Programmed death-ligand 1 (PD-L1) polymorphisms as predictive biomarkers for the development of liver cirrhosis and hepatocellular carcinoma in HCV Egyptian patients.

BACKGROUND: Considering the immune evasion role of programmed death-ligand 1 (PD-L1) in cancer development, its genomic variations might be closely associated with disease development and cancer risks. Accordingly, this study was performed to investigate how the PD-L1 gene polymorphisms affect the susceptibility to hepatitis C virus (HCV)-induced liver cirrhosis and cancer development in the Egyptian population. METHODOLOGY: Two single nucleotide polymorphisms of the PD-L1 gene; rs2297136 (A > G) and rs4143815 (C > G), were studied in 50 HCV, 51 liver cirrhosis, and 52 hepatocellular carcinoma (HCC) patients as well as 50 healthy subjects using real-time PCR. RESULTS: The frequencies of PD-L1 rs2297136 AA and rs4143815 GG genotypes were significantly higher in the liver cirrhosis than the control and HCV groups. The rs4143815 CG and GG genotypes were linked to a higher risk of developing HCC and were positively associated with the clinicopathological features of HCC. CONCLUSIONS: The PD-L1 rs2297136 AA and rs4143815 GG genotypes increase the susceptibility to liver cirrhosis. The rs4143815 CG and GG genotypes are positively associated with HCC risk and its clinicopathological characteristics. Therefore, HCV patients carrying the PD-L1 rs4143815 G-allele should be followed up on a regular basis to allow for early HCC management.

Egyptian revalidation of non-invasive parameters for predicting esophageal varices in cirrhotic patients: A retrospective study.

BACKGROUND AND STUDY AIMS: In resource-limited countries, non-invasive tests for assessing liver fibrosis are a potential alternative to costly endoscopic screening for esophageal varices. We aimed to validate several non-invasive parameters for predicting the presence of varices. PATIENTS AND METHODS: Between September 2006 and August 2017, a total of 46,014 patients who underwent upper gastrointestinal endoscopy as one of the perquisites for receiving hepatitis C virus (HCV) therapy were enrolled and divided into group I (without varices) and group II (with varices). Non-invasive parameters of fibrosis, namely Lok index, Bonacini score, liver stiffness, FIB-4, Baveno, and extended Baveno criteria, were validated. RESULTS: Lok index, Bonacini score, liver stiffness, and FIB-4 had areas under the receiver operating characteristic curve (AUCs) of >0.6 (all P < 0.01 for the null hypothesis that the AUC was 0.5) for determination of the presence/absence of varices, with cutoff values of 0.80, 6.5, 21.9 kPa, and 2.94, and sensitivities of 74%, 74%, 66%, and 83%, respectively. The expanded Baveno VI criteria performed better than the Baveno VI criteria (spared endoscopy rate 81% versus 63%). CONCLUSION: The use of non-invasive methods is of limited value in predicting esophageal varices. The limited accuracy of ≤60% may delay the use of appropriate primary prophylaxis against variceal bleeding in a large proportion of cirrhotic patients.

Colorectal cancer in Arab world: A systematic review.

BACKGROUND: The incidence of colorectal cancer (CRC) is increasing among young individuals in the Arab world as well as in other regions of the world. AIM: To explore the incidence and prevalence of CRC in the Arab world. METHODS: The PubMed, Scopus, Web of Science, EBSCO and Wiley databases were searched to retrieve relevant articles irrespective of the language or the publication year. The search terms were "("colon OR rectum OR sigmoid OR rectal OR colonic OR colorectal") AND ("cancer OR malignancy OR malignant OR neoplasm") AND ("Jordan" OR "United Arab Emirates" OR "Bahrain" OR "Tunisia" OR "Algeria" OR "Djibouti" OR "Saudi Arabia" OR "Sudan" OR "Syria" OR "Somalia" OR "Iraq" OR "Oman" OR "Palestine" OR "Qatar" OR "Comoros" OR "Kuwait" OR "Lebanon" OR "Libya" OR "Egypt" OR "Morocco" OR "Mauritania" OR "Yemen"). Reviews, meta-analyses, and articles containing nonoriginal data were excluded. Retrieved articles were screened, and relevant data were extracted. Descriptive statistics were used for data analysis. RESULTS: Nine studies were included. Five of the studies provided information regarding the prevalence of CRC. The prevalence of CRC was 0.72% in Saudi Arabia and 0.78% in the United Arab Emirate, while in Egypt, it ranged from 0.4% to 14%. Four studies showed information regarding the incidence. The annual incidence rate of CRC in Qatar was 7.5/100000/year. In Egypt, the crude incidence rate (CIR) in males was 3.1 for colon cancer and 1 for rectal cancer, while in females, it was 2.3 for colon cancer and 0.8 for rectal cancer. The age-standardized rate for CRC incidence in 2003 was 36.90 for males, 26.50 for females, and 30.49 for both sexes in Saudi Arabia. In 2016, the CIRs in Saudi Arabia were 3.6 and 2.1 in females for colon cancer and rectal cancer, respectively, while in males, it was 3.3 and 2.8 for colon cancer and rectal cancer, respectively. One study in Egypt revealed that 25% of CRC cases occurred among individuals younger than 40 years old. CONCLUSION: There is a considerable prevalence of CRC in some Arab countries. More studies are needed to explore the incidence and prevalence of CRC in the rest of the Arab world.

Egyptian liver library: An indexed database for liver disease evidence in Egypt.

Liver diseases are among the most challenging health care problems worldwide. In Egypt, we established different care programs to combat liver diseases including schistosomiasis and viral hepatitides. A lot of research work addressing liver diseases in Egypt have been published with special focus on these two major fields. Other liver disease seems to be neglected although present and contributing to the liver disease burden in Egypt. In this report we reviewed the available evidence published from Egypt and elucidate areas of weakness and future research needs. Our search for Egyptian liver disease evidence retrieved 4683 articles, 67% of them were relevant to the topic. Out of the relevant articles; 1646/3265 (50.4%) were discussing clinical science, 1131 (34.7%) were discussing basic science and 488 (14.9%) were discussing both basic and clinical sciences. Cairo university (16.8%, n = 513) and Mansoura university (9.3%, n = 285) had the largest number of publications related to liver disease in Egypt respectively. The most commonly reported diseases were hepatitis C in 719/3361 articles (21.4%), parasitic liver infestations in 663 articles (19.7%), hepatocellular carcinoma in 544 articles (16.2%), liver fibrosis or cirrhosis in 537 articles (16%), and drug induced liver injury in 516 articles (15.4%). Most of the reviewed articles (36%) were discussing treatment of chronic liver diseases (n = 1201) followed by diagnostics (28%, n = 940), pathogenesis and pathophysiology (21%, n = 706). This review will direct attention to areas with less research like hepatitis B related liver disease, HIV/HCV co-infections, and non-alcoholic fatty liver disease (NAFLD) to encourage future research in these topics. In conclusion; our results ring a bell inviting the development of a roadmap for liver research in Egypt targeting to put future policies to cover areas of weakness in liver research with an ultimate goal of tackling liver disease and its overwhelming socioeconomic burden in our developing country.

Real-world results of direct-acting antivirals use for the treatment of chronic hepatitis C in old patients.

BACKGROUND AND AIM: Old people with chronic hepatitis C (HCV) were considered a difficult-to-treat category with more frequent adverse events until recently. Interferon-free direct-acting antivirals (DAAs) improved treatment adherence and quality of life of old patients. In this study, we aimed at reporting the real-world efficacy and safety of DAAs, in addition to predictors of sustained virological response (SVR) in old chronic HCV population. METHODS: This is a prospective observational intention-to-treat analysis that included old chronic hepatitis C genotype-4 patients (> 65 years) treated in a single specialized viral hepatitis treatment center in Egypt. Treatment regimens were allocated according to national guidelines for treatment of hepatitis C. Primary outcome was undetectable HCV-RNA at 12-week post-treatment by PCR. Secondary outcomes were identification of predictors of SVR and assessment of safety related issues. RESULTS: Our study included 864 patients (64% females) with mean age of 67.7 ± 2.8 years. Overall SVR rate was 98.9% while SVR rates for sofosbuvir/daclatasvir/ribavirin, paritaprevir/ombitasvir/ritonavir/ribavirin, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir/ribavirin, sofosbuvir/simeprevir/daclatasvir/ribavirin, sofosbuvir/simeprevir, interferon/sofosbuvir/ribavirin and sofosbuvir/ribavirin were 100%, 100%, 100%, 100%, 100%, 99.3%, 98% and 94.2%, respectively. DAAs were well tolerated. None of the patients discontinued the treatment due to adverse effects. Higher albumin, higher platelet count, lower bilirubin and lower stage of fibrosis were among predictors of favourable response. CONCLUSION: Different DAAs regimens were safe and effective in old Egyptian patients with chronic HCV.

Risk of hepatitis B virus reactivation with direct-acting antivirals against hepatitis C virus: A cohort study from Egypt and meta-analysis of published data.

BACKGROUND & AIMS: Hepatitis B virus (HBV) reactivation in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs) became an issue. However, its frequency has been poorly estimated, because of the varying definitions used and evaluation of heterogeneous study populations, including those concurrently treated for HBV. METHODS: We prospectively followed HBV surface antigen (HBsAg)-positive Egyptians undergoing interferon-free DAAs, to estimate the risk of HBV reactivation and HBV-related hepatitis. We also conducted a meta-analysis to estimate the reactivation risk using published data obtained from a systematic review of PubMed/Embase, in addition to our Egyptian data. We applied a standard definition of HBV reactivation proposed by the international liver associations (APASL and AASLD). RESULTS: Of 4471 CHC patients, 35 HBsAg-positive patients started interferon-free DAAs without HBV nucleos(t)ide analogues in our Egyptian cohort. Ten experienced HBV reactivation (28.6%), of whom 1 developed hepatitis (10.0%). Our systematic review identified 18 papers. The pooled reactivation risk in HBsAg-positive patients was 18.2% (95% CI: 7.9%-30.7%) without HBV therapy and 0.0% (95% CI: 0.0%-0.0%) with HBV nucleos(t)ide analogue. The pooled risk of hepatitis in those with HBV reactivation was 12.6% (95% CI: 0.0%-34.7%). The pooled reactivation risk in HBsAg-negative, antibody to HBV core antigen-positive (anti-HBc-positive) patients was negligible (0.1%, 95% CI: 0.0%-0.3%), irrespective of the presence of antibody to HBsAg (anti-HBs). CONCLUSIONS: We confirmed high HBV reactivation risk in HBsAg-positive patients undergoing DAAs, with only a minority developing clinically important hepatitis. The risk is negligible for HBsAg-negative anti-HBc-positive patients.

Visceral Adiposity Index and the Degree of Hepatic Fibrosis and Inflammation in Egyptian Patients with Chronic Hepatitis C.

INTRODUCTION: Many clinical studies suggest a direct association between hepatic fat content and visceral adiposity and the progression of fibrosis. AIM: This work aims to clarify the relation between the Visceral Adiposity Index (VAI) and severity of necroinflammatory activity and liver fibrosis in Egyptian patients with chronic Hepatitis C Virus (HCV) infection. MATERIALS AND METHODS: A cross-sectional study, over a period of six months, was performed on 50 chronic HCV patients subjected to routine laboratory investigations, abdominal ultrasonography, measurement of Waist Circumference (WC), calculation of Body Mass Index (BMI) and VAI, ultrasound guided liver biopsy and assessment of hepatic fibrosis by METAVIR staging. RESULTS: A total of 50 HCV positive patients, 29 (58%) males and 21 (42%) females were included in the study. Age ranged from 29-60 years (44.4±8.4). BMI was ranged from 20.3 to 41.4 kg/m2 (31.7±5.5). VAI for males was 0.4±0.2 and for females was 0.5±0.3. There were significant positive correlations between VAI and BMI, Triglycerides (TG), fibrosis stages, grades of liver inflammation and FIB-4 Fibrosis-4 score. There were significant negative correlations between VAI and high density lipoprotein, platelets and haemoglobin. CONCLUSION: There is an association between visceral obesity represented by VAI and the severity of hepatic inflammatory response in chronic hepatitis C patients. Other studies are recommended to measure the clinical implication of visceral obesity on the response to the novel directly acting antivirals.

MicroRNAs and clinical implications in hepatocellular carcinoma.

AIM: To assess the role of some circulating miRNAs (miR-23a, miR-203, miR338, miR-34, and miR-16) as tumor markers for diagnosis of hepatocellular carcinoma (HCC). METHODS: One hundred and seventy-one subjects were enrolled, 57 patients with HCC, 57 patients with liver cirrhosis (LC) and 57 healthy subjects as control group. Severity of liver disease was assessed by Child Pugh score. Tumor staging was done using Okuda staging system. Quantification of Micro RNA (miR-23a, miR-203, miR338, miR-34, and miR-16) was performed. RESULTS: All studied miRNA showed significant difference between HCC and cirrhotic patients in comparison to healthy control. miR-23a showed statistically significant difference between HCC and cirrhotic patients being higher in HCC group than cirrhotic. miR-23a is significantly higher in HCC patients with focal lesion size equal or more than 5 cm, patients with multiple focal lesions and Okuda stage III. At cutoff value ≥ 210, miR-23a showed accuracy 79.3% to diagnose HCC patients with sensitivity 89.47% and specificity about 64.91%. At cut off level ≥ 200 ng/mL, serum alpha fetoprotein had 73.68% sensitivity, 52.63% specificity, 43.75% PPV, 80% NPV for diagnosis of HCC. CONCLUSION: MicroRNA 23a can be used as a screening test for early detection of HCC. Also, it is related to larger size of tumour, late Okuda staging and multiple hepatic focal lesions, so it might be a prognostic biomarker.

Does Helicobacter pylori infection play a role in iron deficiency anemia in hemodialysis patients?

BACKGROUND: Among the disorders that may affect patients with end-stage renal disease (ESRD), anemia is the most responsive to treatment; any reversible cause should be identified, and the most common reversible cause is iron deficiency. We investigated the relationship between Helicobacter pylori infection and iron deficiency anemia in a hemodialysis population. MATERIALS AND METHODS: This cross-sectional study included 90 adult patients with ESRD on maintenance hemodialysis. Iron deficiency anemia (IDA) was determined by hemoglobin, serum iron, ferritin, and transferrin saturation (TSAT) values. H. pylori diagnosis was done by detection of H. pylori antigen in stool. RESULTS: It was found that H. pylori stool antigen was positive in 50 patients (55.6%), while 40 patients were negative for H. pylori (44.4%). 71% of patients had anemia (Hb < 10 g/dL), and 63% of patients had iron deficiency anemia (TSAT < 30%). No significant differences were found between H. pylori positive and -negative groups in any of the variables analyzed: hemoglobin (8.96 ± 1.8 vs.9.76 ± 1.4 g/dL), serum iron (86 ± 17.5 vs. 87 ± 18.2 pg/dL), ferritin (284.8 ± 60.5 vs. 301.4 ± 50.1 ng/dL), or TSAT index (26.79 ± 18.42% vs. 29.83 ± 18. 01% µg/dL). CONCLUSION: H. pylori infection has a nonsignificant effect on iron deficiency anemia in hemodialysis patients. We recommend that routine screening for H. pylori is not needed among dialysis patients with iron deficiency anemia.
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Detection of occult hepatitis C virus among healthy spouses of patients with HCV infection.

The criterion standard for the diagnosis of occult hepatitis C virus (HCV) infection is detection of HCV-RNA in liver cells. However, because of the invasive nature of liver biopsy, other methods have been studied. The present study aimed to identify subjects with occult HCV-4 infection among healthy sexual partners of patients with chronic HCV-4 infection by detecting HCV-RNA in peripheral blood mononuclear cells (PBMCs) using real-time polymerase chain reaction (PCR). Fifty healthy Egyptian spouses of patients with chronic HCV-4 infection were included in this study. Real-time PCR was used to detect HCV-RNA in PBMCs in all the study subjects. The prevalence of occult HCV-4 infection was 4%, and a statistically significant higher prevalence was found among patients with a history of sexually transmitted infection. The results of the present study indicate the importance of intra-spousal transmission of HCV-4 infection, especially in subjects with a history of sexually transmitted infection.

Clinical spectrum of fever of unknown origin among adult Egyptian patients admitted to Ain Shams University Hospitals: a hospital based study.

This prospective study was designed to analyze the clinical spectrum of fever of unknown origin (FUO) among adult Egyptian patients admitted to Ain Shams University Hospitals during the period from May 2009 till the end of December 2010. All Egyptian patients fulfilling the criteria of FUO admitted during this period were followed up till reaching the diagnosis. 93 patients were included in the study. They were 48 (51.6%) females and 45 (48.4%) males, their ages ranged from 15 to 65 years (34.39 +/- 13.6). Infections were the commonest cause of FUO (41.94%) followed by malignancies (30.11%). While autoimmune diseases represented 15.05% and in 12.9% of patients the diagnosis was not established. Brucellosis and infective endocarditis were the commonest infections, while hematological malignancies were the commonest oncological diseases. Systemic lupus erythematosus (SLE) was the commonest auto-immune disease. Brucellosis, infective endocarditis, hematological malignancies and SLE must be considered in the differential diagnosis of adult FUO in Egypt.

Antimicrobial resistant bacteria among health care workers in intensive care units at Ain Shams University Hospitals.

Fifty HCWs in ICUs of Internal medicine, Chest, Neonatology and Burn were included in prospective cohort study. Collection of nasal, hand and rectal swabs, proper biochemical identification, culture media and antibiotic sensitivity tests were used to detect Methicillin-resistant Staphylococcus aureus (MRSA); vancomycin-resistant Enterococci (VRE) & extended spectrum beta-lactamase producing gram -ve bacilli (ESBLs). S. aureus was isolated from 34% of HCWs; 28% were nasal carriers, 4% were hand carriers and 2% had S. aureus at both sites. Nasal and hand carriage rates of MRSA were 20% & 4% respectively, with an overall rate of 22%. Gram -ve bacilli were isolated from 8% of HCWs hand swabs & showed Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Hand carriage rate of ESBLs was 2%. Hand contamination with gram -ve bacilli and S. aureus was in 14% of HCWs. VRE carriage rate was 9.5%. ESBLs carriage rate in rectal swabs was 21.43%. K. pneumoniae was the most common ESBLs producing isolate (33.3%), followed by E. coli (18.75%). In combined disc method, aztreonam was the most sensitive (90%) in detecting ESBLs. Burn ICU had highest % of MRSA & ESBLs carriage. Neonatal ICU showed highest % of VRE carriage. An insignificant association was between infection control training or antimicrobial intake and carriage of antimicrobial resistant bacteria.