. .

: < 6
: > 6

(%)

0
5-10
> 85

D
E
F
G

45
0

A
B
C
D
E

HAV
HBV
HCV
HDV
HEV

(Kb)

RNA
DNA
RNA
RNA
RNA

7,5
3,2
9,4
1,7
7,5

HbsAg
+
HBsAg
-

Picorna
Hepadna
Flavi
Plant
Calici

A
O (HAV, HBV, HCV, HDV,
HEV)
H

(CMV, Epstein-Barr,
, parvo, herpes 6 )
, ,
I

K 5-10%
)

(,

( ).

(HBV, HDV, , . Wilson.)







(
)


, , ,
, , ,
,
, ,
.
,
.

,

(10-20%)

IANH
OEIA HATITIA
ALT>10XA
I .

,

H X. Quick.
A: , ,
.

IANH
OEIA HATITIA

-HAV IgM
-HBc IgM (+/- HBsAg)
- IgM
-HCV
IgM


OEIA HATITIA

18%

32%

5%
9%
36%

HCV
HBV
HAV

: C
: -
,

Quick /3
:
Quick, .






5 - 14
( 50%,
1-2%)

Anti-HAV



,
(- ),
)
,
(..
, )
()
(.. ,
,
(T)
O )



M
.

M
A
T

E:
.

10 .

anti-HAV (%)

100

50

10
60

20

()

30

40

50

Prevalence of Anti-HAV (%)

PREVALENCE CHANGE WITH

IMPROVEMENT IN HYGIENE
100
80
60
40

Improvement
In Hygiene

20
0

10

20

30

40

Age (Years)

50

60

70

TO KINIKO AMA TH OEIA

HATITIA A

A (A-HAV IgM +, ALT ).

Y (A-HAV IgM +, ALT +,
-).
K (A, I,
K).
E .
K

 -

()

(
)

30
15-50
E
.


<6 : <10%
6-14 : 40%-50%
>14 : 70%-80%

(05-1,5%)

antiHAV

ALT

HAV

IgM anti-HAV

12

24




50%

5%
<3

10%

4-6
>6
()

POHH TH HATITIA A
:
- - (0,02-0,06 ml/kg),
6

E :
- E

1 min

96%

100%





(
)






,
,

O IO HATITIA E
RNA-, calici-.
, 27-34 nm, ,
.
O
(, , ).
E HEVAg .

35

HATITIA E
E: I, A, M.
.
A: -HEV IgG (+) 1-5%.
K ().
(swine, sheep, rats)
E 2-9 ( 6) .
O . .
O A.
X 50%.
20% .
36

IANH TH HATITIA E

: ANTI-HEV IgM, ANTI-HEV IgG

(ELISA)
OEIA: -HEV IgM & -HEV IgG (+)
AAIA - IAEIA - ANOIA: -HEV IgG (+)
: HEV RNA

 HEV

()
HEV-RNA

HEV

HEV-RNA

Anti-HEV IgG
ALT
Anti-HEV IgM

HEV

HEV-RNA
Anti-HEV IgG
ALT

POHH TH HATITIA

: -

 Hepadna-

Duck
Hepatitis B Virus

Tree Squirrel
Hepatitis Virus

Hepatitis B Virus

Ground Squirrel
Hepatitis Virus

Woodchuck
Hepatitis Virus

 B
2 ,

350
100 HIV
To 25-40% +/-
1

HV
(300.000/)

 HBV
HBV
HLA

HLA
+
CD8
-

HBcAg
HBV-


30000

25000

HCV

20000
15000
10000
5000
0
75 76 77 78 79 80 81 82 83 84 85 86 87 88
89 90 91 92

kuda K, Liver Cancer, 1997

 O
HBV

HBsAg
>8 % -
2-7 % -
< 2 % -

H H H O
HBV

~ 2 million Asins

~ 930.000
Europeans

~
400.000
South
America
ns
HBsAg
>8 % -

~ 350.000
Africans

2-7 % -

Immigration numbers
< 2 % -
summed by continent from
1. World Health Organization, Geographic Prevalence of HBsAg. Data
from 1996 (unpublished)
1996-2002
http://www.who.int/vaccines-surveillance/graphics/htmls/hepbrev.htm. Accessed: Semptember 13, 2004

2. 2002 Yearbook of Immigration Statistics.

http://uscis.gov/graphics/shared/aboutus/statistics/IMM02yrbk/IMM2002list.htm. Accessed: Semptember 2

 HBV

-N: 0,14-0,53%
: 2-3%
: >3%

100
HIV

 HBV


HBV
(
)

70%

30%

<1%

3-5%

100
%

100

HBV

80

60

60

80

40

20

40

20

0
1-6

7-12

1-4

HBeAg

Anti-HBeAg

anti-HBc

HBsAg

IgM anti-HBc

52
4 8 12 16 20 24 28 32 36

Anti-HBs

100

(6
)

()

HBeAg

anti-HBe

HBsAg

Anti- HBc

IgM anti- HBc

0 4 8 12162024283236 52


HBV

IANH TH XPONIA HBV

OIMH
O (HBsAg,
HbeAg)
I (HBV-DNA )
A
()
H ()

IANH TH XPONIA HBV

OIME
HBsAg (+)
A-HBc (+)
HBeAg (+) (-)
A-HBe (+) (-)
HBV DNA
A-HBc IgM

 HBV

HBsAg

Anti-HBs

HBeAg

Anti-HBe

/
( ),

Anti-HBc

Anti-HBcIgM

 HBV
HBsAg
HBeAg (-)/-HBe

IgM

HBcAg

-HBc

ALT HBV-DNA

HBeAg (+)

()

() (KIPHKK)

()
(KIP)

()
(KIP-HKK)

+
(KIP-)

(-)

HBV DNA

ALT

Anti-Hbc
IgM


HBeAg HBsAg

HBeAg0% - 20% (~10%)

HBsAg0% - 1.5% (~1%)


B
HBV

20-40%

1-3%/
H

I I
H-H O

Xo

HBsAg (+)

sAg (+)
ALT
HBeAg (+/-)

HBeAg (-)
HBV DNA
(<2000IU/ml)

ALT: ..

HBV DNA
(>2000IU/ml)


HBV

30-50

()

O A
HBV

HBV


HBV


Yeast Gene for
Origin of
Replication
Selection

HBsAg Gene

Yeast Promoter

% Reduction of cases

0
10

High-risk group

20
30
40

Universal infant

50
60
70
80
90

Adolescent

Infant & Adolescent

100
1990
Year

2000
Year

Infant/
2015 Adolescent/
Year High-risk group

 H Y

, /100 000

70
60
50
40
30
20

10
0
78

79

80

81

82

83

84

85

86

87

Margolis HS, 1991




: 1998

, 11-12


: 3 0,1,6

4 0,1,2,12

K : 0,1,6 0,1,2,12
( 1 )

4 40g 0,1,2,6



HBsAg



HBV & HAV;
X ;
;

;


,
,

ALT

AMEOI TH EPAEIA
TH
XPONIA HBV OIM
K :
HBV DNA <104-5
o/ml
HBeAg (-), +/- -HBe
:
ALT:
I:
( ?)

ATEPOI OI
TH EPAEIA
HKK.
B .
E
E HBV
HBsAg (-), -HBs (+), HBV DNA (-)
PCR , cccDNA (-)
.

 XPONIA
HATITIA B
(K: -2 Roferon
A, -2 Intron-A : -2
Pegasys, -2 PegIntron)
()
(Zeffix)

A (Hepsera)

E (Baraclude
03/05)

, HIV

OIOI AENEI XPEIAZONTAI

EPAEIA
E : HBV
DNA > 104-5
A ALT
E : HBc IgM > 0.200.
I: +/-



% Survival
100

79
% et al
Perrillo

80

65
Villeneuve
et
%

60

55%
Cirrhosis1

al

40
20

14%
Decompensated cirrhosis2

0
0

Years1 Weissberg et al, 2De Jongh et






ALT + IgM anti-HBc
/2-3 2 /6-12

EASL Consensus, J Hepatol 03

DELTA AGENT
HBsAg
RNA
35- 40 nm
Antigen

MODES OF HDV INFECTION

Coinfection

D
Superinfection

B
D

CLINICAL SEQUELAE OF HDV

INFECTION
Coinfection

Superinfection

Acute hepatitis

Acute exacerbation

Uneventful
recovery

Fulminant
hepatitis

Chronic
hepatitis

Cirrhosis
and HCC

HDV CO-INFECTION

ALT
HDV RNA
IgM anti-HDV

IgG anti-HDV

HDAg
IgM anti-HBc
HBsAg
Months

IgG
IgG anti-HBc
anti-HBc
anti-HBs
anti-HBs

HDV SUPERINFECTION
ALT
HDV RNA
IgM anti-HDV

IgG anti-HDV

HDAg
HBV DNA
HBsAg, IgG anti-HBc
Years

IANH TH XPONIA HDV

OIMH
A-HDV (+) >1/1000
A-HDV IgM (+)
HDV RNA (RT-PCR)
HDAg (EIA)
HDAg ,

2-20%

90-95% 2-7%

70-95% 5-10%

70-80%

10-20%


HEPACI-
-
-
-

Flaviviridae

--
Hepaci-

St Louis
HCV I-VI G/GBV-C GBV-B

CBV-A

HCV Epidemiology and Impact on Intravenous Drug User Risk and Screening

HCV
Genotypes 1-6
75% genotype 1 in United
States
Genotype 3 common in IDUs in
Europe and Australia

Most important predictor of

IFN treatment response
Does not predict amount of
liver damage

1a

NHANES III
1b
2a
2b
3a
6%

1% 2%

10%
3%
51%

27%
NIH Consensus Development Conference Statement. Bethesda, Md:
National Institutes of Health; June 10-12, 2002. Nainan OV, et al.
Gastroenterology. 2006;131:478-484.

clinicaloptions.com/hep

 HCV

,
70 % - 90 %

~ 50 .
~ 5 .
~ 4 .
~ 12.000 /

Rate per 100.000 persons

/ B,C
HIV
7
HIV
6
5
4
3

Hepatitis C

2
1 Hepatitis B
0

1999

2000 2001

2002

2003

Year

2004 2005

2006

2007

HCV:

<1%
12.4 %
2.54.9 %
510 %
> 10 %

HCV Epidemiology and Impact on Intravenous Drug User Risk and Screening

Hepatitis C Virus
3.0
Anti-HCV Positive (%)

All patients
Infection for > 20 years*

2.0

1.0

1960 1970 1980 1990

2000
Year

2010

2020 2030

*Associated with more sever liver damage, requiring more medical attention if untreated.
Armstrong GL, et al. Hepatology. 2000;31:777-782.
clinicaloptions.com/hep

E HCV

: 0,14-0,83%
: 0,8-1,4%
( 0,6-7,83)
: 5,77%


CV

()

()

()

,
()

/ -HCV(+) ;

HCV- ;

HCV Epidemiology and Impact on Intravenous Drug User Risk and Screening

Estimated Seroprevalence (%)

100
80
HCV

60

HBV
HIV

40

HTLV

20
0

0-4

5-8

9-12

13-24 25-36 37-48 49-60 61-72

Duration of Injection Drug Use (Months)

HTLV, human T-lymphotropic virus.
Garfein RS, et al. Am J Public Health. 1996;86:655-661.

clinicaloptions.com/hep

 CV

,



,

 HCV
(
))





-
(
99%)


C
(-HCV)
(HCV RNA )

(, )

(ELISA)

1.
RT-PCR, Amplicor, 100
/ml
MA, 50 /ml
2.
Amplicor Monitor, 1000
/ml
bDNA, 200.000 / ml

3.

ONOTYH TOY HCV

O


.

K ,


HCV
.

A
.


C
ALT >10
-HCV (+)
HCV RNA (+)

iu/L

HCV RNA

-HCV

ALT

40
2

10

12

14


HCV
(
). <10%

 HCV

HCV
60%-85%
HCV

~ 20%

20%-50%

~ 20%

NIH Consensus
Development Conference
Statement. Hepatology. 2002;36(suppl. 1):S3.
Davis GL et al. Gastroenterol Clin North Am.
1994;23:603.
Koretz RL et al. Ann Intern Med. 1993;119:110.
Takahashi M et al. Am J Gastroenterol.
1993;88:240.

 HCV

>50 /

10

20

30

HCV INFECTION:
EXTRAHEPATIC MANIFESTATIONS
Haematological

Mixed cryoglobulinemia
Aplastic anaemia
Thrombocytopenia
Non-Hodgkins -cell lymphoma

Dermatological
Porphyria cutanea tarda
Lichen planus
Cutaneous necrotising
vasculitis

Renal
Glomerulonephritis
Nephrotic syndrome

Endocrine
Anti-thyroid antibodies
Diabetes mellitus

Salivary
Sialadenitis

Ocular
Corneal ulcer
Uveitis

Vascular
Necrotising vasculitis
Polyarteritis nodosa
Pulmonary fibrosis

Neuromuscular
Weakness/myalgia
Peripheral neuropathy
Arthritis/arthralgia

Autoimmune
Phenomena
CREST syndrome
Granuloma
Autoantibodies

POYAH META
EKEH TON HCV
-

POYAH META


& (HBVHBsAg, -HBc, -HBs, -HCV, HIV)
+/- -HBs
V
HIV, HAART 1

ALT/
3
( 99%)


C
M ()
=
> 6
=
= (I, A)
!!!!!
:
I
M
A HKK ()
B
M

HCV RNA

-
(, )








-
, C

C
100

PegIFN

SVR (%)

Standar
d
IFN
60
1991

1998

2014

2011

90+

70+
55

42
34

40
20

2001

RBV

80

DAAs

39

16
6
PegIFN/ PegIFN/ DAA
+ RBV
RBV
RBV/
PegIFN
12 mos
DAADrugs
Adapted from the US Food and Drug Administration, Antiviral
Advisory
Committee Meeting,
April 27-28, 2011, Silver Spring, MD.
IFN
6 mos

IFN
12 mos

IFN/RBV IFN/RBV
6 mos
12 mos

PegIFN
12 mos

AASLD/IDSA RECOMMENDATIONS FOR

HCV GENOTYPE 1 TREATMENTEXPERIENCED PTS
Genotype 1
Treatment Experienced
Yes/No Prior Protease Inhibitor?No
Sofosbuvir 400 mg/d
x 12 wks + PEG +
RBV x 12-24 wks

Sofosbuvir 400 mg/d

Simeprevir 150 mg/d
RBV
x 12 wks
Alternative Regimens

Sofosbuvir 400 mg/d

+ RBV PEG x 24 wks

RBV dose: 1000-1200 mg/day

Sofosbuvir
400 mg/d x 12
wks + PEG + RBV
x 12 wks

Simeprevir 150
mg/d x 12 wks +
PEG + RBV x 48
wks
GT1b
GT1a Q80K
neg

AASLD/IDSA treatment recommendations.

PROJECTED LAUNCH FOR NEW IFN-FREE

REGIMENS
SIM + SOF
RBV
SIM or
SOF + P/R

GT1

2013

IFNs last
hurrah
DCV +
ASV
2014
SOF/LDV
RBV

ABT-450/RTV/OMB
+ DSV RBV

DCV/ASV/
BMS-791325
2015

2016-?
MK-5172 + MK-8742
SOF + DCV
SOF/GS-5816
Others

AASLD/IDSA RECOMMENDATIONS FOR HCV

GENOTYPE 4 TREATMENT-EXPERIENCED
PTS
Genotype 4
Treatment Experienced

Sofosbuvir 400 mg/d

+ PEG + RBV x 12 wks

Alternative Regimens
Sofosbuvir 400 mg/d
+ RBV x 24 wks
RBV dose: 1000-1200 mg/day

AASLD/IDSA treatment recommendations.


C

-
98%.