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Background Early detection of biliary atresia (BA) is a great challenge providing the main useful way to improve its clinical consequence. Promising metabolomics provides an effective method for determining innovative biomarkers and biochemical ways for improving early diagnosis. This study aimed to determine the benefit of serum and urinary potential bile acid metabolites in the differentiation of BA from non-biliary atresia (non-BA) cases using tandem mass spectrometry (MS/MS). Fourteen bile acids metabolites were measured quantitively by MS/MS in serum and urine samples from 102 cholestatic infants and 102 control infants, in addition to the assay of the total serum bile acid enzymatically. Results After the diagnostic clinical and laboratory workflow, cholestatic infants were divided into BA (37 infants) and non-BA (65 infants) subgroups. Remarkably on analysis of serum individual bile acid concentrations, there were significant differences between cholestatic BA and non-BA regarding serum (glycocenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and GCDCA/chenodeoxycholic acid (CDCA) ratio) (p < 0.001, for all), while there was no significant difference between the two groups regarding serum level of (cholic acid (CA), glycocholic (GCA), or TCDCA/CDCA ratio). There were no significant differences in either the urinary individual bile acids or urinary primary bile acids (conjugated or unconjugated) between BA and non-BA. Further principal component analysis (PCA) analysis was done and receiver operating characteristic (ROC) analysis was performed using score plots of the positive factors in the first two principal components PC1 (CA, GCA, GCDCA, TCA, TCDCA) and PC2 (CA, CDCA, lithocholic (LCA), ursodeoxycholic acid (UDCA)) for establishing the differences between the two diseased groups and revealed that the area under the curve (AUC) for PC1 was (0.770) higher than AUC for PC2 (0.583) indicating that the positive components of PC1 may be potential biomarkers for differentiation between the two cholestatic groups. Conclusions Metabolomics of serum bile acid levels using tandem mass spectrometry might change the paradigm differentiating BA from non-BA saving patients from unnecessary invasive procedures.

Background Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. Methods Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. Results Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. Conclusions HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. Trial registration This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients’ medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).

Background Inborn errors of metabolism (IEMs) represent a special challenge in pediatric practice. Despite the unquestionable clinical significance of newborn screening, it just offers a snapshot of an extremely minor subgroup of metabolic disorders. So, it is crucial to use multiple techniques for accurate diagnosis of a wider spectrum of IEMs early in infancy to prevent overwhelming irreversible neurological complications in a cohort of high-risk Egyptian pediatrics. This study included four thousand and eighty suspected IEMs patients. They were referred to the Chromatography Unit, Clinical Biochemistry and Molecular Diagnostics Laboratories, National Liver Institute (NLI) for laboratory assessment in the period from March 2016 to November 2020. Separation of amino acids and acylcarnitines using tandem mass spectrometry (LC/MS) and organic acids using gas chromatography mass spectrometry (GC/MS) was done. Results Three hundred and twenty (320/4080, 7.8%) patients were diagnosed with IEMs. The following disorders were identified: organic acidopathies—200 (62.5%) including methylmalonic acidemia (MMA) (48/320, 15%), glutaric academia (GA) (40/320, 12, 5%), propionic acidemia (PA), (32/320, 10%), isovaleric acidemia (IVA) (40/320, 12.5%), methylcrotonyl glyceinuria (16/320, 5%), and orotic acidemia (24/320, 7.5%); amino acidopathies—80 (25%) including maple syrup urine disease (MSUD) (32/320, 10%), phenylketonuria (24/320, 7.5%), homocystinuria (16/320, 5%), and nonketotic hyperglycinemia (8/320, 2.5%) in addition to fatty acid disorders (FAO): 24 (7.5%) and lactic academia (LA), 16 (5%). Conclusion Early detection of IEMs by rapid non-invasive techniques. LC/MS and GC/MS. is a crucial process for early diagnosis of different types of IEMs to install therapeutic clue in a group of high-risk Egyptian pediatrics for proper treatment and better outcome

Metformin (MET) has been reported to have antidepressant effects in animal models and in diabetic patients with depression, owing to its anti-inflammatory, antioxidant, and neuroprotective activity. Accordingly, we proposed that MET would show antidepressant effects in patients with major depressive disorder (MDD) without other comorbidities. In this double-blind placebo-controlled study, 80 adult outpatients with MDD (DSM-IV criteria) and a Hamilton Depression Rating Scale (HAM-D) score >18 were randomized to receive fluoxetine 20 mg once daily plus placebo (n = 40) or fluoxetine 20 mg once daily plus MET 1000 mg once daily for 12 weeks. Patients were assessed by HAM-D score (weeks 0, 4, 8, and 12). The serum levels of TNF–α, IL-1β, IL-6, IGF-1, MDA, CRP, BDNF, and serotonin were measured before and after therapy. Mixed-effects model repeated-measures analysis of covariance was used to compare the HAM-D scores and the biological markers between the two groups. After 4, 8 and 12 weeks, patients in the MET group showed a statistically significant decline in HAM-D score relative to the placebo group (least squares mean difference [LSMD] –2.347, p = 0.000, LSMD –3.369, p = 0.000, and LSMD –3.454, p = 0.000, respectively). Response and remission rates were significantly higher in the MET group (89% and 81%, respectively) than in the placebo group (59% and 46%, respectively). Moreover, the MET group was superior in conserving the measured biological markers compared with the placebo group. Our findings suggest MET as a promising, effective, and safe short-term adjunctive approach in nondiabetic MDD patients. Trial registration ID: NCT04088448. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00878-7) contains supplementary material, which is available to authorized users.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly affects respiratory system. Later, liver affection has also been reported in the form of marked elevated liver enzymes. However, the association of coronavirus disease-19 (COVID-19) and autoimmune diseases is not clear. Case presentation A female patient with a known history of autoimmune hemolytic anemia (AIHH) for which she was treated with prednisolone was admitted for uncontrolled anemia followed by fever and elevated liver enzymes. All the laboratory and radiological investigations were not typical for COVID-19 or any other etiology. Liver biopsy revealed numerous pale eosinophilic trichrome-positive intracytoplasmic globules. The pathology raised the suspicion for SARS-CoV-2-associated hepatitis, which was confirmed by a positive IgG titer. The patient showed a dramatic improvement on the maintenance dose of prednisolone. Conclusions AIHA patients co-infected with SARS-CoV-2 may be at risk of uncontrolled disease and should continue their treatment regimen. Histopathology has a role in the diagnosis of liver affection due to SARS-CoV-2 infection.