Correspondence
Our centre at the Hôpital Européen
Georges Pompidou developed an
accurate method to detect tumour
mutations in plasma from next-
generation sequencing data on the
basis of quantifying the error rate of
each base position of the gene panel.4
This method is now used in France
for routine analysis in patients with
colorectal cancer throughout the
course of their disease. Analysis of
base-position error rate has also been
used to evaluate tumour burden and
track early relapse in the perioperative
setting of systemic, surgical, or
locoregional therapies.5
The complexities of ctDNA
assessment for patients with
oligometastatic disease necessitate
an individualised approach to ctDNA
analysis, as we believe that dynamics
might differ substantially both
between patients and depending
on the local therapy used. Our
hypothesised assertion is that serial
analysis of ctDNA in the aftermath
of local therapy could yield insights
into both the mechanisms of tumour
ctDNA release and the therapeutic
effects of cellular damage, ultimately
leading to improved patient
management across the continuum of
the disease.
We would like to draw the attention
of colorectal cancer researchers to the
possibility of including the assessment
of ctDNA throughout all treatment
settings, including in local therapies
that could modify the standard
dichotomy between curable and
advanced disease stages. Such efforts
could contribute substantively to the
personalised management of patients
with colorectal cancer and further
elevate standards of care.
We declare no competing interests.
*Tom Boeken, Hélène Blons,
Carole Dean, Marc Sapoval,
Olivier Pellerin
tom.boeken@aphp.fr
Université de Paris Cité, Paris, France (TB, HB, MS, OP);
Department of Vascular and Oncological
Interventional Radiology (TB, CD, MS, OP) and
Department of Biochemistry, Pharmacogenetics and
www.thelancet.com/gastrohep Vol 8 December 2023
Molecular Oncology (HB), Hôpital Européen
Georges Pompidou, AP-HP, Paris, France; INSERM
PARCC U 970, Paris, France (TB, MS, OP); Paris
Cancer Institute CARPEM, Paris, France (HB);
HeKA team, Inria, Paris, France (TB)
1 Loft M, To YH, Gibbs P, Tie J. Clinical application
of circulating tumour DNA in colorectal cancer.
Lancet Gastroenterol Hepatol 2023; 8: 837–52.
2 Boysen AK, Pallisgaard N, Andersen CSA,
Spindler KG. Circulating tumor DNA as a
marker of minimal residual disease following
local treatment of metastases from colorectal
cancer. Acta Oncol 2020; 59: 1424–29.
3 Chu KF, Dupuy DE. Thermal ablation of
tumours: biological mechanisms and advances
in therapy. Nat Rev Cancer 2014; 14: 199–208.
4 Pécuchet N, Rozenholc Y, Zonta E, et al. Analysis
of base-position error rate of next-generation
sequencing to detect tumor mutations in
circulating DNA. Clin Chem 2016; 62: 1492–503.
5 Bayle A, Basile D, Garinet S, et al. Next-
generation sequencing targeted panel in
routine care for metastatic colon cancers.
Cancers 2021; 13: 5750.
WHO awards Egypt with
gold tier status on the
path to eliminate
hepatitis C
On Oct 9, 2023, WHO Director-
General Tedros Adhanom Ghebreyesus
presented the Egyptian President
Abdel Fattah El-Sisi with a certificate
declaring that Egypt had been
awarded gold tier status on the path to
elimination of hepatitis C. Egypt, which
had once had the highest prevalence
of hepatitis C globally, is now the
first country to have undergone
validation for elimination by WHO and
has achieved a milestone in disease
elimination.
A nationwide screening and
treatment campaign (100 Million
Healthy Lives)1 in 2018–19 screened
nearly 63 million individuals for
hepatitis C virus (HCV) antibodies,
substantially increasing the total
number of individuals diagnosed with
hepatitis C and subsequently treated.
After completion, the Egyptian Ministry
of Health and Population requested
that WHO validate their achievements
towards eliminating HCV.
On April 19, 2023, WHO conducted
a global consultation in Geneva,
Switzerland, to define the path to
elimination and update the interim
guidance for validating the elimination
of viral hepatitis B and C as public
health threats. This consultation
established tiered classifications (gold,
silver, and bronze) for elimination
targets related to blood safety,
injection safety, harm reduction
programmes, diagnosis rate, treatment
rate, and the implementation of a
sentinel surveillance programme for
monitoring hepatitis sequelae.2
On Aug 11, 2023, the Egyptian
Ministry of Health and Population,
in collaboration with the National
Validation Taskforce, submitted an
HCV path to elimination dossier to
the WHO country office in Cairo.3
Subsequently, the Regional Validation
Committee of the WHO Eastern
Mediterranean region appraised
the dossier. On Sept 14, 2023, after
thorough evaluation, the committee
unanimously agreed to award Egypt
gold tier status. This decision was
officially endorsed by the WHO Global
Validation Advisory Committee on Published Online
Oct 3, 2023. October 19, 2023
https://doi.org/10.1016/
Egypt qualified for gold tier status S2468-1253(23)00364-3
due to the diagnosis of 86·7% of
those living with HCV, treatment of
93·7% of those diagnosed with HCV,
screening of 100% of donated blood
units for bloodborne pathogens, strict
adherence to zero reuse of syringes, a
remarkable 100% increase in needle
and syringe programme coverage over
the past 2 years, and the establishment
of five sentinel sites for sequelae
surveillance.3
This remarkable achievement has
paved the way for other countries to
begin the process of validation for the
elimination of hepatitis B and C. We
hope this will ultimately lead to the
achievement of WHO’s 2030 target of
eliminating viral hepatitis.
We declare no competing interests.
*Mohamed Hassany, Wael Abdel-Razek,
Mohamed AbdAllah
mohamadhassany@yahoo.com
National Hepatology and Tropical Medicine
Research Institute, Ministry of Health and
Population, Cairo, Egypt (MH); Hepatology and
1073
 Correspondence

Gastroenterology Department, National Liver infection) has been observed for 52 provided serology 1–8 weeks
Institute, Menoufia University, Shibin Al Kawm, SARS-CoV-2 variants of concern, after bivalent dose, and 52 provided
Egypt (WA-R); Tropical Medicine Medical Research
Division, National Research Center, Giza, leading to the development of serology 8 or more weeks after
Egypt (MA) bivalent vaccines.3,4 We assessed the bivalent dose (appendix p 4). All
1 Waked I, Esmat G, Elsharkawy A, et al. immunogenicity and safety of bivalent participants had seroconversion at
Screening and treatment program to eliminate SARS-CoV-2 vaccines in participants both 1–8 weeks (GMT 20973 AU/mL
hepatitis C in Egypt. N Engl J Med 2020;
382: 1166–74. with IBD. [95% CI 15983–27521]) and 8 or more
2 WHO. Guidance for country validation of viral Adults with IBD and at least weeks (12768 AU/mL [8874–18371])
hepatitis elimination and path to elimination. three mono­ v alent doses and after bivalent dose (figure; appendix
https://www.who.int/publications/i/
item/9789240078635 (accessed one bivalent dose of a SARS-CoV-2 p 4). Univariate analyses indicated
Oct 15, 2023). mRNA vaccine (BNT162b2 or that antibodies 8 or more weeks
3 The Arab Republic of Egypt Ministry of Health
and Population. Viral hepatitis path to
mRNA-1273) were recruited from after vaccination were diminished
elimination dossier. August, 2023. the STOP COVID-19 in IBD study. 2 for patients with Crohn’s disease
Antibodies to the spike protein (anti- (appendix p 5). Compared with
spike) were measured 1–8 weeks participants on vedolizumab
Bivalent mRNA and 8 or more weeks after bivalent and ustekinumab, participants
vaccination. Geometric mean titres on anti-TNF therapies had lower
SARS-CoV-2 vaccination (GMT) were used to report anti-spike antibodies 1–8 weeks and 8 or more
in patients with concentrations. Adverse events were weeks after vaccination (appendix
captured with the Adverse Events p 5). GMTs for those on anti-
inflammatory bowel Following Immunization form at least TNF therapies were diminished
disease 30 days after receiving a bivalent compared with those without any
dose. Electronic medical records were immunosuppressive therapies at
Published Online Individuals with inflammatory bowel reviewed for a flare of IBD within 8 or more weeks after vaccination
October 6, 2023 disease (IBD) have shown adequate 30 days of vaccination (appendix (appendix p 5). Multivariable analyses
https://doi.org/10.1016/
S2468-1253(23)00310-2 serological responses to SARS-CoV-2 pp 2–3). were not conducted due to small
See Online for appendix
monovalent vaccines. 1,2 Increased Of 78 total participants, 70 were sample sizes within serology timing
vaccine escape (ie, breakthrough interviewed for adverse events, groups.
Overall, 45 (64%) of 70 participants
100 000 reported an adverse event following
n=52 n=52
bivalent vaccination. Injection site
reaction was the most common
adverse event (36 [51%]), followed
by fatigue or malaise (20 [29%])
10 000
and musculoskeletal (nine [13%];
Anti-spike IgG concentration (AU/mL)

appendix p 6). No participants

For serological data from the
study see https://kaplan-gi.
shinyapps.io/COVID_Serology/
reported a severe adverse event
requiring a visit to an emergency
1000 department or hospitalisation. No
participants experienced an IBD flare
within 30 days following vaccination.
Our study shows strong serological
100
responses following bivalent SARS-
CoV-2 vaccination in people with IBD.
We identified diminished responses for
participants taking anti-TNF therapies
compared with those not taking any
10 immunosuppressive therapies and
Post-bivalent dose (1–8 weeks) Post-bivalent dose (8+ weeks)
Serology timing
those on vedolizumab or ustekinumab.
Adverse events following bivalent dose
Figure: Anti-SARS-CoV-2 spike antibody concentration per timepoint were mild and objective evidence of
The black points represent geometric mean titres and the black bars represent bounds of 95% CI associated
IBD flare within 30 days of vaccination
with each geometric mean titre. The dashed line represents the threshold for positive seroconversion
(50 AU/mL). The upper limit of detection is 50 000 AU/mL as per the Abbott Quant II IgG Assay. Serological was not observed. Overall, our study
data from the STOP COVID-19 in IBD study are available online. shows serological responses to bivalent

1074 www.thelancet.com/gastrohep Vol 8 December 2023