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Drug-induced liver injury (DiLi) is a frequent cause of liver injury and acute liver failure. We aimed to review all hospitalized DILI cases in a tertiary Egyptian center from January 2015 through January 2016. Cases with elevated alanine aminotransferase more than 3-fold and/or alkaline phosphatase more than 2-fold the upper limit of normal value were prospectively recruited and followed for one year. Drug history, liver biopsy whenever feasible and application of Roussel Uclaf causality Assessment Method (RUcAM) were the diagnostic prerequisites after exclusion of other etiologies of acute liver injury. in order of frequency, the incriminated drugs were: Diclofenac (31 cases, 41.3%), amoxicillin-clavulanate (14 cases, 18.7%), halothane toxicity (8 cases, 10.7%), ibuprofen (4 cases, 5.3%), Khat (3 cases, 4%), tramadol (3 cases, 4%), Sofosbuvir with ribavirin (2 cases, 2.7%), and acetylsalicylic acid (2 cases, 2.7%) with one offending drug in 93.3% of cases. Forty-four cases (58.7%) were males; while 56 cases (74.7%) had HCV related chronic liver disease. Thirty-two cases (42.7%) presented with pattern of hepatocellular injury, while 23 cases (30.7%) were with cholestasis, and 20 cases (20.7%) with a mixed hepatocellular/ cholestatic injury. One case received a transplant (0.75%), 7 cases died (9.3%), 23 cases (30.6%) developed liver decompensation (hepatic encephalopathy and ascites), and 44 cases completely resolved (58.7%). In conclusion, Diclofenac is the commonest offender in DILI occurrence in an Egyptian cohort. Age and prothrombin concentration were the only predictors of unfavorable outcomes of DiLi. Drug induced liver injury (DILI) is one of the least understood areas in hepatology research. Since 1960, DILI is considered one of the commonest causes of withdrawal of approved medications from the marketplace 1. The mounting rates of DILI reports had notified it as a leading confusion of acute liver failure (ALF) 2. Despite critical DILI presentations, resolution of injury is common. Typical incriminating factors that were attributed to DILI occurrence were the medical personnel's' unawareness of the drugs morbid effects upon the liver and the availability of the over the counter drugs to the general public. On review of these cases, the main challenges that presented were the paucity of national well-structured notification programs with a subsequent substantial shortage of data registries. In addition, the lack of an objective test for the diagnosis of DILI, similarities to other liver diseases and the difficulty in defining the offending drug in patients on many medicines, complicated its recognition 3. Nevertheless, a high index of suspicion is necessarily to establish the diagnosis 4. In Egypt, there is lack in epidemiological data and DILI registry. This was the reason for designing this prospective study investigating DILI occurrence, demographic, clinical, laboratory and histopathological characteristics along with disease outcomes in an Egyptian cohort. patients and methods This prospective study...

Aim of the studyAutoimmune hepatitis (AIH) is characterized histologically by aggressive inflammation with interface hepatitis and prominent lymphoplasmacytic infiltration. Programmed death-1 (PD-1) is expressed on activated lymphocytes. Engagement of PD-1 by its ligand PD-L1 leads to cell apoptosis and death. We aimed to evaluate the immunohistochemical expression of PD-1 and PD-L1 in children with AIH, and its relation to treatment outcome.Material and methodsPre-treatment liver biopsies of 31 children with AIH were compared to 30 children with chronic hepatitis C virus (HCV) infection as a control group. PD-1 was evaluated in lymphocytes, while PD-L1 was evaluated in lymphocytes, hepatocytes, biliary epithelial cells, sinusoidal endothelial cells and Kupffer cells. All AIH patients received the standard treatment.ResultsThe mean PD-1 was significantly higher in AIH than HCV patients (29.19 ±18.5% vs. 15.2 ±10.1%; p = 0.002) while there was no statistically significant difference as regards PD-L1 on lymphocytes (p = 0.853). Neither PD-1 nor PD-L1 correlated with either liver fibrosis or the inflammatory activity (p > 0.05 for all). PD-1/PD-L1 ratio was significantly higher in AIH compared to HCV patients and in non-responder AIH patients compared to responders (46.9 vs. 6.58). PD-1 expression was comparable in both responders and non-responders (p = 0.813), while PD-L1 was significantly upregulated in responders (4.17 ±3.15% vs. 0.63 ±1.3%; p = 0.046). PD-L1 expression on hepatocytes, biliary epithelial cells, sinusoidal endothelial cells and Kupffer cells was comparable in AIH and HCV groups.ConclusionsPD-1/PD-L1 ratio, which reflects immune aggression, was significantly higher in AIH compared to HCV patients and in non-responder AIH patients compared to responders.

Helal TESA, Ehsan NA, Radwan NA, Abdelsameea E. Relationship between hepatic progenitor cells and stellate cells in chronic hepatitis C genotype 4. APMIS 2018; 126: 14-20.Hepatitis C virus (HCV) infection represents a major health problem in many areas of the world, especially Egypt. Hepatic progenitor cells (HPCs) and hepatic stellate cells (HSCs) have been implicated in fibrosis progression in chronic HCV. The aim of this study was to investigate the role of HPCs and HSCs in chronic HCV infection and the relationship between both cell types. This retrospective study was conducted on 100 chronic HCV patients. Immunohistochemistry was performed on liver tissue sections for cytokeratin 19 (progenitor cell markers), smooth muscle actin (stellate cell markers), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta (TGF-ß). The necroinflammatory activity was significantly related to the number of isolated HPCs and TGF-ß expression (p = 0.003 and p = 0.001 respectively). Advanced stages of fibrosis showed significantly increase number of HPCs (p = 0.001), higher ratio of HSCs (p = 0.004), more expression of TGF-ß (p = 0.001) and MMP-9 (p = 0.001). There was a significant direct correlation between immunoexpression of HPCs and HSCs for isolated cells (r = 0.569, p = 0.001) and ductular reaction (r = 0.519, p = 0.001). Hepatic progenitor cells and stellate cells play a significant role in the development and progression of fibrosis in chronic HCV. More interestingly, the significant direct correlation between HPCs and HSCs suggests a synergistic interrelation.

Aim of the study: Chronic hepatitis B virus (HBV) infection is one of the major health problems worldwide. Use of non-invasive tests for assessment of hepatic fibrosis such as the FIB-4 index could be used to avoid liver biopsy. Another promising noninvasive test, FIB-5, could also be used to detect significant hepatic fibrosis. The aim of the study was to compare the use of FIB-5 and FIB-4 as noninvasive markers to assess chronic HBV-related hepatic fibrosis. Material and methods: This study was done on 176 chronic HBV patients who underwent liver biopsy. Grading and staging of liver fibrosis was done according to the METAVIR scoring system. FIB-5 and FIB-4 scores were calculated for all patients. Results: As regards FIB-4 for differentiation between non-significant fibrosis (group I) and significant fibrosis (group II), at a cutoff level of 1.28 with positive predictive value (PPV) 41.4% and specificity 48% while at a cutoff level of 7.08 with PPV 98.8% and specificity 98% for FIB-5. Conclusions: As regards both scores, the FIB-5 score was more specific than FIB-4 for diagnosing significant from nonsignificant hepatic fibrosis in patients with chronic HBV infection.