Current and future burden of HCV infection in...

Current and future burden

of HCV infection

in Russia

St. Petersburg, 05 May, 2015

Olga Sagalova

Clinic of South Ural State Medical University of

Ministry of Healthcare of Russian Federation

1

Disclosures

• Consultant: MSD, Gilead

• Sponsored Lectures (National or International): BMS,

MSD, Janssen, AbbVie, Gilead

2

Current Disease Burden

-Gower, E., et al., Global epidemiology and genotype distribution of the hepatitis C virus, J Hepatol (2014)

Prevalence(Viremic)

0.0%-0.6%

0.6%-0.8%

0.8%-1.3%

1.3%-2.9%

2.9%-7.8%

Total Infected (Viremic)

200K-650K

650K-1.9M

0-200K

1.9M-3.5M

3.5M-9.2M

3


• The number of chronic HCV cases per 100,000 increased from

12.9 in 1999 to a peak of 40.9 in 2009. In 2012 there were 39.1

cases per 100,000 individuals (1)

1Viral hepatitis in Russian Federation. Analytical review. 9 ed. 2013; 113.

4

0

5

10

15

20

25

30

35

40

45

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

ХГС

12.9

39.4

pe

r 1

00

00

0

39.1


2010 anti-HCV Prevalence Total Cases

Russia 4.10% 5,861,500

2010 Viremic Prevalence Total Viremic Cases

Russia 2.91% 4,161,700

• The estimate for anrti-HCV prevalence in the general Russian

population derives from a general consensus of 4.1% in 2010, reported

in multiple sources (VHPB 2011, Lavanchy 2011, Pimenov 2012)

• Applying a viremic rate of 71% (Iashina 1993), the viremic prevalence in

2010 was estimated at 2.9%, corresponding to 4.2 million infections

-Viral Hepatitis Prevention Board. Russia: Burden of disease. January 2011.

http://www.vhpb.org/files/html/Meetings_and_publications/Viral_Hepatitis_Newsletters/vhv19n1.pdf

-Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infec 2011 Feb; 17(2):107-15.

-Pimenov NN, Vdovin AV, Komarova SV, Mamonova NA, Chulanov VP, Pokrovskii VI. [The relevance and prospeсts of introducing a uniform federal register

of patients with viral hepatitis B and C in Russia.] Ter Arkh 2012; 85(11):4-9.

-Iashina TL, Favorov MO, Shakhgil'dian IV, Iarasheva DM, Nazarova OI, Derevianko EN, Ommadova MI, Onishchenko GG, Watanabe Y, Nishioka K. [The

spread of hepatitis C markers among the population of regions of Russia and Central Asia]. Zh Mikrobiol Epidemiol Immunobiol 1993 September;(5):46-9.

5


-Pimenov N.N, Chulanov V.P., Komarova S.V. et al. [Hepatitis C in Russia: current epidemiology and approaches to improving diagnosis and surveillance].

Epidemiology and Infectious Diseases, 2012; (4):4-10.

Prevalence Age and Gender Distribution

• The age and gender distribution was developed using the

age distribution and gender ratio of infection as presented in

Pimenov et al (2012)

6


Genotype Distribution

• The genotype distribution was developed using data from

regional registries of more than 40,000 patients with chronic viral

hepatitis (Pimenov et al. 2012)

• G1: 54.9%

‒ G1a: 2.1%

‒ G1b: 52.8%

• G2: 8.1%

• G3: 36.3%

• Other: 0.7%

-Pimenov N.N, Chulanov V.P., Komarova S.V. et al. [Hepatitis C in Russia: current epidemiology and approaches to improving diagnosis and surveillance].

Epidemiology and Infectious Diseases, 2012; (4):4-10.

7

52,8%

8,1%

36,3%

1a

1b

2a

3a

39%

25%

16%

9%

11%

F0

F1

F2

F3

F4

Federal register of patients with viral hepatitis (2014)

n=9851

F0-F1 64%

F2-F4 36%

Distribution of fibrosis


8


Diagnosed

• According to the National Reference Center for Viral Hepatitis

the number of previously diagnosed (viremic) in 2012

was1,789,500 individuals

• The number of newly diagnosed (viremic) in 2012 was 55,900

patients (National Reference Center for Viral Hepatitis)

• According to an analysis of regional registries conducted by the

Russian National Reference Center for Viral Hepatitis,

approximately 43% of the infected population in 2012 had

received anti-HCV testing

9


Treated Patients

• 2011: 5,500 patients were on treatment (regional registries),

corresponding to a 0.1% treatment rate

Year 2004 2005 2006 2007 2008 2009 2010

2011-

2030

Tx Pts 666 1,662 2,254 3,010 2,735 3,807 5,500 5,500

10


Incidence

• Using the known number of total HCV infections in 2010, a

mathematical model was used to calculate the annual number of

all-cause mortality, liver-related deaths and cured cases as

described by Razavi et al. According to this calculation, there

were an estimated 236,000 new cases of HCV in Russia in 2013

- Razavi H, Waked I, Sarrazin C, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat

2014; 21 Suppl 1: 34-59

11


• A progression model constructed to quantify the size of the

HCV infected population, by stages of liver disease until 2030

-Razavi H, et al. J Viral Hepat. 2014;Suppl 1:34-59;

12

Количество в 2013

Total ~ 4 500 000

Treated 5 500

Compensated cirrhosis ~ 145 500

Decompensated cirrhosis ~ 17 000

HCC ~ 5 000

Total living with the diagnosis ~ 1 800 000

Annual newly diagnosed 55 900

Future Disease Burden Continue Current Treatment Program

0

1 000 000

2 000 000

3 000 000

4 000 000

5 000 000

6 000 000

7 000 000

2013 2030

Total Infected

0

5 000

10 000

15 000

20 000

2013 2030

LRD

0

10 000

20 000

30 000

40 000

50 000

60 000

2013 2030

Decompensated Cirrhosis

0

5 000

10 000

15 000

20 000

2013 2030

HCC

13

2013 2030

Treated (annual) 5,500

SVR by Genotype (G)G1 50% and G4 and

75% G2 and 60% G3%

Impact

# Total infected 4,525,000 6,164,000

% change +36%

# Liver-related deaths 5,110 16,100

% Change +215%

# Decompensated

cirrhosis 17,140 52,000

% change +203%

# HCC 5,170 16,530

% change +220%

Future Disease Burden Can we control the disease? What needs be done?

0

20 000

40 000

60 000

80 000

100 000

120 000

140 000

201

32

01

62

01

72

01

92

02

22

02

5

Treated

0

100 000

200 000

300 000

400 000

500 000

600 000

700 000

201

32

01

62

01

72

01

92

02

22

02

5

Newly diagnosed

0

50 000

100 000

150 000

200 000

250 000

201

3

201

6

201

7

201

9

202

2

202

5

New infections

• 40% reduction in viremic individuals

by 2030

• 68% drop in HCV-related mortality by

2030

• We need to:

– Increase annual number

of treated patients to 123,800 with

high SVR therapies

– Increase diagnosed

patients accordingly

– Reduce new infections by 20%

annually starting in 2017

14

Future Disease Burden Impact of Disease Control Strategy

4 500 000

6 200 000

3 700 000

01 000 0002 000 0003 000 0004 000 0005 000 0006 000 0007 000 000

Today 2030CurrentStrategy

2030ControlStrategy

Total Infected

-40%

150 000

400 000

100 000

0100 000200 000300 000400 000500 000

Today 2030CurrentStrategy

2030ControlStrategy

# Compensated Cirrhosis

-75%

Impact

# Total infected 4,500,000 6,200,000 3,700,000

Change (%) +27% -40%

Today

2030

Current Strategy

Control Strategy

Treated (Annual) 5,500 5,500 123,800

Treatment rate 0.1% 0.1% 3%

SVR by genotype

G1 50% and

G4 and 75%

G2 and 60%

G3%

G1 50% and

G4 and 75%

G2 and 60%

G3%

90% for all genotypes

Total diagnosed 1,800,000 2,200,000 4,100,000

Common treatment age 15 - 64 15- 64 15-69Treated Stages ≥ F1 ≥ F1 ≥ F2

# Compensated cirrhosis 150,000 400,000 100,000

Change (%) +63% -75%

15

• Adopting this scenario will result in 2,490,000 fewer viremic

individuals in 2030 vs the base case, a 40% reduction

• Between 2015 and 2030

– 1,610,000 new infections avoided

– 67,000 HCV-related mortalities prevented

– 1,500,000 patients cured

– 300,000 cirrhotic cases averted


16


Importance of Preventing Transmission

• If effective measures are

not adopted to reduce

incidence and the number

of new cases only

decreases as an effect of

increased cure

• There will be >1.2 million

more cases by 2030

• Disease elimination will

not be reached

Prevalence in

2030

Increased

treatment, SVR,

without incidence

reduction

4,930,000 -20%

Increased

treatment, SVR,

reduce incidence

3,680,000 -40%

17

Conclusions

• Without significantly changing treatment strategies,

HCV infection will remain a highly prevalent problem for

the next 20–30 years

• With treatment rates of 3% and SVR 90% along with

treatment initiated at ≥F2, it will be possible to control

HCV disease burden in Russia

• The availability of highly effective therapy,

coupled with increased diagnosis and treatment,

and marked reduction in new cases, has the potential

to significantly reduce hepatitis C morbidity and mortality

in Russia within the next 15 years

18

Cпасибо

Thank you

19

References • Abdourakhmanov DT, Hasaev AS, Castro FJ, Guardia J. Epidemiological and clinical aspects of hepatitis C virus infection in the Russian Republic

of Daghestan. Eur.J.Epidemiol. 1998 Sep;14(6):549-53.

• Andreytseva O.Il, Zhao A.V. Oral presentation at Immune System and Liver Disease conference, May 16, 2009, Nakhabino

• Gautier SV, Moysyuk YG, Khomyakov SM, Ibragimova OS. Progress in organ donation and transplantation in Russian Federation in 2006-2010. 3rd reprot of national registry. Journal of Transplantation and Artificial Organs 2011;2:6-20.

• Gautier SV, Moysyuk YG, Khomyakov SM, Ibragimova OS. Organ donation and transplantation in Russian Federation in 2011. 4th report of national registry. Journal of Transplantation and Artificial Organs 2012;3:6-18.

• Gower, E., et al., Global epidemiology and genotype distribution of the hepatitis C virus, J Hepatol (2014).

• Granov A.M., Granov D.A., Zherebtsov F.K., Gerasimova O.A., Borovik V.V., Osovskikh V.V., Maystrenko D.N., Rutkin I.O., Tsurupa S.P., Tileubergenov I.I., Shapoval S.V., Mikhaylichenko T.G. Liver Transplantation. A single center experience of 100 cases. Journal of Transplantation and Artificial Organs 2012;4:11-16.

• Iashina TL, Favorov MO, Shakhgil'dian IV, Iarasheva DM, Nazarova OI, Derevianko EN, Ommadova MI, Onishchenko GG, Watanabe Y, Nishioka K. [The spread of hepatitis C markers among the population of regions of Russia and Central Asia]. Zh Mikrobiol Epidemiol Immunobiol 1993 September;(5):46-9.

• Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infec 2011 Feb; 17(2):107-15.

• Pimenov N.N, Chulanov V.P., Komarova S.V. et al. [Hepatitis C in Russia: current epidemiology and approaches to improving diagnosis and surveillance]. Epidemiology and Infectious Diseases, 2012; (4):4-10.

• Pimenov NN, Vdovin AV, Komarova SV, Mamonova NA, Chulanov VP, Pokrovskii VI. [The relevance and proscpets of introducing a uniform federal register of patients with viral hepatitis B and C in Russia.] Ter Arkh 2012; 85(11):4-9.

• Razavi H, Waked I, Sarrazin C, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014; 21 Suppl 1: 34-59

• UC Berkeley, Max Planck Institute for Demographic Research, The Human Mortality Database (http://www.mortality.org). 2008-2031 mortality rate was calculated from historical trends and allocated to five year age cohorts.

• United Nations - Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, World Population Prospects: The 2010 Revision and World Urbanization Prospects: The 2010 Revision, http://esa.un.org/unpd/wpp/unpp/panel_indicators.htm

• Viral hepatitis in Russian Federation. Analytical review. 9 ed. 2013; 113.

• Viral Hepatitis Prevention Board. Russia: Burden of disease. January 2011. http://www.vhpb.org/files/html/Meetings_and_publications/Viral_Hepatitis_Newsletters/vhv19n1.pdf

20


Other Assumptions

• Population – 1950-2030 (United Nations 2010)

• Mortality – 1950-2007 (University of California Berkeley)

• Risk Factors

– Percent of the population infected through IDU- 16% in 1995

(Abdourakhmanov 1998)

– Percent of the population infected through Transfusion - 26% in

1995 (Abdourakhmanov 1998)

-UC Berkeley, Max Planck Institute for Demographic Research, The Human Mortality Database (http://www.mortality.org). 2008-2031 mortality rate was

calculated from historical trends and allocated to five year age cohorts.

-United Nations - Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, World Population Prospects: The 2010

Revision and World Urbanization Prospects: The 2010 Revision, http://esa.un.org/unpd/wpp/unpp/panel_indicators.htm

-Abdourakhmanov DT, Hasaev AS, Castro FJ, Guardia J. Epidemiological and clinical aspects of hepatitis C virus infection in the Russian Republic of

Daghestan. Eur.J.Epidemiol. 1998 Sep;14(6):549-53.

21


Liver Transplants • Liver transplant data for 2006-2011 was available through Gautier 2011 and

Gautier 2012. Estimates for 2004 and 2005 were trended from the available

data. The calculated weights were applied to generate the number of HCV-

Related Transplants by year

• Assumed 32% of all transplants were due to HCV (Granov 2012 and

Andreytseva 2009)

-

50

100

150

200

250

2004 2005 2006 2007 2008 2009 2010 2011

Liv

er

Tra

nsp

lan

ts

Actual Transplants HCV-Related Transplants

-Gautier SV, Moysyuk YG, Khomyakov SM, Ibragimova OS. Progress in organ donation and transplantation in Russian Federation in 2006-2010. 3rd reprot of

national registry. Journal of Transplantation and Artificial Organs 2011;2:6-20.

-Gautier SV, Moysyuk YG, Khomyakov SM, Ibragimova OS. Organ donation and transplantation in Russian Federation in 2011. 4th report of national registry.

Journal of Transplantation and Artificial Organs 2012;3:6-18.

-Granov A.M., Granov D.A., Zherebtsov F.K., Gerasimova O.A., Borovik V.V., Osovskikh V.V., Maystrenko D.N., Rutkin I.O., Tsurupa S.P., Tileubergenov I.I.,

Shapoval S.V., Mikhaylichenko T.G. Liver Transplantation. A single center experience of 100 cases. Journal of Transplantation and Artificial Organs 2012;4:11-

16.

-Andreytseva O.Il, Zhao A.V. Oral presentation at Immune System and Liver Disease conference, May 16, 2009, Nakhabino.

22

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