2. In multivariate analyses, CP score, ALBI grade, hepatitis B, performance status, and macrovascular invasion were significantly associated with survival. Conclusions CP score is an important prognostic tool for patients with HCC receiving atezolizumab plus bevacizumab, and this regimen remains a viable option for patients with CP-B7 with no additional safety concern, although the benefit is significantly less than those with CP-A. ALBI score has independent predictive value in patients with CP-A liver function. [ABSTRACT FROM AUTHOR]

Objective: Our aim in this study is, does 29-day regular consumption of Pleurotus ostreatus water extract by volunteer individuals who meet the study criteria have an effect on blood and cytokine values? Method: In accordance with the purpose of the study, volunteers were asked to consume 100 ml of the extract every morning for 29 days. Three tubes of blood samples were taken from the volunteers on the 15th and 29th days of the study. Biochemical and hematological analysis of the blood samples were performed and immunomodulatory effects through cytokines were examined. The values obtained from 3 tubes of blood obtained from volunteers before the use of mushroom extract were used as control. The chemical composition and β-glucan content of 100 ml of mushroom water extract were also analyzed. Result: IL-4, IL-6, IL-10 and IL-13 could not be detected because the values were below the lowest standard value. TNF-α, IFN-γ and IL-1β 15th and 29th day values decreased compared to the 1st day (control) values (p < 0.05). However, there was no significant difference observed between the 15th and 29th day. No abnormalities were observed in biochemical and hematological values. Also, the β-glucan content of extract was found 38.12 mg/100 ml. Conclusion: The frequency range of kidney and liver function test results confirmed that P. osreatus is a reliable food source. Considering the cytokine values these results indicate that P. ostreatus water extract has an anti-inflammatory effect. As no significant difference was observed in 29 days of use, it is thought that 15 days of daily consumption of the extract may be sufficient for the anti-inflammatory effect to occur. However, a large number of qualified clinical trials are needed to support the issue. [ABSTRACT FROM AUTHOR]

Glycation is among the underlying mechanisms attributed to ageing and associated morbidities. There is no drug available to combat this deleterious phenomenon. The present study aimed to explore phloroglucinol (PHL) for its anti-glycation potential at preclinical level. The rats were treated with methylglyoxal (MGO, 17.25 mg/kg, i.p. for 14 days) to induce glvcative stress. The treatment groups received additional administration of test drug (PHL; 0.25mg/kg, 0.5mg/kg, and 1mg/kg) or standard aminoguanidine (AG, 50 mg/kg) or saline (control, 5ml/kg). During 14 days, the weight and food intake was noted. Afterwards, the cognitive function was evaluated using Morris Water Maze (MWM) while hepatic and renal functions were assessed through liver function test (bilirubin, alkaline phosphatase, SGPT, and SGOT) and creatinine respectively, using chemical analyzer. The carboxymethyllysine (CML) levels were quantified in the blood using ELISA technique. Histopathological study was performed on the brain, liver, and kidney using H&E staining. Additionally, the qPCR was used to quantify the expression of TNF-α, RAGE and BACE-1 (brain), RAGE, TNF-α, and glyoxalase-I (liver) and RAGE, TNF-α, and VEGF (kidney), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference housekeeping gene. The data regarding weight and food intake did not reveal significant alterations. In MWM, the MGO treatment caused significant increase in the time to reach target quadrant, while decrease in the time spent in target quadrant and number of crossings through platform position. All these effects were inhibited by both AG and PHL. The navigation maps also exhibit that the retention of spatial memory. Additionally, the MGO-induced alteration in hepatic and renal function indicators was ameliorated by both AG and PHL treatments. The plasma CML levels were found to be elevated following MGO treatment, while the concomitant administration of AG and PHL has resisted this raise. Histopathological assessment revealed no specific pathology in liver kidney and brain tissues. The qPCR data revealed enhanced expression of all genes, especially TNF-α and BACE, which were found to be reduced following both AG and PHL treatments. PHL prevented the brain, hepatic, and renal impairments caused by MGO induced glycative stress. Hence, the PHL, a clinically used anti-spasmodic drug, presents itself as a potential candidate to be repurposed as anti-glycation drug. [ABSTRACT FROM AUTHOR]

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]

Rising global pediatric obesity rates, increase non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) prevalence, with MetS being a NAFLD risk factor. NAFLD can be asymptomatic, with liver function tests insensitive to mild disease, and liver biopsy, risking complications. Thus, we investigated multiparametric MRI (mpMRI) metrics of liver fat (proton density fat fraction, PDFF) and disease activity (fibro-inflammation; iron-corrected T1, cT1), in a Hispanic pre-pubertal pediatric cohort, with increased risk of NAFLD. Pre-pubertal boys (n = 81) of varying Body-Mass Index (BMI) were recruited in Mexico City. Most children (81%) had normal liver transaminase levels, 38% had high BMI, and 14% had ≥ 3 MetS risk factors. Applying mpMRI thresholds, 12%, 7% and 4% of the cohort had NAFLD, NASH and high-risk NASH respectively. Participants with ≥ 3 MetS risk factors had higher cT1 (834 ms vs. 737 ms, p = 0.004) and PDFF (8.7% vs. 2.2%, p < 0.001) compared to those without risk factors. Those with elevated cT1 tended to have high BMI and high insulin (p = 0.005), HOMA-IR (p = 0.005) and leptin (p < 0.001). The significant association of increased risk of MetS with abnormal mpMRI, particularly cT1, proposes the potential of using mpMRI for routine pediatric NAFLD screening of high-risk (high BMI, high MetS risk score) populations. [ABSTRACT FROM AUTHOR]

Background: To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP). Methods and findings: From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) <450 ms and liver enzyme tests (ALT/AST) below 3× the upper limit of normal (ULN), before they were individually randomized 1:1 in an open-label design. Recruitment was sequential, by age group. Pediatric dosages were weight adjusted. Follow-up was done at day 1 post-dose (including ECG) and day 14 (including ALT/AST), with repeat of ALT/AST on the last follow-up at day 30 in case of elevation on day 14. The primary outcome was non-inferiority of BE-PEP based on a <10 ms difference in QTc 24 h after treatment administration, both unadjusted and adjusted for baseline QTc. Of 408 screened participants, 313 were enrolled, starting with 187 adults, then 38 children aged 13 to 17 years, and finally 88 children aged 5 to 12 years, of whom 310 (99%) completed all visits. Across all ages, the mean QTc change on BE-PEP was from 393 ms to 396 ms, not significantly different from the change from 392 ms to 394 ms on SDR-PEP (difference between arms 1.8 ms, 95% CI −1.8, 5.3, p = 0.41). No individual's QTc increased by >50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; −1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group. Conclusions: In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros. Trial Registration: ClinicalTrials.gov NCT05406479. Bouke C. de Jong and team assess the safety of a Bedaquiline enhanced post-exposure prophylaxis regimen in the Comoros Islands. Author summary: Why was this study done?: Worldwide, leprosy is diagnosed in 200,000 persons annually. Those living near a patient with leprosy can reduce their risk of developing leprosy by half if they take a single dose of the antibiotic rifampicin, known as "post-exposure prophylaxis," or PEP. Dual antibiotic treatment given as PEP may reduce the risk further, and bedaquiline has been shown to have a high degree of effectiveness against leprosy in animal studies, although the safety of PEP containing bedaquiline had not previously been tested. What did the researchers do and find?: In a village in the Comoros affected by leprosy, first adults and then children were invited to participate in a randomized study in which they could receive either a single dose of the regular PEP, or bedaquiline-enhanced PEP, in which regular rifampicin PEP was combined with bedaquiline. They had their heart rhythm and liver enzymes checked before and after taking PEP to screen for asymptomatic drug toxicity. There was no statistically significant difference in the heart rhythm or liver function between the 2 groups. While the analysis in children showed that the spread around the difference just exceeded the predetermined safety margin, the analysis controlled for baseline values did not show increased risk. What do these findings mean?: The findings suggest that regular PEP can safely be combined with bedaquiline, although it is not yet known if this provides stronger protection against developing leprosy. Limitations in this study include a technical error in liver function testing of adult participants, which may have hidden a low-level elevation. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over‐the‐counter turmeric supplements can cause drug‐induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements.We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37–66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan‐lobular and three zone 3‐predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement‐associated liver injury to be probable (eight cases) and possible (three).Histological features in the ‘possible’ cases were consistent with drug‐induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over‐the‐counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric. [ABSTRACT FROM AUTHOR]

Hydatid cysts near the porta hepatis present notable medical challenges due to their intricate positioning and potential influence on crucial structures within the liver and its vicinity. While relatively rare, their presence can lead to intricate medical scenarios because of their proximity to vital liver and bile duct structures, but their occurrence can present complex medical situations due to their proximity to critical structures in the liver and bile ducts. We present an unusual case of a 33-year-old male with no known comorbidities presented to the outpatient department of general surgery with pain, insidious in onset and gradually progressive, in the right hypochondrial region for the past 3 months, along with mild fever, reduced appetite, and weight loss of 3 kg. Managing hepatic cysts, especially when near the porta hepatis, poses significant diagnostic challenges. Imaging scans revealed multiple hypodense lesions suggestive of hepatic cysts, with the largest one measuring 5 cm × 8 cm in segment VI. Native post-contrast lesions were also observed in the right lower lobe. Although hepatic duct dilation was not observed, the presence of a cyst near the porta hepatis an atypical site for hydatid cyst, complicated potential PAIR procedures (puncture, aspirate, injection, re-aspirate), raising concerns about the risk of damaging vital structures like the hepatic artery or major bile duct. A multidisciplinary approach engaged interventional radiology to evaluate PAIRS feasibility. PAIRS was performed successfully, except for the cyst near the porta hepatis to avoid complications. Despite this, the patient continued to experience abdominal discomfort post-operation, although liver function tests improved in the postop period. This case underscores the uncommon occurrence of hydatid cysts near the porta hepatis and highlights the need for additional research to comprehend its prevalence and causes. Further investigation is crucial to enhance our understanding of the epidemiology and optimal management strategies involving PAIRS in such challenging cases. [ABSTRACT FROM AUTHOR]

The diagnosis of common bile duct (CBD) stones is conducted through various imaging tests, endoscopic examinations, and the patient's clinical presentation. In patients with symptomatic gallstone disease, initial tests such as liver function tests, abdominal ultrasound, and abdominal computed tomography can be performed. Based on the results of these initial tests, symptomatic patient with cholelithiasis can be classified into low risk, intermediate risk, and high risk groups. Low risk of choledocholithiasis is characterized by normal liver function test results and absence of CBD dilation on abdominal ultrasound. For patients in this category, additional tests are not necessary unless symptoms indicating CBD stones persist. Intermediate risk of choledocholithiasis is identified by abnormal liver function test results or CBD dilation on abdominal ultrasound. Additional tests such as endoscopic ultrasound or magnetic resonance cholangiopancreatography can be performed. If CBD stones are confirmed in the additional tests, endoscopic retrograde cholangiopancreatography (ERCP) is required. High risk of choledocholithiasis is diagnosed when there is clinical evidence of cholangitis or CBD stones are identified on imaging tests. In such cases, ERCP is recommended for both diagnosis and treatment purposes without the need for further additional tests. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic poses severe risks for immunocompromised patients, especially those with neutropenia due to chemotherapy. This study evaluates the safety and effectiveness of remdesivir use in COVID-19 patients with neutropenia. Methods: This retrospective study used the Chang Gung Research Database (CGRD) and extracted data from 98,763 patients with COVID-19 diagnosed between April 2021 and September 2022. The patients were divided into groups based on their remdesivir use and the presence of neutropenia. The adverse effects of remdesivir and their outcomes were analyzed after propensity score matching. Results: We compared common adverse effects of remdesivir in neutropenic patients before and after a 5-day regimen. A slight decrease in heart rate was observed but lacked clinical significance. There were no significant differences observed in hemoglobin, liver function tests, and blood glucose levels. After propensity score matching of COVID-19 patients with neutropenia according to gender, age, dexamethasone use, oxygen use, MASCC score, and WHO ordinal scale, no significant differences were found in length of stay, intubation rate, or ICU admission rate between the matched patients. Conclusions: Our study found remdesivir to be safe for COVID-19 patients with neutropenia, with no common adverse reactions observed. However, its effectiveness for these patients remains uncertain. [ABSTRACT FROM AUTHOR]

Background: The coexistence of sepsis and hematological malignancies increases patient vulnerability, revealing the need for precise prognostic markers. This study explores the prognostic significance of lactate levels and clearance in septic patients with hematological malignancies. Materials and methods: A retrospective cohort study from January 2016 to December 2019 in a tertiary hematological intensive care unit (ICU) included 167 adults with hematological malignancies and sepsis. The relationship between lactate levels, hyperlactatemia, lactate clearance, and ICU outcomes was investigated. ICU survivors and non-survivors were compared to identify the factors affecting ICU mortality. Results: Patients were primarily with lymphoma and acute leukemia (66%) and had frequent hyperlactatemia (64%) on ICU admission. ICU non-survivors demonstrated higher lactate levels and hyperlactatemia frequency at various time points (0, 6, and 12 h) than survivors. Lactate clearance and liver function tests did not differ significantly between the two groups. Invasive mechanical ventilation [OR (95% confidence interval-CI): 20.4 (2.4–79.8), p < 0.01], requirement of vasopressors [OR (95% CI): 5.6 (1.3–24.5), p < 0.01], lactate level at the 6th hour [OR (95% CI): 1.51 (1.1–2.07), p = 0.01], and APACHE II score (OR (95% CI): 1.16 (1.01–1.34), p = 0.05) were independent risk factors for ICU mortality. The Area Under the Curve for APACHE II score and lactate level at the 6th hour were 0.774 (95% CI: 0.682–0.866) and 0.703 (95% CI: 0.602–0.804), respectively. Conclusion: While elevated lactate levels correlate with mortality rate and lactate level at the 6th hour is an independent risk factor for mortality, the absence of a significant difference in lactate clearance challenges traditional assumptions. These results question the commonly accepted perspective regarding lactate dynamics in sepsis among individuals with hematological malignancies. Oral Presentation: İnci K, et al. "Hyperlactatemia, lactate clearance and outcome in critically ill patients with hematological malignancies," 22nd ınternational intensive care symposium, 2019. [ABSTRACT FROM AUTHOR]

(1) Background: Liver damage is an important component of acute COVID-19, and the advancement of preexisting liver disease is associated with a worse prognosis; (2) Methods: A nationwide retrospective study including 7444 patients aimed to evaluate levels of selected markers of liver damage and disease advancement and their association with mortality and mechanical ventilation (MV); (3) Results: Elevation of the following markers in multivariate models were associated with increased odds of mortality: Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), fibrosis-4 score (FIB-4), AST-to-platelet ratio index (APRI), and decreased levels of platelet count (PLT). Elevated levels of AST, LDH, APRI, FIB-4, and the AST/ALT ratio and decreased levels of PLT were associated with increased odds of MV in multivariate models. The best predictive accuracy against mortality was achieved with FIB-4 with AUC = 0.733 (95% CI, 0.718–0.749) at the optimal cut-off point of 2.764, while against MV was achieved with LDH with AUC = 0.753 (95% CI, 0.727–0.778) at the optimal cut-off point of 449.5 IU/L. (4) Conclusions: Our study confirms that the advancement of liver damage contributes to a worse prognosis in COVID-19 patients. Markers for liver damage and the advancement of liver disease can provide predictive value in clinical practice among COVID-19 patients. [ABSTRACT FROM AUTHOR]

Problem: This study aims to evaluate the effectiveness of inflammation indexes (systemic immune‐inflammation index [SII], systemic inflammation response index [SIRI], pan‐immune inflammation value [PIV], and neutrophil‐to‐lymphocyte ratio [NLR]) in the diagnosis of intrahepatic cholestasis of pregnancy (ICP). Method of Study: A retrospective study was conducted, reviewing medical records of patients diagnosed with ICP who delivered between October 1, 2022, and May 31, 2023, at the Perinatology clinic of Etlik City Hospital, Ankara. A control group of healthy pregnant women with uncomplicated pregnancies was also included. Demographic data, clinical characteristics, and laboratory results, including systemic inflammation indices and liver enzyme levels, were collected and analyzed. Results: A total of 242 participants were included, with 121 ICP patients and 121 controls. White blood cell count, neutrophil count, and monocyte count showed significant differences between the two groups (p = 0.011, p = 0.004, and p = 0.039, respectively). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly elevated in the ICP group (p < 0.001 for both). SII and NLR were higher in the ICP group compared to controls (p = 0.032 and p = 0.010, respectively). Receiver operating characteristic (ROC) analysis revealed moderate predictive values for SII (area under the curve [AUC] = 0.581, p = 0.030) and NLR (AUC = 0.598, p = 0.009), with no significant difference in their predictive power (p = 0.502). Conclusions: Systemic inflammation indices such as SII and NLR offer a cost‐effective and rapid means of diagnosing ICP, potentially complementing or surpassing traditional biomarkers like bile acid levels and liver function tests (LFTs). These indices can be easily integrated into routine clinical practice, providing timely intervention to improve maternal and fetal outcomes. Further research is warranted to confirm these findings and establish standardized protocols for their use in ICP management. [ABSTRACT FROM AUTHOR]

Background: Early detection of liver dysfunction is crucial for timely intervention and management. Traditional liver function tests (LFTs) have limitations in sensitivity and specificity, necessitating the evaluation of newer diagnostic criteria. Objective: This study aims to compare the efficacy of different diagnostic criteria including Standard LFTs, Enhanced Liver Fibrosis (ELF) Test in detecting early liver dysfunction. Methods: A retrospective analysis was conducted on 125 patients suspected of early liver dysfunction at a tertiary care center. Diagnostic efficacy was assessed through sensitivity, specificity, and odds ratios calculated for each diagnostic criterion. Statistical significance was determined using p-values. [ABSTRACT FROM AUTHOR]

Background: Recurrent pregnancy loss is considered as two or more miscarriages. Clinical investigation may be initiated after two pregnancy losses. The occurrence of spontaneous miscarriage in India is reported to be around 6.37%, recurrent miscarriage is around 1 to 2%. The risk of miscarriage in subsequent pregnancy is 30% after 2 losses compared to 33% after 3 losses. The prevalence of Hyperhomocysteinemia in recurrent pregnancy loss in India is 38%. Objective: to study the levels of maternal serum homocysteine in pregnant women with 2 or more consecutive miscarriages and compare with control group and to determine if hyperhomocysteinemia is associated with RPL Methods: 100 patients with history of 2 or more consecutive pregnancy losses are taken as cases and 100 pregnancy lady with alteration one previous live mother are taken as controls. In the study both cases and controls had not taken folic acid in the last 3 months was confirmed by history. Both cases and control group previous records were examined for laboratory investigation to rule out associated co-morbidities like uterine anomaly on ultrasound, complete blood count for platelets, coagulation profile, thyroid profile, blood glucose, renal and liver function test, urine albumin, urine routine and microscopy and serology test for Human immune virus, Hepatitis B, syphilis, TORCH infection. Results: Out of 100 cases, 17 patients show increased homocysteine levels. Homocysteine group shows P value of 0.001, which is significant at 1% levels. Homocysteine levels more than 10.5 µmol/dl is a risk factor for pregnancy loss. This shows positive correlation between RPL and hyperhomocysteinemia. Conclusions: This study shows there is positive correlation of socioeconomic class with hyperhomocysteinemia. Pregnant women belonging to Lower class of Kuppuswamy class had higher serum homocysteine level indirectly indicating poor nutrition among this pregnant. [ABSTRACT FROM AUTHOR]

Background:: Liver plays a vital role in lipid metabolism. It contributes both in exogenous and endogenous cycles of lipid metabolism and transport of lipids through plasma. Liver disease impacts on hepatic synthesis of lipoproteins and lipogenesis but data on dyslipidemia during disease progression are limited. Aims & Objectives: To assess the serum Lipid profile in patients diagnosed with chronic alcoholic liver disease (ALD) in a tertiary care level hospital and to assess the association of Serum Lipid profile alterations with the severity of alcoholic liver disease. Materials & Methods: The present study was conducted in the Department of Medicine, Dr Panjabrao Alias Bhausaheb Deshmukh Memorial Medical College and Research Centre, Amravati on 73 patients with chronic alcoholic liver disease and >18 years of age of both sex. Then they were subjected to Clinical data, including demographic information, medical history, liver function tests, imaging findings. Serum Lipid Profile Levels including triglycerides, cholesterol, and lipoproteins were measured using standardized laboratory assays, with values expressed in mg/dL. Disease severity was assessed using established scoring systems such as Child-Pugh classification. Results: Mean S Cholesterol levels was 192±43.67 mg/dl,S triglyceride was 136.9±87.23 mg/dl,HDL was 31.4±11.76 mg/dl,LDL was 92.58±32.64 mg/dl and VLDL was 27.54±14.12 mg/dl. One way Anova was applied which states that the S Cholesterol, Triglyceride and HDL had statistical significant difference among 3 groups with p value <0.05. Conclusion: The severity of Chronic alcoholic Liver Disease increases from Child pugh score class A to Child pugh score class C, the lipid panel profile decreases exponentially. [ABSTRACT FROM AUTHOR]

Objective: In thalassemia major, repeated blood transfusions result in iron overload causing organ damage. The objective of this study was assessment of liver enzymes in patients with Thalassemia major and to observe their association with ferritin. Method: A cross-sectional study was performed, at Islamabad Medical and Dental College and its affiliated Akbar Niazi Teaching Hospital from November 2021 till August 2022. Serum ferritin, AST, ALT, and total bilirubin levels were determined, in 135 patients of beta thalassemia major receiving transfusions. Data analysis was performed using SPSS Version 20. For categorical variables, calculation of frequencies and percentages was performed. Mean (± standard deviation) was determined for quantitative variables. ANOVA with post hoc Tukey’s test was used for determining association between liver enzymes and serum ferritin. A p-value of <0.05 was considered significant. The correlation between ferritin and LFTs was determined by Pearson’s correlation coefficient. Results: Patients had an age range of 7-30 years, and males constituted 51% of sample. Mean level of ferritin was 6062.61 + 3641.79 ng/ml, with an insignificant difference between the genders (p =0.366). The levels of AST, ALT and bilirubin were perceived to show a significant increase in patients with ferritin levels >5000ng/ml, when compared with patients having ferritin levels < 2,500 ng/ml. A significant positive correlation of increasing serum ferritin levels was observed with ALT (r= 0.682), to a lesser extent with AST (r = 0.532), and only a weak correlation with serum bilirubin (r = 0.350) Conclusion: Liver damage was caused by increased iron deposition. LFTs should be performed regularly to detect and reduce liver damage by increasing chelation therapy, thereby reducing morbidity and mortality due to thalassemia. [ABSTRACT FROM AUTHOR]

Background: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity. Methods and results: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in both hepatocellular and cholestatic patterns. Two patients stopped the ketogenic diet acutely and 3 patients continued ketogenic diet with changes in medications and/or addition of choline—all patients had improvement and normalization of liver function tests in the short term. One patient had acute normalization of chronically elevated liver function tests on ketogenic diet initiation. Conclusion: Ketogenic diet can cause acute changes in liver function tests during initiation of ketogenic diet, with both hepatocellular and cholestatic patterns, with and without the concurrent use of hepatotoxic medications. In most patients, ketogenic diet can be continued successfully by making changes to medications or addition of choline. [ABSTRACT FROM AUTHOR]

Background and Aims: Adaptive immunity is gaining a significant role in progression of metabolic dysfunction‐associated steatotic liver disease (MASLD). B‐cell activity can be assessed by serum‐free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non‐invasive biomarkers for the stratification of MASLD. Methods: We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction‐associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay. Results: We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m2. A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction‐associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction‐associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (p <.01), and patients with CSPH showed higher sFLC levels than patients without CSPH (p <.01). At multivariable analysis, sFLCs were associated with cACLD (p <.05) independently from γ‐globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (p <.05) independently from γ‐globulins and other known dysmetabolic risk factors. Conclusion: sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients. [ABSTRACT FROM AUTHOR]

Background The current hepatitis B (HBV) and hepatitis C virus (HCV) screening practices may fail to detect many infected patients who could benefit from new therapeutic agents to limit progression to cirrhosis and hepatocellular carcinoma. Objectives This study assessed the test positivity rate and cascade of care of viral hepatitis patients in primary care in a low endemic region as well as the testing policy of abnormal alanine aminotransferase (ALT) level. Methods This is a retrospective clinical audit among primary health care practices in Flanders, Belgium, assessing patients with an active medical file between 2019 and 2021. Results A total of 84/89 (94.4%) primary health care practices participated representing 621,573 patients of which 1069 patients (0.17%) were registered as having viral hepatitis, not further specified. Detailed information was available from 38 practices representing 243,723/621,573 (39.2%) patients of which 169 (0.07%) were HBsAg positive and 99 (0.04%) anti-HCV positive. A total of 96/134(71.6%) chronic HBV-infected and 31/77(40.3%) chronic HCV-infected patients were referred to a hepatologist. A total of 30,573/621,573(4.9%) patients had an abnormal ALT level, and by at random selection, more detailed information was obtained on 211 patients. Information on high-risk groups was missing in up to 60%. In patients with abnormal ALT level, HBsAg and anti-HCV testing were conducted in 37/211(17.5%) and 25/211(11.8%), respectively. Conclusion In a low endemic region, the testing rate and cascade of care of HBV and HCV-infected patients can be improved in primary care, especially in high-risk groups and patients with abnormal ALT levels. [ABSTRACT FROM AUTHOR]

Background: Aging leads to a decline in muscle mass and strength, contributing to frailty and decreased quality of life. Sirolimus (rapamycin) , an mTOR inhibitor, has shown potential in preclinical studies to extend lifespan and improve health span. This study evaluates the safety and efficacy of once-weekly sirolimus (rapamycin) administration on muscle strength and endurance in older adults engaged in a 13-week exercise program. Methods: This randomized, double-blind, placebo-controlled trial will enroll 40 participants aged 65–85. Participants will be randomly assigned to receive either sirolimus (rapamycin) 6 mg/week or placebo for 13 weeks, in conjunction with an at-home exercise program. The primary outcome measure is the change in muscle strength and endurance, assessed by the 30-Second Chair-Stand Test. Secondary outcome measures include adverse events, changes in muscle strength and endurance as measured by the 6-min walk test, handgrip strength, and participant-reported outcomes using the SF-36 survey. Assessments will be conducted at baseline, mid-intervention (week 6), and post-intervention (week 13). Blood samples will be collected for hematology and biochemistry analyses, including full blood count, urea and electrolytes, liver function tests, HbA1c, lipids, serum IGF-1, and hs-CRP. DNA methylation will be analyzed using TruDiagnostic™ to explore changes in biological age. Discussion: This study aims to provide insights into the potential benefits of intermittent sirolimus (rapamycin) administration on muscle performance in older adults. By alternating periods of mTOR inhibition through rapamycin and activation via exercise, this study will explore a novel approach to enhancing muscle strength and endurance in the aging population. The results could have significant implications for developing interventions to improve physical function and overall health outcomes in older adults. Safety and tolerability will also be closely monitored to ensure the feasibility of this regimen for wider application. Trial registration: Australia New Zealand Clinical Trials Registry, ACTRN12624000790549. Registered on 26 June 2024 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12624000790549. [ABSTRACT FROM AUTHOR]

AbstractObjective: Fumaric acid is a dicarboxylic acid that belongs to the phenolic class enriched in fruits and vegetables that are traditionally used for the treatment of various ailments. The research was planned to find out the anti-inflammatory and anti-arthritic activities of fumaric acid using in-vitro and in-vivo assays. Moreover, safety study was also done.Materials and methods: The 0.1 ml complete Freund’s adjuvant was injected in left hind paw in all Wistar rats except normal rats at day 1 to induced arthritis. The treatment with fumaric acid at 10, 20, 40, and fumaric acid 40 mg/kg together with methotrexate (MTX) was administered to immunized rats at 8th day via oral gavage and continued till 28th day though, MTX was administered as standard control.Results: The fumaric acid notably (p < 0.0001) lessened the paw edema and arthritic scoring, reinstated body and immune organ weight, and oxidation status in treated rats. Fumaric acid notably restored altered C-reactive protein, rheumatoid factor, liver function tests, ESR, WBCs, RBCs and Hb levels in treated rats. The fumaric acid in combination noticeably (p < 0.01–0.0001) suppressed the expression of TNF- α, IL-6, IL-1β, NF-kβ, and COX-2, and over expressed IL-4, and IL-10 in contrast to other treated groups. Fumaric acid had presented a dose-dependent antioxidant, anti-inflammatory and anti-arthritic activities while notable activity exhibited by fumaric acid in combination with MTX. The fumaric acid exhibited non-significant clinical signs of toxicity and mortality in acute toxicity study. The LD50 was more than 2000 mg/kg.Conclusion: Fumaric acid in combination can be used as disease-modifying anti-rheumatic drug but it will need extensive pre-clinical and clinical studies. [ABSTRACT FROM AUTHOR]

Children with anti-neutrophil cytoplasmic antibody-associated vasculitis benefit immensely from avacopan as it reduces the requirement for steroids. However, descriptions of adverse drug reactions in children are lacking, and the dosage and follow-up intervals are unclear. A 10-year-old boy with initial granulomatosis and polyangiitis presented with diffuse pulmonary hemorrhage. Rituximab and 30 mg avacopan were administered twice daily as induction therapy following methylprednisolone pulse therapy. However, sudden liver function test abnormalities were observed on day 31 of avacopan treatment, despite liver enzyme levels being within the normal range 5 days earlier. A drug-induced lymphocyte stimulation and various infectious disease tests yielded negative results. Discontinuation of rituximab and avacopan resulted in improved liver function; no change in the Birmingham Vasculitis Activity Score during liver function test abnormalities was observed. Avacopan-associated abnormalities in liver function tests suggest that drug-induced liver injury may occur rapidly in children, and appropriate dosing strategies should be reconsidered. [ABSTRACT FROM AUTHOR]

In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3. [ABSTRACT FROM AUTHOR]

Introduction: Hemoglobinopathies are the most common single gene disorders. Beta-thalassemia is one of the most common hemoglobinopathies worldwide, and a high prevalence is seen in Mediterranean region, central Asia, India, and Far East countries. Recurrent ischemic insults with parenchymal necrosis can result in hepatic fibrosis, chronic liver disease, and cirrhosis. Liver biopsy has historically been the primary means to evaluate for fibrosis and monitor disease progression, but it has significant limitations. Vibration controlled transient elastrography (VCTE) utilizing fibroscan uses an ultrasound transducer probe to create an elastic shear wave through vibrations of mild amplitude and low frequency (50Hz) which are transmitted through liver tissue. Material & Methods: Hospital based cross sectional study was conducted involving patients under 18 years of age registered for treatment of haemoglobinathies in the Department of Pediatrics, of Rajendra Institute of Medical Sciences, Ranchi during June 2021 to June 2022. Result: It was observed that AST, ALT & ALP showed some progressive increase with increase in stage of fibrosis. Higher incidence of liver fibrosis was observed as patients age advances. Conclusion: Fibroscan is a recent technology which could detect the earliest changes in hepatic pathology without invasion, it is a painless technique and correlates well with changes in hepatic enzyme leading to identification of pathologic changes. [ABSTRACT FROM AUTHOR]

Hospital waste dumpsites pose significant environmental and health risks due to the leachate generated, which contains a complex mixture of hazardous substances. This study investigates the biochemical effects of continuous exposure to hospital waste dumpsite leachate on Wistar rats, with a comparative analysis of the effects of abatement and discontinuation of leachate exposure. Male Wistar rats, aged 7 to 8 weeks, were randomly assigned to two groups and allowed to acclimatize for two weeks. Group A served as the control, while Group B was administered hospital waste leachate with an abatement agent for a duration of 30 days. Following this exposure period, both the control group and a subset of the treatment group were assessed and euthanized. Blood samples were collected for biochemical analysis. The remaining rats in the treatment group were then divided into two additional groups: Group C, where leachate administration was halted, and Group D, where leachate was continued alongside abatement. After an additional 30 days, the surviving rats were examined and sacrificed, with blood samples taken for biochemical analysis. The results indicated that continuous leachate exposure significantly elevated serum urea, hydrogen carbonate, sodium, chloride, total bilirubin (5.50±0.01 mg/dl), conjugated bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) (5.50±0.01 mg/dl) levels, suggesting nephrotoxicity and hepatotoxicity. Upon discontinuation of leachate exposure, there was a marked recovery in most biochemical parameters, demonstrating the potential reversibility of some toxic effects. Conversely, abatement with a mixture of garlic extract, ginger extract, and honey also promoted recovery but to a lesser extent than discontinuation alone. The findings contribute to a better understanding of the toxicological impacts of leachate and provide a foundation for future research into mitigation measures. [ABSTRACT FROM AUTHOR]

Background and Aims Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. Methods We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. Results Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18–66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAF N486_P490 (29.6%), BRAF V600E (18.5%), and MAP2K1 (14.8%). Outcomes After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550–7.388, P  = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P  = .010) correlated with superior PFS versus chemotherapy. Conclusions In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives Xylopia aethiopica (XAE), commonly known as African pepper or Ethiopian pepper, is a plant native to West Africa and known for its aromatic and medicinal properties. It was used to investigate the antioxidative, antihepatotoxic, and antinephrotoxic potentials of XAE in benign prostatic hyperplasia (BPH) in Wister albino rats. Methods The proximate, and vitamin composition, oxidative stress indicators, and indices of kidney and hepatic functions were performed by standard methods. Results The proximate composition of the XAE leaf showed varied concentrations of Mg, Ca, Na, Zn, Se, and Cl, as well as vitamins A, E, B3, D, C, K, B2, and Bi. The activities of catalase glutathione, superoxide dismutase, malondialdehyde levels, K, Na, Cl − , urea, uric acid, and creatinine in the kidney were increased in testosterone propionate (Tp)-induced BPH compared with the control groups. Total protein levels significantly decreased in Tp-induced BPH compared with XAE-treated groups increased on XAE treatment. The aspartate transaminase, alanine aminotransferase, and alkaline phosphatase activities were not significantly different in Tp-induced BPH, XAE, and normal controls. Conclusion The study revealed that XAE can be used in the management of oxidative stress and hepatorenal damage in BPH condition. [ABSTRACT FROM AUTHOR]

The defect in the hepatobiliary transport system results in an impairment of bile flow, leading to accumulation of toxic compounds with subsequent liver disorders. Vincamine, a plant indole alkaloid that is utilized as a dietary supplement, has been known for its promising pharmacological activities. For the first time, the present study was planned to estimate, at the molecular level, the potentiality of vincamine against alfa-naphthyl isothiocyanate (ANIT)-induced hepatic cholestasis. Liver function tests were analyzed. Hepatic activity of SOD and levels of GSH and MDA were assessed. Hepatic contents of bax, bcl2, NF-kB, PPARγ, catalase, heme-oxygenase-1, NTCP, and BSEP were evaluated using ELISA. mRNA levels of NF-kB, IL-1β, IL-6, TNFα, PDGF, klf6, PPARγ, and P53 were examined using qRT-PCR. PI3K, Akt and cleaved caspase-3 proteins were assessed using western blotting. Histopathological analyses were performed using hematoxylin & eosin staining. ANIT-induced hepatic cholestasis elevated liver function tests, including AST, ALT, GGT, ALP, and total bilirubin. ANIT reduced the protein expression of NTCP and BSEP hepatic transporters. It induced the expression of the inflammatory genes, TNFα, IL-6, IL-1β, and PDGF, and the expression of NF-kB at the genetic and protein level and suppressed the anti-inflammatory genes, klf6 and PPARγ. Also, antioxidant markers were reduced during ANIT induction such as GSH, SOD, catalase, heme-oxygenase-1 and PI3K/Akt pathway, while MDA levels were elevated. Furthermore, the expression of P53 gene, bax and cleaved caspase 3 proteins were activated, while bcl2 was inhibited. Also, the histopathological analysis showed degeneration of hepatocytes and inflammatory cellular infiltrates. However, vincamine treatment modulated all these markers. It improved liver function tests. It inhibited the expression of NF-kB, TNFα, IL-6, IL-1β and PDGF and activated the expression of klf6 and PPARγ. Furthermore, vincamine reduced MDA levels and induced GSH, SOD, catalase, heme-oxygenase-1 and PI3K/Akt pathway. Additionally, it inhibited expression of P53 gene, bax and cleaved caspase 3 proteins. More interestingly, vincamine showed better outcomes on the hepatic histopathological analysis and improved the alterations induced by ANIT. Vincamine alleviated hepatic dysfunction during ANIT-induced intrahepatic cholestasis through its anti-inflammatory and antioxidant efficacies by the modulation of NF-kB/PDGF/klf6/PPARγ and PI3K/Akt pathways. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the effects of probiotic (Bacillus subtilis) addition on behaviour, some health indicators and intestinal histology of broiler chickens. 210 one day old Broiler chicken was supplied by diets with probiotics at concentrations of 0 (control), 0.25 (0.25X), and 0.5 (0.5X) g/kg. Also, 4 days old, blood samples were collected for measuring liver and kidney function tests, also microbial analysis, internal morphology, and relative and absolute weight of some internal organs were done. In comparison with control, probiotics had no significant effect on broiler chickens' behavior, however, birds fed 0.25X had the highest percentage of feeding behavior among the experimental groups. Furthermore, probiotic treated groups had higher absolute weights of heart, spleen, liver, intestine and gizzard while the relative weights were not changed. Also, the Lactobacillus population increased while the total bacterial count decreased in probiotic-fed groups. Moreover, probiotics increased duodenum villus width and height and enhanced jejunum villus width, height, and villus height/crypt depth. In addition, it did not affect the levels of total, indirect and direct bilirubin, albumin, total protein, globulin, and albumin: globulin ratio and alkaline phosphatase regardless of its dose. The findings imply that the probiotic dietary supplement effect based on its dose and that probiotic (Clostat ™) improved broilers health under normal condition and may prove to be an important way for possibly protection the health of broiler chickens. [ABSTRACT FROM AUTHOR]

Background & aims: Current screening pathways, developed from tertiary care cohorts, underestimate the presence of Metabolic-dysfunction associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) in the community. We developed, validated, and assessed cost-effectiveness of a new score for screening the presence of fibrosis due to MASLD in primary care. Methods: Consecutive T2DM patients underwent screening for liver diseases with transient elastography (TE). Based on predictors of significant/advanced fibrosis, we generated the BIMAST score (based on aspartate aminotransferase (AST) and body mass index (BMI)) and validated it internally and externally (Royal Free Hospital, London and Palermo Hospital). For cost-effectiveness analysis, 6 screening strategies were compared against standard of care: BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, ELF and transient elastography (TE). A Markov model was built based on fibrosis status. Cost per quality-adjusted life year (QALY) gained and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime. Results: Among 300 patients enrolled, 64% (186) had MASLD and 10% (28) other causes of liver disease. In the whole population, patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287), and 3% (8/287), respectively. In primary care, BIMAST performed better than other non-invasive markers at predicting significant and advanced fibrosis. Moreover, BIMAST reduced false negatives from 54% (ELF) and 38% (FIB-4) to 10%. In both validation cohorts, BIMAST performance was as good as FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST. Conclusion: The BIMAST predicts the presence of significant fibrosis in the community, reduces false negatives and is cost-effective. The BIMAST score should be included in the holistic assessment of diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Human T-cell leukemia virus type 1 (HTLV-1) is a well-known retrovirus, particularly prevalent in northeastern Iran, where it is associated with a range of disorders, including liver dysfunction. Previous studies have demonstrated that HTLV-1 infection can alter lipid profiles, yet no research has examined lipid indices and liver function tests in these patients in the long term. Methods: This data is part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. A total of 1116 participants were randomly selected, including 837 healthy individuals and 279 HTLV-1-infected patients. Following a 10-year follow-up period, Serum levels of liver enzymes were measured. Lipid indices such as the Atherogenic Index of Plasma (AIP), Body Adiposity Index (BAC), Castelli risk index (CRI-I, CRI-II), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), Triglyceride-glucose index (TyG), and Triglyceride and HDL-C Ratio (THR) were calculated. Results: Multivariable-adjusted regression analysis demonstrated a significant coefficient for the Visceral Adiposity Index (VAI) in HTLV-infected patients compared to healthy controls (B: -0.014, 95% CI: -0.02, 0.00, p = 0.046). However, no significant differences were observed in other lipid indices between HTLV-infected patients and healthy individuals. Regarding liver enzymes, significant variations were noted in HTLV-infected patients compared to healthy controls: Aspartate Aminotransferase (AST) (B: 2.978, 95% CI: 1.34, 4.61, p < 0.001), Alanine Aminotransferase (ALT) (B: 3.687, 95% CI: 1.59, 5.78, p = 0.001), Alkaline Phosphatase (ALP) (B: 18.232, 95% CI: 6.81, 29.65, p = 0.002), and Gamma-Glutamyl Transferase (GGT) (B: 3.714, 95% CI: 0.18, 7.24, p = 0.039). Conclusion: Individuals with HTLV-1 infection exhibit reduced VAI but elevated levels of liver enzymes such as AST, ALT, ALP, and GGT, indicating liver damage. These findings emphasize the virus's involvement in liver pathology. Also, HTLV-I is associated with reduced visceral fat tissue. [ABSTRACT FROM AUTHOR]

Karyomegalic interstitial nephritis (KIN) is a rare entity associated with biallelic FAN1 (FANCD2/FANCI‐Associated Nuclease 1) gene variants. In FAN1‐related KIN, abnormal liver function tests and respiratory involvement are common, in addition to chronic kidney disease. Karyomegalic changes have also been reported in many other organs in patients with FAN1‐related KIN in various studies. We report the case of a 35‐year‐old male with chronic kidney disease of unknown aetiology, concurrent recurrent upper and lower respiratory tract infections, and elevated liver function test results with unidentified aetiology. The patient's family history was remarkable for consanguineous parent marriage and history of kidney transplantation in his aunt. A kidney biopsy was performed, which was consistent with KIN. Clinical exome sequencing revealed a homozygous nonsense variant NM_014967.5 (FAN1): c. 2260C > T (p.Arg754Ter). According to the American College of Medical Genetics (ACMG) criteria, this variant is pathogenic and, to the best of our knowledge, has not been previously reported, homozygously. Therefore, the histopathological and clinical diagnoses of KIN were confirmed by genetic studies in our patient. This case report expands the genetic spectrum of FAN1‐related KIN, and briefly reviews the current literature data. [ABSTRACT FROM AUTHOR]

Paclitaxel plus carboplatin is the most common regimen for the treatment of ovarian cancer. While generally effective, these chemotherapy agents can cause adverse events such as myelotoxicity, nausea, vomiting, and rarely, hepatotoxicity. Paclitaxel is associated with mild elevations in serum aminotransferase levels, but significant hepatotoxicity is uncommon, particularly in patients without prior liver disease. We present a patient with ovarian cancer who developed significant elevation of serum aminotransferases up to 12 times the upper limit of normal after the first cycle of paclitaxel plus carboplatin chemotherapy. Extensive evaluations excluded other potential causes of liver injury and the diagnosis of paclitaxel-induced liver injury was confirmed. The patient was treated with liver protective medications and a reduced dose of paclitaxel (135 mg/m2) for subsequent cycles. Her liver function tests stabilized within 2 to 3 times the upper limit of normal, allowing continuation of chemotherapy and achieving a favorable outcome. [ABSTRACT FROM AUTHOR]

Introduction: Liver fibrosis is a significant global health burden that lacks effective therapies. It can progress to cirrhosis and hepatocellular carcinoma (HCC). Aberrant hedgehog pathway activation is a key driver of fibrogenesis and cancer, making hedgehog inhibitors potential antifibrotic and anticancer agents. Methods: We evaluated simvastatin and STA-9090, alone and combined, in rats fed a high-fat diet (HFD) and exposed to diethylnitrosamine and thioacetamide (DENA/TAA). Simvastatin inhibits HMG-CoA reductase, depleting cellular cholesterol required for Sonic hedgehog (Shh) modification and signaling. STA-9090 directly inhibits HSP90 chaperone interactions essential for Shh function. We hypothesized combining these drugs may provide liver protective effects through complementary targeting of the hedgehog pathway. Endpoints assessed included liver function tests, oxidative stress markers, histopathology, extracellular matrix proteins, inflammatory cytokines, and hedgehog signaling components. Results: HFD and DENA/TAA caused aberrant hedgehog activation, contributing to fibrotic alterations with elevated liver enzymes, oxidative stress, dyslipidemia, inflammation, and collagen deposition. Monotherapies with simvastatin or STA-9090 improved these parameters, while the combination treatment provided further enhancements, including improved survival, near-normal liver histology, and compelling hedgehog pathway suppression. Discussion: Our findings demonstrate the enhanced protective potential of combined HMG CoA reductase and HSP90 inhibition in rats fed a HFD and exposed to DENA and TAA. This preclinical study could help translate hedgehog-targeted therapies to clinical evaluation for treating this major unmet need. [ABSTRACT FROM AUTHOR]

AIM: Our goal was to examine the effect of high-intensity physical activity on changes in the lipid profile, complete blood count (CBC), iron metabolism, and kidney and liver function tests of professional water polo players. METHODS: This study included twenty professional male water polo players. Blood sampling was carried out at the beginning of the season and during periods of high-intensity training. CBCs were determined with a Siemens Advia 2120i hematology analyzer. A Beckman CoulterAU680 chemistry analyzer was used to determine the serum concentrations/activities of lipid profiles and liver and kidney function test analytes. The lipid athlete scores were also determined. RESULTS: The mean corpuscular volume (p = 0.006), platelet count (p = 0.008), and mean platelet volume (p < 0.001) significantly decreased during the high-intensity period, compared with the beginning of the season. The total iron-binding capacity increased (p = 0.001), and ferritin concentrations significantly declined (p = 0.017). The lipid profiles revealed a significant difference between phases, with slight increases in serum total (p = 0.025) and LDL cholesterol (p = 0.002) levels and a decrease in triglyceride concentrations (p = 0.040) in the high-intensity period. During the high-intensity period, the liver and kidney function tests showed a substantial positive effect on lactate dehydrogenase levels (p < 0.001), aspartate aminotransferase (p = 0.028) serum activity, and total protein concentrations (p = 0.033), compared with the beginning of the season. CONCLUSIONS: Water polo players might exhibit a decrease in some CBC parameters, an increase in LDL cholesterol, and a decrease in liver function biomarkers due to intense training at the peak of the competitive season. Kidney function biomarkers remain unchanged. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous melanoma (CM) is an aggressive skin cancer that develops from melanocytic cells. The most important prognostic factor is still the vertical tumour thickness according to Breslow. Liver function is associated with better overall patient outcomes and is currently under increasing investigation in cancer patients. Current findings show that liver function is an important factor in different tumour entities and represents a potential biomarker. Therefore, we aimed to evaluate liver metabolism by using liver scores in CM. High tumour thickness (≥1.66 mm) and aspartate transaminase-to-platelet ratio index (APRI ≥ 0.2241) at the initial diagnosis were associated with a worse prognosis in stage I and II melanoma. Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan–Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37–126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5–126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14–5.75; HR 2.94, 95% CI 1.42–6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms. [ABSTRACT FROM AUTHOR]

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: Monitoring liver changes is crucial in the management of liver fibrosis. Current diagnostic methods include liver function tests such as the Liver Maximum Capacity (LiMAx) test and measurements of liver stiffness. While the LiMAx test quantifies liver function through 13C-methacetin metabolism, ultrasound (US) elastography noninvasively assesses liver stiffness. The relationship between the findings of these methods in patients with liver fibrosis is not fullyunderstood. OBJECTIVE: This study evaluated the correlation between LiMAx measurements of liver function and US elastography-based liver stiffness measurements to better understand the interplay between functional and structural liver parameters in fibrotic liver disease. Additionally, the relationship between body mass index (BMI) and these parameters isevaluated. METHODS: This retrospective study analysed data from 97 patients who underwent both LiMAx testing and real-time elastography, resulting in a total data set of 108 examinations. The correlations between the results of the LiMAx test and elastography and their relationships with body mass index (BMI) were analysed. RESULTS: There was a significant negative correlation (r = –0.25, p < 0.05) between LiMAx test values and liver stiffness measurements. BMI was significantly negatively correlated with LiMAx values (r = –0.29, p < 0.001) but not significantly correlated with liver stiffness values. CONCLUSIONS: This retrospective study confirms the results of previous studies showing a notable but weak association between liver function and liver stiffness. Our results highlight the potential value of both tests as complementary tools for the evaluation of liver health, reinforcing the necessity for a multimodal approach to liver assessment. [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]

Background: Primary biliary cholangitis (PBC) is a condition affecting the liver and immune system. In this study, the impact of autologous bone marrow-derived mononuclear cell (BM-MNC) transplantation on PBC patients was investigated. Methods: Sixteen eligible PBC patients participated at the National Scientific Medical Center in Astana, Kazakhstan, between 2017 and 2022, and BM-MNCs were harvested from their anterior iliac crest. After isolating and cultivating the BM-MNCs, they were infused back into the patient's peripheral veins. Changes in BM-MNC and peripheral blood mononuclear cell (PB-MNC) phenotypes were assessed before and after a 24-hour cultivation period and 72 hours post-transplantation. We monitored liver function parameters over 6-month intervals and conducted flow cytometry analysis to assess CD markers on BM-MNCs before and after cultivation and PB-MNCs before and after transplantation. Statistical analysis included the Friedman test for liver parameters and the Wilcoxon signed-rank test for BM-MNC and PB-MNC comparisons. Results: Our findings revealed significant reductions in liver function tests after multiple transplantations. Flow cytometry analysis before and after a 24-hour culture and autologous BM-MNC infusion revealed the expansion of specific cell populations, with significant increases in CD3+, CD4+, CD16+, CD20+, CD25+, CD34+, CD105+, CD73+, CD117+, and CD34+populations, while CD4+25+, CD34+105+, and CD4+FOXP3+ populations decreased. Interestingly, a contradictory finding was observed with a decrease in bone marrow CD34+105+ cell lines (P=0.03) alongside an increase in peripheral CD34+105+ population (P=0.03). Conclusion: In summary, our study shows that BM-MNC transplantation in PBC patients leads to changes in immune cell populations and liver function. These findings suggest potential therapeutic applications of BM-MNC transplantation in managing PBC and offer insights into the dynamics of immune cells associated with this treatment approach. [ABSTRACT FROM AUTHOR]

Simple Summary: Repurposing the diabetes drug dapagliflozin and the natural agent silymarin, this study tackled the liver damage caused by the chemotherapy drug cisplatin. Thirty female Wistar rats were treated with cisplatin alone, silymarin, dapagliflozin, or their combination for 45 days. The results were promising; cisplatin-induced liver damage, marked by elevated ALT, AST, and TB levels, and decreased TP and albumin levels, was significantly mitigated by dapagliflozin and silymarin. The combination of both showed promising results as well, restoring the liver enzyme levels and tissue structure. This novel approach not only highlights the powerful hepatoprotective effects of dapagliflozin and silymarin but also opens new avenues for safer chemotherapy treatments. Further mechanistic research could turn these findings into clinical practice, offering new hope for cancer patients undergoing cisplatin-based therapy. Recognizing the challenges posed by chemotherapy, specifically the hepatotoxic effects of drugs like cisplatin, this study aimed to examine the hepatoprotective potential of dapagliflozin to mitigate cisplatin-induced hepatotoxicity in a rat model. This study focused on repurposing drugs such as dapagliflozin and natural agents like silymarin as potential interventions to address cisplatin-induced hepatotoxicity. Thirty adult female Wistar rats were distributed into five groups and treated with cisplatin alone, silymarin, dapagliflozin, or a combination of dapagliflozin and silymarin accordingly for 45 days. Body weight, fasting blood glucose levels, liver function tests, and histopathological analysis were conducted to evaluate the hepatoprotective effects. Cisplatin-induced hepatotoxicity significantly (p < 0.05) increased the serum levels of ALT, AST, TB, and reduced the TP and albumin levels. Dapagliflozin administration led to significant reductions in ALT, AST, TB, and increased albumin levels. Silymarin demonstrated comparable effects. Combining dapagliflozin and silymarin showed synergistic effects, further reducing the liver enzymes and improving albumin levels. Histopathological examination supported these findings, revealing the restoration of liver structure with dapagliflozin and silymarin treatment. Dapagliflozin and silymarin exhibited substantial hepatoprotective benefits against cisplatin-induced hepatotoxicity in rats. The combination therapy demonstrated synergistic effects, highlighting a potential therapeutic approach for mitigating chemotherapy-induced liver damage. Further research into molecular mechanisms and clinical translation is warranted, offering hope for improved clinical outcomes in cancer patients undergoing cisplatin-based chemotherapy. [ABSTRACT FROM AUTHOR]

Nitrofurantoin (NFR) is an antibiotic commonly used in the management of uncomplicated urinary tract infections. The study examined histoarchitectural and biochemical alterations in the liver and kidney of Wistar rats following exposure to nitrofurantoin. Fifteen (15) adult Wistar rats comprising five (5) animals per group were randomly assigned into three groups. Group A was the control group while Groups B and C received 30mg kg-1 and 60mg kg-1 body weight of NFR respectively for thirty (30) days. Data generated from liver and renal functional markers was analyzed on graph pad prism using descriptive statistics and outcomes implicated as standard error of the mean and mean. Mean value differences were evaluated using analysis of variance (ANOVA) considering p<0.05 as statistically significant value. Upshot display periportal hepatitis in the group given 30mg kg-1 of nitrofurantoin, the hepatocytes appeared polygonal and there was vascular congestion with inflammatory cell infiltration in rats given 60mg kg-1 NFR. These features were consistent with inflammatory responses. However, liver function tests showed a significant increase in Alanine transaminase (ALT), Aspartate aminotransferase (AST), and Alkaline phosphatase (ALP) levels across treated groups when rationalized to control group (p<0.05). Also observed is a statistically significant increase in mean serum level of total protein, direct and indirect Bilirubin across treatment groups compared to control. More so, there were features consistent with normal renal histoarchitecture with tubules comprising of multiple segments and corpuscle made up of the Glomerulus surrounded by the podocytes. Conversely, renal function parameters showed a decrease in the urea level across treatment groups. Nitrofurantoin displays no histoarchitectural outcome of the kidney but elucidated negative outcome on the liver histology, therefore caution should be considered when administered as a therapeutic agent. [ABSTRACT FROM AUTHOR]