Faculdade de Medicina
Sandra Regina Xavier Santos
Desordens tireoideanas em pacientes
portadores de Hepatite C.
Uberlândia
Sandra Regina Xavier Santos
Desordens tireoideanas em pacientes
portadores de Hepatite C.
Dissertação apresentada ao Programa de Pós Graduação em Ciências da Saúde da Faculdade de Medicina da Universidade Federal de Uberlândia como parte das exigências para obtenção do título de Mestre em Ciências da Saúde.
Área de concentração: Ciências da Saúde Orientador: Prof. Dr. PAULO TANNÚS JORGE
Universidade Federal de Uberlândia
Faculdade de Medicina
Sandra Regina Xavier Santos
Desordens tireoideanas em pacientes
portadores de Hepatite C.
Dissertação apresentada ao Programa de Pós Graduação em Ciências da Saúde da Faculdade de Medicina da Universidade Federal de Uberlândia como parte das exigências para obtenção do título de mestre em Ciências da Saúde.
Área de concentração: Ciências da Saúde
Uberlândia, 19 de março de 2009.
Banca Examinadora:
___Dr. Marcus Aurelho de Lima (UFTM)________
___Dr. Luiz Carlos M. Oliveira (UFU)____________
Aos meus filhos
A descoberta consiste em ver o que todos
viram e pensar o que ninguém pensou. A
mente que se abre a uma nova idéia jamais
voltará ao seu tamanho original.
!
"
#
$
#
%
&
'
(
)
)%
)%
(
&
% *
+
&
% ,
-
-
.
-
& " )
(
/
01 2*2
)%
$
"
#
0
-
(
1
3
)%
4
!
1 5
%
)6
)%
7
)
"
' 8
4
3
9
#"
"
" :
%
"
7
)
( 3
;
7
<
%
1
-
7
"
)%
" +
%
& "
-7
3
)%
/
-
"
%
0
1
)6
"
'
" '
"
#"
=>?
@A?B
)%
)%
#
)%
;
"
0
1
%
/
-
"
*
"
7 '
%
CA
0
1
/
-
"
=5>B DC
0
1
=5CB
EC
0
1 =5
1
B
&0
=
B
=
5B
7
0
1
=@D?B
7
7 '
%
'
"
=>C?
5>: E FD?
5C: >G FG?
1
B
H F IAA
J%
3"
7 '
)
+
0
1
/
-
"
7
0
1 7
"
)%
;#
/
:
-
"
:
0
1:
+
:
/
-
"
0
1
K
K
;
& "
"
L
"
" K =>?
@A?B
K
M
;
"
K L
K
K
K
0
1
L
/
-
"
N
"
7
K
K
CA
L
1
L
-
"
=5>B DC
L 0
1 L
=5CB
EC
L
0
1 =
B
&0
=
B
=
5B
K
K
L
7
K
0
1
=@D?B L
7
K
K
L
" K =>C?
5>: E FD?
5C
>G FG?
B / L
"
K
K
0
1
L
/
-
"
:
"
K
K
7
K
0
1
M
M
K
K
K
Frequência de desordens tireoideanas (TSH alterado e/ou anticorpos
antitireoideanos positivos) nos pacientes portadores de Hepatite C (com e sem
tratamento com alfa Interferon e Ribaverina) e o grupo controle...40
Tabela 2- Frequência de Hipotiroidismo nos pacientes portadores de Hepatite C
(com e sem tratamento com alfa Interferon e Ribaverina) e o grupo controle...41
Tabela 3-
Frequência de anticorpos antitireoideanos nos pacientes portadores de
Hepatite C (com e sem tratamento com alfa-Interferon e Ribaverina) e o grupo
Gráfico 1-
Frequência de Hipotiroidismo e de Anticorpos Antitireoideanos em
portadores de Hepatite C (com e sem tratamento com Interferon alfa e Ribaverina)
ANTI-HCV- Anticorpo anti vírus da hepatite C
Anti-TG- Anti- tireoglobulina
Anti-TPO- Anti-tireoperoxidase
APC- Células apresentadoras de antígenos
CTLA-4- Linfócito citotóxico T associado ao Antígeno 4
CXCL-10- CXC Chemokine ligand 10
DAOE- Doenças Autoimunes Órgão Específicas
DAT- Doença Autoimune da Tireóide
DG- Doença de Graves
FT4- Tiroxina livre
HBV – Vírus da Hepatite B
HC-UFU- Hospital de Clínicas da Universidade Federal de Uberlândia
HCV- Vírus da Hepatite C
HCV-RNA- RNA do vírus da Hepatite C
HIV- Vírus da Imunodeficiência Adquirida (AIDS)
HLA- Human Leukocyte Antigen
IFRs- Interferons
IL- Interleucinas
NHI- National Institute of Health
OMS - Organização Mundial de Saúde
PCR- Polymerase Chain Reaction
SBH- Sociedade Brasileira de Hepatologia
Tg- Tireoglobulina
TGO- Aspartato Aminotransferase
TGP- Alanina Aminotransferase
TH- Tiroidite de Hashimoto
TPO- Peroxidase tireóidea
TSH- Hormônio Estimulante da Tireóide
TSH.R-Receptor de TSH
!
1-
INTRODUÇÃO...13
2-
REFERENCIAL TEÓRICO...17
2.1- Hepatite C...18
2.1.1- Epidemiologia, História natural, manifestações clínicas...18
2.1.2- Diagnóstico...19
2.1.3- Tratamento e Efeitos colaterais...20
2.2- Interferon Alfa...22
2.3- Ribaverina...23
2.4- Doenças Autoimunes da Tireóide (DAT)...24
2.4.1- Histórico...24
2.4.2- Tiroidite Autoimune...25
2.4.2.1-
Epidemiologia...25
2.4.2.2-
Diagnóstico...26
2.4.2.3-
Patogênese...27
2.4.2.4-
Fatores Genéticos e Ambientais...29
2.5- Hepatite C, Interferon alfa e desordens tiroideanas...31
3-OBJETIVOS...34
4- MÉTODOS...36
5- RESULTADOS...40
6- DISCUSSÃO...45
7- CONCLUSÃO...54
8- REFERÊNCIAS...56
Apêndice 1...64
Apêndice 2...65
Apêndice 3...66
1-Introdução
0
1
)
'
7
>GF
6
)%
(
&
= (&B
>=N -9
0! 9
-5 J/P
/ J CFF@B
1
+
)
EA?
" "
Q
7
CF? "
>A?
3
CF
= 0 ( &
9 :
&!!* 9 ,
CFFA : N J5
CFFDB
;
"
%
)%
"
"<
"
7
"
GF?
+
"3
1 = - J 0
:
J!&
9 : ,
!R - 5
CFFA:
0&/!0
CFFFB
J%
" '
)%
"3
1 =01.B
,
7
;
>?
)%
=-!9
S-/
& 1/!
! ,- &/9!/-
! 0!
9 5/
=&,0B
CFFAB
/
)%
-
"
%
0
1
)%
"
+
7 3
TF?
%
# "
)6
)%
"
)
= -2((!9 ( : 9 2-,!-5
CFF@: 1 -!99
CFFTB !
"
'
"
+
)6
=1 -!99
CFFCB
2
)6
0
1
/
-
"
)
+
=
B
7
+
)%
"3
)%
/
%
7
;
$
)%
=( -1!99/J
:
" '
0
1
%
<
3
$
)
)%
)%
+
$
)%
+
=,!
!-99!
CFFFB
U
$
3
3
)
/
)%
)%
)
,
L 5 "
" =N J5
CFFC: ( - P2!99
>IIDB
*
)%
/
"
=
0
)
5 "
)%
B:
%
=
"
0
B =( J
1
CFFDB
)%
"
)
"
#"
3
7
7
"
+
= - J 0
:
J!&
9 :
,
!R - 5 CFFA: 1 -!99
CFFT: ( - P2!99
>IIDB
'
" "
)6
)
" "
)%
=( -1!99/J
:
2 ! 2 ( : ,!J0 ( 2
>IIA:
(/9
CFFE: 5!92 &/(! J
CFFIB
J
"
)
)%
#
"
)%
)
0
1 =*!-J J !P &
>IIEB
;
"
7V'
%
0
1 %
/
-
"
0
1 3
C >
"#
# $
%& & ' # (#) * *+ , " - . / # ) . 0# 12# $ !. $
"3
0
1 =01.B
1
>IEI
'
3
3
-J
"
7V'
Q
D
+
J
,
DF?
+
>
7
'
"
" '
0
1
> G? =N J5
: 9!! & &
CFFDB
>?
,
=-!9
S-/
&,0 CFFAB &
(& >GF
6
" "
01.
)
)%
"
)
#
=N0
CFF@B J
"
)
#
"
)%
+
7
.3
1
%
= J
J!99/
CFFEB
%
"
%
; #"
:
6
3
>IIC
7
+
%
"
:
#
%
"
= %
B
"
% #
#
)%
+
)%
"3
#
3
)%
D
E
)%
DF
GA?
%
#
>A
AF?
)%
AF
EA?
" "
Q
7
+
!
"
)
3
"
3
"
Q
)%
#
= 5
5 B
"
)
C
CF?
3
CF
" "
1
0
#
>
T?
= 0 ( &
9 : &!!*
9 ,
CFFA: N J5
: 9!!
& &
CFFD: &!!** 9 , :
0
*J 59!
0 CFF@: *
./10
CFFTB *
%
0
1
%
.3
/
'
7
=0/.B
"3
0
, =0,.B
#
#
= 0 ( &
9 : &!!*
9 ,
CFFA:
J
J!99/
CFFE:
& -
!-
CFFTB
%& &%' ( +.- $*
+
0
1 =
01.B
7
)
=J/0B !
)%
#
"
"
"3
TA
EF?
+
#
)%
#
#
#
)%
,
)6
%
)
%
#
=&!!** 9 ,
0
*J 59!
0
CFF@B
#
=!9/& B
7
01.
01. =!9/& B
3"
>IIF
)%
IA
II?
"
DW
EW
+
)%
&
01.
= 1-B
01. -J
#
"
<
O 7
01.
" :
:
)%
7
01.
"
#
= J
J!99/
CFFE: &!!** 9 ,
0
*J 59!
0 CFF@B
%& &3' )#. * # #0# * $* #
%
"
"
"
#
O
/
'
;# 7
"
)
#
)%
"#
:
3
"
)
#
)
:
%
)
'
:
)
)6
/
-
"
:
1
"
)%
'
3
)6
% O
)
@
#
;#
"
%
'
"
+ D
7 #
)
3
"
'
7
"
J
CFFT
7
1
)6
"
"
=&0!-( J
CFFGB
"
7 3
+
"
)%
;
"
"
)6
)%
01.
)
)%
1
)
7
01. -J
="3
1B
%
3"
+
D
=*
./10
CFFTB
"3
1
<
"
)
)%
&
"#
7
+
>
'
#
"
TE
"
+
"
TC AC?
#
+
C
@
+
=GD EE?B
#
CT
7
=9/J & R
CFF>: ( JJ&
CFF>:
*-/!
CFFCB
/
"
1
>II>
!
"
+
'
01. -J
D
+
)%
CF? 7
7V
)%
-
"
/
TF TA? =(1 02 10/& J
>IIE:
9/J -
>IIEB
"
)
1
" "
=/
)% B
"
)%
$
"
)%
)%
/
C
>EF
<
-
"
>FFF
"
)%
0
1
"
"
$
= J
J!99/
CFFE: 0
*J 59!
0 : &!!*
9 ,
CFFDB
/
)
#
>IIF =& - 11
>IIF:
-2((!9
(
9 2-,!-5
CFF@: 1 -!99
CFFTB
%&% . # 0# *.
0
/
=/*- B
3
+
)6
"
/
"
)%
"
"3
7
)%
"
)%
-J
"
"
+
%
)%
+
+
X
Y
=,2-( J
>IED: N J5
CFFCB
7
/
"
"
%
#
=&
-Z
>IIE:
J
J!99/
CFFEB *
/
#
)%
)%
)%
#
7V
)%
7
=& (2!9
1 !
CFF>B
1
" "
= !5 /J*B
+
%
"
"
)%
+
"
)6
)
#
"
Q
0
1 =1 -!99
CFFTB
U
7V'
7
#
"Q
)%
)%
)
O
0
3
9
!
'
(
> %
"
)
+
7V
=*
./10
CFFT:
J
J!99/
CFFEB
/
$
)%
*
>IEA 7
'
<
=*!J /( J
>IEAB
)%
)
0
1
/
>IIF
&
=& - 11
>IIFB
"#
)%
= J
J!99/
CFFT: -
/
>IID:
-!P/
/
>IIA: (
&2
>IIAB
*
&
01.
/
)%
)
"
+
7
3
01.
"
)%
/
=
+
B
<
/
"
+
)%
+
7
"3
)%
=*!-J J !P &
>IIEB
%&3'
4 5#
.
-
"
#
7
-J
"
)%
"3
'
)%
)%
" "
+
3"
7
)%
/
)
=&J!99 J
CFF>B
"3
)%
"3
-
"
+
)%
'
+
=
9RJ -
>IIEB
)%
-
"
/
0
1 %
%
#
=1 -!99
CFFCB !
>FF
0
1
3
7
/
-
"
"3
7
7
)
"
#
=( &
CFFEB
%&6' (*#.1
/ * )/.# (#
#- (# 7(
8
%&6& " - $*
)
)%
3
[[
)%
X
Y
!
>IFT
X
!"
#
J
0 M
0
>I>C
7
"
)%
3
+
<
+
= Z (/P2
(/J
J
! 5-
9
CFFEB
J
AF
3
N
MK
J
-
=- &! J - N/ !,&ZR
! >IADB 7
"
'
7
+
"
3
#
%
)
!
>IAE
<
7
=
5B
"
Q
=- /
/ ( : 1 ( ,!99
J
J/ 10
>IAEB
)
"
+
=
-J!&
CFFDB
%&6&% 9 * ( # / * )/.#
%&6&%& ' #:
0
= 0B
)
5 "
= 5B
)
+
)
+
=
B
1 Q
0
= 0B
#
7
=
R J 1 ( :
J/!9& 5 0
>IIDB &
'
7
"
F @
A
>FFF
"3
>A
CF "
7V
7
=. J !- 2(
(
:
2(,-/ 5! N ( CFFC:
Z (/P2
:
(/J
J :
! 5-
9
CFFEB
)%
'
)
7
+
)%
3
=N!! ( J
: (15-!5 -
( >IITB
"
)%
)%
)
Q
=( -N 0
CFF@B \
%
)
%
3
0
" "
$ %
> "
+
9
3
&;]
=-
-/52!& - : 5 J^ 9.!& *
:
-5!
CFFE: !JZ/J& - 1 : N!! ( J
CFFCB
" '
)
)%
"
"
#"
"
+
= 2J,-/ 5!
>IGG: . J !- 2(
>IIA: 0 99 N!99
CFFCB *
$
7
)%
)%
)%
7
)%
)
%
#"
)
%&6&%&%' ( ;
3"
=
B
#
3
+
=
B
5
=
B
%
%
IA?
"3
7
5
DF?
)
"
3"
"
&0
=0 99 N!99
CFFCB
CF
"
N M
+
=>>?
)% B
"
" "
&0
"
%
3
@E
"
=. J !- 2(
>IIAB
#
' 7
'
)%
3
<
+
"
=( P/
/
CFF@B
%&6&%&3' <
%
)
+ %
3
=
!B
%
3
+ %
&%
)
"#
7
(01 =
&
%
"
B
09
=
'
B
%
7
!
'
3
+
O
=
B
+
=
B
&0 = &0 -B
3
%
)
+
7
<
+
_
<
7
+
3
+
%
+
&
<
+
3
%
3
%
+
&
3
'
#
1 T
"
)6
>
C
+
>
=/9B
/
/9 C 7
)%
"
)%
+
+
C
=
+
B
)%
3
3
+
=
&0B
1
3
=
1B
+
3
7
&
)%
3
3
+
1
3
/
//
=(01B 7
%
#"
; )%
" )%
3
!
" )%
7
)%
3
3
3
,G
"
,G >
)%
>
7
,G C
)%
C
3
,G
1 CE
1 9
T =9
+
+
3
TB
)%
,G
1 CE
+
"
"
1 9
T 7
+
1 CE
)%
,G >
,G C !
)%
,G
1 9
T
)%
"
<
+
>
)%
3
,G >
1 CE
)%
3
0
U
<
C
)%
3
,G C
'
1 CE
)%
)%
#
)%
)
5 "
J
)
1 9
T
7
+
*
3
%
)%
3
+
1
"
3
+
<
+
)%
+
7
"
)
<
+
"
3
+
3
=
+
,B
7
' 7
<
+
)%
)%
3
%
3
)
)
>
C J
7
" "
0
7
C
"
+
,
&0
+
)
5 "
= Z (/P2
: (/J
J :
! 5-
9
CFFEB
%&6&%&6 9 0 + =
*
09
)
5 "
"
'
09
,E
09
-@
09
,LTD
09
,A
09
,>G
)6
'
+
+
)%
$
!
%
)
%
)
'
"#
;
7
7
)
+
(01
!
)6
)
+
(01
(01
" "
(01
#
)%
3
$
" "
)6
)%
3
'
$
)
+
#
7
)%
3
+
)%
3
(01
(01
3
)
)%
3
)6
3
(01 \
3"
7
+
)
3
+
7
%
7
+
3
+
%
09
"
"
3"
)6
3
7
6
3
(01
)6
*
.3
7
%
-T
3
" "
/
'
+
#
Q
2
"
%
/
'
+
)6
'
93
3
/
" "
"
)%
+
Q
J
'
#
+
)%
"
)%
(/
=
B
/
=
B 7
%
@
T =
J &
&/ 2
CFFGB !
,
3"
"
=` @FF
_
B
3"
7
"
=1 ( -5
CFFDB
7
" '
Q
1
3
7
"
7
"3
3"
Q
3
<
+
Q
"
)%
3
"
= !J5
CFFDB
#
)6
\
"
7
)%
$
+
)
<
+
%
"
7
)%
+
"3
+
+
)%
3
+
3
3
#
"3
'
%&>' "#
# $, . # 0# *.
0
# (# * (#.
* (# . &
)%
+
0
1
)
+
=
B
7
/
#
7V
=J
!!(
CFFIB
01.
)
/
-
"
)%
= -2((!9 ( : 9 2-,!-5
CFF@: 1 -!99
CFFTB
0
3
01.
)%
" )%
X
(
#
)%
)%
3
7V
3
7
<
+
)%
)%
7
/
%
)%
3
" "
)%
)%
= -
/
>IID: 1 - 11/
CFFAB
+
01.
/
$
" 3"
3
3
"
%
+
2
+
;
= - J 0
CFFGB
2
1
"
TD>
0
1
;
"
"
)%
"
&0
/
-
"
"
AE
)%
=>C D?B
= -BH C EA IA? /
"
1
)
=/1BH> D A >
)
"
" "
)%
= -HA E IA? /1H > C CG IB =Z!!
CFFDB
/ "
)%
+
/
-
"
"
)
%
7
;
)%
)%
=02 J5
>III:
N -
9 : ,/J5 R 2 - 5 CFF>B
-
;
"
"
<
7
'
)%
0
1
/
3"
7 3
)
'
*+
=1[19>FB J3"
1[19>F
"
7
"
CA
0
1
)
1[19>F
"
= aF FAB
7
7
)%
7
"
<
/
=-
J /
CFFGB
3-Objetivos
;
"
O
"
7 '
%
0
1 %
/
-
"
"
0
1
%
4- Métodos
*
"
CF>
7
%
"
%
7
@C
"
%
"
3
"
'
3
O
5
> = H CABO
0
1
/
-
"
:
5
C = H DCBO
0
1
:
5
@ = H ECBO
1
>
C
0
1 ;#
+
0
& " )
(
/
0
1 3
2 "
*
2
<
=01 2*2B 7
%
%
*
"
7
$
)
&0
* T
=
B
=
5B =
'
>B
>
/
C
>EF
_
<
-
"
= #
CAF
B
"
D
>
"
@
@I
>D @C
>F
@
>C
I
>@
CT
D
CT
TE
>
"
#
7
1
"
+
"
01 2*2
+
!
7
>
C
1
"
7
$
)
&0 * T
5 =
'
CB
3
CFFD
* "
CFFE
1
"
7
"
=
'
@B
!
/
U
'
(
/((2J 9/ ! CFFF
M
$
=
1B (
9
1
+
!2
"
'
O
&0 H F T
T F
2_
: * T H F E
> I
_ :
=
B H
@A /2_
:
=
5B H
TF
/2_
*
7
7
7
)%
= &0
B
%
7
"
93
)%
:
#"
.3
/
'
7
=0/.B
7
7
)
"
)%
+
$
)%
"
#
3
7
7
)%
(
1
>F FFF
"
7V'
7
A
'
#
"
<
"
#"
+
)%
,
1
"
"
7
F FA
L
#
!
"
1
'
\
7
2 "
*
2
<
_(5
FC_>F_CFFD
1!
5- Resultados
CA
>
0
1
/
-
"
DT?
@D?
7
"
CE
D@
TA IC
J
C
0
1
DC
AD TA?
T@ AT?
"
>E
GT
TE >C
7
7
EC
7
AG @>?
TC DE?
>G
GT
TD A>
J%
"
)
3
=
H F DCIIB
U
$
7 '
%
"
)
'
=
>B J
7 '
0
1
/
-
"
7
0
1
=
CB
Tabela 1- Frequência de desordens tireoideanas (TSH alterado e/ou anticorpos
antitireoideanos positivos) nos pacientes portadores de Hepatite C (com e sem
tratamento com alfa Interferon e Ribaverina) e o grupo controle.
Hepatite C em tto (G1) (n/%)
Hepatite C sem tto (G2) (n/%)
Grupo Controle (GC) (n/%) Com
desordens tireoideanas
10 (40%) 13 (20,96%) 26 (31,70%)
Sem
desordens tireoideanas
15 (60%) 49 (79,03%) 56 (68,29%)
Total de pacientes 25 (100%) 62 (100%) 82 (100%)
Tto= tratamento.
Tabela 2- Frequência de Hipotiroidismo nos pacientes portadores de Hepatite C
(com e sem tratamento com alfa Interferon e Ribaverina) e o grupo controle.
Hepatite C em tto (G1) (n/%)
Hepatite C sem tto (G2) (n/%)
Grupo Controle (GC) (n/%) Com Hipotiroidismo 9 (36%) 10 (16,12%) 13 (15,85%)
Sem Hipotiroidismo 16 (64%) 52 (83,87%) 69 (84,14%)
Total de pacientes 25 (100%) 62 (100%) 82 (100%)
Tto= tratamento.
Hipotiroidismo- TSH > 4,0 microUI/ml, com anticorpos presentes ou ausentes
G1 x GC (p= 0,0291) G2 x GC (p= 0,96) G1 x G2 (p= 0,0423)
U
$
)
%
)
= H F IAAB=
@B
1
;
"
3"
"
#
3
"
"
_
7
>FF
2/_ 9
%
"
)
7
$
" '
J
>
=E?B
"
3
"
' =T E@?B
C
=I GA?B
= H F AT@GB J%
3
Frequência de anticorpos antitireoideanos nos pacientes portadores de
Hepatite C (com e sem tratamento com alfa-Interferon e Ribaverina) e o grupo
controle.
0 ? <
&
" : $
7 @A8
" : $
7 @A8
+ :
$
7 @A8
: ' * C =E?B T =D TA?B >>=>@ T>?B
: ' > =T?B T =D TA?B I =>F IG?B
' *
'
F =F?B @ =T E@?B D =G @>?B
' *
@ '
@ =>C?Bb A =E FD?Bb >T =>G FG?Bb
: CA =>FF?B DC =>FF?B EC =>FF?B
Acs.: Anticorpos; tto: tratamento; Anti-TPO: Anticorpos antiperoxidase;
Anti-Tg: Anticorpos Antitireoglobulina. * (p= 0,955)
#
>
7 '
0
1
7
/
-
"
3"
Gráfico 1- Frequência de Hipotiroidismo e de Anticorpos Antitireoideanos em
portadores de Hepatite C (com e sem tratamento com Interferon alfa e Ribaverina)
e o grupo controle.
0% 5% 10% 15% 20% 25% 30% 35% 40%
Hepatite C em tto Hepatite C sem tto Grupo Controle
Hipotiroidismo
6- Discussão
.#
;#
)%
0
1
/
-
"
)
+
=
B
" '
"
#"
3
)%
=1 -!99
CFFTB
(
" %
7V'
A
>C?
"
=( -1!99/J
:
2 ! 2 ( :,!J0 ( 2
>IIAB
1
=12&
->IIGB
"
>FT
0
1
AE
0
1
/
IE
#"
)%
G G?
>A A?
> @?
"
"
/
)%
!
%
3"
7 '
0
1
/
-
"
" "
"
$
" '
#"
7
)6
"
#
)%
"
/
_
-
"
=, 2 /J
>II@: Z
(
>IIT: J 5 R (
>IIT: Z ,,
CFFDB
N
>FI
0
1
/
"
)%
)%
E T?
7
)
3
"
)% =N
J ,!
>IITB
%
7V'
"
)%
/
GF
0
1
)%
3
*
)6
7
#
)%
" '
"3
#"
!
CFF>
/
%
3
"
)%
#
,
=DE?
"3
3"
#
@FF
_9B J
(
5
>FF?
"
AFF
_9
7
#
7
>F _
=- &&/
CFF>B !
6
&%
7
0
+
;
)%
J
7
)%
"
#
7
"#
)6
)%
Q
)%
7
"
= 2 - !
CFFTB
)%
(
&
,
3
"
7V'
"
$
A _
>AF
=N0
CFFEB
" '
)%
+
"
"
)%
2
#
1 Q
/
#
=*!/,!9( JJ
CFFGB
"
)%
-
+
=5 J^ 9.!&
CFFIB J
7V'
"
!
,
)%
)
0
1
/
"
>>>
0
1
!
7
)%
/
-
"
=
- Jc
CFFFB
/
-
"
=
- Jc
CFFFB
" %
=
J -
!
CFFEB
U
$
0
1
" "
%
"
7V'
C
TE? =12& -
>IIG:
*!-J J !P &
>IIE: ,!
!-99!
CFFF:
-2((!9 ( :
9 2-,!-5
CFF@B
"
"3
#"
0
,
2
" %
>E
0
1
>>
= J
J!99/
CFFDB &%
"#
+
)%
)%
+
"3
1
)%
/
+
"3
= -2((!9 ( : 9 2-,!-5
CFF@: *!--/
CFFEB
+
"3
1
)%
)%
3
"3
1
+
+
=
(! R : ,9 1Z1
-:
Z!J
J CFFGB ,
)
"3
1
+
01.
"
1-=
K
1
-
B
7
01.
+
)%
=, -
9 (\
CFFEB
!
%
)
7 '
7
0
1
7
0
1 ;
" "
" '
)%
J
3
C>A
0
1
" '
#
)%
E?
%
.3
1
" "
=J 2N R
>IIEB:
*
=*9 -! J/
CFFDB
-
"
>@F
0
1
)%
+ D
C> >?
/
" "
>F @?
7
%
"
)%
%
= HF >TCB
+
"3
1
)
=- 11
CFF>B
" '
0
1
=
!- J
>IIC: - J
>II@B !
<
d
3
)6
%
#
"3
=( - P2!99
>IIDB
%
3
)%
"
=/( 5 N
>IIAB
)
7
"
0
1
3
7
%
" "
)
=( -1!99/J
:
2 ! 2
(
,!J0 ( 2
>IIA:
J &
&/ 2
CFFG:
02 J5
CFFD: 1 -!99
>IIAB
U
$
)
"
&0
%
)
3
'
7
"
"
"
7
)%
0
1
/
-
"
"
%
7 '
0
1
=@D?B
7
7
0
1
=>D >C?B
<
3
= HF FTC@B
/
-
"
)%
J
%
)6
3
!
(
"
)%
/
"
=
0
)
5 "
B
%
=
"
"
B =( J
1
CFFDB
"
"
7V'
7
"
#
/
-
"
7
J
"
)%
"
3
#
"
=N J5
CFFC: , 0,
CFFD:
- Jc
CFFF: J
!!(
CFFIB
!
%
"
ED
0
1
/
>T
0
1
)%
"
+
@@ G?
7
/
G >?
7
7
/
"
"
3"
= &2, /
>IIEB
%
"
D
>>T
0
1
/
/
" "
=1 -!99
CFF>B /
L
)%
" "
/
=/( 5 N
>IIAB
7
" "
)%
<
/
+
"
"
$
0
"
= (!J ( -/
>IIEB
/
-
"
7
" '
)%
1
1
GC
0
1
/
-
"
TC
/
3
7
)%
-
"
/
%
%
=1 -!99
CFFCB
-
"
#
7
+
7
/
%
" "
"
T @
" "
=
B
7V'
" )%
> 7
= 1 -!99
CFFTB
2
"
7 '
0
1
7V'
%
!
'
)
"3
" "
" "
+
"3
1
)%
7
)%
/
%
#
%
)
= - J 0
CFFG: Z 0 9 Z 0 :
5-!!J&
J * & : R!
,
>IIG:
!2 &10
>IIGB !
7
/
+
+
7
'
)%
=1 -!99
CFFT:
- J 0
:
J!&
9 : ,
!R - 5
CFFAB
"
/
%
" "
"
>
"
7
7V
)%
7
"
#
"
#
3"
7 '
;# 7
)%
+
" "
"
)%
)%
)%
<
)%
)
)%
"3
1
" )%
+
0
(
#
)%
/
+
)%
"
$
)%
+
7
"3
= - J 0
:
J!&
9 : ,
!R - 5 CFFA: 1 -!99
CFFTB
5
/
"
)%
)
01.
3
"
"
>> >?
)
0
1
C G?
)
"
=--B
T AD !
"3
1
" "
)
%
=/J
9*/
CFFEB J%
+
%
7
<
)%
"
+
3
<
7
01.
7
"
;
#"
=
+
)%
7
)%
J%
3"
7 '
)
+
0
1
/
-
"
0
1 7
"
AKAMIZU, T.; AMINO, N.; DE GROOT, L.J. Hashimoto’s thyroiditis. In; De Groot L J. Thyroid Disease Manager. Chapter 8. Disponível em < http://www.thyroidmanager.org> Acesso em 28 set. 2008.
AMENOMORI, M.; MORI, T.; FUKUDA, Y.; SUGAWA, H. et al. Incidence and characteristics of thyroid dysfunction following Interferon therapy in patients with chronic Hepatitis C . Int Med.,
Kioto, v. 37, n. 3, p. 246-252, Oct. 1998.
ANDRADE, L.J.O.; ATTA, A.M.; JUNIOR, A.D.; PARANÁ, R. Thyroid dysfunction in Hepatitis C individuals treated with Interferon alfa and Ribavirin – a Review. Braz J Infect Dis., Salvador, v. 12, n. 2, p. 144-148, Apr. 2008.
ANTONELLI, A.; FERRI, C.; PAMPANA, A.; FALLAHI, P. et al. Thyroid disorders in chronic hepatitis C. Am J Med. Pisa, v. 117, p. 10-13, Jan. 2004.
ANTONELLI A.; FERRI, C.; FALLAHI, P.; FERRARI, S.M.; GHINOI,A.; ROTONDI, M.; FERRANNINI, E. (Review) Thyroid disorders in chronic hepatitis C vIrus infection. Thyroid, Pisa, v. 16, n. 6. p. 563-572, 2006.
ANTONELLI, A.; FERRI, C.; GALEAZZI, M.; GIANNITTI, C.; MANNO, D.; MIELI-VERGANI G. et al. HCV infection: pathogenesis, clinical manifestations and therapy. Clin Exp Rheumatol., Pisa, v. 26, n. 48, p. S39-47, Jan- Feb. 2008.
BARTOLOMÉ, J.; RODRIGUES-IÑIGO, E.; QUADROS, P.; VIDAL, S.; PASCUAL-MIGUELAÑEZ, I. et al. Detection of hepatitis C virus in thyroid tissue from patients with chronic HCV infection. J Med Virol., Madrid, v. 80, n. 9, p. 1588-1594, Sep. 2008.
BAUDIN, E.; MARCELLIN, P.; POUTEAU, M.; COLAS-LINHART, N.; LE FLOCH, J. P.; LEMMONIER, C.; BENHAMOU, J. P.; BOK, B. Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis. Clin Endocrinol., France, v. 39, n. 6, p. 657-661, Dec. 1993.
BETTERLE, C.; FABRIS, P.; ZANCHETA, R. et al. Autoimmunity against pancreatics islets and other tissues before and afther interferon alpha therapy in patients with Hepatitis C virus chronic infection. Diabetes Care, Itália, v. 23, p. 1177-1181, Aug. 2000.
BOHBOT, N.L.; YOUNG, J.; ORGIAZZI, J.; BUFFET, C. et al. Interferon –induced hyperthyroidism: a three stage evolution from silent thyroiditis towards Grave’s disease. Eur J Endocrinol.,
France, v. 154, n. 3, p. 367-372, 2006.
BURMAN, P.; TOTTERMAN, T.H.; OBERG, K.; KARLSSON, F.A. Thyroid autoimmunity in patients on long term therapy with leukocyte-derived Interferon. J Clin Endocrinol Metab, New York, v. 63, n. 5, p. 1086-1090, Nov. 1986.
CARACCIO, N.; GUANNINI, R.; CUCCATO, S. et al. Type I interferons modulate the expression of thyroid peroxidase, sodium/iodine symporter, and thyroglobulin genes in primary human thyrocyte cultures. J Clin Endocrinol Metab, Pisa,v. 90, n. 2, p. 1156-1162, Feb. 2005.
CARELLA, C.; AMATO, G.; BIONDI, B.; ROTONDI, M.; MORISCO, F. et al. Longitudinal study of antibodies against thyroid in patients undergoing interferon-alpha therapy for HCV chronic hepatitis. Horm Res, Italy, v. 44, n. 3, p. 110-114, 1995.
CARELLA, C.; MAZZIOTTI, G.; MORISCO, F.; MANGANELLA, G.; ROTONDI, M. et al. Long-trem outcome of Interferon alpha induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment. J Clin Endocrinol Metabol., Italy, v. 86, n. 5, p. 1925-1929, 2001.
CARELLA, C.; MAZZIOTTI, G.; MORISCO, F. et al. The addition of ribavirin to Interferon-alpha therapy in patients with Hepatitis C Virus-related chronic hepatitis does modify the thyroid autoantibody pattern but increased the risk of developing hypothyroidism. Eur J Endocrinol., Nápoles, v. 146, p. 743-49, Feb. 2002.
CARELLA, C.; MAZZIOTTI, G.; AMATO, G.; BRAVERMAN, L.E.; ROTI, E. Interferon alpha- related thyroid disease: Pathophysiological, epidemiological and clinical aspects. J Clin Endocrinol Metabol., Milan, v. 89, n. 8, p. 3656-3661, Apr. 2004.
CHOO, Q.L.; KUO, G.; WEINER, A.J. et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science , New York, v. 244, p. 359-62, Apr. 1989.
CUSTRO, N.; MONTALTO, G.; SCAFIDI, V.; SORESI, M.; GALLO, S.; TRIPI, S.; NOTARBARTOLO, A. Prospective study on thyroid autoimmunity and dysfunction related to chronic hepatitis C and interferon therapy. J Endocrinol Invest., Italy, v. 20, n. 7, p. 374-380, Jul-Aug. 1997.
DAYAN, C.M.; DANIELS, G.H. Chronic Autoimmune Thyroiditis. N Engl J Med., USA, v. 335, n. 2, p. 99-107, Jul. 1996.
DEUTSCH, M.; DOURAKIS, S.; MANESIS, E.K.; GIOUSTOSI, A.; HESS, G.; HORSCH, A.; HADZIYANNIS, S. Thyroid abnormalities in chronic viral Hepatitis and their relationship to Interferon alpha therapy. Hepatology, Greece, v. 26, n. 1, p. 206-210, Mar. 1997.
DUARTE, G.C.; TOMIMORI, E.K.; BORIOLI, R.A.; CATARINO, J.E.F. ; CAMARGO, R.Y.A.; MEDEIROS-NETO, G.. Avaliação ultra-sonográfica da tireóide e determinação da iodúria em escolares de diferentes regiões do Estado de São Paulo. Arq Bras Endocrinol Metab., São Paulo, v. 48, n. 6, Dec. 2004.
FATTOVICH, G.; STROFFOLINI, T.; ZAGNI, I.; DONATO F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology, Verona, v. 127, n. 1, p. S35-S50, Nov. 2004.
FEIBELMANN, T.C.M.; GONÇALVES, F.T.; DAUD, M.S.; JORGE, A.S.; MANTESE, S.A.O.; JORGE, P.T. Avaliação da associação entre Doença Autoimune de Tireóide e Urticária Crônica Idiopática.
Arq Bras Endocrinol Metab , São Paulo, v. 51, n.7, p. 1077-83, 2007.
FERNANDEZ SOTO, L.; GONZALES, A.; ESCOBAR-JIMENEZ, F.; VAZQUEZ, R. et al. Increased risk of Autoimmune Thyroid Disease in hepatitis C vs hepatitis B before, during and after discontinuing Interferon therapy. Arch Intern Med., Granada,v. 158, n. 13, p. 1445-1448, July 1998.
FERRI, S.; MURATORI, L.; LENZI, M; GRANITO, A.; BIANCHI, F.B.; VERGANI, D. HCV and autoimmunity. Curr Pharm Des., London, v. 14, n. 17, p. 1678-1685, 2008.
FLOREANI, A.; BETTERLE, C.; CARDERI, I.; PRESSOTO, F.; PEDINI, B.; MOSCON, A. et al. Is Hepatitis C virus a risk factor for thyroid autoimmunity? J Viral Hepatol., Italy, v. 13, n. 4, p. 272-277, Apr. 2006.
FRIED, M.W.; SHIFFMAN, M.L.; REDDY, K.R. et al. Peginterferon alpha-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med., USA, v. 347, n. 13, p. 975-982, Sep. 2002. GELU-SIMEON, M.; BURLAUD, A.; PELLETIER, G.; BUFFET, C. Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of Hepatitis C. J Gastroenterol.,
France, v. 15, n. 3, p. 328-333, Jan 2009.
GONÇALVES, F.T.; FEIBELMANN, T.C.M.; RANZA, R.; DAUD, M.S.; TALIBERTI, B.H.B.; PINTO, R.M.C.; JORGE, P.T. Autoimmune thyroiditis and Rheumatoid Arthritis: Is there realty an association? Endocrinologist, v.19, n.1, p. 31-34, Jan 2009.
HOLLOWELL, J.G.; STAEHLING, N.W.; FLANDERS, W.D.; HANNON, W.H. et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. USA, v. 87, n. 2, p. 489-499, Feb. 2002.
HOOFNAGLE, J.H.; SEEFF, L.B. Peginterferon and Ribavirin for chronic Hepatitis C (Clinical Therapeutics). N Eng J Med, Massachusetts, v. 355, n. 23, p. 2444-2451, Dec. 2006.
HSIEH, M.C.; YU, M.L.; SHIN, S.J.; DAI, C.Y.; LIN, Z.Y.; HSIEH, M.Y. et al. Virologic factors related to Interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C. Eur J Endocrinol. Taiwan, v. 142, n. 5, p. 431-437, May. 2000.
HUANG, J. F.; CHUANG, W.L.; DAY, C.Y.; et al. The role autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon alpha and ribavirin combination therapy. J. Viral Hepatol., Taiwan, v.13 n. 6 p. 396-401, jun. 2006
IMAGAWA A.; ITOH, N.; HANAFUSA, T.; ODA, Y. et al. Autoimmune endocrine disease induced by recombinant Interferon alpha therapy for chronic active type Hepatitis. J Clinl Endocrinol Metabol., Japão, v. 80 n. 3 p.922-26, 1995.
INDOLFI, G.; STAGI, S.; BARTOLINE, E.; SALTI, R.; DE MARTINO, M.; AZZARI, C.; RESTI, M. Thyroid function and anti- thyroid autoantibodies in untreated children with vertically acquired chronic hepatitis C virus infection. Clin Endocrinol. (Oxf) Italy, v. 68, n. 1, p. 117-21, 2008.
JAMIL,K.M.; LEEDMAN,P.J.; KONTORINIS,N.; TARQUINIO,L.; NAZARETH, S. et al. Interferon-induced thyroid dysfunction in chronic hepatitis C. J Gastroenterol Hepatol., Austrália, Dec 2008 [Epub ahead of print]
KABBAJ, N.; GUEDIRA, M.M.; EL ATMANI, H.; EL ALAOUI, M. et al. Thyroid disorders during Interferon alpha therapy in 625 patients with chronic hepatitis C: a prospective cohort study.
Ann Endocrinol., Rabat, v. 67, n. 4, p. 343-347, Sep. 2006.
KEE, K.M.; LEE, C.M., WANG, J.H.; TUNG, H.D. et al. Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of Interferon and Ribavirin: Incidence, associated factors and prognosis. J Gastroenterol Hepatol, v. 21, n. 1, p. 319-326, Jan.2006.
KODAMA, T.; KATABAMI, S.; KAMIJO, K.; KATANUMA, A.; YAMASHITA, K.; AZUMA, N.; TAMAKI, T.; YACHI, A. Development of transient thyroid disease and reaction during treatment of chronic hepatitis C with Inteferon. J Gastroenterol., Japan, v. 29, n.3, p. 289-292, Jun. 1994.
KOH, L.K.H.; GREENSPAN, F.S.; YEO, P.P.B. Interferon-alpha induced thyroid dysfunction: Three clinical presentations and review of the literature. Thyroid, Singapore, v. 7, n. 6, p. 891-896, 1997.
LINDSAY, K.L.; TREPO, C.; HEINTGES, T. et al. A randomised, double-blind trial comparing pegylated interferon alpha-2b to interferon alpha-2b as initial treatment for chronic hepatitis C.
Hepatology, Califórnia, v. 34, n. 2, p. 395-403, Aug. 2001.
MANDAC, J.C.; CHAUDHRY, S.; SHERMAN, K.E.; TOMER, Y. The clinical and physiological spectrum of interferon-alpha induced thyroiditis: Toward a new classification. Hepatology, Cincinnati, v. 43, n. 4, p. 661-672, Apr. 2006.
MANNS, M.P.; McHUTCHISON, J.G.; GORDON, S.C. et al. Peginterferon alpha 2b plus Ribavirin compared with interferon alpha 2b plus ribavirin for initial treatment of chronic hepatitis C; a randomized trial. Lancet , Hannover, v. 358, n. 9286, p. 958-965, Sep. 2001.
McHUTCHISON, J.G.; GORDON, S.C.; SCHIFF, E.R.; SHIFFMAN, M. L. et al. Interferon alpha 2b alone or in combination with Ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy. N Engl J Med, USA, v. 339, n. 21, p. 1485-1492, Nov. 1998.
MARAZUELLA M.; MONZONT, L.G.; ARRANZ A.; BOURQUET, M.J.; MORENO-OTERO, R. Thyroid Autoimmune disorders in patients with chronic hepatitis C before and during Interferon alpha therapy. Clin Endocrinol. ,Oxford, v. 44, p. 635-642, Mar. 1996.
MARCELLIN, P.; POUTEAU, M.; BENHAMOU, J. P. Hepatitis C virus infection, alpha interferon therapy and thyroid dysfunction. J Hepatol., France, v. 22, p. 364-369, 1995.
MARWAHA, R.K.; SEN, S.; TANDON, N.; SAHOO, M. et al. Familial aggregation of autoimmune thyroiditis in first- degree-relatives of patients with juvenile autoimmune thyroid disease.
Thyroid, Delhi v. 13, n. 3, p. 297-300, Mar. 2003.
MASSOOD, N.; GHORI, R.; MEMON, A.; MEMON, S.; MEMON, K.I. et al. Frequency of thyroid disorders during Interferon and Ribavirin therapy in chronic hepatitis C infection. J Coll Physicians Surg Pak., Hyderabad, v. 18, n.6, p. 347-351, Jun. 2008.
MAZZIOTTI, G.; SORVILLO, F.; IORIO, S.; CARBONE, A.; ROMEO, A et al. Grey-scale analysis allows a quantitative evaluation of thyroid echogenicity in the patients with Hashimoto’s thyroiditis. Clin Endocrinol., Italy, v. 59, n.2, p. 223-229, Aug. 2003.
NADEEM, A.; ASLAM, M.; KHAM, D.A.; HUSSAIN, T.; KHAN, S.A. Effects of combined interferon alpha and ribavirin therapy on thyroid functions in patients with chronic hepatitis C. Coll Physicians Surg Pak, v. 19, n. 2, p. 86-89, Feb 2009.
NAGAYAMA, Y.; OHTA, K.; TSURUTA, M.; TAKESHITA, A.; KIMURA, H. et al. Exacerbation of thyroid autoimmunity by Interferon alpha treatment in patients with chronic viral hepatitis: our studies and review of the literature. J Endocrinol., v. 41, n. 5, p. 567-572. Oct. 1994.
NDUWAYO, L.; BACQ, Y.; VALAT, C.; GOUDEAU, A.; LECOMTE, P. Thyroid function and autoimmunity in 215 patients seropositive for the Hepatitis C virus. Ann Endocrinol., France, v. 59, n. 1, p. 9-13. Apr. 1998.
ORLENT, H.; VROLIJK, J. M.; VELDT, B. J.; SCHALM, S. W. Hepatitis C 2002 guidelines: summary and annotations. Scand J Gastroenterol suppl., Rotterdan, v. 239, p. 105-110, 2003.
PAPANASTASIOU, L.; VATALAS, I.A.; KOUTRAS, D.A.; MASTARAKOS, G. et al. Thyroid autoimmunity in the current iodine environment. Thyroid, Athens, v.17, n. 8, p. 729-739, Oct. 2007.
PARANÁ, R.; CRUZ, M.; LYRA, L.; CRUZ, T. Subacute thyroiditis during treatment with
combination therapy (Interferon plus Ribavirin) for hepatitis C virus. J Viral Hepatitis, Brasil, v. 7, p. 393-395, Apr. 2000.
PARANÁ, R.; CRUZ, M.; SANTOS-JESUS, M.; FERREIRA, K.; CODES, L.; CRUZ, T. Thyroid disease in HCV carriers undergoing antiviral therapy with Interferon plus Ribaverin. Braz J Infect Dis.,
Brasil, v. 4 n. 6, p. 284-290, Dec. 2000.
PARNES, O. Autoimmune disease. Lancet, USA, v. 367, n. 9508, p. 389 (1). Feb. 2006.
PATERON, D.; HARTMANN, D.J.; DUCLOS-VALLEE, J.C.; JOUANOLLE, H.; BEAUGRAND, M. Latent autoimmune thyroid disease in patients with chronic HCV hepatitis. J Hepatol. v. 16, n. 1-2, p. 244-245, Sep. 1992.
POLYNARD, T.; MARCELLIN, P.; LEE, S.S. et al. Randomised trial of interferon alpha 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha 2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet, Paris, v. 352, n. 9138, p. 1426-1432, Oct. 1998.
PREZIATI, D.; LA ROSA, L.; COVINI, G.; MARCELLI, R.; RESCALLI, S., et al. Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha 2-a. Eur J Endocrinol., Milan, v. 132, n. 5, p. 587-593, May. 1995.
PRUMMEL, M.; LAURBERG, P. Interferon-alpha and Autoimmune Thyroid Disease. Thyroid, Amsterdam, v. 13, n. 6, p. 547-551, Aug. 2003.
RELATÓRIO DO GRUPO DE ESTUDOS DA SOCIEDADE BRASILEIRA DE HEPATOLOGIA. Epidemiologia da infecção pelo vírus da Hepatite C no Brasil. Disponível em
WWW.sbhepatologia.org.br.
