Š MdM
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia Results of a respondent driven sampling survey by MĂŠdecins du Monde June 2013
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia: Results of a respondent driven sampling survey by Médecins du Monde Report prepared by: Julie Bouscaillou1, Julie Champagnat1, Niklas Luhmann1, Dominique Pataut1 Principal investigator: Dominique Pataut1 Research team: Kakha Abesadze3, Elisabeth Avril1, Julie Bouscaillou1, Maia Bustshahvili5, Julie Champagnat1, Eka Gardaphkhadze3, Ina Inaridze2, George Kamkamidze5, Nana Kapanadze3, Irma Kirtadze4, Koka Labartkava3, Niklas Luhmann1, Véronique Miollany2, Irina Natroshvili3, Dominique Pataut1, Paata Porchkhidze3, Guram Shapatava3
1: Médecins du Monde, France 2: Médecins du Monde, Georgia 3 : New Vector, Georgia 4 : Alternative Georgia, Georgia 5 : Neolab, Georgia
Preface About Médecins du Monde Healthcare plus Médecins du Monde is an international humanitarian organisation providing medical care to vulnerable populations affected by war, natural disasters, disease, famine, poverty or exclusion. Originally established in France in 1980, the Médecins du Monde international network now extends to 16 countries in Europe, Asia and the Americas. Médecins du Monde’s work depends on the efforts of nearly 3,000 medical and logistics professionals who volunteer their time. Thanks to their dedication and expertise, we are able to run emergency and development programmes in more than 60 countries while minimising costs.
Beyond medical care Although Médecins du Monde’s primary aim is to provide medical care, our work goes further to ensure longlasting effectiveness. We draw on our experience on the ground to bear witness to obstacles to healthcare and to advocate for change.
At home and abroad Our projects take place in both developing and developed countries. Across the countries where the Médecins du Monde network is present, our medical teams provide healthcare to the most vulnerable groups in their society.
Harm reduction MDM has been running Harm Reduction programs since 1987 in France, Russia, Serbia, Georgia, Tanzania, Kenya, China, Myanmar, Vietnam and Afghanistan. Médecins du Monde has built a strong medical and human expertise on HIV and HCV prevention and care with high risk groups, and harm reduction approaches. Access to HCV diagnosis and treatment is currently a main advocacy priority of Médecins du Monde.
Acknowledgements We would like to thank first of all participants of this study who have shared their personal information with us and who have taken the time to enroll in the study. We would furthermore like to acknowledge the help and support of all our Georgian partners.
3
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
List of Figures Figure 1: Chain of referral of the participants Figure 2: Distribution of participants according to the year of first injection Figures 3: Distribution of answers to questions regarding knowledge about HCV Figure 4: HCV prevalence according to duration of drug use Figure 5: Genotype distribution according to the year of first injection Figure 6: Severe liver fibrosis according to duration of drug use Figure 7: Chronology of products used as injecting drugs in Georgia List of tables Table 1: Socio-demographic characteristics of the participants Table 2: Sample characteristics: drug use Table 3: Pattern of drug use Table 4: HCV prevalences and genotype distribution Table 5: Factors associated with severe liver fibrosis among male participants chronically infected with HCV  Abbreviations
4
aPR
Adjusted Prevalence Ratio
BMI
Body Mass Index
BSS
Behavioral Surveillance Survey
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
HR
Harm Reduction
IQR
InterQuartile Range
MdM
MĂŠdecins du Monde
PCR
Polymerase Chain Reaction
PR
Prevalence Ratio
PWID
People who inject drugs
RDS
Respondent Driven Sampling
RDT
Rapid Diagnostic Test
STI
Sexually Transmitted Disease
USSR
Union of Soviet Socialist Republic
95CI
95% Confidence Interval
Table of contents Executive summary ........................................................................ 6 Background .................................................................................... 8 Methods ......................................................................................... 10 Preparation, research tools, ethics Data collection Laboratory testing Liver fibrosis assessment Variables and definitions Statistical analysis
Results ........................................................................................... 13 Study population HCV epidemic among PWID
Discussion ..................................................................................... 20 Results and hypothesis Strengths and limitations Conclusion and recommendations ............................................. 23 Annexes ......................................................................................... 24 Annexe 1: Consent form Annexe 2: Questionnaire
References ..................................................................................... 34
5
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Executive summary Background
of HCV. After each interview, participants underwent a clinical examination (height and weight for body mass index
An estimated 10 million of the 16 million People Who Inject
assessment) and an HCV antibody-based rapid diagnostic
Drugs (PWID) worldwide are infected with Hepatitis C (HCV).
test. When a test was positive, a further evaluation was
The disease progresses silently over some twenty years,
conducted and included direct detection of HCV by qualita-
before causing life-threatening liver affections in about 20%
tive PCR, genotyping of the virus, and liver fibrosis assess-
of cases. There is no vaccine against HCV but low threshold,
ment using Fibroscan® or APRI score (using platelet count
high coverage Harm Reduction (HR) programs have proven
and aspartate aminotransferase). We also performed HIV
their effectiveness in preventing the infection of injecting
and HBV tests, and capillary blood sugar measurements.
drug users. HCV can be cured, but access to treatment is
People needing treatment were defined as those who were
still very limited in low- and middle-income countries, mainly
chronically infected (with a positive PCR) and with severe
due to the prohibitive cost of patented treatments and a lack
liver fibrosis (liver stiffness above 10kPa according to
of competition with cheaper alternatives.
Fibroscan®, or an APRI score of over 1.5 in the event of a
Drug use and HCV are major public health issues in Georgia.
Fibroscan® failure).
Along with its geographic location, which makes it an easy target for all kinds of trafficking, the decade of turmoil that
Analysis
followed the collapse of the Soviet Union led to a rapid
Descriptive analysis was used to describe socio-demo-
increase in drug use in the country. HCV seroprevalence has
graphics, patterns of drug use and knowledge about HCV.
been estimated at around 7% in the general population, and
Prevalence of people with HCV antibodies (seropreva-
at 70% among drug users. However, the reference survey
lence), prevalence of chronically infected people, genotype
on HCV in the general population and PWID was conducted
distribution and the proportion of infected PWID needing
in 2003 and does not provide in-depth results.
treatment were obtained using crude values, and then
Médecins du Monde (MdM) conducted this study to exa-
weighted to adjust for the sampling method. We studied
mine the HCV epidemic among PWID in Tbilisi, and assess
HCV prevalence, genotype distribution and severe liver
the treatment needs of this most-at-risk population.
fibrosis depending on the duration of drug use to understand the dynamic of the epidemic and the progression of
Methods Sampling Respondent-Driven Sampling (RDS) methodology was used
the disease among PWID. HCV risk and protective factors were then studied using generalized linear models.
Results
to obtain a representative sample of PWID in Tbilisi. Although probability-based sampling methods are the gold standard
Socio-demographics
for obtaining representative samples, their application is
A total of 217 PWID where recruited in October 2012. One
limited when surveying hard-to-reach populations. RDS com-
refused to give a blood sample and was excluded from the
bines “snowball sampling” and mathematical modeling that
survey. In the study sample, 199 (92.1%) were males and 17
weights individuals to compensate for the sampling method.
(7.9%) females. Ages ranged from 22 to 59, and the mean age
People aged over 18, living in Tbilisi, speaking Georgian, and
was 40.1 among males and 34.1 among females (p =0.004).
who had injected at least one psychoactive substance in the month preceding the survey were eligible.
Drug use The mean age of the first injection was 19.4 (interquartile
6
Data collection
range 17-21). Most of the participants (57%) became injec-
Each participant was interviewed face-to-face about their
ting drug users between 1988 and 2003, and it appears
backgrounds, drug use, and risk factors in the progression
there has been a decrease in the number of new injectors
since that time. The most common drugs injected by partici-
to duration of drug use, HBV coinfection was associated
pants were homemade products. Krokodil (Desomorphine),
with severe liver fibrosis among the chronically infected
an opiate derived from Codein, was injected at least once in
males with a prevalence ratio of 3.61; 95% confidence
the month prior to the study by 50.9% of participants, and
interval 1.02-12.80.
Vint, a stimulant made from Pseudoephedrine, by 37.0%. Heroin was the third most injected product, with 22.7% of
HBV and HIV
users. Participants reported to use drugs at least once a
Prevalence of HBV was 3% in people chronically infected
week in 89.4% of cases, and 17.6% were daily injectors.
with HCV, while no cases of HIV were identified in our participants.
HCV prevalence A total of 199 people surveyed had HCV antibodies and 180 a positive PCR, corresponding to a crude seroprevalence of 92.1%; 95% confidence interval (95CI) 88.5%95.7% (RDS weighted 91.9%) and a crude prevalence of chronic infection of 83.3%; 95CI 78.3%-88.3% (RDS weighted 82.0%).
Incidence estimate There was a significant correlation between seroprevalence, prevalence of chronic infection, and duration of drug use (p <0.001). From the seroprevalence according to duration of drug use, the incidence of HCV infection was indirectly estimated at around 20% per year (i.e., out of 100 noninfected PWID, 20 will become infected within a year of injecting drug use).
Genotypes
Conclusion In our survey, 92.1% of the participants had HCV antibodies, and 83.3% an active chronic infection. Prevalence according to duration of injecting drug use suggests an incidence of 20% of new infections per year of drug use. Genotype 3, the easiest to treat along with genotype 2, is predominant in this population (70%). The high proportion of mixed-genotype infections confirms frequent exposure to the virus. The proportion of severe liver fibrosis is high among PWID infected with HCV (22.2%), resulting both from the effect of the infection itself (mostly observed after 15 to 30 years of drug use), and from a high level of liver fibrosis at baseline among drug users. Among the chronically infected, HBV coinfection appears to be a major risk factor. No HIV infection was identified in our sample.
Among chronically infected participants, 70% had at least a virus from genotype 3 (RDS weighted 66.9%), 23.3% from genotype 2 (RDS weighted 20.3%), and 17.8% from
Three recommendations can be drawn
genotype 1 (RDS weighted 22.0%). Twenty people were
from these results:
infected with two viruses of different genotypes (11.1%,
- As Georgian PWID are highly exposed to HCV,
RDS weighted 10.4%).
prevention programs and HR initiatives must be immediately scaled-up in Georgia.
Liver fibrosis Forty chronically infected participants had severe liver fibrosis (22.2%; 95CI 16.1%-28.4%, RDS weighted 24.2%).
- Based on the prevalence of severe liver fibrosis and the estimated number of PWID, up to 5,000Â people in Tbilisi need urgent treatment for HCV. HCV treatment programs must be implemented now, and include PWID.
The proportion of severe liver fibrosis according to duration
- Other risk factors of liver fibrosis, such as alcohol
of drug use was stable around 15% among participants who
abuse and HBV infection, should be specifically
had used drugs for less than 15 years, and then increased
addressed among PWID.
steadily to stabilize at approximately 35% after 26 to 30 years of drug use. Severe liver fibrosis was found in 15.8% of participants with HCV antibodies but no active infection, confirming high levels of liver fibrosis among PWID at baseline. Females infected with HCV did not have severe liver fibrosis, and were less exposed to risk factors than males. In addition
7
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Background Hepatitis C (HCV) is a blood-borne virus that primarily
HCV treatment does exist, but is particularly expensive and
infects the liver. Some 80% of exposed individuals develop
virtually inaccessible to low- and middle-income countries.
chronic infection while the remaining 20% are able to clear
Pretreatment evaluation is demanding, but overall costs of
the virus. Within 20 years, around 20% of chronic infections
diagnosis, treatment and care are mainly due to Pegylated
progress into life-threatening liver diseases, namely cirrho-
Interferon5, a drug that must be taken for at least 24 weeks.
sis, hepatocellular carcinoma or liver failure1. About 170
Furthermore, similar to other diseases, PWID are less likely
million people are chronically infected worldwide, and HCV
to seek and receive HCV prevention and treatment9.
is responsible for 350,000 deaths annually2. Drug use and HCV are both major public health issues The virus is transmitted through parenteral exposure, and is
in Georgia. In addition to its geographic location in the
therefore the most common viral infection to affect People
South Caucasus, which makes it vulnerable to all kinds of
Who Inject Drugs (PWID). HCV infections are much more
trafficking, the decade of turmoil that followed the collapse
common than HIV among drug users3. Out of 16 million
of the Soviet Union led to a rapid increase in drug use in
PWID worldwide, an estimated 10 million would be infected
the country. It was estimated in 2012 that there were around
with HCV3.
45,0007 PWID out of a total population of about 4,500,000 people in Georgia (3,900,000 over the age of 15)8. However,
There is no vaccine against HCV, but low threshold and
access to HR, substitution therapy and rehabilitation ser-
scaled-up Harm Reduction (HR) programs have proven their
vices for drug users has been introduced quite recently, and
effectiveness in preventing HCV transmission among PWID.
such programs are still not widely available in the country.
A recent meta-analysis found that multiple combined stra-
National legislation on drugs remains very repressive, and
tegies (including education, syringe exchange, and access
there is no real coordinated and comprehensive national
to substitution therapy) reduced risk of seroconversion by
strategy to address the public health issues arising from
75% in PWID4.
drug use9.
MĂŠdecins du Monde (MdM) in Georgia MdM has been running a HR program
support and condoms. Technical
work. During the year, the program
in Tbilisi in partnership with New
and organizational capacities are
distributed 200,000 syringes and
Vector, a Georgian self-support
strengthened through training of health
conducted 364 voluntary counseling
association, since 2011. The overall
and social workers, and community
and testing sessions. MdM and
objective of the project is to contribute
volunteers. In addition, MdM works with
New Vector also provided medical,
to the reduction of HIV/HCV/HBV
the Georgian Harm Reduction Network
psychological and dental consultations
transmission among drug users, and
(GHRN) in advocating for national laws
(respectively 322, 62 and 1,040 in
to reduce the harm related to drug
and policies to be amended so as to
2012).
use in accordance with the declaration
grant drug users full rights to healthcare
of Vancouver10. Its activities include
with a particular focus on HCV.
a drop-in center (with outreach
8
workers) providing quality education,
In 2012, the HR program reached 1,069
distribution of drug paraphernalia, HIV-
beneficiaries (between 300 and 700
STI-hepatitis counseling and testing,
a month), around 40% at the drop-in
dental and medical care, psychological
center, and the rest during outreach
In a study published in 2006 (but conducted in 2003), HCV seroprevalence was estimated at around 7% of the general population11. Little is known about the HCV epidemic among PWID in Georgia. According to previous studies, approximately 70% of these individuals have HCV antibodies11. However, the principal survey was carried out ten years ago, and does not provide in-depth results. More particularly, we do not have precise insight into the dynamic of the epidemic, genotype distribution, progression of the disease and the treatment needs of this vulnerable population. More generally, HCV infection is a growing public health concern, and global coordinated efforts to decrease the burden of the disease and fight the epidemic are becoming more structured and visible. Similarly, the Georgian health authorities are becoming increasingly aware of the seriousness of the epidemic in their country and appear to be ready to take action, notably in prisons where treatment programs are in the pipeline. The extortionate price of Pegylated Interferon (between 4,500 to 9,000 euros for one course of treatment in Georgia) remains the main obstacle to HCV treatment in Georgia. Yet, several low priced biosimilars or alternatives of interferon have been developped; including one that should be imported soon in Georgia. The country has arrived at a crucial juncture in its fight against HCV, and must be supported in its future efforts. This study was funded, designed and conducted by MdM in order to provide new and supplementary evidence regarding the HCV epidemic among PWID in Tbilisi, and assess the treatment needs of this most-at-risk population. The study was conducted in collaboration with New Vector and Alternative Georgia.
9
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Methods Preparation, research tools, ethics
duals to compensate for the sampling design. Recruitment starts with a fixed number of individuals, called seeds, selected from the relevant population. Seeds are then trai-
The study was conducted from October 16th to October
ned to recruit a set number of individuals from their social
31st (12 days for the recruitment phase) at the New Vector
network of peers. People recruited by the seeds are then
drop-in center in Tbilisi. The study was an MdM initiative
themselves trained to recruit, and so on. The dual incentive
and the organization designed the protocol, supervised data
system means that participants are rewarded for being
collection and performed the data analysis. MdM presented
interviewed, and for recruiting other participants. According
the study to New Vector over one week in July 2012, and
to research on incentives, this system works particularly
contacts were made with the other partners—Neolab for the
well when enrolling people in surveys. In the coupon sys-
biological analysis and Alternative Georgia for the sampling.
tem, participants are not asked to identify their peers to
The questionnaire was drawn up in English using previous
the investigators, but to directly recruit them into the study.
surveys conducted in similar contexts, with additional
Such a system is essential in a repressive environment. The
questions on HCV. It was translated in Georgian by a pro-
collection of the size of the networks makes it possible to
fessional translator, then pre-tested by the social workers
calculate and take into account the probability of selection
and adjusted taking their comments into account. All the
for each participant.
procedures and documents were finalized in France and the team who conducted the survey was trained in the days before the inclusions started.
In practice
The protocol received ethical clearance from ethics com-
Five seeds were recruited by the study team. Two
mittee Maternal and Child Care Union in Georgia and each
females and three males were chosen to reflect the
participant signed a written informed consent.
theoretical panel of drug users in Tbilisi; only two had links to an existing syringe exchange program. Each seed had three coupons and was allowed to
Sampling With the practical assistance of union Alternative Georgia regarding methodology, we used Respondent-Driven
network of drug injectors. They received an incentive of 10 Laris (5 euros) for their participation and for each participant they brought to the drop-in centre. The participant brought to the centre was then given 10
Sampling (RDS) to obtain a representative sample of PWID
Laris and three coupons to distribute. The recruitment
in Tbilisi.
process was conducted in waves.
Inclusion criteria were predefined as follows:
The coupons were numbered according to the seed
- Aged over 18
and the wave of recruitment, which allowed us to map
- Living in Tbilisi for at least one year at the time of the survey
the origin of the participants and to strictly control the
- Injection of at least one psychoactive substance during
money distributed. A social worker from New Vector
the month prior to the survey - Georgian-speaking Although probability-based sampling methods are the gold standard for obtaining representative samples, their application is limited when surveying hard-to-reach groups, i.e., small groups of stigmatized people for whom no exhaustive list of members is available. This includes groups relevant to public health, such as drug users and sex workers. In short, RDS combines “snowball sampling�, a dual incentive system, and a mathematical model that weights indivi-
10
recruit a maximum of three people among their social
was responsible for managing the coupons (collection, distribution) and the treasurer was in charge of giving out the incentive. Inclusions stopped as soon as we reached the number of participants required for the survey.
Data collection
Laboratory testing
Each participant was interviewed face-to-face in Georgian
The presence of HCV antibodies was first tested using rapid
at the study site, using an anonymous, structured question-
diagnostic test (RDT) SD-Bioline HCV.
naire. The following data were collected: background (age,
Hepatitis C virus was detected in the blood using qualitative
gender, accommodation, education), network size, drug use
PCR (HCV Real-TM Qual, Sacace biotechnologies), and
(duration of drug use, products used, frequency of injec-
in the case of a positive PCR, genotyping was performed
tions, any associated consumption), knowledge about HCV,
(HCV Real-TM Genotype, Sacace biotechnologies). HIV
and risks and protective factors in the progression of HCV.
antibodies and HBs antigen from the hepatitis B virus
Each interview was followed by a quick assessment by a
(HBV) were detected using RDT (SD Bioline HIV-1/2 v3.0
nurse, during which participants underwent an HCV rapid
and SD-Bioline HBsAG respectively), and ELISA (ELISA
diagnostic test and a fast capillary glycaemia measurement.
using HIV 1&2 ImmunoLISA test-kit - Orgenics Ltd, Yawne,
When participants tested positive for HCV antibodies, a
Israel) for HIV. A blood count (Human GmbH - Weisbaden,
blood sample was collected for further laboratory inves-
Germany) and quantification of aspartate aminotransferase
tigations (HBV and HIV tests, direct detection of HCV by
were then performed (Liquid UV Test - Human GmbH,
qualitative PCR, genotyping of the virus, blood count and
Weisbaden, Germany).
quantification of aspartate aminotransferase) and their height and weight measured in order to calculate their Body Mass Index (BMI). Liver fibrosis was then assessed using
Liver fibrosis assessment
Fibroscan® during a medical consultation. Transient elastography (Fibroscan®) is a non-invasive and
In practice Data collection was carried out between 11am and 6pm at the drop-in center, with an average of 20 inclusions per day. The supervisory team was made up of the head of New Vector, the MdM Harm reduction program coordinator in Tbilisi and two medical doctors from MdM France headquarters.
rapid method to assess liver stiffness. Its accuracy in diagnosing liver fibrosis has been proven in patients infected with hepatitis C13. Therefore, Fibroscan® has become a successful alternative to liver biopsy, which can have severe complications and requires hospitalization. The Fibroscan® examination procedure is as follow: - A mechanical pulse is generated at the surface of the skin triggers propagation through the liver. The velocity of an
Consent forms and face-to-face questionnaires were
elastic wave is measured by ultrasound.
administered by New Vector social workers who had
- The wave’s velocity is governed by the hardness of the
been trained by the supervisory team. They had agreed
environment it crosses
to accompany all the participants right through the
- The stiffness of the liver directly correlates to the level of
process. To ensure privacy and confidentiality, three
fibrosis: the stiffer the liver, the more severe the fibrosis.
closed rooms at the drop-in center were allocated
- The exam is fast, easy, and reproductible: the measure-
for the interviews. All the participants agreed to allow
ment is unequivocal and expressed in kilo-Pascal (kPa). The
their social worker to be present during nursing and medical consultations. Two nurses were seconded for the study, one from New Vector, and one from Neolab, the laboratory that performed the biological analyses. A counselor communicated the results of the tests to those who wanted to know them. At the end of each working day, the team members met
patient lies on his or her back, right arm raised behind the head. The measurements are made on the right lobe of the liver using an ultrasound probe fitted on a vibrating system placed in an intercostal space. The examination lasts about five minutes and the result is immediate.
to share their experiences, and discuss and solve any issues encountered during the day. Coordination between the team, the participants and the partners went very smoothly. The New Vector team, partly made up of peer drug users, was very interested in the study and in the issue of HCV.
11
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Statistical analysis
Using Fibroscan® in a HR program The Fibroscan® can be viewed as a tertiary prevention tool in a HR
Descriptive analyses were performed for all variables by
program. The device is particularly adapted to PWID infected with
gender and age group, with differences assessed using
HCV as they are excluded from the conventional care system, and
chi-2 or Fisher exact tests for categorical data, and Student,
tend to accumulate liver fibrosis risk factors. The Fibroscan® can
Wilcoxon Mann Whitney or Kruskal Wallis tests for conti-
allow them to know the degree of their liver fibrosis and monitor its
nuous data. Patterns of drug users were identified using
progression, which enables them to make an objective assessment
principal component analysis and the study of the correla-
of the impact of their behaviors on their health.
tion matrix between the main variables.
When the Fibroscan® failed, we used the APRI score to determine the liver fibrosis (see below variables and definition).
Prevalences of people with HCV antibodies, chronic infections, liver fibrosis, and of each genotype were calculated crude, and then weighted to take into account the respondent-driven sampling method. We estimated HCV incidence indirectly from the distribu-
Variables and definitions
tion of HCV prevalences according to duration of drug use (considered as equal to the duration of exposure to HCV).
The following variables were viewed to be the main out-
Thus, assuming that the risk of infection is the same for each
comes of the survey:
individual and does not vary with the duration of exposure,
- HCV seroprevalence refers to people with HCV antibo-
we identified the level of incidence that best explains the
dies detected by RDT. These individuals have encountered
data.
the virus at least once. They can be chronically infected, or
HCV in PWID is generally contracted during the first years
healed (spontaneously or with treatment).
of drug use. After confirming that incidence was high in our
- We considered people with antibodies and a positive
sample, we considered that the time when people started
PCR as chronically infected. People with HCV antibo-
injecting drugs reflects roughly the date of infection. We
dies and PCR (the virus is detected in the blood) can have
were thus able to study the evolution of severe liver fibro-
an acute infection as well as being chronically infected.
sis according to the duration of the HCV infection, as well
However, acute infections last for a maximum of six months,
as the evolution of genotype distribution according to the
and the likelihood to find an acute case in our cross sectio-
approximate date of infection.
nal sample is very low.
We studied risk factors of liver fibrosis using generalized
- Severe liver fibrosis refers to people with a liver stiffness
linear models (Poisson regression) adjusted to take into
equal to or over 10 kPa. When the Fibroscan® failed, we
account potential confounding factors. Results are reported
used the APRI score with a cut-off value of 1.5 to determine
as prevalence ratios. Prevalence ratio indicates how much
sever liver fibrosis. The APRI score is calculated based on
the prevalence of a disease (here severe liver fibrosis) is
the following formula: (AST (UI/40) x 100) / platelets (10 /L) .
increased in case of exposure to a given risk factor. Factors
9
14
examined were gender, age and duration of infection, Other variables were calculated from the initial data and
alcohol consumption, HBV and HIV coinfections, obesity,
need to be defined:
hyperglycemia, consumption of cannabis and coffee.
- Heavy alcohol consumption corresponds to drinking at
Tests were considered significant for a two-sides alpha level
least seven units per session, at least four times a week.
of 0.05. Analyses were performed using STATA software
A unit corresponds to a standard drink with ten grams of
12.1, and RDSAT for the RDS weighted estimates.
alcohol (e.g., half a pint of beer or a 100 ml glass of wine). - Obesity was defined as a BMI equal to or over 30 (weight in kilograms divided by the square of height in meters). - Hyperglycemia is defined as a capillary glycaemia equal to or over 1.4 grams per liter if the latest meal was eaten within the previous 2 hours, and 1.1 grams per liter when it was not15.
12
Results Study population
Sample demographics In the study sample, 199 (92.1%) were males and 17 (7.9%)
Recruitment
females. Ages ranged from 22 to 59 (mean age 39.6), and the
A total of 217 PWID where recruited in October 2012. One of
mean age was 40.1 for males and 34.1 for females (p =0.004).
them refused to give a blood sample and was excluded from
The socio-demographic characteristics of the population
the survey. The maximum amount of recruitment waves in
are described in Table 1. One hundred fifty-seven people
the 5 different participant networks was 9.
(72.7%) had received vocational training or a higher education. More than half (56.9%) of the participants lived in
Figure 1 Chain of referral of the participants
their own homes, while the others stayed mainly with their parents (35.7%) or with friends or relatives (4.6%). Five participants reported living at hosting centers and one on the street. Level of education and accommodation differed significantly between age groups but not between genders. Thus, 53.3% of participants aged between 20 and 29 as opposed to 78.1% of those aged 59 and over said they had received a higher education or vocational training. Similarly, 48.8% of under 40 year-olds lived in their own accommodation compared to 68.5% of over 40 year-olds. The majority of respondents (85.3%) had always lived in Tbilisi.
Table 1 Socio-demographic characteristics of the participants Total N=216 Age (mean, IQR)
Gender comparison
n
%
M (199)
F (17)
39.6
(33 - 46)
40.1
34.1
Age group
p
Age group comparison 20-29
30-39
40-49
50-59
p
0.004 0.004
20-29
30
13.9%
11.1%
47.1%
30-39
85
39.4%
40.2%
29.4%
40-49
69
31.9%
33.7%
11.8%
50-59
32
14.8%
15.1%
11.8%
Education
0.023
1
Primary/secondary
59
27.3%
27.8%
23.5%
46.7%
30.6%
17.7%
21.9%
Higher education*
157
72.7%
72.2%
76.5%
53.3%
69.4%
82.4%
78.1%
Hosting center/street
6
2.8%
3.0%
0.0%
6.7%
3.5%
1.5%
0.0%
Relatives/parents
87
40.3%
40.7%
35.3%
50.0%
49.4%
34.8%
18.8%
Private place
123
56.9%
56.3%
64.7%
43.3%
47.1%
63.8%
81.3%
Living place
0.007
0.88
n : number of participants, IQR: Interquartile; M: Male; F: Female; *Higher education include vocational training – Age was compared using Wilcoxon Mann Whitney or Kruskal Wallis tests (depending on the number of groups), categorical variables were compared using chi square or exact tests (depending on the headcount).
13
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Drug use (Table 2) Alcohol, tobacco, cannabis Around half of the participants (53.5%) reported drinking alcohol less than once a month, while drinking once a week or more was reported by 27.4% of the sample. The number of units per drinking session was 7 or more for 70.9% of participants. There were more male “heavy drinkers� (over 7 drinks, at least four times a week) than females (11.6% vs. 5.8%) but this disparity was not significant. A majority of participants reported being active smokers (94.4%), and smoked on average 30 cigarettes a day. Smoking habits did not differ between males and females. A daily consumption of cannabis was reported by 16.2% of the participants (17.1% of the males vs. 5.9% of the females, non significant), and was negatively associated with age (spearman correlation rho=-0.162, p=0.017).
Table 2 Sample characteristics: drug use Total N=216
Gender comparison
Age group comparison
n
%
M (199)
F (17)
p
20-29
30-39
40-49
50-59
p
Heavy alcohol consumption*
24
11.1%
11.6%
5.8%
0.701
13.3%
10.6%
8.7%
15.6%
0.687
Tobacco smokers
204
94.4%
94.5%
94.1%
0.951
96.7%
10.6%
8.7%
15.6%
0.687
Smoking cannabis on a daily basis
35
16.2%
17.1%
5.9%
0.229
23.3%
21.2%
10.1%
9.4%
0.130
19.40
(17-21)
19.25
21.00
0.714
19.40
19.00
19.70
19.90
0.604
- Krokodil
110
50.9%
53.3%
23.5%
0.023
53.3%
61.2%
44.9%
34.4%
0.043
- Vint
80
37.0%
34.7%
64.7%
0.018
36.7%
34.2%
42.0%
34.4%
0.770
- Heroin
49
22.7%
22.1%
29.4%
0.547
20.0%
20.0%
23.2%
31.3%
0.611
- Other***
31
14.4%
15.6%
0.0%
0.141
10.0%
10.6%
18.8%
18.8%
0.386
Use of two or more products
50
23.2%
24.1%
11.8%
0.371
16.7%
23.5%
27.5%
18.8%
0.659
Daily consumption
38
17.6%
18.6%
5.9%
0.318
30.0%
21.2%
13.2%
6.3%
0.050
Injecting drug use** Mean age at first injection (IQR) Products used
n: number of participants, IQR : Interquartile; M: Male; F: Female; * 7 drinks per session 4 times a week or more – ** During the last month - *** Subutex, coaxil, methadone, opium, other, Age at first injection was compared using Wilcoxon Mann Whitney or Kruskal Wallis tests (depending on the number of groups), categorical variables were compared using chi square or exact tests (depending on the headcount).
14
Injecting drug use
three or more products. Regarding the frequency of use,
The age of first injection ranged from 14 to 40. The mean
89.4% of participants reported at least one weekly drug
age of first injection in the sample was 19.4 (interquartile
injection, and 17.6% were daily injectors.
rang 17-21), 19.3 for males and 21 for females. Age of first injection did not differ according to age group (under 30 year-olds, over 50 year-olds and the other participants star-
Table 3 Pattern of drug use
ted injecting drugs at around the same age). Figure 2 shows the distribution of participants according to the year of their
Krokodil users
Krokodil users are younger compared to the other PWID, rarely female, and tend to be more unstable (in terms of accommodation and level of education). Krokodil is injected very frequently and appears to be less associated with poly drug use than other products.
Poly drug users
The second most common pattern of consumption in the sample. There is no significant association between poly drug use and sociodemographics. Using several injected products is also associated with smoking cannabis on a daily basis.
Vint users
The proportion of female users is higher among Vint users. Vint tends to be used more sporadically than other drugs, and is frequently associated with injecting other products and smoking of cannabis.
Heroin users
Heroin users are long-term drug users. Heroin use is negatively correlated with alcohol consumption.
Other (mainly Subutex)
The other PWID are mostly longterm, male drug users, with a higher education and their own home.
first injection. Most of the participants (57%) began injecting between 1988 and 2003, and there appears to have been a decrease in the number of new injecting drug users since.
Figure 2 Distribution of participants according to the year of first injection 25%
20%
15%
10%
5%
0% <1977
1978 - 1982
1983 - 1987
1988 - 1992
1993 - 1997
1998 - 2002
2003 - 2007
2008 - 2012
The most common drugs injected by the participants during the last month prior to the survey were homemade products. Krokodil, a Desomorphine-based opiate derived from Codeine, was used by 50.9% of participants, and Vint,
Patterns of drug use were identified through principal component analysis and examination of the correlation matrix between age, gender, education, accommodation, duration of drug use, use of Krokodil, use of Vint, use of Heroin, use of other drugs, alcohol consumption, number of products injected, smoking cannabis on a daily basis, number of cigarettes smoked a day
a stimulant made from Pseudoephedrine, by 37.0%. Heroin was the third most injected product, with 22.7% of users. The other drugs participants reported using were Subutex (6%), Opium (3.7%), Methadone (2.8%) and Coaxil, a selective serotonin re-uptake enhancer usually used to treat major depressive episodes (0.9%). Most of the respondents (76.9%) had used only one type of product during the previous month. Two different products were used by 21.8%, and only three people (1.4%) used
15
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Knowledge about HCV We used 17 questions to assess the participants’ knowle-
Figures 3 Distribution of answers to questions regarding knowledge about HCV
dge about HCV. The questions examined were: - HCV transmission: Can hepatitis C be transmitted through tattoos, syringe, filters, or toilets? Can hepatitis C be transmitted to the fetus during pregnancy? Can hepatitis C be transmitted when the disease is asymptomatic?
HCV can be transmitted ..
Do not know No
100%
Yes 80%
- Evolution of the disease: Is hepatitis C exclusively an acute disease? Can hepatitis C be chronic? Can hepa-
60%
titis C heal spontaneously? Can hepatitis C progress to cirrhosis? Can hepatitis C progress to hepatocellular carcinoma? - Risk factors and progression of the disease: we asked whether HIV, alcohol, obesity, diabetes, sport and joint
40% 20% 0%
pain accelerate the progression of the disease.
through tattoo
Answers to these questions are described in Figures 3.
through syringe
if asymptomatic
through toilets
from mother to fetus
through filter
Figure 3a knowledge regarding HCV transmission
Participants had insufficient knowledge on how the disease is transmitted, particularly concerning the possibility of transmission from mother to fetus (known by only 49% of participants), and transmission through filters
HCV... 100%
(known by 65.7% of participants). Regarding the evolution of the disease, we observed a lack of knowledge regarding the ability to heal spontaneously (known by 37% of participants), while the progression to cirrhosis and hepatocellular carcinoma
80% 60% 40%
were better known (respectively 99.1% and 78.2% of participants). The question “Is hepatitis C exclusively an
20%
acute disease?” may have been misunderstood, since the answers are not consistent with the fact that almost 100%
0% Is exclusively an acute disease
of participants were aware that hepatitis C can be chronic. Knowledge regarding risk factors and progression of the disease was average, with correct answers given by 85.6% on HIV, 98.6% on alcohol, 66.7% on obesity,
Can be chronic
Can heal spontaneousl
Can progress to cirrhosis
Can progress to hepatocellular carcinom
Figure 3b knowledge regarding evolution of HCV
79.6% on diabetes, 26.9% on sport and 20.4% on joint pain.
HCV progression is accelerated by...
No participant answered all 17 questions correctly. The total number of right answers was significantly higher
100%
among females (13.2 vs. 11.9, p=0.017) and people with a higher education (12.3 vs. 11.1, p<0.001), but was not associated to age or HCV status.
80% 60% 40% 20% 0% VIH
Alcohol
Obesity
Diabetes
Joint pains
Sport
Figure 3c knowledge regarding risk factors of progression of HCV
16
HCV epidemic among PWID HCV prevalence
Previous screening and status awareness
Out of the 216 participants, A total of 199 people sur-
In the sample:
veyed had HCV antibodies and 180 a positive PCR,
- 176 participants (81.5%) had been screened for HCV prior
corresponding to a crude seroprevalence of 92.1%; 95%
to the study
confidence interval (95CI) 88.5%-95.7% (RDS weighted
- 158 of these participants reported a positive result (in fact,
91.9%) and a crude prevalence of chronic infection of
155 of them had HCV antibodies)
83.3%; 95CI 78.3%-88.3% (RDS weighted 82.0%). These
- 119 participants (55.1%) thought they were chronically
prevalences were significantly lower among females than
infected (in fact, 107 of them had a positive PCR)
males (crude seroprevalence 58.8% vs. 95.0%, p<0.001
Finally, 73 participants found out they were chronically
and crude prevalence of active chronic infection 58.8% vs.
infected during the survey.
85.4%, p=0.005). As shown in Figure 4, seroprevalence and prevalence of
Genotype distribution
active chronic infection were significantly correlated to the duration of drug use (Spearman rho=0.47, p<0.001 for
Among chronically infected people, 126 (70%) had at least
seroprevalence), with roughly 20% new infections every
a virus from genotype 3 (RDS weighted 66.9%), 42 (23.3%)
year. According to this estimate, 50% of PWID encounter
from genotype 2 (RDS weighted 20.3%), and 32 (17.8%)
the virus during their first 3.5 years of drug use.
from genotype 1 (RDS weighted 22.0%) - 31 cases of genotype 1b and one case of genotype 1a. Twenty people were
Figure 4 HCV prevalence according to duration of drug use
infected with two viruses of different genotypes (11.1%, RDS weighted 10.4%). According to Figure 5, genotype distribution according to the year of first injection is fairly constant. Genotype distribution was not significantly dif-
100%
ferent between males and females. Among people with HCV antibodies, six participants were infected with the hepatitis B virus (HBV). No participant
80%
tested positive for HIV. 60% HCV antibodie Positive PCR 40%
Figure 5 Genotype distribution according to the year of first injection 80% 70%
20% >5 years
6-10 years
11-15 years
16-20 years
21-25 years
26-30 years
31-35 years
>36 years
60%
Genotype 3 Genotype 2
50%
Genotype 1 40% 30%
20% 10% 0% > 1978
1978-1987
1988-1997
1998-2007
>2008
17
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Table 4 HCV prevalences and genotype distribution
Crude prevalence
RDS-weighted prevalence
HCV antibodies (seroprevalence)
92.1% [88.5%-95.7%]
91.9% [85.8%-96.1%]
Active chronic infection
83.3% [78.3%-88.3%]
82% [76.1%-90.3%]
Genotype 1
17.8% [12.1%-23.4%]
22% [12.6%-36.4%]
Genotype 2
23.3% [17.1%-29.6%]
20.3% [11.6%-32.9%]
Genotype 3
70% [63.2%-76.7%]
66.9% [50.2%-76.6%]
Mixed genotype
11.1% [6.5%-15.7%]
10.4% [4.5%-12.2%]
Severe liver fibrosis
22.2% [16.1%-28.4%]
24.2% [12.3%-39.6%]
Among chronically infected
Prevalences are given with their 95% confidence interval
Liver fibrosis
recently infected), confirming high levels of liver fibrosis, even before the effects of HCV. Thereafter, the prevalence
The Fibroscan速 was used to assess liver fibrosis in all 199
of severe liver fibrosis increases steadily along with duration
participants with HCV antibodies. As we failed to obtain
of use to stabilize at about 35% after 26 to 30 years. We
results for 12 people, we used the APRI score instead.
can therefore estimate that about 23% of patients with no
Among participants with a Fibroscan速 result, there was
severe fibrosis initially go on to develop severe liver fibrosis
a significant correlation between the APRI score and liver
within 30 years after their first injection.
stiffness (rho 0.43, p<0.001). Based on the cut-off value of 1.5 found in the literature, the APRI score had good specificity (83.6%) but weak sensibility (21.9%) in detecting severe liver fibrosis when compared with the Fibroscan速 results in our sample. Therefore, prevalence of severe liver fibrosis may have been underestimated for the 12 partici-
Figure 6 Severe liver fibrosis according to duration of drug use 50%
pants. Nevertheless, analyses performed excluding these individuals found very close results.
40%
Among chronically infected PWID, 40 had severe liver fibrosis (22.2%; 95CI 16.1%-28.4%, RDS weighted 24.2%). There was a significant correlation between the
30%
degree of liver fibrosis and duration of drug use (Spearman rho=0.20, p=0.006); reflecting, as mentioned above, the duration of the progression of the disease.
20%
A prevalence of 15.8% of severe liver fibrosis was found among participants with HCV antibodies but not chronically infected, suggesting a high degree of liver fibrosis among
10%
PWID at baseline (i.e., not related to HCV). Figure 6 shows the proportion of severe liver fibrosis according to duration of drug use among chronically infected people. This proportion remains stable at around 15% among participants who had used drugs for less than 15 years (i.e., the most
18
0% >5 years
6-10 years
11-15 years
16-20 years
21-25 years
26-30 years
31-35 years
>36 years
Risk factors for liver fibrosis
Apart from alcohol and cannabis consumption, the factors under examination were distributed as expected among the
The associations between severe liver fibrosis and typical
participants according to their liver fibrosis (i.e., known risk
risk and protective factors in the progression of the disease
factors were more prevalent in people with severe fibrosis
among the chronically infected participants in our sample
than those without). Yet, among the males, duration of drug
are described in Table 5.
use (aPR 1.04; 95% confidence interval (95CI) 1.01 – 1.08)
No severe liver fibrosis was observed in female participants
and HBV coinfection (aPR 3.61; 95CI 1.02 – 12.80) were
chronically infected, which were much less exposed to other
the only two factors associated with severe liver fibrosis.
risk factors. Not one chronically infected female was obese,
The proportion of severe liver fibrosis did not significantly
hyperglycemic, a heavy alcohol drinker or coinfected with
differ according to the genotype (18.8% among participants
HBV. Only one out of the 10 smoked cannabis on a daily
infected with genotype 1, 23.8% with genotype 2 and
basis. And, 76.5% of females were coffee drinkers compa-
23.0% with genotype 3).
red to 46.5% of the males (p=0.016). Table 5 Factors associated with severe liver fibrosis among male participants chronically infected with HCV
Total
No severe liver fibrosis (n=130)
Severe liver fibrosis (n=40)
P
Adjusted analyses aPR; 95CI
P
Age (m,sd)
40.7 (8.5)
39.9 (8.6)
43.5 (7.5)
0.02
-
-
Duration of consumption (m,sd)
21.5 (8.8)
20.5 (8.6)
24.4 (8.9)
0.01
1.04 [1.01 - 1.08]
0.04
Coffee (>3 cup/day)
45.9%
49.2%
35.0%
0.11
0.67 [0.34 - 1.29]
0.229
Heavy alcohol consumption
11.8%
12.3%
10.0%
0.69
0.56 [0.18 - 1.70]
0.307
Using cannabis on a daily basis
13.5%
13.9%
12.5%
0.83
1.02 [0.39 - 2.65]
0.967
Hyperglycemia
22.9%
18.5%
37.5%
0.01
1.64 [0.83 - 3.23]
0.156
Obesity
20.0%
16.9%
30.0%
0.07
1.64 [0.81 - 3.33]
0.172
HBV coinfection
3.0%
1.6%
7.7%
0.05
3.61 [1.02 - 12.80]
0.047
m: mean; sd: standard deviation; aPRR: adjusted prevalence rate ratio obtained using Poisson regression; 95CI: 95% confidence interval Age and duration of use were compared using Student t-test in univariate analyses; categorical variables were compared using chi square or exact tests in univariate analyses (depending on headcount)
Results among women • 7.9% of the sample • Younger than men (mean age 34.1 years) • Mostly Vint users • Less likely to be infected with HCV: seroprevalence (equal to the prevalence of chronic infection) of 58.8%; CI95 32.7%-84.9% • Did not suffer from severe liver fibrosis • Much less exposed to other risk factors of liver fibrosis
19
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Discussion Results and hypothesis
The age of the participants and the distribution of drug use in our survey are consistent with recent studies on drug
Socio-demographic profiles and drug use patterns
users in Tbilisi, and the chronology of products consumed in
The profile of the drug users in our sample appears to be
Survey on injecting drug users (BSS) conducted in 2012
consistent with the history of drug use in Georgia.
shows fairly close results for PWID living in Tbilisi in terms
The distribution of PWID according to the year of first
of age (41-50 years: 43.8%; 31-40: 32.2%; 25-30: 18.1%;
injection shows that the majority began to use drugs in the
18-24: 5.9%), socio-demographics (62.2% had a higher
1990s. This period corresponds to the decade of turmoil
education), and products used (Vint: 55.7%, Krokodil:
that followed the collapse of the USSR in 1991. The opening
44.9%, Heroin: 13.6%)17.
Georgia. More particularly, the latest Behavioral Surveillance
up of borders, the conflict, chronic poverty, and the lack of a legal framework regulating the movement of psychoactive
Hepatitis C and liver fibrosis
substances led to a sharp increase in drug use. Injecting
Prevalence of hepatitis C (seroprevalence of 92.1%, and
drug use was frequent even before this period, as the Soviet
prevalence of chronic infection of 83.3%) appears to be
Union had started to liberalize its drug control policies in the
particularly high in our survey, and we cannot exclude the
1960s. However, in our survey, there were less PWID who
possibility of a selection bias. Free HCV check-ups were
began to inject before the 1990s, which can be explained
provided by the survey, and may have attracted PWID
either by a lower level of drug use at the time, or by the fact
who were aware of their positive HCV status. Equally high
that many have already died. The decrease in the number
HCV prevalence can be found among drug users in other
of PWID since the early 2000s may be related to the end
settings20, but there is little data on PWID in Georgia to
of the crisis.
compare. The principal studies are detailed below.
Figure 7 Chronology of products used as injecting drugs in Georgia
Krokodil Jeff-Vint Subutex Heroin Opium-poppy 1970
1975
1980
1985
1990
1995
2000
2005
Information from the 2003 and 2010 “Drug situation in Georgia� reports, and the 2002 Behavioral Surveillance Surveys.9 15 18 19
20
2010
In Georgia, the most commonly survey cited as a reference,
tions in the circulating strains among PWID over the last 30
a population-based sample of about 2,000 adults from
years. While this distribution differs from what is observed
Tbilisi, was conducted over ten years ago. The findings
in the general population in Georgia (genotype 1b: 62%,
were as follows: 8% of the participants were PWID and
genotype 2: 11%, genotype 3: 27%)11, it does not diverge
6.7% of the total sample and 70% of PWID had HCV anti-
from the genotype distribution among other European
bodies (meaning that the 6.7% of HCV infected people in
injecting drug users23-24.
the general population were for the most part drug users). The mean age of PWID in the survey was 29 years, i.e., ten
High levels of liver fibrosis in our sample are the result
years younger than in our survey . Considering that there
of the high levels of liver fibrosis at baseline among PWID,
have been very few new injectors since that time, and that
and of the significant proportion of advanced active HCV
the incidence of HCV among PWID rises to about 20% per
infections. Liver fibrosis among not chronically infected
year of drug use (as suggested by our results), the 92.1%
PWID, or in the early stages of infection, can be explained by
prevalence in our population is not in contradiction with this
frequent exposure to other fibrosis risk factors such as alco-
data. In addition, the products used have changed over the
hol, tobacco, hyperglycemia, obesity and frequent cannabis
past 10 years. The common use of Krokodil, a short acting
consumption. In addition, we cannot exclude the damaging
opiate that needs to be injected several times a day, may
effect of the injected drugs themselves25. The progression
have accelerated the spread of the disease.
of chronic HCV to liver fibrosis after about 20Â years in about
11
20% of patients is fairly typical1. There are frequent Behavioral Surveillance Surveys on injecting drug use in Tbilisi but, apart from the one conducted in
The females infected with HCV did not have severe liver
2006; they do not generally include hepatitis testing. In the
fibrosis. While a physiological effect may exist, this diffe-
2006 study, 65% of the participants selected by RDS had
rence may be due to low exposure to other risk factors, and
hepatitis C antibodies. The difference with our result can be
a shorter duration of drug use in our sample.
explained once again by the young age of the participants (about 30 years) at the time18. The age distribution in our
Unsurprisingly, duration of drug use was closely associated
sample is much more in line with the results of the two latest
to severe liver fibrosis in our sample. This variable reflects
BSS conducted in 2009 and 201217-19.
the effect of liver fibrosis on the infection itself, as well as the effect of age and the drugs injected; all three are known
Another study of HIV infected patients enrolled in a treat-
risk factors. However, the effect of each one cannot be
ment program in Georgia between 2003 and 2008 found
assessed individually.
a 73.4% HCV seroprevalence among PWID infected with HIV21. However, the population in the study was not at all
HBV coinfection was the only other risk factor associated
representative.
with severe liver fibrosis in multivariate analysis among chronically infected male participants. However, the sample size
The drop-in-center supported by MĂŠdecins du Monde in
was small, and despite non-significant associations, obe-
Tbilisi found 62% of positive results among the 364 bene-
sity, hyperglycemia and coffee drinking were distributed as
ficiaries who accepted to be tested in 2012. Once again,
expected among participants according to their liver status.
these beneficiaries were not representative of all PWID in
Surprisingly, this was not the case for cannabis and alcohol
Tbilisi, and were younger than the surveyed participants.
consumption, which may be explained by a reporting bias, and by the cross-sectional design of the survey (we did not
The HCV incidence of around 20% per year suggested by
know the history of alcohol consumption, but only the beha-
the prevalence of infection according to duration of injecting
viors reported in the month prior to the survey). Age was not
drug use is high, but consistent with levels found in pros-
taken into account in the multivariate analysis in addition
pective studies on drug users in other settings in Europe .
to duration of drug use because of the over-adjustment.
The elevated level of mixed-genotype infections confirms our population’s high exposure to HCV.
The association between genotype 3 and progression to liver fibrosis suggested in the literature was not found in
Genotype distribution according to the year of first injec-
our data26.
tion appears quite constant, suggesting no major modifica-
21
High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Knowledge about HCV was average in our survey. The lack
Our study gives not only an estimate of HCV prevalence,
of awareness regarding the possibility of transmission of
but also information on the incidence, genotypes, and the
hepatitis C through filter is particularly concerning given the
progression of the disease within this particular population.
high level of exposure in this population. According to the
Since drug use and HCV are both major public health issues
last BSS17, HIV transmission ways were known by 89.4%
in Georgia, these findings have direct and practical implica-
of the PWID in Tbilisi. Until now, prevention messages tar-
tions to assist policy-makers in choosing and implementing
geting PWID might have more focused on HIV than HCV.
strategies to fight the epidemic.
Many people (81.5%) of our sample reported a previous screening for HCV, which can possibly be explained by the
The study also has its limitations. We cannot exclude a
selection bias related to the free HCV check-up. However,
selection bias overestimating the prevalences, related to
many of them reported a wrong or unknown HCV-status,
the free HCV check-up provided by the survey. However,
and 73 participants eventually found out they were chroni-
the reliability of this result has been discussed above. In
cally infected during the survey.
addition, the cross-sectional design of the survey did not allow us to properly assess the incidence of HCV and liver
HIV
fibrosis. However, the study of prevalences by subgroup of different durations of exposure to the disease gives a fairly
Although it is gradually increasing, HIV prevalence in Georgia
good picture of the epidemic dynamic within the population.
remains very low (0.2% of the adult general population in
And lastly, the study of fibrosis risk factors is also limited
201128) compared to the other countries in the region. The
by the design, as we have no information regarding the
27
2012 BSS , which studied HIV in five Georgian cities, found
chronology of events, or the duration of exposure to each
an average prevalence of 3% among PWID, with values
supposed risk factor.
from 0.4% (Telavi) up to 9.1% (Zugdidi). Among the 350
 
17
PWID surveyed in Tbilisi, 1.9% were infected with HIV, whereas there were none in our survey. This result may be due to sampling fluctuations, as the difference is not significant (p 0.052 with exact Fisher test), and to a potential recruitment bias. Known HIV-HCV coinfected individuals receive full diagnosis and treatment free of charge in Georgia through Global Fund programs, and so may have not felt there was any added value to be had from participating in the study.
Strengths and limitations As stated above, data on HCV among PWID in Georgia are rare, out-of-date, unrepresentative, or imprecise. Our study provides reliable information on HCV infection among PWID for the first time. The methods we used for our survey were particularly appropriate. Unlike most of the other HCV studies, we used RDS to obtain the sample the most representative possible of this hard-to-reach population. Furthermore, peer drug users implemented the recruitment process and the data collection for the most part, which established trust between participants and the team. Thus, participating in the survey and answering the questionnaire were not hindered by fear of being judged.
22
Conclusion and recommendations Out of the 216 PWID of our survey, 92.1% had HCV
PWID in Georgia are highly exposed to HCV, and the
antibodies, and 83.3% an active chronic infection.
progress made over the past years in terms of HR needs
Prevalence according to the duration of injecting drug
to be continued and reinforced.
use suggests an incidence of 20% of new infections per year of drug use. Genotype 3, the easiest to treat along with genotype 2, was predominant in this population.
2
HCV treatment programs must be implemented now, and include PWID
According to our findings and the estimates of 27,000
The proportion of severe liver fibrosis (22,2%) is high
PWID in Tbilisi19, around 5,000 drug users require
among PWID infected with HCV, a result of both the
treatment urgently, as they are suffering from severe
effect of the infection itself (mostly seen after 15 to 30
hepatic fibrosis or cirrhosis. Giving the time to the onset
years of drug use), and the high level of liver fibrosis
of severe liver fibrosis among HCV infected people, and
at baseline among drug users. HBV coinfection
the distribution of PWID according to the year of first
appears to be a major risk factor of severe liver fibrosis
injection (most of them began to use drugs in the 1990s,
among the chronically infected. No HIV infection was
i.e., 10 to 20 years ago), a large number of people will
observed in our sample.
need treatment within the next decade. In addition to avoiding the death of thousands of Georgians, providing
Three main recommendations can be drawn from these results.
1
treatment to PWID for HCV may well prove a good strategy for reducing the spread of the disease among this population29.
HCV Prevention and HR programs should be scaled-up immediately in Georgia
It is proven that HR programs can lead to a 75% reduction4 in the risk of HCV infection, on condition
3
Other risk factors of liver fibrosis should be specifically addressed among PWID
The PWID in our sample show high levels of severe
that they combine multiple strategies and that high
liver fibrosis, even at the onset of HCV infection. This
coverage is achieved. Mainly supported by NGOs, HR
can be explained by their frequent exposure to other
programs in Georgia have only been available since
liver disease risk factors, such as alcohol, obesity and
1999. In 2009, 4,000 people were enrolled in such
hyperglycaemia. These factors can and should be
programs around the country, meaning that about 90%
addressed to avoid more severe liver fibrosis cases
of PWID had no effective access to harm reduction9.
among chronically infected PWID, and reduce the
Important progress has been made since then,
number of people needing treatment in the future.
and 24% of PWID now have access to prevention
More particularly, coinfection with HBV is associated
services . Similarly, opioid substitution treatment
with an almost fourfold increase in severe liver fibrosis
was introduced less than ten years ago, and has only
among PWID infected with HCV. Only one participant
been widely available since 2008 when the Georgian
reported having been vaccinated, indicating extremely
government started to provide funding9. About 2,000
poor immunization coverage within this population.
people now benefit from opioid substitution.
Vaccination is a very simple and effective way to prevent
Although practices reported among PWID have
HBV, and should especially target PWID in Georgia.
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improved over the past 4 years (8.5% of people shared needles during their latest injection in the 2012 BSS17 vs. 46.4% in the 2008-09 BSS19), according to the findings of our survey, knowledge about HCV remains insufficient.
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High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Annexes Annexe 1: consent form
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High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
Annexe 2 : Questionnaire
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High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
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High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
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High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
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High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia
REFERENCES 1- Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002 Nov;36(5 Suppl 1):S35-46.
17- Curatio International Foundation, Behavioral surveillance Survey on injecting drug users in five cities of Georgia, 2012.
2- Perz JF, Armstrong GL, Farrington LA, Hutin Y, Bell B. The contributions of hepatitis B virus and hepatitis C virus to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45:529–538
18- Dershem L, Tabatadze M, Sirbiladze T, Tavzarshvili L, Tadadze K, Tsagareli T. Characteristics, high-risk behaviors and knowledge of STI/HIV/AIDS, and Prevalence of HIV, Sypjhilis and Hepatitisamong injecting drug users inTbilisi, Georgia: 2002 – 2006. 2007 report.
3- Nelson PK, Mathers BM, Cowie B, Hagan H, Des Jarlais D, Horyniak D, Degenhardt L. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011 Aug 13;378(9791):571-83. 4- Hagan H, Pouget ER, Des Jarlais DC. A systematic review and meta-analysis of interventions to prevent hepatitis C virus infection in people who inject drugs. J Infect Dis. 2011 Jul 1;204(1):74-83.
20- Aceijas C, Rhodes T. Global estimates of prevalence of HCV infection among injecting drug users. Int J Drug Policy. 2007 Oct;18(5):352-8.
5- Solomon M, Bonafede M, Pan K, Wilson K, Beam C, Chakravarti P, Spiegel B. Direct medical care costs among pegylated interferon plus ribavirin-treated and untreated chronic hepatitis C patients. Dig Dis Sci. 2011 Oct;56(10):3024-31.
21- Karchava M, Sharvadze L, Gatserelia L, Badridze N, Tsertsvadze T. Prevailing HCV genotypes and subtypes among hiv infected patients in Georgia. Georgian Med News. 2009 Dec;(177):51-5.
6- Stoové MA, Gifford SM, Dore GJ. The impact of injecting drug use status on hepatitis C-related referral and treatment. Drug Alcohol Depend. 2005 Jan 7;77(1):81-6.
22- Roy K, Hay G, Andragetti R, Taylor A, Goldberg D, Wiessing L. Monitoring hepatitis C virus infection among injecting drug users in the European Union: a review of the literature. Epidemiol Infect. 2002 Dec;129(3):577-85.
7- Consensus letter on number of IDU in Georgia, 2013 8- CIA, The World Factbook. https://www.cia.gov/library/publications/the-world-factbook/geos/gg.html 9- Javakhishvili DJ, Sturua L, Otiashvili D, Kirtadze I, Zabransky T. Drug Situation in Georgia, 2010. Overview. 10- International Network of People who Use Drugs, The Vancouver Declaration, Why the World Needs an International Network of Activists who Use Drugs. 2006 Apr. 11- Sharvadze L, Nelson KE, Imnadze P, Karchava M, Tsertsvadze T. Prevalence of HCV and genotypes distribution in general population of Georgia. Georgian Med News. 2008 Dec;(165):71-7. 12- Heckathorn DD. Respondent Driven Sampling, a new approach to the study of hidden population. Social problems. 1997 May:44(2):174-198. 13- Cross TJ, Calvaruso V, Maimone S, Carey I, Chang TP, Pleguezuelo M, Manousou P, Quaglia A, Grillo F, Dhillon AP, Dusheiko GM, Burroughs AK, Harrison PM. Prospective comparison of Fibroscan, King’s score and liver biopsy for the assessment of cirrhosis in chronic hepatitis C infection. J Viral Hepat. 2010 Aug;17(8):546-54. 14- Yilmaz Y, Yonal O, Kurt R, Bayrak M, Aktas B, Ozdogan O. Noninvasive assessment of liver fibrosis with the aspartate transaminase to platelet ratio index (APRI): Usefulness in patients with chronic liver disease: APRI in chronic liver disease. Hepat Mon. 2011 Feb;11(2):103-6. 15- World Health Organization, About Diabetes, Intermediate states of Hyperglycemia, http://www.who.int/diabetes/action_ online/basics/en/index2.html 16- Gamkrelidze A, Javakhishvili JD, Kariauli D, Lejava G, Stvilia K, Todadze K, Tsintsadze M. Drug situation in Georgia in 2003. Annual report.
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19- Sirbiladze T, Tavzarshvili L, Zabransky T, Sturua, L. Estimating the prevalence of injection drug use in five cities of Georgia, 2009 report.
23- Gigi E, Sinakos E, Sykja A, Androulakis G, Tanis C, Stayridou V, Tsirogianni E, Zouridakis K, Bellou AL, Orfanou E, Raptopoulou-Gigi M. Epidemiology, clinical data, and treatment of viral hepatitis in a large cohort of intravenous drug users. J Addict Med. 2013 Jan-Feb;7(1):52-7. 24- Ciccozzi M, Zehender G, Cento V, Lo Presti A, Teoharov P, Pavlov I, Bogdanova V, Perno CF, Ciotti M. Molecular analysis of hepatitis C virus infection in Bulgarian injecting drug users. J Med Virol. 2011 Sep;83(9):1565-70. 25- Ilic G, Karadzic R, Kostic-Banovic L, Stojanovic J, Antovic A. Ultrastructural changes in the liver of intravenous heroin addicts. Bosn J Basic Med Sci. 2010 Feb;10(1):38-43. 26- Larsen C, Bousquet V, Delarocque-Astagneau E, Pioche C, Roudot-Thoraval F; HCV Surveillance Steering Committee; HCV Surveillance Group, Desenclos JC. Hepatitis C virus genotype 3 and the risk of severe liver disease in a large population of drug users in France. J Med Virol. 2010 Oct;82(10):1647-54 27- World Health Organization. Epidemiologiacal fact sheet on HIV and AIDS, Georgia, 2008 Update. http://apps.who.int/globalatlas/predefinedReports/EFS2008/full/EFS2008_GE.pdf 28- World Health Organization. Georgia statistics summary. http://apps.who.int/gho/data/view.country.9100 29- Martin NK, Vickerman P, Foster GR, Hutchinson SJ, Goldberg DJ, Hickman M. Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modeling analysis of its prevention utility. J Hepatol. 2011 Jun;54(6):1137-44.
Conception graphique : Isabelle Martija-Ochoa