International multicenter validation of GES score for HCC risk stratification in chronic hepatitis C patients.

We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6-7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12,038 patients with chronic HCV were analyzed in this study, of whom 11,202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and log-rank tests. The performance of the GES score was evaluated using Harrell's C-index (HCI). The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (p < .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs.

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.

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 (/cm3 ) 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.

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

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.

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

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.

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

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.

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

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.

High spontaneous clearance of symptomatic iatrogenic acute hepatitis C genotype 4 infection.

Acute hepatitis C (AHC) infection resolves spontaneously in 15% to 40% of patients. Factors favoring spontaneous viral clearance remain undefined. In this study, predictors of spontaneous viral clearance in patients with symptomatic AHC were investigated. Epidemiological, clinical, and virologic parameters were also examined. Patients with symptomatic AHC were enrolled and followed up prospectively. The patients were followed up every 2 weeks in the first month and then monthly for the following 5 months, with a follow-up visit 6 months after the last hepatitis C virus (HCV)-RNA negative sample for those who had cleared the virus. Interleukin (IL)-28B.rs12979860 single-nucleotide polymorphism and HCV genotype were tested at baseline. HCV-RNA was tested during each visit. Patients who remained RNA-positive at 24 weeks were treated with pegylated interferon plus ribavirin for 24 weeks. A total of 30 patients, mostly with iatrogenically acquired AHC genotype 4 infections completed 6-months' follow-up, to either spontaneous clearance or start of treatment. The mean age of the patients was 37 ± 13 years. In total, 67% of patients were females, and the mean incubation period was 7.6 ± 3.5 weeks. Viral clearance occurred spontaneously in 19 (63.3%) patients. The average time to clearance was 24.3 ± 9.6 weeks. A total of 11 patients received therapy, and 8 (72.7%) cleared the virus and had a sustained virologic response to the treatment 24 weeks after the therapy. A total of three patients were treatment nonresponders. IL28B.rs12979860 CC genotype, female gender, and viremia level were not associated with self-limiting AHC in this cohort. In conclusion, patients with symptomatic AHC genotype 4 infection caused by an iatrogenic exposure had higher rates of spontaneous resolution than previously reported. Predicting spontaneous viral clearance after iatrogenic AHC exposure was not possible in this population.

Excess mortality rate associated with hepatitis C virus infection: A community-based cohort study in rural Egypt.

BACKGROUND & AIMS: >80% of people chronically infected with hepatitis C virus (HCV) live in resource-limited countries, yet the excess mortality associated with HCV infection in these settings is poorly documented. METHODS: Individuals were recruited from three villages in rural Egypt in 1997-2003 and their vital status was determined in 2008-2009. Mortality rates across the cohorts were compared according to HCV status: chronic HCV infection (anti-HCV antibody positive and HCV RNA positive), cleared HCV infection (anti-HCV antibody positive and HCV RNA negative) and never infected (anti-HCV antibody negative). Data related to cause of death was collected from a death registry in one village. RESULTS: Among 18,111 survey participants enrolled in 1997-2003, 9.1% had chronic HCV infection, 5.5% had cleared HCV infection, and 85.4% had never been infected. After a mean time to follow-up of 8.6years, vital status was obtained for 16,282 (89.9%) participants. When compared to those who had never been infected with HCV in the same age groups, mortality rate ratios (MRR) of males with chronic HCV infection aged <35, 35-44, and 45-54years were 2.35 (95% CI 1.00-5.49), 2.87 (1.46-5.63), and 2.22 (1.29-3.81), respectively. No difference in mortality rate was seen in older males or in females. The all-cause mortality rate attributable to chronic HCV infection was 5.7% (95% CI: 1.0-10.1%), while liver-related mortality was 45.5% (11.3-66.4%). CONCLUSIONS: Use of a highly potent new antiviral agent to treat all villagers with positive HCV RNA may reduce all-cause mortality rate by up to 5% and hepatic mortality by up to 40% in rural Egypt.

Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian.

Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.

Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

BACKGROUND: We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). METHODS: A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. RESULTS: A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. CONCLUSIONS: The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

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

BACKGROUND AND AIM: Many HCC risk prediction scores were developed to guide HCC risk stratification and identify CHC patients who either need intensified surveillance or may not require screening. There is a need to compare different scores and their predictive performance in clinical practice. We aim to compare the newest HCC risk scores evaluating their discriminative ability, and clinical utility in a large cohort of CHC patients. PATIENTS AND METHODS: The performance of the scores was evaluated in 3075 CHC patients who achieved SVR following DAAs using Log rank, Harrell's c statistic, also tested for HCC-risk stratification and negative predictive values. RESULTS: HCC developed in 212 patients within 5 years follow-up. Twelve HCC risk scores were identified and displayed significant Log rank (p ≤ 0.05) except Alonso-Lopez TE-HCC, and Chun scores (p = 0.374, p = 0.053, respectively). Analysis of the remaining ten scores revealed that ADRES, GES pre-post treatment, GES algorithm and Watanabe (post-treatment) scores including dynamics of AFP, were clinically applicable and demonstrated good statistical performance; Log rank analysis < 0.001, Harrell's C statistic (0.66-0.83) and high negative predictive values (94.38-97.65%). In these three scores, the 5 years cumulative IR in low risk groups be very low (0.54-1.6), so screening could be avoided safely in these patients. CONCLUSION: ADRES, GES (pre- and post-treatment), GES algorithm and Watanabe (post-treatment) scores seem to offer acceptable HCC-risk predictability and clinical utility in CHC patients. The dynamics of AFP as a component of these scores may explain their high performance when compared to other scores.

Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial.

INTRODUCTION: Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery. AIM: To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine. PATIENTS AND METHODS: This trial included 43 patients with low lying (4-7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4-6 weeks by total mesorectal excision technique. RESULTS: Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3-23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5-85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5-62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3-23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8-17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3-23.1) respectively. CONCLUSION: In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate.

Seroprevalence and risk factors for human herpesvirus 8 infection, rural Egypt.

To determine whether human herpesvirus 8 (HHV-8) is associated with schistosomal and hepatitis C virus infections in Egypt, we surveyed 965 rural household participants who had been tested for HHV-8 and schistosomal infection (seroprevalence 14.2% and 68.6%, respectively, among those <15 years of age, and 24.2% and 72.8%, respectively, among those > or =15 years of age). Among adults, HHV-8 seropositivity was associated with higher age, lower education, dental treatment, tattoos, > or =10 lifetime injections, and hepatitis C virus seropositivity. In adjusted analyses, HHV-8 seropositivity was associated with dental treatment among men (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.2) and hepatitis C virus seropositivity among women (OR 3.3, 95% CI 1.4-7.9). HHV-8 association with antischistosomal antibodies was not significant for men (OR 2.1, 95% CI 0.3-16.4), but marginal for women (OR 1.5, 95% CI 1.0-2.5). Our findings suggest salivary and possible nosocomial HHV-8 transmission in rural Egypt.

An educate, test, and treat programme towards elimination of hepatitis C infection in Egypt: a community-based demonstration project.

BACKGROUND: Egypt has one of the highest prevalences and burdens of hepatitis C virus (HCV) worldwide, and a large government treatment programme. However, identifying and treating people who are infected in rural communities can be a substantial challenge. We designed and evaluated a comprehensive community-led outreach programme for prevention, testing, and treatment of HCV infection in one village in northern Egypt, with the goal to eliminate HCV infection from all adult villagers, and as a model for potential adoption in rural settings. METHODS: A community-based education and test-and-treat project was established in Al-Othmanya village. The programme consisted of community mobilisation facilitated by a network of village promoters and establishment of partnerships; an educational campaign to raise awareness and promote behavioural changes; fundraising for public donations in the local community; and comprehensive testing, diagnosis, and treatment. For the educational campaign, we used public awareness events, house-to-house visits, and promotional materials (eg, booklets, cartoons, songs) to raise awareness of HCV and its transmission, and changes in knowledge, attitudes, and practices were measured through the use of a survey done before and after the educational campaign. Comprehensive testing, linkage to care, and treatment was offered to all eligible villagers (ie, those aged 12-80 years who had not previously been treated for HCV). Testing was done by use of HCV antibody and hepatitis B surface antigen (HBsAg) rapid diagnostic tests, with HCV-RNA PCR confirmation of positive cases, and staging of liver disease by use of transient elastography. HCV-RNA-positive participants were offered a 24-week course of sofosbuvir (400 mg orally, daily) and ribavirin (1000-1200 mg orally, daily) with an assessment of cure (sustained virological response) at 12 weeks after completion of treatment (SVR12). FINDINGS: Between June 6, 2015, and June 9, 2016, 4215 (89%) of 4721 eligible villagers were screened for HCV antibodies and HBsAg. Of these participants, 530 (13%) were HCV antibody positive and eight (<1%) were HBsAg positive. All HCV-antibody-positive individuals had an HCV-RNA assay, and 312 (59%) were HCV-RNA positive. All 312 completed a full baseline assessment with staging of liver disease, and 300 (96%) were given 24 weeks of sofosbuvir and ribavirin treatment within a median of 2·3 weeks (IQR 0·0-3·7) from serological diagnosis. 293 (98%) of the treated participants achieved SVR12. 42 (13%) HCV-RNA-positive participants had cirrhosis as determined by transient elastography, of whom 12 (29%) were diagnosed with hepatocellular carcinoma on the basis of α-fetoprotein measurement and ultrasound. 3575 (85%) of 4215 eligible villagers completed the baseline and after educational campaign survey, and awareness, knowledge, and adoption of safer practices to prevent HCV transmission all significantly increased (p<0·0001). INTERPRETATION: This community-led educate, test-and-treat demonstration project achieved high uptake of HCV testing, linkage to care and treatment, and attainment of cure in one village, as well as awareness and adoption of practices to prevent transmission in the community. This approach could be an important strategy for adoption in rural settings to complement the national government programme towards the elimination of HCV in Egypt. FUNDING: Egyptian Liver Research Institute and Hospital.

Author Correction: Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder.

Chromosomal aberrations (CAs) in blood lymphocytes have been shown to be associated with overall cancer risk and aging. However, their relationship to bladder cancer risk remains to be elucidated. In a case-control study of bladder cancer in Egypt, we examined the relationship between the increased frequency of CAs in blood lymphocytes and bladder cancer risk. High frequency of CAs was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 3.90, 95% confidence interval (CI) = 2.65-5.73]. The associations were somewhat stronger in squamous cell carcinomas (SCC, OR = 4.90) than in urothelial carcinomas (UC, OR = 3.62). We also identified chromosome specific CAs for chromosomes 3, 4, 5, 8, 9, 10, 11, 12, 17, 19 that were significantly associated with an increased risk of bladder cancer. We observed particularly strong associations between aberrations of chromosomes 12, 13, 17 and risk of SCC (OR = 7.06, 6.91 and 6.23, respectively). CONCLUSION: increased frequency of chromosomal aberrations in blood lymphocytes was significantly associated with bladder cancer risk. Overall and chromosome specific aberrations in blood lymphocytes may be a unique set of biomarkers for risk assessments of SCC and UC.

Transmission of hepatitis C virus between parents and children.

Egyptian children with infected parents are at high risk of infection with hepatitis C (HCV). Analysis of data collected during surveys of rural communities show children whose parents had antibodies to HCV (anti-HCV) were at higher risk for having anti-HCV than children whose parents did not. The association was greater with mothers than fathers and when the parent had HCV RNA. For instance, 87 (14%) of 612 children had anti-HCV whose mothers had HCV RNA compared with 28 (7%) of 401 whose mothers only had anti-HCV and 79 (2.6%) of 3,086 whose mothers were seronegative. These associations persisted after controlling for age, parenteral exposures, and serologic status of the other parent. Sequencing isolates from 13 families with parent(s) and children having HCV RNA showed 10 of 18 had genetically similar viruses. These findings suggest Egyptian children are at high risk of being infected with HCV by their parents and identification of the transmission routes would allow for preventive measures.

Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers.

This study examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H: quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. Logistic regression was used to analyze data from a multicenter case-control study and estimate adjusted odds ratio (OR) and 95% confidence interval (CI). Exposure to pesticides was associated with increased bladder cancer risk (odds ratio (95% confidence interval): 1.68 (1.23-2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25-2.56)) than for squamous cell (1.55 (1.03-2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19-3.85)) activities as compared with those with high NQO1 and low SOD2 genotypes (1.53 (0.73-3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism.