Hepatitis

Dr. Lukman Hakim Zain Divisi Gastroenterologi Bag IPD FKUSU/RS HAM Medan.

Many causes of hepatitis

Infectious Bacterial
Leptospirosis Syphillis Tuberculosis Toxoplasmosis Amebiasis Epstein Barr Herpes Simplex Varicella Zoster Coxsackievirus Rubella Yellow Fever Alcohol Drugs

Parasitic

Viral

Noninfectious

Vial agents that primarily or exclusively infect the liver

Hepatitis A virus Hepatitis B virus Hepatitis C virus Infectious hepatitis Serum hepatitis Parenterally transmitted

Hepatitis E virus
Hepatitis D virus Hepatitis G virus

Enterically transmitted
Coinfection with HBV Parenterally transmitted

Viral Hepatitis - Historical Perspective

Infectious

A
NANB

Enterically E transmitted

Viral hepatitis Serum

B D
F, G, ? other

Parenterally C transmitted

Viral Hepatitis - Overview

Type of Hepatitis

A
Source of virus Route of transmission Chronic infection feces

E
feces

blood/ blood/ blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids

fecal-oral percutaneous percutaneous percutaneous fecal-oral permucosal permucosal permucosal no yes yes yes no

Prevention

pre/postpre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification

Initial laboratory evaluation of jaundiced patient

TEST PERFORMED
Urine bilirubin Serum bilirubin Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Alkaline phosphatase Prothrombin time, partial thromboplastin time, platelet count, bleeding Blood count with blood smear exam

MEASUREMENT
Conjugated bilirubin Conjugated and unconjugated bilirubin Hepatocellular damage Hepatocellular damage Intrahepatic or extrahepatic obstruction Clotting mechanism

Red blood cell morphology, parasites, atypical lymphocytes

HEPATITIS A VIRUS
RNA Picornavirus
Single serotype worldwide Acute disease and asymptomatic infection

No chronic infection
Protective antibodies develop in response to infection - confers lifelong immunity

ACUTE HEPATITIS A CASE DEFINITION FOR SURVEILLANCE

Clinical criteria
An acute illness with: discrete onset of symptoms (e.g. fatigue, abdominal pain, loss of appetite, intermittent nausea, vomiting), and jaundice or elevated serum aminotransferase levels Laboratory criteria IgM antibody to hepatitis A virus (anti-HAV) positive Case Classification
Confirmed. A case that meets the clinical case definition and is laboratory confirmed or a case that meets the clinical case definition and occurs in a person who has an epidemiologic link with a person who has laboratoryconfirmed hepatitis A (i.e., household or sexual contact with an infected person during the 15-50 days before the onset of symptoms).

HEPATITIS A - CLINICAL FEATURES

Jaundice by

age group:
Rare complications:

<6 yrs 6-14 yrs >14 yrs

<10% 40%-50% 70%-80%

Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Average 30 days Range 15-50 days None

Incubation period: Chronic sequelae:

EVENTS IN HEPATITIS A VIRUS INFECTION

Clinical illness

Infection

ALT IgM IgG

Response

Viremia

HAV in stool

10

11

12

13

Week

CONCENTRATION OF HEPATITIS A VIRUS IN VARIOUS BODY FLUIDS

Feces

Body Fluids

Serum Saliva

Urine

100

102

104

106

108

1010

Infectious Doses per mL

Source: Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890

GLOBAL PATTERNS OF HEPATITIS A VIRUS TRANSMISSION

Endemicit y Hig h Moderate Diseas e Rate Low to high High Peak Age of Infection Early childhood Late childhood/ young adults Young adults Adult s Transmission Patterns Person to person; outbreaks uncommon Person to person; food and waterborne outbreaks Person to person; food and waterborne outbreaks Travelers; outbreaks uncommon

Low Very low

Low

Very low

GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS INFECTION

HEPATITIS A VIRUS TRANSMISSION

Close personal contact (e.g., household contact, sex contact, child day-care centers) Contaminated food, water (e.g., infected food handlers) Blood exposure (rare) (e.g., injection drug use, rarely by transfusion)

PREVENTING HEPATITIS A Hygiene (e.g., hand washing) Sanitation (e.g., clean water sources) Hepatitis A vaccine (pre-exposure) Immune globulin (pre- and post-exposure)

HEPATITIS A VACCINES
Highly immunogenic 97%-100% of children, adolescents, and adults

have protective levels of antibody within 1 month of receiving first dose; essentially 100% have protective levels after second dose
Highly efficacious In published studies, 94%-100% of children

protected against clinical hepatitis A after equivalent of one dose

HEPATITIS A VACCINE EFFICACY STUDIES

Vaccine

Site/ Age Group

Vaccine Efficacy (95 % Cl)

HAVRIX (GSK) 2 doses 360 EL.U. VAQTA (Merck) 1 dose 25 units

Thailand 1-16 yrs

38,157

94% (79%-99%)

New York 2-16 yrs

1,037

100% (85%-100%)

JAMA 1994;271:1363-4; N Engl J Med 1992;327:453-7

SAFETY OF HEPATITIS A VACCINE

Most common side effects Soreness/tenderness at injection site - 50% Headache - 15% Malaise - 7% No severe adverse reactions attributed to vaccine Safety in pregnancy not determined risk likely low Contraindications - severe adverse reaction to previous dose or allergy to a vaccine component No special precautions for

DURATION OF PROTECTION AFTER HEPATITIS A VACCINATION

Persistence of antibody

At least 5-8 years among adults and children No cases in vaccinated children at 5-6 years of follow-up

Efficacy

Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years Other mechanisms, such as cellular memory, may contribute

COMBINED HEPATITIS A HEPATITIS B VACCINE

Approved by the FDA in United States for persons >18 years old Contains 720 EL.U. hepatitis A antigen and 20 g. HBsAg Vaccination schedule: 0,1,6 months Immunogenicity similar to single-antigen vaccines given separately Can be used in persons > 18 years old who need vaccination against both hepatitis A and B Formulation for children available in many other

HEPATITIS A PREVENTION IMMUNE GLOBULIN

Pre-exposure

travelers to intermediate and high HAV-endemic regions

Post-exposure (within 14 days)

Routine household and other intimate contacts Selected situations institutions (e.g., day-care centers) common source exposure (e.g., food prepared by infected food handler)

Hepatitis B Virus
HBV

HBV nomenclature
HBV: hepatitis B virus HBsAg: hepatitis B virus surface antigen HBcAg: hepatitis B virus core antigen

HBV Epidemiology
Horizontal transmission
Person-to-person spread
Parenteral Sexual

Vertical transmission
Chronically infected mother to child
At birth or via breast milk

HBV Pathology
Portal of entry
Percutaneous is most efficient Sexual or perinatal is less efficient but major source

Into bloodstream and to liver

Hepatocytes
Little cytopathology Immune pathology

HBV Epidemiology

HBV Clinical Syndromes

ACUTE INFECTION
Incubation phase: long Prodromal phase: insidious
Flu-like: malaise, fatigue, anorexia, nausea, abdominal discomfort, chills

Icteric phase: liver damage: jaundice, dark urine, pale stools Recovery: decline in fever; renewed appetite

HBV Diagnosis
Clinical
Symptoms Looks like HAV

HBV Diagnosis
Laboratory
Liver enzymes Serology
HBeAg, HBcAg, virus: active infection Anti-HBc IgM: acute active infection Anti-HBe IgG: acute infection

HBV Treatment
Supportive Interferon-: many side effects Other antiviral drugs
Lamivudine: during viral infection Famciclovir: reverse transcriptase inhibitor

HBV Complications
Fulminate hepatitis Chronic hepatitis
5%-10% of HBV infections 10% of these progress to cirrhosis/liver failure At higher risk for fulminant hepatitis

HBV Complications
Chronic HBsAg antigenemia Chronic persistent hepatitis (CPH)

Postviral; asymptomatic carrier state; HBsAg only

Postviral; elevated transaminase; no progression to liver disease

Chronic active hepatitis (CAH)

Chronic lobular hepatitis (CLH) Liver cirrhosis Hepatocellular carcinoma

Postviral; progresses to liver disease

Postviral; no progression to liver disease; elevated transaminase levels

20-30 years of persistent HBV infection leading to liver injury

HBV Prevention
Screen blood products Sterilization of needles, etc. Avoiding intimate contact, e.g., household or sexual contacts Vaccination
Subunit vaccines HBsAg