Che materia stai cercando?

Evidenze II - HCV Appunti scolastici Premium

Appunti di Evidenze medico chirurgiche II del professor Coppola sulla terapia dell'epatite cronica da HCV con analisi dei seguenti argomenti: statistiche dell'infezione, genotipi HCV, trattamenti e terapie, farmaci attuali, parametri di risposta alla terapia, fattori di rischio dell'uomo e ambientale.

Esame di Evidenze II docente Prof. N. Coppola

Anteprima

ESTRATTO DOCUMENTO

Definition of Response to treatment

DURING THERAPY

th NR = Non Response

HCV-RNA pos.(3 mo)

END OF FOLLOW UP

(6 or 12 mo. after discontinuation)

ALT normal SR = Complete Sustained Response

HCV-RNA neg.

ALT increased or normal R = Relapse

HCV-RNA positive

Parametri “on treatment” di risposta alla terapia

EVR undetectable HCV-RNA or 2 log

reduction from baseline at week 12

of treatment

• reliably predicts negative treatment outcome

• a good parameter to make a decision on

discontinuation of treatment

• a less robust parameter to predict positive

treatment outcome

Early Virologic Response (EVR)

Ferenci P, AASLD, 2001. EVR SVR 65% PPV

(n=253) 65%

86%

(n=390) 35%

Week 12 )

No SVR (n=137

α µ 2-log drop or

PEG-IFN -2a 180 g undetectable

+ HCV-RNA SVR

Ribavirin 1000-1200 mg 3%

(n=453) (n=2)

14%

(n=63) 97% NPV

(n=61)

No SVR

No EVR 97%

ALL Patients EVR SVR 72% PPV

)

(n=273 72%

74%

(n=380) 28%

Week 12 (n=107)

No SVR

α µ

PEG-IFN -2b 1.5 g/kg 2-log drop or

undetectable

+ HCV-RNA

Ribavirin 800 mg SVR 0%

(n=511) (n=0)

26%

(n=131) 100% NPV

(n=131)

No SVR

No EVR 100%

Davis G, Hepatology, 2003.

Parametri “on treatment” di risposta alla terapia

RVR undetectable HCV-RNA at week 4

of treatment

• may be used to individualize treatment duration

• patients with genotype 2 or 3 infection and RVR could

be treated for 12-16 weeks

• patients with genotype 1 infection, low baseline viremia

and RVR could be treated for 24 weeks

Meta-analysis of interferon therapy

for chronic hepatitis C

6 MU x 6 mo 3 MU x 6 mo

n.s.

response 60 62 n.s.

40 53

% 20 28 18

0 Complete response Sustained response

6 MU x 12 mo 3 MU x 12 mo

p<0.005

response p<0.001

60 69

40 54 46

% 20 28

0 Poynard et al., 1995

IFN alpha+Ribavirin

Sustained response in naive patients

α

α IFNα -2b 3MU+ Ribavirin

IFNα -2b 3MU

for 48 weeks (1-1.2 g/die) for 48 weeks

pts % pts %

Poynard, 98 278 19.0 277 42.6

McHutchinson 98 225 12.8 227 38.3

Total 503 16.3 504 40.6

α

PegIFN 2a in patients with chronic hepatitis C

Sustained response in naive patients

α

PegInterferon 2a for 48 weeks

α

-IFN 2a 3MU tiw for 48 weeks

39

40

35 26

30 19

25

20

15 7

10

5

0 Zeuzem 2000 Heathcote 2000*

n° pts: 267 264 87 88

* All patients with histological evidence of cirrhosis

α

PegIFN 2b in patients with chronic hepatitis C

Sustained response in naive patients

α µ

PegInterferon 2b (1.5 g/kg) for 48 weeks

α µ

PegInterferon 2b (1.0µ

g/kg) for 48 weeks

α µ

PegInterferon 2b (0.5µ

g/kg) for 48 weeks

α

-IFN 2b 3MU tiw for 48 weeks

30 25

23

20 18

% 12

10

0

n° pts: 304 297 315 303 Lindsay 2001

α

PegIFN 2b+Ribavirin in patients with chronic hepatitis C

Sustained response in naive patients

α µ

PegInterferon 2b (1.5 g\kg)+Ribavirin for 48 weeks

α → µ

PegInterferon 2b (1.5→

0.5 g\kg)+Ribavirin for 48 weeks

α

-IFN 2b 3MU tiw+Ribavirin for 48 weeks

60 54 47 47

50

40

% 30

20

10

0

n° pts: 511 514 505 Manns 2001

α

PegIFN 2a+Ribavirin in patients with chronic hepatitis C

Sustained response in naive patients

α µ

PegInterferon 2a (180µ

g)+Ribavirin for 48 weeks

α

-IFN 2b 3MU tiw+Ribavirin for 48 weeks

α µ

PegInterferon 2a (180µ

g) for 48 weeks

56

60

50 44

40

% 29

30

20

10

0

n° pts: 453 444 224 Fried, 2002

Factors associated

with a sustained response

Hepatitis C virus genotype

Age < 40 years

other than 1 Lean or normal body

Low Viral load

weigth

Low number and genetic

Female gender

diversity of viral strains Insufficienza renale cronica

Absence of cirrhosis

γ

Low -GT level

Short duration of disease

Normal or low hepatic iron

Alcohol abstinence

content

Low fibrosis score

No confounding viral

African-American

ethnicity disease (HBV or HIV)

Prognostic factors for sustained response

% of Sustained response in naive patients

α

treated with Interferon2b 3MU TIW + Ribavirin for 48 weeks

Genotype

Viral Load

64

70 Degree of Fibrosis

60 47 46

40

50 33

31

40 2

3

30 4

20 <2M >2M

5

10 mL mL

1 6

0 Genotype Viral Load Fibrosis

n° pts: 180 97 115 162 209 46

Poynard T, 1998

Prognostic factors for sustained response

α

% of Sustained response to Peg-IFN -2b in naive patients

µ

treated with Peg-Interferon 1.5µ

g/Kg + Ribavirin for 48 weeks

Genotype

100 Viral Load

82 78 Degree of Fibrosis

80 57

60 50 44

42 42

% 40 4

5

2 <2M >2M

20 mL mL

6

1 3

0 Genotype Viral Load Fibrosis

n° pts: 348 147 16 160 351 333 136

Manns MP, 2001

Prognostic factors for sustained response

% of Sustained response in naive patients

α µ

treated with Peg-Interferon 2a 180µ

g/Kg + Ribavirin for 48 weeks

Genotype

76 77 Viral Load

80 Degree of Fibrosis

62 58

53

60 46 43

% 40

20 2 <2M >2M

mL mL

1 4

3

0 Genotype Viral Load Cirrhosis

n° pts: 298 140 13 159 293 397 56

Fried MW, 2002

Predictors of response to antiviral treatment:

multivariate analysis in patients with HCV-CH

Poynard Z Heathcote Lindsay Manns Fried

McHutchinson euzem

IFN+Riba IFN+Riba Peg Peg Peg Peg+Rib Peg+Rib

1998 1998 2000 2000† 2001 2001 2002

Genotype X X X X X X X

Viral load X X X X X X NS

Gender X X NS NS NS NS

Age NS X X NS X X

Fibrosis NS X X NS NS

Weight NS X X X

X: with statistical significance

† :PegInterferon in patients NS: not significant

with cirrhosis or bridging necrosis

α

PegIFN 2a+Ribavirin in patients with chronic hepatitis C

Sustained response in HCV genotype 1

for 24 weeks and low dose (800mg/d) of Ribavirin

for 24 weeks and standard dose (1000-1200mg/d) of Ribavirin

for 48 weeks and low dose (800mg/d) of Ribavirin

for 48 weeks and standard dose (1000-1200mg/d) of Ribavirin

N° cases

101

118

All patients 250

271

51

71

Low viral load 60

85

<2.000.000cps/ml 50

47

High viral load 190

>2.000.000cps/ml 186

% of patients 0 20 40 60 80 100

Hadziyannis SJ, 2004

α

PegIFN 2a+Ribavirin in patients with chronic hepatitis C

Sustained response in HCV genotypes 2 and 3

for 24 weeks and low dose (800mg/d) of Ribavirin

for 24 weeks and standard dose (1000-1200mg/d) of Ribavirin

for 48 weeks and low dose (800mg/d) of Ribavirin

for 48 weeks and standard dose (1000-1200mg/d) of Ribavirin

N° cases

96

144

All patients 99

153

34

47

Low viral load 33

48

<2.000.000cps/ml 62

97

High viral load 66

>2.000.000cps/ml 105

% of patients 0 20 40 60 80 100

Hadziyannis SJ, 2004

Genotype 1 48 weeks (AI)

Genotype 2 24 weeks (AI)

Genotype 3 24 weeks (AI)

SVR % Berg T, Gastroenterology 2006

Relapse rate % Berg T, Gastroenterology 2006

Peg-IFN+Riba for 24 weeks

in HCV genotype 1 ad low viral load

235 patients:

- genotype 1

- HCV viral load <600.000IU/ml

Peg-IFN a2b: 1.5 mg/kg/week+

Ribavirin 800-1400 mg/die for 24 weeks

Patients negative at week 4:

All patients: SR: 89%

SR: 50% - 48-week historical control 85%

- 48-week historical control 71% (Manns et al., Lancet 2001)

(Manns et al., Lancet 2001) Zeuzem S, J Hepatol 2006

Genotype 1 48 weeks (AI)

Low viral load and negative at week 4 24weeks (BII)

- without early virological response

- 72 weeks (BII)

Genotype 2 24 weeks (AI)

Genotype 3 24 weeks (AI)

Mangia A, 2005

Peg-IFN+Riba for 12 vs. 24 weeks

in HCV genotype 2 or 3

% of Sustained response 85

100 78

76

80 64

60

% 40

20

0 standard duration variable duration

n° pts: 70 213 133 80

∗: HCV-RNA negative at week 4

**: HCV-RNA positive at week 4 Mangia A, 2005

Peg-IFN+Riba for 12 vs. 24 weeks

in HCV genotype 2 or 3

152 patients:

- 39 genotype 2

-- 113 genotype 3

HCV-RNA negative HCV-RNA positive

at week 4 at week 4

24 weeks 24 weeks

16 weeks Von Wagner M, Gastroenterology 2005

Peg-IFN+Riba for 12 vs. 24 weeks

in HCV genotype 2 or 3

% of Sustained response

100 82 80

80

% 60 36

40

20

0 negative at week 4 positive at week 4

SR in HCV-3 and a low viral load vs HCV-3 and high viral load:

85% vs. 59%, p<0.003 Von Wagner M, Gastroenterology 2005

Peg-IFN+Riba for 16 vs. 24 weeks

in HCV genotype 2 or 3

1469 patients

randomized

in 16 or 24

weeks arms

Shiffman LM, NEJM 07

Peg-IFN+Riba for 16 vs. 24 weeks

in HCV genotype 2 or 3

1469 patients

randomized

in 16 or 24

weeks arms

P<0.05

P<0.001

Shiffman LM, NEJM 07

48 weeks (AI)

Genotype 1

Low viral load and negative at week 4 24weeks (BII)

- without early virological response

- 72 weeks (BII)

Genotype 2 24 weeks (AI)

Genotype 3 24 weeks (AI)

Genotype 3 and low viral load 12 weeks (BI)

Genotype 3 and high viral load 24 weeks (BI)

or 48 weeks (BIII)

Peg-IFN+Riba in 287 egyptian patients

with HCV genotype 4

100 % of Sustained response 69

80 66

60

% 29

40

20

0 24 weeks 36 weeks 48 weeks

n° pts: 95 96 96

Kamal SM, GUT 2005

Genotype 1 48 weeks (AI)

Low viral load and negative at week 4 24weeks (BII)

- without early virological response

- 72 weeks (BII)

Genotype 2 HCV-RNA negative at 12-16 weeks (BI)

week 4 or 24 weeks (AI)

Genotype 2 with HCV-RNA positive 24 weeks (BI)

at week 4 or 48 weeks (BIII)

Genotype 3 and low viral load 12 weeks (BI)

Genotype 3 and high viral load 24 weeks (BI)

or 48 weeks (BIII)

Genotype 4 36 weeks (BI)

48 weeks (BIII)

Genotype 1 48 weeks (AI)

Low viral load and negative at week 4 24weeks (BII)

- without early virological response

- 72 weeks (BII)

Genotype 2 24 weeks (AI)

Genotype 3 24 weeks (AI)

Genotype 3 and low viral load 12 weeks (BI)

Genotype 3 and high viral load 24 weeks (BI)

or 48 weeks (BIII)

Genotype 4 36 weeks (BI)

48 weeks (BIII)


PAGINE

76

PESO

5.82 MB

PUBBLICATO

+1 anno fa


DETTAGLI
Esame: Evidenze II
Corso di laurea: Corso di laurea magistrale in medicina e chirurgia (ordinamento U.E. - durata 6 anni) (CASERTA, NAPOLI)
SSD:

I contenuti di questa pagina costituiscono rielaborazioni personali del Publisher valeria0186 di informazioni apprese con la frequenza delle lezioni di Evidenze II e studio autonomo di eventuali libri di riferimento in preparazione dell'esame finale o della tesi. Non devono intendersi come materiale ufficiale dell'università Seconda Università di Napoli SUN - Unina2 o del prof Coppola Nicola.

Acquista con carta o conto PayPal

Scarica il file tutte le volte che vuoi

Paga con un conto PayPal per usufruire della garanzia Soddisfatto o rimborsato

Recensioni
Ti è piaciuto questo appunto? Valutalo!

Altri appunti di Evidenze ii

Evidenze II - terapia HIV
Appunto
Anatomia umana - apparato locomotore
Appunto
Igiene - acqua
Appunto
Ginecologia e ostetricia - ciclo mestruale
Appunto