Elevated Liver Transaminases Research Articles

Deficiency of myeloid NPC1 exacerbates liver injury and fibrosis by impairing macrophage efferocytosis.

Niemann-Pick C1 (NPC1), a lysosomal cholesterol transport protein, is required for efficient efferocytosis. Patients with Npc1 mutation are frequently accompanied with hepatic symptoms, including hepatomegaly, elevated liver transaminases, or even acute liver failure, but the pathogenic mechanism remains unknown. Our work aims to characterize the functional role of myeloid NPC1 in liver injury and elucidate its underlying mechanism. Analyses of injured livers from patients with liver diseases and mouse models were conducted to examine NPC1 expression. Myeloid cell-specific Npc1 knockout mice were constructed to determine the functional role of macrophage NPC1 in liver injury. Isolated macrophages were subjected to in vitro mechanistical assays. We found that NPC1 is mainly expressed in hepatic macrophages. Its mRNA and protein expression are significantly elevated in injured livers from both patients and mouse models. Tissue-specific deletion of myeloid Npc1 increased liver inflammation, levels of serum liver function enzymes, and liver fibrosis in mouse models of liver injury induced by carbon tetrachloride (CCl4) injection and methionine-and-choline-deficient (MCD) diets. Further analyses indicate that Npc1 deficiency in mouse models of liver injury resulted in increased levels of serum HMGB1 and mitochondrial DNA, promoted hepatic macrophage proinflammatory activation, M1 polarization, led to overproduction of hepatic inflammatory cytokines/chemokines, e.g. CCL2 and STING/NFκB pathway activation. In vitro mechanistical studies reveal that Npc1-deficient macrophages exhibited inefficient efferocytosis, partly due to impaired cargo degradation. These findings indicate that elevated expression of myeloid NPC1 in liver diseases protects liver from injury by promoting macrophage efferocytosis of damaged cells. Dysfunction of NPC1 aggravates liver injury, suggesting that NPC1 may be a potential therapeutic target for treating liver diseases.

Comparison of SPISE and METS-IR and Other Markers to Predict Insulin Resistance and Elevated Liver Transaminases in Children and Adolescents.

Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population. Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points. All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point. SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

The safety and feasibility of colchicine uptitration in the management of idiopathic recurrent pericarditis

Abstract Introduction Colchicine is recommended first line in the management of idiopathic recurrent pericarditis (IRP) at low doses (0.5 - 1 mg/24h). In cases refractory to low dose colchicine, corticosteroid use is common, despite an increased risk of disease recurrence and the risk of complications resulting from corticosteroid dependence. Biologic agents that block interleukin-1, anakinra and rilonacept, are highly effective in IRP, but their use is limited by expertise and cost. Colchicine uptitration is recommended by consensus international guidance in familial Mediterranean fever, a disease characterised by recurrent serositis, and, hence, offers an accessible steroid sparing approach to the management of treatment-refractory idiopathic recurrent pericarditis Purpose To explore the safety and feasibility of colchicine uptitration in patients with IRP refractory to low dose colchicine (0.5-1 mg/24h). Methods Retrospective review of electronic medical records of all patients with IRP and familial Mediterranean fever reviewed at a tertiary centre 2013-2023. Treatment-refractory IRP cases were defined as active disease despite colchicine 1mg/24h or disease requiring other prophylactic drugs, and corticosteroid dependence as daily corticosteroid use for 6 months. Results Of 121 IRP cases, 77 (63.6%) were treatment refractory at first review. Median follow up was 24 months (IQR 6 – 36). Corticosteroid dependence complicated 34/77 (44.2%) cases. Of treatment-refractory cases without corticosteroid dependence, 42/43 (97.7%) were treated with colchicine uptitration and 4/43 (9.3%) with anti-interleukin-1 biologic(s); none became corticosteroid dependent. Of corticosteroid dependent cases, 30/34 (88.2%) were treated with colchicine uptitration and 13/34 (38.2%) with anti-interleukin-1 biologic(s). Corticosteroids were fully discontinued in 25/34 (73.5%): 8/25 (32.0%) weaned with colchicine uptitration alone, 14/25 (56.0%) with anti-interleukin-1 biologic(s) and 3/21 (14.3%) with azathioprine. Median corticosteroid duration was 17.5 months (IQR 13 - 44.25) and corticosteroid toxicity occurred in 8/34 (23.5%). Among the 76/77 cases (98.7%) treated with colchicine (median maintenance dose 2 mg/24h (IQR 1.5-2)), permanent discontinuation was uncommon (3/76, 3.9%) and due to gastrointestinal symptoms. Self-limiting liver transaminase elevation was common (29/76, 38.2%) but did not lead to discontinuation in any case. The prevalence of liver transaminase elevation among patients with familial Mediterranean fever on life long colchicine was 181/568 (31.9%). Conclusions In this treatment-refractory pericarditis cohort, colchicine uptitration enabled avoidance of new corticosteroid dependence, facilitated corticosteroid discontinuation and was well tolerated. This contrasts with the frequent toxicity seen with prolonged corticosteroid use and offers an accessible steroid sparing approach to IRP management that warrants prospective investigation.

Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study.

The aim was to investigate the effects of lotiglipron, a once-daily, oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity. A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study. In total, 901 participants were treated with at least one dose of the study drug (T2D cohort: n = 512, obesity cohort: n = 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least squares mean decreases up to -1.44% (90% confidence interval [CI]: -1.63, -1.26) (lotiglipron 80 mg), versus placebo, -0.07% (90% CI: -0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to -7.47% (90% CI: -8.50, -6.43) (lotiglipron 200 mg, five-step titration), versus placebo, -1.84% (90% CI: -2.85, -0.83). Across cohorts, the most frequently reported treatment-emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four-step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort). The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated. GOV: NCT05579977.

Prognostic value of elevated transaminase levels as predictors of adverse outcomes in patients with acute myocardial infarction

Aim. To assess the prevalence of elevated serum liver transaminases (LTs), including alanine aminotransferase (ALT) and aspartate aminotransferase (ALT), and their impact on in-hospital and long-term mortality in patients with acute myocardial infarction (AMI).Materials and methods. The prospective observational study included 416 consecutive AMI patients (median age 65 years, 40.9% female, 46.9% with ST elevation) without prior liver diseases, who underwent coronary angiography within 24 hours after hospitalization. AST and ALT levels were measured upon admission. LTs were considered as abnormal when their levels exceeded the local upper limit of normal. Clinical endpoints were all-cause in-hospital and 18-month mortality. Associations between clinical endpoints and various risk factors, including LT levels, were assessed by the multivariate logistic regression analysis.Results. Elevated LT levels were seen in 28.6% of AMI patients: an isolated increase in ALT was noted in 17.8% of patients, while an isolated increase in AST was registered in 25% of cases. In-hospital and 18-month mortality was 5.8 and 11.3%, respectively. Abnormal LT levels were associated with the presence of ST elevation (odds ratio (OR) 1.873, 95% confidence interval (CI) 1.218–2.881, p = 0.004), lower systolic and diastolic blood pressure (OR 0.993, 95% CI 0.986–1.0, p = 0.04 and 0.979, 95% CI 0.964–0.994, p = 0.007, respectively), higher Killip class (OR 1.510, 95% CI 1.142–1.999, p = 0.004), and higher creatinine level (OR 1.010, 95% CI 1.003–1.016, p = 0.004). In the multivariate analysis, elevated LT levels were independently associated with in-hospital and 18-month mortality (OR 3.607, 95% CI 1.199–10.848, p = 0.022 and 2.182, 95% CI 1.011–4.708, p = 0.047, respectively).Conclusion. Elevated LT levels were present in about a third of patients with AMI. They were associated with specific clinical, biological, and prognostic features, including in-hospital and long-term mortality in AMI patients.

Highly Sensitive Molecular Diagnostic Platform for Scrub Typhus Diagnosis Using O. tsutsugamushi Enrichment and Nucleic Acid Extraction.

Scrub typhus is caused by the Gram-negative obligate intracellular bacterium Orientia tsutsugamushi, and this tick-borne disease is difficult to distinguish from other acute febrile illnesses as it typically presents with symptoms such as rash, crusting at the bite site, headache, myalgia, lymphadenopathy, and elevated liver transaminases. It can often be diagnosed clinically, but not all patients present with characteristic symptoms, so serological diagnosis and molecular techniques may be required. However, existing diagnostic tests often have low sensitivity and specificity, making early detection difficult. This study presents a nucleic acid extraction method using large volumes of plasma and buffy coat to increase sensitivity, as well as an improved detection method using two target genes. Using the I-PULL device, nucleic acids can be extracted from up to 4 mL of sample in 30 min, avoiding contamination. The extracted DNA detects two genes of O. tsutsugamushi, increasing sensitivity compared to single-gene detection. Clinical validation in 38 patient samples showed 100% specificity and 95.24% sensitivity for the single target gene, with specificity and sensitivity rising to 100% when both genes are analyzed. This molecular diagnostic platform can be useful for distinguishing scrub typhus from similar diseases.

7494 Glycerol Phenylbutyrate Treatment of Two Patients with Monocarboxylate Transporter 8 Deficiency

Abstract Disclosure: A. Zung: None. N. Sonntag: None. U. Schweizer: None. E. Banne: None. D. Braun: None. Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Currently, the two thyromimetic agents 3,5-diiodothyropropionic acid (DITPA) and triiodothyroacetic acid (TRIAC) have been evaluated in the treatment of these patients, as they both partially restore intracellular TH action independent of MCT8. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods: We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, serum markers of peripheral hyperthyroidism, vital signs, anthropometric measurements and neurocognitive functions by several neurodevelopment validated tests. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P32[1]L mutation. Results: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment yielded a dose-dependent decrease in FT3 and an increase in FT4 serum levels. The patients showed an elevation in cholesterol levels in parallel with GPB dose, but sex-hormone binding protein (SHBG), another marker of peripheral hyperthyroidism was not affected. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, mainly in hyperreflexia score, slight improvement in gross motor functions and a mild progression in cognitive functions. Serum metabolites of GPB did not exceed the toxic range but elevated liver transaminases restricted the dose intensification of GPB. Conclusions: In the first report of GPB treatment in MCT8 deficiency patients we found an improvement in TH profile and body-mass index (BMI). The reduction in T3 levels could contribute to the remarkable increase in BMI-SDS, since various aspects of peripheral hyperthyroidism in MCT8 deficiency, including poor weight gain, were attributed to elevated T3. The limited effects of GPB treatment on cognitive and motor functions can derive from the advanced age of the patients at the time of the intervention. Presentation: 6/2/2024

Clinical and genetic profile of Chinese children with Danon disease: A single-center retrospective cohort study

BackgroundDanon disease (DD) is a rare X-linked dominant lysosomal storage disorder. Studies on DD pediatric patients are limited due to the small number of cases and challenges in early detection. MethodsWe retrospectively analyzed clinical and genetic data of 29 pediatric patients who visited our hospital for treatment or genetic counseling of DD from July 2014 to December 2023. ResultsThe mean age at diagnosis was 7.2±5.9 years for males (n=21) and 9.4±5.0 years for females (n=8). Asymptomatic elevated liver aminotransferase and/or creatine kinase (CK) levels were initial manifestations detected in 10 (48%) male patients and absent in female patients. Hypertrophic cardiomyopathy (HCM) was observed in 20 (95%) male and 7 (88%) female patients, while dilated cardiomyopathy (DCM) was not detected. Ventricular preexcitation (VP) was observed initially in 10 (36%) patients and in 15 (54%) at latest evaluation. Patients with VP had higher left ventricular posterior wall thickness in diastole z-scores than those without VP (5.6±2.2 vs. 3.5±2.1, p=0.029). During a median 2.7-years follow-up, two males received heart transplants. One boy and one girl died of heart failure and sudden cardiac arrest, respectively. Twenty-three pathogenic LAMP2 variants were identified, including seven novel variants. ConclusionsA retrospective review of 29 DD cases suggests an underrecognized asymptomatic period in male DD patients, characterized by elevations in serum CK and transaminases. HCM appears to be the only cardiac manifestation in pediatric female patients, unlike a high incidence of DCM in adult female patients. The incidence of VP may increase with disease progression.

Redefining the phenotype of alpha-methylacyl-CoA racemase (AMACR) deficiency

BackgroundAlpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal enzyme deficiency caused by biallelic variants in the AMACR gene. This deficiency leads to the accumulation of toxic bile acid intermediates (R)-trihydroxycholestenoic acid (THCA) and (R)-dihydroxycholestenoic acid (DHCA) and pristanic acid. With less than 20 patients described in literature, the phenotype of AMACR deficiency is poorly defined and no data on the natural history are available.ResultsHere we describe a cohort of 12 patients (9 adults and 3 children) with genetically confirmed AMACR deficiency (median age at diagnosis 56 years, range 3–69), followed for an average of 6 years (between 2015 and 2023). Five novel pathogenic variants are described. In 5/9 adult patients, retinitis pigmentosa was detected at a median age of 45 years (range 30–61). The median delay to diagnosis of AMACR deficiency after the diagnosis of retinitis pigmentosa was 24 years (range 0–33). All adult patients subsequently developed neurological signs and symptoms after the age of 40 years; most frequently neuropathy, ataxia and cognitive decline with prior normal cognitive functioning. One patient presented with a stroke-like episode. All adult patients showed a typical MRI pattern involving the thalami and gray matter structures of the pons and midbrain. One patient had a hepatocellular carcinoma at the time of the AMACR deficiency diagnosis and two patients suffered from gallstones. All three included children had elevated liver transaminases as single presenting sign and showed no brain MRI abnormalities.ConclusionAMACR deficiency can be considered as an adult slowly progressive disease with a predominant neurological phenotype. The main signs comprise retinitis pigmentosa, neuropathy, ataxia and cognitive decline; stroke-like episodes may occur. Recognition of typical MRI abnormalities may facilitate prompt diagnosis. In addition, there is a risk of liver fibrosis/cirrhosis and hepatocellular carcinoma in these patients, requiring active monitoring.

The impact of consuming different types of high-caloric fat diet on the metabolic status, liver, and aortic integrity in rats

Consumption of high-caloric diets contributes to the alarming number of overweight and obese individuals worldwide, which in turn leads to several diseases and multiple organ dysfunction. Not only has the number of calories taken per day but also the type of fat in the diet has an important impact on health. Accordingly, the purpose of the current study was to examine the impact of different types of high-caloric fat diets on the metabolic status and the integrity of the liver and aorta in albino rats. Adult male albino rats were divided into 6 groups: Control group, long chain-saturated fat group (SFD), long chain-monounsaturated fat (MUFAs) group, long chain-polyunsaturated fat (PUFAs) group, medium-chain fat (MCFAs) group, and short-chain fat (SCFAs) group. Body mass index (BMI), Lee index, and visceral fat amount were reported. Serum levels of insulin, liver transaminases, lipid profile, and different oxidative stress and inflammatory markers were evaluated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and adiponectin/leptin ratio were also calculated. Histopathological examinations of liver and aorta with Masson’s trichrome stain, and immune-staining for Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) were also done. SFD group showed significantly elevated liver transaminases, inflammatory markers, HOMA-IR, dyslipidemia, reduced adiponectin, and deficient anti-oxidative response compared to other groups together with disturbed hepatic and aortic architecture. Other treated groups showed an improvement. PUFAs group showed the highest level of improvement. Not all high-fat diets are hazardous. Diets rich in PUFAs, MUFAs, MCFAs, or SCFAs may protect against the hazards of high caloric diet.

Prediction of insulin resistance and elevated liver transaminases using serum uric acid and derived markers in children and adolescents.

To investigate the relationship of serum uric acid (Uacid) and derived parameters as predictors of insulin resistance (IR) and elevated liver transaminases in children and adolescents METHODS: Data of 1648 participants aged 10-18 years was analyzed using nationwide survey. Logistic regression analysis was performed with IR and elevated liver transaminases as dependent variables, and odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles 2 and 3 of each parameter in comparison to tertile 1, which served as the reference. Receiver operating characteristic (ROC) curves were generated to assess predictability of the parameters for IR and elevated liver transaminases. Hyperuricemia, IR, and elevated liver transaminases were significantly associated with each other. All Uacid and derived markers showed continuous increase in ORs and 95% CIs for IR and elevated liver transaminases across the tertiles of several biochemical and metabolic variables of interest (all p < 0.001), and were also significantly predictive in ROC curve. Overall, Uacid combined with obesity indices showed higher ORs and area under the curve (AUC) compared to Uacid alone. Uacid-body mass index (BMI) standard deviation score presented the largest AUC for IR. For elevated liver transaminases, Uacid-BMI and Uacid-waist-to-height ratio showed the largest AUC. Uacid combined with obesity indices are robust markers for prediction of IR and elevated liver transaminases in children and adolescents. Uacid and derived markers have potential as simple markers which do not require fasting for screening of IR and elevated liver transaminases in children and adolescents.

Pregnancy Outcome in Pregnancies Complicated by Fetal Growth Restriction and Severe Preeclampsia

Abstract Background common pathophysiological feature favors parallel occurrence of severe pre-eclampsia (PET) and fetal growth restriction. Objective To identify pregnancy and neonatal outcome differences between early-onset and late-onset preeclampsia, in relation to fetal growth restriction (FGR) Methods this retrospective study included 50 singleton pregnancies with FGR and severe PET who were admitted in Ain Shams University Maternity Hospital. Fetal growth restriction was defined as EFW and/or AC &amp;lt; 10th percentile. Preeclampsia with severe features included patients with systolic BP ≥ 160 mmHg, diastolic BP ≥ 110 mmHg, elevated liver transaminases twice the normal values, elevated serum creatinine twice the normal levels, or &amp;gt; 1.1mg/dl, HELLP syndrome, features of impending eclampsia, pulmonary edema, and/or thrombocytopenia with platelets level &amp;lt; 100 x 109/L. obstetric and neonatal outcomes were compared in early and late onset PET. Results The current study revealed that there was no difference between early and late onset PET in fetal and pregnancy outcomes while there was significant difference in neonatal outcomes. Conclusion the current study showed that risk of adverse neonatal outcomes as respiratory distress syndrome and neonatal death were higher in cases with early onset PET.

Turmeric-Induced Liver Injury in a Patient with Concurrent Semaglutide Use

Turmeric has surged in popularity as one of the most widely used dietary supplements in the United States. Recognized for its antiinflammatory and antioxidant properties, it has traditionally been regarded as safe. Recent literature and reports in LiverTox have documented over a dozen cases of acute liver injury associated with the use of turmeric supplements. However, potential drug interactions with turmeric have been described but not well-documented. Thus, we present a case of drug-induced liver injury (DILI) correlated with turmeric supplement use and the concurrent use of semaglutide. INTRODUCTION Drug-induced liver injury (DILI) from herbal and dietary supplements (HDS) in the United States has increased as the usage of HDS has become more popular. According to the United States Drug-Induced Liver Injury Network (DILIN), approximately 20% of cases of DILI can be attributed to HDS, an increase from 7% in 2004.1 Turmeric supplements have become one of the top selling HDS in the United States. It is promoted for arthritis, pain, and digestive disorders. Common side effects include dermatitis and gastrointestinal upset, while instances of hepatotoxicity are rare. Different formulations that increase the bioavailability of curcumin, the active ingredient in turmeric, have been linked to cases of liver injury and acute hepatitis outbreaks outside of the United States.2 Possible interactions between turmeric and other drugs, such as anticoagulants, antiplatelets, antidiabetics, and chemotherapeutic agents, have been described in in vitro and animal studies, but have not been well studied in humans.3 In this report, we describe a possible drug interaction in a patient who had been using turmeric supplements and semaglutide injections and presented with elevated liver transaminases and bilirubin, with improvement upon cessation of the supplement.

Evaluation of Adverse Drug Events of Remdesivir for the Treatment of COVID-19 in Patients Contacting the 13-Aban Pharmacy Drug and Poison Information Center

Background: One of the FDA-approved treatments for COVID-19 is remdesivir. In this study, we investigated adverse drug events (ADEs) of remdesivir in COVID-19 patients who contacted 13-Aban pharmacy’s drug and poison information center (DPIC). Methods: In this study, data of patients receiving remdesivir who contacted the 13-Aban pharmacy’s DPIC between April 2021 and May 2022 were extracted. For the evaluation of potential ADEs, we reviewed all contacts related to remdesivir recipients. Results: Out of 223 patients enrolled, 108 (48.40%) developed 120 ADEs. Elevated liver transaminase levels (26.67%) were the most common ADE, followed by weakness (7.5%), nausea, and vomiting (7.5%). The causality assessment of ADE using the Naranjo scale revealed that 41.67% were probable and 58.33% were possible. Conclusion: Based on the results of this study, hepatic dysfunction was the most prevalent ADE among remdesivir recipients; thus, in order to ensure safe use of remdesivir, patients should be closely monitored for this ADE.

Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab versus Transarterial Chemoembolization Alone in Intermediate-stage Hepatocellular Carcinoma: A Multicenter Retrospective Study.

Combining transarterial chemoembolization (TACE) with systemic therapy has shown significant efficacy for intermediate-stage hepatocellular carcinoma (HCC) patients. This study aimed to validate the therapeutic efficacy of TACE combined with atezolizumab and bevacizumab (TACE + Atez/Bev) compared to TACE alone. A retrospective study was conducted across three centers in China, encompassing 155 patients at the intermediate-stage of HCC. Propensity Score Matching (PSM) was used to minimize selection bias, with a ratio of 1:1. Primary outcomes were TACE-specific Progression-Free Survival (PFS) and Overall Survival (OS). Objective Response Rate (ORR) and Disease Control Rate (DCR) were assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Adverse events (AEs) related to treatment were analyzed to evaluate safety. Before PSM, the TACE + Atez/Bev group demonstrated extended median OS (not reached vs 20.3 months, P = 0.004) and PFS (20.0 months vs 9.8 months, P = 0.029) compared to the TACE-alone group. The TACE + Atez/Bev group also had a higher ORR (60.9% vs 41.3%, P = 0.026) and DCR (89.1% vs 58.7%, P < 0.001) than the TACE-alone group. After applying the PSM, the study included 42 pairs of patients. Compared to the TACE-alone group, the combination therapy group also showed significantly longer median OS (not reached vs 21.4 months, P = 0.008) and PFS (21.7 vs 9.7 months, P = 0.009). The combination therapy group also had a higher ORR (66.7% vs 38.1%, P = 0.009) and DCR (92.9% vs 57.1%, P < 0.001). AEs in the combination therapy group were mostly manageable, with the most common being elevated liver transaminase. In treating intermediate-stage HCC, the survival benefit of combining TACE with atezolizumab and bevacizumab was significantly higher than TACE alone, and the treatment was well-tolerated.

Phage therapy in prosthetic joint infections caused by Staphylococcus aureus - A literature review.

Prosthetic joint infections (PJIs) are dreaded arthroplasty complications often caused by Staphylococcus aureus. Due to methicillin-resistant S. aureus (MRSA) strains or biofilm formation, successful treatment remains difficult. Currently, two-stage revision surgery constitutes the gold standard therapy of PJIs, sometimes replaced or supplemented by debridement, antibiotics, and implant retention (DAIR). Given the dire consequences of therapeutic failure, bacteriophage therapy might be another treatment option. Here we provide a comprehensive literature review addressing theefficacy of phages applied against S.aureus as causative agent of PJIs. The included 17 publications had in common that the applied phages proved to be effective against various S. aureus isolates including MRSA even in biofilms. Experiments with mice, rats, rabbits, and moth larvaeconfirmed favorable features of phage preparations in PJI treatment in vivo; including its synergistic with antibiotics. Case reports of PJI patients unanimously described the bacterial eradication following, alongside other measures, intravenous and intra-articular phage administration. Generally, no major side effects occurred, but in some cases elevated liver transaminases were observed. To conclude, our review compiled promising evidence suggesting the safety and suitability of phage therapy as an adjuvant to DAIR in S. aureus PJIs, and thus, underscores the significance of further research.

Does starting naltrexone in a patient with alcohol use disorder and elevated baseline liver transaminases cause further liver injury compared with acamprosate and gabapentin?

Does starting naltrexone in a patient with alcohol use disorder and elevated baseline liver transaminases cause further liver injury compared with acamprosate and gabapentin?

An Uncommon Cause of Elevated Liver Transaminases: Immune Reconstitution Inflammatory Syndrome from Unmasking of Occult Mycobacterium Avium Complex Infection in an HIV Infected Patient

Abnormal liver chemistry from the development of immune reconstitution inflammatory syndrome (IRIS) may reflect an unmasking of subclinical disease. We present the case of a 37-year-old female with a mixed pattern of liver injury from disseminated mycobacterium avium complex infection after starting antiretroviral therapy (ART). Presenting symptoms were fever, confusion, dysphagia, and abdominal discomfort for one week. Exam revealed a fever of 103.2°F, hypotension, encephalopathy, and abdominal tenderness. Lab work was significant for acute normocytic anemia, leukopenia, absolute CD4 count 28 cells/cmm, HIV viral load 276 viral copies/ml (vc/ml), ALT 267 U/L, AST 484 U/L, alkaline phosphatase 342 U/L, and normal total bilirubin. Imaging revealed hepatomegaly with steatosis and mesenteric and retroperitoneal lymphadenopathy. Percutaneous liver biopsy demonstrated noncaseating granulomas with AFB-positive organisms, with AFB blood cultures growing Mycobacterium avium complex (MAC), consistent with disseminated MAC infection. Clinicians must have a high index of suspicion for IRIS when determining the etiology of elevated liver transaminases in patients with HIV.

Elevated liver transaminases among patients with psychiatric disorders.

Hepatocyte injury is assessed by serum aspartate transaminase and alanine transaminase estimation. In psychiatric populations, antipsychotic drugs (AD) are culprit in hepatic dysfunction. To assess transaminitis among psychiatric patients treated by AD. This cross-sectional study was conducted in Zagazig University Hospitals in Egypt, from December 2022 to February 2023. A total of 135 adult patients aged ≥ 18 years, were diagnosed with psychiatric disorders after exclusion of patients receiving any hepatotoxic drugs, viral hepatitis, having chronic liver or kidney diseases, diabetes mellitus, mental retardation, and pregnant females. Among the 135 patients, 104 (77.0%) were males. Their age was 32 ± 9, The most popular used class of AD was atypical AD 84 (62.2%). The overall incidence of transaminitis among patients receiving AD was 23/135 (17.04%) of patients; 13 (56.5%) were on atypical AD compared to 10 (43.5%) patients receiving combined AD, without any statistically significant difference. The use of AD in patients with psychiatric disorders is potentially safe with minimal transaminitis (<one-fold elevation). However, baseline and regular monitoring of serum aminotransferase is recommended during treatment.

Glycerol Phenylbutyrate Treatment of 2 Patients With Monocarboxylate Transporter 8 Deficiency.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. We treated 2 monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, vital signs, anthropometric measurements, and neurocognitive functions. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P321L mutation. The effects of GPB were compared to the effects of DITPA and TRIAC, thyromimetic medications that the patients had received in the past. NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment reduced high T3 and increased low T4 levels. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neurocognitive improvement was observed, in hyperreflexia score and in cognitive functions. Serum metabolites did not exceed the toxic range, but elevated liver transaminases were observed. In the first report of GPB treatment in MCT8 deficiency we found an improvement in TH profile and body mass index, with minor neurodevelopmental changes.