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Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited.A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure.Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe ( 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score 4 on kidney biopsy were associated with kidney failure.Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

IgA vasculitis (IgAV) is the most common type of vasculitis in children. There is a lack of consensus for management of significant IgAV nephritis (IgAVN). This study was designed to identify the most used treatment options and describe their efficacy.This is a multicenter retrospective study of children age 1-21 years with IgAVN who were managed for at least 6 months by a nephrologist. Subjects with at least microscopic hematuria and proteinuria and/or decreased kidney function were enrolled. Kidney outcome was assessed by eGFR and urine protein/creatinine (UPC) ratios at 2-4 weeks, 3, 6, and 12 months post-diagnosis.A total of 128 subjects with median age of 7 years (range 2-18) were included. Of these, 69 subjects had kidney biopsy with crescents detected in 53%. AKI (P = 0.039), nephrosis (P = 0.038), and crescents on biopsy (P = 0.013) were more likely in older patients. Patients with UPC 1 mg/mg were more likely to get a kidney biopsy (P 0.001) and to be treated with steroids ± immunosuppressive (IS) agents (P = 0.001). Sixty-six percent of patients were treated with steroids and/or IS agents for variable durations. Anti-metabolite agents were the most common IS agents used with variability in dosing and duration. At 12 months, most subjects had a normal eGFR (79%) (median 123, range 68-207 mL/min/1.73 mIS agents are frequently used in managing IgAVN associated with heavy proteinuria, nephrosis, and/or AKI. Prospective studies are needed to determine indications and needed duration of IS therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Toll-like receptor 7 (TLR7) can recognize single-stranded RNA viruses like hepatitis C virus (HCV) with subsequent induction of different interferon (IFN) types including IFN lambda (IFNL), which activate an immediate anti-viral response. However, the role of TLR7 in inflammation and fibrosis, characteristics of HCV-induced liver injury, is still controversial. The present work was designed to investigate the potential role of TLR7 and IFNL1 in chronic hepatitis C (CHC) in relation to viral replication and liver injury.Forty two treatment-naïve patients with CHC and 20 healthy subjects were enrolled in the study. TLR7 expression on peripheral blood CD14+ monocytes was studied by color flow cytometry and the frequency of TLR7+CD14+ cells was expressed as percentage of total monocyte count. Quantification of IFNL1 levels in serum was determined using enzyme-linked immunosorbant assay. Liver biopsies were examined for assessment of histological activity grade (A0-A3) and fibrosis stage (F0-F4) according to METAVIR scoring system as well as steatosis grade. Immunohistochemical staining was performed using human antibodies against TLR7 and IFNL1 and was scored semi-quantitatively (score 0-3). Hepatic expression of TLR7 and IFNL1 was further classified using a two-grade scale as low expression (score 0 or 1) and high expression (score 2 or 3).Percentages of circulating TLR7+CD14+ monocytes and serum IFNL1 levels were significantly higher in patients with CHC than in healthy controls (P = 0.025 and P 0.001 respectively) and were positively correlated with corresponding hepatic TLR7 and IFNL1 expression (P 0.001 and P = 0.010 respectively). Significantly lower peripheral blood and hepatic TLR7 expression and IFNL1 levels were found in patients with viral loads between 200,000-600,000 IU/ml and600,000 IU/ml than in those with viral load200,000 IU/ml (P 0.05), in patients with severe necroinflammation than in those with mild-to-moderate necroinflammation (P 0.05) and in patients with advanced fibrosis than in those with early fibrosis (P 0.01). Also, changes in TLR7 expression and IFNL1 production in peripheral blood and the liver were inversely correlated with serum levels of aspartate and alanine aminotransferases (P 0.05) and HCV RNA (P 0.01), histological activity grade (P 0.01) and fibrosis stage (P 0.01). By plotting receiver operating characteristics (ROC) curve, serum IFNL1 showed higher sensitivity and specificity than percentages of circulating TLR7+CD14+ monocytes in discriminating patients with CHC according to the severity of hepatic necroinflammation (area under the curve (AUC) = 0.901 vs. 0.816 respectively) and fibrosis (AUC = 0.971 vs. 0.825 respectively) at a cut-off value of 44.75 pg/ml and 10.25% respectively.TLR7 activation and IFNL1 production in CHC may play an important role in controlling viral replication and limiting hepatic inflammation and fibrosis and their downregulation may result in viral persistence and disease progression. The immunoregulatory role of TLR7-IFNL1 pathway in the pathogenesis of chronic HCV infection should be further studied. Clinical trials with a large number of patients are needed to assess the usefulness of serum IFNL1 as a potential biomarker for severity of liver injury in chronic HCV infection and other liver diseases.

Background Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwide. Early recognition of the onset of HCC would help to select more effective therapies for patients leading to a better prognosis and life span. So, the development of effective markers for the diagnosis of HCC could have an impact on HCC-related cancer mortality. MicroRNAs (miRNAs) are reported as a group of small noncoding RNAs that can function as endogenous RNA interference to regulate the expression of targeted genes. Aim To study serum miR-143 expression level in patients with hepatitis C virus (HCV)-related HCC. Patients and methods The present study was conducted on 60 participants classified into group A: 30 patients with HCV-related cirrhosis with HCC; group B: 15 patients with HCV-related cirrhosis without HCC; and group C: healthy participants as control. Expression of miR-143 in the serum of all participants was obtained in all groups. Total serum RNA was extracted with small RNA enrichment followed by reverse transcription real-time PCR. Expression of miR-143 in the serum of all participants was obtained using the comparative cycle threshold method (2–ΔΔCT) after normalization for the expression of Syn-cel-miR-39 mi script miRNA mimic as control. MiR-143 expression levels were then compared in different groups. Results The mean serum miR-143 levels were significantly higher in cirrhotic patients without and with HCC than in healthy participants (1.69±0.64, 13.0±6.23 vs. 0.56±0.29, P˂0.001, respectively) and in patients with HCC than in patients without HCC (P

Background and aims Spontaneous bacterial peritonitis (SBP) is a common bacterial infection in patients with liver cirrhosis and ascites. Cirrhotic patients frequently have vitamin D (Vit-D) deficiency. Vit-D induces the production of LL-37, an important molecule of innate immunity, in macrophages. The aim of this study is to assess Vit-D and LL-37 levels in the ascitic fluid (AF) of cirrhotic patients with SBP in comparison to patients with simple ascites. Patients and methods Forty male cirrhotic patients with ascites were included and were divided into two groups, 20 with culture-positive SBP (group I) and 20 with simple ascites (group II). AF Vit-D and LL-37 levels were measured. Results Vit-D and LL-37 levels were significantly lower in patients with SBP than those with simple ascites. In univariate analysis, the risk factors for SBP were lower platelet count, higher leukocytic count, higher serum bilirubin, lower prothrombin activity, lower serum albumin, higher Child–Pugh and model for end-stage liver diseases scores, and lower AF Vit-D and LL-37 levels, while in multivariate analysis, a lower AF Vit-D level was the only risk factor for SBP. Conclusion Patients with SBP have lower levels of AF Vit-D and LL-37 than simple ascites, where an inadequate expression of LL-37 in AF due to the low Vit-D level may increase the susceptibility to SBP.

Nonalcoholic fatty liver disease (NAFLD) is related to lifestyle practices including dietary intake and sedentary lifestyle. The common treatment is directed towards weight loss, which is usually difficult to be achieved or maintained. Therefore, a nutritional intervention program aiming at improving the metabolic health not only focusing on weight loss was conducted. Total of 110 patients referred to the hepatology outpatient clinic in the Main Alexandria University Hospital were selected based on ultrasound examination. Data about dietary intake, habits, and practices, and lifestyle practices were collected. Body composition measurements, laboratory investigations, clinical examination and measuring liver fat by ultrasound were assessed. A Mediterranean diet reduced in total carbohydrates, very low in refined sugars, rich in vegetables, moderate in fruits and low fat dairy, with more incorporation of fish, legumes, olive oil, nuts and seeds; was used for 12 weeks and different exercise advices were provided to patients. A significant reduction in the amount of liver fat, together with improvement in lipid profile, liver enzymes, blood pressure, fasting blood glucose and waist circumference were reported. The criteria of metabolic syndrome and gastrointestinal tract symptoms were improved among the majority of patients, with moderate reduction in body weight 5-6%. Liver fat content estimated by ultrasound was associated with the amount of dietary fat and carbohydrate intake, eating meals at irregular times, and unhealthy cooking methods. Nutrition intervention with Mediterranean diet has significant positive impact on metabolic health of NAFLD patients.

Background Oxaliplatin is used in adjuvant treatment of colorectal cancer and is associated with sinusoidal obstruction syndrome. Few data are available on its effects in patients in whom portal hypertension was diagnosed before cancer treatment. Objective Our aim was to investigate short- and long-term outcomes of surgery for colorectal cancer in patients with portal hypertension with or without cirrhosis, particularly regarding effects of adjuvant chemotherapy with oxaliplatin. Design and setting This was a prospective cohort study performed at an academic medical center. Patients Patients with stage II or III colorectal cancer and portal hypertension who underwent curative resection were included. Intervention All patients received adjuvant chemotherapy with oxaliplatin (FOLFOX 4) or 5-fluorouracil and leucovorin. Main outcome measures Potential predictive laboratory and clinical variables and postoperative (30-day) and long-term morbidity and mortality were recorded. Results Of 63 patients enrolled, 23 (37%) had a total of 82 postoperative complications; 5 patients (8%) died within 30 days postoperatively. Univariate analysis showed that severe portal hypertension, preoperative Child class B, low albumin, the presence of ascites, preoperative upper GI tract bleeding, and high intraoperative blood loss were linked to postoperative morbidity. Presence of postoperative infection (p = 0.004), presence of preoperative ascites (p = 0.01), high intraoperative blood loss (p = 0.02), and preoperative upper GI tract bleeding (p = 0.03) were significantly related to mortality. Of 58 patients receiving adjuvant chemotherapy, 20 received the oxaliplatin regimen and 38 received 5-fluorouracil/leucovorin without oxaliplatin. The median length of follow-up was 26 (range, 6-36) months. Kaplan-Meier analyses showed that patients who received oxaliplatin had higher cumulative incidences of newly developed esophageal varices (p = 0.002), GI tract bleeding (p = 0.02), and newly formed ascites (p = 0.03). Death occurred in 8 of 20 patients (40%) in the oxaliplatin group and in 5 of 38 patients (13%) in the 5-fluorouracil group. Kaplan-Meier estimates of mean survival time were 34.4 months (95% CI, 32.4-36.5) in the 5-fluorouracil/leucovorin group vs 29.9 months (95% CI, 26-33.7) in the oxaliplatin group, and patients receiving oxaliplatin had a significantly higher relative risk of death (HR = 2.98; 95% CI, 1.03-8.65). Cancer-specific mortality was not related to treatment type. Limitations The study was limited by the relatively small sample size and lack of randomization, which may have led to selection bias in treatment regimens. Conclusions Colorectal cancer surgery can be done safely in portal hypertensive patients with good hepatic function; however, higher mortality is expected in patients with compromised hepatic function reserve. Compared with adjuvant chemotherapy without oxaliplatin, oxaliplatin-based chemotherapy does not significantly reduce cancer-specific mortality and may increase overall morbidity and mortality. Therefore, oxaliplatin-based chemotherapy should be used with caution in patients who have portal hypertension, even in those with good liver function.

Goals Our aim was to study the efficacy and the safety of argon plasma coagulation (APC) in secondary prophylaxis against esophageal varices in view of many contraindications and side effects to β-blockers in cirrhotic patients. Background Rebleeding rates from esophageal varices after endoscopic variceal ligation (EVL) are high; thus, the current recommendation is to combine nonselective β-blockers to it, but side effects and relative contraindications to nonselective β-blockers hinder their usage or require discontinuation in 15% to 20% of the cirrhotic patients. Thus, it is important to find another combination. Study This study included all patients admitted to the Alexandria Main University Hospital during the period between April 2012 and October 2012 with variceal bleeding. After exclusions, the total number of included patients was 40. All participants were subjected to EVL and eradication of varices, and then they were randomized to either APC (group 1) or just observation (group 2). Both groups were followed up by endoscopy every 3 months for 30 months. Results During the 2.5-year follow-up, 21% of the participants in group 1 experienced esophageal variceal recurrence, but no one needed rebanding. In group 2, 68.4% of the participants experienced esophageal variceal recurrence (P=0.003) and 63.2% underwent rebanding (P Conclusions APC after esophageal variceal eradication using EVL can decrease the risk of recurrence of esophageal varices and the need for rebanding. This technique may be recommended in secondary prophylaxis against esophageal variceal bleeding in those who have contraindications, are intolerant, or are noncompliant to nonselective β-blockers.

Study background: Hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC), however, the mechanism of hepatocarcinogenesis in HCV infection is still undefined. Chemokines, which induce leukocyte migration and activate inflammatory/immune responses, have recently been implicated in the regulation of tumour growth. This work was designed to study the role of macrophage inflammatory protein-1α (MIP- 1α), a potent macrophage chemo-attractant, in the development and progression of HCV-related HCC. Methods: Thirty patients with HCV-related cirrhosis (15 patients with HCC who underwent surgical hepatic resection and 15 patients without HCC) and 15 healthy subjects were enrolled in the study. Immunohistochemical staining of HCC and adjacent non-neoplastic liver tissue was performed using antibodies against MIP-1α, CD68 [for assessment of tumour-associated macrophage (TAM) count] and CD105 [for determination of microvessel density (MVD)]. Pre-operative serum MIP-1α levels were measured using enzyme linked immunosorbant assay kit. Results: HCV-related HCCs showed significantly higher MIP-1α expression, CD68+ TAM count and CD105-MVD compared with adjacent non-neoplastic liver tissue. Serum MIP-1α levels were significantly higher in patients with and without HCC than in healthy subjects and in HCC patients than in patients without HCC. The sensitivity and specificity of serum MIP-1α in discriminating cirrhotic patients with and without HCC were 100% and 93.3% respectively at a cut-off value of 17.5 pg/ml. The MIP-1α expression in HCCs showed positive correlations with serum MIP-1α levels; tumour size, stage and histopathological grade; and intratumoural CD68+ TAM count and CD105-MVD. Moreover, CD68+ TAM count had direct correlation with CD105-MVD in HCC. Conclusion: MIP-lα plays an important role in the development and progression of HCC in chronic HCV infection, possibly through recruitment of macrophages into tumour microenvironment and fostering tumour angiogenesis. MIPlα may also serve as a potential serum biological marker and a useful therapeutic target in HCV-related HCC.

Introduction Hepatitis C virus (HCV) is a major risk factor for development of hepatocellular carcinoma (HCC), however, the mechanism of hepatocarcinogenesis in HCV infection is still undefined. Chemokines, which can induce the migration of leucocytes and activate inflammatory/immune responses, have recently been implicated in the regulation of tumour growth. Aim Therefore, the aim of the present work was to study the role of macrophage inflammatory protein-1 α/CC chemokine ligand 3 (MIP-1α/CCL3), a potent macrophage chemoattractant, in the pathogenesis of HCV-related HCC in relation to tumour progression and angiogenesis. Method 30 patients with HCV-related cirrhosis (15 patients with histologically-proven HCC and 15 patients without HCC) and 15 healthy subjects were enrolled in the study. The severity of liver disease was assessed according to Child-Pugh classification and the Model for End Stage Liver Disease (MELD) score. The tumour stage was classified using the Cancer of the Liver Italian Program (CLIP) scoring system. Histological tumour grading was performed according to the Edmondson and Steiner9s criteria and the surrounding liver tissue was examined for assessing the modified histological activity index (HAI), presence of cirrhosis and the grade of steatosis. Expressions of MIP-1α/CCL3, CD68 [a marker for tumour-associated macrophages (TAM)] and CD105 (Endoglin) [for tumour angiogenesis and determination of microvessel density (MVD)] were studied in HCC and adjacent non-neoplastic liver tissues by immunohistochemistry. Serum MIP-1α/CCL3 levels were measured using solid phase sandwich enzyme linked immunosorbant assay kit. The sensitivity and specificity of serum levels of MIP-1α/CCL3 as markers for diagnosis of HCC have been assessed by plotting a receiver-operating characteristic (ROC) curve. Results Patients with HCV-related HCCs showed significant increases in MIP-1α/CCL3 expression, CD68 + TAM count and CD105 + MVD in tumour tissues compared with adjacent non-neoplastic liver tissues (p=0.0004, p + TAM count and CD105 + MVD in HCCs (p + TAM count and CD105 + MVD in HCC tissues were positively correlated (p + TAM count and CD105 + MVD in HCCs on one hand and serum levels of aminotransferases, Child-Pugh score, MELD score and HAI and steatosis grade in the surrounding liver tissue (p>0.05). Conclusion The CC chemokine, MIP-1α/CCL3, may play an important role in the pathogenesis and progression of HCC in HCV-related liver disease, possibly, through migration of macrophages to tumour microenvironment and enhancement of angiogenesis. MIP-1α/CCL3 may also serve as a potential serum biological marker and a useful therapeutic target for HCC.

Introduction Hepatitis C virus (HCV) is a major risk factor for development of hepatocellular carcinoma (HCC), however, the mechanism of hepatocarcinogenesis in HCV infection is still undefined. Heat shock protein (HSP) 27 is a ubiquitous chaperone molecule induced in cells exposed to different stress conditions, including carcinogenesis. It also has potent anti-apoptotic properties through inhibition of caspase-3 activation. Therefore, the aim of the present work was to study the expression of HSP27 and caspase-3 in HCV-related HCCs in relation to tumour progression. Methods Twenty cirrhotic patients with HCV-related HCC were enrolled in the study. The severity of liver disease was assessed according to the Model for End Stage Liver Disease (MELD) score. Serum levels of α-fetoprotein (AFP) were measured by enzyme immunoassay kit. The tumour stage was classified using the scoring system proposed by the Cancer of the Liver Italian Program (CLIP). Histological grading of tumour s was performed according to the Edmondson and Steiner9s criteria and the surrounding liver tissue was examined for the presence of cirrhosis and steatosis. Expression of HSP27 and caspase-3 was studied in HCC and adjacent non-neoplastic liver tissues by immunohistochemistry and the staining intensity of the tumour was designated as “negative/low expression” or “high expression” if 25% of cells were positively-stained, respectively. Results HCV-related HCCs showed a significant increase in HSP27 expression and a significant decrease in caspase-3 expression as compared with adjacent non-neoplastic liver tissues (p=0.029 and p=0.040, respectively). The expression of HSP27 showed an inverse correlation with caspase-3 expression in HCC tissues (r=−0.691, p=0.001). High HSP27 expression and negative/low caspase-3 expression in HCCs were associated with significant increases in serum levels of aminotransferases, HCV RNA and AFP, MELD score, tumour size, tumour stage, histological tumour grade, body mass index and the presence of steatosis in the surrounding liver tissue (P 0.05). Conclusion HSP27 plays an important role in the pathogenesis and progression of HCC in HCV infection through inhibition of caspase-3 mediated cell apoptosis and may serve as a potentially useful therapeutic target.

Background Celiac disease (CD) is a chronic autoimmune disorder induced in genetically susceptible individuals after ingestion of gluten proteins Aim of the work To highlight the utility of abdominal CT/enterography in diagnosis of CD. Subjects & methods This retrospective study included 12 patients presented to our institute during the period from May 2011 till April 2013 with vague abdominal symptoms, performed abdominal CT/enterography. The final diagnosis was reached in all patients through upper GI endoscopy, duodenal biopsy and serological tests including anti-tissue transglutaminase and anti-endomysial antibodies. Results The sensitivity of different CT signs was calculated against the diagnostic standard of reference (biopsy & serology). The jejuno-ileal fold reversal pattern was detected in 100% of patients. Other findings included (in descending order): Enlarged mesenteric lymph nodes in eight patients (66.5%); jejunal wall thickening, dilated jejunal loops, and cavitating lymph nodes in six patients (50%); dilated ileal loops in four patients (33%); ileal wall thickening in three patients (25%); thickened duodenum, and small bowel intussusception in two patients (16.5%). Conclusions CT is an efficient imaging tool in diagnosis of CD. The jejuno-ileal fold reversal pattern is highly in favor of the diagnosis of CD.