Publications by authors named "Gamal Shiha"

94 Publications

Reply to: The best predictive model for post-SVR HCC: can it be universal?

Hepatol Int 2022 May 12. Epub 2022 May 12.

Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansûra, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-022-10349-0DOI Listing
May 2022

Prediction of hepatocellular carcinoma in Hepatitis C patients with advanced fibrosis after sustained virologic response.

Clin Res Hepatol Gastroenterol 2022 Apr 8:101923. Epub 2022 Apr 8.

AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, APHP, Liver Unit, Bobigny, France; Université Sorbonne Paris Nord, Bobigny, France; Inserm, UMR-1138 « Functional Genomics of solid tumors », Centre de Recherche des Cordeliers, Université de Paris, France. Electronic address:

Background & Aims: Prediction of hepatocellular carcinoma (HCC) occurrence in patients with chronic hepatitis C (HCV) who achieved a sustained virological response (SVR) after direct acting antivirals (DAAs) remains challenging.

Methods: Among HCC-free HCV patients with advanced fibrosis enrolled in the ANRS CO22 HEPATHER cohort who achieved SVR 12 weeks after treatment with DAAs, HCC predictive models were developed using Cox multivariable regression. The derived score was externally validated in a large Egyptian cohort. Our main outcome was the HCC-free survival.

Results: During follow-up (median 3.05 years), 153 out of 3531 patients developed a HCC. Main variables associated with HCC occurrence were: male gender, HCV genotype 3, esophageal varices, albumin < 40 g/L, total bilirubin >11 µmol/L and hypercholesterolemia before DAA initiation, together with age > 58 years, FIB-4 index ≥3.25 evaluated at SVR. A score was established allowing the stratification of patients by high (score ≥ 12/22), intermediate (7 ≤ score <12) and low risk of HCC (score < 7/22) with 3-yrs HCC incidence of 18.96%, 5.50% and 1.65%, respectively. The integrated time-dependent area under the ROC curve (i-AUC) was 0.76 in our patients and 0.61 in the validation cohort.

Conclusion: The externally validated HEPATHER HCC score has good short-term predictive performance in HCV- patients who achieved SVR12 after DAAs allowing to identify high-risk patients in whom HCC screening may be cost-effective and low-risk patients in whom HCC screening may be superfluous in the first 3 years after SVR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2022.101923DOI Listing
April 2022

Umbilical Cord Mesenchymal Stem/Stromal Cells and Low-Dose Obeticholic Acid as a Possible Combined Treatment for Liver Fibrosis.

Stem Cell Rev Rep 2022 Feb 4. Epub 2022 Feb 4.

Egyptian Liver Research Institute and Hospital (ELH), Mansoura, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-022-10346-8DOI Listing
February 2022

The egyptian clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.

Saudi J Gastroenterol 2022 Jan-Feb;28(1):3-20

Department of Hepatology, NTHMRI, Cairo, Egypt.

The landscape of chronic liver disease in Egypt has drastically changed over the past few decades. The prevalence of metabolic-associated fatty liver disease (MAFLD) has risen to alarming levels. Despite the magnitude of the problem, no regional guidelines have been developed to tackle this disease. This document provides the clinical practice guidelines of the key Egyptian opinion leaders on MAFLD screening, diagnosis, and management, and covers various aspects in the management of MAFLD. The document considers our local situations and the burden of clinical management for the healthcare sector and is proposed for daily clinical practical use. Particular reference to special groups was done whenever necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/sjg.sjg_357_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919931PMC
March 2022

Predictive performance and clinical utility of HCC risk scores in chronic hepatitis C: a comparative study.

Hepatol Int 2022 Feb 16;16(1):159-170. Epub 2022 Jan 16.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.

Background And Aim: Many HCC risk prediction scores were developed to guide HCC risk stratification and identify CHC patients who either need intensified surveillance or may not require screening. There is a need to compare different scores and their predictive performance in clinical practice. We aim to compare the newest HCC risk scores evaluating their discriminative ability, and clinical utility in a large cohort of CHC patients.

Patients And Methods: The performance of the scores was evaluated in 3075 CHC patients who achieved SVR following DAAs using Log rank, Harrell's c statistic, also tested for HCC-risk stratification and negative predictive values.

Results: HCC developed in 212 patients within 5 years follow-up. Twelve HCC risk scores were identified and displayed significant Log rank (p ≤ 0.05) except Alonso-Lopez TE-HCC, and Chun scores (p = 0.374, p = 0.053, respectively). Analysis of the remaining ten scores revealed that ADRES, GES pre-post treatment, GES algorithm and Watanabe (post-treatment) scores including dynamics of AFP, were clinically applicable and demonstrated good statistical performance; Log rank analysis < 0.001, Harrell's C statistic (0.66-0.83) and high negative predictive values (94.38-97.65%). In these three scores, the 5 years cumulative IR in low risk groups be very low (0.54-1.6), so screening could be avoided safely in these patients.

Conclusion: ADRES, GES (pre- and post-treatment), GES algorithm and Watanabe (post-treatment) scores seem to offer acceptable HCC-risk predictability and clinical utility in CHC patients. The dynamics of AFP as a component of these scores may explain their high performance when compared to other scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-021-10284-6DOI Listing
February 2022

Letter: evaluation and proposed re-classification of HCC prediction model in patients with chronic hepatitis C genotype 4.

Aliment Pharmacol Ther 2022 01;55(2):255-257

Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16704DOI Listing
January 2022

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure.

Hepatol Int 2022 Feb 25;16(1):171-182. Epub 2021 Nov 25.

Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India.

Background And Aims: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database.

Methods: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis.

Results: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred.

Conclusions: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-021-10266-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844167PMC
February 2022

Management of liver disease patients in different clinical situations during COVID-19 pandemic.

Egypt Liver J 2021 26;11(1):21. Epub 2021 Mar 26.

Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Chronic liver diseases are common worldwide, especially in developing countries. The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) leads to the infection of many patients with underlying chronic liver diseases. As a relatively new disease, management of COVID-19, in the context of chronic liver disease, is mainly based on the experience of the treating physician and the available data. In this review, we summarize the available evidence about the management of liver disease patients, in the context of COVID-19 infection, which can increase the severity of viral hepatitis B. Also, its clearance in HBV patients is delayed. A sixfold increased severity of COVID-19 was reported in obese patients with metabolic associated fatty liver disease (MAFDL). In patients with autoimmune liver disease (AILD), it is not recommended to change their immunosuppressive therapy (as long as they are not infected with COVID-19), in order to avoid a flare of liver disease. However, immunosuppressant drugs should be modified, in the case of infection with COVID-19. To date, no data suggest an increased risk or severity in metabolic liver diseases, such as hemochromatosis, Wilson's disease, or alpha-1 antitrypsin deficiency. Patients with liver cirrhosis should be carefully managed with minimum exposure to healthcare facilities. Basic investigations for follow-up can be scheduled at wider intervals; if patients need admission, this should be in COVID-19-clean areas. Patients with hepatocellular carcinomas may have a poor prognosis according to preliminary reports from China. The course of COVID-19 in liver transplant recipients on immunosuppression seems to have a benign course, based on few reports in children and adults. The hepatotoxicity of COVID-19 drugs ranges from mild liver enzyme elevation to a flare of underlying liver diseases. Therefore, the decision should be customized. Telemedicine can minimize the exposure of healthcare workers and patients to infection with COVID-19 and decrease the consumption of personal protective equipment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s43066-021-00091-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994958PMC
March 2021

Development and multicenter validation of FIB-6: A novel, machine learning, simple bedside score to rule out liver cirrhosis and compensated advanced chronic liver disease in patients with chronic hepatitis C.

Hepatol Res 2022 Feb 24;52(2):165-175. Epub 2021 Nov 24.

Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.

Background: Non-invasive tests (NITs), such as Fibrosis-4 index (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI), developed using classical statistical methods, are increasingly used for determining liver fibrosis stages and recommended in treatment guidelines replacing the liver biopsy. Application of conventional cutoffs of FIB-4 and APRI resulted in high rates of misclassification of fibrosis stages.

Aim: There is an unmet need for more accurate NITs that can overcome the limitations of FIB-4 and APRI.

Patients And Methods: Machine learning with the random forest algorithm was used to develop a non-invasive index using retrospective data of 7238 patients with biopsy-proven chronic hepatitis C from two centers in Egypt; derivation dataset (n = 1821) and validation set in the second center (n = 5417). Receiver operator curve analysis was used to define cutoffs for different stages of fibrosis. Performance of the new score was externally validated in cohorts from two other sites in Egypt (n = 560) and seven different countries (n = 1317). Fibrosis stages were determined using the METAVIR score. Results were also compared with three established tools (FIB-4, APRI, and the aspartate aminotransferase-to-alanine aminotransferase ratio [AAR]).

Results: Age in addition to readily available laboratory parameters such as aspartate, and alanine aminotransferases, alkaline phosphatase, albumin (g/dl), and platelet count (/cm ) correlated with the biopsy-derived stage of liver fibrosis in the derivation cohort and were used to construct the model for predicting the fibrosis stage by applying the random forest algorithm, resulting in an FIB-6 index, which can be calculated easily at http://fib6.elriah.info. Application of the cutoff values derived from the derivation group on the validation groups yielded very good performance in ruling out cirrhosis (negative predictive value [NPV] = 97.7%), compensated advance liver disease (NPV = 90.2%), and significant fibrosis (NPV = 65.7%). In the external validation groups from different countries, FIB-6 demonstrated higher sensitivity and NPV than FIB-4, APRI, and AAR.

Conclusion: FIB-6 score is a non-invasive, simple, and accurate test for ruling out liver cirrhosis and compensated advance liver disease in patients with chronic hepatitis C and performs better than APRI, FIB-4, and AAR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13729DOI Listing
February 2022

'First week' is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure.

Hepatol Int 2021 Dec 4;15(6):1376-1388. Epub 2021 Oct 4.

Department of Hepatology, Cardinal Santos Medical Centre, Manila, Philippines.

Background And Aims: Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).

Methods: Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant.

Results: The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01).

Conclusions: ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. 'Emergent LT' should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-021-10206-6DOI Listing
December 2021

Seroprevalence and epidemiological characteristics of HDV infection among HBV patients in the Nile Delta, Egypt.

J Viral Hepat 2022 01 7;29(1):87-90. Epub 2021 Oct 7.

Department of Gastroenterology & Hepatology and Infectious Diseases Department, Al-Azhar University, Cairo, Egypt.

The epidemiology of HDV infection worldwide is obscure. Mapping the epidemiology of the infection is highly required, so, we aimed to estimate the prevalence of hepatitis D virus infection among chronic hepatitis B patients and the epidemiological characteristics in the Nile delta in Egypt. This was a prospective observational cross-sectional study including consecutive chronic hepatitis B patients in the out-patient clinics at the Egyptian Liver Research Institute and Hospital (ELRIAH) and its satellites in the Nile Delta from January 2016 until August 2018. They were recruited from patients enrolled in Educate, Test and Treat program, which was implemented in 73 Egyptian Villages. Subjects were tested by using HBsAg serological rapid diagnostic tests (RDTs), and then HBV DNA by PCR was done in HBsAg-positive cases. HDV IgG antibody testing and confirmatory HDV RNA PCR were done. Complete liver functions, abdominal ultrasonography and FibroScan were also performed. The prevalence of HDV was 3.4% using anti-delta antibody (22/631), and only 8 were positive for HDV RNA (8/22, 36.4%). Overall HDV prevalence using PCR was 8/631(1.27%). HDV-positive cases were mainly males (68.2%). Eight cases were cirrhotic (36.4%), 3 (13.6%) had HCC and 7 (31.8%) were HBeAg positive. HDV prevalence is low among chronic hepatitis B patients in the Nile delta, Egypt. Screening for HDV IgG is recommended in CHB patients who had cirrhosis, HCC or HBeAg positive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13621DOI Listing
January 2022

Stem cell therapies for autoimmune hepatitis.

Stem Cell Res Ther 2021 07 7;12(1):386. Epub 2021 Jul 7.

Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt.

Autoimmune hepatitis is a chronic inflammatory hepatic disorder which may cause liver fibrosis. Appropriate treatment of autoimmune hepatitis is therefore important. Adult stem cells have been investigated as therapies for a variety of disorders in latest years. Hematopoietic stem cells (HSCs) were the first known adult stem cells (ASCs) and can give rise to all of the cell types in the blood and immune system. Originally, HSC transplantation was served as a therapy for hematological malignancies, but more recently researchers have found the treatment to have positive effects in autoimmune diseases such as multiple sclerosis. Mesenchymal stem cells (MSCs) are ASCs which can be extracted from different tissues, such as bone marrow, adipose tissue, umbilical cord, and dental pulp. MSCs interact with several immune response pathways either by direct cell-to-cell interactions or by the secretion of soluble factors. These characteristics make MSCs potentially valuable as a therapy for autoimmune diseases. Both ASC and ASC-derived exosomes have been investigated as a therapy for autoimmune hepatitis. This review aims to summarize studies focused on the effects of ASCs and their products on autoimmune hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-021-02464-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262021PMC
July 2021

Development of a simple dynamic algorithm for individualized hepatocellular carcinoma risk-based surveillance using pre- and post-treatment general evaluation score.

Liver Int 2021 11 8;41(11):2768-2776. Epub 2021 Jul 8.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.

Background And Aims: With the growing number of treated hepatitis C patients, the current 'one-size-fits-all' hepatocellular carcinoma (HCC) surveillance strategies for patients with advanced fibrosis represents a great burden on healthcare systems. An individualized HCC risk strategy incorporates the dynamic changes of HCC risk are lacking.

Methods: This single-centre observational study included 3075 patients, with advanced fibrosis (≥F3) who achieved SVR following DAAs at Egyptian Liver research institute and hospital (ELRIAH) with follow-up period (range 6-72 months). The performance of a recently developed General Evaluation Score (GES) HCC risk stratification score was calculated pre- and post-treatment using Harrell's c statistic. Times to HCC and cumulative incidences were calculated with Kaplan-Meier method and compared using log-rank (Mantel-Cox) test.

Results: Pre-treatment GES score stratified patients into low (60.4%), intermediate (23.4%), and (16.2%) high-risk score where 5-year cumulative incidences of HCC were 1.66%, 4.45% and 7.64%, respectively. Harrell's c statistic was 0.801. Post-treatment GES score stratified patients into low (57.4%), intermediate (30.7%) and (11.9%) high-risk score where 5-year cumulative incidences of HCC were 1.35%, 3.49% and 11.09% respectively. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.818. Using pre- and post-treatment GES score, GES algorithm was developed with higher predictive value. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.832.

Conclusion: A dynamic algorithm incorporating both pre- and post-GES scores have better performance and predictive value compared with only pre-treatment assessments. The proposed algorithm would help to stratify those who need intensive or being excluded from screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14995DOI Listing
November 2021

Usability and acceptability of self-testing for hepatitis C virus infection among the general population in the Nile Delta region of Egypt.

BMC Public Health 2021 06 22;21(1):1188. Epub 2021 Jun 22.

Department of Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland.

Background: Self-testing for hepatitis C virus antibodies (HCVST) may be an additional strategy to expand access to hepatitis C virus (HCV) testing and support elimination efforts. We conducted a study to assess the usability and acceptability of HCVST among the general population in a semi-rural, high-HCV prevalence region in Egypt.

Methods: An observational study was conducted in two hospitals in the Nile Delta region. A trained provider gave an in-person demonstration on how to use the oral fluid HCVST followed by observation of the participant performing the test. Usability was assessed by observing errors made and difficulties faced by participants. Acceptability of HCV self-testing was assessed using an interviewer-administered semi-structured questionnaire.

Results: Of 116 participants enrolled, 17 (14.6%) had received no formal education. The majority (72%) of participants completed all testing steps without any assistance and interpreted the test results correctly. Agreement between participant-reported HCVST results and interpretation by a trained user was 86%, with a Cohen's kappa of 0.6. Agreement between participant-reported HCVST results and provider-administered oral fluid HCV rapid test results was 97.2%, with a Cohen's kappa of 0.75. The majority of participants rated the HCVST process as easy (53%) or very easy (44%), and 96% indicated they would be willing to use HCVST again and recommend it to their family and friends.

Conclusion: Our study demonstrates the high usability and acceptability of oral fluid HCVST in a general population. Further studies are needed to establish the optimal positioning of self-testing alongside facility-based testing to expand access to HCV diagnosis in both general and high-risk populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-11169-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218412PMC
June 2021

Temperature responsive smart polymer for enabling affinity enrichment of current coronavirus (SARS-CoV-2) to improve its diagnostic sensitivity.

Comput Struct Biotechnol J 2021 14;19:3609-3617. Epub 2021 Jun 14.

Research Center for Functional Materials, National Institute for Materials Science (NIMS), 1-1Namiki, Tsukuba, Ibaraki 305-0044, Japan.

The current commercially available SARS-CoV-2 diagnostic approaches including nucleic acid molecular assaying using polymerase chain reaction (PCR) have many limitations and drawbacks. SARS-CoV-2 diagnostic strategies were reported to have a high false-negative rate and low sensitivity due to low viral antibodies or antigenic load in the specimens, that is why even PCR test is recommended to be repeated to overcome this problem. Thus, in anticipation of COVID-19 current wave and the upcoming waves, we should have an accurate and rapid diagnostic tool to control this pandemic. In this study, we developed a novel preanalytical strategy to be used for SARS-CoV-2 specimen enrichment to avoid misdiagnosis. This method depends on the immuno-affinity trapping of the viral target followed by in situ thermal precipitation and enrichment. We designed, synthesized, and characterized a thermal-responsive polymer poly (N-isopropylacrylamide-co-2-hydroxyisopropylacrylamide-co-strained alkyne isopropylacrylamide) followed by decoration with SARS-CoV-2 antibody. Different investigations approved the successful synthesis of the polymeric antibody conjugate. This conjugate was shown to enrich recombinant SARS-CoV-2 nucleocapsid protein samples to about 6 folds. This developed system succeeded in avoiding the misdiagnosis of low viral load specimens using the lateral flow immunoassay test. The strength of this work is that, to the best of our knowledge, this report may be the first to functionalize SARS-CoV-2 antibody to a thermo-responsive polymer for increasing its screening sensitivity during the current pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.csbj.2021.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200327PMC
June 2021

The Potential Safe Antifibrotic Effect of Stem Cell Conditioned Medium and Nilotinib Combined Therapy by Selective Elimination of Rat Activated HSCs.

Biomed Res Int 2021 28;2021:6678913. Epub 2021 Mar 28.

Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansoura, Egypt.

Hepatic fibrosis is a progressive disease with serious clinical complications that arise from abnormal propagation and activation of multiple inflammatory pathways. Nilotinib is an oral tyrosine kinase inhibitor with antifibrotic activity. Mesenchymal stem cells (MSCs) are blank cells and can differentiate into specific cell types. They have the potential to repair and regenerate cells. MSCs have a special paracrine fashion where they produce special exosomes, microvesicles, and cytokines like IL-6, transforming growth factor-beta (TGF-), and HGF as well as hepatic stellate cell suppressors. This paracrine fashion can decrease collagen deposition, enhance antifibrotic, anti-inflammatory, and angiogenic activity in vitro and in vivo. In our study, the rat's hepatic stellate cells (HSCs) in addition to different normal cell lines were treated with Nilotinib alone and in combination with liver mesenchymal stem cells conditioned medium (LMSCs-CM) for 24 h. Mono and combined therapy antifibrotic and cytotoxicity effects were evaluated using different parameters including -SMA, cytochrome c, P53 expression, collagen deposition, DNA content, oxidative stress parameters, cell viability, and apoptosis by flow cytometry analysis. Our results showed that Nilotinib and LMSCs-CM in combination had a significantly potent antifibrotic and anti-inflammatory effect on activated hepatic stellate cells than Nilotinib alone; otherwise, this combination showed the best safety with minimal cytotoxicity on different normal cell lines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6678913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021473PMC
May 2021

Coronavirus (SARS-CoV-2) in gastroenterology and its current epidemiological situation: An updated review until January 2021.

EXCLI J 2021 16;20:366-385. Epub 2021 Feb 16.

Research Center for Functional Materials, National Institute for Materials Science (NIMS), 1-1Namiki, Tsukuba, Ibaraki 305-0044, Japan.

Coronaviruses are positive-sense single-strand RNA viruses that infect amphibians, birds, and mammals. Coronavirus Disease 2019 (COVID-19) has become a major health problem caused by one of the coronaviruses called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread fast throughout the globe since its first identification in Wuhan, China, in December 2019. Although COVID-19 is principally defined by its respiratory symptoms, it is now clear that the virus can also affect the digestive system causing gastrointestinal (GI) symptoms like diarrhea, loss of appetite, nausea/vomiting, and abdominal pain as a major complaint. GI symptoms could be the initial signs of preceding respiratory signs, carrying a potential for slowed investigation and raised disease transmission opportunities. Various studies recognized the COVID-19 RNA in stool specimens of infected patients, and its viral receptor angiotensin-converting enzyme-2 (ACE-2) is highly expressed in GI epithelial cells. Many cases were reported negative using nasopharyngeal/oropharyngeal swabs and finally, SARS-CoV-2 RNA was detected in their anal/rectal swabs and stool specimens. These suggest that COVID-19 can actively infect and replicate in the GI tract. In this review, we elaborate on the close relationship between SARS-CoV-2 and the digestive system, focusing on the current status in the field of COVID-19 in gastroenterology, liver injury, endoscopy, inflammatory bowel disease, imaging, and the potential underlying mechanisms with illustrating the current epidemiological status regarding this pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17179/excli2021-3417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975638PMC
February 2021

Novel combined single dose anti-hepatitis C therapy: a pilot study.

Sci Rep 2021 02 25;11(1):4623. Epub 2021 Feb 25.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY, 12144, USA.

The new anti-hepatitis C virus (HCV) molecules improve treatment regimens and outcomes, but there are drawbacks. New combinations should target the HCV infectious cycle and be effective against all HCV genotypes. We developed the novel formulation Catvira, composed of epigallocatechingallate (EGCG) + sofosbuvir + ribavirin. Here, we compared Catvira to sofosbuvir + ribavirin tablets in patients with CHC genotype 4 in a randomized open-label efficacy and safety study. Treatment-naïve and treatment-experienced patients (n = 80) were randomly assigned to receive a single daily fixed dose of Catvira or sofosbuvir + ribavirin for 12 or 24 weeks. Both Catvira and sofosbuvir + ribavirin yielded similar outcomes of viral load (p < 0.001). Patients receiving Catvira had a significantly more rapid rate of viral load decline with sustained virologic response (SVR12) achieved by 90% of patients receiving 12 weeks of treatment. Catvira did not impact hemoglobin levels while sofosbuvir + ribavirin showed significant decline in hemoglobin levels after 24 weeks (p < 0.05). In this clinical trial (ClinicalTrials.gov Identifier NCT02483156), we found that Catvira administered daily for 12 or 24 weeks is safe, effective, and well-tolerated in both naïve and treatment-experienced patients with HCV genotype 4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-84066-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907074PMC
February 2021

Non-alcoholic steatohepatitis or metabolic-associated fatty liver: time to change.

Hepatobiliary Surg Nutr 2021 Jan;10(1):123-125

Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/hbsn-20-438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867717PMC
January 2021

HCC developed in CHC patients who achieved SVR following DAAs tend to display less aggressive pattern.

Clin Res Hepatol Gastroenterol 2021 05 5;45(3):101608. Epub 2021 Jan 5.

Hepato-gastroenterology and Infectious Diseases Department, Al-Azhar University, Cairo, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.101608DOI Listing
May 2021

External validation of aMAP risk score in patients with chronic hepatitis C genotype 4 and cirrhosis who achieved SVR following DAAs.

J Hepatol 2021 04 16;74(4):994-996. Epub 2020 Dec 16.

Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt; Tropical Medicine Department, Faculty of Medicine, Port Said University, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2020.10.008DOI Listing
April 2021

Nomenclature and definition of metabolic-associated fatty liver disease: a consensus from the Middle East and north Africa.

Lancet Gastroenterol Hepatol 2021 01 9;6(1):57-64. Epub 2020 Nov 9.

Egyptian Liver Research Institute and Hospital, Mansoura, Egypt; Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt.

With the increasing prevalence of obesity and type 2 diabetes, fatty liver disease associated with metabolic dysfunction is a global health problem, especially because it is one of the earliest consequences of obesity and it precedes diabetes development. Fatty liver disease associated with metabolic dysfunction is of particular concern in the Middle East and north Africa, where its prevalence is greater than that in the rest of the world. Despite the magnitude of the problem, no regional guidelines have been developed to address this disease. This Review describes suggestions of redefining fatty liver disease associated with metabolic dysfunction, including its terminology and criteria for diagnosis. Experts have raised serious concerns on the current nomenclature, which labels the disease as non-alcoholic fatty liver disease (NAFLD), and its diagnostic criteria. The panel reached a consensus that the disease should be renamed as metabolic-associated fatty liver disease (MAFLD) and that the disease should be diagnosed by positive criteria. The aim is now to work with authorities across the region to implement these proposed changes and reflect them in health-care policy and to improve health care for patients in this region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2468-1253(20)30213-2DOI Listing
January 2021

Reply to: Suboptimal accuracy of GES score to stratify post SVR HCC risk in a single-centre cohort of European cirrhotics.

Liver Int 2021 05 23;41(5):1155-1156. Epub 2020 Nov 23.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14724DOI Listing
May 2021

The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease.

Int Urol Nephrol 2021 Apr 27;53(4):749-761. Epub 2020 Oct 27.

Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Background/aim: Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies for those with chronic-kidney disease (CKD) has not been evaluated.

Patients/methods: This single-center retrospective study included 235 renal patients: i.e., 70-CKD patients not on hemodialysis (42 with anemia, 28 without); 40 hemodialysis patients (16 anemic; 24 non-anemic), and 125 kidney-transplant (KTx) recipients (40 anemic; 85 non-anemic). Anemia was defined by a hemoglobin level < 10.5 g/dL. Hemodialysis patients received ritonavir-boosted paritaprevir/ombitasvir. KTx patients received sofosbuvir/daclatasvir. CKD patients with eGFR > 30 mL/min/1.73 m received sofosbuvir/daclatasvir. Those with eGFR < 30 mL/min/1.73 m received ritonavir-boosted paritaprevir/ombitasvir; 64 non-anemic patients also received ribavirin therapy.

Results: Mean age of CKDs was 49.1 years, 43.2 years for HDs, and 45.2 years for KTx patients. Most were male; body-mass index was ~ 23.8. Anemia did not affect the efficacy of DAAs in hemodialysis, CKD, or KTx patients. Most patients achieved a rapid virologic response (RVR), and a 12- and 24-week sustained viral response. Worsening of anemia among the non-anemic group was mostly related to ribavirin therapy in hemodialysis patients (11/16 patients). Acute kidney injury in CKDs occurred more frequently within the anemic group (59.5%) compared to the non-anemic group (32.1%). For KTx, graft impairment was more common among the anemic group (7/40) compared to the non-anemic group (2/85).

Conclusion: Hemoglobin levels of < 10.5 g/dL prior to DAA treatment did not affect the virological response in renal patients but was associated with increased serum creatinine among KTx and those with CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11255-020-02656-yDOI Listing
April 2021

Redefining fatty liver disease: an international patient perspective.

Lancet Gastroenterol Hepatol 2021 01 5;6(1):73-79. Epub 2020 Oct 5.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia. Electronic address:

Despite its increased recognition as a major health threat, fatty liver disease associated with metabolic dysfunction remains largely underdiagnosed and undertreated. An international consensus panel has called for the disease to be renamed from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) and has suggested how the disease should be diagnosed. This Viewpoint explores the call from the perspective of patient advocacy groups. Patients are well aware of the negative consequences of the NAFLD acronym. This advocacy group enthusiastically endorses the call to reframe the disease, which we believe will ultimately have a positive effect on patient care and quality of life and, through this effect, will reduce the burden on health-care systems. For patients, policy makers, health planners, donors, and non-hepatologists, the new acronym MAFLD is clear, squarely placing the disease as a manifestation of metabolic dysfunction and improving understanding at a public health and patient level. The authors from representative patient groups are supportive of this change, particularly as the new acronym is meaningful to all citizens as well as governments and policy makers, and, above all, is devoid of any stigma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2468-1253(20)30294-6DOI Listing
January 2021

The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.

Hepatol Int 2020 Dec 1;14(6):889-919. Epub 2020 Oct 1.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia.

Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-020-10094-2DOI Listing
December 2020

GES: A validated simple score to predict the risk of HCC in patients with HCV-GT4-associated advanced liver fibrosis after oral antivirals.

Liver Int 2020 11;40(11):2828-2833

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.

Background & Aims: Hepatocellular carcinoma (HCC) risk persists after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs), particularly in patients with cirrhosis. Identifying those who are likely to develop HCC is a critical unmet medical need. Our aim is to develop a score that offers individualized patient HCC risk prediction.

Methods: This two-centre prospective study included 4400 patients, with cirrhosis and advanced fibrosis who achieved a sustained virologic response (SVR), including 2372 patients (derivation cohort). HCC-associated factors were identified by multivariable Cox regression analysis to develop a scoring model for prediction of HCC risk; and subsequently internally and externally validated in two independent cohorts of 687 and 1341 patients.

Results: In the derivation cohort, the median follow-up was 23.51 ± 8.21 months, during which 109 patients (4.7%) developed HCC. Age, sex, serum albumin, α fetoprotein and pretreatment fibrosis stage were identified as risk factors for HCC. A simple predictive model (GES) score was constructed. The 2-year cumulative HCC incidence using Kaplan-Meier method was 1.2%, 3.3% and 7.1% in the low-risk, medium-risk and high-risk groups respectively. Internal and external validation showed highly significant difference among the three risk groups (P < .001) with regard to cumulative HCC risk. GES score has high predictive ability value (Harrell's C statistic 0.801), that remained robustly consistent across two independent validation cohorts (Harrell's C statistic 0.812 and 0.816).

Conclusion: GES score is simple with validated good predictive ability for the development of HCC after eradication of HCV and may be useful for HCC risk stratification in those patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14666DOI Listing
November 2020

Reduced incidence of hepatitis C in 9 villages in rural Egypt: Progress towards national elimination goals.

J Hepatol 2021 02 12;74(2):303-311. Epub 2020 Sep 12.

Department of Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland.

Background & Aims: Egypt has a major HCV burden and a well established treatment programme, with an ambitious goal of HCV elimination. Our aim was to assess the impact of a comprehensive HCV prevention, test and treat programme on the incidence of new HCV infections in 9 villages in rural Egypt.

Methods: An HCV "educate, test and treat" project was implemented in 73 villages across 7 governorates in Egypt between 06/2015 and 06/2018. In 2018, in 9 of the villages we re-tested individuals who originally tested HCV antibody (HCV-Ab) and HBsAg negative using rapid diagnostic tests (RDTs); confirmatory HCV RNA testing was performed for positive cases. The incidence rate per 1,000 person-years (py) was calculated, and risk factors for incident HCV infections assessed through an interviewer-administered questionnaire in 1:3 age- and gender-matched cases and controls.

Results: Out of 20,490 individuals who originally tested HCV-Ab negative in the 9 villages during the 2015-2016 implementation of the "educate, test and treat" programme, 19,816 (96.7%) were re-tested in 2018. Over a median of 2.4 years (IQR 2.1-2.7), there were 19 new HCV infections all of which were HCV RNA positive (incidence rate 0.37/1,000 py) (95% CI 0.24-0.59). Compared to a previous estimate of incidence in the Nile Delta region (2.4/1,000 py) from 2006, there was a substantial reduction in overall incidence of new HCV infections. Exposures through surgery (odds ratio 51; 95% CI 3.5-740.1) and dental procedures (odds ratio 23.8; 95% CI 2.9-194.9) were significant independent predictors of incident infections.

Conclusions: This is the first study to show a substantial reduction in incidence of new HCV infections in a sample of the general population in Egypt following attainment of high testing and treatment coverage. New infections were significantly associated with healthcare-associated exposures.

Lay Summary: Egypt has a major national HCV testing and treatment programme with the goal of eliminating HCV infection. We assessed the impact of a comprehensive HCV prevention, test and treat programme in 73 villages that achieved high coverage of testing and treatment on the subsequent incidence of new HCV infections in nine of the villages. We re-tested people who were previously HCV antibody negative and found that the rate of new HCV infections was greatly reduced compared to previous estimates. We also found that exposure through surgery and dental procedures were associated with these new infections. This highlights the importance of continued strengthening of infection control and prevention measures, alongside treatment scale-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2020.09.008DOI Listing
February 2021

Current coronavirus (SARS-CoV-2) epidemiological, diagnostic and therapeutic approaches: An updated review until June 2020.

EXCLI J 2020 20;19:992-1016. Epub 2020 Jul 20.

Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansoura, Egypt.

Coronaviruses are a group of enveloped viruses with non-segmented, single-stranded, and positive-sense RNA genomes. In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Wuhan City, China. The World Health Organization (WHO) declared the coronavirus outbreak as a global pandemic in March 2020. Fever, dry cough and fatigue are found in the vast majority of all COVID-19 cases. Early diagnosis, treatment and future prevention are keys to COVID-19 management. Currently, the unmet need to develop cost-effective point-of-contact test kits and efficient laboratory techniques for confirmation of COVID-19 infection has powered a new frontier of diagnostic innovation. No proven effective therapies or vaccines for SARS-CoV-2 currently exist. The rapidly increasing research regarding COVID-19 virology provides a significant number of potential drug targets. Remdesivir may be the most promising therapy up till now. On May 1, 2020, Gilead Sciences, announced that the U.S. Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for the investigational Remdesivir as a potential antiviral for COVID-19 treatment. On May 7, 2020, Gilead Sciences, announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval of Veklury® (Remdesivir) as a treatment for SARS-CoV-2 infection, the virus that causes COVID-19 acute respiratory syndrome, under an exceptional approval pathway. Also, Corticosteroids are recommended for severe cases only to suppress the immune response and reduce symptoms, but not for mild and moderate patients where they are associated with a high-risk side effect. Based on the currently published evidence, we tried to highlight different diagnostic approaches, side effects and therapeutic agents that could help physicians in the frontlines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17179/excli2020-2554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415934PMC
July 2020
-->