Occult HCV infection in liver transplanted patients: frequency and consequences.

Aim of the study: Occult hepatitis C virus (HCV) infection (OCI) is a potential source of relapse after liver transplantation with subsequent graft damage. The aim of the study was to detect OCI in patients with living donor liver transplantation (LDLT) who achieved sustained virological response (SVR) after sofosbuvir-based antiviral treatment, and to detect risk factors associated with the development of OCI as well as to determine the effect of direct acting antiviral (DAA) therapy after liver transplantation. Material and methods: 41 patients with living donor liver transplantation who did not receive DAAs before with recurrent HCV infection who achieved a SVR with sofosbuvir-based therapy for 12-24 weeks were recruited. These patients were tested for OCI by HCV-RNA in peripheral blood mononuclear cells (PBMNCs). Those patients with OCI were followed up every 6 months with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum HCV-RNA by PCR for 2 years. Results: 92.7% of treated patients achieved HCV SVR 12 weeks. OCI was detected in 4 patients. After follow-up for 18 months, 3 patients continued to have OCI, but one patient presented with progressive elevation of liver enzymes and developed overt HCV infection with positive HCV-RNA PCR in the serum. This patient was retreated with sofosbuvir 400 mg + ledipasvir 90 mg for 12 weeks with resultant negative HCV-RNA PCR in both serum and PBMNCs in addition to normalization of liver enzymes. Conclusions: Occult HCV infection is a potential source of HCV relapse after liver transplantation which should be investigated for in PBMNCs or liver biopsy.

The Role of Diffusion-Weighted MRI and Apparent Diffusion Coefficient in Assessment of Diabetic Kidney Disease: Preliminary Experience Study.

BACKGROUND: Diabetic kidney disease is the most common cause of ESRD. There is poor correlation between the degree of renal fibrosis and current screening markers. A noninvasive imaging technique is needed to assess the degree of structural changes in the kidney. The aim of this study was to assess the role of apparent diffusion coefficient (ADC) in the diagnosis of diabetic kidney disease. Forty adult diabetic patients with chronic kidney disease as well as 20 age- and sex-matched adult healthy controls were recruited from Nephrology Department of our University Hospital. All patients underwent renal MR-DWI and ADC mapping on a 1.5-T scanner (Philips Achieva) using phased array body coil. RESULTS: Among the studied 40 diabetic patients, five groups of patients were resulted 8 patients for each and the ADC values were inversely correlated with advancement in renal parenchymal affection, ie, in late stages of the disease the ADC values were lower than in early stages. The mean ADC values of renal parenchyma in patients with diabetic kidney disease were considerably lower than that of healthy controls with normal renal function (2.1±0.3x10-3 mm2/s vs 2.4±0.1x10-3 mm2/s with p<0.001). CONCLUSION: ADC value is a possible noninvasive technique in evaluating the stage of renal dysfunction with assessment of disease progression.

Osteocalcin and vascular calcification in hemodialysis patients: an observational cohort study.

BACKGROUND: Vascular calcification contributes to morbidity and mortality in patients with ESRD on maintenance hemodialysis. AIMS: To study the relationship between osteocalcin and vascular calcification. METHODS: 160 patients with ESRD on maintenance hemodialysis and 60 age-and sex-matched healthy controls were recruited. Serum vitamin K2 and osteocalcin both intact and undercarboxylated were measured. Transthoracic echocardiography was done for valvular calcification and thickening, and carotid duplex was done for carotid intimal medial calcification and thickening. RESULTS: Hemodialysis patients have higher median serum vitamin K2 (p < 0.001), higher undercarboxylated osteocalcin (p < 0.001). Only older age, duration of hypertension, and duration of established cardiovascular disease are associated with carotid media-intimal calcification. Old age is a strong predictor of carotid media intimal thickening. Female sex is associated with a valvular thickening. CONCLUSIONS: Functional vitamin K deficiency is present in maintenance hemodialysis patients and serum osteocalcin is not associated with cardiovascular calcification.

Value of the cell cycle arrest biomarkers in the diagnosis of pregnancy-related acute kidney injury.

BACKGROUND: Pregnancy-related acute kidney injury (PRAKI) is still a common serious problem in developing countries. Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor metalloproteinases-2 (TIMP-2) can identify critically ill patients at risk for the development of severe AKI. AIM: To identify main causes and timing of PRAKI and to study the G1 cell cycle arrest biomarkers in cases diagnosed with (PRAKI) as a diagnostic tool. METHODS: 80 pregnant women diagnosed with PRAKI were recruited from a single hospital as well as 30 age-matched pregnant women with normal pregnancy participated in the present study. A urine specimen was collected from all study participants with established AKI within 24 h of ICU admission to measure [TIMP-2]*[IGFBP7]. RESULTS: The incidence of PRAKI was 1.1%. The most common cause of PRAKI is pre-eclampsia/eclampsia spectrum (61%). Most of the cases occur in the third trimester (60%) and postpartum period (23%). At a cutoff 0.33 ng/ml, the estimated sensitivity and specificity of urinary [TIMP-2]*[IGFBP7] in predicting PRAKI is 100% (95% CI) with NPV and PPV are 100%. CONCLUSION: Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker in the diagnosis of PRAKI.

Serum and ascitic fluid interleukin-17 in spontaneous bacterial peritonitis in Egyptian patients with HCV-related liver cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a potentially lethal complication of ascites. The inflammatory response is very intense in case of SBP despite low concentration of bacteria in the ascitic fluid with IL-17A overproduced by intestinal Paneth cells and may have role in host immune defense and inflammatory response. AIMS: To study the diagnostic performance of serum and ascitic fluid IL-17A as a marker of SBP and its correlation with renal function. METHODS: 120 cirrhotic patients including 80 patients with HCV-induced cirrhotic ascites but not with SBP and 40 patients with HCV-induced cirrhotic ascites with SBP were recruited. Serum and ascitic fluid IL17A were measured before and after treatment. RESULTS: The mean serum and ascitic fluid levels of IL-17 in cirrhotic patients with SBP were significantly higher than in patients with cirrhosis without SBP (p < 0.001). Also, we found significant decline in both serum and ascitic fluid IL17 levels with successful treatment of SBP (p < 0.001). The sensitivity and specificity of serum IL17 was 100 % when using 92 pg/mL as cutoff. Meanwhile, sensitivity and specificity of ascitic fluid IL-17were 100 % when using 132 pg/mL as cutoff. CONCLUSIONS: IL-17 could be used as a possible diagnostic biomarker for SBP especially in culture negative and non-neutrocytic SBP and in monitoring therapeutic response. Also, it was shown to be related to hepatic and renal functions deterioration.

Signaling pathways modulated by fish oil in salt-sensitive hypertension.

Although many studies have indicated that fish oil (FO) improves cardiovascular risk factors and reduces histopathological manifestations of injury in experimental renal injury models, potential mechanisms underlying this protective effect have not been adequately defined. The objective of this study was to identify potential signaling pathways that confer protection in the Dahl rat model of salt-sensitive hypertension. Male Dahl salt-sensitive rats (n = 10/group) were provided with formulated diets containing 8% NaCl, 20% protein, and 25% FO or 25% corn oil (CO) for 28 days. FO reduced blood pressure (-11% at 4 wk; P < 0.05), urine protein excretion (-45% at 4 wk; P < 0.05), plasma cholesterol and triglyceride levels (-54%, P < 0.001; and -58%, P < 0.05), and histopathological manifestations of renal injury, including vascular hypertrophy, segmental and global glomerular sclerosis, interstitial fibrosis, and tubular atrophy. Interstitial inflammation was significantly reduced by FO (-32%; P < 0.001), as assessed by quantitative analysis of ED1-positive cells in sections of the renal cortex. FO reduced tubulointerstitial proliferative activity, as assessed by Western blot analysis of cortical homogenates for PCNA (-51%; P < 0.01) and quantitative analysis of Mib-1-stained sections of the renal cortex (-42%; P < 0.001). Decreased proliferative activity was associated with reduced phospho-ERK expression (-37%; P < 0.005) and NF-kappaB activation (-42%; P < 0.05). FO reduced cyclooxygenase (COX)-2 expression (-63%; P < 0.01) and membrane translocation of the NADPH oxidase subunits p47(phox) and p67(phox) (-26 and -34%; P < 0.05). We propose that FO ameliorates renal injury in Dahl salt-sensitive rats through the inhibition of ERK, decreased NF-kappaB activation, inhibition of COX-2 expression, and decreased NADPH oxidase activation.