Simplification of hepatitis C testing: a time to act
Mario Poljak1 ✉
1Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
129
2020;29:129-132 
doi: 10.15570/actaapa.2020.27
Introduction
Chronic infection with hepatitis C virus (HCV) affects 71 million 
people worldwide and accounts for 9.7 million disability-adjusted 
life years annually (1, 2). Global mortality related to its complica-
tions (cirrhosis, liver failure, and hepatocellular carcinoma) is es-
timated at 580,000 person per year (1, 2). Although initially only 
rarely connected with sexual transmission, recent evidence of 
HCV outbreaks in Europe, the United States, and Australia among 
men who have sex with men (MSM) who denied injecting drugs 
clearly showed that HCV should be considered an emerging sexu-
ally transmissible agent (3). In addition, the high reinfection rates 
among MSM who cleared HCV infection spontaneously or who 
were successfully treated further underline the importance of sex-
ual behavior in HCV transmission (3).
The development of reliable virological diagnostic and moni-
toring tools in the last 2 decades and the recent implementation 
of highly potent, safe, well-tolerated direct-acting antiviral (DAA) 
drug combinations with a high barrier to resistance have paved the 
way to potential elimination of HCV as a public health threat by 
2030 (4). Although HCV elimination can now be envisaged in sev-
eral countries, HCV remains a global public health concern. Many 
parts of the world are lacking political will and advocacy, econom-
ic support, or adequate implementation infrastructure and are in 
urgent need of simplified screening, diagnosis, linkage to care, 
treatment, and monitoring procedures to achieve this ambitious 
elimination goal (5, 6). To eliminate HCV globally, we desperately 
need creative solutions throughout the complete cascade of care.
This narrative review briefly discusses current and upcoming 
solutions for simplification of HCV testing, taking into account the 
most recent guidance documents issued by the European Associa-
tion for the Study of the Liver (EASL) (7), the American Association 
for the Study of Liver Diseases (AASLD) jointly with the Infectious 
Diseases Society of America (IDSA) (8), and the World Health Or-
ganization (WHO) (4).
How to screen for HCV infection
There is a general consensus that all patients with suspected HCV 
infection should be tested for anti-HCV antibodies in serum or 
plasma as a first-line diagnostic test (7, 8). Highly standardized, 
reliable, and rapid anti-HCV enzyme immunoassays performed 
on automated analyzers with random access modality are the 
standard of care in many countries. However, in many parts of the 
world more simplified screening approaches are needed, such as 
affordable rapid diagnostic tests (RDTs) using serum, plasma, fin-
gerstick whole blood, or crevicular fluid (saliva) as matrices that 
can be used instead of standard enzyme immunoassays at the pa-
tient’s care site to facilitate screening and improve access to care 
(7). An ideal RDT must meet the WHO “ASSURED” criteria (9), and 
it must be easy to use with minimal training. Some anti-HCV RDT 
tests have already attained the performance level of standard en-
zyme immunoassays (10); for more details, see recent reviews and 
a meta-analysis on the topic (11, 12). Good examples of important 
recent technical achievements in the field are the development of 
RDT for simultaneous detection of hepatitis A, B, and C viruses (13)
Abstract
Hepatitis C virus (HCV) affects 71 million people worldwide. The development of reliable diagnostic tools in the last 2 decades and 
recent implementation of highly potent and safe antiviral drug combinations have paved the way to potential elimination of HCV 
as a public health threat by 2030. This article briefly discusses current and upcoming solutions for simplification of HCV testing 
taking into account the most recent guidance documents issued by major professional societies. The general consensus is that all 
patients with suspected HCV infection should be tested for anti-HCV antibodies as a first-line diagnostic test. Some anti-HCV rapid 
diagnostic tests have already attained the performance of standard anti-HCV enzyme immunoassays. If anti-HCV antibodies are 
detected, the presence of HCV RNA or HCV core antigen should be determined to identify patients with ongoing infection. Several 
innovative devices for detecting HCV in serum or plasma are in the late stages of development and are based on loop-mediated 
isothermal amplification, smartphone-operated instruments, biosensors, lab-on-a-chip solutions, paper-based microfluidics, and 
CRISPR-Cas. An important solution for low- and middle-income countries is the availability of HCV tests that could perform equally 
reliably from whole blood and dried blood spots as well as from serum or plasma. Another interesting diagnostic concept for these 
countries is near-to-patient diagnostics using mobile microbiological laboratories, following either the lab-on-a-drone or rent-a-
point-of-care-test concepts. Using current and upcoming diagnostic approaches, the elimination of HCV is plausible, but in several 
countries this is probably not possible within the timeframe suggested by the World Health Organization. Two different elimination 
approaches have already been successfully tested in real-life conditions: micro-elimination and macro-elimination. The micro-
elimination approach has resulted in successful elimination in specific population subgroups in some high-income countries. In 
at least two countries, Georgia and Egypt, a macro-elimination approach has shown impressive real-life results relatively quickly.
Keywords: hepatitis C, HCV, diagnosis, testing, simplification
Acta Dermatovenerologica 
Alpina, Pannonica et Adriatica
Acta Dermatovenerol APA
Received: 1 June 2020 | Returned for modification: 15 July 2020 | Accepted: 6 August 2020
✉ Corresponding author: mario.poljak@mf.uni-lj.si
130
Acta Dermatovenerol APA | 2020;29:129-132M. Poljak
and the development of a simple paper-based device allowing 
separation of plasma from whole blood without the use of cen-
trifugation (14).
In addition to anti-HCV, screening for HCV RNA in serum or 
plasma is now inevitable in transfusion settings, and HCV RNA 
testing should be part of the initial evaluation in cases of suspect-
ed acute hepatitis C, in immunocompromised patients, and in pa-
tients on hemodialysis (7). In some screening settings where a lab-
oratory mainly serves high-risk populations such as intravenous 
drug users, 24-mini-pool HCV RNA screening of anti-HCV negative 
samples has been shown to be valuable and cost-effective (15, 16).
How to proceed after anti-HCV positivity
If anti-HCV antibodies are detected, the presence of HCV RNA in 
serum or plasma should be determined to identify patients with 
ongoing infection, preferably using a sensitive molecular method 
with a lower limit of detection (≤ 15 IU/ml) and following the reflex 
testing approach to increase linkage to care (7). Highly standard-
ized and reliable HCV RNA assays performed on fully automated 
sample-to-result fashion analyzers with sample number flexibil-
ity and the ability to perform multiple tests concordantly are now 
becoming the standard of care in many countries, replacing older 
batch-based testing platforms. Alternatively, smaller and portable 
molecular devices such as GeneXpert (Cepheid, Sunnyvale, CA) 
(17–19) or Genedrive (Genedrive Diagnostics, Manchester, UK) can 
be used for reliable, highly sensitive, and rapid detection of HCV 
RNA (11, 20). In addition, there are several commercial portable 
molecular devices in the launching stage or late stage of develop-
ment, and some of them are even suitable for use in extreme en-
vironmental conditions (20, 21). The goal with portable molecular 
instruments is to have a self-contained, fully integrated, sample-
to-report device that accepts raw, untreated specimens (preferably 
whole blood), performs all of the molecular steps, and provides 
interpreted test results in less than an hour.
However, all these solutions are not easily affordable for low- 
and middle-income countries (LMIC), and so new molecular as-
says that facilitate easy and inexpensive access and linkage to care 
are desperately needed. In 2018, EASL recommended the use of 
qualitative, not necessarily quantitative, HCV RNA assays with a 
limit of detection ≤ 1,000 IU/ml (3.0 log IU/ml) (7). In the settings 
where these assays will be used, the exceptionally low risk of a 
false-negative result in a small percentage of infected individuals 
(22) is outweighed by the benefit of scaling up access to diagno-
sis and care (11, 23). Namely, a recent study performed on a global 
dataset showed that a test with a limit of detection of 1,318 IU/ml 
would identify 97% of viremic HCV infections among almost all 
populations (24). Such future assays with lower but acceptable 
sensitivity and based on already existing molecular device pro-
totypes will use instruments based on loop-mediated isothermal 
amplification (LAMP) technology (25, 26), smartphone-operated 
instruments (26), biosensors (27), lab-on-a chip solutions (28), pa-
per-based microfluidics solutions (29, 30), CRISPR-Cas (31, 32), and 
even wearable devices (33). All these technical solutions should 
have a low frequency of invalid results and an affordable price. 
Among all technical solutions, those based on smartphones are 
most appealing because about 80% of the world population uses 
smartphones as of 2020, offering an ideal interface for different 
portable medical instruments.
Although available for almost two decades (34), and despite 
strong supporting scientific evidence (22–24, 35), as well as guide-
line recommendations (7), detection of HCV core antigen in serum 
or plasma in settings where HCV RNA assays are not available and/
or not affordable to identify patients with ongoing infection is still 
slowly making its way into wider implementation. One of the main 
reasons is marginally lower analytical sensitivity of HCV core an-
tigen detection in comparison to conventional HCV RNA assays. 
However, as already mentioned in real-life cohorts, the prevalence 
of low HCV viremia in untreated individuals is below 5%, and so 
the benefits of the HCV core antigen assay as a rapid, low-cost, 
and potential point-of-care test in population-based screening still 
outweigh the risk of a small number of false negatives in a subset 
of patients (23). A recent study showed that a great majority of pa-
tients with low viremia are patients with cirrhosis and excessive 
alcohol use, allowing stratified testing with HCV core antigen or 
HCV RNA to reliably identify patients with ongoing infection (22).
Alternative specimen types and alternative transport of 
samples and point-of-care devices
An important solution for LMICs is the availability of HCV diag-
nostic tests that can perform equally reliably from whole blood 
and dried blood spots (DBSs) as well as from serum or plasma 
(7). The main advantage of DBSs is to allow storage of desiccated 
blood that can be easily transported to reference centers, where 
state-of-the-art serological and molecular tests are available (11). 
Although standardization and better automation of DBS handling 
are needed, recent systematic reviews and meta-analyses showed 
only marginally inferior performance of anti-HCV testing, HCV 
RNA testing, and HCV genotype determination from DBSs in com-
parison to plasma or serum, with the exception of HCV core anti-
gen testing (11, 36–39).
Alternatively, whole blood samples can be rapidly and easily 
transported to reference centers in LMICs using drones. In the 
last decade, the use of drones has gradually spread into various 
healthcare settings (40). Rwanda and Tanzania recently launched 
a large delivery network with more than 1,000 health facilities 
connected by drones parachuting blood, vaccines, and malaria 
and HIV/AIDS drugs (40). Specimen transport by drones between 
several hospitals and a central laboratory has been routinely used 
in Lugano (Switzerland) and in Antwerp (Belgium) since 2018 and 
2019, respectively (40).
Another interesting concept for LMICs is near-to-patient or 
point-of-care (POC) diagnostics using mobile microbiological lab-
oratories. This can be achieved following the lab-on-a-drone (41) 
or rent-a-POC-test concepts (40). In the lab-on-a-drone prototype, 
an innovative and robust sample preparation device coupled 
with an isothermal amplification instrument and smartphone 
for measuring readouts and recording results are all attached to 
a quadcopter drone (41). In addition, the drone’s propellers are 
removable and replaceable with locally 3D-printed centrifuge ro-
tors of different shapes, capable of speeds up to 10,000 rpm and 
performing column-based extraction of high-quality RNA/DNA 
(40). The recently proposed rent-a-POC-test concept (40) follows 
the principle of a drone network pilot program built to deliver au-
tomated external defibrillators (42). The rent-a-POC-test concept 
is based on a central microbiology laboratory responsible for vali-
dation, calibration, and maintenance of POC instruments, their 
delivery, and quality control. Drones can be deployed to deliver 
on-demand portable POC instruments and test reagents to remote 
healthcare facilities, eliminating the need for local storage of in-
struments or tests and associated maintenance costs (40). In an 
131
Acta Dermatovenerol APA | 2020;29:129-132  HCV testing simplification
HCV elimination scenario, one could imagine drones loaded not 
only with portable POC instruments able to detect HCV viremic 
patients but also with prepacked DAAs for 8 to 12 weeks’ treat-
ment allowing an HCV test-and-treat strategy to be implemented 
in the most remote parts of the world.
Is large-scale screening for HCV infection achievable?
Using the diagnostic approaches described above, I strongly be-
lieve that large-scale elimination of HCV is plausible, but in sev-
eral countries this is probably not possible within the timeframe 
suggested by the WHO. Two different elimination approaches 
have already been successfully tested in real-life conditions: “mi-
cro-elimination” and “macro-elimination” (6).
The majority of high-income countries, including Slovenia, re-
cently launched a micro-elimination strategy as a first step toward 
universal national elimination. This practical and comprehensive 
concept, which breaks down national goals into smaller goals, 
uses a population segmentation approach in order to tailor con-
centrated elimination efforts to specific population subgroups; 
for example, individuals with HIV, patients with hemophilia, 
β-thalassemia major, decompensated cirrhosis, or organ trans-
plantation, patients treated with hemodialysis, (ever) injection 
drug users, MSM, migrants from high endemic countries, health-
care workers, and prisoners (43). Micro-elimination, by way of 
targeting smaller and clearly delineated HCV risk groups, allows 
faster and more efficient delivery of interventions. For this reason, 
micro-elimination as a “bottom-up” approach may be a more fea-
sible and efficient path to nationwide HCV elimination in some 
settings (43).
In contrast to micro-elimination strategies, the macro-elimina-
tion approach does not focus on a specific group(s) but is instead 
directed toward the entire population of a country or a large seg-
ment of it (6). Macro-elimination is initiated with either a mass-
screening program of the entire population or a cohort screening 
of a segment of the population with a historically high prevalence 
of HCV infection (6). In at least two countries, Georgia and Egypt, 
a macro-elimination approach has shown impressive real-life re-
sults relatively quickly (44–47).
Georgia, with a high prevalence of HCV infection, launched 
the world’s first national hepatitis C elimination program in April 
2015 (46). A key strategy was identifying, treating, and curing the 
estimated 150,000 HCV-infected people living in the country. As of 
the end of 2018, more than one million adults (40% of the adult 
population) had been screened for anti-HCV antibodies, of whom 
8.9% tested positive (47). Of the individuals that tested anti-HCV 
positive, 80% were tested for the presence of HCV RNA, of whom 
85.3% tested positive for active HCV infection. A total of 52,576 
people with active HCV infection initiated treatment, and 48,879 
had completed their course of treatment as of the end of 2018 (47). 
Sustained virologic response was achieved in 98.5% of individu-
als treated. Reflex testing for HCV core antigen, implemented in 
March 2018, increased the rates of monthly viremia testing by 
97.5% among those that screened positive for anti-HCV (47). Be-
tween 2015 and 2018, over one-third of people presumably living 
with HCV in Georgia were detected and linked to care and treat-
ment; however, identification and linkage to care of the remaining 
individuals with HCV infection is challenging (47).
Egypt has the highest rate of hepatitis C infection in the world. 
Ten years ago, it was estimated that nearly 15% of Egyptians were 
infected; the majority of them were infected during the country’s 
decades-long fight against schistosomiasis (48). On October 1st, 
2018, Egypt launched the “100 Million Healthy Lives” program. 
The goal was to screen all Egyptians 12 years of age or older for 
HCV infection, hypertension, diabetes, and obesity, and to offer 
free treatment or counseling for people that tested positive (44). 
Of a target population of 62.5 million, a total of 50 million (80%) 
spontaneously participated in screening between October 2018 
and April 2019. More than 4.6% of them had anti-HCV antibod-
ies, of whom 76.5% had active viremia (45). Sustained virologic 
response was achieved in 98.8% of individuals treated. Due to a 
very strong and transparent negotiation policy, the total cost of 
the HCV testing and treatment amounted to only $207.1 million. 
Negotiations led to a price reduction to only $0.58 per screening 
test, $4.80 per HCV RNA test, and $85 for 12 weeks of sofosbuvir 
plus daclatasvir treatment (45). The cost of identifying a patient 
with HCV viremia was $85.41, and the cost of identifying and cur-
ing a patient was $130.62 (45).
Acknowledgments
I am grateful to Anja Šterbenc for her help with the references and 
technical support. This work was presented in part at the Euro-
pean Society of Clinical Microbiology and Infectious Diseases (ES-
CMID) graduate education course “Elimination of viral hepatitis: 
are we ready?” which was held in Ljubljana, Slovenia (September 
27th–28th, 2019) in the form of the oral presentation “How do we 
diagnose the undiagnosed? A challenge for simplification.”
References
1. Blach S, Zeuzem S, Manns M, Altraif I, Duberg AS, Muljono DH, et al. Global 
prevalence and genotype distribution of hepatitis C virus infection in 2015: a 
modelling study. Lancet Gastroenterol Hepatol. 2017;2:161–76.
2. World Health Organization (WHO). Global Hepatitis Report 2017 [Internet]. [Ac-
cessed on May 1, 2020]. Available from: https://www.who.int/hepatitis/publi-
cations/global-hepatitis-report2017/en/.
3. Nijmeijer BM, Koopsen J, Schinkel J, Prins M, Geijtenbeek TB. Sexually transmit-
ted hepatitis C virus infections: current trends, and recent advances in under-
standing the spread in men who have sex with men. J Int AIDS Soc. 2019;22: 
e25348.
4. World Health Organization (WHO). Global health sector strategy on viral hepati-
tis 2016–2021. [Accessed on May 1, 2020]. Available from: https://apps.who.int/
iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf?sequence=1.
5. Pawlotsky JM. Interferon-free hepatitis C virus therapy. Cold Spring Harb Per-
spect Med. 2020: a036855.
6. Matičič M, Lombardi A, Mondelli MU, Colombo M; ESCMID Study Group for Vi-
ral Hepatitis (ESGVH). Elimination of hepatitis C in Europe: can WHO targets be 
achieved? Clin Microbiol Infect. 2020;26:818–23.
7. European Association for the Study of the Liver. EASL recommendations on 
treatment of hepatitis C 2018. J Hepatol. 2018;69:461–511.
8. Ghany MG, Marks KM, Morgan TR, Wyles DL, Aronsohn AI, Bhattacharya D, et al. 
Hepatitis C guidance 2019 update: AASLD-IDSA recommendations for testing, 
managing, and treating hepatitis C virus infection. Hepatology. 2020;71:686–
721.
9. Peeling RW. Testing for sexually transmitted infections: a brave new world? Sex 
Transm Infect. 2006;82:425–30.
10. Poiteau L, Soulier A, Lemoine M, Mohammed Z, Wlassow M, Rwegasha J, et al. 
Performance of a new rapid diagnostic test for the detection of antibodies to 
hepatitis C virus. J Virol Methods 2018;261:153–5.
132
Acta Dermatovenerol APA | 2020;29:129-132M. Poljak
11. Chevaliez S, Pawlotsky JM. New virological tools for screening, diagnosis 
and monitoring of hepatitis B and C in resource-limited settings. J Hepatol. 
2018;69:916–26.
12. Khuroo MS, Khuroo NS, Khuroo MS. Diagnostic accuracy of point-of-care tests 
or hepatitis C virus infection: a systematic review and meta-analysis. PLoS One. 
2015;10:e0121450.
13. Kweon OJ, Lim YK, Kim HR, Kim TH, Lee MK. Analytical performance of newly 
developed rapid point-of-care test for the simultaneous detection of hepatitis A, 
B, and C viruses in serum samples. J Med Virol. 2019;91:1056–62.
14. Carmona S, Seiverth B, Magubane D, Hans L, Hoppler M. Separation of plasma 
from whole blood by use of the cobas plasma separation card: a compelling 
alternative to dried blood spots for quantification of HIV-1 viral load. J Clin Mi-
crobiol. 2019;57:e01336-18.
15. Seme K, Mocilnik T, Fujs K, Babic DZ, Todorović A, Fras-Stefan T, et al. Twenty-
four mini-pool HCV RNA screening outside a blood transfusion setting: results of 
a 2-year prospective study. J Virol Methods. 2007;140:218–21.
16. Seme K, Mocilnik T, Poljak M. Twenty-four mini-pool HCV RNA screening in a 
routine clinical virology laboratory setting: a six-year prospective study. J Virol 
Methods 2011;171:303–5.
17. Wlassow M, Poiteau L, Roudot-Thoraval F, Rosa I, Soulier A, Hézode C, et al. The 
new Xpert HCV viral load real-time PCR assay accurately quantifies hepatitis C 
virus RNA in serum and whole-blood specimens. J Clin Virol. 2019;117:80–4.
18. Gupta E, Agarwala P, Kumar G, Maiwall R, Sarin S. Point-of-care testing (POCT) 
in molecular diagnostics: performance evaluation of GeneXpert HCV RNA test in 
diagnosing and monitoring of HCV infection. J Clin Virol. 2017;88:46–51.
19. McHugh MP, Wu AHB, Chevaliez S, Pawlotsky JM, Hallin M, Templeton KE. Multi-
center evaluation of the Cepheid Xpert Hepatitis C Virus Viral Load assay. J Clin 
Microbiol. 2017;55:1550–6.
20. Židovec Lepej S, Poljak M. Portable molecular diagnostic instruments in micro-
biology: current status. Clin Microbiol Infect. 2020;26:411–20.
21. Drain PK, Dorward J, Bender A, Lillis L, Marinucci F, Sacks J, et al. Point-of-care 
HIV viral load testing: an essential tool for a sustainable global HIV/AIDS re-
sponse. Clin Microbiol Rev. 2019;32:e00097-18.
22. Bertisch B, Brezzi M, Negro F, Müllhaupt B, Ottiger C, Künzler-Heule P, et al. 
Very low hepatitis C viral loads in treatment-naive persons: do they compromise 
hepatitis C virus antigen testing? Clin Infect Dis. 2020;70:653–9.
23. Mathur P, Kottilil S. Hepatitis C core antigen testing: still an effective diagnostic 
method for global elimination of hepatitis C. Clin Infect Dis. 2020;70:674–5.
24. Freiman JM, Wang J, Easterbrook PJ, Horsburgh CR, Marinucci F, White LF, et al. 
Deriving the optimal limit of detection for an HCV point-of-care test for viraemic 
infection: analysis of a global dataset. J Hepatol. 2019;71:62–70.
25. Curtis KA, Rudolph DL, Morrison D, Guelig D, Diesburg S, McAdams D, et al. 
Single-use, electricity-free amplification device for detection of HIV-1. J Virol 
Methods. 2016;237:132–7.
26. Ong DSY, Poljak M. Smartphones as mobile microbiological laboratories. Clin 
Microbiol Infect. 2020;26:421–4.
27. Ahmed A, Rushworth JV, Hirst NA, Millner PA. Biosensors for whole-cell bacterial 
detection. Clin Microbiol Rev. 2014;27:631–46.
28. Gurrala R, Lang Z, Shepherd L, Davidson D, Harrison E, McClure M, et al. Novel 
pH sensing semiconductor for point-of-care detection of HIV-1 viremia. Sci Rep. 
2016;6:36000.
29. Reboud J, Xu G, Garrett A, Adriko M, Yang Z, Tukahebwa EM, et al. Paper-based 
microfluidics for DNA diagnostics of malaria in low resource underserved rural 
communities. Proc Natl Acad Sci USA. 2019;116:4834–42.
30. Tsaloglou MN, Nemiroski A, Camci-Unal G, Christodouleas DC, Murray LP, Con-
nelly JT, et al. Handheld isothermal amplification and electrochemical detection 
of DNA in resource-limited settings. Anal Biochem. 2018;543:116–21.
31. Gootenberg JS, Abudayyeh OO, Lee JW, Essletzbichler P, Dy AJ, Joung J, et al. 
Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017;356:438–42.
32. Strich JR, Chertow DS. CRISPR-Cas biology and its application to infectious dis-
eases. J Clin Microbiol. 2019;57:e01307–18.
33. Kuehn BM. Wearable biosensors studied for clinical monitoring and treatment. 
JAMA. 2016;316:255–7.
34. Seme K, Poljak M, Babič DZ, Močilnik T, Vince A. The role of core antigen detec-
tion in management of hepatitis C: a critical review. J Clin Virol. 2005;32:92–101.
35. van Tilborg M, Al Marzooqi SH, Wong WWL, Maan R, Vermehren J, Maasoumy B, 
et al. HCV core antigen as an alternative to HCV RNA testing in the era of direct-
acting antivirals: retrospective screening and diagnostic cohort studies. Lancet 
Gastroenterol Hepatol. 2018;3:856–64.
36. Greenman J, Roberts T, Cohn J, Messac L. Dried blood spot in the genotyping, 
quantification and storage of HCV RNA: a systematic literature review. J Viral 
Hepat. 2015;22:353–61.
37. Soulier A, Poiteau L, Rosa I, Hezode C, Roudot-Thoraval F, Pawlotsky JM, et al. 
Dried blood spots: a tool to ensure broad access to hepatitis C screening, diag-
nosis, and treatment monitoring. J Infect Dis. 2016;213:1087–95.
38. Lange B, Cohn J, Roberts T, Camp J, Chauffour J, Gummadi N, et al. Diagnostic 
accuracy of serological diagnosis of hepatitis C and B using dried blood spot 
samples (DBS): two systematic reviews and meta-analyses. BMC Infect Dis. 
2017;17:700.
39. Lange B, Roberts T, Cohn J, Greenman J, Camp J, Ishizaki A, et al. Diagnostic 
accuracy of detection and quantification of HBV DNA and HCV RNA using dried 
blood spot (DBS) samples: a systematic review and meta-analysis. BMC Infect 
Dis. 2017;17:693.
40. Poljak M, Šterbenc A. Use of drones in clinical microbiology and infectious dis-
eases: current status, challenges and barriers. Clin Microbiol Infect. 2020;26: 
425–30.
41. Priye A, Wong S, Bi Y, Carpio M, Chang J, Coen M, et al. Lab-on-a-drone: toward 
pinpoint deployment of smartphone-enabled nucleic acid–based diagnostics 
for mobile health care. Anal Chem. 2016;88:4651–60.
42. Boutilier JJ, Brooks SC, Janmohamed A, Byers A, Buick JE, Zhan C, et al. Opti-
mizing a drone network to deliver automated external defibrillators. Circulation. 
2017;135:2454e65.
43. Lazarus JV, Wiktor S, Colombo M, Thursz M. EASL International Liver Founda-
tion. Micro-elimination—a path to global elimination of hepatitis C. J Hepatol. 
2017;67:665–6.
44. Haseltine WA. Universal disease screening and treatment—the Egyptian exam-
ple. N Engl J Med. 2020;382:1081–3.
45. Waked I, Esmat G, Elsharkawy A, El-Serafy M, Abdel-Razek W, Ghalab R, et al. 
Screening and treatment program to eliminate hepatitis C in Egypt. N Engl J Med. 
2020;382:1166–74.
46. Tsertsvadze T, Gamkrelidze A, Chkhartishvili N, Abutidze A, Sharvadze L, Kerash-
vili V, et al. Three years of progress towards achieving hepatitis C elimination in 
the country of Georgia, April 2015 – March 2018. Clin Infect Dis. 2019;ciz956.
47. Averhoff F, Shadaker S, Gamkrelidze A, Kuchuloria T, Gvinjilia L, Getia V, et al. 
Progress and challenges of a pioneering hepatitis C elimination program in the 
country of Georgia. J Hepatol. 2020;72:680–7.
48. Elgharably A, Gomaa AI, Crossey MME, Norsworthy PJ, Waked I, Taylor-Robinson 
SD. Hepatitis C in Egypt—past, present, and future. Int J Gen Med. 2016;10:1–6.