Hepatitis C infection in Egypt: prevalence, impact and management strategies

Gomaa, Asmaa; Allam, Naglaa; Elsharkawy, Aisha; Kassas, Mohamed El; Waked, Imam

doi:10.2147/hmer.s113681

Cited by 156 publications

(108 citation statements)

References 35 publications

(49 reference statements)

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“…In Egypt, the prevalence of HCV infection is the highest in the world,13,14 and genotype-4 is the most prevalent genotype 15–17. Although screening for HCV is recommended18,19 and the current available screening test has a 97% sensitivity and 100% specificity,20–22 up to 60% of cases in Egypt are diagnosed with decompensated cirrhosis or HCC23,24 mainly due to the lack of a national screening program.…”

Section: Introductionmentioning

confidence: 99%

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

Tag-Adeen

Sabra

Akazawa

et al. 2017

HMER

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BackgroundLiver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 pre-dominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication.Patients and methodsThe study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p-value <0.05 was statistically significant.ResultsFollowing DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m2. Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of −5.8 occurred in F4 versus −2.79, −1.28 and +0.08 in F3, F2 and F0–F1 respectively (p<0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 (p<0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement (p=0.01) and APRI improvement (p=0.01) and 81% showed Fib-4 improvement (p=0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement.ConclusionSuccessful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

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Section: Introductionmentioning

confidence: 99%

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

Tag-Adeen

Sabra

Akazawa

et al. 2017

HMER

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“…The virtually designed 1H-imidazole-2,5-dicarboxamide appeared to satisfactorily reproduce the stereochemistry of these NS4A features. Indeed, we could experimentally confirm that such compounds display binding affinity towards NS3 genotype-4, the most abundant type in the Middle East [49,50]. Our work allowed quantifying the binding affinity of our designed MOC compounds.…”

Section: Resultsmentioning

confidence: 71%

1H-Imidazole-2,5-Dicarboxamides as NS4A Peptidomimetics: Identification of a New Approach to Inhibit HCV-NS3 Protease

et al. 2020

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The nonstructural (NS) protein NS3/4A protease is a critical factor for hepatitis C virus (HCV) maturation that requires activation by NS4A. Synthetic peptide mutants of NS4A were found to inhibit NS3 function. The bridging from peptide inhibitors to heterocyclic peptidomimetics of NS4A has not been considered in the literature and, therefore, we decided to explore this strategy for developing a new class of NS3 inhibitors. In this report, a structure-based design approach was used to convert the bound form of NS4A into 1H-imidazole-2,5-dicarboxamide derivatives as first generation peptidomimetics. This scaffold mimics the buried amino acid sequence Ile-25' to Arg-28' at the core of NS4A 21'-33' needed to activate the NS3 protease. Some of the synthesized compounds (Coded MOC) were able to compete with and displace NS4A 21'-33' for binding to NS3. For instance, N 5 -(4-guanidinobutyl)-N 2 -(n-hexyl)-1H-imidazole-2,5-dicarboxamide (MOC-24) inhibited the binding of NS4A 21'-33' with a competition half maximal inhibitory concentration (IC 50 ) of 1.9 ± 0.12 µM in a fluorescence anisotropy assay and stabilized the denaturation of NS3 by increasing the aggregation temperature (40% compared to NS4A 21'-33' ). MOC-24 also inhibited NS3 protease activity in a fluorometric assay. Molecular dynamics simulations were conducted to rationalize the differences in structure-activity relationship (SAR) between the active MOC-24 and the inactive MOC-26. Our data show that MOC compounds are possibly the first examples of NS4A peptidomimetics that have demonstrated promising activities against NS3 proteins.

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“…A national database was also established to monitor HCV elimination progress. Furthermore, the National Committee for Control of Viral Hepatitis was able to negotiate with Gilead Sciences to provide sofobuvir at a reduced price of 300 USD per bottle (compared to 28,000 USD per bottle in the United States) …”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the National Committee for Control of Viral Hepatitis was able to negotiate with Gilead Sciences to provide sofobuvir at a reduced price of 300 USD per bottle (compared to 28,000 USD per bottle in the United States). (44,45) Australia has made progress in eliminating HCV by initiating DAA treatment in 32,400 patients, a 10-fold increase from the previous year and equating to 14% of the total patients with HCV nationally. (46) There were two main factors contributing to this success.…”

Section: Field-proven Strategiesmentioning

confidence: 99%

Toward the elimination of hepatitis C in the United States

Saab

Saggi

et al. 2018

Hepatology

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The emergence of effective direct-acting antiviral (DAA) agents has reignited discussion over the potential for hepatitis C elimination in the United States. Eliminating hepatitis C will require a critical examination of technical feasibility, economic considerations, and social/political attention. Tremendous advancement has been made with the availability of sensitive diagnostic tests and highly effective DAAs capable of achieving sustained viral response (SVR) in more than 95% of patients. Eliminating hepatitis C also requires escalating existing surveillance networks to monitor for new epidemics. All preventive interventions such as clean syringe and needle exchange programs, safe injection sites, opioid substitution therapies, and mental health services need to be expanded. Although costs of DAAs have raised budget concerns for hepatitis C elimination, studies have shown that eliminating hepatitis C will produce a savings of up to 6.5 billion USD annually along with other intangible benefits such as increased work productivity and quality of life. Economic models and meta-analyses strongly suggest universal hepatitis C screening for all adults rather than just for birth cohort and high-risk populations. Social and political factors are at least as important as technical feasibility and economic considerations. Due to lack of promotion and public awareness, HCV elimination efforts continue to receive inadequate funding. Social stigma continues to impede meaningful policy changes. Eliminating hepatitis C is an attainable public health goal that will require intense collaboration and sustained public support. (Hepatology 2018;67:2449-2459).

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Hepatitis C infection in Egypt: prevalence, impact and management strategies

Cited by 156 publications

References 35 publications

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

1H-Imidazole-2,5-Dicarboxamides as NS4A Peptidomimetics: Identification of a New Approach to Inhibit HCV-NS3 Protease

Toward the elimination of hepatitis C in the United States

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