Evaluation of the effect of direct-acting antiviral agents on melatonin level and lipid peroxidation in chronic hepatitis C patients.

Background: Oxidative stress and its end products, such as malondialdehyde (MDA) play a leading role in the pathogenesis of hepatitis C. Melatonin is a hormone that helps regulate circadian rhythms, which likely play a role in infectious diseases in terms of susceptibility, clinical expression, and outcome. Objective: The present study was conducted to assess serum malondialdehyde and melatonin levels in patients with chronic hepatitis C infection before and after the intake of direct-acting antivirals. Method: Forty hepatitis C patients were the subjects of this study. While ten healthy volunteers who matched in age and socioeconomic status served as the control subjects. Malondialdehyde and melatonin were assayed in the serum of the three groups, and the results were statistically analyzed. Results: Hepatitis C patients had significantly higher malondialdehyde (p < 0.001) but significantly lower melatonin (p < 0.001) as compared to the healthy controls. After 12 weeks of treatment with direct-acting antivirals, the malondialdehyde level decreased significantly (p < 0.001) and the melatonin level increased significantly (p < 0.001). A significant negative correlation between malondialdehyde and melatonin was observed. Conclusion: The present findings suggest that treatment of hepatitis C patients with Direct-acting antivirals improves liver function parameters and antioxidant profiles.

Treatment of Hepatitis C Cirrhotic Patients With Directly Acting Antivirals: A Multicenter Study.

BACKGROUND: With the introduction of sofosbuvir-based regimens, high cure rates and decreased duration has been achieved. Several studies showed variances in SVR rates between different genotypes, with lower rates of SVR among cirrhotic patients. The aim of our study was to assess the safety and effectiveness of sofosbuvir-based antiviral regimens for the treatment of HCVinfected Egyptian cirrhotic patients. METHODS: This was a retrospective, observational, and comparative study. A total of nine hundred and forty-six cirrhotic patients with chronic HCV genotype 4 infection, who were eligible for direct acting drugs (DAAs) therapy, were enrolled. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by SVR at 12 weeks after discontinuation of therapy (SVR12), and the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. RESULTS: Among the 946 patients enrolled in the study, 527 patients (55.7%) were males and 419 patients (44.3%) were females with a mean age of 54.00±8.88 years. 20.2% were diabetics and 19.1% were hypertensive. Patients were classified according to Child-Pugh classifications; 818 patients (86.46%) were Child-Pugh class A cirrhosis, while 28 patients (13.53%) were Child-Pugh class B cirrhosis. The SVR12 rate was 96.93% (917 /946). Treatment response in the Child-Pugh class A cirrhosis was 794 (97%) after 12 weeks, while treatment response in the Child-Pugh class B cirrhosis was 123 (96%). Mild side effects were observed in 76 patients. CONCLUSIONS: Sofosbuvir based regimens were effective and safe in the treatment of cirrhotic patients with chronic hepatitis C genotype 4.

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.

Comparative Evaluation of Colon Cancer Specific Antigen-2 Test and Chromocolonoscopy for Early Detection of Egyptian Patients with Colorectal Cancer.

BACKGROUND: Effective screening of colorectal cancer (CRC) in early stage could reduce the advancement of CRC and therefore mortality. Effective screening is based on either stool dependent tests or colon dependent examination. AIMS: The aim of the study was a comparative evaluation of chromocolonoscopy and Colon Cancer-Specific Antigen-2 test for early detection of colorectal cancer in Egyptian patients. METHODS: This case control study was carried out on 55 patients classified into 3 groups: Group I consisted of twenty patients with precancerous lesions detected by colonoscopy, Group II consisted of twenty patients diagnosed with colorectal cancer and Group III consisted of fifteen individuals (who underwent colonoscopy for other indications) as a control group. All the subjects were subjected to measure occult blood in the stool, measurement of Colon Cancer-Specific Antigen-2 level in serum and tissue and chromo colonoscopy using Indigo Carmine stain. RESULTS: In group II, there was a statistically significant increase in CCSA2 in serum as compared to the other 2 groups. Cutoff >11.3 CCSA2 in serum showed 65% sensitivity, 85% specificity, 81.2% PPV, 70.8% NPV and 70.3% accuracy in the differentiation of group II with cancer colon from group I with premalignant colonic lesions. A cutoff > 9.1 CCSA2 in serum showed 95% sensitivity, 46.67% specificity, 70.4% PPV, 87.5% NPV and 73.5% accuracy in differentiating group II with cancer colon from normal controls (group III). CONCLUSION: CCSA-2 level in serum was significantly higher in cancer colon. Chromoendoscopy has a role in the detection of polyps, both neoplastic and non-neoplastic.

Study of Serum Soluble Programmed Death Ligand 1 as a Prognostic Factor in Hepatocellular Carcinoma in Egyptian Patients.

BACKGROUND: The expression of programmed cell death ligands on tumor cells has a role in the suppression of antitumor immunity, resulting in tumor immune evasion. OBJECTIVE: In this study, we evaluated the prognostic value of the soluble form of programmed death-ligand1 (sPD-L1) in Egyptian hepatocellular carcinoma (HCC) patients. METHODS: This prospective cohort study was performed between November 2016 to November 2018 on 85 individuals (25 HCC patients, 25 HCC with vascular invasion and/or extrahepatic metastasis, 25 patients with liver cirrhosis, 10 healthy controls). The levels of sPD-L1 were determined in all subjects and compared in different groups and stages of cirrhosis and HCC. The association between sPD-L1 levels and overall survival (OS) was assessed. RESULTS: Significant statistical difference in sPD-L1 was detected between different study groups. The cut-off value for normal sPD-L1 was defined by high sPD-L1 levels determined in a healthy control cohort. It was 2.522 ng/ml. In HCC patients, cut-off value was 7.42 ng/ml (sensitivity 88%, specificity 100%). In HCC with vascular invasion or metastasis, cut-off value was 9.62 ng/ml (sensitivity 88%, specificity 88%). Patients with high serum sPD-L1 or serum bilirubin concentrations had an increased risk of mortality. CONCLUSION: High sPD-L1 level could be a possible prognostic indicator for a poor outcome in liver cirrhosis and HCC patients. The predictive value of sPD-L1 levels for a successful anti- PD1/PD-L1 therapy should be investigated in the future.

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.

Copeptin as a novel marker predicting prognosis of liver cirrhosis and its major complications.

OBJECTIVES: The aim of the work was to assess the level of copeptin as a surrogate marker predicting the severity of liver diseases and its major complications. PATIENTS AND METHODS: This was a cross-sectional study that included 40 patients and 10 controls and was performed in Tanta University Hospital between June 2016 and November 2016. The studied cases were divided into five groups: group I (10 patients): compensated cirrhosis; group II (10 patients): cirrhosis with gastrointestinal hemorrhage due to portal hypertension; group III (10 patients): cirrhosis with hepatorenal syndrome; group IV (10 patients): cirrhosis with liver cell failure; and group V (10 controls): normal healthy individuals. RESULTS: Regarding serum copeptin in the studied groups, copeptin showed a significant decrease in group I vs group II' group I vs group III, and group I vs group IV; and there was a significant increase in group II vs group III' group II vs group IV' group II vs control' group III vs control, and group IV vs control. No significance was detected between group I vs control and group III vs group IV. CONCLUSIONS: Copeptin is a novel marker for the determination of prognosis of liver cirrhosis. There is significant association between serum level of copeptin and complications of liver cirrhosis.

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.

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.

Role of low-molecular-weight heparins in prevention of thromboembolic complication after transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). This is the first clinical study to evaluate the role of low-molecular-weight heparins (LMWHs) with TACE in HCC for the prevention of thromboembolism complications (PVT). PATIENTS AND METHODS: This study was carried out on 40 patients with HCC requiring TACE who presented to the Tropical Medicine Department, Tanta University and Interventional Radiology Department of Ain-Shams University Hospitals starting from April 2015. Patients were divided in two groups: group I included 20 patients with HCC treated by TACE only. Group II included 20 patients with HCC treated by TACE and an adjuvant dose of LMWH. Radiological assessment of efficacy of procedure and detection of PVT as a complication was performed using ultrasound abdomen and pelvis and triphasic spiral computed tomography with contrast. RESULTS: This study was carried out on 40 patients with HCC requiring TACE who presented to the Tropical Medicine Department of Tanta University and Interventional Radiology Department of Ain-Shams University Hospitals. The incidence of PVT after TACE was higher in group I than group II, with seven cases in group I and only one case in group II. CONCLUSION: LMWH with TACE in HCC is strongly recommended for prevention of thromboembolism complications (PVT). However, larger randomized-controlled studies are needed to confirm these obvious findings.