Publications by authors named "Reham Soliman"

37 Publications

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 2021 Nov 12. Epub 2021 Nov 12.

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.
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http://dx.doi.org/10.1111/hepr.13729DOI Listing
November 2021

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

J Viral Hepat 2021 Sep 28. Epub 2021 Sep 28.

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.
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http://dx.doi.org/10.1111/jvh.13621DOI Listing
September 2021

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

Circadian Control of Sodium and Blood Pressure Regulation.

Am J Hypertens 2021 Jun 24. Epub 2021 Jun 24.

Section of Cardio-renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

The attention for the control of dietary risk factors involved in the development of hypertension, includes a large effort on dietary salt restrictions. Ample studies show the beneficial role of limiting dietary sodium as a lifestyle modification in the prevention and management of essential hypertension. Not until the past decade or so have studies more specifically investigated diurnal variations in renal electrolyte excretion, which led us to the hypothesis that timing of salt intake may impact cardiovascular health and blood pressure regulation. Cell autonomous molecular clocks as the name implies, function independently to maintain optimum functional rhythmicity in the face of environmental stressors such that cellular homeostasis is maintained at all times. Our understanding of mechanisms influencing diurnal patterns of sodium excretion and blood pressure has expanded with the discovery of the circadian clock genes. In this review, we discuss what is known about circadian regulation of renal sodium handling machinery and its influence on blood pressure regulation, with timing of sodium intake as a potential modulator of the kidney clock.
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http://dx.doi.org/10.1093/ajh/hpab100DOI Listing
June 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.
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http://dx.doi.org/10.1186/s12889-021-11169-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218412PMC
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.
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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.
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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.
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http://dx.doi.org/10.1038/s41598-021-84066-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907074PMC
February 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.

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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.

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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.
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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.

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http://dx.doi.org/10.1111/liv.14724DOI Listing
May 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.
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http://dx.doi.org/10.1016/S2468-1253(20)30294-6DOI Listing
January 2021

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

Evidence for G-Protein-Coupled Estrogen Receptor as a Pronatriuretic Factor.

J Am Heart Assoc 2020 05 10;9(10):e015110. Epub 2020 May 10.

Division of Nephrology Department of Medicine University of Alabama at Birmingham AL.

Background The novel estrogen receptor, G-protein-coupled estrogen receptor (GPER), is responsible for rapid estrogen signaling. GPER activation elicits cardiovascular and nephroprotective effects against salt-induced complications, yet there is no direct evidence for GPER control of renal Na handling. We hypothesized that GPER activation in the renal medulla facilitates Na excretion. Methods and Results Herein, we show that infusion of the GPER agonist, G1, to the renal medulla increased Na excretion in female Sprague Dawley rats, but not male rats. We found that GPER mRNA expression and protein abundance were markedly higher in outer medullary tissues from females relative to males. Blockade of GPER in the renal medulla attenuated Na excretion in females. Given that medullary endothelin 1 is a well-established natriuretic factor that is regulated by sex and sex steroids, we hypothesized that GPER activation promotes natriuresis via an endothelin 1-dependent pathway. To test this mechanism, we determined the effect of medullary infusion of G1 after blockade of endothelin receptors. Dual endothelin receptor subtype A and endothelin receptor subtype B antagonism attenuated G1-induced natriuresis in females. Unlike males, female mice with genetic deletion of GPER had reduced endothelin 1, endothelin receptor subtype A, and endothelin receptor subtype B mRNA expression compared with wild-type controls. More important, we found that systemic GPER activation ameliorates the increase in mean arterial pressure induced by ovariectomy. Conclusions Our data uncover a novel role for renal medullary GPER in promoting Na excretion via an endothelin 1-dependent pathway in female rats, but not in males. These results highlight GPER as a potential therapeutic target for salt-sensitive hypertension in postmenopausal women.
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http://dx.doi.org/10.1161/JAHA.119.015110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660860PMC
May 2020

Diurnal Control of Blood Pressure Is Uncoupled From Sodium Excretion.

Hypertension 2020 06 20;75(6):1624-1634. Epub 2020 Apr 20.

From the Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham (J.G.J., B.K.B., M.K., R.H.S., M.K.R., B.T., C.J., K.A.H., J.S.P., D.M.P.).

The diurnal rhythms of sodium handling and blood pressure are thought to be regulated by clock genes, such as Bmal1. However, little is known about the regulation of these factors by Bmal1, especially in rats. Using a novel whole-body Bmal1 knockout rat model (), we hypothesized that time of day regulation of sodium excretion is dependent on Bmal1. Using telemetry to continuously record mean arterial pressure, we observed that male and female rats had significantly reduced mean arterial pressure over the course of 24 hours compared with littermate controls. The circadian mean arterial pressure pattern remained intact in both sexes of rats, which is in contrast to the mouse model. Male rats had no significant difference in baseline sodium excretion between 12-hour active and inactive periods, indicating a lack of diurnal control independent of maintained mean arterial pressure rhythms. Female rats, however, had significantly greater sodium excretion during the active versus inactive period similar to controls. Thus, we observed a clear dissociation between circadian blood pressure and control of sodium excretion that is sex dependent. These findings are consistent with a more robust ability of females to maintain control of sodium excretion, and furthermore, demonstrate a novel role for Bmal1 in control of diurnal blood pressure independent of sodium excretion.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228023PMC
June 2020

Antifibrotic Effect of Combination of Nilotinib and Stem Cell-Conditioned Media on CCl-Induced Liver Fibrosis.

Stem Cells Int 2020 3;2020:6574010. Epub 2020 Feb 3.

Biochemistry Department, Faculty of Science, Zagazig University, Egypt.

Liver fibrosis is the excessive extracellular matrix accumulation of proteins, such as collagen, which follows the chronic liver diseases. Advanced liver fibrosis leads to cirrhosis and liver failure. Nilotinib is a second-generation tyrosine kinase inhibitor, which showed antifibrotic efficacy. Stem cell therapy still has some limitations such as oncogenesis, unexpected differentiation, and ethical consideration. Stem cells secrete cytokines and growth factors that showed paracrine-mediated antifibrotic and anti-inflammatory effects in vivo and in vitro. Thus, stem cell-conditioned medium (SC-CM), which contains the secretory proteins of stem cells, may have an antifibrotic role. This study was carried out to examine the antifibrotic effect of Nilotinib and stem cell exosomes on CCl-induced liver fibrosis in rats. Male Wistar rats were injected intraperitoneally with CCl twice a week for 9 weeks and given daily treatments of Nilotinib (20 mg/kg), stem cell exosomes (0.5 ml/rat), and the combination treatment of Nilotinib and stem cell exosomes during the last 5 weeks of CCl intoxication. Liver fibrosis and also antifibrotic efficacy of the treatments were estimated with liver function tests, oxidative stress parameters, apoptotic parameters, histopathological examination, and hydroxyproline contents. Results showed that the combination of Nilotinib and stem cell-conditioned media had more antifibrotic effects than each one alone ( value < 0.001).
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http://dx.doi.org/10.1155/2020/6574010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023822PMC
February 2020

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study.

J Viral Hepat 2020 07 4;27(7):671-679. Epub 2020 Mar 4.

Internal Medicine Department, Faculty of Medicine, Minya University, Minya, Egypt.

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%-8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long-term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis-related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow-up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow-up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow-up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942-2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407-3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333-1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.
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http://dx.doi.org/10.1111/jvh.13276DOI Listing
July 2020

A same day 'test and treat' model for chronic HCV and HBV infection: Results from two community-based pilot studies in Egypt.

J Viral Hepat 2020 06 10;27(6):593-601. Epub 2020 Mar 10.

Global Hepatitis Programme, Department of HIV, Hepatitis and STIs (HHS), World Health Organization, Geneva, Switzerland.

Prompt access to confirmatory viral load testing and staging of liver disease are key barriers in uptake of treatment for chronic hepatitis B and C infection. Our objective was to establish the feasibility of a same day 'test and treat' model in two distinct community-based settings in Egypt through use of key point-of-care (POC) portable tools for HCV and HBV viral load assessment and staging of liver disease followed by treatment initiation. Community sites were a village in northern Egypt (site 1) and a government office in Cairo (site 2). The following model was adopted: community awareness raising in the week before project initiation; site assessment to ensure optimal placement and calibration of equipment and clinical care set-up; transfer of key portable laboratory instruments to the sites (four cartridge GeneXpert, FibroScan and abdominal ultrasound); screening using rapid diagnostic tests for HCV-Ab and HBsAg, with immediate venous or finger-stick blood sampling for HCV-RNA and HBV-DNA assay, FibroScan staging of liver disease and ultrasound screening for liver cancer. At site 1, 475 individuals were screened over a single day, 125 were positive for HCV-Ab and 4 for HBsAg, 43 of 56 new HCV diagnoses were HCV RNA positive, and 3 of 4 HBsAg positive were HBV DNA positive, 40 initiated HCV treatment, and one HBV treatment . At site 2, 3188 individuals were screened over 3 days, 157 were positive for HCV-Ab, and 27 for HBsAg; 38 of 76 new HCV diagnoses were HCV RNA positive, and 15 of 18 HBsAg positive were HBV-DNA positive. Across both sites, 78 patients were counselled and initiated on treatment for HCV and 12 for HBV within 3 and 4 hours, respectively, of initial positive rapid diagnostic test result. We have shown the feasibility of a same day 'test and treat' model for chronic HCV and HBV infection in two community-based settings in Egypt that achieved high levels of linkage to care and initial treatment.
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http://dx.doi.org/10.1111/jvh.13268DOI Listing
June 2020

Greater natriuretic response to ENaC inhibition in male versus female Sprague-Dawley rats.

Am J Physiol Regul Integr Comp Physiol 2020 02 8;318(2):R418-R427. Epub 2020 Jan 8.

Section of Cardio-renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical α-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.
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http://dx.doi.org/10.1152/ajpregu.00060.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052599PMC
February 2020

Loss of circadian gene in the collecting duct lowers blood pressure in male, but not female, mice.

Am J Physiol Renal Physiol 2020 03 6;318(3):F710-F719. Epub 2020 Jan 6.

Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Kidney function follows a 24-h rhythm subject to regulation by circadian genes including the transcription factor . A high-salt diet induces a phase shift in expression in the renal inner medulla that is dependent on endothelin type B (ET) receptors. Furthermore, ET receptor-mediated natriuresis is sex dependent. Therefore, experiments tested the hypothesis that collecting duct regulates blood pressure in a sex-dependent manner. We generated a mouse model that lacks expression in the collecting duct, where ET receptor abundance is highest. Male, but not female, collecting duct knockout (CDBmal1KO) mice had significantly lower 24-h mean arterial pressure (MAP) than flox controls (105 ± 2 vs. 112 ± 3 mmHg for male mice and 106 ± 1 vs. 108 ± 1 mmHg for female mice, by telemetry). After 6 days on a high-salt (4% NaCl) diet, MAP remained significantly lower in male CDBmal1KO mice than in male flox control mice (107 ± 2 vs. 113 ± 1 mmHg), with no significant differences between genotypes in female mice (108 ± 2 vs. 109 ± 1 mmHg). ET receptor blockade for another 6 days increased MAP similarly in both male and female CDBmal1KO and flox control mice. However, MAP remained lower in male CDBmal1KO mice than in male flox control mice (124 ± 2 vs. 130 ± 2 mmHg). No significant differences were observed between female CDBmal1KO and flox mice during ET blockade (130 ± 2 vs. 127 ± 2 mmHg). There were no significant genotype differences in amplitude or phase of MAP in either sex. These data suggest that collecting duct has no role in circadian MAP but plays an important role in overall blood pressure in male, but not female, mice.
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http://dx.doi.org/10.1152/ajprenal.00364.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099501PMC
March 2020

An educate, test and treat model towards elimination of hepatitis C infection in Egypt: Feasibility and effectiveness in 73 villages.

J Hepatol 2020 04 14;72(4):658-669. Epub 2019 Nov 14.

Global Hepatitis Programme, HIV Department, World Health Organization, Geneva, Switzerland.

Background & Aims: Egypt has one of the highest burdens of HCV infection worldwide. It has a large treatment programme, but reaching rural communities represents a major challenge. We report on the feasibility and effectiveness of a comprehensive community-based HCV prevention, testing and treatment model whose goal was to eliminate infection from all adult villagers.

Methods: An HCV "educate, test and treat" programme was implemented in 73 villages across 7 governorates in Egypt between 06/2015 and 06/2018. The programme model comprised community mobilisation facilitated by a network of village promoters to support the education, testing and treatment of patients, as well as fundraising in the local community. Comprehensive testing, linkage to care and treatment were provided for all eligible villagers aged 12 to 80 years.

Results: Of 221,855 eligible villagers, 204,749 (92.3%, 95% CI 91.6-93.5) were screened for HCV antibody and HBsAg, of whom 33,839 (16.5%, 95% CI 12.2-16.1) and 763 (0.4%, 95% CI 0.3-0.5) were positive, respectively. Nearly all 33,839 HCV antibody positive individuals had a sample immediately collected for HCV RNA testing, and 15,892 were HCV RNA positive. The overall prevalence of HCV viraemia was 7.8%. A total of 14,495 (91.2%, 95% CI 89.9-96.4) patients received treatment within a median of 2.1 weeks from serological diagnosis (IQR 0.6-3.3 weeks) and a sustained virological response was achieved among 14,238 of the treated cases (98.3%, 95% CI 96.7-98.6). Cirrhosis was present in 3,192 patients (20.1%), of whom 166 (5.2%) were diagnosed with hepatocellular carcinoma. There was treatment coverage and cure of 84.6% of the estimated 17,137 infected persons aged 12-80 years across the 73 villages.

Conclusion: In this study of more than 200,000 villagers, we demonstrated the feasibility and effectiveness of a community-based "educate, test and treat" programme as a model for the elimination of HCV infection in rural communities.

Lay Summary: A large community-based educate, test and treat hepatitis C programme was conducted in more than 200,000 villagers across 73 villages in Egypt. This study demonstrates that a simplified care model can achieve high uptake of testing, linkage to care and treatment, with high cure rates. We consider this a model for the elimination of hepatitis C virus infection in rural communities, which can be applied to other countries highly affected by hepatitis C.
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http://dx.doi.org/10.1016/j.jhep.2019.11.004DOI Listing
April 2020

Addition of Epigallocatechin Gallate 400 mg to Sofosbuvir 400 mg + Daclatisvir 60 mg With or Without Ribavirin in Treatment of Patients with Chronic Hepatitis C Improves the Safety Profile: A Pilot Study.

Sci Rep 2019 09 19;9(1):13593. Epub 2019 Sep 19.

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

Emergence of new molecules acting directly on the hepatitic C virus (HCV) has improved treatment outcomes. However, there is a risk of selecting viral escape mutants, so a new combination is needed using different inhibitors that target different steps of the HCV infectious cycle. Novel single tablet formulations were developed: Dactavira, composed of sofosbuvir (SOF) 400 mg/daclatisvir (DCV) 60 mg/epigallocatechin gallate (EGCG) 400 mg without ribavirin (RBV); and Dactavira plus, which includes RBV 800 mg. A randomized, open-label study was carried out on treatment-naïve non-cirrhotic (Group A, n = 50) and treatment-naïve cirrhotic (Group B, n = 22) patients with genotype 4 HCV infection. Group A was randomly assigned to receive a single daily fixed-dose (Dactavira, n = 25) or the standard of care [SOF 400 mg/DCV 60 mg] (n = 25) daily for 12 weeks. Group B was randomly assigned to receive a single daily fixed-dose (Dactavira plus, n = 11) or the standard of care + RBV 800 mg (n = 11) daily for 12 weeks. Patients receiving Dactavira or Dactavira plus had a significantly more rapid rate of viral load decline as compared to patients receiving the standard of care therapy. Sustained virological response for 12 weeks for Dactavira or Dactavira plus showed no statistically significant difference when compared to the standard of care. Also, they did not affect normal hemoglobin levels (p < 0.001) versus the standard of care. The incorporated EGCG interferes with the viral entry mechanisms, as reported by several investigators, and in turn enhances efficacy and prevents relapse as compared to the standard of care. Also, its antihemeolytic and antifibrotic activities may improve the safety and tolerability of the therapy.
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http://dx.doi.org/10.1038/s41598-019-49973-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753069PMC
September 2019

Deriving the optimal limit of detection for an HCV point-of-care test for viraemic infection: Analysis of a global dataset.

J Hepatol 2019 07 21;71(1):62-70. Epub 2019 Feb 21.

Boston Medical Center, Section of Infectious Diseases, Boston University School of Public Health, Boston, USA; Department of Epidemiology, Section of Infectious Diseases, Boston University School of Public Health, Boston, USA. Electronic address:

Background & Aims: Affordable point-of-care tests for hepatitis C (HCV) viraemia are needed to improve access to treatment in low- and middle-income countries. Our aims were to determine the target limit of detection (LOD) necessary to diagnose the majority of people with HCV eligible for treatment, and identify characteristics associated with low-level viraemia (LLV) (defined as the lowest 3% of the distribution of HCV RNA) to understand those at risk of being misdiagnosed.

Methods: We established a multi-country cross-sectional dataset of first available quantitative HCV RNA measurements linked to demographic and clinical data. We excluded individuals on HCV treatment. We analysed the distribution of HCV RNA and determined critical thresholds for detection of HCV viraemia. We then performed logistic regression to evaluate factors associated with LLV, and derived relative sensitivities for significant covariates.

Results: The dataset included 66,640 individuals with HCV viraemia from across the world. The LOD for the 95th and 99th percentiles were 3,311 IU/ml and 214 IU/ml. The LOD for the 97th percentile was 1,318 IU/ml (95% CI 1,298.4-1,322.3). Factors associated with LLV, defined as HCV RNA <1,318 IU/ml, were younger age 18-30 vs. 51-64 years (odds ratios [OR] 2.56; 95% CI 2.19-2.99), female vs. male sex (OR 1.32; 95% CI 1.18-1.49), and advanced fibrosis stage F4 vs. F0-1 (OR 1.44; 95% CI 1.21-1.69). Only the younger age group had a decreased relative sensitivity below 95%, at 93.3%.

Conclusions: In this global dataset, a test with an LOD of 1,318 IU/ml would identify 97% of viraemic HCV infections among almost all populations. This LOD will help guide manufacturers in the development of affordable point-of-care diagnostics to expand HCV testing and linkage to care in low- and middle-income countries.

Lay Summary: We created and analysed a dataset from 12 countries with 66,640 participants with chronic hepatitis C virus infection. We determined that about 97% of those with viraemic infection had 1,300 IU/ml or more of circulating virus at the time of diagnosis. While current diagnostic tests can detect as little as 12 IU/ml of virus, our findings suggest that increasing the level of detection closer to 1,300 IU/ml would maintain good test accuracy and will likely enable development of more affordable portable tests for use in low- and middle-income countries.
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http://dx.doi.org/10.1016/j.jhep.2019.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014921PMC
July 2019

Treatment of Chronic Hepatitis C Infection Among Egyptian Kidney Transplant Recipients: A Pilot Study.

Exp Clin Transplant 2019 01;17(Suppl 1):62-67

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

Objectives: Chronic hepatitis C infection incidence and prevalence are high in Egypt and represent a major health burden. Hepatitis C virus infection can affect graft outcomes in kidney transplant recipients. Treatment of hepatitis C virus infection among this special group was difficult during the interferon era; however, with advances in direct-acting antivirals, treatment outcomes have become more promising.

Materials And Methods: This is a pilot, observational, single-center, one arm study that included 50 kidney transplant recipients seen at the Mansoura (Egypt) Urology and Nephrology Center. Patients were consented to receive a sofosbuvir-based regimen as all had creatinine clearance of greater than 30 mL/min/1.73 m2.

Results: All patients achieved rapid virologic responses 4 weeks after starting treatment. Forty-nine of 50 patients achieved 12-week and 24-week sustained viral responses. Six patients had increased serum creatinine levels. Four graft biopsies were performed. Anemia was the most common adverse effect among the patients who were maintained on ribavirin.

Conclusions: Treatment of chronic hepatitis C infection has become easier and safe with the advance of new direct-acting antivirals.
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http://dx.doi.org/10.6002/ect.MESOT2018.L57DOI Listing
January 2019

Autonomic nerves and circadian control of renal function.

Auton Neurosci 2019 03 10;217:58-65. Epub 2019 Jan 10.

Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, United States of America. Electronic address:

Cardiovascular and renal physiology follow strong circadian rhythms. For instance, renal excretion of solutes and water is higher during the active period compared to the inactive period, and blood pressure peaks early in the beginning of the active period of both diurnal and nocturnal animals. The control of these rhythms is largely dependent on the expression of clock genes both in the central nervous system and within peripheral organs themselves. Although it is understood that the central and peripheral clocks interact and communicate, few studies have explored the specific mechanism by which various organ systems within the body are coordinated to control physiological processes. The renal sympathetic nervous innervation has long been known to have profound effects on renal function, and because the sympathetic nervous system follows strong circadian rhythms, it is likely that autonomic control of the kidney plays an integral role in modulating renal circadian function. This review highlights studies that provide insight into this interaction, discusses areas lacking clarity, and suggests the potential for future work to explore the role of renal autonomics in areas such as blood pressure control and chronic kidney disease.
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http://dx.doi.org/10.1016/j.autneu.2019.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415626PMC
March 2019

Hepatitis C incidence 3 years after implementation of an educate, test, and treat programme in an Egyptian village.

Lancet Gastroenterol Hepatol 2019 01 6;4(1):13-14. Epub 2018 Dec 6.

Global Hepatitis Programme, HIV Department, World Health Organization, Geneva, Switzerland.

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http://dx.doi.org/10.1016/S2468-1253(18)30336-4DOI Listing
January 2019
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