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Hep B Dan C Virus Infection
Hep B Dan C Virus Infection
~ 2 million Asians
~ 930, 000
Europeans
~ 400,000
South Americans
HBsAg Prevalence
> 8% - High ~ 350,000
2-8% - Intermediate Africans
< 2% - Low
Immigration numbers summed by continent from 1996-2002
Indonesia :
· 10% (3.4-20.3%) of the population
are HBV carriers
Prevalensi di Indonesia
Penduduk Koja (Jakarta) 4.8 Budihusodo, 1990
Penduduk daerah Irian Jaya 10.5 Mulyanto, 1991
Penduduk Desa Sokong Lombok 11.3 Gunawan, 1985
Anggota TNI AD Mataram 8.5 Sumarsidi, 1982
Donor Darah Mataram 7.3 Nuryandari, 1987
Penduduk Gili Air, Selat Lombok 10.9 Suwignyo, 1987
Penduduk Segenter Lombok 20.3 Gunawan, 1987
· HBsAg
· HBeAg
· HBcAg*
· Polymerase
· X Protein
VHB tidak bersifat sitopatik
Sistem kekebalan
Tubuh mendeteksi
Keberadaan virus
Virus
masuk ke
sel hati Membunuh virus dengan
menyerang sel hati yang
terinfeksi
Berkembang biak
Sel Hati
VHB tidak bersifat sitopatik
SGPT/ALT
meningkat
Sel Hati
Progresi infeksi hepatitis B
5%-10% of
Liver
chronic HBV-
infected Cancer
individuals1 (HCC)
>30% of CHB
Acute Chronic individuals1
Infection Infection Cirrhosis Death
chronic disease1
cccDNA
4. Transcription
1. HBV binds to
membrane receptors
and enters the cell 5. mRNA
molecules leave
6. Translation to the nucleus
Extracellular Space produce viral
proteins
Hepatocyte 7. Core assembly
and RNA
packaging 8. (-) strand synthesis
(reverse transcriptase)
11. Complete Viron Antiviral Drugs
buds from cell
10. Assembly of
membrane 9. (+) strand synthesis
nucleocapsid and
envelope proteins (DNA polymerase)
Ibu HBsAg (+) HBeAg (+) 90%
menularkan pada janin
VHB
Penularan vertikal
Hepatitis B akut
pada umumnya asimtomatik
Inflamasi (+) aktif
SGPT ↑ persisten / intermitent
HBeAg (+)
HBV DNA Tinggi
Serokonversi HBeAg → anti HBe
FASE INACTIVE CARRIER
HBeAg (-) Anti HBe (+)
SGPT N persisten
HBV DNA low / undetected
FASE REACTIVATION
HBeAg (-) anti HBe (+)
(kadang reversi HBeAg)
HBV DNA ↑
SGPT ↑ fluktuasi
Hepatitis B Kronis Hepatitis B kronis
HBeAg (+) HBeAg (-)
80 80
60 60
Chronic Symptomatic
Infection Infection
(%) 40 40 (%)
20 20
0 0
Birth 1 to 6 7 to 12 1 to 4
Older
months months years
Children
& Adults
Age at Infection
HBsAg, Anti HBs
GEJALA
HBeAg Anti-HBe
Total anti-HBc
Titer
0 4 8 12 16 20 24 28 32 36 52 100
Minggu setelah infeksi
PROGRESI KE INFEKSI KRONIK
Akut Kronik
(6 months) (years)
HBeAg Anti-HBe
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36 52 Tahun
Hepatitis B + - + + +
+
Akut
Pengidap + +/- + - - -
Vaksinasi - + - - - -
Sembuh - + + - - -
KORELASI
HBeAg
ALT
HBV DNA
terhadap progresifitas Penyakit
24
HBeAg
(Hep. B e Antigen)
25
HBeAg yang persistence, berhubungan dengan
Insidensis Sirosis lebih tinggi
50
Cumulative incidence of cirrhosis
Non-seroconverters
40
30
20
10 Seroconverters
(Months)
0
0 24 48 72 96 120 144 168 192 216
74 60 49 39 32 22 14 6 4
134 106 81 64 52 39 17 5 2
Lin SM et al. J Hepatol. 2007;46:45−52
HBeAg Positif menyebabkan pogresifitas
penyakit lebih cepat
Disease progression
100
cirrhosis development (%)
Cumulative incidence of
80
40
HBeAg-negative hepatitis (24%)
20
Sustained remission (67%)
0
0 2 4 6 8 10 12 14 16 18
Years after HBeAg seroconversion
No. at risk
9 8 8 8 8 7 7 7 4 3 2
62 61 61 59 54 52 49 43 36 33 30 25 23 17 15 11 9 5 2
28
1. Chu CJ et al. Hepatology 2002; 36: 1408–15.
HBeAg dan Risiko terhadap Kanker Hati
P < .001
Cases/100,000 PYs
1400
Incidence of HCC,
1200 1169.4
1000
800
600 P < .001
400 324.3
200 39.1
0
HBsAg(-) HBsAg(+) HBsAg(+)
HBeAg(-) HBeAg(-) HBeAg(+)
30
ALT NORMALIZATION
31
ALT and Komplikasi Hati
Korea Medical Insurance Corporation
- 94,533 men; 47,522 women
- 35-59 yrs old
- Relative risk for liver mortality compared with AST
and ALT <20 IU/l
Men Women
AST (IU/l)
20-29 2.5 3.3
30-39 8.0 18.2
ALT (IU/L)
20-29 2.9 3.8
30-39 9.5 6.6
Conclusion: People with AST and ALT levels in the upper ranges of
“normal” are at risk of liver disease/mortality
32
Kim HC, et al. BMJ 2004;
ALT and Hepatic Complications
3,233 Chinese CHB patients
Stratified: ALT < 0.5 x ULN
30 ALT > 0.5-1 x ULN, ALT > 1-2 x ULN
ALT > 2-6 x ULN, ALT > 6 x ULN
Risk of
Complications
ALT >6 X ULN
(%) 20
10
ALT >1 - 2 X ULN
33
Yuen MF et al. Gut 2005; 54:1610
Fakta 2
35
R.E.V.E.A.L: high HBV viral load is associated with increased
incidence of HCC
4 3.57% 2.7
(1.3-5.6)
2 1.37%
1.0
1.30% (0.5-2.2)
0 1.0
(reference)
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Year of follow-up
Chen CJ, et al. JAMA. 2006; 295:65–73.
R.E.V.E.A.L: high HBV viral load is associated with increased incidence
of HCC – independent of ALT level
14
Cumulative incidence of HCC, %
12 ≥106
105–<106
10 104–<105
300–<104
8 <300 7.96%
4
3.15%
2
0.89%
0 0.74%
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Year of follow-up
Chen CJ, et al. JAMA. 2006; 295:65–73.
VARIABLE MULTIVARIATE ADJUSTED
RELATIVE-RISK
Gender
Female 1.0
Male 2.1 (1.4-3.2)‡
Cigarette smoking
No 1.0
Yes 1.2 (0.8-1.6)
Alcohol drinking
No 1.0
Yes 1.6 (1.1-2.3)*
Anti-HCV
Negative 1.0
Positive 1.4 (0.8-2.5)
HBeAg
Negative 1.0
Positive 2.3 (1.6-3.3)‡
ALT
<1x ULN 1.0
≥1x ULN 1.7 (1.2-2.6)†
30 105–<106 (n=333)
cirrhosis (% subjects)
104–<105 ( n=628)
300–<104 ( n=1,150)
23.5% 5.9
<300 (n=869) (3.9-9.0)
20
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Years of follow-up
Fakta 3
Faktor yang paling penting yang berkaitan
dengan perkembangan komplikasi ( sirosis hati
dan kanker hati) adalah Viral Load
40
Chen CJ.et al JAMA, 2006
MANFAAT PEMERIKSAAN
HBV-DNA
HBeAg Positive
· Menghilangkan HBV-DNA serum.
· Menghilangkan HBeAg serta mencapai serokonversi
menjadi Anti HBeAg.
· Normalisasi ALT.
· Perbaikan histologi hati.
HBeAg Negative
· Menghilangkan HBV-DNA serum.
· Normalisasi ALT.
· Perbaikan histologi hati.
HBeAg Positive
ALT ALT
Normal Elevated
HBeAg Negative
ALT ALT
Normal Elevated
1 IU = 5.6 copies/mL
Consider treatment
(long-term required)
Wait list for transplant
1 IU = 5.6 copies/mL
Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936.
49
Fresh APASL 2008 - Seoul
guidelines for HBV management
HBeAg Positive
HBV DNA
> 20,000 IU/mL
( 105 copies/ml )
Biopsi
Treat:
• Conventional IFN
If :Advanced Fibrosis / Cirrhosis • Peg IFN
• Lamivudine
Treat • Adefovir
• Entecavir
• Telbivudine
Yun FL.al.Liver Int 2005;25:472
Yun FL. Guidelines for HBV management, APASL 2008 50
Fresh APASL 2008 - Seoul
guidelines for HBV management
HBeAg Negative
HBV DNA
> 2,000 IU/mL
( 104 copies/ml )
Biopsi
Treat:
• Conventional IFN
if: Advanced Fibrosis / Cirrhosis • Peg IFN
• Lamivudine
Treat • Adefovir
• Entecavir
• Telbivudine
Yun FL.al.Liver Int 2005;25:472
Yun FL. Guidelines for HBV management, APASL 2008 51
Fresh APASL 2008 - Seoul
guidelines for HBV management
Decompensated
Patient
Treat:
• Lamivudine
• Entecavir
• Telbivudine
6 month
Serokonversi HBeAg Stop Check ALT & HBV DNA
Check HBV DNA (-) / 3 month
Check HBV DNA (-) Therapy
Stop
6 month 6 month
Therapy
-Continue
-Add on or switch Check ALT & HBV DNA / 3
month
Fresh APASL 2008 - Seoul
guidelines for HBV management
Stop Therapy
B Animal studies have revealed no evidence of harm to the fetus. However, there
are no adequate and well-controlled studies in pregnant women.
Pregnancy
Drug
Or
Animal studies have shown an adverse effect, but adequate and well-
Category controlled studies in pregnant women have failed to demonstrate a risk to
the fetus.
Adefovir C C Animal studies have shown an adverse effect and there are no adequate and
well-controlled studies in pregnant women.
Or
Entecavir C No animal studies have been conducted and there are no adequate and
well-controlled studies in pregnant women.
Telbivudine
B X Studies, adequate well-controlled or observational, in animals or pregnant
women have demonstrated positive evidence of fetal abnormalities. The
use of the product is contraindicated in women
who are or may become pregnant
Pencegahan :
Sangat Penting!
Melindungi pasien…
Melindungi petugas kesehatan…
Promosi pelayanan kesehatan
yang berkualitas!
Virus Hepatitis C
(VHC)
57
• Virus golongan RNA
• Famili Flaviridae
• Terdiri dari 6 genotype
• Replikasi di hepatosit
58
Penegakan diagnosis :
Serokonversi anti-HCV pada pasien yang
sebelumnya diketahui anti-HCV negatif
• Skrining awal :
Pemeriksaan anti-HCV
• Tahap lanjutan :
HCV RNA kuantitatif, genotipe virus
60
Tahapan Pemeriksaan
Infeksi Hepatitis C
Hepatits C Akut
63
Penegakan Diagnosis :
Anti-HCV dan HCV RNA tetap
terdeteksi > 6 bulan sejak terinfeksi
(kriteria ideal)
Dapat disertai maupun tanpa
gejala-gejala penyakit hati kronik
Umumnya pasien tanpa sumber
penularan yang jelas dalam 6 bulan
terakhir dianggap sebagai kasus
hepatitis C kronik
64
HEPATITIS C KRONIK
(80% kasus asimtomatik)
65
Situation in Indonesia
General population : Anti-HCV (+) : 2.08%
National Basic Health Survey 2007 (N = 27,536)
67
Pengkajian Pra-terapi
Mencari etiologi lain penyakit hati kronik
Koinfeksi HIV dan VHB
Kemungkinan penyakit komorbid (NAFLD,
penyakit hati autoimun, penyakit hati alkohol)
Pemeriksaan fungsi hati: AST/ALT, GGT,
alkalin fosfatase, bilirubin, PT, albumin,
globulin, darah perifer lengkap
69
HCV DRUGS IN DEVELOPMENT
… asvir
… buvir
… previr 70
Pengobatan Hepatitis Dengan DAA :
Pusat
• dilakukan oleh dokter Ahli Penyakit
Hati/Penyakit Dalam di Pusat
Provinsi
• dilakukan oleh dokter Ahli Penyakit
Hati/Penyakit Dalam di Daerah
Kabupaten
• Dilakukan oleh dokter Ahli Penyakit
Hati/Penyakit Dalam di Daerah 71