High prevalence of hepatitis C infection and important treatment needs among people who inject drugs

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 partnersâ&#x20AC;&#x201D;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 â&#x20AC;&#x153;snowball samplingâ&#x20AC;?, 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 â&#x20AC;&#x201C; 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 â&#x20AC;&#x153;heavy drinkersâ&#x20AC;? (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 â&#x20AC;&#x201C; ** 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 â&#x20AC;&#x153;Drug situation in Georgiaâ&#x20AC;? 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 populationâ&#x20AC;&#x2122;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

â&#x20AC;&#x192;

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.

18

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.

23

High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia

Annexes Annexe 1: consent form

24

25

High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia

Annexe 2 : Questionnaire

26

27

High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia

28

29

High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia

30

31

High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia

32

33

High prevalence of hepatitis C infection and important treatment needs among people who inject drugs in Tbilisi, Georgia

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Conception graphique : Isabelle Martija-Ochoa