Hepatocellular carcinoma (HCC) is a worldwide health problem. HCC patients show a 50% mortality within two years of diagnosis. To better understand the molecular pathogenesis at the level of lipid metabolism, untargeted UPLC MS—QTOF lipidomics data were acquired from resected human HCC tissues and their paired nontumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to chronic liver disease (CLD) (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The lipidomics data yielded 604 identified lipids that were divided into six super classes. Five-hundred and twenty-four blood lipids were found as significantly differentiated (p < 0.05 and qFDR p < 0.1) between the three study groups. In the blood of CLD patients compared to healthy control subjects, almost all lipid classes were significantly upregulated. In CLD patients, triacylglycerides were found as the most significantly upregulated lipid class at qFDR p = 1.3 × 10⁻⁵⁶, followed by phosphatidylcholines at qFDR p = 3.3 × 10⁻⁵¹ and plasmalogens at qFDR p = 1.8 × 10^-46. In contrast, almost all blood lipids were significantly downregulated in HCC patients compared to CLD patients, and in HCC tissues compared to nontumor hepatic tissues. Ceramides were found as the most significant lipid class (qFDR p = 1 × 10⁻¹⁴) followed by phosphatidylglycerols (qFDR p = 3 × 10⁻⁹), phosphatidylcholines and plasmalogens. Despite these major differences, there were also common trends in the transitions between healthy controls, CLD and HCC patients. In blood, several mostly saturated triacylglycerides showed a continued increase in the trajectory towards HCC, accompanied by reduced levels of saturated free fatty acids and saturated lysophospatidylcholines. In contrast, the largest overlaps of lipid alterations that were found in both HCC tissue and blood comparisons were decreased levels of phosphatidylglycerols and sphingolipids. This study highlights the specific impact of HCC tumors on the circulating lipids. Such data may be used to target lipid metabolism for prevention, early detection and treatment of HCC in the background of viral-related CLD etiology.

The major risk factors for hepatocellular carcinoma (HCC) are hepatitis C and B viral infections that proceed to Chronic Liver Disease (CLD). Yet, the early diagnosis and treatment of HCC are challenging because the pathogenesis of HCC is not fully defined. To better understand the onset and development of HCC, untargeted GC-TOF MS metabolomics data were acquired from resected human HCC tissues and their paired non-tumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to CLD (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The GC-TOF MS data yielded 194 structurally annotated compounds. The most strikingly significant alteration was found for the class of sugar alcohols that were up-regulated in blood of HCC patients compared to CLD subjects (p < 2.4 × 10⁻¹²) and CLD compared to healthy controls (p = 4.1 × 10⁻⁷). In HCC tissues, sugar alcohols were the most significant (p < 1 × 10⁻⁶) class differentiating resected HCC tissues from non-malignant hepatic tissues for all HCC patients. Alteration of sugar alcohol levels in liver tissues also defined early-stage HCC from their paired non-malignant hepatic tissues (p = 2.7 × 10⁻⁶). In blood, sugar alcohols differentiated HCC from CLD subjects with an ROC-curve of 0.875 compared to 0.685 for the classic HCC biomarker alpha-fetoprotein. Blood sugar alcohol levels steadily increased from healthy controls to CLD to early stages of HCC and finally, to late-stage HCC patients. The increase in sugar alcohol levels indicates a role of aldo-keto reductases in the pathogenesis of HCC, possibly opening novel diagnostic and therapeutic options after in-depth validation.

Background and Aim. Hepatitis B virus (HBV) infection causes a variety of clinical manifestations, including liver cirrhosis and hepatocellular carcinoma (HCC). Toll‐like receptors (TLRs) have crucial functions in immune and inflammatory control. Therefore, this study highlights the impact of TLR2 gene polymorphism on the progression of HBV‐linked liver diseases (liver cirrhosis and HCC). Methods. In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case‐control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL‐6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real‐time PCR. Results. IL‐6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups (p < 0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL‐6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (p = 0.03, OR = 2.45, and 95% CI: 1.69–3.65), IL‐6 levels (p = 0.04, OR = 3.45, and 95% CI: 2.01–6.9), and TRL2 variants (p = 0.01, OR = 4.25, and 95% CI: 2.14–13.5) are independent risk factors associated with disease progression from cirrhosis to HCC. Conclusion. In chronic HBV patients, TRL2 polymorphism and higher IL‐6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.

Background: Intraventricular hemorrhage (IVH) is a major cause of morbidity and mortality in preterm neonates. It is essential to obtain new biomarkers for its early diagnosis. This can mainly occur by understanding its pathophysiology and mechanism of occurrence. Objective: To investigate the metabolic changes (blood amino acids and carnitine concentrations) associated with IVH in preterm neonates, and the ability to discover new biomarkers for early diagnosis of such disease that enable early intervention. Patients and Methods: This study was conducted on twenty preterm infants with IVH in the period from July 2019 to July 2020. Preterm infants were evaluated for IVH according to Velisavljev-Fillpoviewith head US scans performed within 24 h after birth, on the 3rd day of life and thereafter weekly till discharge in survivors (Cases). Twenty preterm infants were chosen as a control group matching with the case group in gestational age, gender, and birth weight. Results: There was significant rise of alanine, aspartate, glutamate, and ornithine amino acids in IVH group than control in day 1 (P value < 0.05) in addition to glycine, valine, and proline in day 3. Alanine amino acid > 112.5 μmol/L showed the highest accuracy 80%, sensitivity 70% and specificity 90% for diagnosis of IVH in premature neonates among all tested amino acids in day 1with significant rise in C3:C2 at cut off point 0.095 (p= 0.001) and C6 cut off point 0.08 (P=0.001) and acylcarnitine cut off point >0.045 μmol/L (P=0.002) for diagnosis of IVH. Conclusion: Preterm neonates with IVH showed significant changes in amino acids and carnitines that might guide us to new biomarkers for early diagnosis and intervention.

HCC is the most prevalent gastrointestinal malignant tumour worldwide. Genetic determinants of HCC occurrence have been always an interest for most hepatologists. The aim of our research to discover link between TLR2 gene (rs3804099) polymorphism, MicroRNA 301 gene expression and HCC incidence in an Egyptian cohort. Methodology: 247 participants were divided to 3 groups. Group 1: 85 adult HCC patients on top of HCV. Group 2: 82 chronic HCV patients. They were followed up for one year. 80 supposedly healthy subjects who were matched in age and sex with patients (Group 3). All participants were subjected to clinical evaluation and history-taking, laboratory investigations and molecular testing (TLR2 SNP analysis and microRNA 301 gene expression by qPCR). Results: Our study found that HCC patients were mainly males (60%), aged 53.67 ± 7.62years. TLR2 (rs3804099) CC genotype was significantly prominent in HCC patients (37,6%), CT prevails in hepatitis C patients (47,8%), while TT was the main genotype of healthy controls. Individuals carrying genotype TT were significantly associated with decreased risk of HCC (OR 1, 95% CI, P = 0.0001), while those of CC showed a higher HCC risk (OR 3.048 95% CI (1.269 – 7.320), P = 0.013). A highly significant variation in MicroRNA301 level regarding Barcelona B, D stages (P <0.001) and TNM classification with increased serum level in advanced stages, increased tumour size mainly with CC genotype [T3=27 (84.4%) T4 =5 (15.6%), lymph nodes (N2) and metastasis (M1)]. We concluded that TLR2 SNP CC variant carries the highest risk of HCC development, while microRNA301 expression can be considered diagnostic and prognostic marker in HCC Egyptian patients.