Role of Both Protein C and Antithrombin III as Predictors of Stage of Liver Disease in Chronic Viral Hepatitis B or C Infected Patients.

BACKGROUND & AIMS: Chronic liver disease is characterized by complex hemostatic disorders because the liver is the site where most of the coagulation factors and their inhibitors are synthesized. The aim of this study was the evaluation of protein C and antithrombin III in different stages of chronic hepatitis B and C and to determine their possible role as markers of liver cell damage in different clinical stages. METHODS: The study included 60 subjects who were subdivided into 4 groups: (Group I): 15 patients diagnosed as chronic viral hepatitis B or C, (Group II): 15 patients with compensated liver cirrhosis, (Group III): 15 patients with decompensated liver cirrhosis, and (Group IV) (control group): 15 healthy individuals. History taking, clinical examination and abdominal ultrasonography were made for all subjects. Investigations were done in the form of liver function tests (ALT, AST, ALP, serum bilirubin, and serum albumin), PT, PTT, CBC. Plasma levels of Antithrombin III & protein C were estimated by automated Stago compact coagulation analyzer. RESULTS: In all patient groups, the mean value of Protein C showed significant decrease when compared to control group, mean value of antithrombin III showed a significant decrease in compensated and decompensated subjects when compared to chronic hepatitis and control groups. Antithrombin III and protein C showed a significant negative correlation with (ALT, AST, PT, PTT, INR). However, this correlation was positive with Albumin. CONCLUSION: Antithrombin III and protein C are natural anticoagulants and can be considered as markers of different stages of chronic liver disease. This is supported further by the comparison between the levels of these parameters and clinical stages of liver disease. Protein C is more sensitive than ATIII as a marker of hepatocellular damage.

Clinical significance of fibroblast growth factor-23 and soluble alpha klotho in different stages of chronic kidney disease.

Most chronic kidney disease (CKD) biomarkers in the current clinical use are not sensitive enough and cannot be used to identify the early stage of the disease. Klotho is a transmembrane protein predominantly expressed in the renal tubules and implicated in managing phosphate homeostasis, together with fibroblast growth factor-23 (FGF-23); a bone-derived protein that increases urinary phosphate excretion. The present study was carried out on 50 patients CKD with different etiologies referred to the Internal Medicine Department and Out Patient Clinic of Tanta University Hospitals and 30 apparently healthy individuals of matched age and sex as a control group. They were subjected to the following assessment: detailed history taking, careful clinical examination, and laboratory investigations, including urea, creatinine, estimated glomerular filtration rate (eGFR), serum electrolytes, urinary albumin, urinary phosphorus (U-Ph), and specific laboratory tests for: Alpha Klotho (α-klotho) and FGF-23 by using ELISA technique. The present study shows that the mean value of serum creatinine, urea, phosphorus, urinary albumin, and FGF-23 were significantly increased, whereas there was a significant decrease in the mean value of eGFR, calcium, and U-Ph in the patients with CKD when compared with control group. Plasma level of serum α-klotho is significantly decreased in all patients with CKD when compared to the control group and there was a significant positive correlation between serum α-klotho level and eGFR, serum calcium level and U-Ph level. Plasma level of serum α-klotho is significantly decreased in all patients with CKD and serum α-klotho can be used as a good marker for early diagnosis and staging of CKD.

Overexpression of Hepassocin in Diabetic Patients with Nonalcoholic Fatty Liver Disease May Facilitate Increased Hepatic Lipid Accumulation.

BACKGROUND & AIMS: Insulin resistance is the real determinant of both Nonalcoholic fatty liver disease (NAFLD) and diabetes, and can facilitate the accumulation of triglycerides in the liver. Overexpression of hepassocin (HPS) increased the accumulation of hepatic fat and NAFLD activity scores (NAS) in mice. The aim of this study was to investigate the relationship between hepassocin and steatosis of the liver in diabetic patients with or without NAFLD in humans. METHODS: The study enrolled 60 patients plus 20 healthy controls that were divided into 4 groups: Group I: included 20 patients who were diagnosed as diabetes mellitus type 2, Group II: included 20 patients who were diagnosed as nonalcoholic fatty liver disease (NAFLD), Group III: included 20 patients who were diagnosed as diabetes type 2 and NAFLD, and Group IV (control group): included 20 healthy person or controls who were matched in age and sex with patients group. All patients and controls were subjected to full history taking, thorough clinical examination, laboratory investigations including measurement of serum hepassocin in peripheral blood by ELISA technique. RESULTS: There was a significant overexpression of serum hepassocin in patients with type 2 diabetes and NAFLD patients (Group 3) more than diabetic patients (Group 1) and even more than non-alcoholic fatty liver disease (Group 2). CONCLUSION: This study provides evidence that increased HPS may facilitate increased hepatic lipid accumulation with NAFLD and type 2 diabetes.

Prevalence of occult hepatitis C virus among hemodialysis patients in Tanta university hospitals: a single-center study.

Occult hepatitis C virus infection (OCI) is a newly defined type of infection by the chronic hepatitis virus (HCV) distinguished by the existence of HCV RNA in liver tissue and/or peripheral blood mononuclear cells (PBMCs) in patients whose plasma are devoid of both positive serology and RNA. Patients on maintenance hemodialysis evince a higher HCV prevalence than the general population due to high nosocomial transmission by the dialysis units. We investigated the prevalence of occult HCV infection in patients attending our university hemodialysis centers for maintenance hemodialysis. Sixty-two CHD patients negative for serum HCV tests were enrolled in the study. PMNCs were tested by real-time PCR for the presence of HCV RNA. For the 62 patients, the average duration since starting dialysis was 32.7 months and the mean (SD) alanine transaminase and aspartate transaminase were 25.74 ± 9.75 and 28.81 ± 11.32 IU/l, respectively. Out of the 62 CHD patients negative for serum anti-HCV and HCV RNA patients, only three (4.84%) were shown to have HCV RNA in their PBMCs implying the diagnosis of OCI; their viral load range was 1.24-4.15 IU/ml. All three OCI-proven patients gave no history of hepatic disease. In this study, we found that patients considered to be free of HCV can have HCV replicating in their PBMCs. This awareness points to the possibility of HCV being transmitted from apparently uninfected persons. A positive HCV RNA detection in PBMCs is dependable in determining OCI among high-risk subjects particularly when a liver biopsy is not an option. HCV transmission can occur through hemodialysis units signaling incorrect application of infection control measures in our Egyptian dialysis units. Additional studies on hemodialysis patients are necessary to realize the true magnitude of OCI among this patient group and to highlight the importance of incorporating HCV viral assays in PBMCs into the diagnostic algorithm.

Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection.

BACKGROUND AND AIMS: Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection. PATIENTS AND METHODS: In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled. The patients were classified into two groups: group I included 100 patients who received single therapy with sofosbuvir plus ledipasvir for 12 weeks and group II included 100 patients who received sofosbuvir plus oral weight-based ribavirin for 24 weeks. The primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative polymerase chain reaction for HCV RNA. RESULTS: Group I patients showed statistically significant (p<0.05) higher SVR12 compared with group II patients (99% vs. 80%). There was no statistical difference (p>0.05%) between the studied groups regarding the frequencies of the side effects (26% vs. 29%). The most common adverse effects were headache, fatigue, myalgia, and cough. CONCLUSION: Sofosbuvir and ledipasvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 99% SVR for all patients who received 12 weeks of the study drugs. ClinicalTrials.gov Identifier: NCT02992457.

Nonalcoholic fatty liver disease in patients with acute ischemic stroke is associated with more severe stroke and worse outcome.

BACKGROUND: There is a paucity of data regarding the association between nonalcoholic fatty liver disease (NAFLD) and acute ischemic stroke. Stroke is largely preventable, so that knowledge of risk factors is essential to achieve reductions in the stroke rate and resulting disease burden. OBJECTIVE: The aim of the present study was to evaluate the prognostic value of NAFLD on stroke severity and outcome. METHODS: We prospectively studied 200 patients who were admitted with acute ischemic stroke between September 2013 and August 2015. Demographic and vascular risk factors were detailed for all subjects. The severity of stroke was assessed with National Institutes of Health Stroke Scale score at admission. NAFLD was defined as serum alanine aminotransferase and/or aspartate aminotransferase levels above the upper limit of normal in the absence of other causes of elevated aminotransferase levels. The outcome was assessed with the modified Rankin scale score at discharge. RESULTS: NAFLD was found in 42.5% of the study population. The prevalence of diabetes was significantly higher among patients with NAFLD than those without NAFLD (P = .001). Waist circumference was significantly higher among patients with NAFLD than those without NAFLD (P < .05). Patients with NAFLD had significantly higher glucose, Triglycerides, Low density lipoprotein, serum alanine aminotransferase and aspartate aminotransferase than those without NAFLD (P < .05 for each comparison). National Institutes of Health Stroke Scale score at admission and modified Rankin scale score at discharge were significantly higher in patients with NAFLD than those without NAFLD (P < .05 for each comparison). CONCLUSION: NAFLD was found in 42.5% of acute ischemic stroke patients. NAFLD might be associated with more severe stroke and worse outcome.