acute & chronic hepatitis.docx

VIRAL HEPATITIS

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Acute hepatitis
Inflammation of liver
parenchyma that resolves
within 6 months after
infection
Viral infections :
 hepatitis A, B ± D, C, E
 Cytomegalovirus
 Epstein-Barr virus
 Herpes simplex
 Yellow fever
Drug- induced liver injury:
paracetamol
Autoimmune hepatitis
Non-viral infection:
Toxoplasma gondii,
leptospira, coxiella burnettii
Alcohol
Poison: Amanita phalloides
(mushrooms), Aflatoxin,
Carbon tetrachloride
Others: pregnancy,
circulatory insufficiency,
Wilson's disease
Hepatocyte injury with cell
death, inflammation and
regeneration without
structural change to the liver
Extent of damage : varies
from only single and small
group of hepatocytes die
(focal necrosis) to multiacinar necrosis involving
substantial part of liver
(massive hepatic necrosis)
Acute liver failure
Cholestatic hepatitis (hep A)
Aplastic anaemia
Chronic liver disease and
cirrhosis (hep B, C)
Relapsing hepatitis

Definiton

Chronic hepatitis
- Liver inflammation that last
for 6 months or longer
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Etiology
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Pathology

Complication
s

Viral: Hepatitis B, C
Drugs: Methyldopa,
Isoniazid, Ketoconazole,
Nitrofurantoin
Hereditary: Wilson's disease
Others: Inflammatory bowel
disease like Ulcerative colitis

Characterized by:
- Portal tract inflammation
- Interface hepatitis
- Portal-based fibrosis,
bridging fibrosis or cirrhosis
- Also lobular inflammation
and apoptosis

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Liver failure
Portal hypertension
Coagulopathy
Hypoalbuminaemia
Hepatorenal syndrome
Liver cirrhosis

ACUTE HEPATITIS
Clinical Features:
- Non-specific prodromal illness: headache, myalgia, arthralgia, nausea, anorexia
- Jaundice : few days to 2 weeks
- Vomiting, diarrhoea
- Abdominal discomfort
- Dark urine, pale stools
- Liver tenderness, minimally enlarged
- Mild splenomegaly, cervical lymphadenopathy
Investigations:
- Liver function tests: serum transaminases between 200 and 2000 U/L (lower in
chronic)
- Plasma bilirubin, ALP increased
- Prolonged prothrombin time
- White cell count: relative lymphocytosis
- Serological test to confirm aetiology of infection
1. HEPATITIS A
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Epidemiology
Picornavirus group of
enterovirus
Transmission by faecooral route
Infected individual may
be asymptomatic, but
excrete the virus in faeces
for about 2-3 weeks
before the onset of
symptoms
Common in children but
often asymptomatic,
common in areas of
overcrowding and poor
sanitation
In outbreaks: water and
shellfish have been
vehicles of transmission
No chronic carrier state
Acute liver failure is rare
in hepatitis A

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Investigations
Anti- HAV antibody is
important as HAV is only
present in blood
transiently during
incubation period; antiHAV (IgM type)
indicating a primary
immune response thus is a
diagnostic of an acute
HAV infection; fall to low
levels within about 3
months of recovery, antiHAV (IgG type)is no
diagnostic value as HAV
infection is common but
can be used as a marker
of previous infection,
indicates immunity to
HAV
Excretion of virus in
stools occur only 7-14
days after onset of the
clinical illness, cannot be
grown readily

Managements
Can be prevented by
improving social
conditions
Substantial protection by
active immunisation with
an inactivated virus
vaccine for those in
particular risk (close
contacts of HAV- infected
patients, the elderly, those
with other major disease,
pregnant women)
Antiviral drugs has no
role

2. HEPATITIS B
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Epidemiology
One of the most common
causes of chronic liver
disease and hepatocellular
carcinoma
Acute infection is often
asymptomatic, particularly
when acquired at birth,
many individuals with
chronic infection also
asymptomatic
The risk of progression to
chronic liver disease
depends on the source and
timing of infection
Source of Hep B infection
and risk of chronic
infection: Horizontal
transmission (10%): drug
user injection, infected
blood products, tattoo or
needle puncture, sexual
contact, close living;
vertical transmission
(90%) ; HBsAg-positive
mother
Chronic hepatitis can lead
to cirrhosis or HCC
Virus is not directly
cytotoxic to cells, rather is
is an immune response to
viral antigens displayed
on infected hepatocytes
that initiates liver injury

Investigations
1. Serology
- HBV contains several
antigens and their
antibodies are important in
identifying the infection
- HBsAg is an indicator of
active infection; appear late
in the incubation period, but
before the prodromal phase;
present for a few days only
and disappear even before
jaundice developed; lasts
for 3-4 weeks and can
persist for up to 5 months;
if persists longer than 6
months indicates chronic
infection; anti- HBs
antibody usually present
after 3-6 months and
persists for many years or
perhaps permanently, it
implies either a previous
infection (anti- HBc
present) or previous
vaccination (anti- HBc
absent)
- HBcAg is not found in
blood, but antibody (antiHBc) appears early in the
illness and rapidly reaches a
high titre and subsides
gradually; initially IgM
type with IgG antibody
appearing later; IgM reveal
an acute infection when
HBsAg has disappeared and
before anti-HBs developed
- HBeAg is an indicator of
active viral replication;
appear transiently followed
by production of anti-HBe
- Chronic HBV infection;
presence of HBsAg and
anti-HBc (IgG) in the blood
2. Viral load and genotype
- PCR: measure viral DNA
levels in peripheral blood;
excess of 105 copies/ml in
presence of active
replication (HBeAg)

Managements
1. Acute hepatitis B
- Supportive with
monitoring for acute liver
failure
- No definitive evidence
that antiviral therapy
reduces the severity or
duration of infection
- Full recovery occurs in
90-95% of adults within 6
months, 5-10% develop a
chronic hepatitis B
infection (vertical
transmission recovery is
rare)
2. Chronic hepatitis B
- Treatments are still
limited, no drug is
consistently able to
eradicate infection
completely
- The goals are HBeAg
seroconversion, reduction
in HBV-DNA and
normalisation of the LFTs
- Indication: high viral load
in the presence of active
hepatitis
- Direct-acting nucleoside/
nucleotide antiviral
agents; inhibiting the
reverse transcription of
pre-genomic RNA to
HBV-DNA by HBV-DNA
polymerase but not
cccDNA (relapse is
common); lamivudine,
entecavir and tenofovir
- Interferon-alpha; most
effective in patient with
low viral load and serum
transaminases greater than
twice; side effects are
common
- Liver transplantation with
post-transplant
prophylaxis
- A recombinant hep B
vaccine

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3. HEPATITIS C
Epidemiology
Caused by RNA
flavivirus
Acute symptomatic
infection is rare, most
individual remains
asyptomatic until
progression to cirrhosis
occur
80% of the exposed
become chronically
infected and late
spontaneous viral
clearance is rare
Hep C is cause of‘non-A,
non-B hepatitis’
Risk factors of chronic
hep C infection:
intravenous drug misuse,
unscreened blood
products, vertical
transmission, needlestick
injury, iatrogenuc
parenteral transmission,
sharing
toothbrushes/razors

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3.
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Investigations
Serology and virology
HCV protein antigens
give rise to antibodies that
may be appear in blood
about 6-12 weeks
following acute infection
Hep C RNA in the blood
as early as 2-4 weeks
after infection
Active infection: presence
of serum hep C RNA in
anyone who is antibody
positive
Anti-HCV antibodies
persist even after viral
clearance
Molecular analysis
Six common genotypes
Genotypes has no effect
on progression but does
affect response to
treatment
Genotype 1 is common in
northern Europe and is
less easy to eradicate than
genotypes 2 and 3 with
traditional pegylated
interferon alpha/ribavirinbased treatement
Liver function tests
Normal or show
fluctuating serum
transaminases between 50
and 200 U/L
Liver histology
Liver biopsy; to stage the
degree of liver damage
The degree of
inflammation and fibrosis
can be scored
histologically. Metavir
system

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Managements
Aim to eradicate
infection
Treatment of choice: dual
therapy with pegylated
interferon-alpha given
weekly subcutaneous
injection together with
oral ribavirin
Side effects of ribavirin:
haemolytic anaemia,
teratogenicity; of
interferon: flu like
symptoms, irritability,
depression
Virological relapse can
occur in the first 3
months after stopping
treatment
Cure is defined as loss of
virus from serum 6
months after completing
therapy
Triple therapy with the
addition of protease
inhibitors such as
teleprevir and boceprevir
Liver transplantation
should be considered
when complication of
cirrhosis occur
No active or passive
protection against HCV

4. HEPATITIS D (DELTA VIRUS)
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Epidemiology
HDV is an RNAdefective that has no
independent existence;
required HBV for
replication
Same sources and modes
of spread as HBV
Simultaneous infections
give rise to acute hepatitis,
chronic infection with
HBV and HDV causes
rapidly progressive
chronic hepatitis and
eventually cirrhosis
Modes of transmission: in
endemic are by close
personal contact, vertical
transmission; in nonendemic areas mainly by
parenteral drug misuse

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Investigations
Managements
HDV contains a single
- Effective management of
antigen producing an
hepatitis B prevents
antibody (anti-HDV)
hepatitis D
Delta antigen appears in
blood only transiently and
diagnosis depends on
detecting anti-HDV
Simultaneous infection of
HBV and HDV associated
with appearance of low
titres of anti-HDV of IgM
type within a few days of
the onset of illness
Antibody disappear
within 2 months but
persists in a few patients
Super-infection patient
with chronic HBV
infection produce high
titres of anti-HDV
initially IgM and later
IgG; anti-HDV titres
plateau at high levels

5. HEPATITIS E
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Epidemiology
Investigations
Caused by an RNA virus - In acute infection, IgM
that endemic in India and
antibodies to HEV are
the Middle-East
positive
Clinical presentation of
hepatitis E similar to that
of hepatitis A; but differs
from hep A in that
infection during
pregnancy is associated
with development of acute
liver failure which has a
high mortality
Transmission: faeco- oral
route
Self-limiting acute
hepatitis and does not
cause chronic liver disease

Managements
- Management of hepatitis E
similar to that of hepatitis
A