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Importance of Prolidase Enzyme Activity and Serum Cytokeratin 18 Levels for Differential Diagnosis between Asymptomatic Hepatitis B Carriers and HBeAg Negative Chronic Hepatitis B Patients

Background: In this study, it was aimed to evaluate the relationship between the severity of necroinflammation in the liver and the stage of fibrosis and the serum levels of Serum Prolidase Activity (SPA) and Cytokeratin (CK)-18 in patients with active Chronic Hepatitis B (CHB) and asymptomatic Hepatitis B Virus (HBV) carriers. Methods: Biochemical analyses, serological parameters associated with HBV and serum prolidase activity and CK-18 levels were measured in asymptomatic HBV carriers (n=65), active CHB patients (n=60) and healthy controls (n=27). Liver biopsies were performed on asymptomatic HBV carriers and active CHB patients. Findings: SPA level was significantly higher in active CHB patients (819.92 ± 123.74 IU/L) compared to asymptomatic HBV carriers (732.99 ± 124.70 IU/L) and was higher in asymptomatic HBV carriers compared to healthy controls (529.4 ± 74.73 IU/L) (p=0.001). The diagnostic cut-off value of SPA level was found 751.15 U/L. When this cut-off value was taken to differentiate HBe-Ag negative CHB in asymptomatic HBV carriers, sensitivity and specificity of efficacy were 72% and 63% respectively (c-statistics: 0.707). A strong positive correlation was observed between serum prolidase level and the severity of fibrosis in asymptomatic HBV carriers (r=0.603, p=0.000). A positive correlation was determined between SPA level and Histological Activity Index (HAI) scores in patients with active CHB and asymptomatic HBV carriers. The serum CK-18 levels were significantly lower in the healthy control group when compared to the asymptomatic HBV carriers and active CHB patients (p=0.001). Conclusion: Prolidase enzyme may be beneficial in differentiating asymptomatic HBV carriers from HBeAg-negative CHB patients when used in combination with ALT and HBV-DNA levels.

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Liver Fibrosis Conventional and Molecular Imaging Diagnosis Update

Liver fibrosis is a serious, life-threatening disease with high morbidity and mortality that result from diverse causes. Liver biopsy, considered the "gold standard" to diagnose, grade, and stage liver fibrosis, has limitations in terms of invasiveness, cost, sampling variability, inter-observer variability, and the dynamic process of fibrosis. Compelling evidence has demonstrated that all stages of fibrosis are reversible if the injury is removed. There is a clear need for safe, effective, and reliable non-invasive assessment modalities to determine liver fibrosis in order to manage it precisely in personalized medicine. However, conventional imaging methods used to assess morphological and structural changes related to liver fibrosis, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), are only useful in assessing advanced liver disease, including cirrhosis. Functional imaging techniques, including MR elastography (MRE), US elastography, and CT perfusion are useful for assessing moderate to advanced liver fibrosis. MRE is considered the most accurate noninvasive imaging technique, and US elastography is currently the most widely used noninvasive means. However, these modalities are less accurate in early-stage liver fibrosis and some factors affect the accuracy of these techniques. Molecular imaging is a target-specific imaging mechanism that has the potential to accurately diagnose early-stage liver fibrosis. We provide an overview of recent advances in molecular imaging for the diagnosis and staging of liver fibrosis which will enable clinicians to monitor the progression of disease and potentially reverse liver fibrosis. We compare the promising technologies with conventional and functional imaging and assess the utility of molecular imaging in precision and personalized clinical medicine in the early stages of liver fibrosis.

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Tripartite Motif Cofactors, a Novel Gene Target for Liver Cancer via Regulating the Immune Cells and Gut Microbiome: A Review

TRIM, a multi-domain protein associated with N-terminal ring finger E3 ligase and C-terminal plant homeodomain/ bromodomain PHD chromatin interacting module, N-terminal ring finger known as ring B-boxes and coiled-coil RBCC domain with structure that underscores biochemical reaction which requires enzymes like E1, E2 and E3 of which E3 serves as receptor recognition for target proteins. Most TRIM proteins are E3 ligases in the ubiquitination cascade that translated in diverse physiological and biological processes such as differentiation, growth, transcription and oncogenesis. Implicated in pathological processes from Mendelian inherited disorders, cellular (plethora) processes like cell cycle regulation, innate immune response and apoptosis to cancer. Genetic factors are at high risk and contributed between 30%-50% disease prevalence like obesity, cirrhosis. TRIM28 (TIF1β), TRIM24 (TIF1α), TRIM33 (TIF1γ) are cofactors of tripartite motif TRIM subfamily protein, distinct transcriptional factors that correlate with each other and interact with other proteins both in functional and physical in cancer disease. Studies have shown that TRIM protein is a regulator in inflammatory, infectious and cancer diseases. This review focused on tripartite genes as a liver cancer target via regulating immune cells and the gut microbiome. More on research so far, disease development, progression and influence. Considering the incident rate and progression, genetic involvement remain challenging thus needs more insight on prognosis that will potentiate clinical effect with lesser adverse events and recurrences that will benefit the patients.

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Quantification of Hepatic Lipid Using 7.0T Proton Magnetic Resonance Spectroscopy and Computed Tomography in Mild Alcoholic Steatotic Mice.

Background:In vivo proton magnetic resonance spectroscopy (1H MRS) has been used to semi-quantify hepatic lipids in preclinical and clinical studies of fatty liver disease. Quantifying absolute amount of liver lipids utilizing 1H MRS and computerized tomography (CT) is essential to accurately interpret hepatic steatosis.Purpose:To establish reliable parameters to convert relative hepatic lipid levels obtained by 1H-MRS and liver volumes by CT to the absolute amount of liver lipids in a mild hepatic steatosis, and to determinate the correlation between these absolute liver lipids with liver triglyceride (TG) and cholesterol (Chol) measured by biochemistry assays.Methods:Mild steatosis was induced in mice by a 3 week ethanol diet containing standard lipids. Evaporated liver water was measured after baking liver tissues and volume of liver was measured using water displacement. 1H MRS semiquantitation of hepatic lipids and CT measurement of liver volume were performed and then used to calculate amount of liver lipids. These data were compared with liver TG and Chol.Results:Percentage of liver water and liver density were persistent in two groups and were used to convert the percentage of liver lipids to liver water by 1H-MRS to the absolute amount of liver lipids per gram of liver or per milliliter of CT volume. Using 1H-MRS and biochemical assays, an increase of liver lipids was confirmed in mild steatosis mice compared to controls (P<0.01). The amounts of imaging detected liver lipids were strongly correlated to liver TG and Chol measured by biochemical assays in mild steatosis mice.Conclusion:1H MRS and CT liver imaging techniques are able to quantify absolute hepatic lipid levels utilizing relative persistent parameters percentage of liver water and liver density in a preclinical mild steatosis setting.

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