HEPATITIS

Diah Puspita Rini, dr., SpPK

 Hepatitis is inflammation of the liver which can be caused by viruses, medications, or toxic agents. Non viral : miliary TB, staphylococcal bacteriemia, salmonelloses, amebiasis, drugs, etc. Viral hepatitis :, Hepatitis A,B,C,D,E CMV, Herpes, Epstein Barr virus, Rubella

Viral Hepatitis
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Hepatitis A Title Click to add

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6

Hepatitis E

Hepatitis B Title Click to add

Hepatitis G

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4

Hepatitis C

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8

Hepatitis TT

Hepatitis D

Hepatitis Sen

VIRAL HEPATITIS
A Major Public Health Problems

Cause Morbidity & Mortality Chronic Hepatitis B & C

Liver Cirrhosis

HCC

SYMPTOMS
a short, mild, flu-like illness nausea, vomiting and diarrhoea loss of appetite weight loss jaundice (yellow skin and white of eyes, darker yellow urine and pale faeces) itchy skin abdominal pain

Type of Hepatitis
A
Source of virus feces

E
feces

blood/ blood/ blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids percutaneous percutaneous percutaneous permucosal permucosal permucosal

Route of transmission

fecal-oral

fecal-oral

Chronic infection
Prevention

no

yes

yes

yes

no

pre/postexposure immunization

pre/postexposure immunization

blood donor pre/postscreening; exposure risk behavior immunization; modification risk behavior modification

ensure safe drinking water

Hepatitis A (HAV)
Due to non enveloped, single stranded RNA picornavirus Serum AST and ALT increased to hundreds for 1 to 3 weeks Relative lymphocytosis is frequent

Serologic test for HAV

Ig M anti HAV :
appears at the same time as syptoms in > 99% of cases peaks within first month, becomes non detectable in 12 (usually 6) Presence confirms diagnosis of recent acute infection

Anti HAV total:

Predominantly IgG Almost always positive at onset of acute hepatitis and is usually detectable for life Found in 50% of population, indicates previous exposure to HAV

Hepatitis A Infection
Typical Serological Course
Symptoms

Total antiHAV

Titre

ALT

Fecal HAV

IgM anti-HAV

12

24

Months after exposure

Hepatitis B (HBV)
Due to enveloped, double stranded DNA hepadna virus Divided into 3 stages: 1. Acute hepatitis: lasts 1-6 months, mild/ no symptoms
AST & ALT increased > tenfolds Serum bilirubin is usually normal or slightly increased HBsAg gradually arises to high titer and persist, HBeAg also appears

2. Chronic hepatitis: transaminase increased > 50% for > 6 months, most cases resolve but some develop cirrhosis and liver failure
AST & ALT fall to 2-10x normal range HBsAg usually remains high and HBeAg remains present

3. Chronic carrier: are usually but not always healthy and asymptomatic
AST and ALT fall to normal or < 2x normal HBsAg positive > 6 months, HBc IgM negative, but anti HBc positive

Hepatitis B Virus Modes of Transmission

Sexual - sex workers and homosexuals are particular at risk.
Parenteral - IVDA, Health Workers are at increased risk. Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.

Concentration of Hepatitis B Virus in Various Body Fluids

High Moderate
Low/Not Detectable urine feces sweat tears breastmilk

blood semen serum vaginal fluid wound exudates saliva

HBV : Structure

SEROLOGICAL TEST OF HBV

A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection. HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity to HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course

Acute (6 months) HBeAg HBsAg Total anti-HBc Chronic (Years) anti-HBe

Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36

52

Years

Weeks after Exposure

Serologic diagnosis of viral hepatitis

Significance HBsAg HBeAg Anti-HBc
IgG Acute HBV Chronic HBV, Active replication

Anti-HBc
IgM

Anti-HBs IgG -

+ +

+ +

+
-

Chronic HBV, quiescent Resolved HBV Postvaccine Immune HBV

+
-

+
-

+
-

Quiescent = inactive = quiet

18

Possible Outcomes of HBV Infection

Acute hepatitis B infection
3-5% of adultacquired infections 95% of infantacquired infections Chronic HBV infection

Chronic hepatitis 12-25% in 5 years

6-15% in 5 years
Hepatocellular carcinoma
Death

Cirrhosis

20-23% in 5 years Liver failure

Liver transplant

Death

Prevention
Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries. Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive.

Other measures - screening of blood donors, blood and body fluid precautions.

HEPATITIS C (HCV)

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Risk Factors Associated with Transmission of HCV

Transfusion or transplant from infected donor Injecting drug use Hemodialysis (yrs on treatment)

Accidental injuries with needles/sharps

Sexual/household exposure to anti-HCVpositive contact

Multiple sex partners

Birth to HCV-infected mother

HCV INFECTION
INCUBATION 1 PERIOD 6 -7 WEEKS (Range 2 26 weeks)
80 -85% CHRONIC HEPATITIS

ACUTE 2 INFECTION
60 -80% ASYMPTOMATIC 20- 30% WITH JAUNDICE

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Hepatitis C Virus Infection

Typical Serologic Course
anti-HCV Symptoms

Titre

ALT

Normal 0 1 2 3 4 Months 5 6 1 2 3 Years 4

Time after Exposure

PROGRESSION
ACUTE HEPATITIS C
15-40% will spontaneously resolve, generally within the first 6-18 months after acute onset. 60-85% will progress to chronic infection

CHRONIC
85-90% stable 10-15% progress to cirrhosis

PROGRESSION
CIRRHOSIS
75% slowly progressive 25% progress to HCC 2-4% liver failure
Factors of poor prognosis:
-Age >40 years -Alcohol > 50g/Hour -Male gender -Duration of infection -Co-infection HBV/HIV -Tobacco consumption

HCC

Risk increases for every year for a patient with chronic hepatitis C. Patients without signs of cirrhosis can develop HCC

Diagnosis
of HCV Infection

Indirect tests: detect antibody against HCV 1. Anti HCV 2. RIBA

(recombinant immunoblot assay)

Direct tests : components of the HCV particle 1.HCV RNA(PCR) Qualitative

Quantitative

2. HCV Core antigen

Usefull in detecting window peroid

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Prevention of Hepatitis C
Screening of blood, organ, tissue donors High-risk behavior modification

Blood and body fluid precautions

HEPATITIS D
Double stranded enveloped RNA virus Depends upon HBV for expression and replication Often severe with relatively high mortality in acute disease and frequent development of cirrhosis in chronic disease Chronic HDV inf. Is more severe and higher mortality rate than other types of viral hepatitis Serologic test :
Anti HDV in px with HBsAg positive hepatitis

HEPATITIS E
Unveloped, single stranded enveloped RNA virus Endemic area: Mexico, India, Africa, Burma, Russia Serologic test:
- Antibody to hepatitis E establish dx. - IgM antibodies indicate recent infection - Serologic markers for HVA, HBV, HCV and other cause of acute hepatiti are absent

??QUESTIONS??