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Viral Hepatitis
Dept. of Infectious Diseases
SunYat-sen University
Q.F.XIE
Introduction
• Viral hepatitis are a group of diseases,
Caused by A、B、C、D and E 5 hepatitis virus
• Hepatitis A and E
Transmitted by fecal-oral route, present acute
and self-limited course
• Hepatitis B ,C and D
Spread parenterally easily lead to chronic
hepatitis
• Clinical characters including
fatigue, intestinal symptoms
tender and enlarged liver
abnormal LFTs
jaundice in some cases
very variable in severity
Significance
Highly endemic
Wide clinical spectrum
High fatality rate in severe cases
No specific pathogenic therapy available now
Chronic hepatitis B and C very common,
some may develop to cirrhosis even HCC
Successful vaccination for HBV and HAV
Etiology-HAV
Heparnavirus
Appeared in bile and feces, spreaded via feces
No chronic carrier status observed
Anti-HAV antibody to HAV
Anti-HAV IgM
indicative of current or recent infection
appeared very early, disappear in about 3months
most useful for confirm the diagnosis
Anti HAV IgG
current or previous infection
a protective antibody, conferring
immunity
persist for life long time
Etiology-HBV
• Orthohepadnavirus, Dane particle
• 4 open reading frame: S,C,P,X
• 8 genotypes A-H, B and C
predominantly in China
• Strong ability against to environment
• 3 antigen and antibody system
• HBsAg
found in serum and other body fluid
not infectious itself
suggesting current infection and
infectivity
Anti-HBs
a protective antibody to HBsAg
an indicator of past infection and
immunity to HBV reinfection
suggesting non-infectious
• HBeAg
suggesting HBV replication and high
infectivity
negative when pre-C mutation but with
high level of replication
useful for evaluation of anti-HBV
therapy
Anti-HBe
antibody to HBeAg
HBe seroconversion
HBeAg(+) →(-)and anti-HBe(-) →(+)
• HBcAg
existing in the core of virion
a marker of replication and infectivity
Anti-HBc IgM
a marker of acute primary HBV infection
Anti-HBc IgG
appeared in almost all HBV present and
past infection host body
• HBVDNA
the genome of HBV
suggesting active virus replication and
infectivity
useful for diagnosis and evaluation of
anti-HBV therapy
Hepatitis B Virus
Etiology-HCV
• RNA virus, 6genotypes, mainly 1b in the
country
• Molecular heterogeneity driven by high
mutation rate usually proceed to
chronic course
• Anti-HCV IgM and IgG types
antibody to HCV
suggesting HCV infection
• HCVRNA
the genome of HCV
suggesting replication and infectivity
of HCV
useful for the diagnosis and evaluation
of antivirus treatment
Etiology-HDV
• An incomplete RNA virus
• Causes hepatitis only patients with either
acute(coinfection) or chronic (superinfection)
hepatitis B
• HDVAg and anti-HDV
•
both the markers of HDV infection
• HDVRNA
•
the genome of HDV
•
a marker of existing HDV infection
•
suggesting virus replication and infectivity
Etiology-HEV
Nonenveloped RNA virus
Appeared in bile and feces, spreaded via
feces
No chronic carrier status observed
Anti-HEV IgM and IgG
both appeared in acute infection
useful for the diagnosis of HEV infection
• HEVRNA
the genome of the virus
suggesting existing of HEV infection
not available for routine clinical
diagnosis
Epidemiology
• Source of infection
Patients with acute or chronic viral
hepatitis
Carriers of hepatitis virus, particularly
asymptomatic carriers
• Transmission
Hepatitis A and E transmitted by the
fecal- oral route, water-borne and
food-transmitted infection in epidemics
Hepatitis B
transmitted parenterally
mother-to-infant play a key role in China
blood ,blood products and body fluid
others
Hepatitis C and D
similar to hepatitis B
intravenous drug abusers most common
hepatitis C for the time being
Prevalence rate in China 1992
• Hepatitis
• Hepatitis
A
B
• Hepatitis
• Hepatitis
• Hepatitis
C
D
E
anti-HAV+
80.90%
HBsAg +
9.75%
(2006) 7.18%
anti-HCV+
3.20%
anti-HDV+
1.15%
anti-HEV+
17.2%
Pathogenesis
• Hepatocellular damage produced by
viral replication directly only in
hepatitis D
• Other types of viral hepatitis
induced mainly by immunemediated attack on the liver
Pathology
• The varying lesion could be seen in
entire liver, but variable in severity
and in different stages of the disease
• No specific lesion suggesting etiologic
type of hepatitis virus
Clinical manifestations
• Wide clinical spectrum from
asymptomatic form to fatal outcome such
as liver failure
• Similar clinical course in different
etiological type of viral hepatitis
The clinical types viral hepatitis
Acute hepatitis
Chronic hepatitis
Liver failure (severe hepatitis)
Cholestatic viral hepatitis
Hepatitis cirrhosis
Asymptomatic virus carrier status (usually
only in HBV)
Incubation period
Hepatitis A
Hepatitis E
2---6w
2---9w
Hepatitis B
Hepatitis C
Hepatitis D
1---6m
2w---6m
4---20w
~4w
~6w
~3m
~ 6w
Acute hepatitis
3 phases of the icteric hepatitis
•
•
•
•
Prodromal phase
sudden or insidious onset, lasting 3-7d
constitutional symptom: malaise,
fatigue, mild fever some time, dark
urine
gastrointestinal symptoms: anorexia,
nausea, vomiting
serum ALT level rise deeply
Jaundice phase
jaundice appeared and peak level often
in 2 weeks after the onset
other symptoms subside after jaundice
tender liver palpable
serum bilirubin elevated
lasting for 2—6 weeks
Convalescent phase
symptoms and jaundice gradual
resolution
liver return to normal size
serum ALT and bilirubin decreased
1 to 2 months needed
Anicteric acute viral hepatitis more
common, mild manifastation
Chronic hepatitis
Seen only in hepatitis B,C and D,
virus infection over 6 months
Severity variable, 3 subtypes: mild,
typical and advanced
Common manifestations: malaise,
fatigue, poor appetite, nausea,
distension of abdomen
• Jaundice seen in some cases
• Enlargement of liver and/or spleen
• Spider naevi, hepatic palms in cases with
long history
• Abnormal LFTs: transaminase, bilirubin
A/G
Prognosis different: stable, breakthrough or
flare, develop to Cir or Ca
Liver failure (severe hepatitis)
Bad prognosis
Pathological basis: extensive necrosis of
hepatic cells
4 subtypes: acute liver failure, subacute
acute-on-chronic, chronic
Clinical syndrome including:
jaundice deepen rapidly
liver size become smaller
bleeding, prolonged prothrombin
time, PTA less than 40%
cerebral edema, high intracranial
pressure
complicated infection: SBP
hepatic encephalopathy
toxic abdominal distension and
ascites
hepatic-renal syndrome
Cholestatic viral hepatitis
acute and chronic
mild manifestation but deepen
jaundice
Hepatitis cirrhosis
hepatic fibrosis
compensated cirrhosis
decompensated cirrhosis
Asymptomatic HBV carrier
HBV infection more than 6 months
have no symptoms and signs
normal LFTs
70%-80%have no pathologic change
in liver biopsy
Diagnosis
Clinical Data
Epidemiological evidences
Laboratory investigations
Ultrasound
Biopsy
Differential diagnosis
Jaundice caused by other
etiological agents
Hepatitis caused by other
etiological agents
Treatment
Basic principles of management
guideline for daily living,
physical activity , food and
drink intake of the patients
supportive and symptomatic
treatment
Hepatic function protective agents
Anti-virus therapy
most important treatment for
chronic hepatitis B、acute and
chronic hepatitis C
hepatitis B indication: HBVDNA
≥105copies/ml for HBeAg~,
HBVDNA ≥104copies/ml for HBeAg+;
ALT ≥2ULN, or biopsy ≥G2S2
Drugs: interferon-α(typical or
pegylated) or,
nucleotide analogues:3TC,adfovir,
entecavir,Ldt…
Hepatitis C indication: HCVRNA+
drugs: interferon-α(typical or
pegylated) +ribavirin
Traditional Chinese medicine
Management for liver failure
basic supportive therapy
treatment of complications
bleeding
infection complications
encephalopathy
renal failure
Hepatic transplantation
Management of asymptomatic HBV
carrier
medical check up periodically
no any alcohol intake
liver biopsy when patient’s age more
than 40 years and HBV replication
in high level
Prevention
Improvement of sanitation
Blood screening of donors
Anti-virus treatment for hepatitis B and
hepatitis C
Immunoprophylaxis
active immunization
vaccines for hepatitis A and B are
available around world, very
successful for pre-exposure
prevention
passive immunization
IG for hepatitis A, HBIG for
hepatitis B; post-exposure
Thanks !