Treatment guidelines are considered to be an important tool in steering patients to medical treatment. Thisstudy was conducted to analyze guidelines for the treatment of hepatitis C virus (HCV) infection in injectiondrug users (IDUs) in the European Union (EU) countries as a component of treatment access. National and
international databases, expert contacts, professional societies, and health administrations were approachedto acquire guidelines. According to their quality standard, guidelines were divided into expert opinions, semiofficial guidelines, official guidelines, and consensus processes. Recommendations for the treatment ofHCV infection in IDUs vary substantially, from lack of recommendations and outright treatment disapproval to recommendations for treatment under specified circumstances. Recent guidelines that apply qualified processprocedures that include literature research tend to be more permissive.
Qualified guideline processes in each
EU country and subsequently renewed pan-European guidelines are needed.
Chronic infection with hepatitis C virus (HCV) is considered
to be a major burden, both to those infected
and to the public health system [1]. Besides alcoholism,
chronic HCV infection is the major cause of liver cirrhosis
and end-stage liver disease and the main reason
for liver transplantation [2]. Moreover, chronic HCV
infection is associated with increased rates of depression
and fatigue and leads to impaired quality of life [3, 4].
The future health costs in 10 European Union (EU)
countries for 1 year of drug-related HCV, hepatitis B
virus, and HIV infection were estimated at i1.89 billion,
with HCV accounting for nearly 40% [5]. Within the
EU countries, the prevalence of HCV infection in the
general population is as high as 3%; among injection
drug users (IDUs), the prevalence of HCV infection is
30%–98% [6–8]. The introduction of antiviral com-
bination therapy with ribavirin and pegylated IFN has
led to sustained virological response in 150% of patients;
however, rates depend on the HCV genotype [9,
10]. Nevertheless, treatment of HCV infection in IDUs
is still the subject of controversy. Reasons for withholding
antiviral therapy from IDUs may include the
assumption of poor adherence, fear of adverse effects,
and the risk of reinfection [11]. There is evidence that
IDUs can adhere to medical protocols in the same manner
as do non-IDUs [12], and early pilot studies showed
that antiviral treatment of chronic HCV infection in
IDUs is both safe and effective [13–17]. Rates of reinfection
in IDUs may not necessarily be higher than
in non-IDU populations [18]. Despite these promising
results, IDUs may face barriers when trying to gain
access to treatment for chronic HCV infection. Treatment
guidelines have an increasing effect on the provision
of therapies, because, in times of limited resources,
allocation of even these limited resources
follows, among other considerations, the recommendations
of guidelines. In addition, treatment guidelines
may have an effect on the provision of qualifications
for professionals and on the willingness of sponsors to pay for
treatment and of professionals to provide treatment [19, 20].
This study was undertaken to analyze guidelines for the treatment
of HCV infection as applied in the EU countries with
regard to treatment accessibility for IDUs.
METHODS
Guidelines for the treatment of HCV infection were retrieved
by researching international databases and requesting information
from professional societies and experts. The MEDLINE
database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) was
used with the keywords “guidelines,” “management,” “guidance,”
and “treatment”—in combination with the terms “hepatitis,”
“hepatitis C,” and “HCV.” The first 200 publications
that were presented for each keyword were considered.
Publications from non-EU countries except for Norway were
not taken into account. Authors of relevant references were
screened for further publications about these topics. Internet
home pages of international and national professional societies
in the areas of addiction medicine, gastroenterology, and
hepatology were screened for guidelines and experts. Experts,
as identified by the European Monitoring Centre for Drugs and
Drug Addiction (http://www.emcdda.eu.int) and the Centre for
Interdisciplinary Addiction Research of the University of
Hamburg (http://www.zis-hamburg.de), were asked to provide
both guidelines and expert contacts in their country. In addition,
we contacted experts and/or institutions discovered via
the European Society for the Study of the Liver (EASL; http:
//www.easl.ch), European Network for HIV/AIDS and Hepatitis
Prevention in Prisons, and European Information Network
on Drugs and Drug Addiction (http://www.emcdda.eu
.int/index.cfm?fuseactionppublic.Content&nNodeIDp403&s
LanguageISOpEN). To assess quality levels, guidelines were
divided into consensus papers, official guidelines, semiofficial
guidelines, and expert opinions. To qualify as a consensus paper,
guidelines had to follow, at least partially, recommendations
for development in the areas “scope and purpose,” “stakeholder
involvement,” “rigor of development,” “clarity of presentation,”
“applicability,” and “editorial independence,” as suggested by
the Appraisal of Guidelines Research and Evaluation collaboration
[21]. To qualify as official guidelines, guidelines had to
be authored by a professional organization; to qualify as semiofficial
guidelines, the authorship of at least 3 experts on the
topic was required. Recommendations by single experts on the
topic were rated as expert opinions.
RESULTS
The results of this research are presented by country, guideline
quality level, and content analysis.
EU. The latest consensus paper of the EASL was published
in 1999. It states that “Active intravenous drug users should
not be treated due to the risk of reinfection. In addition, compliance
with treatment is poor in patients in whom alcoholism
has not been interrupted and in whom drug addiction continues”
[22, p. 958].
Austria. The Austrian Society of Gastroenterology and Hepatology
published in 1998 official guidelines for the treatment
of viral hepatitis. This publication states, “For persons actively
injecting drugs and/or drinking alcohol antiviral treatment is
absolutely contraindicated. Patients after successful detoxification
and/or patients in methadone maintenance therapy may
receive antiviral treatment” [23, p. 25]. A group of 7 authors
who are specialists in addiction medicine published guidelines
for treatment of chronic hepatitis C in drug users in Austria
from the point of view of addiction medicine, which was categorized
as semiofficial guidelines [24]. These authors indicate
that patients are eligible for treatment after at least 6 months
of abstinence or, in case of substitution treatment, without
additional drug use or, in case of drug use, no injection drug
use or intoxication and few psychosocial deficits. Patients definitely
not eligible for treatment are characterized by periodically
or continuously uncontrolled drug use or by injection
drug use without applying safer-use criteria. Patients undergoing
substitution treatment who follow safer-use criteria when
injecting intravenously or IDUs who follow safer-use criteria
are possibly eligible for treatment. Recently, Ferenci [25] published
his expert opinion, which is largely in concordance with
the 1998 recommendations of the Austrian Society for Gastroenterology
and Hepatology.
Belgium. The Steering Committee of the Belgian Association
for the Study of the Liver published official guidelines
[26]; however, these guidelines lack recommendations for patients
with drug-related problems. A group of 4 authors published
guidelines categorized as semiofficial, which stated that
“…current studies support that the anti-HCV therapy of
IVDUs [IDUs] should be the same as in other HCV-infected
patients” but excluded certain IDUs by saying that “Patients
with uncontrolled active intravenous drug use are not candidates
for medical treatment due to lack of compliance and a
high risk of re-infection” [27, p. 99].
Denmark. One expert opinion was acquired in Denmark.
It was reported that most Danish treatment centers adhere to
the EASL consensus report. “[Being an] IDU is not a reason
for exclusion and certainly substitution treatment is not. Most
centres would however not treat IDUs actively injecting” (B.
P. Christensen, personal communication).
Finland. Two semiofficial guidelines were acquired for Finland.
In the guidelines from the year 2002 it is assumed that
IDUs “…even if drug dependence does not exist any longer,
cannot profit from therapy” [28, p. 1261]. The other guidelines,
published in 2003, states that “…long-term intravenous
consumption…represents a clear contra-indication of therapy…”
[29, p. 525].
France. The French consensus paper states that “occasional
intravenous drug use by an otherwise stabilized patient does
not contraindicate treatment” [30, p. 306]. Expert opinions and
literature research constituted an integral component of the
consensus process. An expert mapped out that a nonstabilized
IDU with ongoing drug use must not be treated [31]; on behalf
of the bibliographic group, a case-by-case decision was recommended
[32].
Germany. One official guidelines and 2 semiofficial guidelines
exist. The author of the official guidelines is the German
Society of Digestive and Metabolic Diseases. This publication
states that “an interferon-based therapy should not be initiated
in active drug and/or alcohol users. Drug users should be abstinent
before initiation of interferon-based therapy for at least
twelve months, alcoholics for at least six months. No consensus
exists as to treatment of patients in methadone maintenance
programs” [33, p. 981]. Semiofficial guidelines authored by the
president of the German Society of Addiction Medicine recommends
postponing treatment in cases of !12 months of
abstinence in drug users or in cases of substantial alcohol intake
[34]. A second semiofficial guidelines was authored by 8 experts
on the topic under the auspices of the German Ministry of
Health and the Robert Koch Institute. This publication recommends
treatment of IDUs within a methadone maintenance
program, restricts treatment of IDUs after detoxification to
specialized centers, and recommends treatment of abstinent
IDUs in general in close collaboration with experts in addiction
medicine (U. Marcus, Ministry of Health and Social Security,
personal communication).
Greece. No data were acquired.
Ireland. No data were acquired.
Italy. An expert on the topic stated that there are no specific
guidelines for the treatment of HCV infection in IDUs (G.
Rezza, personal communication). Guidelines of the Italian Association
for the Study of the Liver will be published soon (M.
Strazzabosco, personal communication).
Luxembourg. No data were acquired.
The Netherlands. According to an expert opinion, treatment
for HCV infection is offered to IDUs within a special
treatment program [35], although inclusion criteria remain
unclear.
Norway. According to guidelines classified as semiofficial,
“Patients addicted to alcohol should not be treated. The same
applies to those addicted to other substances, although heroin
addicted sometimes are successfully treated. Drug addicts
treated with methadone are in exceptional cases also treated
with IFN and ribavirin. Until now, six months abstinence before
initiating HCV-therapy has been required” [36, p. 927].
Portugal. No data could be acquired.
Spain. Two official guidelines, authored by the Spanish
College of Hospital Pharmacists and the Society of Primary
Care Physicians, respectively, do not address the problem of
treatment for HCV infection in IDUs [37, 38]. Two semiofficial
guidelines, each authored by a group of 6 experts, do not consider
injection drug use as a treatment contraindication [39,
40]. An expert opinion promoted by the Spanish Association
for the Study of the Liver (http://www.aeeh.org) does not specifically
address the topic of treatment of HCV among IDUs.
On this Web page, consensus papers of the National Institutes
of Health [41] and the EASL [22] are also presented. Therefore,
the official position of this professional society remains unclear.
In the autonomous region of Catalonia, official guidelines published
by the Department of Health and Social Security [42]
considers injection drug use a contraindication for the treatment
of HCV infection.
Sweden. Official guidelines authored by 19 experts considers
“ongoing or recent drug or alcohol abuse” a contraindication
for treatment [43]. The official guidelines of the Swedish
Medical Products Agency considers “ongoing or recent drug
use” a relative contraindication for treatment [44].
United Kingdom. The official guidelines of the Royal College
of Physicians of London and the British Society of Gastroenterology
states that “current IVDUs should not be treated
although in selected cases ex-IVDUs taking regular oral methadone
may be considered for treatment” [45, p. i7]. The official
guidelines of the National Institute for Clinical Excellence states
that “treatment of people who continue to use drugs intravenously
is often not indicated due to the high probability of
reinfection, presumed likelihood of relatively high levels of noncompliance
and the possibility of drug interactions. Cessation
of intravenous drug use before starting antiviral treatment is
therefore important. Combination therapy is not contra-indicated
for former intravenous drug users whose drug use has
been stabilized on oral methadone or other products such as
buprenorphine” [46].
Scotland. The official guidelines of the Scottish Executive
states that “treatment is not recommended for drug users who
continue to inject, where drug interactions, compliance and the
possibility of reinfection are issues. This will need to be assessed
on a case-by-case basis” [47, p. 7]. Table 1 encapsulates the
findings described above.
CONCLUSION
This study was conducted to provide an overview on the guidelines
for treatment of chronic HCV infection in IDUs. Because
of the disabling potential of HCV infection and its high prevalence
among IDUs, it is considered to be a major burden to
both the public and the individual. Treatment guidelines have
an effect of allocation of resources and provision of therapy in
terms of finances, qualification, and outreach. Therefore
ment access is influenced by guidelines. Treatment guidelines
allowing for or even recommending treatment of a specific
disease can facilitate access to treatment [19, 20].
Data were gathered in Austria, Belgium, Denmark, Finland,
France, Germany, Italy, The Netherlands, Norway, Spain including
Catalonia, Sweden, and the United Kingdom (including
Scotland). Contacts were established in Greece, Ireland, Luxembourg,
and Portugal as well, but data quality and sources
remain unclear yet and are therefore not considered. According
to their quality level, guidelines were categorized into expert
opinions, semiofficial guidelines, official guidelines, and consensus
papers (table 1). Taking into account only guidelines
with the highest level, the EU and French guidelines met criteria
of consensus papers; in Austria, Belgium, Germany, Spain (including
the autonomous region of Catalonia), Sweden, and the
United Kingdom (including Scotland), guidelines met the criteria
of official guidelines; semiofficial guidelines were found
for Finland and Norway; and expert opinions were retrieved
in Denmark (P. Christensen, personal communication), Italy
(M. Strazzabosco and G. Rezza, personal communications), and
The Netherlands [22, 23, 26, 28, 29, 30, 33, 36, 41–43, 45–47].
Treatment of HCV infection in active IDUs is allowed under
specific circumstances according to the French consensus;
methadone maintenance was regarded as a treatment requirement
by the official guidelines of Austria and the United Kingdom
and the expert opinion from Finland (M. Fa¨rkkila¨ and
H. Nuutinen, personal communication) [23, 30, 45, 46]. Abstinence
was a pretreatment prerequisite in the EU consensus,
in the official guidelines of Germany, Sweden, Scotland, and
Catalonia, in the semiofficial guidelines of Finland and Norway,
and in the expert opinion of Denmark (P. B. Christensen, personal
communication) [22, 28, 29, 33, 36, 42, 43, 47]. Treatment
recommendations were lacking in the official guidelines from
Belgium and Spain as well as in the expert opinion from Italy
(M. Strazzabosco and G. Rezza, personal communications) [26,
41].
Treatment recommendations remain unclear in the expert
opinion from The Netherlands [35]. Publication dates of guidelines
vary from 1997 to 2003 and therefore cannot consider
the evidence published thereafter. Besides mentioned guidelines
which qualify for the highest level of quality in the respective
country, additional and more recent guidelines with a lower
level of quality exist in Austria, Belgium, Germany, and Spain.
Two of these guidelines [25, 34] are as restrictive as and 5 are
more permissive than the older and higher-level guidelines in
the respective country (U. Marcus, personal communication)
[24, 27, 39, 40]. Overall, treatment guidelines qualifying for a
higher quality level and/or published more recently are more
likely to allow for treatment of IDUs under specific conditions
and/or under methadone maintenance therapy (U. Marcus,
personal communication) [24, 27, 30, 39, 40]. First clinical
studies showing that treatment of HCV infection in IDUs is as
safe and effective as in non-IDUs [13–17] and that rates of
reinfection are not necessarily higher than in non-IDU populations
[18] may have contributed to this process. Generally,
it is desirable to implement a structured high-quality guideline
process in each country to improve acceptance. An update of
the EU consensus [22] would be helpful in establishing widely
accepted state-of-the-art guidelines. The problem of HCV infection
in IDUs is recognized in most EU countries. Guidelines
represent 1 component in enabling access to treatment, accompaniment
by implementation of outreach programs, qualification
of professionals, and adequate funding.
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