In vitro activities and mechanisms of action of anti-cancer molecules from African medicinal plants: a systematic review.

Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this pathology. Management is often complicated by the high treatment costs, side effects and the increasing occurrence of resistance to treatments. The identification of new active ingredients extracted from endemic medicinal plants is definitively an interesting approach for the implementation of new therapeutic strategies: their extraction is often lower cost; their identification is based on an ethnobotanical history and a tradipratic approach; their use by low-income populations is simpler; this can help in the development of new synthetic molecules that are more active, more effective and with fewer side effects. The objective of this review is to document the molecules derived from African medicinal plants whose in vitro anti-cancer activities and the mechanisms of molecular actions have been identified. From the scientific databases Science Direct, PubMed and Google Scholar, we searched for publications on compounds isolated from African medicinal plants and having activity on cancer cells in culture. The data were analyzed in particular with regard to the cytotoxicity of the compounds and their mode of action. A total of 90 compounds of these African medicinal plants were selected. They come from nine chemical groups: alkaloids, flavonoids, polyphenols, quinones, saponins, steroids, terpenoids, xanthones and organic sulfides. These compounds have been associated with several cellular effects: i) Cytotoxicity, including caspase activation, alteration of mitochondrial membrane potential, and/or induction of reactive oxygen species (ROS); ii) Anti-angiogenesis; iii) Anti-metastatic properties. This review points out that the cited African plants are rich in active ingredients with anticancer properties. It also stresses that screening of these anti-tumor active ingredients should be continued at the continental scale. Altogether, this work provides a rational basis for the selection of phytochemical compounds for use in clinical trials.

Prevalence of Glu323Lys Mutation of the TIGR/MYOC Gene and Risk Factors amongst Primary Open-angle Glaucoma Patients in Ouagadougou, Burkina Faso.

Aim: Glaucoma is a group of degenerative diseases of the optic nerve whose predisposing factors may be genetic. The objective of this study was to estimate the frequency of the Glu323Lys mutation as a genetic risk factor for glaucoma. Materials and methods: A cross-sectional study over 6 months from October 2020 to March 2021 in Ouagadougou, Burkina Faso. A total of 89 samples of patients with primary open-angle glaucoma (POAG) were collected. The frequency of the Glu323Lys mutation of the myocilin, trabecular meshwork inducible glucocorticoid response (TIGR/MYOC) gene by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Results: In glaucoma patients, only homozygous nonmutated guanine-guanine (GG) and heterozygous mutated adenine-guanine (AG) genotypes were found in 96.63 and 3.37% of cases, respectively. Around 69.66% of patients had a family history of glaucoma, 28.09% had a history of hypertension, and 7.86% had a history of diabetes. Conclusion: The frequency of the Glu323Lys mutation of the TIGR/MYOC gene was 3.37% in the glaucoma population in Ouagadougou. A case-control study is necessary to know the contribution of the Glu323Lys mutation as a genetic risk factor for glaucoma in our study population. Clinical significance: This study constituted the beginning of genetic investigations of glaucoma in our context and showed a low Glu323Lys mutation. How to cite this article: Traoré L, Sanou J, Bakyono BS, et al. Prevalence of Glu323Lys Mutation of the TIGR/MYOC Gene and Risk Factors amongst Primary Open-angle Glaucoma Patients in Ouagadougou, Burkina Faso. J Curr Glaucoma Pract 2023;17(2):79-84.

A simple synthesis of α-Costic acid analogue with antibacterial potential, DFT and molecular docking.

Natural products extracted from plants has been recognized as the most efficient starting materials to synthesize new derivatives of medicinal interest. Our research focuses on the isolation and characterization of sesquiterpene derivatives from Dittrichia Viscosa (L), as well as their hemisynthesis. To that end, a phytochemical study of Dittrichia viscosa leaves was conducted in order to obtain a sesquiterpenoid, α -Costic acid, which will be further transformed to γ -Costic acid with high yield using simple processes. Optimized molecular geometry and vibrational frequencies of both products were computed using the density functional theory. In addition, the antibacterial activity of isolated and hemisynthesized products were analyzed in vitro against Escherichia coli resistant to ß-lactamase 616, Pseudomonas aeruginosa, and Staphylococcus aureus. The obtained compounds were investigated by in silico biological method to evaluate their potential inhibitory activity against same strains using FtsA, LasR proteins and DNA polymerase III enzyme.

Screening of BRCA1 (c.5177_5180delGAAA rs80357867 and c.4986+6T>C rs80358086) and the BRCA2 (c.6445_6446delAT rs80359592) Genes for Breast Cancer Prevention in Burkina Faso.

Background: The objective of this study is to search for mutations in the BRCA1 (c.5177_5180delGAAA and c.4986+6T>C) and BRCA2 genes (c.6445_6446delAT) in a population of women diagnosed with breast cancer. Methods: This is a case-control study that involved 140 participants, including 70 patients with histologically diagnosed breast cancer and 70 healthy women without breast cancer. Mutations in the BRCA1 (rs80357867, rs80358086) and BRCA2 (rs80359592) genes were tested by real-time PCR. The 95% confidence interval Odds Ratio (OR) was used to estimate the associations between specific genotypes and breast cancer. Results: The study revealed that no mutations were detected for rs80359592. Similarly, no reference allele (TTTC/TTTC) of rs80357867 was found in this study. However, the homozygous double mutant (-/) genotype of this rs80357867 was observed in 11.43% and 1.43% of patients and controls respectively, while 88.57% of patients and 98.57% of controls had a heterozygous deletion (TTTC/-). Concerning rs80358086, 8.57% of the patients had a heterozygous mutation (A/G) with no significantly risk association with occurrence of breast cancer (OR = 6.46; 95% CI: 0.75-55.21; p = 0.11). In addition, this heterozygous mutation was significantly associated with a family history of breast cancer (OR=128; 95% CI: 9.46-1730.93) and breast cancer risk in nonmultiparous women (OR=6; 95% CI: 1-35.90; p= 0.05) but no association with overweight/obesity (OR=1.66; 95% CI: 0.18-15.35; p=1). Conclusion: This study shows high frequencies of heterozygous mutation of rs80357867 and rs80358086 from patients. In Burkina Faso, these results could help with early diagnosis of breast cancer in patients.

MDP Salts: A New Bonding Strategy for Zirconia.

Durable resin-ceramic adhesion may influence the clinical success of ceramic restorations, which has been one of the challenging issues in dentistry. The present study assessed the bond strength and chemical interaction of 10-methacryloxydecyl dihydrogen phosphate (MDP), MDP+silane, and MDP-salt primers to alumina-blasted zirconia ceramic by tensile bond strength test, surface elemental composition with x-ray photoelectron spectroscopy analysis, contact angle measurement, surface morphology with scanning electron microscopy, and surface topography with 3-dimensional confocal laser scanning microscope analyses. MDP-salt showed the highest tensile bond strength before and after thermocycling when compared with MDP and MDP+silane (P < 0.05). The measured contact angle values differed significantly (P < 0.001) in the order of MDP-salt > control (no chemical pretreatment) > MDP+silane > MDP. There was no difference in surface roughness (P = 0.317) and surface topography among all tested groups. Zirconia treated with MDP-salt showed phosphorus peaks in addition to zirconia and alumina peaks. MDP-salt has zirconia priming properties, which improves bonding performance to resin cement.

Covid-19 in recipients of living donor liver transplantation: a worse or an equivalent outcome?

BACKGROUND: Coronavirus disease 2019 (Covid-19) pandemic is representing a massive burden to the community with the new virus. There is few data regarding Covid-19 in liver transplant patients. Concerns were raised regarding the course of the disease in transplanted patients due to immunosuppression and risk of hepatic injuries. AIM: To describe the outcomes of Covid-19 infection in recipients of living-donor liver transplantation (LDLT). METHODS: Retrospective analysis of 41 recipients of LDLT diagnosed with Covid-19 by real-time PCR or CT chest criteria of Covid-19 between April 2020 and April 2021. This Cohort was derived from Ain Shams Center for Organ Transplantation database, Ain Shams Specialized Hospital, Cairo, Egypt, which is considered one of the largest centers of LDLT in the Middle East. Patients were classified to mild, moderate, severe and critics according to clinical classification released by the National Health Commission of China. RESULTS: A total of 41 patients and 2 patients with reinfection were included in this cohort with mean age 54 years with 74% male and 26% female. The body mass index ranged from 19.3 to 37. About 30% were described as a mild case, 46.5% were moderate, 14% were severe and 9% were critical cases. Two cases developed infection twice. Total of 20 patients (46.5%) were managed in home isolation setting, 17 patients (39.5%) needed admission to ward, 4 patients (9%) in intermediate care unit and 2 patients (4%) admitted to intensive care unit. About 60% of cases were on room air, only 3 patients needed invasive methods, 2 patients needed face mask and 1 case needed invasive CPAP. In total, 41 patients recovered (95%) and 2 patients (5%) died; 1 was Covid related and the other one was non-Covid related. Female gender, higher BMI and hypertension were associated with severe course of the disease. CONCLUSION: In the setting of LDLT, the possibilities of catching Covid-19 infection are high due to chronic immunosuppression use. Yet, the outcome of infection in term of morbidity and the needs for hospital admission or intensive care is generally matched to general population.

The impact of carcinoma in situ in ureteral margins during radical cystectomy: A case-controlled study.

BACKGROUND AND OBJECTIVE: The presence of carcinoma in situ (Cis) in association with bladder cancer is associated with a poor prognosis. However, the prognosis associated with the presence of Cis in ureteral margins (CUM) during radical cystectomy has been poorly defined. To assess the prognosis associated with the presence of Cis in ureteral margins in patients with pM0 bladder cancer who have not undergone neoadjuvant chemotherapy. MATERIALS AND METHODS: A retrospective case-control study was conducted between 2001 and 2016 using data from one academic center in France. From 1,450 radical cystectomies, 122 patients (case) who had CUM were matched according to age, sex, pTNM stage and urinary diversion method with a population sample of 122 patients (controls) who did not have Cis in ureteral margins during radical cystectomy. The survival analysis was performed by Kaplan-Meier using a (95%) CI. Multivariate Cox regression analysis was used to test the effect of CUM on cancer-specific survival. Recurrence-free survival was defined as a recurrence of urothelial carcinoma in the upper urinary tract. RESULTS AND LIMITATIONS: The mean follow-up period was 55.43 ± 39.6 months. The rate of Cis in the bladder in the CUM cases group was evaluated at 11.47%. The median overall and specific survival was inferior in the CUM cases group estimated at 43.3 [35.33-56.93] months, 52.43 [42.16-68.93] months respectively compared to the control group with a significant difference (P= 0.001, P= 0.0039). The cumulative probability of urothelial recurrence-free survival was decreased in the case group compared with the control group (63.9% vs. 92.6%, P = 0.0001). Multivariate analysis shown that urothelial recurrence was associated with CUM [(P <0.001), (HR adjusted =11.31), (95% CI): (3.38-37.77)] and the macroscopic appearance of the ureter (thickened, dilated) [(P= 0.003), (HR adjusted =4.62), (95% CI): (3.31-8.84)]. CONCLUSION: CUM is a poor prognostic factor that impacts cancer-specific survival and Recurrence-free survival. The presence of CUM has been independently associated with a significant increase in the risk of urothelial recurrence, and a decrease in both overall and specific survival. This supports the use of frozen section analysis to complete radical cystectomy without CUM.

Degree of Conversion Contributes to Dentin Bonding Durability of Contemporary Universal Adhesives.

CLINICAL RELEVANCE: The degree of conversion of contemporary universal adhesives positively correlates with the bond strength to dentin. The correlation is more marked after thermocycling, suggesting that a high degree of conversion is required for long-term dentin bonding durability. SUMMARY: Purpose: The objectives of this study were to evaluate the micro-tensile bond strength (µTBS) of five contemporary universal adhesives to dentin after 24 hours and thermocycling (TC), to measure their degrees of conversion (DC) and to test the correlation between µTBS and DC.Methods and Materials: Four commercially available universal adhesives, Prime&Bond universal (PBU), Ecosite Bond (EB), G-Premio Bond (GPB), and Clearfil Universal Bond Quick (UBQ), and one experimental adhesive, UBQ without an amide monomer (UBQ-A), were used in this study. For the µTBS test, midcoronal dentin of 50 human molars was exposed, ground using 600-grit SiC paper, and the adhesives were applied according to the manufacturers' instructions. After resin-composite buildup and 24-hour water storage, one-half of the specimens were subjected to 15,000 thermal cycles. The specimens were sectioned into beams and stressed in tension at a crosshead speed of 1 mm/min until failure. The DC of adhesives applied to dentin was evaluated using attenuated total reflectance Fourier-transform infrared spectroscopy immediately after light-curing. All data were statistically analyzed at a significance level of 0.05.Results: The highest µTBSs were obtained with UBQ, UBQ-A, and PBU, which were not significantly different from each other both after 24 hours and TC. The µTBS of GPB was lower compared with the aforementioned adhesives, but significantly only after TC, and the lowest µTBSs were obtained with EB. TC did not affect the µTBSs of UBQ, UBQ-A, and PBU significantly, but a significant decrease was observed with GPB and EB. The highest DC was obtained with PBU and UBQ, followed by 2-hydroxyethyl methacrylate-rich adhesives UBQ-A and EB, which exhibited significantly lower DCs. The DC of GPB could not be determined because the reference peak at 1608 cm-1 was not detected in its spectra. A significant positive correlation was shown between µTBS and DC after 24 hours (r=0.716) and TC (r=0.856).Conclusion: µTBS and DC were positively correlated, more markedly after TC, which suggests that DC may be an important factor for bond durability.

Detection of virulence and multidrug resistance operons in Pseudomonas aeruginosa isolated from Egyptian Baladi sheep and goat.

BACKGROUND: Pseudomonas aeruginosa is a pit of an enormous group of free-living bacteria that are able to live everywhere and suggested to be the causative agent of great scope of acute and chronic animal infections. AIM: The current study was carried out to illustrate the prevalence of P. aeruginosa in small ruminants and existence of some virulence operons as well as its antimicrobial resistance. MATERIALS AND METHODS: A total of 155 samples from sheep and 105 samples from goats (mouth abscesses, fecal swabs, nasal, tracheal swabs, and lung tissue) were collected for bacteriological study, existence of some virulence expression operons with the study of their sensitivity to the antimicrobials using disc diffusion and presence of mexR operon which is responsible for multidrug resistance (MDR). RESULTS: The bacteriological examination revealed that P. aeruginosa was isolated from nine out of 155 samples from sheep (5.8%) and four isolates out of 105 samples from goat (3.8%). It is found that 12 (92.3%), 10 (76.9 %), and 8 (61.5%) of P. aeruginosa isolates harbored hemolysin phospholipase gene (pcl H), gene (exo S), and enterotoxin gene (tox A), respectively. The results of antibiotic sensitivity test showed that all tested isolates were resistant to ampicillin, bacitracin, erythromycin, streptomycin, tetracycline, trimethoprim-sulfamethoxazole, and tobramycin but sensitive to ciprofloxacin and norfloxacin. The MDR (mex R) operon was existed in all isolates. CONCLUSION: There is a growing risk for isolation of virulent MDR P. aeruginosa from sheep and goat illness cases, and this should be regarded in the efficient control programs.

Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution.

The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.

[12-year history of radical surgery indications for the treatment of prostate cancer]. / Évolution sur 12 ans des indications de prostatectomie totale pour cancer.

AIM: To analyze the indications of radical prostatectomy and lymph node dissection retained during the last 12 years in an academic surgical center in the Paris region in order to ensure their adequacy in relation to the current clinical guidelines. METHOD: Monocentric retrospective study of prospectively collected data, between 2007 and 2019. Analysis of the clinical and pathological characteristics which were taken into account during multidisciplinary meeting discussion for the treatment decision, and comparison of their evolution over the four 3-year period corresponding to the clinical guideline updates. RESULTS: Two thousand eighty-eight consecutive patients treated by radical prostatectomy between 16/03/2007 and 17/03/2019 were included. The proportion of patients classified as low, intermediate or high risk according to D'Amico system was 13.2%, 80.8% and 6.0% respectively. An increase in the frequency of surgical treatment of high-risk cancers has been observed. At the same time, there has been a decrease in the frequency of prostatectomies to treat low-risk cancers. CONCLUSION: The indications for radical prostatectomy and lymph node dissection have evolved in line with the current clinical guidelines which were taken into consideration in a onco-urological multidisciplinary meeting. LEVEL OF EVIDENCE: 3.

Association of ficolin-2 gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multicenter study.

BACKGROUND: Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE. OBJECTIVES: The objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions -986 (G/A), -602 (G/A), -4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents. METHODS: This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at -986 G/A (rs3124952), -602 G/A (rs3124953), -4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay. RESULTS: The frequencies of the FCN2 GG genotype and G allele at -986 and -602 positions were significantly more represented in patients with pSLE than in controls (p < 0.001). Conversely, the FCN2 AA genotype and A allele at position -4 were more common in patients than in controls (p < 0.001). Moreover, patients carrying the FCN2 GG genotype in -986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4-4.78); p = 0.006). The FCN2 AA genotype at position -4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25-7.84); p = 0.024). CONCLUSION: The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position -986 and AA genotype at position -4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.

[Acute lower limb ischemia secondary to femoral osteochondroma]. / Ischémie aiguë du membre inférieur secondaire à un ostéochondrome fémoral.

Osteochondromas or bone exostoses are bone tumors commonly found in adolescents or young adults. These benign tumors are usually incidentally discovered, exceptionally by a vascular or nervous complication. We report the case of a 22-year-old patient presenting with left femoral exostosis revealed by an acute ischemia of the lower limb. Clinical examination of the contralateral limb was without abnormality. Computed tomography angiography revealed a thrombosed aneurysm of the supra articular popliteal artery associated to an exostosis of the lower extremity of the femur. Surgical treatment was recommended in this patient: resection of the popliteal aneurysm associated with a end-to-end suture of the popliteal artery and resection of bone exostosis.

The research gap in chronic paediatric pain: A systematic review of randomised controlled trials.

BACKGROUND AND OBJECTIVE: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. METHODS: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. RESULTS: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. CONCLUSIONS: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. SIGNIFICANCE: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases.

Adsorption and photocatalysis for methyl orange and Cd removal from wastewater using TiO2/sewage sludge-based activated carbon nanocomposites.

Nanocomposite TiO2/ASS (TiO2 nanoparticle coated sewage sludge-based activated carbon) was synthesized by the sol-gel method. The changes in surface properties of the TiO2/ASS nanocomposite were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and X-ray fluorescence. The prepared TiO2/ASS nanocomposite was applied for simultaneous removal of methyl orange dye (MO) and Cd2+ from bi-pollutant solution. The factors influencing photocatalysis (TiO2 : ASS ratios, initial pollutant concentrations, solution pH, nanocomposite dosage and UV irradiation time) were investigated. The results revealed that high removal efficiency of methyl orange dye (MO) and Cd2+ from bi-pollutant solution was achieved with TiO2/ASS at a ratio (1 : 2). The obtained results revealed that degradation of MO dye on the TiO2/ASS nanocomposite was facilitated by surface adsorption and photocatalytic processes. The coupled photocatalysis and adsorption shown by TiO2/ASS nanocomposite resulted in faster and higher degradation of MO as compared to MO removal by ASS adsorbent. The removal efficiency of MO by ASS adsorbent and TiO2/ASS (1 : 2) nanocomposite at optimum pH value 7 were 74.14 and 94.28%, respectively, while for Cd2+ it was more than 90%. The experimental results fitted well with the second-order kinetic reaction.

Splenic histiocyte-rich pseudotumor following chemotherapy for non Hodgkin diffuse large B cell lymphoma.

Chemotherapy may induce mass lesion in rare conditions, which can be easily mistaken as a residual tumor mass. In this report, we describe a mass affecting spleen in a patient received chemotherapy for non Hodgkin diffuse large B cell lymphoma. This mass proved histologically to be non neoplastic formed of sheets of histiocytes and xanthoma cells, which is called histiocyte-rich pseudotumor. This report describes this rare lesion and the possible differential diagnosis.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.