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Learning outcomes
Modes of transmission and the pathogenesis of viral hepatitis in humans Main clinical features of viral hepatitis Principles of diagnosis, management and prevention viral hepatitis in humans
A
NANB
Enterically E transmitted
Serum
B D
Hepatitis A-E
A
Source of virus Faeces
E
Faeces
Blood/ Blood/ Blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids Percutaneous Percutaneous Percutaneous permucosal permucosal permucosal Yes Yes Yes
Fecal-oral
Fecal-oral
No
No
Pre/postPre/postBlood donor Pre/postEnsure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification
Hepatitis A virus
Hepatitis A virus
Non enveloped RNA virus Related to enteroviruses, formerly known as enterovirus 72, now put in the family: heptovirus Only one stable serotype 4 genotypes exist but in practice most of them are group 1
Incubation period:
Average 30 days Range 15-50 days <6 years, <10% 6-14 years, 40%-50% >14 years, 70%-80% Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis None
Complications:
Chronic sequelae:
Hepatitis A infection
Typical Serological Course
Symptoms
Total anti-HAV
Titre
Faecal HAV
ALT
IgM anti-HAV
1 2
2 4
Transmission of Hepatitis A
Close personal contact (Household contact, sexual contact and child care centers) Contaminated food and water (Infected food handlers & raw shellfish) Blood exposure (very rare) (Injecting drug use and transfusion)
Laboratory diagnosis
Acute infection is diagnosed by the detection of HAV - IgM in serum by ELISA Past Infection i.e. immunity is determined by the detection of HAV - IgG by ELISA Direct Detection - EM, RT-PCR of faeces
Many cases occur in community-wide outbreaks No risk factor identified for most cases Highest attack rates in 5-14 year olds Children serve as reservoir of infection Persons at increased risk of infection Travelers Homosexual men Injecting drug users
Prevention Immunoglobulin
Pre-exposure
Hepatitis B Virus
Enveloped DNA virus Core - HBcAg and HBeAg Coat HBsAg HBV - 8 genotypes (A-H)
15%-25%
Chronic Hepatitis B
1. Chronic persistent hepatitis asymptomatic 2. Chronic active hepatitis symptomatic exacerbations 3. Cirrhosis 4. Hepatocellular carcinoma (HCC)
Total anti-HBc
Titre
HBsAg IgM anti-HBc anti-HBs
12 16 20 24 28 32 36
52
100
Titre
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36
52
Years
Diagnosis
An array of serological tests are used for the diagnosis of acute and chronic HBV infection HBsAg Used as a general marker of infection Anti-HBs - 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/infectiveness Anti-HBe - Virus no longer replicating The patient can still be positive for HBsAg HBV-DNA - Indicates active replication of virus, more accurate than HBeAg Used mainly for monitoring response to therapy
Treatment
Prevention
Vaccination - Highly effective recombinant vaccines Vaccinate those at increased risk of HBV infection (health care workers) Given routinely to neonates as universal vaccination Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B It is particular efficacious within 48 h of the incident Given to neonates who are at increased risk of contracting hepatitis mothers HBsAg + HBeAg positive
Other measures - Screening of blood donors, blood and body fluid precautions (ABC)
HCV has a total of six genotypes (type 1 to 6) Genotype 1 and 4 has a poorer prognosis and response to interferon therapy
The spectrum of chronic HCV infection is essentially the same as chronic HBV infection All the manifestations of chronic HBV infection may be seen, with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis and HCC
antiHCV
Titre
ALT
Laboratory diagnosis
HCV antibody - Used to diagnose HCV infection Not useful in the acute phase as it takes at least 4 weeks for the antibody to appear
HCV RNA - Various techniques are available e.g. PCR and qPCR used to diagnose HCV infection in the acute phase and in monitoring the response to antiviral therapy HCV antigen - An ELISA for HCV antigen is available It is used in the same capacity as HCV RNA tests but is much easier to carry out
Treatment
Prevention of Hepatitis C
Screening of blood, organ and tissue donors High-risk behavior modification Blood and body fluid precautions (ABC)
RNA
Hepatitis E virus
Average 40 days Overall, 1%-3% Pregnant women, 15%-25% Increased with age None identified
Outbreaks: Faecally contaminated drinking water Large epidemics have occurred in the Indian subcontinent, China, Africa and Mexico
Avoid drinking water of unknown purity, uncooked shellfish & uncooked fruits/vegetables Vaccine?
Following serological data for a 42 year old male that had a history of unprotected sexual encounter during his travel 5 weeks ago to China presented with fever, jaundice and malaise.
Laboratory findings HBsAg IgG anti-HBc IgM anti-HBc Anti-HBsAg positive positive positive negative
Your diagnosis based on these findings is? A. acute HBV infection B. acute HCV infection C. vaccinated against HBV D. super infection with HDV E. chronic HBV infection