SYNOPSIS Review of Update on the management of chronic hepatitis C: 2018 consensus guidelines from the Canadian Association for the Study of the Liver
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SYNOPSIS
Review of Update on the management of chronic
hepatitis C: 2018 consensus guidelines from the
Canadian Association for the Study of the Liver
Requestor: Public Health Unit request
Request prepared by: Michelle Murti, Jennifer Pritchard
Date: 07/09/2018
Contact information: michelle.murti@oahpp.ca
Article citation: Shah H, Bilodeau M, Burak KW, Cooper C, Klein M, Ramji A, et al. The management of
chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver.
CMAJ. 2018;190(22):E677-E687. Available at: http://www.cmaj.ca/content/190/22/E677
Key Messages of Synopsis
o Hepatitis C virus (HCV) has a high prevalence with national estimates of approximately 1% of
the overall Canadian population being anti-HCV-positive, between 0.64% to 0.71% living with
chronic HCV infection, and approximately 44% of those living with chronic HCV infection
remaining undiagnosed.1
o Risk-factor based screening is universally recommended to identify undiagnosed infection in
those at elevated risk of HCV. Recent Canadian guidelines have disagreed in terms of whether
birth cohort population-based screening for Baby Boomers should be added to risk-factor
screening.
o The recent 2018 guideline from the Canadian Association for the Study of the Liver (CASL) by
Shah et al, has recommended population-based screening for Baby-Boomers in addition to
risk-factor based screening to address the burden of illness and under-diagnosis in this age
cohort.2
o This synopsis is a summary and critical appraisal of the strengths and limitations of the Baby-
Boomer screening recommendation by Shah et al.
SynoposisBackground on HCV Screening
There are approximately 3,500 newly reported cases of HCV annually in Ontario, and in a 2010
burden of illness report, it was the highest burden reportable infectious agent in Ontario based on
potential years of life lost.3 National estimates by the Public Health Agency of Canada (PHAC), using a
back-calculation methodology, estimated that 0.64% to 0.71% % of the Canadian population has
chronic HCV, and this was highest among those born between 1955-1959 (1.5%), followed by those
born in 1950-1954 (1.25%).1 The same model estimated that 44% of those with chronic HCV were
unaware of their infection.1 Early identification of HCV exposure and current infectious status
through testing for HCV RNA are necessary steps to ensure timely engagement in care and treatment
in order to prevent long-term complications (such as cirrhosis, liver cancer and death) and to reduce
the risk of transmission to others. In recent years, treatment options, such as direct acting antivirals
(DAAs), have become highly effective as well as safer and more tolerable, affordable and accessible.2
In 2018, the Canadian Association for the Study of the Liver (CASL) published guidelines on the
management of chronic hepatitis C which recommended population-based screening for those born
between 1945-1975 in addition to risk-factor based screening.2 Public Health Ontario’s (PHOs)
objective was to conduct a critical appraisal of the population-based screening recommendation
included in the guideline, including both the published manuscript and the online Appendix. It should
be noted the CASL guideline also addressed treatment recommendations which are not covered in
this synopsis.
In addition to the CASL guideline, there have been a number of other recent relevant guidelines from
Canadian jurisdictions regarding HCV screening, including the following:
o Nationally, the Public Health Agency of Canada recommends screening individuals for hepatitis C
using a risk-based approach.4
o This recommendation is based on the 2017 Canadian Task Force on Preventive Health
Care recommendation against screening for hepatitis C in asymptomatic Canadian adults
unless they are at risk for hepatitis C infection (strong recommendation, very low quality
evidence).5
o The 2016 Canadian Liver Foundation’s Hepatitis C Screening and Testing Quick Reference Guide
included a recommendation for birth cohort screening of all adults born between 1945-1975.6
This Guide is an infographic listed in the Clinical Practice Guidelines section of the Canadian Liver
Foundation’s website. It does not describe the basis of this recommendation or have a reference
to a guideline on which this recommendation is based.
o A 2017 guideline from Quebec did not find the data to be sufficiently compelling to justify a
systematic screening program for those born between 1950 to 1969, but recommended
considering offering one-time opportunistic screening of those born between 1950 and 1969
regardless of other risk factors.7
Synopsis: HCV screening recommendations 2Summary of 2018 CASL Guideline
The CASL recommendation under ‘screening and linkage to care’ was:
To increase the identification of the large proportion of persons living with undiagnosed HCV, we
recommend that screening be both risk-based and target the birth cohort of individuals born from
1945 to 1975, which currently encompasses the majority of persons chronically infected with HCV
in Canada. (Class 2a – weight of evidence or opinion is in favour of usefulness or efficacy, Level C –
only consensus opinions of experts, case studies, or standard of care).
The online Appendix version of the recommendation is similar except that the birth cohort years
included are from 1945 to 1970.
The authors listed four reasons for supporting birth cohort screening:
1. HCV prevalence is highest in the Baby Boomer birth cohort and that the burden of liver
disease is expected to increase in this population. Supporting evidence for this statement
included an Ontario laboratory serosurvey study and a national modeling estimate study.
o The Ontario study was a serosurvey of laboratory samples of individuals born between 1945
and 1974 where seroprevalence rates, based on anti-HCV antibodies, were highest in those
born between 1950-54 and 1960-64 (1.98% each), followed by those born in 1955-1959
(1.80%), 1965-1969 (1.38%), 1970-74 (1.14%) and 1945-1950 (1.02%).8
o The PHAC modeling study estimated chronic HCV prevalence in Canada between 1991 and
2011. Based on estimates for 2011, they found that those born between 1955 and 1959 had
the highest prevalence of chronic HCV (1.5%), followed by those born in 1950-54 (1.25%),
1960-64 (1.2%), 1965-69 (1.1%) and 1970-74 (0.8%).1
2. Approximately 44-70% of HCV-infected Canadians are unaware of their infection. Supporting
evidence for this statement includes two studies.
o The upper estimate (70%) is based on an analysis from the 2007-2009 and 2009-2011
Canadian Health Measures Survey comparing seroprevalence of anti-HCV antibody to
participant’s (14-79 years old) awareness of their infection status, and found that 69.5%
(95%CI: 49.3% to 84.3%) were unaware of their infection.9
o The lower estimate (44%) is a based on the PHAC modeling estimate described above.1
o The CASL recommendation also noted that risk-based strategies perpetuate stigma
associated with HCV, whereas population-based screening normalizes the process.
Synopsis: HCV screening recommendations 33. New lowered pricing for HCV treatment makes screen-and-treat strategies even more cost-
effective than previously estimated.
o Previous cost-effectiveness estimates include a 2015 Canadian study that concluded “in
Canada, a 1-time program to screen for and treat HCV infection, aimed at birth cohort
populations (25-64 years or 45-64 years of age) is likely to be cost-effective.”10 The ages for
one-time screening in this cost-effectiveness analysis translate into birth cohorts of 1951-
1990 or 1951-1971.
4. Canada will not meet World Health Organization 2030 HCV elimination targets without birth
cohort screening.
The authors also listed five rebuttals to the 2017 CTFPHC Guideline that recommended against Baby
Boomer screening, indicating that in the CTFPHC Guideline document:
I. There was an overemphasis on harms of screening
II. Benefits of screening were under-valued
III. Costs of therapy used were inaccurate and misleading, and included mention of
outdated treatment regimens
IV. Costs of no therapy for patients with HCV were not included
V. Concerns about the diagnostic accuracy of HCV testing are inaccurate and outdated
Study Methodological Rigour and Transparency
Two PHO reviewers assessed the CASL population-based screening recommendation using a modified
approach to the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. The
recommendation was assessed broadly within the six domains of the AGREE II instrument without
assigning numeric scoring to each domain and without a numeric score to the overall assessment.
The reviewers also did not provide a statement on whether they would recommend the use of this
guideline. An overall assessment was determined based on the overall quality of the
recommendation after consideration of the six domains; this assessment involves judgement by the
reviewers and is subjective.11 The synopsis was reviewed by all contributors.
1. Scope and Purpose
This guideline updates previous guidance from CASL published in 2015.12 The 2015 version of
this guideline did not include specific screening recommendations, and the stated scope of
the 2018 guideline document did not include making recommendations on screening. The
Synopsis: HCV screening recommendations 4scope of the 2018 guideline was “to support clinical practice, it makes recommendations on
the assessment, evaluation and management of HCV-infected persons.” The specific health
question and target population of this guideline is the clinical management of HCV-infected
persons. Nonetheless, the 2018 guideline documents do make screening recommendations
for the Baby Boomer cohort.
2. Stakeholder Involvement
o Stakeholder input was received from nine CASL members including physicians and allied
health workers.
o Persons with lived experience of HCV and persons who are born between 1945 and 1975
were not included in the guideline development or review.
3. Rigour of Development
o The methodology included a focused literature search of published and unpublished English-
language literature in MEDLINE from January 15, 2015 up to October 17, 2017 using search
terms: hepatitis C, hepatitis and treatment.
o The primary section author reviewed the previous 2015 guideline, added the new
recommendations and graded the evidence. The secondary author reviewed the
recommendations and supporting evidence and disagreements were resolved by consensus.
o The entire guideline panel reviewed the recommendations with support from two-thirds of
the members required for recommendation inclusion and grading. The panel used the same
grading system (class of evidence levels 1-3 and grade of evidence A-C) as their 2015
recommendations.12
o The literature review did not specifically include ‘screening’ as part of the search strategy.
The results of the search strategy and the papers reviewed in developing the
recommendation are not published in the manuscript or the Appendix.
o There is no description of critical appraisal tools used to assess the quality of studies included
as supporting literature.
o The methods did not describe whether any established framework13 or methodology, such as
procedures used by the CTFPHC14, the United States Preventive Services Task Force15, or
Public Health England16, was used in the process of developing this screening
recommendation.
4. Clarity of Presentation
o There is inconsistency between the published manuscript and the online Appendix in terms
of the birth cohort years included in the recommendation, and it is unclear which cohort
Synopsis: HCV screening recommendations 5(1945-75 in the published manuscript vs. 1945-70 in the Appendix) is the intended/preferred
option.
o There is inconsistency between the supporting literature for the HCV prevalence and cost-
effectiveness and the recommendation in terms of the years chosen for inclusion as the Baby
Boomer cohort.
In the referenced PHAC modeling study, the birth cohort between 1955 to 1979 had
an increasing prevalence of chronic HCV from 1991 to 2011, whereas the birth cohort
between 1945 to 1954 had a decreasing prevalence in that time frame.1 While the
prevalence in the 1945 to 1954 cohort was still higher than the overall prevalence in
the population, it is unclear how the authors of the CASL guideline assessed these
declining trends in their determination of which cohorts to recommend for screening.
The guideline does not establish a specific chronic HCV prevalence threshold above
which screening is considered cost-effective. Without a threshold to assess each five-
year birth cohort within the 1945 to 1975 birth years, it is unclear why the entire 30
years range was included in the recommendation.
o The referenced 2015 Canadian cost-effectiveness study used a baseline scenario of screening
in those born between 1951 and 1990 or 1951 and 1971.10 The guideline does not discuss the
applicability of these results to their recommendation of the 1945 to 1975 birth cohort.
5. Applicability
o The two main supporting articles on population prevalence referenced by the CASL
recommendation are based on national modeling estimates and Ontario seroprevalence.1,8
Because of the inclusion of Ontario data, these estimates have greater applicability to
Ontario than to the rest of Canada.
o The article cited as the source for the upper end estimate of the undiagnosed fraction of HCV
infected Canadians (70%) is based on a national survey from 2007 to 2011, and may not
reflect more recent efforts to raise awareness and testing of HCV with the advent of new
therapies.9
o The cost-effectiveness study cited by the CASL recommendation likely had a higher cost per
quality of life years saved than are expected to result from current cost-effectiveness
analyses given recent decreases in HCV treatment pricing and improvement in outcomes
associated with treatment.10
o The authors of the CASL recommendation have not included feasibility considerations for the
implementation of a one-time population-based birth cohort screening program, such as:
o The clinical, social and ethical acceptability to patients and providers
Synopsis: HCV screening recommendations 6o An assessment of the benefits and harms from screening
o An assessment of the health care system capabilities for offering accessible testing
and provision of care and treatment for newly diagnosed patients
6. Editorial Independence
o The guideline panel consisted of co-chairs appointed by the CASL Executive Committee and
six selected panel members. Members of the guideline panel disclosed financial relationships
with HCV treatment pharmaceutical companies and were not excluded from voting on
recommendations.
o The authors declared that no funding, direct or in-kind, was provided to the guideline panel
for the guideline development.
o CASL membership vetted the guideline for the presence of commercial bias. The financial
relationships of the CASL members who vetted the guidelines were not included.
Overall, the main strength of the CASL recommendation for population-based screening is the
authors’ identification of the high prevalence of chronic HCV in this population and the undiagnosed
burden of illness. The authors also include important considerations of the new lower costs
associated with treatment, new evidence on health benefits of treatment, and the potential for
stigma associated with risk-based screening. The main limitation is the absence of a described
methodological framework for guiding the development of this recommendation, and thereby to
assess the validity of the recommendation. This also includes absence of a feasibility assessment for
implementing population-based screening from which to assess applicability. There is a lack of clarity
in application of findings from supporting literature and potential for bias based on stakeholder
involvement and editorial independence. As such, the overall quality of this screening
recommendation was assessed as relatively low.
Ontario Applicability
The treatment of HCV has been significantly improved with the advent of DAAs which are safe, better
tolerated and highly effective treatment options. Ontario has recently updated the drug formulary
such that DAA treatment is available to essentially all patients with chronic HCV infection.17
Interpretation of the recent recommendation to include population-based screening for HCV for
those born between 1945 and 1975 should consider the strengths and limitations of this guideline
recommendation and its applicability at the individual and population levels.
Synopsis: HCV screening recommendations 7References 1. Trubnikov M, Yan P, Archibald C. Estimated prevalence of Hepatitis C Virus infection in Canada, 2011. CCDR 2014;40-19; 429-436. Available from: https://www.canada.ca/en/public- health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly- issue/2014-40/ccdr-volume-40-19-december-18-2014/ccdr-volume-40-19-december-18-2014- 2.html 2. Shah H, Bilodeau M, Burak KW, Cooper C, Klein M, Ramji A, et al. The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver. CMAJ. 2018;190(22):E677-87. Available from: http://www.cmaj.ca/content/190/22/E677 3. Kwong JC, Crowcroft NS, Campitelli MA, Ratnasingham S, Daneman N, Deeks SL, et al. Ontario Burden of Infectious Disease Study Advisory Group; Ontario Burden of Infectious Disease Study (ONBOIDS): An OAHPP/ICES Report. Toronto, ON: Ontario Agency for Health Protection and Promotion, Institute for Clinical Evaluative Sciences; 2010. Available from: http://www.ontla.on.ca/library/repository/mon/24012/306590.pdf 4. Government of Canada. For Health Professionals: Hepatitis C [Internet]. Ottawa, ON: PHAC; 2016- 03-16. Available from: https://www.canada.ca/en/public-health/services/diseases/hepatitis- c/health-professionals-hepatitis-c.html#a2 5. Canadian Task Force on Preventive Health Care. Recommendations on hepatitis C screening for adults. CMAJ 2017;189(16):E594-604. Available from: http://www.cmaj.ca/content/189/16/E594 6. Canadian Liver Foundation (CLF). Hepatitis C in Canada: Primary care physicians are the 1st point of screening [Infographic]. Ontario, Canada: CLF; 2016. Available from: https://www.liver.ca/wp- content/uploads/2017/09/CLF_HepC_Screening_Infographic_FINAL_ENG.pdf 7. Noël L, Drouin MC. Avis sur la pertinence d’un dépistage du VHC chez les baby-boomers au Québec. Québec : Institut national de santé publique du Québec; 2018. Available from: https://www.inspq.qc.ca/sites/default/files/publications/2333_pertinence_depistage_vhc_baby_ boomers.pdf 8. Bolotin S, Feld JJ, Garber G, Wong WW, Guerra FM, Mazzulli T. Population-based estimate of hepatitis C virus prevalence in Ontario, Canada. PloS One. 2018;13(1):e0191184. Available from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191184 9. Rotermann M, Langlois K, Andonov A, et al. Seroprevalence of hepatitis B and C virus infections: results from the 2007 to 2009 and 2009 to 2011 Canadian Health Measures Survey. Health Rep 2013;24:3-13. Available from: https://www.researchgate.net/publication/258824951_Seroprevalence_of_hepatitis_B_and_C_v Synopsis: HCV screening recommendations 8
irus_infections_Results_from_the_2007_to_2009_and_2009_to_2011_Canadian_Health_Measur
es_Survey
10. Wong WW, Tu HA, Feld JJ, Wong T, Krahn M. Cost-effectiveness of screening for hepatitis C in
Canada. CMAJ. 2015;187(3):E110-E121. Available from:
http://www.cmaj.ca/content/cmaj/early/2015/01/12/cmaj.140711.full.pdf
11. Brouwers M, Kho ME, Browman GP, Cluzeau F, Feder G, Fervers B et al. on behalf of the AGREE
Next Steps Consortium. AGREE II: Advancing guideline development, reporting and evaluation in
healthcare. CMA J. 2010; 182:E839-842. Available from: http://www.agreetrust.org/wp-
content/uploads/2013/10/AGREE-II-Users-Manual-and-23-item-
Instrument_2009_UPDATE_2013.pdf
12. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ. An update on the management of chronic
hepatitis C: 2015 consensus guidelines from the Canadian Association for the Study of the Liver.
Canadian Journal of Gastroenterology and Hepatology. 2015;29(1):19-34. Available from:
https://www.liver.ca/wp-
content/uploads/2017/09/CASL_Hep_C_Consensus_Guidelines_Update_-_Jan_2015.pdf
13. Wilson JMG, Jungner G. Principles and practice of screening for disease. Public Health Papers.
1968;34. Geneva: World Health Organization. Available from:
http://apps.who.int/iris/bitstream/handle/10665/37650/WHO_PHP_34.pdf;sequence=17
14. Canadian Task Force on Preventive Health Care. Canadian Task Force on Preventive Health Care
procedure manual. 2014. Available from: https://canadiantaskforce.ca/wp-
content/uploads/2016/12/procedural-manual-en_2014_Archived.pdf
15. U.S. Preventive Services Task Force. Standards for guideline development. Rockville, MD: Agency
for Healthcare Research and Quality.2017. Available from:
https://www.uspreventiveservicestaskforce.org/Page/Name/standards-for-guideline-
development
16. Public Health England. Criteria for appraising the viability, effectiveness and appropriateness of a
screening programme. London, UK: Public Health England. 2015. Available from:
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-
programmes/criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-
screening-programme
17. Ontario Ministry of Health and Long-Term Care. Notice from the Executive Officer: Funding of
hepatitis C drug products under the Ontario Drug Benefit program. Ottawa, ON: Queen’s Printer
for Ontario; 2017. Available from:
http://www.health.gov.on.ca/en/pro/programs/drugs/opdp_eo/notices/exec_office_20170227.p
df
Synopsis: HCV screening recommendations 9Contributors Bryna Warshawsky, Medical Director, Communicable Diseases, Emergency Preparedness and Response, Public Health Ontario Karin Hohenadal, Manager, Communicable Diseases, Emergency Preparedness and Response, Public Health Ontario Lee Goneau, Clinical Microbiologist, Public Health Ontario Laboratories, Public Health Ontario Shelley Deeks, Chief, Communicable Diseases, Emergency Preparedness and Response, Public Health Ontario Disclaimer This document was developed by Public Health Ontario (PHO). PHO provides scientific and technical advice to Ontario’s government, public health organizations and health care providers. PHO’s work is guided by the current best available evidence at the time of publication. The application and use of this document is the responsibility of the user. PHO assumes no liability resulting from any such application or use. This document may be reproduced without permission for non-commercial purposes only and provided that appropriate credit is given to PHO. No changes and/or modifications may be made to this document without express written permission from PHO. Citation: Ontario Agency for Health Protection and Promotion (Public Health Ontario). Synopsis: Article review: The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver. Toronto, ON: Queen’s Printer for Ontario; 2018. Synopsis: HCV screening recommendations 10
Public Health Ontario acknowledges the financial support of the Ontario Government. Synopsis: HCV screening recommendations 11
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