Publications by authors named "Imam Waked"

93 Publications

Optimised systematic review tool: Application to candidate biomarkers for the diagnosis of hepatocellular carcinoma.

Cancer Epidemiol Biomarkers Prev 2022 May 11. Epub 2022 May 11.

Imperial College London, London, United Kingdom.

This review aims to develop an appropriate review tool for systematically collating metabolites that are dysregulated in disease and applies the method to identify novel diagnostic biomarkers for hepatocellular carcinoma (HCC). Studies that analysed metabolites in blood or urine samples where HCC was compared with comparison groups (healthy, pre-cirrhotic liver disease, cirrhosis) were eligible. Tumour tissue was included to help differentiate primary and secondary biomarkers. Searches were conducted on Medline and EMBASE. A bespoke 'risk-of-bias' tool for metabolomic studies was developed adjusting for analytical quality. Discriminant metabolites for each sample type were ranked using a weighted score accounting for the direction and extent of change and the risk of bias of the reporting publication. A total of 84 eligible studies were included in the review (54 blood, 9 urine and 15 tissue), with six studying multiple sample types. High-ranking metabolites, based on their weighted score, comprised energy metabolites, bile acids, acylcarnitines and lysophosphocholines. This new review tool addresses an unmet need for incorporating quality of study design and analysis to overcome the gaps in standardisation of reporting of metabolomic data. Validation studies, standardised study designs and publications meeting minimal reporting standards are crucial for advancing the field beyond exploratory studies.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0687DOI Listing
May 2022

Case study of hepatitis C virus control in Egypt: impact of access program.

Authors:
Imam Waked

Antivir Ther 2022 Apr;27(2):13596535211067592

RinggoldID:68873National Liver Institute, Shebeen El Kom, Egypt.

Background: Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure more than 4 million chronically infected patients.

Purpose: This is a small tribute to John Martin.

Methodology And Conclusion: Here I present a summary of the HCV problem in Egypt, and how we, through Gilead's Access program under his leadership, were able to eliminate the disease.
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http://dx.doi.org/10.1177/13596535211067592DOI Listing
April 2022

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

Arab J Gastroenterol 2022 Apr 23. Epub 2022 Apr 23.

National Committee for Control of Viral Hepatitis, Egypt; Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background And Study Aims: In resource-limited countries, non-invasive tests for assessing liver fibrosis are a potential alternative to costly endoscopic screening for esophageal varices. We aimed to validate several non-invasive parameters for predicting the presence of varices.

Patients And Methods: Between September 2006 and August 2017, a total of 46,014 patients who underwent upper gastrointestinal endoscopy as one of the perquisites for receiving hepatitis C virus (HCV) therapy were enrolled and divided into group I (without varices) and group II (with varices). Non-invasive parameters of fibrosis, namely Lok index, Bonacini score, liver stiffness, FIB-4, Baveno, and extended Baveno criteria, were validated.

Results: Lok index, Bonacini score, liver stiffness, and FIB-4 had areas under the receiver operating characteristic curve (AUCs) of >0.6 (all P < 0.01 for the null hypothesis that the AUC was 0.5) for determination of the presence/absence of varices, with cutoff values of 0.80, 6.5, 21.9 kPa, and 2.94, and sensitivities of 74%, 74%, 66%, and 83%, respectively. The expanded Baveno VI criteria performed better than the Baveno VI criteria (spared endoscopy rate 81% versus 63%).

Conclusion: The use of non-invasive methods is of limited value in predicting esophageal varices. The limited accuracy of ≤60% may delay the use of appropriate primary prophylaxis against variceal bleeding in a large proportion of cirrhotic patients.
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http://dx.doi.org/10.1016/j.ajg.2022.04.003DOI Listing
April 2022

Reply to: "correspondence about "Efficacy and safety of basiliximab".

Ann Hepatol 2022 Mar-Apr;27(2):100679. Epub 2022 Jan 29.

Department of Hepatology, National Liver Institute, Menoufiya University, Shebin Elkom, Egypt.

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http://dx.doi.org/10.1016/j.aohep.2022.100679DOI Listing
April 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.
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http://dx.doi.org/10.4103/sjg.sjg_357_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919931PMC
March 2022

Lymphoepithelioma-like Hepatocellular Carcinoma: a Case Report and Review of Literature.

J Gastrointest Cancer 2021 Nov 23. Epub 2021 Nov 23.

Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin Al Kawm, Egypt.

We report a case of hepatic lymphoepithelioma-like carcinoma-hepatocellular carcinoma subtype (LEL-HCC) in a 41-year-old man with chronic hepatitis C virus (HCV) infection. The patient presented with abdominal pain and further assessment revealed a hypoechoic mass on ultrasonography. Serum alpha-fetoprotein (AFP) was 13·6 ng/dl. The patient was diagnosed as hepatocellular carcinoma based on the established triphasic computed tomography (TCT) diagnostic criteria and he underwent a surgical resection of the mass. Microscopic examination showed sheets and cords of malignant epithelial cells intermixed with heavy lymphoid infiltrate, with more than 100 tumor-infiltrating lymphocytes (TILs) per 10 high-power-field (HPF). Based on immunohistochemical studies, the malignant cells were positive for Hep Par 1 and glypican 3, focally positive for cytokeratin 7 (CK7), and negative for cytokeratin 20 (CK20). TILs were diffusely positive for cluster of differentiation 3 CD3 with an approximately equal CD4/CD8 ratio. The patient was recurrence free at 25 months after surgery, as evident by CT and serum alpha-fetoprotein level. LEL-HCC is a rare variant of HCC with a relatively better prognosis. Exploring the potential for immune modulator-based therapy in this subset of tumors is highly recommended.
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http://dx.doi.org/10.1007/s12029-021-00757-0DOI Listing
November 2021

Survival of a case of pre-eclampsia complicated with acute fatty liver of pregnancy and acute pancreatitis.

Trop Doct 2022 Jan 22;52(1):205-208. Epub 2021 Sep 22.

Professor, Department of Hepatology and Gasteroentology, National Liver Institute, Menoufia University, Shebeen El Kom, Egypt.

Acute fatty liver of pregnancy (AFLP) and acute pancreatitis are peculiar complications of pregnancy. When acute pancreatitis occurs co-incidentally with acute fatty liver of pregnancy, mortality is high. Here, we report a case of a 22-year-old lady in her 36th week of gestation, who presented with pre-eclampsia, acute fatty liver of pregnancy and acute pancreatitis. She fulfilled six Swansea criteria for diagnosis of AFLP, and the diagnosis of acute pancreatitis was based on clinical suspicion, elevated pancreatic enzymes and the sonographic appearance of a swollen pancreatic head.
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http://dx.doi.org/10.1177/00494755211041870DOI Listing
January 2022

Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis.

J Hepatocell Carcinoma 2021 12;8:925-935. Epub 2021 Aug 12.

Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt.

Background And Aim: Existing data are controversial regarding the incidence of hepatitis C (HCV)-related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4).

Methods: Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined.

Results: The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×10/mL, and high AFP were independent risk factors of developing HCC.

Conclusion: Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.
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http://dx.doi.org/10.2147/JHC.S295330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367200PMC
August 2021

Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID-19: A randomized controlled trial.

J Med Virol 2021 12 24;93(12):6750-6759. Epub 2021 Aug 24.

National Liver Institute, Shebeen El-Kom, Menoufia, Egypt.

Only a few treatments are approved for coronavirus disease-2019 (COVID-19) infections, with continuous debate about their clinical impact. Repurposing antiviral treatments might prove the fastest way to identify effective therapy. This trial aimed to evaluate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or ravidasvir (RDV) added to standard care (SOC) for patients with moderate and severe COVID-19 infection. Multicentre parallel randomized controlled open-label trial. One hundred and twenty eligible patients with moderate and severe COVID-19 infection were randomized to one of the study arms. Ten days of treatment with SOF plus DCV or RDV in addition to the standard of care compared to SOC. Follow up in 7 days. Sum of the counted symptoms at 7 and 10 days, mean change in oxygen saturation level, viral negativity, and rate of intensive care unit (ICU) admission. Compared to SOC, the SOF-DCV group experienced a significantly lower sum of the counted symptoms (fever, headache, generalized aches, or respiratory distress) combined with no evidence of deterioration (ICU admission and mechanical ventilation) on Days 7 and 10 of treatment. Oxygen saturation also significantly improved among the SOF-DCV group compared to SOC starting from Day 4. The study also showed positive trends regarding the efficacy of SOF-DCV with a lower incidence of mortality. On the other hand, adding SOF-RDV to SOC did not show significant improvements in endpoints. The results support the efficacy and safety of SOF-DCV as an add-on to SOC for the treatment of moderate to severe COVID-19 infections.
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http://dx.doi.org/10.1002/jmv.27264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426808PMC
December 2021

Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma.

Expert Rev Anti Infect Ther 2022 Feb 15;20(2):307-314. Epub 2021 Jul 15.

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

Background: There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV.

Research Design And Methods: This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein.

Results: Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01).

Conclusion: Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.
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http://dx.doi.org/10.1080/14787210.2021.1951230DOI Listing
February 2022

Retreatment of Chronic Hepatitis C Infection: Real-World Regimens and Outcomes From National Treatment Programs in Three Low- and Middle-Income Countries.

Clin Infect Dis 2022 02;74(3):513-516

Clinton Health Access Initiative, Boston, Massachusetts, USA.

Access to recommended second-line treatments is limited for patients who fail initial hepatitis C virus (HCV) therapy in low- and middle-income countries. Alternative regimens and associated outcomes are not well understood. Through a pooled analysis of national program data in Egypt, Georgia, and Myanmar, we observed SVR rates >90% for alternative retreatment regimens.
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http://dx.doi.org/10.1093/cid/ciab461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835629PMC
February 2022

Direct acting antivirals are associated with more liver stiffness regression than pegylated interferon therapy in chronic hepatitis C patients.

Expert Rev Anti Infect Ther 2021 08 29;19(8):1053-1059. Epub 2020 Dec 29.

Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt.

Objectives: Extent of post-treatment fibrosis change in patients with different stages of fibrosis not fully known. We aimed to study changes in liver fibrosis in chronic hepatitis C patients who were treated with pegylated interferon/ribavirin (PEG/RBV) or direct acting antivirals (DAAs).

Methods: Retrospective evaluation of results of transient elastography (TE) was done before and 1 year after end of treatment for patients treated with PEG/RBV ( = 268) and DAAs ( = 245).

Results: The average age was 45.54 ± 10.64 years; mainly males. All patients in the DAAs group achieved sustained virological response (SVR), unlike 56.3% of the patients in the PEG/RBV group. F3-F4 fibrosis was predominant in the PEG/RBV nonresponder patients (51.3%) and DAAs responders (57.1%). TE decreased 1 year after end of treatment ( = 0.001) in the viral responders of the PEG/RBV group (7.44 ± 4.02 vs. 10.24 ± 7.29 kPa) and DAAs group (12.12 ± 9.21 vs. 16.81 ± 12.84 kPa) respectively. The delta TE change in the DAAs responders was higher than the PEG/RBV responders ( = 0.001) and PEG/RBV nonresponders ( = 0.001). The percentage of patients with liver fibrosis regression was higher in DAAs responders (52.5%) than in PEG/RBV responders (23.3%).

Conclusion: Treatment with DAAs is associated with fibrosis improvement more than treatment with PEG/RBV in chronic hepatitis C patients.
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http://dx.doi.org/10.1080/14787210.2021.1864326DOI Listing
August 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

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

Impact of COVID-19 on global HCV elimination efforts.

J Hepatol 2021 01 7;74(1):31-36. Epub 2020 Aug 7.

Gastroenterology and Hepatology Unit, Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.

Background & Aims: Coronavirus disease 2019 (COVID-19) has placed a significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in HCV liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination programs.

Methods: Previously developed models were adapted for 110 countries to include a status quo or 'no delay' scenario and a '1-year delay' scenario assuming significant disruption in interventions (screening, diagnosis, and treatment) in the year 2020. Annual country-level model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the 'no-delay' estimates from the '1-year delay' estimates.

Results: The '1-year delay' scenario resulted in 44,800 (95% uncertainty interval [UI]: 43,800-49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths, relative to the 'no-delay' scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries.

Conclusions: The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so.

Lay Summary: COVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate to do so.
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http://dx.doi.org/10.1016/j.jhep.2020.07.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411379PMC
January 2021

Efficacy and safety of basiliximab as initial immunosuppression in liver transplantation: A single center study.

Ann Hepatol 2020 Sep - Oct;19(5):541-545. Epub 2020 Aug 5.

Department of Hepatology, National Liver Institute, Menoufiya University, Shebin Elkom, Egypt.

Introduction And Aim: The interleukin-2 receptor antagonist; basiliximab is used to allow delayed introduction of Calcineurin inhibitors (CNI) after liver transplantation and thus delay their renal insult. However, there is only little evidence for the safety and the efficacy of this regimen. This study aimed to evaluate the effectiveness and safety of basiliximab induction in liver transplantation.

Materials And Methods: This study included 89 patients who were classified into two groups: standard triple immunosuppression (IS) regimen of steroid, tacrolimus (TAC) and mycophenolate mofetil (MMF) (n = 47) and induction IS regimen of basiliximab, low dose steroids and MMF with delayed introduction of CNI (n = 42). All patients were followed after liver transplantation for at least six months or until death.

Results: There were no significant differences in patient survival, graft dysfunction, infection rate or type, or wound healing between both groups. The acute rejection rate was equivalent in both groups. Renal dysfunction in the first six months post-transplant was less in the basiliximab group in comparison to the other group (7.1% and 19.1% respectively).

Conclusion: Basiliximab-induced IS protocol is a safe regimen that reduces medium-term renal dysfunction and achieves similar survival without increasing the acute rejection or infection rate in liver transplantation recipients.
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http://dx.doi.org/10.5604/01.3001.0012.2246DOI Listing
August 2021

What's in a name? Renaming 'NAFLD' to 'MAFLD'.

Liver Int 2020 06 28;40(6):1254-1261. Epub 2020 Apr 28.

Department of Hepatology, Gastroenterology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-suef, Egypt.

In medicine, language matters and the words used to name and describe a disease can have a profound impact on patients and their families. Over the last two decades, many criticisms have been voiced about the nomenclature and definition of non-alcoholic fatty liver disease (NAFLD) in regards not only to the prominent role that alcohol plays in the definition but also on the negative impacts of the nomenclature including trivialization, stigmatization and less consideration of the disease in health policy. Recently, a consensus of international experts proposed that the disease acronym be changed from NAFLD to metabolic (dysfunction) associated fatty liver disease or 'MAFLD'. This change goes far beyond a mere semantic revision and may be the first step that catalyses the process to better conceptualize the disease for health promotion, patient orientation, case identification, ongoing clinical trials and for health services delivery. Here we review the history of, and definitions of MAFLD in the context of advancing our understanding of the pathogenesis of the disease. We also address the reasons, signals, promises, challenges and the way going forward from the name change from various stakeholder perspectives.
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http://dx.doi.org/10.1111/liv.14478DOI Listing
June 2020

Platelet-albumin-bilirubin score - a predictor of outcome of acute variceal bleeding in patients with cirrhosis.

World J Hepatol 2020 Mar;12(3):99-107

Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin Elkom 32511, Egypt.

Background: The albumin-bilirubin (ALBI) score was validated as a prognostic indicator in patients with liver disease and hepatocellular carcinoma. Incorporating platelet count in the platelet-albumin-bilirubin (PALBI) score improved validity in predicting outcome of patients undergoing resection and ablation.

Aim: To evaluate the PALBI score in predicting outcome of acute variceal bleeding in patients with cirrhosis.

Methods: The data of 1517 patients with cirrhosis presenting with variceal bleeding were analyzed. Child Turcotte Pugh (CTP) class, Model of End-stage Liver Disease (MELD), ALBI and PALBI scores were calculated on admission, and were correlated to the outcome of variceal bleeding. Areas under the receiving-operator characteristic curve (AUROC) were calculated for survival and rebleeding.

Results: Mean age was 52.6 years; 1176 were male (77.5%), 69 CTP-A (4.5%), 434 CTP-B (29.2%), 1014 CTP-C (66.8%); 306 PALBI-1 (20.2%), 285 PALBI-2 (18.8%), and 926 PALBI-3 (61.1%). Three hundred and thirty-two patients died during hospitalization (21.9%). Bleeding-related mortality occurred in 11% of CTP-B, 28% of CTP-C, in 21.8% of PALBI-2 and 34.4% of PALBI-3 patients. The AUROC for predicting survival of acute variceal bleeding was 0.668, 0.689, 0.803 and 0.871 for CTP, MELD, ALBI and PALBI scores, respectively. For predicting rebleeding the AUROC was 0.681, 0.74, 0.766 and 0.794 for CTP, MELD, ALBI and PALBI scores, respectively.

Conclusion: PALBI score on admission is a good prognostic indicator for patients with acute variceal bleeding and predicts early mortality and rebleeding.
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http://dx.doi.org/10.4254/wjh.v12.i3.99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097503PMC
March 2020

Screening and Treatment Program to Eliminate Hepatitis C in Egypt.

N Engl J Med 2020 03;382(12):1166-1174

From the Hepatology Department, National Liver Institute, Menoufia University, Shebeen El Kom (I.W., W.A.-R.), and the Endemic Medicine Department, Faculty of Medicine, Cairo University (G. Esmat, A.E., M.E.-S., A.C., W.E.A., W.D.), the Ministry of Health and Population (R.G., G. Elshishiney, A.S., S.A.M., M.A.S., K.A.H., S.A.G., N.E.N., A.E.S., S.E.S., H.E.T., E.E., H.G., A. Hashem, N.H., A.N.H., A.K., K.L., F.M., S. Mamoun, T.M., S. Mekky, A.M., A.O., O.R., E.R., A.R., T.S., R.S., M. Sharshar, H. Shawky, M. Shawky, W.S., H. Soror, M. Taha, M. Talha, A.T., M.Z., H.Z.), the National Committee for Control of Viral Hepatitis (K.K.), the Pediatrics Department (M.H.E.-S.), the Hepatology and Tropical Medicine Department (H.D.), and the Department of Medicine (Y.E.S., Y.O.), Ain Shams University, the Hepatology Department, National Hepatology and Tropical Medicine Research Institute (M.H.), the Communicable Diseases Control Cluster, World Health Organization (A. Hashish), the Medical Research Division, National Research Center (E.K., M.A.), and the Tropical Medicine Department, Al-Azhar University (I.A.), Cairo - all in Egypt.

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http://dx.doi.org/10.1056/NEJMsr1912628DOI Listing
March 2020

Hepatitis C Virus in Egypt: Interim Report From the World's Largest National Program.

Clin Liver Dis (Hoboken) 2019 Dec 29;14(6):203-206. Epub 2020 Jan 29.

Hepatology Department National Liver Institute, Menoufia University Shebeen El Kom Egypt.

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http://dx.doi.org/10.1002/cld.868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988418PMC
December 2019

Elastography and serum markers of fibrosis versus liver biopsy in 1270 Egyptian patients with hepatitis C.

Eur J Gastroenterol Hepatol 2020 12;32(12):1553-1558

Departments of Hepatology and Gastroenterology.

Background: Chronic hepatitis C (CHC) is a leading cause of liver fibrosis.

Objective: To compare utility of liver transient elastography, AST-to-platelet ratio index (APRI), fibrosis-4 index (FIB4), Forns Index and Goteborg University cirrhosis index (GUCI) in predicting fibrosis stage assessed by liver biopsy in Egyptian CHC patients.

Methods: One thousand two-hundred and seventy CHC patients undergoing liver biopsy in preparation for therapy and 40 healthy potential living liver donors had transient elastography and calculation of APRI, FIB4, Forns and GUCI scores on the same day or day preceding the biopsy.

Results: Mean age was 39.89 (17-60 years) and most were males (70.7%). All donors had F0 fibrosis, most patients had F1-F2 fibrosis (n = 1011, 79.6%) and 259 (20.4%) had F3-F4 fibrosis. Patients with F3-F4 fibrosis had higher median values of APRI (0.99 vs. 0.46), FIB4 (2.15 vs. 0.95) and Forns (7.34 vs. 4.79) indices, GUCI score (1.16 vs. 0.49) and transient elastography (19.2 vs. 6.2 kPa) (all P = 0.001). For F1 discrimination, AUROC of transient elastography was higher than both Forns and GUCI scores (P = 0.001). APRI, FIB4 and GUCI had lower AUROC than transient elastography for predicting fibrosis stage in F2 and F3 patients (P = 0.001). Transient elastography had the best area under receiver operating characteristic curve for predicting fibrosis stage in F4 patients (P = 0.001). The transient elastography cutoff values (kPa) were F1 (>4.8), F2 (>8.3), F3 (>10.1) and F4 (>13.4). Age, APRI, FIB4, Forns, GUCI and transient elastography were independent predictors of F3-F4 fibrosis.

Conclusion: Liver elastography is superior to APRI, FIB4, Forns and GUCI scores in predicting fibrosis in CHC patients.
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http://dx.doi.org/10.1097/MEG.0000000000001672DOI Listing
December 2020

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

Hepatology 2020 07 27;72(1):198-212. Epub 2020 May 27.

Department of Internal Medicine and Gastroenterology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.

Background And Aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable.

Approach And Results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years.

Conclusions: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.
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http://dx.doi.org/10.1002/hep.31022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496334PMC
July 2020

Direct-acting antiviral drugs improve the female sexual burden associated with chronic HCV infection.

Expert Rev Anti Infect Ther 2019 11 22;17(11):919-926. Epub 2019 Oct 22.

Hepatology Department, National Liver Institute, Menoufia University, Shebeen Elkom, Egypt.

: The impact of patient cure by direct-acting antiviral agents (DAAs) on female sexual dysfunction (FSD) associated with HCV hasn't been studied.: To study the impact of DAAs on associated FSD in patients with chronic HCV infection.: In patients with chronic HCV infection who were eligible for DAAs, the self-administered female-sexual-function index (FSFI) questionnaire was completed by 300 sexually active females' patients before treatment and compared to equal number of age and socioeconomically matched controls. FSFI questionnaire results after treatment were compared to patients' baseline results.: The mean total score for the patients was significantly lower than that for controls (16.77 ± 1.36 versus 17.52 ± 0.99, P < 0.001). Patients after treatment with DAAs significantly scored better results than baseline results in the total score and all domains of the questionnaire and significantly less patients had FSD compared to baseline (2.7% versus 29.3% P < 0.05). Patients' mean FSFI score significantly improved after cure (18.8 ± 0.27 vs. 16.77 ± 1.36, P < 0.001).: Hepatitis C has negative impacts on FSF and affecting all domains of FSFI. The DAAS improve the sexual burden associated with hepatitis C in patients who achieved sustained virologic response.
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http://dx.doi.org/10.1080/14787210.2019.1682551DOI Listing
November 2019

Liver stiffness measurements and FIB-4 are predictors of response to sofosbuvir-based treatment regimens in 7256 chronic HCV patients.

Expert Rev Gastroenterol Hepatol 2019 Oct 16;13(10):1009-1016. Epub 2019 Aug 16.

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

: To assess the role of baseline liver stiffness (LS) by Transient elastography (TE) and FIB-4 in the prediction of virological response to sofosbuvir - based regimens in chronic HCV patients.: A retrospective, multicenter study including 7256 chronic HCV patients who received different sofosbuvir-based regimens. Baseline demographic and laboratory data were recorded. TE was performed with FIB-4 calculation at baseline.: Sustained virological response at week 12 post-treatment (SVR12) was 91.4%. Pretreatment TE values and FIB-4 were significantly lower among sustained responders (17.8 ± 11.5 kPa, 2.66 ± 1.98, respectively) versus relapsers (24.5 ± 13.9 kPa, 4.02 ± 3.3, respectively). Best cutoff levels for LS by TE and FIB-4 score for prediction of failure to treatment response were 16.7 kPa and 2.4, respectively. Among different treatment protocol, patients with FIB-4 > 2.4, TE values >16.7 kPa are more prone to treatment failure except when using SOF/SIM treatment regimens.: Baseline LS by TE and FIB-4 score may be useful for predicting treatment outcome in the new era of DAAs and could be integrated into pretreatment assessment of chronic HCV patients for better optimization of patient management.
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http://dx.doi.org/10.1080/17474124.2019.1653183DOI Listing
October 2019

HCV treatment with direct acting antivirals improves the insulin sensitivity.

Expert Rev Anti Infect Ther 2019 09 17;17(9):749-754. Epub 2019 Aug 17.

Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University , Shebeen Elkoom , Egypt.

: There is strong link between hepatitis C virus (HCV) infection and the insulin resistance panel. Homeostatic model assessment (HOMA) β is an indirect measurement of insulin secretion from pancreatic β cells, while HOMA-S accounts for insulin sensitivity. : We examined the impact of HCV treatment with direct acting antivirals (DAAs) on HOMA-β and HOMA-S results. : HOMA-IR, HOMA-β, and HOMA-S were calculated before and 12 weeks after treatment in 511 treatment eligible patients with HCV. Five DAA treatment protocols were used. Values before and after treatment were compared. : The mean age of patients was 50.63 years with a 3.2:1 male: female ratio. A total of 29.7% of patients were treatment experienced and 24.7% had diabetes. HCV sustained virological response (SVR) was achieved in 91% of patients. Unlike non-responders, SVR patients showed significantly decreased post-treatment HOMA-Β. Delta HOMA-Β was comparable between groups. HOMA-S increased significantly in patients with SVR compared to in non-responders, as did delta HOMA-S. HOMA-S and HOMA-β improved significantly under 5 and 2 DAA protocols, respectively. The treatment status did not affect the HOMA-β and S dynamics during treatment. : Insulin sensitivity improved markedly in patients who achieved HCV SVR.
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http://dx.doi.org/10.1080/14787210.2019.1653184DOI Listing
September 2019

Intermediate stage hepatocellular carcinoma: a summary review.

J Hepatocell Carcinoma 2019 11;6:105-117. Epub 2019 Jul 11.

Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt.

It is well known that intermediate stage hepatocellular carcinoma (HCC) encompasses the widest class of patients with this disease. The main characteristic of this special sub-group of patients is that it is extensively heterogenous. This substantial heterogeneity is due to the wide range of liver functions of such patients and variable tumor numbers and sizes. Real world clinical data show huge support for transarterial chemo-embolization (TACE) as a therapeutic modality for intermediate stage HCC, applied in 50%-60% of those class of patients. There are special considerations in various international guidelines regarding treatment allocation in intermediate stage HCC. There is an epidemiological difference in HCC in eastern and western cohorts, and various guidelines have been proposed. In patients with HCC, it has frequently been reported that there is poor correlation between the clinical benefit and real gain in patient condition and the conventional way of tumor response assessment after locoregional treatments. This is due to the evaluation criteria in addition to the scoring systems used for treatment allocation in those patients. It became clear that intermediate stage HCC patients receiving TACE need a proper prognostic score that offers valid clinical prediction and supports proper decision-making. Also, it is the proper time to study more treatment options beyond TACE, such as multimodal regimens for this class of patients. In this review, we tried to provide a summary of the challenges and future directions in managing patients with intermediate stage HCC.
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http://dx.doi.org/10.2147/JHC.S168682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628956PMC
July 2019

Validation of modified albumin-bilirubin-TNM score as a prognostic model to evaluate patients with hepatocellular carcinoma.

World J Hepatol 2019 Jun;11(6):542-552

Departemnt of Hepatology, Gastroenterology and Liver Transplantation, National Liver Institute, Menoufia University, Menoufia 3511, Egypt.

Background: An ideal staging system for hepatocellular carcinoma (HCC) should rely on the hepatic reserve function and tumor burden. With the improvement in diagnostic and treatment strategies for HCC, in addition to recent treatment of viral hepatitis, finding a suitable assessment tool for hepatic reserve has become mandatory.

Aim: To validate a recently proposed modified albumin-bilirubin-TNM (mALBI-T) grade as a prognostic model for patients with HCC in Egypt.

Methods: For patients diagnosed with HCC, Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, albumin-bilirubin (ALBI), plateltet-albumin-bilirubin (PALBI), ALBI-based BCLC, ALBI-T and mALBI-T grades were estimated. Patients were followed from time of diagnosis to date of death or date of data collection if they remained alive. Overall survival and received treatments were determined. Survival data were analyzed.

Results: A total of 1910 patients were included (mean age, 57 years; 1575 males). At presentation, 50.6% had CTP A, 36.1% had CTP B and 13.4 % had CTP C; 12% had ALBI grade 1, 62.3% had ALBI grade 2 and 24.7% had ALBI grade 3. Overall median survival was 13 mo; survival was better in patients with ALBI 1 than in those with ALBI 2 and 3 (28.6 14 and 5.8 mo, respectively, < 0.001). Patients with ALBI-T grades 0 and 1 had better survival than those with ALBI-T grades 2, 3, 4 and 5 ( < 0.001). The modified ALBI-T showed better stratification and significant improvement in prediction of survival.

Conclusion: ALBI-T grade is a superior prognostic tool that selects patients with HCC who have better liver reservoir and tumor stage. mALBI-T is a better prognostic model in patients with HCC.
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http://dx.doi.org/10.4254/wjh.v11.i6.542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603504PMC
June 2019

High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study.

Expert Rev Gastroenterol Hepatol 2019 Sep 23;13(9):907-914. Epub 2019 Jun 23.

Hepatology Department, National Liver Institute, Menoufiya University , Shebeen EL Kom , Egypt.

Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment. Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point. We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis. SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.
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http://dx.doi.org/10.1080/17474124.2019.1629287DOI Listing
September 2019

Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial.

Lancet Gastroenterol Hepatol 2019 06 4;4(6):454-465. Epub 2019 Apr 4.

Onxeo, Paris, France.

Background: Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed.

Methods: We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m doxorubicin-loaded nanoparticles (30 mg/m group), 20 mg/m doxorubicin-loaded nanoparticles (20 mg/m group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01655693.

Findings: Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m group; 130 to the 20 mg/m group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2-34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1-10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1-11·8) in the control group (HR 1·00 [95% CI 0·78-1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group.

Interpretation: Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed.

Funding: Onxeo.
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http://dx.doi.org/10.1016/S2468-1253(19)30040-8DOI Listing
June 2019
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