Produce clinically similar

HBV HCV - Asymptomatic, inapparent to

fulminant and fatal acute Distinguished
infections by molecular
Acute Infection -Subclinical persistent infections and antigenic
properties
to rapidly progressive CLD with
cirrhosis and hepatocellular
carcinoma
HAV
 Acute Hepatitis :
self limited liver injury of less than 6 month duration

•Involves CD8+ and CD4+ T-cell responses

Cell mediated •Production of cytokines in liver and systemically
immune mechanism
Hepatocyte
injury
•Postulated in immunosupressed patients with
Direct viral exceedingly high level of viral replication (no
cytopathic effect direct evidence)
 Innate immunty
cell-mediated
T cell-dependent
immunity (CMI)
NK T
neutralizing antibodies
humoral
NK Adaptive Human leukocyte antigen
Cytokine incl. (HLA) class II-restricted CD4+
interferon immunity helper T cell + B cells + CD8+
celluler
cytotoxic T lymphocytes (CTLs),

Noncytopathic mechanism Cytopathic mechanism

 Common symptoms :
Majority are asymptomatic Mialgia, Nausea and vomiting
Fatigue and malaise
Change in sense of smell or taste
Preicteric
Hepatitis B and D from 30–180systemic
•Nonspesific days (mean,
symptoms 8–12 wk),
Right upper abdominal pain
•Hepatomegaly, splenomegaly &
Hepatitis C from 15–160 days (mean, 7 be
wks),
seen Coryza, photophobia, headache
phase lymphadenopathy may
Diarrhea (may have pale stools and dark urine)

Icteric phase •Jaundice after onset /upon lysis of fever

•Development of hepatic encephalopathy :

Fulminant confusion,drowsiness w/in 8 wk of symptoms or
hepatitis w/in 2 wk of jaundice
•Hypoglycemia, prolonged prothrombin time (PT)
 Laboratory findings
↑ Aminotransferase (ALT>AST)
Bilirubin normal (anicteric)/↑(icteric)
Alkaline phosphatase normal-mildly ↑
Protrombin time normal- ↑ 1-3second/ INR>1.7
Albumin normal-minimally depressed
Peripheral blood count : normal-mild leukopenia w/w.o relative
lymphocytosis

Imaging study:
Rarely necessery unless biliary
tract disease suspect
Histologic evaluation :
Liver biopsi rarely necessery
 Spilled blood
contaminated
Important point for patient w/ suspect viralROUTE
hepatitis can be infectious
up to 1 week
Of
HBV
Transmission
Contact w/ Perinatal, percutaneus,
History of blood sexual,close person to
jaundice IV drug use person contact (open
transfusion
patient cuts & sores)

Family history of HCV

Surgery or
chronic liver Occupation Blood transfusions,organ
hospitalization transplants, percutaneus (IV
disease
drug use, sexual, perinatal)
 Sign-symptoms
Aminotransferase ↑ (10-
100x) and
hyperbilirubinemia Fulminant
Severe cases : Acute liver Hepatic Failure Transplantation
poor hepatic synthetic failure (1%)
complicated by (1/2 cases)
function = prothrombin
time (PTT) of 16 seconds hepatic
or an international encephalopathy.
normalized ratio (INR) of
1.5 in the absence of
previous liver disease.

Resolve over a
Chronic
period of days,
Hepatitis
weeks, or months.
CHRONIC HEPATITIS
Persisten inflammation of the liver for 6 month or more after
initial exposure and/or initial detection of liver disease

Chronic Infection HBV HCV

HDV
 HCV 20-30%
neonatus
approaching 100%,
children 70%, healthy Hepatic
adult 1%;
syntetic
HBV failure 2-5% of HCV
cirrhotics/year
(usually after 20-
30 years)
Chronic Infection

HCV Portal
hypertension
70-85%

HBV
10-390x increase risk
even without cirrhosis
(highest: perinatal
acquired and
HBeAg+/↑viral load)
 acute infection/ resolving infection/false
Anti-HCV positive (confirm HCV qualitative)

in serum, livertissue, peripheral blood lymphocytes

HCV RNA

quantitative
qualitative

viral load ( high >800.000 IU/ml), (+) 2 weeks, marker active infection (< 50IU/ml),
along with genotyping determination to order with HIV & hemodyalisis
define treatment schedule & evaluate
response therapy
 IgM Anti-
HBcAg

HBsAg 1st AB to appear; acute infection

Anti HBcAg
HBsAg
IgG Anti-
appears before not found in blood test
symptoms; used to HBcAg
resolution of acute
screen blood disease & immunity
donor; negative = (sole marker after previous (HBsAg-) or chronic (HBsAg +)
viral clearence vaccination) HBV infection

HBeAg HBV DNA

by product (evidance) of viral active viral replication

replication (↑ infectivity/acute
infection)

Anti waning viral

replication,
HBeAg  infectivity
 HBV
Avoid unprotected sexual
intercourse, use condom
Screen for STD
Abstinence or limited use of
alcohol
HCV
PARTNER NOTIFICATION
Advise patient : not to PATIENT EDUCATION
SUPPORTIVE CARE Contact tracingdonate
(any sexualblood,
contactor needlesemen,organs;
sharingpartners)2 stop Emphazise the disease’s long-term
HOSPITALIZATION wk before onset jaundice implication for their & partner
using illicit drugs
(vomiting, dehydration, sign of health
Trace back time of Avoid
infection: sharing
(blood
hepatic decompensation) transfusion, 1 needle
st personal sharing)
hygiene Provide clear, accurate, written
information
Screen &(toothbrush,
vaccinationshaving);
IMMUNOSTIMULANT (e.g. levamisole, unprotected sex
selenium, zink- plant derived : phylantus,
glycyrrhiza, schizandra)
Ursodeoxycholoc acid (UDCA)
Phytotherapeutics FOLLOW UP
Monitor patient for fulminant liver failure
(essential phospholipids, EVALUATION
silymarin/silybin)
LFT’s every 1-4 wk until normal
Biochemical or clinical
Repeat serologic test after infection to improvement
rule out development of chronic
hepatitis (HBV 6 mth, HCV 8-16 wk)
 ACUTE HBV/ HCV

General care
• Partner notification Expert referral
• Patient education (HCV)
• Consider hospitalization
Evaluation HC
no
spontaneous Consider R/with
resolve after 2-4 Interferon or
Follow up mth? peginterferon

yes
no
Diagnosis persisten HBs Ag after
6 mth? Resolved HB/HC
infection
yes

History & physical exam

Evaluation Measure HBeAg, Anti-HBe, HBV DNA& ALT
CBC,PT
Screen HCC in high risk paient
Liver biopsi
PRIMER Virological
Permanently supress HBV or to eliminate it

Biological Histological
CLINICAL CONSIDERATION:
- Short term goal : sustained supression
of HBV DNA, ALT normalization, ENDPOINT USED TO ASSES RESPONSE
prevent decompensation,
decrease hepatic inflammation &
fibrosis during & after therapy Complete
- Long term goal : to avoid hepatic
decompensation, reduce or
prevent progression to cirrhosis &
or HCC and prolong survival

Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

Clinical profile Inactive Immune Immune reactive
carrier tolerant HBeAg+ HBeAg mutant
HBeAg - + + -

HBeAb + - - +

HBV-DNA (copies/ml) < 104 > 105 > 105 > 104

ALT normal normal elevated elevated

Liver biopsy Inactive Inactive active active

Treatment Not recom Not recom recommend recommend

Avunduk C. Manual of Gastroenterology Diagnosis and Therapy, 4 th ed, 2008.

Issues for consideration in the
selection of therapy
- EFFICACY,
- SAFETY,
- INCIDENCE OF RESISTANCE,
- METHOD OF ADMINISTRATION,
AND
- COST
LAMIVUDINE
(3TC-HBV)  ACTION : competitively inhibit viral reverse trascriptase,
blocking DNA polymerase activity, premature termination of
ADEFOVIR viral DNA chain thereby inhibiting DNA synthesis
DIPIVOXIL
(Hepsera)
ENTECAVIR  ADVANTAGES : oral administration, excellent tolerance, use in
(Baraclude) advanced liver disease, and high potency in lowering serum
HBV DNA levels.
TENOFOVIR  DISADVANTAGES : long-term administration, and variable rates
TELBIVUDINE of antiviral drug resistance.
(Sebivo)
CLEVUDINE &
PRADEVOFIR

Keefe EB. Hepatitis B: Advances in Screening, Diagnosis, and Clinical Management -Vol 3, 2008
INTERFERON  ACTION : supresses HBV replication & induce remission of liver
disease (inert polyethylene glycol decrease drug’s renal clearance
(IFN) & increase half life) → antiviral, antiproliferative & immunomodulatory
INTERFERON-α effect
REKOMBINAN
INTERFERON -  ADVANTAGES : a 1-year finite duration of therapy, higher rate of
α2a/2b HBeAg seroconversion at 1 year, lack of resistance, and higher
POLIETILEN likelihood of HBsAg loss and seroconversion.
GLIKOL (PEG-  DISADVANTAGES : parenteral administration, frequent side effects
(especially flu-like symptoms, depression or irritability, and cytopenias),
IFN2a/2b = need for more intensive laboratory monitoring, contraindication in
Pegasys, Peg advanced liver disease, and higher cost
Intron)

Keefe EB. Hepatitis B: Advances in Screening, Diagnosis, and Clinical Management -Vol 3, 2008
Virus HBV HCV
Viral genom DNA RNA(+)
Screening test HBsAg or Anti-HBc Anti-HCV
Main transmission Parenteral Parenteral
Incubation period (days) 26-160 21-84
Acute hepatitis yes yes
Chronic hepatitis yes yes
Antiviral therapy during acute phase no yes
Immune prophylaxis
-Passive + -
-Active + -

Thimme R et al. Clinical Gastroenterology and Hepatology 2005

 o Virus lenyap1
Primary: HCV RNA undetectable
o Stop perkembangan penyakit

o Hilangkan gejala

Secondary: Inhibit the progression of the disease

o Cegah fibrosis1

o Cegah terjadinya sirosis2

o Cegah Gagal Hati

o Cegah Kanker Hati2

1. Worman HJ. Hepatitis C: current treatment. 2. Peters MG et al. Medscape HIV/AIDS eJournal. 2002;8(1).
 End point of T/
 If RVR is achieved at week 4, continue R/ only up 24
week
 If EVR is achieved at week 12, continue R/ to 48 week
If EVR is not achieved at week 12, discontinue R/
 Optimal duration of therapy based on virus genotipe


Genotipe 1/4 PegIFN alfa-2a PegIFN alfa-2b

HCV genotype 1 (around 50% of SVR)
Dose of PegIFN (weekly) 180 µg 1.5 µg/kg
Dose of RBV (daily) 1000 mg if BW ≤ 75 kg 800 mg if ≤ 65 kg
1200 mg if BW > 75 kg 1000 mg if > 65 to 85 kg
1200 mg if > 85 to 105 kg
1400 mg if >105 kg
Duration of therapy 48 weeks 48 weeks

Genotipe 2/3 PegIFN alfa-2a PegIFN alfa-2b

HCV genotype 2 or 3 (>80%of SVR)
Dose of PegIFN (weekly) 180 µg 1.5 µg/kg
Dose of RBV (daily) 800 mg 800 mg
Duration of therapy 24 weeks 24 weeks

Ghany MG, et al. Hepatology. 2009;49:1335-1374.

 Serologic Tests of Patient's Serum
HBsAg IgM Anti-HAV IgM Anti-HBc Anti-HCV Diagnostic Interpretation
+ – + – Acute hepatitis B
+ – – – Chronic hepatitis B
+ + – – Acute hepatitis A superimposed on chronic hepatitis B
+ + + – Acute hepatitis A and B
– + + – Acute hepatitis A and B (HBsAg below detection threshold)

– – + – Acute hepatitis B (HBsAg below detection threshold)

– – – + Acute hepatitis C