HEPATITIS

 A general term that means inflammation of the liver

 Inflammation of the liver :
 Infection
 Exposure to alcohol
 Certain medication
 Chemical
 Poison
 Disorder of the immune system
Hepatitis A
 Hepatitis A is an acute inflammatory
condition of the liver caused by
hepatitis A virus and characterized by
constitutional symptoms including
anorexia, fatigue, weight loss, and
jaundice.
History
 Bamberger and Virchow in 1855, the
disease became known as “catarrhal
jaundice”, that the disease was
caused by blockage of the common
bile duct by a plug of inspissated
mucus.
cont..
 In 1923, Blumer analyzed a large
number of epidemics of hepatitis in
the US and identified its predilec-
tion for young adults and children
and peak incidence in winter and
fall.
 In 1973, Feinstone et al., detected 27
nm virus-like particles in the stool
of volunteers infected with
hepatitis A.
VIROLOGY
 HAV is a 27 to 28 nm spherical, nonen-
veloped, ss-RNA virus member of the
Picornaviridae family, which includes
the enterovirus, and rhinovirus of
human.
 HAV genome consist of 7478 nucleotides.
cont..
 HAV strains have been divide into three
genotypes, I, II, and III on the basis of
phylogenetic analysis of sequences of
the complete VP1 region.
Resistance
 HAV is a relatively stable virus under a variety of
environmental conditions.
 HAV is more resistant to heat than other picornavirus
and may not be completely inactivated by exposure to
60 C for 10 to 12 hours.
 Complete inactivation in food requires heating to
higher than 85 C for at least 1 minute.
 The virus is resistant to most organic solvents and
detergents and to a pH as low as 3.
 HAV can be inactivated by many common disinfecting
chemical including hypochlorite and ammonium
containing 23% HCl.
Modes of Transmission
 HAV is primarily transmitted by the
fecal-oral route. After replication in the
liver, the virus is excreted in bile and is
found in highest concentration on the
stool.
cont..
 Infectivity of stools was demonstrated
for 14 to 21 days before to 8 days after
onset of jaundice, but the highest
concentrations occur during the 2-week
period before jaundice develops or liver
enzymes , followed by rapid decrease
after the appearance of jaundice.
Person to Person
 PTP transmission by the fecal-oral route
remains the primary means of HAV
transmission throughout most of the
world.
 Transmission can occur among close
contacts, particularly in household and
extended family setting.
Foodborne and Waterborne
 Occur from expose to fecally
contaminaed food or water.
 Many uncooked foods have been
recognized as the source of
outbreaks.
cont..
 Cooked foods also can transmit HAV if
the cooking is inadequate to kill the
virus or if the food is contaminated after
cooking, as commonly occurs in
outbreaks associated with infected food
handlers.
Bloodborne
 Transfussion-related hepatitis A is rare
because HAV does not result in chronic
infection, and in the developed country,
blood donors have been screened for
many years for elevated aminotransfe-
rase levels.
Vertical
 Two published case reports describe
intrauterine transmission of HAV during
the first trimester, resulting in fetal
meconium peritonitis.
 After delivery, both infants were found
to have a perforated ileum.
 PATHOGENESIS
 Replicate initially in the enteric mucosa
 It can be demonstrated in feces for 10-14 days before
onset of disease
 Multiplication in the intestine is followed by a period
of viremia with spread to the liver
 Respon to replication in the liver :
 Lymphoid cell infiltration
 Necrosis of liver parenchimal cells
 Proliferation of Kupffer cells
 Increased Risk
 Household contacts of people infected with HAV
 International travelers
 People who may come in to contact with HAV at work
 Workers in professions :
 Health care
 Food preparation
 Sewage and waste water management
Incubation Period
 Determination of the incubation period of disease is
imprecise because the early symptoms of hepatitis are
often vague and nonspecific.
 Most usefull marker of the onset of the disease is a
change in urine color.
 Range of incubation is between 15 and 50 days, with a
mean of approximately 28 days.
Site of Viral Replication
 HAV is generally transmitted by the fecal-oral route.
 Because the virus is acid resistant, it probably passes
through the stomach, replicate lower in the intestine,
and is then transported to the liver, which is the major
site replication.
Symptoms
 Patients with hepatitis A often describe a mild illness,
the prodrome that appear 1 to 7 days before the onset
of dark urine and jaundice.
 In the early stage, flulike symptoms, fever (as high as
40 C) may be accompanied by chills, mild headache,
malaise, and fatigue. Loss of appetite, nausea,
vomiting, and weight loss.
 Occasionally with atypical symptoms such as diarrhea,
cough, coryza and arthralgia.
 EXAMS and TESTS
 Tes for liver function
 Increase aminotransferase 1-3 weeks
 Test for antibody to HAV
 IgM anti-HAV
 Large amount of vomiting
 electrolytes
 TREATMENT
 No specific medicines to cure infection with HAV
 Except to relieve symptoms
 Prevent :
 Passive immunization
 Immuneglobulin (ISG) effective when given within 2 W of
expossure
 Is protective if given before or during the incubation period
 Active immunization :
 Formalin-killed vaccine are more promising, they have
efficacy in children
 IMMUNITY
 Antibody to HAV can be detected during early illness
when the virus is still found in feces
 Most patients with symptom or signs of acute HA
already have detectable antibody in serum
 Early antibody are predominantly IgM which can
detected for several weeks or months
 During convalescence : IgG – are immune to
reinfection
Cont…
 Sifat virus :
 Autoclave
 Air mendidih, 5 menit
 Oven sterilisasi
 Radiasi UV (1 menit)
 Formalin
 Klorin (10-15 ppm, 30 mnt)
 Makanan dipanaskan > 85 C, 1 mnt
HEPATITIS B
 Problem kesehatan global
 2 milyar terinfeksi VHB
 350 juta infeksi kronik
 Tanpa interfensi 15-40% berkembang :
 Sirosis hati
 Karsinoma hepatoseluler
RISIKO KRONISITAS
 NEONATUS : 90-95%

 BALITA : 30-50%

 DEWASA : 5-10% (90% SEMBUH)

VIRUS HEPATITIS B
 Non sitopatik
 Kerusakan hati :
 Respon imun
 Sitokin inflamasi
 Hepadnaviridae
 Ds-DNA dengan 3200 bp
 Envelop : HBsAg
 Precore/core : HBeAg, HBcAg
Cont …
 Masa inkubasi 50-180 hr (rata-rata 2 bl)
 Onset penyakit : perlahan
 Kenaikan enzim aminotransferase 1-6 bl
 Symptoms :
 Appetite loss
 Fatigue,
 Nausea and vomiting
 Low-grade fever
 Muscle and joint aches
 Yellow skin and dark urinee due to jaundice
TRANSMISI
 DARAH, CAIRAN TUBUH
 Blood transfusion
 Contact with blood in health care setting
 Had direct contact with blood of an infected person by
touching an open wound or been stuck with a needle
 Had unsafe sex with infected person
 Received a tatto or acupuncture with contaminated
instruments
 Share needles during drug use, unsafe injections
 Share personal item (toothbrushes, razor)
 Perinatal (from mother to baby at birth)
MARKER SEROLOGIK
 HBsAg :
 petanda serologik pertama muncul
 Terdeteksi 1-12 W pascainfeksi
 Mendahului gejala klinik
 Persisten > 6 bl : infeksi kronik
 Anti-HBs :
 Marker sembuh infeksi VHB
 Persist lifelong
MARKER SEROLOGIK
 HBeAg :
 Marker risiko penularan
 Replikasi virus
 Muncul 3-6 W pascainfeksi

 Anti-HBe :
 Remisi penyakit
MARKER SEROLOGIK
 Anti-HBc :

 IgM anti-HBc dengan HBsAg : marker infeksi akut virus

hepatitis B

 IgG anti-HBc dengan HBsAg : penderita kronik VHB

PREVENTION
 VAKSINASI :
 Bayi dari ibu HBsAg imunisasi dalam 12 jam stl lahir
 People who are at high risk : health care workers
 Protection at least 20 years and should be lifelong

 UJI SARING DARAH

 Avoid sexual contact with person who has acute or
chronic hepatitis B :
 Using condoms consistently and properly
TREATMENT
 There is no specific treatment for acute hepatitis B
 Replacement of fluids
 Adequate nutritional balance

 Chronic hepatitis B :
 Interferon
 Anti-viral agent : lamivudin, adefovir
 Patients with cirrhosis : liver transplants
 HEPATITIS C
USA  2 % ( insidensi 3
3 % Populasi – 4 juta / tahun)

Mesir  > 10 %

Indonesia  0,5 – 3,4 %

Seluruh dunia  ± 200 juta

THE VIRUS
 HCV is an RNA virus and a member of the
Flaviviridae family, genus Hepacivirus.

 There are 6 known genotypes and more than

50 subtypes (quasispecies).

 Type 1 (75%), type 2 (10%) and type 3 (10%)

are the commonest genotypes in USA.
VIRUS HEPATITIS C
Ukuran 50
nm

9600 bp 6 genotip

7 protein
3 protein
non
struktural
struktural
NATURAL HISTORY
 Incubation period is up to ~ 8 weeks.
 Acute infection.
 > 80% persistent infection.
 Slower progression if young age at time
of infection and female gender.
 More rapid progression if HIV or HBV
co-infection, alcohol use
IMUNOPATOGENESIS

TIDAK SITOPATIK

INFLAMASI HATI

sel NK
RESPON
IMUN Limfosit T
Sitotoksik
12/8/2019 52
 Liver Damage ?
 Presence of HCV : trigger the human
immune system cause inflammation
 Prolong inflammation may cause
scarring : cirrhosis
 The liver to perform its normal function
: liver failure
TRANSMISSION
 Blood transfusion before 1992.
 Injection drug use.
 Solid organ transplantation from infected donor.
 Unsafe medical practices.
 Occupational exposure to infected blood.
 Infected mother to child during birth.
 High risk sexual practices.
 Intranasal cocaine use.
 Body piercing.
Penularan hepatitis C

Abbott, 2008
 Prevent of Transmission
 Avoiding needle sharing
 Safe needle-usage
 Person with SMP should use barrier
precaution
 Screening test for blood products
 Not share razors or tootbrushes with others
CLINICAL FEATURES
 The majority of infections are asypmtomatic.
 Prodrome of anorexia, nausea vomiting,
myalgia and malaise. Diarrhea or
constipation, low grade fever and abdominal
pain may occur (tender hepatomegaly).
 Icteric phase – jaundice may occur after 5 – 10
days.
 Convalescent phase.
 Acute illness may be mild and subsides in 2 – 3
weeks. Fulminant infection is rare.
LAB
 In acute infection, mild leukopenia,
hyperbilirubinemia and elevated transaminases may
occur.
 HCV RNA detected in blood within 1 – 3 weeks of
exposure.
 HCV antibodies present in 50 – 70% of patients at
onset of symptoms, and 90% at 3 months.
 Alanine aminotransferase (ALT) levels decline with
resolution of symptoms, however, may fluctuate
throughout the course of infection. ALT persistently
normal in up to 40% person with chronic hepatitis.
Alanine Aminotransferase
 Serum ALT testing is inexpensive and noninvasive.
 Insensitive means of monitoring disease activity.
 A single determination gives limited information, and
serial measurements recommended.
 Weak association between the degree of ALT elevation
and severity of histopathological findings on liver
biopsy.
 Resolution of ALT elevation with antiviral therapy
appears to indicate disease response.
Chronic infection and risk of
progression
 Chronic inflammation of the liver with persistence of HCV RNA
> 6 months.

 Sequelae include progressive liver fibrosis, cirrhosis, end-stage

liver disease and hepatocellular carcinoma.

 Little evidence that viral factors (viral load, genotype) affect the
risk of progressive liver disease.

 Risk of progression increased by older age at time of infection,

male gender, immunosuppression, HBV, alcohol.
 Receive antiviral ?
 HCV infection and persistent elevation ALT
 High levels of HCV RNA in the blood
 HCV infection and evidence of fibrosis on liver
biopsy
 HCV infection and evidence of at least
moderate inflammation and necrosis on liver
biopsy
 RESPON TERAPI

• Respon viral 
Genotipe 1 42 – 48 %

Genotipe 2 • Respon viral 

dan 3 76 – 78 %
PENCEGAHAN
 Tidak ada vaksin
 Ditujukan kepada :
 Transfusi darah
 Pengendalian infeksi pd pelayanan kes
 Pekerja sek komersial
Hepatitis D
 Terdeteksi antigen delta dan antibodi pada beberapa
infeksi HBV
 HDV membutuhkn selubung HBsAg untuk transmisi
 Sering dihubungkan dg hepatitis berat pada pasien
HBsAg positif
 Vaksinasi HBV tidak melindungi pembawa HBsAg dar
superinfeksi HDV
Hepatitis E
 Virus RNA untai tunggal
 Ditemukan di New Delhi 1955 pada kontaminasi suplai
air minum
 Ditularkan fekal-oral (NANB )
 Tidak pernah menjadi kronik
 Tidak bersifat onkogenik
 Stabil panas
TERIMA
KASIH
Course of acute HCV in HCW after needle stick injury
Extra-hepatic manifestations of chronic HCV
 ‘Rheumatoid’ symptoms
 Keratoconjunctivitis sicca
 Lichen planus
 Glomerulonephritis
 Lymphoma
 Essential mixed cryoglobulinemia
 Porphyria cutanea tarda
 Psychological disorders
 Leukocytoclastic vasculitis
LABORATORY DIAGNOSIS
 Serologic tests to detect HCV antibodies:

- enzyme immunoassay (EIA). False negative in pts on HD,

immunodeficiency; false positive in autoimmune disorder.

- recombinant immunoblot assay (RIBA)

 Target amplification technique to detect HCV RNA (molecular assay)

- polymerase chain reaction (PCR). A positive test confirms HCV

infection.
 HCV TESTING

EIA
Negative Positive

Measure HCV RNA by PCR

Negative Positive

Low risk High risk

RIBA Consider treatment

for HCV infection

Negative Positive

No further workup Previous infection and clearance

LIVER BIOPSY
 Provides useful information about the degree of fibrosis in HCV infected
patients. This information is important in management decisions.

 Is not used for diagnosis of HCV infection.

 Used for assessment of severity of inflammation, presence of fibrosis, evaluate

possible concomitant disease processes, assess therapeutic intervention.
Liver Histology
 Activity (necro-inflammation) – severity and progress. May fluctuate with
disease activity or therapeutic intervention.

 Fibrosis implies possible progression to cirrhosis. In mild cases, is limited to

portal and periportal area. More advanced changes defined by ‘bridging
fibrosis’.

 Cirrhosis
Fibrosis Scoring Methods

KNODELL METAVIR ISHAK

NONE 0 0 0

PORTAL FIBROSIS (SOME) 1 1 1

PORTAL FIBROSIS (MOST) 1 1 2

BRIDGING (FEW) 3 2 3

BRIDGING (MANY) 3 3 4

INCOMPLETE CIRRHOSIS 4 4 5

ESTABLISHED CIRRHOSIS 4 4 6
The problems associated with liver biopsy
 Cost
 Complications –pain, major bleeding, pneumothorax, inadvertent biopsy of
kidney or colon, perforation of gall bladder.
 Patient aversion
 Physician aversion
 Specimen size – degree of fibrosis more accurately determined in larger
specimens
 Lack of specific findings.
MANAGEMENT – Baseline evaluation
 CBC
 ALT
 TSH
 ANA
 HCV genotype
 HCV quantitative viral load
 Liver biopsy (recommended)
 AFP (if cirrhosis present)
 Pregnancy test
MANAGEMENT
 Previously untreated patients with detectable HCV RNA, persistently
elevated ALT and liver biopsy specimen showing fibrosis (or at least
moderate necrosis and inflammation) are at high risk of disease
progression and are candidates for therapy.

 Pegylated interferon (PEG-INF) combined with ribavirn is currently the

best therapy.

 Treatment associated with significant side effects.

 Several predictors of treatment response have been identified, eg HCV

genotype.

 An absence of serum HCV RNA 6 months after therapy has been

discontinued predicts sustained viral eradication.
MANAGEMENT
 PEG-INF 180µg sc weekly and ribavirin 800 – 1200mg po daily x 24 -48 weeks.

 Genotypes 2 and 3 associated with better response, and treated for 24 weeks.
SVR ~ 76%

 Genotypes 1, 4, 5. 6 are less responsive to therapy; if there is early virological

response after 12 weeks, therapy is continued for a total of 48 weeks. SVR ~ 50%

 Independent predictors of favorable response are non-1 genotype, lower levels

of HCV RNA and lower BMI. Other factor are age, race, gender, and presence of
cirrhosis.
Side effects of Pegylated interferon
 Flu-like syndrome – fever, headache, chills, myalgia, fatigue
 Gastrointestinal – nausea, anorexia, diarrhea
 Neuropsychiatric – depression, irritability
 Skin – alopecia, pruritus, rash, dry skin
 Bone marrow – anemia, neutropenia
 Cardiovascular – arrhythmia, cardiomyopathy, CHF, angina
 Endocrine – hypothyroidism, hyperthyroidism, gynecomastia, DM
exacerbation
 Liver – liver failure, jaundice
 Musculoskeletal – arthritis, muscle weakness and cramps
 Reproductive – amenorrhea, impotence, uterine bleeding
 Other – respiratory, urinary, vision, hearing disturbances, injection site
reaction
Side effects of Ribavirin
 Neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia
 Teratogenic, embryocidal
 Depression, suicidal ideation
 Pulmonary toxicity
 Nausea, vomiting, colitis, pancreatitis
 Hypothyroidism, hyperthyroidism
 Myocardial infraction, arrhythmia
 Hypersensitivity reaction, rash
Contraindication to combination therapy
 Hypersensitivity to drugs
 Pregnant women
 Men whose partners are pregnant
 Hepatic decompensation
 Neonates and children
 Autoimmune hepatitis
 Hemoglobinopathies
Barriers to treatment
 Neuropsychiatric illness
 Alcohol use
 Active illicit drug use
 Cost
 Poor adherence to therapy
 Adverse effects
HCV AND HIV COINFECTION
 All patients with HIV should be screened for HCV.

 Treatment of co-infected persons individualized.

 The course of HCV may be accelerated in HIV co-infection.

 HCV co-infection may be associated more rapid progression of HIV.

 PEG-INF may cause a fall in CD4 cell count.

PEMERIKSAAN LABORATORIUM
Pemeriksaan Anti VHC

 Pemeriksaan Anti VHC Rapid

- metode immunokromatografi
- Serum/plasma akan bergerak dengan gaya
kapilaritas menuju test line , jika mengandung
antibodi VHC, akan terbentuk warna
- Strip tes menggunakan antigen rekombinan
positif negatif
Pemeriksaan Anti VHC dengan
Enzyme-Linked Immunosorbent Assay Sandwich
 Pemeriksaan anti VHC Elisa Sandwich menggunakan antigen
rekombinan spesifik VHC (rAg: core, NS3 dan NS5) yang
dilapisi pada well microtiter (meningkatkan sensitifitas dan
spesifisitas)
 Bila terdapat antibodi dalam spesimen serum atau plasma,
akan terikat pada protein rekombinan VHC yang dilapisi
pada permukaan well microtiter.