C

Shih Yu-Lueng

HCV Infection: Worldwide Prevalence

Taiwan: 0.3-0.6 million carriers 170 million carriers

WHO. Epidemiol Rec. 2000;75:18-1 9

3%

17C

1-2% (~600,000)
0.95% 0.5% 10% 90%

81%
3.5%

HIV (+)

HIV (-)

Blood, Vol 81, No 2 (January 15). 1993: pp412418

Haemophilia Centre and Haemostasis Unit, Royal Free Hospital, London, UK Gut 2000;47:845851

HIV (+)

HIV (-)

BLOOD, 15 JULY 2006 VOLUME 108, NUMBER 2

C
1988 1/2 7~8
Acute Hepatitis C Chronic Hepatitis C Liver Cirrhosis

55~85%

5~20% in 20-25 Yrs

1~4%/Yr

Hepatocellular carcinoma

? ?

C
Fatigue Impaired cognitive funct ions Low grade fevers Abdominal discomfort Appetite disturbances Abdominal pain Digestive disturbances Migratory arthralgia or m yalgia Depression Anxiety Many others

NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html. Accessed April 10, 2007.

C
GOT/GPT
GPT > GOT

( Biopsy )
(F1 ~ F4 )

( EIA; enzyme immunoassay method ) C( anti-HCV ) C C C

anti-HCV6~8

HCV RNA

SYBR Green I

Hybridization Probe

Hydrolysis Probe (TaqMan)

Elongation Phase

Annealing Phase

Elongation Phase

C
Criteria Anti-HCV (+) , ALT 1X, 3 M apart, within 6 M Age: 18 - 60 yrs Fibrosis F1
HCV RNA (+)

Antiviral therapy for chronic hepatitis C in treatme nt-na immunocompetent patients ve

100%

% Sustained Virologic response (Cure)

75% 62% 50% 38% 39%

25% 13% 6% 0%

Interferon 6months

Interferon 12months

Interferon plus Ribavirin

Pegylated Interferon

Peg-IFN plus Ribavirin

McHutchinson,98

Zeuzem,00

Fried,02

Genotype-guided Individualized treatment

Peg-IFN + ribavirin 1000/1200 mg/day HCV genotype

Genotype 1

Genotype 2/3

Tx 48 weeks

Tx 24 weeks

Yu ML, Chuang WL. JGH 2009

SVR Rate with Recommended Regimens

100
90 80 70 SVR (%) 60 50 40 30 20 10 0
298 20021 2 2004 271 95 90 96 46% 52% 52% HCV-1/4, 48 weeks 50% 95% 84% 80%

HCV-2/3: 24 weeks 83%

60%

71

19 20054

20063 20054

20042 20046

1. Fried M, et al. N Engl J Med. 2002;347:975; 2. Hadziyannis S, et al. Ann Intern Med. 2004;140:346; 3. Ferenci P, et al. J Hepatol. 2006;44:275; 4. Zeuzem S, et al. J Hepatol. 2005;43:250; 5. Yu ML. AASLD. 2007; 6. Von Wagner M, et al. Gastroenterology. 2005;129:522;7.

New definitions of on-treatment response

Response Definition

RVR
cEVR pEVR Non-EVR

HCV RNA negative (<50 IU/mL) at week 4 HCV RNA negative (<50 IU/mL) at week 12 HCV RNA decrease 2 log at week 12 <2 log drop from baseline at week 12

On-treatment response
Viral load d ecrease

RVR Complete EVR (cEVR) Partial EVR (pEVR) Slow responder

2log 50 IU/mL 4 12 24 36 48 Time (weeks)

Roadmap for Individualized HCV Therapy (1)

Peg-IFN + ribavirin 1000/1200 mg/day HCV genotype

Baseline

Genotype 1,4

Genotype 2,3

W4

RVR(+) and LVL

RVR(-) and HVL

RVR(+)

RVR(-)

W12

EVR(+)

EVR(-)

Tx 24 wks

Tx 48 wks

Stop or extend Tx

Tx 12-16 wks

Tx 24 wks

Modefied from Yu ML, Chuang WL. JGH 2009

(< 3.5 million copies) (genotype 2 & 3)

(no fibrosis or limited to the portal tract)

(female gender) (< 40 years)

Earlier treatment results in higher SVR rate


Flu-like symptom
Headache, fatigue, myal gia, arthralgia, fever, chill s

Neuropsychiatric disorder
depression, anxiety

Lab. Alteration
neutropenia, anemia, thr ombocytopenia

Alopecia Asthma like sympto m Nausea Diarrhea Weight loss Injection-site reacti on


Increase in Incidenc e/Severity Depression Fatigue Anxiety Flu-like symp toms 0 Months
Dan A, et al. J Hepatol. 2006;44:491-498. Constant A, et al. J Clin Psychiatry. 2005;66:1050-1057.

 ribavirin
hemolytic anemia teratogenicity cough itching, rash nasal stuffiness lymphopenia hyperuricemia


reduction of ribavirin dose discontinuation of therapy Transfusion administration of EPO
(indication: anemia related with renal failure or malignancy during
chemotherapy)