Aya Mostafa

Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors

Background Chronic hepatitis C (HCV) infection is associated with diabetes and favourable lipids. Objective To study the effect of this paradox on atherosclerosis and cardiometabolic response to HCV clearance. Design Cross-sectional study. Setting Egypt. Participants 329 chronically infected, 173 with cleared infection and 795 never infected participants aged ≥35 attended for baseline investigations. A subsample of 192, 115 and 187, respectively, underwent ultrasound. Main outcome measures Diabetes, fasting glucose, lipids and fat deposition on ultrasound. Carotid intima-media thickness (IMT) measured atherosclerosis. Results Diabetes prevalence was raised (10.1% (95% CI 6.6 to 13.6), p=0.04) in HCV chronic, and cleared (10.1% (5.6 to 14.8), p=0.08) individuals versus 6.6% (4.9 to 8.3) in those never infected. Mesenteric fat was raised in chronic (36.4 mm (34.5 to 38.2), p=0.004), and cleared infection (37.8 (35.6 to 40.0), p<0.0001) vs never infected (32.7 (31.0 to 34.4)). LDL cholesterol was lower in chronic (2.69 mmol/l (2.53 to 2.86), p<0.001), but similar in cleared (3.56 (3.34 to 3.78), p=0.4) versus never infected (3.45 (3.30 to 3.60)). Carotid IMT did not differ by infection status: 0.73 (0.70 to 0.76, p=0.4), 0.71 (0.66 to 0.75, p=0.9), 0.71 (0.68 to 0.74), respectively. Adjustment for cardiovascular risk factors increased IMT in chronic infection (0.76 (0.72 to 0.79), p=0.02) versus never infected individuals (0.70 (0.67 to 0.73)). Conclusions Hepatic function normalisation with HCV clearance may account for reversal of favourable lipids observed with HCV infection. Hyperglycaemia and visceral adiposity appear less amenable to HCV resolution. These different cardiovascular risk patterns may determine equivalent atherosclerosis risk by infection status. However, once these factors were accounted for, those with chronic infection had raised IMT, suggesting a direct effect of infection.

HCV iatrogenic and intrafamilial transmission in Greater Cairo, Egypt

Objectives To document hepatitis C virus (HCV) intrafamilial transmission and assess its relative importance in comparison to other current modes of transmission in the country with the largest HCV epidemic in the world. HCV intrafamilial transmission was defined as HCV transmission among relatives living in the same household. Design Case–control study. Cases were adult patients with acute hepatitis C diagnosed in two ‘fever hospitals’ of Cairo. Controls were adult patients with acute hepatitis A diagnosed in the same two hospitals, and family members of cases. All consenting household members of cases provided blood for HCV serological and RNA testing. Homology of viral sequences (NS5b region) within households was used to ascertain HCV intrafamilial transmission. Exposures at risk for HCV during the 1–6 months previous to onset of symptoms were assessed in all cases and controls. Results From April 2002 to June 2007, 100 cases with acute hepatitis C, and 678 controls (416 household members and 262 patients with acute hepatitis A) were recruited in the study. Factors independently associated with HCV infection and their attributable fractions (AFs) were the following: having had a catheter (OR=5.0, 95% CI=1.4 to 17.8; AF=6.7%), an intravenous perfusion (OR=5.8, 95% CI=2.5 to 13.3; AF=20.1%), stitches (OR=2.0, 95% CI=1.3 to 6.6; AF=10.7%), gum treatment (OR=3.7, 95% CI=1.1 to 11.9; AF=3.8%) and being illiterate (OR=2.4, 95% CI=1.4 to 4.4). Of the 100 cases, 18 had viraemic HCV-infected household members. Three long-married (>15 years) couples were infected with virtually identical sequences and none of the three index patients reported any exposure at risk, suggesting HCV intra-familial transmission. Conclusion While three new HCV infections out of 100 could be linked to intra-familial transmission, parenteral iatrogenic transmission (dental care included) was accountable for 34.6% of these new infections. Thus, the relative contribution of intrafamilial transmission to HCV spread seems to be limited.

Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of new hepatitis C virus infections.

Objectives: To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt.

Effect of preventive and curative interventions on hepatitis C virus transmission in Egypt (ANRS 1211): a modelling study

BACKGROUND Most hepatitis C virus (HCV) transmission in Egypt is related to medical injections and procedures. To control the spread of HCV, the Egyptian Ministry of Health initiated awareness and education campaigns, strengthened infection control in health-care facilities, and subsidised anti-HCV treatment. We aimed to investigate the effect of these interventions on the spread of HCV by mathematical modelling. METHODS We developed a mathematical model of HCV transmission in Zawyat Razin, a typical rural community. Our model assumes that each individual has two distinct types of medical procedures: injections and more invasive medical procedures. To quantify the severity of the spread of HCV, we used the notion of the basic reproduction number R0, a standard threshold parameter signalling whether transmission of an infectious disease is self-sustained and maintains an epidemic. If R0 is greater than 1, HCV is self-sustained; if R0 is 1 or less, HCV transmission is not self-sustained. We investigated whether heterogeneity in the rate of injection or invasive medical procedures is the determinant factor for HCV transmission and whether most iatrogenic transmission is caused by a small group of individuals who receive health-care interventions frequently. We then assessed whether interventions targeted at this group could reduce the spread of HCV. FINDINGS The R0 of the spread of HCV without treatment was 3·54 (95% CI 1·28-6·18), suggesting a self-sustained spread. Furthermore, the present national treatment programme only decreased R0 from 3·54 to 3·03 (95% CI 1·10-5·25). Individuals with high rates of medical injections seem to be responsible for the spread of HCV in Egypt; the R0 of the spread of HCV without treatment would be 0·64 (95% CI 0·41-0·93) if everybody followed the average behaviour. The effect of treatment on HCV transmission is greatly enhanced if treatment is provided a mean of 2·5 years (95% CI 0·1-9·2) after chronic infection and with drug regimens with more than 80% efficacy. With these treatment parameters, preventive and curative interventions targeting individuals with high rates of medical injections might decrease R0 below 1 for treatment coverage lower than 5%. INTERPRETATION Targeting preventive and curative interventions to individuals with high rates of medical injections in Egypt would result in a greater reduction the spread of HCV than would untargeted allocation. Such an approach might prove beneficial in other resource-limited countries with health-care-driven epidemics. FUNDING Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS 1211), ANR grant Labex Integrative Biology of Emerging Infectious Diseases.

Effectiveness and Cost-effectiveness of Immediate Versus Delayed Treatment of Hepatitis C Virus–Infected Patients in a Country With Limited Resources: The Case of Egypt

BACKGROUND Because of logistical and economic issues, in Egypt, as in other resource-limited settings, decision makers should determine for which patients hepatitis C virus (HCV) treatment should be prioritized. We assessed the effectiveness and cost-effectiveness of different treatment initiation strategies. METHODS Using a Markov model, we simulated HCV disease in chronically infected patients in Egypt, to compare lifetime costs, quality-adjusted life expectancy (QALE), and the incremental cost-effectiveness ratio (ICER) of different treatment initiation strategies. RESULTS Immediate treatment of patients at stages F1/F2/F3 was less expensive and more effective than delaying treatment until more severe stages or not providing treatment (in patients diagnosed at F1: QALE = 18.32 years if treatment at F1 vs 18.22 if treatment at F2). Treatment of F4 patients was more effective than no treatment at all (QALE = 10.33 years vs 8.77 years) and was cost-effective (ICER =

Graphic health warnings and their best position on waterpipes: A cross-sectional survey of expert and public opinion

1915/quality-adjusted life-year [QALY]). When considering that affordable triple therapies, including new direct-acting antivirals, will be available starting in 2016, delaying treatment until stage F2, then treating all patients regardless of their disease stage after 2016, was found to be cost-effective (ICER =

Harm perceptions of waterpipe tobacco smoking among university students in five Eastern Mediterranean Region countries : a cross-sectional study

33/QALY). CONCLUSIONS In Egypt, immediate treatment of patients with fibrosis stage F1-F3 who present to care is less expensive and more effective than delaying treatment. However, immediate treatment at stage F1 is only slightly more effective than waiting for disease to progress to stage F2 before starting treatment and is sensitive to the forthcoming availability of new treatments. Treating patients at stage F4 is highly effective and cost-effective. In Egypt, decision makers should prioritize treatment for F4 patients and delay treatment for F1 patients who present to care.

Would placing pictorial health warnings on waterpipe devices reduce waterpipe tobacco smoking? A qualitative exploration of Egyptian waterpipe smokers' and non-smokers' responses.

INTRODUCTION Our aim was to assess the visibility and efficiency of graphic health warnings (GHWs) on waterpipe tobacco packs (WTPs) and to explore other more effective places to display them for better impact. We also evaluated the visibility of GHWs when placed on the waterpipe device. METHODS We conducted 3 cross-sectional study phases using face-to-face survey questionnaires in 2014-2015. Phase I surveyed 31 tobacco control experts, while Phase II surveyed 700 participants and Phase III surveyed 348 from the public in Cairo, Egypt. RESULTS Approximately half of the experts and participants in Phases II and III thought that GHWs on WTPs are not adequately visible, and 68.9% and 79.6% in Phases II and III, respectively, suggested posting warnings also in other places. About one-third of experts and 69.1% of Phase II participants suggested posting GHWs inside cafés or in public places, while 46.9% of Phase III participants favored placing them on waterpipes. After viewing our suggested positions on a waterpipe, all experts, 80.6% of participants in Phase II, and 81.6% in Phase III acknowledged that GHWs would be more visible there. The mouthpiece was the location selected most often across all phases (31.1% in Phase I, 35.6% in Phase II and 36.3% in Phase III). Lung and throat cancers were similarly effective in raising participants’ concern about waterpipe smoking health risks (24.7%). CONCLUSIONS This is the first population-based study to explore the best location to place GHWs on waterpipes. Policymakers should consider enacting a regulatory framework for placing GHWs on waterpipe devices.

Multiple tobacco use among young adult waterpipe smokers in Egypt

INTRODUCTION Waterpipe tobacco smoking (WTS) continues to be very common in the Eastern Mediterranean Region (EMR), partially because of cultural acceptance but also because of misconceptions of its harm. This paper aimed to describe the beliefs towards waterpipe harm of university students who smoked waterpipe in five EMR countries. METHODS This study was conducted in 2016 across five EMR countries: Egypt, Jordan, Occupied Palestinian Territories, Oman and United Arab Emirates (UAE). Participants were recruited from among university students in each country. Students’ characteristics, smoking behavior, flavor preference and knowledge of WTS harm were collected using an internet-based survey. Participants were included if they were ever waterpipe tobacco smokers and between 18 and 29 years of age. Bivariate analyses assessed variations in student-perceived WTS harm across the countries. Linear regression analysis was used to assess WTS perceived harm differences between students in the different countries. RESULTS A total of 2 544 university students participated from the five countries. Among ever smoking students, 66% reported WTS in the past 30 days, with the highest proportions (40%) from Occupied Palestinian Territories (OPT) and (41%) Jordan. Dual smoking of waterpipe and cigarettes was highest among students from Egypt. Most participants from the five countries had high level of perceived harm related to WTS during pregnancy. Less than 50% of the students believed that WTS could lead to the death of the smoker, can be harmful for non-smokers and have an addictive effect. Female students, those older than 22 years, and those who didn’t smoke waterpipe in the last 30 days significantly had a higher level of WTS perceived harm. Participating students believed that cigarettes are more addictive and contain more nicotine compared to waterpipe. CONCLUSIONS Misperceptions of waterpipe harm are common among university students in the five EMR countries. Immediate public health action is needed, including enforcement of waterpipe tobacco control regulations along with awareness campaigns.

Is expert opinion reliable when estimating transition probabilities? The case of HCV-related cirrhosis in Egypt

Background Although Egypt places four generic pictorial health warnings (PHWs) on the front and back half of waterpipe tobacco packs (WTPs), waterpipe tobacco smoking (WTS) rates have continued to rise. It has been suggested that PHWs would be more salient if placed on the waterpipe device itself. This qualitative study explored how participants perceived the effects placing PHWs on waterpipe devices would have on warning salience and uptake or quitting of WTS. Methods We conducted 10 focus groups and 10 in-depth interviews with 90 adult waterpipe smokers and non-smokers, men and women, who lived in rural, semi-urban and urban regions of Egypt. We presented participants with four novel PHWs of different sizes positioned randomly at four locations on a waterpipe device (the glass body, metal holder, mouthpiece or hose), one at a time. At each session, participants viewed a PHW on all four locations. Novel warnings were shown on plain labels with a dark uniform background and featured pictures, text and the quitline number. Transcripts were analysed using thematic analysis. Results Participants thought placing PHWs on waterpipe devices might increase salience, prevent WTS initiation or trigger quit attempts; they favoured placing PHWs on the glass body, mouthpiece or waterpipe hose. Both waterpipe smoker and non-smoker participants thought these potential effects would affect non-smokers or non-established smokers more than established waterpipe users. Conclusions Our exploratory study suggests that PHWs featured prominently on waterpipe devices could potentially deter experimentation with waterpipe tobacco products and promote cessation, especially among non-established users.