Prevalence of and Risk Factors for Liver Enzyme Elevation After Hepatitis C Virologic Cure.

A subset of patients with chronic hepatitis C virus (HCV) infection demonstrate liver enzyme elevation (LEE) after achieving sustained virologic response (SVR). Risk factors for LEE are not well characterised. We conducted a single-centre retrospective cohort study of adults with HCV infection in the Duke University Health System who received direct-acting antiviral therapy and achieved SVR. We performed multivariable logistic regression to assess the relationship between potential risk factors and LEE. We used generalised linear mixed-effects models to explore longitudinal relationships between HIV and LEE. Among 1356 patients, 556 (41.0%) had LEE after achieving SVR. Higher pretreatment alanine aminotransferase (ALT) (adjusted odds ratio [aOR] 1.08 per 10 IU/L increase; 95% confidence interval [CI] 1.05-1.11) and pretreatment cirrhosis (aOR 2.26, 95% CI 1.60-3.21) were associated with higher odds of LEE; male sex was associated with lower odds of LEE (aOR 0.28, 95% CI 0.21-0.38). There was insufficient evidence of an association between HIV and LEE (aOR 0.83, 95% CI 0.47-1.44). Pretreatment ALT, cirrhosis and female sex predicted LEE in this cohort of patients with HCV infection who achieved SVR. These findings can help to identify patients at greatest risk of post-SVR liver injury.

Breastfed infants exposed to lamotrigine faced a low risk of toxic effects.

AIM: We aimed to investigate plasma lamotrigine concentrations and clinical effects in infants exposed to lamotrigine through breastfeeding. METHODS: This was a retrospective study of mother-infant dyads in a clinical follow-up programme in Stockholm, Sweden. Data were collected from medical records. RESULTS: We included 47 breastfed infants, born from 2011 to 2021, with a median gestational age of 39 + 6 weeks/days and a median birth weight of 3420 g. The median lamotrigine concentration in the infants' plasma was 2.5 (range 2.5-14.0) µmol/L. These concentrations correlated significantly with both the maternal plasma concentrations and the maternal doses (R = 0.79, p < 0.001 versus R = 0.54, p < 0.001). During the follow up, lamotrigine concentrations within the reference range for epilepsy treatment were detected in six (14%) infants and one had clinical symptoms that were probably related to lamotrigine exposure. Liver transaminases were elevated in three of 21 infants. All infants whose mothers had a dose of 150 mg or less had undetectable plasma concentrations and no symptoms during follow up. CONCLUSION: Infants exposed to lamotrigine through breastfeeding had a low risk of toxic effects. All infants whose mothers had low lamotrigine doses had unmeasurable plasma concentrations and no symptoms of lamotrigine exposure. These low-risk infants might be offered a simplified follow up.

Evaluating the Utility of Liver Transaminases as Predictors of Feto-Maternal Outcome in Lieu of Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy: A Prospective Observational Study.

Introduction: Intrahepatic Cholestasis of Pregnancy (ICP) is a disorder of the second half of pregnancy causing pruritus and abnormal liver function tests (LFT). Incidence in India is 1.2-1.5%. ICP leads to adverse feto-maternal outcomes with early delivery indicated before serum bile acids (SBA) (gold standard) and hepatic transaminases are critically high. With paucity of evidence these levels are not well defined. Objectives: To determine the association of liver transaminases with pregnancy outcomes in ICP and evaluate critical levels for prediction of adverse outcomes. Material and Methods: A prospective observational study was conducted comprising 88 pregnant women with pruritus not associated with rash. After history and examination, LFT and SBA levels were done, treatment given and followed till pregnancy termination to determine the feto-maternal outcome. Results: The mean age of participants was 26.43 ± 3.35 years. The mean SBA, ALT and AST levels were 18.97 ± 10.320 µmol/L, 206.06 ± 45.71units/litre and 175.37 ± 101.088 units/litre respectively. 39.7% of participants were symptomatic for ICP while 38.6% responded to treatment. 34.1% underwent LSCS majorly (43.3%) formeconiumand 23.3% had foetal distress. 33% had preterm delivery. 5.68% of the neonates needed NICU admission and 6.8% had respiratory distress syndrome. The cut off for ALT on ROC curve analysis was 151.5 units/litre with AUC as 0.905, sensitivity and specificity of 89.7 and 70% respectively. Conclusion: ICP leads to adverse pregnancy outcomes. ALT is a promising predictor of adverse outcome and termination of pregnancy can be planned accordingly.

Associations between serum ferritin, iron, and liver transaminases in adolescents: a large cross-sectional study / Asociaciones entre la ferritina sérica, el hierro y las transaminasas hepáticas en adolescentes: un amplio estudio transversal

Introduction: few previous studies suggest that serum iron status may be associated with liver function, but the relevant evidence remainslimited, especially in adolescents.Objective: we aimed to investigate the association between serum ferritin, iron, and liver transaminases in adolescents.Methods: a cross-sectional study including 3,404 adolescents aged 10-19 was performed based on the National Health and Nutrition ExaminationSurvey. Weighted multivariate regression, subgroup analysis, and sensitivity analysis were used.Results: a total of 3,404 adolescents were eventually included. Serum ferritin and iron were positively correlated to alanine aminotransferase(ALT) and aspartate aminotransferase (AST). The association between serum ferritin and ALT remained positive in all genders and races, but onlyremained positive in girls and several races between serum ferritin and AST. The positive correlations kept present among girls between serumiron and ALT, and also kept present among girls and non-Hispanic whites between serum iron and AST. Additionally, serum ferritin and iron werealso positively correlated to elevated ALT and elevated AST using binary logistic regression analysis. After excluding the subjects with serumferritin levels above the upper limit of normal, the main results remained the same basically.Conclusion: the present results add novel evidences about the associations between serum ferritin, iron, and liver transaminases, which requiresmore confirmatory studies. (AU)

Introducción: pocos estudios previos sugieren que el estado del hierro sérico pueda estar asociado con la función hepática, pero la evidenciarelevante sigue siendo limitada, especialmente en adolescentes.Objetivo: nuestro objetivo fue investigar la asociación entre la ferritina sérica, el hierro y las transaminasas hepáticas en adolescentes.Métodos: se realizó un estudio transversal que incluyó a 3,404 adolescentes de diez a 19 años de edad, basado en la Encuesta Nacional deExamen de Salud y Nutrición. Se utilizaron la regresión multivariada ponderada, el análisis de subgrupos y el análisis de sensibilidad.Resultados: finalmente, se incluyó un total de 3.404 adolescentes. La ferritina sérica y el hierro se correlacionaron positivamente con la alaninaaminotransferasa (ALT) y la aspartato aminotransferasa (AST). La asociación entre ferritina sérica y ALT se mantuvo positiva en todos los génerosy razas, pero solo se mantuvo positiva en niñas y en varias razas entre ferritina sérica y AST. Las correlaciones positivas siguieron presentesen las niñas entre el hierro sérico y la ALT, y también en las niñas y personas blancas no hispanas entre el hierro sérico y la AST. Además, laferritina sérica y el hierro también se correlacionaron positivamente con ALT elevada y AST elevada mediante análisis de regresión logísticabinaria. Después de excluir a los sujetos con niveles de ferritina sérica por encima del límite superior de la normalidad, los resultados principalesse mantuvieron básicamente iguales.Conclusión: los presentes resultados agregan evidencias novedosas sobre las asociaciones entre la ferritina sérica, el hierro y las transaminasashepáticas, lo que requiere más estudios confirmatorios. (AU)

Polymyositis: A Case Report.

Inflammatory myopathies are a group of diseases whose common pathway is immune-mediated muscle damage, one of which is polymyositis. The definition of polymyositis is controversial, with proponents advocating a definition based on immunohistochemical and histopathological findings in muscle biopsies, while other proponents advocate a definition based on clinical manifestations and histopathological findings. Polymyositis is a quite rare disease that is clinically characterized by progressive proximal muscle weakness with a symmetric distribution. Within the diagnostic approach, laboratory studies show elevation of sarcoplasmic enzymes; nerve conduction tests are performed, which may aid in distinguishing myopathic causes of weakness from neuropathic disorders; and muscle biopsy is considered the gold standard to diagnose inflammatory myopathy and to distinguish the subclasses. We report the case of a 61-year-old male patient who presented generalized symmetrical weakness, predominantly in the upper extremities, and dysphagia, whose laboratory studies, autoantibodies, and muscle biopsy were confirmatory of this entity.

Association between serum iron and liver transaminases based on a large adult women population.

BACKGROUND: Studies are being focused on the potential roles of iron in various diseases, but remain unclear for the association between serum iron and liver injury, especially in adult women. METHODS: Based on the National Health and Nutrition Examination Survey, we investigated the relationship between serum iron and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among 19,185 adult women. RESULTS: Using weighted multivariate regression analyses, subgroup analyses, and threshold effect analyses, we found that serum iron was independently and positively correlated with ALT and AST. These associations differed in various age or race. Additionally, we found turning points in the curves of the relationship between serum iron and ALT in all women and the non-pregnant women. Using sensitivity analyses, we further found that the associations between serum iron and the liver transaminases remained positive in the non-pregnant women after adjusting for various covariates, but not in pregnant women. Besides, the positive associations between them kept present after excluding the women with high blood pressure, diabetes, and chronic kidney disease. CONCLUSION: The present study indicated a positive association between serum iron and liver transaminases, indicating that serum iron may be a potential biomarker of liver function.

Use of probiotics, prebiotics, and synbiotics in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Patients with non-alcoholic fatty liver disease (NAFLD) exhibit compositional changes in their gut microbiome, which represents a potential therapeutic target. Probiotics, prebiotics, and synbiotics are microbiome-targeted therapies that have been proposed as treatment for NAFLD. We aim to systematically review the effects of these therapies in liver-related outcomes of NAFLD patients. METHODS: We conducted a systematic search in Embase (Ovid), Medline (Ovid), Scopus, Cochrane, and EBSCOhost from inception to August 19, 2022. We included randomized controlled trials (RCTs) that treated NAFLD patients with prebiotics and/or probiotics. We meta-analyzed the outcomes using standardized mean difference (SMD) and assessed study heterogeneity using Cochran's Q test and I2 statistics. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool. RESULTS: A total of 41 (18 probiotics, 17 synbiotics, and 6 prebiotics) RCTs were included. Pooled data demonstrated that the intervention had significantly improved liver steatosis (measured by ultrasound grading) (SMD: 4.87; 95% confidence interval [CI]: 3.27, 7.25), fibrosis (SMD: -0.61 kPa; 95% CI: -1.12, -0.09 kPa), and liver enzymes including alanine transaminase (SMD: -0.86 U/L; 95% CI: -1.16, -0.56 U/L), aspartate transaminase (SMD: -0.87 U/L; 95% CI: -1.22, -0.52 U/L), and gamma-glutamyl transferase (SMD: -0.77 U/L; 95% CI: -1.26, -0.29 U/L). CONCLUSIONS: Microbiome-targeted therapies were associated with significant improvements in liver-related outcomes in NAFLD patients. Nevertheless, limitations in existing literature like heterogeneity in probiotic strains, dosage, and formulation undermine our findings. This study was registered with PROSPERO (CRD42022354562) and supported by the Nanyang Technological University Start-up Grant and Wang Lee Wah Memorial Fund.

Mendelian randomisation reveals Sodium-glucose Cotransporter-1 inhibition's potential in reducing Non-Alcoholic Fatty Liver Disease risk.

Non-alcoholic fatty liver disease (NAFLD) has no approved pharmacological treatments. Sodium-glucose cotransporter (SGLT)-1 is a glucose transporter that mediates small intestinal glucose absorption. We evaluated the impact of genetically proxied SGLT-1 inhibition (SGLT-1i) on serum liver transaminases and NAFLD risk. We used a missense variant, rs17683430, in the SLC5A1 gene (encoding SGLT1) associated with HbA1c in a genome-wide association study (n = 344 182) to proxy SGLT-1i. Outcome genetic data comprised 1483 NAFLD cases and 17 781 controls. Genetically proxied SGLT-1i was associated with reduced NAFLD risk (OR 0.36; 95%CI 0.15, 0.87; P = .023) per 1 mmol/mol HbA1c reduction, and with reductions in liver enzymes (alanine transaminase, aspartate transaminase, gamma-glutamyl transferase). Genetically proxied HbA1c, not specifically via SGLT-1i, was not associated with NAFLD risk. Colocalisation did not demonstrate genetic confounding. Overall, genetically proxied SGLT-1i is associated with improved liver health, this may be underpinned by SGLT-1-specific mechanisms. Clinical trials should evaluate the impact of SGLT-1/2 inhibitors on the prevention and treatment of NAFLD.

The role of liver transaminase levels in methotrexate intolerance in juvenile idiopathic arthritis-a cross-sectional study.

Methotrexate (MTX) plays a key role when treating juvenile idiopathic arthritis (JIA), but MTX-intolerance is challenging. MTX-treatment might affect the liver, causing elevated levels of alanine aminotransferase (ALT), yet the role of ALT-levels in MTX-intolerance in JIA remains unclear. Our study aimed to investigate the association between ALT-levels during MTX-treatment and MTX-intolerance in JIA. Children (> 9 years old) diagnosed with JIA and treated with MTX (> 6 weeks) were eligible for enrollment. MTX-intolerance was assessed using the Methotrexate Intolerance Severity Score (MISS), completed by the parents, and defined as MISS ≥ 6 with at least 1 point for a behavioral/anticipatory/associative symptom. ALT-levels were determined at enrollment. A total of 118 children were enrolled (80 girls; 38 boys). MTX-intolerance was registered in 61%. ALT-levels did not differ between the MTX-intolerant group (median = 17.0 U/L [IQR: 14.0-26.0]) and the MTX-tolerant group (median = 20.5 U/L [IQR: 16.0-27.5]; p = 0.17). MTX-intolerance was prevalent in around 60% of both boys and girls. Nine out of 50 MTX-intolerant girls had elevated ALT-levels compared to 0/22 MTX-intolerant boys, however, there was no difference in median ALT levels between the two groups. Furthermore, the MTX-intolerant girls had a higher MISS (median = 14.0 [IQR: 9.3-17]) than the MTX-intolerant boys (median = 10.0 [IQR: 7.3-12]; p = 0.009). Our study did not find a difference in ALT-levels between MTX-intolerant and MTX-tolerant children. However, only MTX-intolerant girls and no MTX-intolerant boys showed elevated ALT-levels.

Ratio of aspartate aminotransferase to alanine aminotransferase and alkaline phosphatase to total bilirubin in Wilsonian acute liver failure in children.

BACKGROUND: Acute liver failure (ALF) caused by Wilson disease (WD) is always fatal. Therefore, a quick diagnosis of WD is needed to start immediate management. This study aims to determine the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and the ratio of alkaline phosphatase to total bilirubin (ALP/TB) in diagnosing Wilsonian acute liver failure (WALF) in children. METHODS: Sixty children with acute liver failure were included in this study, of whom 40 had WALF and 20 had a non-Wilsonian acute liver failure (non-WALF). The serum ALT, AST, alkaline phosphatase, and total bilirubin of each blood sample were measured. We evaluated the sensitivity and specificity of AST/ALT ratio and ALP/TB ratio in WALF diagnosis. RESULTS: Consanguinity and Kayser-Fleischer (K-F) rings were found in 32.5% and 72.5% of WALF cases, respectively. The mean hemoglobin, median ALT, median alkaline phosphatase, and mean ceruloplasmin of children with WALF were lower than those in the non-WALF group. In WALF cases, the median AST/ALT ratio was higher than in non-WALF cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the ratio of AST to ALT were 70%, 95%, 96.5%, 61.3% and 78.3%, respectively. However, when the cutoff value is ≥ 1.85, the maximum sensitivity produced by the AST/ALT ratio is 77.5% and the specificity is 95%. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the ratio of ALP/TB < 4 were 32.5%, 100%, 100%, 42.5%, and 55%, respectively. The overall mortality rate was 50%, while the WALF mortality was 60%. CONCLUSION: A positive AST/ALT and ALP/TB ratio strongly suggest WALF, but a negative result does not exclude WALF. We cannot use these ratios as a diagnostic tool for children with WALF. In WALF cases, the mortality rate is remarkably high, and the high score of the new Wilson index predicts the mortality rate without liver transplantation.