Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Low Frequency of Aflatoxin Induced TP53 Gene Codon 249 Mutation in Hepatocellular Carcinoma from Egyptian Patients Living in the Nile Delta Region.

OBJECTIVE: Study the frequency of codon 7 (c.747 G>T, p. R249S) mutation associated with Aflatoxin B1 (AFB1) exposure in Egyptian patients with hepatocellular carcinoma (HCC). METHODS: We utilized restriction fragment polymorphism and direct sequencing to assess codon 7 mutations in 104 hepatocellular carcinomas. The expression of TP53 protein in the tumors were assessed in 44 tumors by a monoclonal rabbit antibody. RESULTS: We identified a single 1/104 (1%) with c.747 G>T, p. R249S variant. 28/44 (63.6%) tumors showed no or occasional (less than < 5%) nuclear staining; 9/44 (20.4%) showed mild to moderate (5-49%) and 7/44 (15.9%) showed strong ≥ 50% staining. CONCLUSION: We observed much lower frequency of TP53 gene than previously published results suggesting geographical alterations in AFB1 exposure in Egypt.

Impacts of the Egyptian national screening and treatment programme for viral hepatitis C: A cost-effectiveness model.

BACKGROUND & AIMS: Egypt used to have one of the highest prevalences of HCV infection worldwide. The Egyptian Ministry of Health launched a national campaign for the detection and management of HCV to reduce its burden. This study aims to carry out a cost-effectiveness analysis to evaluate the costs and benefits of the Egyptian national screening and treatment programme. METHODS: A disease burden and economic impact model was populated with the Egyptian national screening and treatment programme data to assess direct medical costs, health effects measured in disability-adjusted life years and the incremental cost-effectiveness ratio. The scenario was compared to a historical base case, which assumed that no programme had been conducted. RESULTS: Total number of viremic cases is expected to decrease in 2030 by 86% under the national screening and treatment programme, versus by 41% under the historical base case. Annual discounted direct medical costs are expected to decrease from $178 million in 2018 to $81 million by 2030 under the historical base case, while annual direct medical costs are estimated to have peaked in 2019 at $312 million before declining to $55 million by 2030 under the national screening and treatment programme. Under the programme, annual disability-adjusted life years are expected to decline to 127 647 by 2030, leading to 883 333 cumulative disability-adjusted life years averted over 2018-2030. CONCLUSIONS: The national screening and treatment programme is highly cost-effective by the year 2021, cost-saving by 2029 and expected to save about $35 million in direct costs and $4705 million in indirect costs by 2030.

IgY antibodies: The promising potential to overcome antibiotic resistance.

Antibiotic resistant bacteria are a growing threat to global health security. Whilst the emergence of antimicrobial resistance (AMR) is a natural phenomenon, it is also driven by antibiotic exposure in health care, agriculture, and the environment. Antibiotic pressure and inappropriate use of antibiotics are important factors which drive resistance. Apart from their use to treat bacterial infections in humans, antibiotics also play an important role in animal husbandry. With limited antibiotic options, alternate strategies are required to overcome AMR. Passive immunization through oral, nasal and topical administration of egg yolk-derived IgY antibodies from immunized chickens were recently shown to be effective for treating bacterial infections in animals and humans. Immunization of chickens with specific antigens offers the possibility of creating specific antibodies targeting a wide range of antibiotic-resistant bacteria. In this review, we describe the growing global problem of antimicrobial resistance and highlight the promising potential of the use of egg yolk IgY antibodies for the treatment of bacterial infections, particularly those listed in the World Health Organization priority list.

Biobanking in LMIC settings for infectious diseases: Challenges and enablers.

Biobanking facilities are well established in high-income settings, where substantial funding has been invested in infrastructure. In contrast, such facilities are much less developed in resource-restricted settings. However, low-and middle-income countries (LMICs) still face a disproportionately high infectious diseases burden. Thus, the further development of infrastructure facilities, including biobanks is warranted as an important component of this unfolding clinical research environment. This perspective manuscript summarises the challenges and enablers for biobanking in LMICs, with a particular focus on infectious diseases, incorporating some of the lessons learned from the recent coronavirus disease 2019 (COVID-19) pandemic.

Sofosbuvir/ledipasvir in combination or nitazoxanide alone are safe and efficient treatments for COVID-19 infection: A randomized controlled trial for repurposing antivirals.

BACKGROUND AND STUDY AIMS: Currently, there is no therapy approved for COVID-19. We evaluated the efficacy and safety of sofosbuvir/ledipasvir and nitazoxanide for the treatment of patients with COVID-19 infection. PATIENTS AND METHODS: A multicenter, open-label randomized controlled trial included one hundred and ninety patients with non-severe COVID-19 infection. Patients were randomized into three groups. All groups received standard care treatment (SCT). In addition, group 1 received sofosbuvir/ledipasvir, and group 2 received nitazoxanide. Follow-up by reverse-transcriptase polymerase chain reaction (RT-PCR) was done at intervals of 5, 8, 11, and 14 days. The primary endpoint was viral clearance. RESULTS: Viral clearance was significantly higher in the sofosbuvir/ledipasvir and nitazoxanide groups compared to the SCT group in all follow-up intervals (p < 0.001). In the sofosbuvir/ledipasvir arm, 36.9% showed early viral clearance by day 5. By day 14, 83.1% of the sofosbuvir/ledipasvir group, 39.7% of the nitazoxanide group, and 19.4% of the SCT group tested negative for SARS-CoV-2. Sofosbuvir/ledipasvir and nitazoxanide treatment were the only significant factors in Cox regression of negative RT-PCR with the highest OR (17.88, 95% CI: 6.66-47.98 and 2.59, 95% CI: 1.11-6.07, respectively). No mortality or serious adverse events were recorded. CONCLUSION: The addition of sofosbuvir/ledipasvir or nitazoxanide to the SCT results in an early and high viral clearance rate in mild and moderate patients with COVID-19. These drugs represent a safe and affordable treatment for COVID-19.

Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium.

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81-0.96) or 7 to 12 months (OR 0.85, 0.79-0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71-0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63-0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53-0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B-ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

The pill of recovery; Molnupiravir for treatment of COVID-19 patients; a systematic review.

Background: Throughout the time of the global pandemic of SARS-CoV-2 virus, there has been a compelling necessity for the development of effective antiviral agents and prophylactic vaccines to limit the virus spread, disease burden, hospitalization, and mortality. Until mid of 2021, the NIH treatment guideline declared no single oral therapy was proven to treat mild to moderate cases. A new hope arose when a repurposed direct acting oral anti-viral agent "Molnupiravir" was shown to be effective in decreasing mortality and need for hospitalization in mild to moderate cases with relatively good safety profile; exhibiting a significant reduction in virus titers only after two days from administration. Molnupiravir recently granted the FDA emergency use authorization to treat mild to moderate COVID-19 patients with at least one risk factor for progression. Methods: We performed a computer-based literature search of (PubMed, Science direct, MedRxiv, BioRxiv, ClinicalTrials.gov, ISRCTN, Cochrane COVID study register, EU registry, and CTRI registry) till February 15th, 2022. The following keywords were used in our search ("Molnupiravir", "NHC", "EIDD-2807", "MK-4482" or "EIDD-1931"). Results: We identified from the initial search a total of 279 articles; 246 articles (BioRxiv and MedRxiv N = 186, PubMed N = 33, Science direct N = 27) and 33 Clinical trials from the following registries (ISCTRN (N = 1), Clinical Trials.gov (N = 6), CTRI (N = 12), Cochrane (N = 14)). Through screening phases, 21 records were removed as duplicates and 198 irrelevant records were also excluded. The included studies in this systematic review were (N = 60) included 39 published papers and 21 clinical trials. After Manual addition (N = 4), the qualitative assessment included (N = 64). Conclusion: Based on the cumulative evidence from preclinical and clinical studies, Molnupiravir is proven to be a well tolerated, direct acting oral anti-viral agent to halt the disease progression in mild to moderate COVID-19 cases; in terms of mortality and hospitalization rates.

Safety and efficacy of sofosbuvir/ledipasvir and sofosbuvir/daclatasvir in the treatment of hepatitis C in patients with decompensated cirrhosis.

BACKGROUND: Hepatitis C virus (HCV)-related decompensated cirrhosis is a severe life-threatening illness. The safety of direct-acting antivirals (DAAs) has opened a gate of hope for that subgroup of patients who were previously contraindicated for interferon therapy. OBJECTIVE: We aimed at the investigation of the safety and efficacy of different DAAs regimens in the treatment of HCV-related decompensated cirrhosis patients, to determine sustained virological response (SVR)12 rates and to analyze the factors associated with response. METHODS: A retrospective, single-center study including HCV-related decompensated cirrhosis patients who received DAAs. Demographic, laboratory and clinical data were analyzed. The SVR12 rate was the primary outcome measure. Secondary outcomes included the predictors of response, changes in the baseline model for end-stage liver disease and child-turcotte-pugh (CTP) scores, and fibroindices (APRI and fibrosis-4 index) at 12 weeks after treatment. RESULTS: In total, 145 eligible patients (141 with CTP class B and 4 with class C) were enrolled in this study. SVR12 was achieved by 88.06% (118/134) of efficacy population on different DAAs regimens, Treatment was discontinued in 11 patients because of severe side effects without any deaths. Younger age showed a significant positive association with SVR12. CONCLUSIONS: DAAs can be used for the treatment of HCV-related decompensated liver disease, with acceptable SVR12 rates and safety profiles.

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

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 <100×103/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.

Effect of disease stage and treatment outcomes on the dynamics of liver functions during and after treatment of hepatitis C with directly acting antivirals.

BACKGROUND: Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs. METHODS: We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup. RESULTS: Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups. CONCLUSION: DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.

MET canonical transcript expression is a predictive biomarker for chemo-sensitivity to MET-inhibitors in hepatocellular carcinoma cell lines.

PURPOSE: Long interspersed nuclear element 1 (LINE-1 or L1) is a dominant non-long terminal repeat (non-LTR) retrotransposon in the human genome that has been implicated in the overexpression of MET. Both the canonical MET and L1-MET transcripts are considered to play a role in hepatocellular carcinoma (HCC) development. The aim of this study was to assess the utility of canonical MET, L1-MET, and MET protein expressions as predictive biomarkers for chemo-sensitivity to MET-inhibitors in HCC cell lines in vitro. Additionally, we assessed their expression in tumour tissues from Egyptian HCC patients. METHODS: MET and L1-MET expressions were assessed by qRT-PCR in six liver cancer cell lines (SNU-387, SNU-475, SK-HEP-1, PLC/PRF/5, SNU-449 and SNU-423) and 47 HCC tumour tissues. MET protein expression was measured by western blot in cell lines and immunohistochemistry in the tumours. Cell proliferation assay was used to assess the effect of crizotinib and tivantinib on the six liver cancer cell lines in correlation with the expression of MET, L1-MET and MET. RESULTS: The antitumor effect of crizotinib and tivantinib correlated with MET gene expression but not with L1-MET transcript or MET protein expressions. No significant difference was observed between HCC tumours and non-tumour samples in MET and L1-MET transcripts expression. There were no significant correlations between the 2-year overall survival rate and the MET, L1-MET transcripts and the MET protein expression. CONCLUSION: MET RNA expression could be useful biomarker for tivantinib and crizotinib targeted therapy in HCC. The value of assessment of MET protein expression is limited.

HBVsvp-Pulsed Dendritic Cell Immunotherapy Induces Th1 Polarization and Hepatitis B Virus-Specific Cytotoxic T Lymphocytes Production.

BACKGROUND: In chronic hepatitis B virus (CHB) patients, both dendritic cells (DCs) and T cells are functionally impaired and consequently the HBV-specific cellular immune responses are downregulated. The present study aims to investigate whether monocyte-derived DC (MoDCs)-pulsed-HBV subviral particles (HBVsvp) can polarize Th1 cells to induce HBV-specific cytotoxic T-lymphocytes (CTL) responses in CHB patients. METHODS AND MATERIALS: To this end, the human hepatoma HepG2.2.15 cell line was used to produce HBVsvp as a culturing system, and HBVsvp were concentrated for highly virus titer using the polyethylene glycol protocol. Peripheral blood mononuclear cells (PBMCs), collected from CHB patients and healthy donors, were differentiated into MoDCs and T cells. PBMCs-derived MoDCs were first pulsed with HBVsvp and then cultured with PBMCs-derived T cells. MoDCs and/or T subsets cells were identified for phenotypic activation by FACS analysis. The cytokine secretion of IL-4, IL-12, and IFN-γ in the culture supernatants was detected. RESULTS: The MoDCs were restored for their activation upon pulsing with HBVsvp in vitro, as identified by significantly overexpression of both CD86 and HLA-DR, and overproduction of IL-4 and IL-12. Furthermore, MoDCs-pulsed-HBVsvp induced Th1 frequencies and activated HBV-specific CTL to produce significantly highest amount of IFN-γ. Enhanced HBV-specific CTL led to strong cytolytic capacity against HepG2.2.15. CONCLUSION: Overall, our data suggest that in vitro activation of MoDCs with HBVsvp overcomes the functionally impaired DCs and T cells in CHB patients offering a promising tool for therapeutic or vaccine-based approaches against HBV.

Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview.

BACKGROUND: Worldwide, hepatocellular carcinoma (HCC) is a universal problem and its epidemiological data showed variation from place to place. Hepatocellular carcinoma (HCC) is the sixth and fourth common cancer in worldwide and Egypt, respectively. Egypt ranks the third and 15th most populous country in Africa and worldwide, respectively. The aim of this review is to compare the status of HCC in Egypt to that in the worldwide from different issues; risk factors, screening and surveillance, diagnosis and treatment, prevention, as well as research strategy. MAIN BODY: The risk factors for HCC in Egypt are of great importance to be reported. The risk factor for HCC are either environmental- or host/genetic-related risk factors. In the last years, there is a tangible improvement of both screening and surveillance strategies of HCC in Egypt. The unprecedented national screening campaign launched by the end of 2018 is a mirror image of this improvement. While the improvement of the HCC prevention requires the governmental health administration to implement health policies. Although the diagnosis of Egyptian HCC patients follows the international guidelines but HCC treatment options are limited in terms of cost. In addition, there are limited Egyptian reports about HCC survival and relapse. Both basic and clinical HCC research in Egypt are still limited compared to worldwide. SHORT CONCLUSION: Deep analysis and understanding of factors affecting HCC burden variation worldwide help in customization of efforts exerted to face HCC in different countries especially large country like Egypt. Overall, the presence of a research strategy to fight HCC in Egyptian patients will help in the optimum allocation of available resources to reduce the numbers of HCC cases and deaths and to improve the quality of life.

Retreatment of chronic hepatitis C patients who failed previous therapy with directly acting antivirals: A multicenter study.

AIM OF THE STUDY: The current study aimed to evaluate the efficacy of different DAAs regimens in the treatment of chronic hepatitis C (CHC) Egyptian patients who failed to achieve SVR after their treatment with SOF-based regimens. METHODS: This was a retrospective observational multicenter study that included CHC patients that failed to achieve cure on SOF-based regimens who were re-treated using different DAAs regimen and were allocated according to national guidelines for the treatment of hepatitis C. Primary outcome was to assess the SVR12 rate among prior non-responders after retreatment with a second course of DAAs. RESULTS: Our study included 172 patients who failed to achieve SVR after treatment with SOF-based treatment regimen [age: 51.2 ± 11.3, 58.7% men]. Included patients were retreated using SOF/DCV/RBV, SOF/ r/PAR /OMB /RBV, SOF/DCV/SIM, SOF/LDV ± RBV or SIM/SOF. SVR12 was successfully attained in 95.35% (164/172) of the included non-responders. CONCLUSION: The current multicenter study proved the efficacy of various DAAs regimens issued by the National Committee for Control of Viral Hepatitis for retreatment of relapsed CHC Egyptian patients.

Transcriptionally Active Androgen Receptor Splice Variants Promote Hepatocellular Carcinoma Progression.

Owing to the marked sexual dimorphism of hepatocellular carcinoma (HCC), sex hormone receptor signaling has been implicated in numerous aspects of liver cancer pathogenesis. We sought to reconcile the clear contribution of androgen receptor (AR) activity that has been established in preclinical models of HCC with the clinical failure of AR antagonists in patients with advanced HCC by evaluating potential resistance mechanisms to AR-targeted therapy. The AR locus was interrogated for resistance-causing genomic modifications using publicly available primary HCC datasets (1,019 samples). Analysis of HCC tumor and cell line RNA-seq data revealed enriched expression of constitutively active, treatment-refractory AR splice variants (AR-SV). HCC cell lines expressed C-terminal-truncated AR-SV; 28 primary HCC samples abundantly expressed AR-SV. Low molecular weight AR species were nuclear localized and constitutively active. Furthermore, AR/AR-SV signaling promoted AR-mediated HCC cell progression and conferred resistance to AR antagonists. Ligand-dependent and -independent AR signaling mediated HCC epithelial-to-mesenchymal transition by regulating the transcription factor SLUG. These data suggest that AR-SV expression in HCC drives HCC progression and resistance to traditional AR antagonists. Novel therapeutic approaches that successfully target AR-SVs may be therapeutically beneficial for HCC. SIGNIFICANCE: Treatment-refractory, constitutively active androgen receptor splice variants promote hepatocellular carcinoma progression by regulating the epithelial-to-mesenchymal transition pathway.

A significant upsurge of body mass index in patients with chronic hepatitis C successfully treated with direct-acting antiviral regimens.

BACKGROUND/AIMS: There is less data regarding the changes in body mass index (BMI) after treating hepatitis C virus (HCV) patients with new direct-acting antiviral agents (DAAs). This study aimed to assess the changes in BMI in chronic HCV patients treated with DAAs in Egypt and to explore other factors influencing this change. MATERIALS AND METHODS: The data of chronic HCV patients who received antiviral therapy with new DAAs in one of Egypt's specialized viral hepatitis treatment centers were retrospectively analyzed. In addition to the routine clinical and laboratory workup, changes in body weight during and after treatment were monitored and BMI was calculated. Viral load was measured at 12 weeks post-treatment to assess a sustained virological response. Patients with documented thyroid abnormalities, bariatric surgery, or ensuing special diets were excluded. BMI of >30 was taken as the cutoff for pa¬tients with obesity. RESULTS: The study included 162 patients with a mean age of 48.56±11.49 years, of whom 61.1% were males, 16% were treatment-experienced, 12% were diabetic, and 29% were obese. Treatment duration was 12 weeks in 84% of patients and 24 weeks in 16% of patients. There was a significant increase in BMI post-treatment as compared to pretreatment measures (28.68±5.35 vs 28.18±4.55) (p=0.03). BMI changes were constant regardless of cirrhosis or previous treatment experience. CONCLUSION: Treatment of chronic HCV with DAAs was associated with increased body mass index. Further studies are needed to explore if this effect is secondary to treatment with DAAs or is an improvement in the liver function and lifestyle of treated patients.

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

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

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

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