Coronavirus disease 19 (Covid-19): A comparative study of pattern of liver injury in adult patients in different waves of Covid-19 infection.

BACKGROUND AND STUDY AIMS: Liver dysfunction is a common manifestation of the COVID-19 infection. We aimed to study transaminase abnormalities through different waves of COVID-19 and their relations to disease severity or mortality. PATIENTS AND METHODS: A retrospective study included 521 Egyptian patients diagnosed with COVID-19. Data was retrieved from the medical records of patients who were admitted from April 2020 to October 2021 in Kasr Al-Ainy Hospitals, Cairo University, with categorization according to disease severity in correspondence to the four waves. RESULTS: The median age was lower in the first wave compared to other waves, with male predominance across all waves. The most commonly encountered comorbidity overall was hypertension, followed by diabetes mellitus. White blood cells, ferritin, and interleukin-6 showed the highest median values in the second wave, with significantly higher median C-reactive protein on day 1 in the first wave. Forty percent of the patients showed elevated hepatic transaminases on admission in four waves, with no statistically significant difference between waves. On day 5, around half of the patients had elevated transaminases, with no significant difference between waves. Most CT findings were of moderate severity. Clinical severity was higher in the second wave. It was observed that the higher the disease severity, the greater the proportion of patients with elevated hepatic transaminases. The mortality rate was markedly high in cases who had elevated ALT or AST on day 5. The association between elevated enzymes on admission and mortality was seen in the first wave only, with a fatality rate of 22.5% in cases with increased baseline ALT and AST versus 5% in those with normal baseline enzymes. CONCLUSION: There was no significant difference in transaminases between the four waves. Elevated transaminases were positively associated with increased mortality and severity, reflecting their prognostic value.

Serum microRNA let-7a-1/let-7d/let-7f and miRNA 143/145 Gene Expression Profiles as Potential Biomarkers in HCV Induced Hepatocellular Carcinoma.

BACKGROUND: Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Which make liver cirrhosis and hepatocellular carcinoma (HCC) major health concerns in Egypt. Circulating microRNAs (miRNAs) have been investigated as biomarkers for malignancies. We investigated miRNA gene expression of Lethal-7 (let-7) cluster: let7-a-1, let-7d-1, let-7f-1 and miRNA (miR)143/145 cluster in sera of HCC patients and chronic HCV patients. METHODS: The study included 40 post HCV-Hepatocellular carcinoma patients, 40 chronic HCV patients divided into 2 subgroups, 20 cirrhotic patients and 20 non-cirrhotic patients, and 40 apparently healthy subjects as a control group. Gene expression analysis for studied miRNAs was done using quantitative SYBR Green reverse-transcription Real-Time polymerase chain reaction (PCR). RESULTS: We found that Let-7a-1 gene expression was significantly downregulated in the serum of HCV-HCC patients than in HCV non HCC cirrhotic group and was significantly upregulated in the serum of liver cirrhosis patients than HCV non-cirrhotic group. miR-143 and miR-145 expressions were significantly downregulated in the serum of HCC patients than in control group and miR-143 was significantly downregulated in the serum of non-cirrhotic HCV patients than in control group. CONCLUSION: The downregulation of serum let-7-a1, miR-143, and miR-145 gene expression may exhibit significant influence on the development of HCC in chronic HCV Egyptian patients and can be used as biomarkers for HCC diagnosis.
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Urinary and Genetic Biomonitoring of Polycyclic Aromatic Hydrocarbons in Egyptian Coke Oven Workers: Associations between Exposure, Effect, and Carcinogenic Risk Assessment.

BACKGROUND: Coke oven workers are exposed to polycyclic aromatic hydrocarbons (PAHs) with possible genotoxicity and carcinogenicity. Metabolizing enzymes genes and DNA repair genes are suspected to be correlated with the level of DNA damage. They may contribute to variable individual sensitivity to DNA damage induced by PAHs exposure at workplace. OBJECTIVE: To investigate the relationship between biomarkers of PAHs: 1-hydroxypyrene (1-OHP), DNA adducts, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in coke oven workers, and to assess the role of cytochrome P2E1 (CYP2E1) gene expression and DNA repairing gene (XRCC1) polymorphism in detecting workers at risk. METHODS: 85 exposed workers and 85 unexposed controls were enrolled into this study. Urinary 1-OHP, 8-OHdG, and BPDE-DNA adduct were measured. CYP2E1 gene expression and genotyping of XRCC1 399 Arg/Gln were evaluated by real-time PCR. RESULTS: The median urinary 1-OHP levels (6.3 µmol/mol creatinine), urinary 8-OHdG (7.9 ng/mg creatinine), DNA adducts (6.7 ng/µg DNA) in the exposed group were significantly higher than those in the unexposed group. Carriers of the variant allele (Gln) of XRCC1 had the highest levels of 1-OHP, DNA adducts and 8-OHdG, and the lowest level of CYP2E1 gene expression. In exposed workers, significant positive correlations were found between 1-OHP level and each of the work duration, 8-OHdG, and DNA adducts levels. There was a significant negative correlation between 1-OHP level and CYP2E1 gene expression. Work duration and CYP2E1 gene expression were predictors of DNA adducts level; 1-OHP level and work duration were predictors of urinary 8-OHdG level. CONCLUSION: Workers with higher exposure to PAH were more prone to oxidative DNA damage and cancer development. DNA adducts level reflects the balance between their production by CYP2E1 and elimination by XRCC1 gene.