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Hepatitis A virus (HAV) is a Hepatovirus related to the Enteroviruses
(see Enterovirus and viruses that infect the gastrointestinal tract
) with four genotypes.
Transmission is by the faecal-oral route. Institutional outbreaks
are associated with summer and point-source outbreaks follow
faecal contamination of water or food (e.g. oysters). Seroprevalence
is highest in individuals of lower socioeconomic groups.
Anicteric infection is more common in the young; the risk of
symptomatic disease increasing with age. Infection is characterized
by a 'flu-like illness followed by jaundice, with most patients
making an uneventful recovery. Virus is shed in stool before jaundice
Treatment and Prevention
- Anti-HAV IgM is diagnostic appearing before jaundice develops
and persisting for 3 months.
- IgG antibodies determine a patient's immune status.
- HAV RNA can be detected in the blood and stool during the
acute phase of infection by nucleic acid amplification test (NAAT).
Treatment is symptomatic and chronic hepatitis does not occur.
Adequate sanitation and good personal hygiene will reduce the
transmission of HAV. Vaccination against HAV is recommended
for travellers to high-risk areas, patients with chronic liver infection and individuals with high-risk occupations (e.g. healthcare
workers, sewage workers). Passive immunity can be provided
using human immunoglobulin.
Hepatitis B (HBV), a hepadnavirus, is an enveloped virus that
contains partially double-stranded DNA encoding surface antigen
(HBsAg), core antigen (HBcAg), pre-core protein (HBeAg), a
large active polymerase protein and transactivator protein. The
virus replicates through a reverse transcriptase. HBV is transmitted
by parenteral, congenital and sexual routes. A quarter of the
global population is infected.
- HBV infection has a long incubation period (up to 6 months).
- Acute hepatitis of variable severity develops insidiously.
- Fulminant disease carries a 1-2% mortality and 10% of patients
develop chronic hepatitis complicated by cirrhosis or hepatocellular
- Congenital infection carries a high risk of hepatocellular
Treatment and Prevention
- Immunoassays for HBsAg, HBeAg, HBcAg and associated antibodies
enable the diagnosis of acute infection and previous exposure
- Viral load can be measured by NAAT and sequencing for resistance
mutations allows monitoring of therapy and directs drug
- Pegylated α-interferon.
- Lamivudine, adefovir, entecavir, tenofovir, telbivudine and clevudine
have antiviral efficacy. Emtricitabine and valtorcitabine are
nearing clinical introduction.
- Therapy should be considered in chronic infection as responders
have a reduced risk of liver damage and liver cancer in the longterm.
HBeAg seroconversion is often taken as a mark of Treatment
- Those at high risk should be immunized with recombinant HBV
- Vaccine and specific immunoglobulin should be administered to
neonates of infected mothers to reduce transmission.
- Blood donations must be effectively screened.
- Needle-exchange programmes for drug misusers and sexualhealth
education schemes can help to reduce transmission.
Hepatitis C (HCV) is a sense RNA virus encoding a single polypeptide.
Transmission is mainly through infected blood. Seroprevalence
is approximately 1% in healthy blood donors, higher in
developing countries and highest in high-risk groups, such as those
who have received unscreened transfusions. Healthcare workers
are at risk. Sexual transmission and vertical transmission do occur
but are uncommon.
Infection may cause a mild acute hepatitis but many cases are
asymptomatic; fulminant disease is rare. HCV infection persists in
up to 80% of patients; up to 35% of these develop cirrhosis, liver
failure and hepatocellular carcinoma between 10 and 30 years
later. This occurs because frequent virus mutation results in immunologically
distinct 'quasi-species', which allow the organism to
escape immunological control.
Treatment and Prevention
- HCV cannot be cultured.
- Diagnosis is by antibody and antigen detection.
- A NAAT is available.
- Sequencing to determine genotype defines the likelihood of
response to therapy (see below).
- Treatment is monitored by measurement of viral load.
- Ribavirin and pegylated α-interferon.
- Response is best in patients with genotypes 1 and 2 and those
with low initial viral load, but up to 80% will clear the virus.
- Liver fibrosis or necrotic inflammation from HCV infection is
an indication for liver transplantation.
- Preventive measures are similar to those employed against HBV.
- There is no vaccine.
This defective RNA virus is surrounded by an HBsAg envelope
and is transmitted with and in the same way as hepatitis B virus
or as a super-infection in an HBV carrier. Although asymptomatic
infection may occur, hepatitis D (HDV) is associated with severe
hepatitis and an accelerated progression to carcinoma. A real-time
NAAT is the most rapid method of making the diagnosis but
antigen detection or IgM antibody detection by enzyme immunoassay
(EIA) can also provide confirmation. Preventive measures
for HBV also protect against HDV.
- Hepatitis E is a small, single-strand, non-enveloped RNA virus.
- Transmission is by the faecal-oral route.
- Outbreaks occur after contamination of water supplies or food.
- It is found in Asia, Africa and Central America.
- It usually causes a self-limiting hepatitis of varying severity.
- Diagnosis is by IgM or NAAT.
- Infection is prevented by hygiene measures.
Viral hepatitis can also be caused by other viruses (e.g. cytomegalovirus
[CMV], herpes simplex and Epstein-Barr virus [EBV]).