Decrease of Pericytes is Associated With Liver Disease Caused by Ligature-Induced Periodontitis in Rats

Background: Damage caused by periodontitis not only affects periodontal tissues, but also increases the severity of various illnesses such as rheumatoid arthritis, diabetes, and liver diseases. The aim of this study is to investigate the association between induced periodontitis and damage caused through its systemic effects on the liver. Methods: Twenty rats were divided into two groups: control and periodontitis. The following parameters were evaluated: gingival bleeding index (GBI), probing depth (PD), myeloperoxidase (MPO) activity, alveolar bone loss (ABL) for periodontal tissues; histopathologic examination of gingival and liver tissues; immunohistochemistry to cells positive for neural/glial antigen 2 (NG2) expressed in hepatic pericytes, glutathione (GSH), and malondialdehyde (MDA) concentrations in liver; and serum levels of alanine aminotransferase and aspartate aminotransferase. Results: GBI, PD, MPO, ABL, and histopathologic examinations demonstrated the development of periodontitis. There was a significant increase in microvesicular steatosis accompanied by a marked reduction in NG2+ pericytes in the periodontitis group compared with the control group. The periodontitis group had significantly lower GSH and higher MDA concentration in the liver compared with the control group. Conclusions: The present study results link the systemic effects of induced periodontitis with changes in hepatic tissues such as microvesicular steatosis, likely caused by an increase in oxidative stress and lipid peroxidation. The findings from the present study implicate an association between a decrease of pericytes and liver disease caused by ligature-induced periodontitis in rat

Assessment of clinically significant portal hypertension by two‐dimensional shear wave elastography

Background and aims: To evaluate two-dimensional shear wave elastography (2DSWE) in parallel with transient elastography (TE) for diagnosing clinically significant portal hypertension (CSPH) and high-risk varices (HRV) in patients with chronic liver disease. Patients and methods: Consecutive patients with suspicion of compensated advanced chronic liver disease (cACLD) [liver stiffness measurement (LSM) ≥ 10 kPa by TE, or morphological signs suggestive of cACLD on imaging], with no history of liver decompensation, underwent hepatic venous pressure gradient (HVPG) measurement, transjugular liver biopsy and esophagogastroduodenoscopy, which served as the reference methods for diagnosing CSPH, cACLD and HRV. All patients underwent LSM and spleen stiffness measurements (SSM) by 2DSWE and TE. Results: Seventy-six (76) patients were included (78% men, mean age 62 years, body mass index 28.3 kg/m2 , 36.8% alcoholic, 30.3% non-alcoholic fatty liver disease, 14.5% viral hepatitis). Of them, 80.3%, 69.7%, 52.6% and 22.4% had cACLD, cirrhosis, CSPH and HRV respectively. LSM performed better than SSM in diagnosing CSPH and HRV. For CSPH, AUROCs (0.926 vs. 0.866), optimal cut-offs (20.1 vs. 20.2 kPa) and sensitivity/specificity (80.5%/94.3% vs. 77.5% /86.1%) were comparable for 2DSWE and TE. Ruling-out of CSPH by 2DSWE (LSM at cut-off with ≥90% sensitivity (13.5 kPa) and platelets ≥ 150 x 109 /L) performed comparably to TE, with 1/24 cases falsely classified as negative. For HRV, AUROCs were similar (0.875 2DSWE, 0.851 TE) with similar optimal LSM cut-offs enabling 100% sensitivity and ruling-out HRV. Conclusion: Liver stiffness measurement by 2DSWE appears to perform equally well as TE for diagnosing CSPH and ruling-out HRV in compensated chronic liver disease

Metabolism of Direct-acting Antiviral Agents (DAAs) in Hepatitis C Therapy: A Review of the Literature

Background: Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease, with chronically infected making up approximately 1% of the global population. Of those infected, 70% (55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death. Objective: Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct- acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects. Methods: We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug-drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation. Results: We present a comprehensive overview of specific direct-acting antiviral metabolism and drug-drug interaction issues in different settings. Conclusion: Despite its complex pharmacokinetics and the possibility of drug-drug interactions, direct-acting antivirals are highly efficacious in providing viral clearance, which is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with tight control of immunosuppressive therapy

Accuracy of Controlled Attenuation Parameter and Liver Stiffness Measurement in Patients with Non-alcoholic Fatty Liver Disease

We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP >= 345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F >= F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (beta = 2.6, p < 0.001) as a positive predictor and lobular inflammation (beta = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis