The current and future disease burden of chronic hepatitis C virus infection in Egypt

Arab Journal of Gastroenterology xxx (2014) xxx–xxx

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Review

The current and future disease burden of chronic hepatitis C virus infection in Egypt Imam Waked a,⇑, Waheed Doss b, Manal Hamdy El-Sayed c, Chris Estes d, Homie Razavi d, Gamal Shiha e, Ayman Yosry b, Gamal Esmat b a

National Liver Institute, Shebeen El Kom, Egypt Cairo University, Cairo, Egypt Ain Shams University, Cairo, Egypt d Center for Disease Analysis (CDA), Louisville, CO, USA e Mansoura University, Mansoura, Egypt b c

a r t i c l e

i n f o

a b s t r a c t

Article history: Received 20 April 2014 Accepted 20 April 2014 Available online xxxx

Ó 2014 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Introduction Hepatitis C virus (HCV) infection is a major public health burden in Egypt [1,2]. A number of studies have characterised HCV infection rate in Egypt [3,1,4,5] but they have focused on quantifying the prevalence or total number of HCV infections. The future outlook of the disease burden is not known. This, however, is expected to increase as the infected population ages [6,7]. A number of new treatment options have become, and will become, available in the immediate future, with much higher efficacy (cure rates >90%) compared to the current standard of care. The policy-makers will need reliable projection data to evaluate how to utilise these therapies most efficiently. The aim of this review is to analyse current number of infections in different disease stages, and to estimate the future burden of HCV disease if the current infection rate, treatment paradigm and response rate are continued. The current and future therapies are reviewed, and a model is used to examine the impact of different treatment strategies on the future disease burden. The objective is to analyse the impact of changes in treatment and response rate on the disease burden as a possible method for disease control. Current epidemiology and disease burden Egypt has the highest prevalence rate of HCV in the world [8,9]. Nosocomial transmission has been [10], and probably still is [11], the most common route for new infections. In particular, ⇑ Corresponding author. E-mail address: [email protected] (I. Waked).

widespread parenteral treatment of schistosomiasis in earlier decades resulted in high levels of HCV transmission [12]. Estimates for prevalence are based upon data reported from the 2008 Egypt Demographic and Health Survey (EDHS), a nationally representative sample that included participants in all major Egyptian regions [13], where seroprevalence and viraemia estimates were reported by a 5-year age group and gender for individuals aged 15–59 years. Total anti-HCV prevalence was 14.7%, and viraemia was 9.8% [13]. In this review, to estimate the prevalence in the population younger than 15 years in 2008, an exponential decline in viraemic prevalence was trended. Prevalence in those aged >59 years was set equal to prevalence in those aged 55– 59 years (Fig. 1). The prevalence of HCV antibody positivity in 2008 after adjusting for younger and older individuals was estimated at 12% [14]. However, only two thirds of the infected population was viraemic in the EDHS, resulting in an all age group viraemic prevalence of 8.5% in 2008. A mathematical model described elsewhere [14] was used to estimate the 2013 HCV infected populations. After taking into consideration mortality, new infections and cured patients, the 2013 viraemic prevalence was estimated at 7.3% (Table 1). Although the viraemic prevalence dropped by 1.2%, the actual number of cases decreased by only three hundred thousand cases. The increase in population in the last five years was responsible for some of the drop in estimated HCV prevalence [15]. The genotype distribution in Egypt is mainly genotype 4 (HCVG4) which is responsible for more than 90% of the infections, with the remaining due to HCV-G1 [16–18] (Table 1). According to the EDHS, only 1.4% (1,052,000 antibody positive or 713,000 viraemic individual) of Egyptians had received a positive HCV diagnosis in 2008 [13]. According to estimates and expert

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Fig. 1. Viraemic HCV Prevalence by age and gender, 2008.

Table 1 HCV Epidemiology in Egypt in 2013 based on data from the 2008 EDHS [13]. 2008

2013

75,200

85,000

Population (000) HCV antibody positive (000) Total cases Prevalence

9387 (8449–10,326) 12.5% (11.2–13.7%)

Viraemic infections (000) Total viraemic cases Viraemic prevalence Viraemic rate

6350 (5700–7000) 8.5% (7.6–9.3%) 68%

Genotypes 1 4

10% 90%

Diagnosed (Viraemic) Total cases Annual newly diagnosed

713,000 125,000

6000 (4500–6700) 7.3% (5.5–8.1%)

new infections occurred in 2013, of which 102,000 went on to have chronic hepatitis C (CHC). In the same year, 31,200 cases were cured and 153,000 individuals with HCV died (33,000 of HCV related complications and 120,000 due to all other causes) resulting in a decline of 82,200 in the number of infections in 2013. The mortality (all-cause and liver related) was driven by the age of the infected population (Fig. 1). Older populations have a higher all-cause mortality rate, and in addition, the disease progression rate increases with age and older individuals are more likely to have more advanced liver disease and associated liver related deaths [26].

Current therapy and future treatments of HCV G4 872,000 125,000

Treated and cured Annual number treated Annual number cured Average SVR Treatment rate

65,000 31,200 48% 1.1%

New infections Total cases Infection rate (per 100 K) New CHC cases

168,600 204 102,000

Mortality All cases All cause mortality Liver related mortality

153,000 120,000 33,000

consensus, 15% (872,000 viraemic individuals) of the HCV-infected population in Egypt was previously diagnosed in 2013, and there were an estimated 125,000 viraemic individuals being newly diagnosed each year. Approximately 65,000 patients were treated annually – 50,000 individuals treated in Ministry of Health centres [19], 10,000 through the Health Insurance Organisation and 5000 individuals who paid cash for their treatment. The total number of HCV infections reported here will be lower than those reported elsewhere since this analysis focuses on estimating the number of viraemic cases in the population after taking into account all age groups, mortality, new infections and cured patients. There is still evidence of high levels of ongoing HCV transmission [20–23] with high HCV prevalence observed among young individuals [24,25]. Table 1 shows that an estimated 168,000

HCV-G4 has been considered ‘‘difficult to treat’’ with pegylated interferon (PEG) and ribavirin (RBV), with sustained virological response (SVR) rates better than HCV-G1, and worse than HCVG2 and G3 [27,28]. With the introduction of the HCV-G1 effective protease inhibitors boceprevir (BOC) [29,30] and telaprevir (TVR) [30–33] in 2011, HCV-G4 became the ‘‘most difficult to treat’’ genotype. The recent approval of sofosbuvir (SOF) for treatment of HCV-G4 [34] promises significant improvement in the outcome of therapy. The Ministry of Health in Egypt has embarked on a national treatment programme for patients with chronic HCV infection since 2006, where all eligible patients are treated with PEG-RBV, with almost 100% of the patients receiving therapy for free. Annually, 40,000–50,000 patients have been treated, and by 2013, 350,000 patients have received therapy in this programme [19]. SVR rates for patients treated with the original pegylated interferon alfa-2a and alfa-2b are 54–59% [35,36], and response rates to a locally produced biosimilar pegylated interferon were reported at 52% [37,38]. Predictors of response of HCV-G4 infected patients to therapy with PEG-RBV include viral load, fibrosis score, and ethnic origin [39–41]. Egyptian patients infected with HCV-G4 treated with PEG-RBV in Europe responded better than French/European patients or Africans infected with the same genotype [42]. HCV subtype 4a accounted for 54% of infections among patients infected in France, and subtype 4a was mostly predominant (93%) among patients infected in Egypt. In sub-Saharan Africa, subtype 4a was found to infect only 11.5%. An overall better response was observed in patients infected with the 4a subtype (60% vs 35% for non-4a subtypes) and SVR rates were higher in patients infected in Egypt, compared with those infected in France or Africa (54.9%, 40.3% and 32.4%, respectively, P < 0.05) [42]. In a similar study, Egyptians

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responded better than French/Europeans of Africans to PEG-RBV therapy [43]. A major predictor of response to PEG-RBV therapy in patients with HCV-G4 is the IL-28B genotype [44–46]. The favourable CC phenotype is found in 20–30% of Egyptian patients with chronic hepatitis C [47,48]. In Europe, SVR rates for HCV-G4 infected patients who are IL-28B CC ranged from >80% [43–45] to 66% [46] and for TT patients between 20% and 30%. Heterozygote patients had response rates between 40 and 50% [43–46]. In Egypt, CC patients had response rates between 67% [47] and 87% [48]. Another predictor of response to PEG-RBV therapy was found to be insulin resistance. High HOMA-IR score was found to impair response rates to PEG-RBV therapy in HCV-G4 patients, and patients with HOMA-IR scores >2 had lower SVR rates than those with scores <2 (36% vs. 72%) [41]. Pioglitazone added to PEG-RBV therapy improved SVR rates in HCV-G4 patients with insulin resistance [49]. During treatment with PEG-RBV, patients with HCV-G4 who achieve a rapid virological response (RVR, HCV-RNA negative at 4 weeks of starting therapy) respond much better than those who do not [50], and in these patients, several studies have shown that response rates are equally high if they are treated for a total of 24 or 48 weeks [51,52]. An expert panel [53] recommended shortening therapy to 24 weeks for those who achieve an RVR and do not have unfavourable predictors of response (high viral load, advanced fibrosis, and insulin resistance). They also recommended extending therapy for 72 weeks for slow responders who have >2 log decrease in HCV-RNA by 12 weeks and become RNA negative at 24 weeks. The national programme in Egypt, however, treats all patients for 48 weeks. Several attempts at improving response to PEG-RBV therapy have explored additions to treatment. Nitazoxanide (NTZ), an antiprotozoal agent, was reported to have some effects in treating patients with HCV-G4 [54,55]. However, more recent trials showed that NTZ does not increase SVR rates. A randomised trial in the National Liver Institute in Egypt showed that response rates were similar in patients treated with PEG-RBV standard therapy (SVR 56%), or with added NTZ whether used for 1 month or 3 months before therapy and continuously during treatment (SVR 52% and 46% respectively). [56]. Similarly, Shehab et al. found that SVR rates were similar with standard of care (48%) or with the addition of NTZ (50%) [57].

Abu-Mouch et al. found that adding vitamin-D to standard of care with PEG-RBV therapy for HCV-G1 infected patients increases SVR rates to 82% compared to 42% [58]. A similar trial in Menoufiya in HCV-G4 patients treated in the Ministry of Health programme found that adding vitamin-D to PEG-RBV for 48 weeks increased SVR to 88% [59]. Although these results need to be validated further, however, with the availability of HCV-G4 effective next generation direct antivirals, there will be no place for 48 weeks of PEG-RBV therapy to allow further trials of adding vitamin-D to PEG-RBV in HCV-G4 patients. The approval of BOC [29,30] and TVR [31–33] as the first direct acting antivirals (DAAs) for HCV-G1 heralded a new era in the management of HCV infection. All the HCV enzymes are drug targets, and DAA agents include NS3/NS4 protease inhibitors, NS5B polymerase inhibitors, and NS5A inhibitors as summarised in Table 2. Although protease inhibitors are potent antivirals, they are highly specific, and since the amino acid sequence of the NS3 protease differs significantly between HCV genotypes, protease inhibitors will not have the same efficacy in different genotypes [60]. Resistance to protease inhibitors is common, and differs significantly between HCV genotypes and within the subtypes of each genotype. Resistance to TVR occurs much more frequently in HCV-G1a compared to HCV-G1b, due to the presence of nucleotide substitution at position 155 in HCV-G1a (R155K; changing R to K at position 155). Similarly, a Q80K mutation conferring resistance to SMV is observed in up to 48% of naive HCV-G1a infected patients, leading to reduced SVR rates, and is rare in HCV-G1b. Resistant mutations are detected in the majority of patients with treatment failure protease inhibitors [61,62]. First generation protease inhibitors BOC and TVR are not indicated for treatment of HCV-G4. A recent publication showed that TVR has some effect on HCV-G4, where 15 days of therapy increased the decline in viral load to PEG-RBV therapy [63]. On the other hand, next generation direct antivirals show excellent response rates for HCV-G4 patients. NS5B polymerase inhibitors can be divided into two distinct categories: nucleoside inhibitors (NIs) and non-nucleoside inhibitors (NNIs). NS5B NIs (Table 2) mimic the natural substrates of the polymerase and are incorporated into the RNA chain causing direct chain termination [60]. Since the active site of NS5B is highly conserved, NIs are effective against all genotypes, and resistance to

Table 2 Drug Development Pipeline for Hepatitis C Therapy in 2014. Status

Approved

DAA

HTA

NS3/NS4 protease inhibitors

NS5B polymerase inhibitors

Telaprevir

Sofosbuvir

Nucleoside inhibitors (NIs)

Non-nucleoside inhibitors (NNIs)

NS-5A inhibitors

Boceprevir

Applied for approval

Simeprevir Faldaprevir

Phase III

ABT-450

Phase II

Asunaprevir Danoprevir MK-5172 ACH-1625 Narlaprevir GS-9256 Vaniprevir

ABT-333

Daclatasvir Ledipasvir ABT-267

Cyclophillin Inh (Alisporovir)

ABT-072 Mericitabine VX-135 IDX-184

Deleobuvir BMS-791325 Setrobuvir Tegobuvir VX-222

ACH-3102

Anti-miR-122 miaversin

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NIs is usually very low [62]. NNIs (Table 2) on the other hand, inhibit the NS5B by binding to one of several discrete sites on the HCV polymerase, resulting in a conformational protein change. They are less potent than NIs and resistance occurs more frequently [62]. Because of their distinct binding sites, different NIs and NNIs can be used in combination or in sequence, and can be combined with protease inhibitors or NS5A inhibitors, with incremental potency and without cross-resistance. SOF when given as part of triple therapy with PEG-RBV for 12 weeks in the phase III Neutrino trial resulted in an SVR rate of 96% in HCV-G4 patients [34]. When given without interferon as dual therapy with RBV to HCV-G4 infected patients of Egyptian origin in the US for 12 weeks resulted in SVR rates of 79% and 59% in naïve and treatment experienced patients respectively [64]. Extending the treatment for 24 weeks improved the SVR rates to 100% and 93%. In phase II studies, ritonavir boosted danoprevir (DNV/r) added to PEG-RBV resulted in SVR rates of 87.5% to 100% in HCV-G4 infected patients [65], and daclatasvir (DCV) when added to PEGRBV for 6 months improved SVR rates to 67% with a single daily oral 20 mg dose and 100% with a 60 mg dose compared to 50% SVR rate with standard treatment with PEG-RBV for 48 weeks [66]. Simeprevir (SMV) when given for 3 months with PEG-RBV for 6–12 months improved SVR in HCV-G4 naïve and experienced patients to above 85% [67]. Several drugs are in advanced stages of development that offer very high cure rates with minimal adverse events. All-oral fixed dose combinations with very high cure rates will be available in the near future [68]. SOF with the NS5A inhibitor ledipasvir in a fixed dose combination resulted in SVR rates >93% when used for 8 weeks in HCV-G1 naive patients, and >97% when used for 12 weeks, and resulted in SVR rates >93% when used in previous null-responders with or without RBV for 12 weeks [69–71]. SOFSMV combination in the COSMOS trial resulted in >92% SVR rates in patients with low fibrosis, and close to 100% SVR in patients with advanced fibrosis/cirrhosis [72]. An all-oral combination of the protease inhibitor ritonavir boosted ABT-450, the NS5A inhibitor ABT 333, and the NNI-NS5B inhibitor ABT-267 for 12 weeks in the phase III SAPPHIRE trial resulting in 96% SVR rates in HCV-G1 treatment naïve and experienced patients [73,74]. Similarly, an all-oral combination of SOF and DCV resulted in close to 100% SVR rate in treatment naïve and experienced patients [75], and a triple combination of DCV with asunaprevir and the NNI BMS791325 resulted in SVR rates in excess of 98% in HCV-G1a and HCV-G1b naïve and treatment experienced patients [76].

Several host cellular factors form part of the HCV RNA replication complex, including the cellular isomerases cyclophilin A, B and C, and hepatocyte miro-RNAs. Host targeted antivirals (HTAs) act on these host factors, and are independent of the virus and its proteins. The cyclophilin-A inhibitor alisporivir has potent antiHCV activity and is pan-genotypic, as it is not directed to a viral component. It inhibits HCV viral replication by interfering with the interaction between cyclophilin-A and NS5A [77]. Alisporivir phase III development was placed on hold for reports of pancreatitis. Another host targeted antiviral targets a cellular micro-RNA. The subcutaneously administered miravirsen specifically targets the liver-specific micro-RNA miR-122 that is involved in gene expression and HCV viral replication, suppressing HCV viraemia without resistance or significant side effects in early trials [78]. Predictors of response to PEG-IFN as known today will probably not be applicable with next generation potent DAA regimens, with SVR rates >90%. These regimens will eliminate factors such as IL28B status, viral load, race, metabolic syndrome, obesity and age. Prior failure of response to PEG-RBV will not hamper response, and even previous null-responders will do as well as naïve patients with SVR rates 90%. And since almost all patients become HCVRNA negative by 4 weeks, RVR and EVR will become invalid. Cirrhosis may still remain a differentiating factor in SVR rates, and can be overcome by using a more potent combination or longer duration. The next generation DAAs will thus offer high efficacy, ease of use and shorter duration. This will ultimately offer the possibility for the control of the huge disease burden of hepatitis C in Egypt as will be discussed in the next parts. Future disease burden of hepatitis C virus with today’s treatment paradigm A disease progression model was constructed to quantify the size of the HCV infected population, by the stages of liver disease, from 1950 to 2030 [14]. For the purpose of the model, it was assumed that the number of treated patients, eligibility, the number of newly diagnosed cases, SVR and treated patient segments would remain constant between now and 2030. This is not meant to be a realistic scenario, but rather a baseline that could be used to compare the impact of new strategies to manage the future disease burden as described in the next section. The model calculated the annual number of new infections, allcause mortality, liver related deaths and cured cases, and the age and gender distribution of these cases [14]. Background mortality

Table 3 Summary of current treatment protocols in 2013 and strategies to minimise HCV morbidity and mortality by 2030. 2013

Treated (annual) Treatment rate Average SVR Newly diagnosed (annual) % Treatment eligible Common treatment age Treated stages Impact # Total infected Change from 2013 (%) # Compensated cirrhosis Change from 2013 (%) # Decompensated cirrhosis Change from 2013 (%) # HCC Change from 2013 (%) # HCV related mortality Change from 2013 (%)

2030 Base case

Increase efficacy only

Increase efficacy and treatment

65,000 1.1% 48% 125,000 50% 15–59 PF2

65,000 1.1% 48% 125,000 50% 15–59 PF2

65,000 1.1% 90% (2014) 125,000 90% (2016) 15–59 PF2

325,000 (2018) 7.1% 90% (2014) 340,500 (2020) 90% (2014) 15–74 PF0

6,000,000

4,420,000 26% 610,000 2% 136,300 0.6% 18,500 +15% 36,500 +10%

4,045,000 32% 507,000 19% 110,000 21% 16,000 0% 30,700 7%

280,000 95% 76,000 88% 17,000 87% 2,400 85% 7,500 77%

630,000 138,000 16,000 33,000

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Fig. 2. Number of HCV patients with viraemia, and with different disease stages over time.

Fig. 3. Number of HCV patients with HCC and decompensated cirrhosis over time.

rates reported by the World Health Organization (WHO) were used [79]. Table 3 compares the change in HCV disease burden in 2013 and 2030 while Figs. 2 and 3 show the projected HCV disease burden between 1950 and 2030. The total number of viraemic infections declined to 6,000,000 (5,400,000–6,700,000) cases by 2013, and is forecasted to further decline by 26% by 2030. The number of HCC cases in 2013 was estimated at 16,000 cases and is forecasted to increase by 15% by 2030. Similarly, the number of liver related deaths will increase by 10% from 33,000 deaths in 2013. The number of cases with decompensated cirrhosis will peak in 2016, at 7% above the 2013 base of 137,700 and will decrease 0.6% from 2013 to 2030. Patients with compensated cirrhosis will peak in 2021, at 7% above the 2013 base of 670,000 and will decrease 2% during 2013–2030. While the total number of infections is expected to decline, the number of cases with more advance liver diseases is expected to increase (Table 3 and Figs. 2 and 3). As the infected population ages, HCV infected individuals will advance to cirrhosis, decompensated cirrhosis and hepatocellular carcinoma (HCC). This suggests that strategies are required to manage the expected increase in HCV disease burden.

The model in this review does not consider the progression of cured HCV patients. Studies have shown that more advanced patients may continue their disease progression after achieving SVR, although at a slower rate [80]. The data presented here may thus overestimate the reduction in HCC and decompensated cirrhosis cases.

Strategies to manage hepatitis C virus (HCV) disease burden In addition to the base case just described, two additional scenarios are evaluated to assess impact of the availability of highly effective therapies on future disease burden. In the second scenario, the impact of increasing the SVR was considered with all other assumptions remaining the same, except that SVR and treatment eligibility were increased over time. SVR rates were increased starting 2014 to 90% as compared to 48%, and in 2016, with the exclusion of PEG-IFN and RBV, medical eligibility will be increased to 90% from 50%. With this scenario, in 2030, there will be 375,000 fewer viraemic individuals compared to the base case, an 8% reduction. The number of HCC cases in 2030 is estimated at

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Fig. 4. Impact of different management scenarios on total cases and different disease stages.

Table 4 Impact of prevention on outcome of scenario 3. Viraemic HCV infections

2013

2030

% Change

Base case Increased treatment and SVR, reduce incidence Increased treatment and SVR, without incidence reduction

6,000,000

4,420,000 285,000

26 95

1,250,000

79

16,000 cases, a 15% decrease from the base case. Similarly, the number of liver related deaths will decrease by 15% from the base with 30,000 in 2030. Decompensated and compensated cirrhosis will decrease by 20% and 17% from the base with 110,000 and 507,000 cases respectively in 2030 (Table 3, Fig. 4). The third scenario outlines the strategy needed to be applied to reach the goals of reducing HCV viraemic prevalence to <2% by

2025, and near-total disease elimination (>90% drop in total infections) by 2030. Achieving these ambitious goals requires increasing SVR, increasing numbers of treated patients, and significantly reducing new infections. In this scenario, in 2014, both SVR and medical eligibility rates increase to 90%. In addition, patients aged 15–74 years with fibrosis scores of PF0 were considered eligible for treatment. The annual number of treated patients increased to 105,000 cases from 65,000. The number of newly diagnosed increased to 150,000 as compared to 125,000. New infections decline from 168,000 to 126,000. Beginning in 2016, the annual number of treated patients increases to 260,000 cases while newly diagnosed cases increase to 225,000 annually. New infections decline to 95,000 cases annually. In 2018, annually treated cases increase to 325,000 and new infections decline further to 70,000. In 2020, number of cases treated is held constant at 325,000 annually, and new infections declined further to 53,000 cases. Adopting this scenario will result in 4,150,000 fewer viraemic individuals in 2030 as compared to the base case, a 95% reduction.

Fig. 5. Impact of prevention on outcome of scenario 3.

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By 2025, overall viraemic prevalence drops below 2%, and by 2030 viraemic prevalence is estimated at 0.4%. The number of HCC cases in 2030 is estimated at 2,540 cases, an 85% decrease from the base case. Similarly, the number of liver related deaths will decrease by 80% from the base with 7,500 in 2030. Decompensated and compensated cirrhosis will decrease by 87% from the base with 17,000 and 76,000 cases respectively in 2030. Finally, 1,770,000 new infections will be avoided during 2013–2030 (Table 3, Fig. 4). This analysis shows that with a treatment rate of approximately 10% and high SVR therapies, it is possible to achieve elimination of HCV (Table 3) and significantly reduce HCV mortality and morbidity. No cost was considered when projecting this scenario, and only numbers needed to treat to reach targets of <2% prevalence by 2025 and disease elimination by 2030 were analysed. A strategy aiming at disease control and markedly reducing prevalence and burden of HCV in Egypt should aim at increasing diagnosis and treatment, coupled by preventing transmission. Table 4 and Fig. 5 show the impact of active prevention on the outcome of this scenario. If effective measures are not adopted to reduce incidence, and number of new cases only decreases as an effect of increased cure, there will be 1 million more cases by 2030 (1,250,000 vs. 285,000), and disease elimination would not be reached. As the majority of infected individuals in Egypt are unaware of their infection, the national control strategy should also emphasise efforts to increase awareness and testing for HCV. The number of diagnosed individuals needs to be increased considerably, to match the projected increase in treatment. In this model, the diagnosis rate was increased to provide a sufficient patient pool to achieve the desired strategy. However, it is not clear that the number of newly diagnosed patients can be increased without a clear screening strategy. Implementation would depend upon the capacity of the healthcare system to diagnose and treat new patients. In this suggested scenario, increases in treatment rate, diagnosis rate, eligibility and SVR took effect immediately without any time for an uptake. In reality, this might not be feasible and need some time, as adoption of new therapies can take several years as the medical community gets familiar with the new drugs and new guidelines are developed. In conclusion, the availability of a highly effective therapy, coupled with increased diagnosis and treatment, and marked reduction in new cases, has the potential to eliminate hepatitis C in Egypt within the next 15 years. References [1] Mohamed MK, Bakr I, El-Hoseiny M, Arafa N, Hassan A, Ismail S, et al. HCVrelated morbidity in a rural community of Egypt. J Med Virol 2006;78:1185–9. [2] Mohamoud YA, Mumtaz GR, Riome S, Miller D, Abu-Raddad LJ. The epidemiology of hepatitis C virus in Egypt: a systematic review and data synthesis. BMC Infect Dis 2013;13:288. http://dx.doi.org/10.1186/1471-233413-288. [3] Arafa N, El Hoseiny M, Rekacewicz C, Bakr I, El-Kafrawy S, El Daly M, et al. Changing pattern of hepatitis C virus spread in rural areas of Egypt. J Hepatol 2005;43:418–24. [4] Eassa S, Eissa M, Sharaf SM, Ibrahim MH, Hassanein OM. Prevalence of hepatitis C virus infection and evaluation of a health education program in ElGhar village in Zagazig, Egypt. J Egypt Public Health Assoc 2007;82:379–404. [5] Strickland GT, Elhefni H, Salman T, Waked I, Abdel-Hamid M, Mikhail NN, et al. Role of hepatitis C infection in chronic liver disease in Egypt. Am J Trop Med Hyg 2002;67:436–42. [6] Razavi H, Elkhoury AC, Elbasha E, Estes C, Pasini K, Poynard T, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology 2013;57:2164–70. [7] Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 2010;138:513–21. [8] Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005;5:558–67. [9] Sievert W, Altraif I, Razavi HA, Abdo A, Ahmed EA, Alomair A, et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int 2011;31(Suppl. 2):61–80.

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