This is the most comprehensive compilation of epidemiological

information on Hepatitis C

Graciously provided by the

University Hepatitis Center

(last updated 2008)

Hepatitis C Update 2008

Tanya Schreibman, MD

University Hepatitis Center

Bradenton, Fl

Hepatitis C Update 2008

• Epidemiology

• Natural History and Clinical Presentation

• Diagnosis, Screening and Barriers

• Treatment

• Final Comments

Hepatitis C Update 2008: Epidemiology

Hepatitis C Virus InfectionMagnitude of the Problem

• Nearly 4 million persons in United States infected• Approximately 35,000 new cases yearly• 85% of new cases become chronic• Leading cause of

Chronic liver disease Cirrhosis Liver cancer Liver transplantation

Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.

True or False?

• You can only get hepatitis C by injecting drugs.

Answer: False

• It is true that you can get Hepatitis C by sharing needles or injecting drugs.

• However, this is not the only way that you can get Hepatitis C.

Hepatitis C Virus InfectionPopulation at Risk

• Transfusion of blood products before 1992

• Intravenous drug use

• Nasal inhalation of cocaine

• Chronic renal failure on dialysis

• Incarceration

• Occupational exposure to blood products

• Transplantation of an organ/tissue graft from an HCV-positive donor

• Body piercing and potentially tattoo

Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.

HCV Sexual TransmissionUnlikely in Heterosexual

Monogamous Couples• 895 monogamous heterosexual partners of

HCV infected patients– Ten year prospective follow up study

• 3 HCV infections during followed up– None were sexually transmitted from partner– In one couple,partners were different genotypes– In two couples, partners had same genotypes

but different strains

Hepatitis C Update 2008: Natural History and Clinical Presentation of Hepatitis C

Infection

4 Stages of Liver DamageStage 1 (F1)

Beginning of liver damageDamage has started with some slight

scarring

Stage 2 (F2)Moderate liver damage scarring advances in the liver & surrounding blood vessels

4 Stages of Liver DamageStage 3 (F3)

Significant liver damage; the liver becomes fibrotic (scarred) and connects

with other scarred areas.

Stage 4 (F4)Final stage of liver damage, also called cirrhosis; the liver is severely damaged

and no longer functions properly

Hepatitis C VirusFate of Acute Infection

15%

Chronic85%

Spontaneousresolution

Alter MJ, et al. N Eng J Med. 1999;341:556-562.

Hepatitis C Virus InfectionNatural History

Stable80% (68%)

HCCLiver failure25% (4%)

Slowlyprogressive75% (13%)

Resolved15% (15%)

Acute HCV

Cirrhosis20% (17%)

Chronic HCV85% (85%)

HCC, hepatocellular carcinoma

True or False?

• You can get hepatitis C and not even feel sick?

Answer: True

• You can have Hepatitis C for many years and not even feel sick or have any symptoms.

• The only way for you to know if you have Hepatitis C is to test your blood.

Chronic HCV InfectionSymptoms

Asymptomatic

Symptomatic

Cirrhosis

0

20

40

60

80

100

Fatigue

Per

cen

tag

e o

f P

atie

nts

37%

7%

56%

Unpublished data from MCV Hepatitis Program, 1995.

Alcohol and HCV: Is a little bit OK?• 800 patients – alcohol questionnaire

– Alcohol intake = lifetime ETOH/time drinking

• Fibrosis increased with > 50 g/day

Monto A et al. Hepatology 2004;39:826 - 834

g/Drinkg/Drink Drinks/50 gDrinks/50 g

BeerBeer12 oz at 12 oz at 4%4%

1111 4.54.5

Wine 5 oz Wine 5 oz at 11%at 11% 1313 3.83.8

MartiniMartini3 oz at 3 oz at 40%40%

2828 1.81.8

Alcohol content in specific beverages

Hepatitis C Update 2008:Screening and Diagnosis

Testing for Hepatitis C VirusAnti-HCV Antibodies

• ELISA screening test

– Sensitivity: 97%

– Detects circulating HCV antibodies

• False positive reactions may occur

– Cross-reacting circulating antibodies

• Positive predictive value

– 95% with risk factors and elevated ALT

– 50% without risk factors and normal ALTIllustration by Mitchell L. Shiffman, MD.

Hepatitis C VirusGenotypes in the USA

All others1%

Type 310%

Type 217%

Type 172%

McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.

Chronic HCV InfectionNormal vs Elevated Serum ALT

Normal ALT Elevated ALT

Portal26%

No fibrosis

23%

Mild39%

Cirrhosis6%

Bridging6%

Portal20%

No fibrosis

16% Mild33%

Cirrhosis18%

Bridging13%

Shiffman ML, et al. J Infect Dis. 2000;182:1595-1601.

Hepatitis C Virus InfectionLiver Biopsy

• Only test that can accurately assess– Severity of inflammation– Degree of fibrosis

• Determines the following– Risk for developing cirrhosis in future– Need for therapy– Need for ongoing therapy when initial

treatment has failed

Hepatitis C Update 2008: Treatment

True or False?

• HIV related disease is the number one cause of death in HIV patients co-infected with hepatitis C.

Answer: False

• Liver-related death is the number one cause of death in co-infected patients. That is why it is important to talk to your healthcare provider about treatment.

Current Treatment Recommendations

• Combination therapy for 6-12 months of pegylated interferon plus ribavirin is the standard of care

• Pegylated interferon (injection) helps fight the virus in two ways:– It helps healthy cells defend themselves against

the virus– It strengthens the immune system, which helps

to stop the virus from growing in number

Ribavirin

• Ribavirin is a pill, that when taken with pegylated interferon, helps the pegylated interferon do its job. It helps slow down the replication of hepatitis C. It is usually taken as long as you are taking pegylated interferon.

• Ribavirin cannot fight HCV on its own.

Treatment of Chronic HCVPeginterferon and Ribavirin

0

20

40

60

80

100

1 2-3

Genotype

Su

stai

ned

Vir

olo

gic

Res

po

nse

(%

)

PegIFN-2a/RBVPegIFN-2b/RBV

Fried MW, et al. N Eng J Med. 2002;347:975-982. Manns MP, et al. Lancet 2001;358:958-965.

Protease Inhibitor: Protease Inhibitor: Telaprevir(VX-950)Telaprevir(VX-950)

Courtesy of Dr. J-M Pawlotsky.

Hepatitis C Update 2008: Final Comments

Hepatitis C Virus Infection Prevalence by Age

0

1.0

2.0

3.0

4.0

5.0

< 11 11-19 20-29 30-39 40-49 50-59 60-69 ≥ 70

Age Group

An

ti-H

CV

Po

siti

ve (

%)

Alter MJ, et al. N Eng J Med. 1999;341:556-562.

Armstrong GL, et al. Hepatology. 2000;31:777-782.

Hepatitis C Virus InfectionThe Burden of Disease

0

1.0

2.0

3.0

1960 1980 2000 2020

Year

All patients

Infection for> 20 years

An

ti-H

CV

Po

siti

ve (

%)

Chronic HCV InfectionProgression to Cirrhosis

0

20

40

60

80

100

0 5 10 15 20Time (Years)

Bridging

Portal

None

Ap

pro

xim

ate

Pe

rce

nta

ge

of

Pa

tie

nts

Wit

h C

irrh

osi

s

Yano M, et al. Hepatology. 1996;23:1334-1340.

Proportion of Patients Developing Cirrhosis According to Initial Level of Fibrosis

Zein CO, et al. Am J Gastroenterol. 2005;100:48-55.

Chronic HCV and Diabetes Mellitus

Case Prevalence• 179 chronic HCV pts• Prevalence of diabetes

mellitus and insulin resistance noted

• Compared with expected rate based on NHANES III study after adjusting for– Age, Sex, Race

• Prevalence of DM or insulin resistance higher in those with chronic HCV

0

4

8

12

16

20

Females Males

Nu

mb

er o

f C

ases

ObservedExpected

Zein CO, et al. Am J Gastroenterol. 2005;100:48-55.

Chronic HCV and Diabetes Mellitus

Relationship to Fibrosis Stage

0

10

20

30

40

0 1 2 3 4

Histologic Stage

Per

cen

tag

e o

f P

atie

nts

Fattovich G, et al. Gastroenterology. 1997;112:463-472.

HCV in Patients With CirrhosisSurvival and Rate of

Decompensation

0

20

40

60

80

100

Su

rviv

al (

%)

StableDecompensation

10-Year Cumulative Survival

0

10

20

30

40

50

0 2 4 6 8 10

Years

Pe

rce

nta

ge

of

Pa

tie

nts

Decompensation

HCC

Cumulative Probability

HCV RNA and Liver HistologyFibrosis

Genotype

NoFibrosis

PortalFibrosis

BridgingFibrosis

Cirrhosis

Serum HCV RNA does not correlate with level of fibrosis

0

2

4

6

8

Lo

g H

CV

RN

A(c

op

ies/

mL

)

1

2

3

4

Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.