Viral Hepatitis

Viral Hepatitis
The First Teaching Hospital of

Zhengzhou University, Department of
Infectious Disease
Gu Junsheng
1
Viral Hepatitis
 Summarization:
 A group of diseases caused by a group of
hepatotropic viruses
 HAV infection rate 80% 910 million
 HBV infection rate 60% (all in China)
carrier rate 10~15% 134 million
 HCV infection rate 0.7~3.1%
 HDV infection rate 1.6%
 HEV
 HGV
 TTV transfusion-transmitted virus (1997) 2
Summarization
pathogens routes of clinical

transmission features
 HAV RNA heparnavirus
fecal-oral route no chronic type
 HEV RNA
 HBV DNA hepadnavirus chronic hepatitis
 HCV RNA flaviviridae blood / body fluid

 HDV RNA mother to baby hepatocirrhosis
 HGV RNA flaviviridae
 TTV DNA transfusion-transmitted virus liver cancer
3
Summarization
 Clinical Features:
 Carrier state is most common.
 Symptoms and signs such as the followings
can usually be seen in all kinds of hepatitis:
 Fatigue, anorexia, jaundice, discomfort in
the right upper quadrant, hepatosplenomegaly,
abnormity of liver function etc.
4
ETIOLOGY: HAV
 Heparnavirus
 RNA
5
ETIOLOGY: HAV
 Characteristics ：
 (1) Only one serotype and one Ag-Ab system
 (2) HAV-IgM: appears early after the infection of
HAV and disappears 6 months later.
 (3) HAV-IgG: appears after the disappearance of
HAV-IgM and last many years.
 (4) Hepatotropic: self-copy in liver cells.
 (5) HAV can not lead cytolysis directly.
6
ETIOLOGY: HAV
 (6) Resistance:
 keep activity: 56℃: 30 min
room temperature: one week
 partly inactivate: 60℃: 12h
70% èthanol, 25 ℃: 3 min
 completely inactivate: seethe: 5 min
ultraviolet radiation: 1 min
7
ETIOLOGY: Structure of HBV
protein spherical
envelope HBsAg synthesized in liver cells
(7nm) lipid no infectivity

 Dane
Granule HBcAg
(42nm) core HBV DNA (circular and partly doubled)
(28nm) DNAP
Question: Where is HBeAg ?
8
ETIOLOGY
Tridimentional Structure of HBV
9
ETIOLOGY
Tabulate Structure of HBV
10
ETIOLOGY : HBV
 Genome of HBV:
 S region
 C region
 P region
 X region
11
ETIOLOGY
Structure of HBV DNA
12
ETIOLOGY: HBV MARKS
 Marksof HBV
 1. HBsAg, HBsAb
 2. HBeAg, HBeAb
 3. HBcAg, HBcAb
 4. HBV DNA
 5. HBV DNAP
13
ETIOLOGY: HBV MARKS
 HBV marks and the clinical significance:
 HBsAg:
 Stand for infection of HBV
 HBsAb:
 The only protective antibody stands for
proper immune response to vaccination or
natural infection(post-infection immunity).
14
ETIOLOGY: HBV MARKS
 HBeAg:
 Comes during the virus` active copy (`soluble).
 Stand for the infectivity of blood
 HbeAb:
 Virus copy is decreased (generally last for 1~2 years)
 If mutation is at preC gene, HBeAg may be negative,
but HBV is in active copying, and perhaps sometimes can
exaggerate the state of illness.
15
ETIOLOGY: HBV MARKS
 HBcAg:
 Active virus copy
 Infectivity of blood
 HBcAb:
 Virus copy and infectivity of blood decreased
 HBc-IgM:
 Acute phase or acute outbreak in chronic type
 HBc-IgG ：
 Past infection 16
ETIOLOGY: HBV MARKS
 Molecular biology of HBV:
 1. HBV DNA ：
 Free HBV DNA ：
The appearance in the blood indicates active
copy of HBV.
 Combined HBV DNA:
 2. HBV DNAP: usually does not detect
17
The relationship of HBV marks
in acute HBV infection
18
ETIOLOGY: HCV
 Only human beings and orang are susceptible to

HCV.
 HCV always maintain a low concentration in
blood.
 HCVAg can not be detected in blood all along.
 HCVAb is not a kind of protective antibody. On
the contrary, HCVAb indicate infectivity of blood.
19
ETIOLOGY: HCV
 HCV-Ab will not transfer from positive

to negative soon after anti-virus therapy.
 The appearance of HCV-IgM indicate
the activity of the disease.
 HCV RNA positive blood also indicate
infectivity.
20
ETIOLOGY: HDV
HDV:
Defective RNA virus
HDV cannot copy itself without HBV or
other DNA virus.
21
ETIOLOGY: HEV
 HEV:
 Discharged through bile and stool
 HEV-IgM and HEV-IgG:
 Appear in blood almost at the same time
but HEV-IgM disappears early.
22
EPIDEMIOLOGY
 1. Source of infection 2. Transmitting routes
A
patients, the covert infection ones fecal-oral route
E
B blood
C the acute, the chronic, body fluid
D and the carriers mother to baby
G sexually
 TTV other routes 23
EPIDEMIOLOGY
 3.Susceptibility and immunity:
 Hepatitis A:
 Few babies get infected with HAV within 6
months because they get HAV-IgG from their
mothers through placenta.
 Host will get permanent immunity after
HAV infection.
24
EPIDEMIOLOGY
 3. Susceptibility and immunity:

 Hepatitis B:
 Generally, new baby has no HBsAb from its
mother, so all babies are susceptible to HBV.
 As time going, many people can get immunity
after covert infection. (In China, HBsAb can be
detected in about half of people older than 30
years.)
25
EPIDEMIOLOGY
 3. Susceptibility and immunity:
 Hepatitis C:
 Anyone is susceptible to HCV.
 HCV-Ab is not a protective antibody.
 Hepatitis D:
 HDV-IgG is not protective.
 Hepatitis E:
 All susceptible to HEV
 Covert HEV infection is common in young
children .
 In adults, HEV infection usually results in overt
infection.
26
EPIDEMIOLOGY
 Distribution of HAV infection:
 1. Sporadic:
 2. Epidemic outbreak:
 More than 310,000 people got overt infection
of HAV in Shanghai in 1988.
 3. Seasonal distribution:
 HAV: autumn and winter
 HEV: rainy season or after flood
 4. Geography distributing:
 Not distinctly
27
EPIDEMIOLOGY: Distribution of HBV infection
 degree carrying rate distribution
 low area 0.2~0.5% north America, west Europe,

Australia
 moderate 2 ~ 7% east Europe, Mediterranean,
Japan, Russia
 high area 8~20% tropic Africa, south-east Asia,
China
 HCV & HDV
 HEV infection is mainly in developing countries in Asia
and Africa.
28
EPIDEMIOLOGY
 Distribution of HBV infection:

 5% of world population (350 million) is in
chronic carrier state of HBV ．
 Asia and Africa with the carrying rate of
about 8%~15%
 Of HBV carrier state, 50%~70% is chronic
hepatitis B.
29
EPIDEMIOLOGY
acute HBV infection
infection in infection in
childhood>95% adults <10%
50-70%
chronic HBV infection recovered
10-20%
chronic hepatitis B carrier state
20%
cirrhosis recovered
HCC liver
1-5% failure
30
EPIDEMIOLOGY
 HCV infection:
 170 million in the world (half of HBV)
 HDV infection:
 HEV infection:
31
Pathogenesis of hepatitis A
 Hepatitis A:
 HAV→digestive tract →blood→liver→bile→stool


 T cell→γ-interferon
 HLA-I Ag
 recognize
 CD T
8
+
HAV-Ag
 Liver cell lysed
 released of HAV
 Which will be cleared later
 Immune complex
32
Pathogenesis of hepatitis B
 The pathological changes of liver cells
is considered mainly due to cell-mediated
immunity.
 The main target antigen of
immunoreaction is HBc-Ag.
 Different immunoreaction, different
clinical manifestations.
33
Pathogenesis:
different result of HBV infection
Carrier state:
 Get infected when the hosts’(new
babies or young children) immunity is
immature and result in immunological
tolerance.
 Those in adults belongs to factors of
descendiblity.
34
Pathogenesis:
Acute hepatitis B:
 Acute hepatitis is common in
adults because they are always with
normal immunity.
35
Pathogenesis:
 Chronic hepatitis B:
 HBV infection sometimes results in chronic
hepatitis because:
 The host is always with decreased immune
function or immunodeficiency.
 Or with incomplete immunological tolerance
 Other reasons such as gene mutation of HBV
36
Pathogenesis:
 Fulminant hepatitis B:
 hypersensitivity
 large quantity of Ag-Ab complex
 activation of complement
 endotoxin
 TNF
 IL-1
 IL-6
 CTL
 necrosis of large quantity of liver cells
37
ADCC
Killer cell liver celll
infected with HBV
Fab
Fc
Anti-LSP
Fab
cytolysis
LSP: liver specific membrane lipoprotein 38
Clinical Manifestations
 IncubationPeriod:
 Hepatitis A: 15~45d
 Hepatitis B: 30~180d
 Hepatitis C: 15~150d
 Hepatitis E: 10~70d
 Hepatitis D: equal to hepatitis B (?)
39
Acute Hepatitis: (mainly hepatitis A and E,

occasionally hepatitis B and C )
Icteric type:
1. Preicteric phase
2. Icteric phase
3. convalescent period
Anicteric type: 40
Acute Hepatitis
Icteric type: 2~4 months
1. Preicteric phase: 5~7d
light fever, fatigue, nausea, vomiting,
being disgusted with oil, abdominal distention,
right upper quadrant pain ， ALT increased
2. Icteric phase:
3. Convalescent period:
Anicteric type: 41
Acute Hepatitis
1. Preicteric phase: 5~7 d
2. Icteric phase: 2~6 weeks
symptoms ?
transient obstructive jaundice
hepatosplenomegaly
TBIL and ALT increased
3. Convalescent period: 1~2 months
Anicteric type:
42
Acute Hepatitis
1. Preicteric phase:
2. Icteric phase:
3. Convalescent period: 1~2 months
symptoms alleviated, jaundice subsidise,
hepatosplenomegaly withdraw, and the liver function
recovered gradually
Anicteric type:
43
Acute Hepatitis (hepatitis A; hepatitis E)
Icteric type:
Anicteric type:
(subclinical infection?)
44
 Chronic hepatitis:
 Definition:
 Chronic hepatitis is a descriptive term used to
denote ongoing inflammation (> 6 months) of the
hepatic parenchyma.
HBV
 The leading cause: HCV
HDV 45
 Chronichepatitis: (Hepatitis B, C and D)
 Symptoms:
 low fever
 fatigue
 dizziness
 symptoms of alimentary tract
 jaundice
 discomfort in the right upper quadrant
46
 Chronic hepatitis: (Hepatitis B, C and D)

 Signs:
 hepatic face
 hepatic palm, liver palm, palmar erythema
 spider angioma, spider telangiectasia,
spider nevi
 jaundice
 progressive splenomegaly
47
48
 Liver function:
 alanine aminotransferase (ALT)
 aspartate aminotransferase (AST)
 alkaline phosphatase (AKP or ALP)
 gamma glutamyltranspeptidase (γ-GT)
 Both AKP and γ-GT denote `biliary obstruction or cholestasis.
 total bilirubin(TBil) albumin (A)
 total protein (TP)
 globulin (G) 49
 Prognosis:
 Stones will be penetrated through
by dripping water.
50
 Fulminant hepatitis:
 Definition:
 Morbidity: 0.2--0.5%
 Mortality: 80%, 70%, 60%
 Clinical types:
 acute fulminant hepatitis
 subacute fulminant hepatitis
 chronic fulminant hepatitis
51
 Fulminanthepatitis:
 Main clinical manifestations of fulminant hepatitis
 progressive symptoms of alimentary tract
 progressive `hemorrhage tendency
 ascites
 hepatic encephalopathy and hydrocephalus
 hepatatrophia
 hepato-renal syndrome
 TBIL>171μmol/L
 PTA (thrombinogen activity)< 40% 52
 Acute fulminant hepatitis:
 Begin with acute icteric hepatitis and the following
clinical manifestations appear within 10 days:
 Hepatic encephalopathy (alteration of character,
fidgety, delirium, somnolence, coma, convulsion,
hydrocephalus, pathologic reflexes)
 jaundice deepened rapidly(TBIL>171μmol/L
within 10 days)
 liver shrinked in a short time
 ascites
 acute renal failure
 PTA<40% 53
 Subacute fulminant hepatitis:
 Begin with acute icteric hepatitis and the
following clinical manifestations appear after 10
days:
 veriest fatigue, awful anorexia, exceeding
nausea, ferocious abdominal distension(flatus),
obvious acites, veriest jaundice and hemorrhagic
tendency, hepatic coma, hepato-renal syndrome
54
 Subacute fulminant hepatitis:
 Rise as acute icteric hepatitis and appear the
followings after 10 days:
 SB>171μmol/L
 PTA<40%
 aminotransferase-bilirubin separation
 ALT/AST converted
 A/G inversion
55
 Chronic fulminant hepatitis:

 Subacute fulminant hepatitis on a
chronic hepatitis or hepatocirrhosis basis
56
Cholestatic hepatitis:
 Cholestasis can result from
extrahepatic biliary obstruction or from
intrahepatic causes, we will talk about
the later only.
 Generally last for 2~4 months
57
 Symptoms and sings of Cholestatic hepatitis:
 One deepened, one lightened:
 urine color deepened, stool color lightened
 One severe, one light:
 severe jaundice, light symptoms
 One big, one little:
 big liver, little gallbladder
 Both painful and itching:
 feel painful when liver knocked
58
 Laboratory test of Cholestatic hepatitis:
 Laboratory data show modest abnormalities
in aminotransferase concentrations but marked
elevations in:
 AKP↑
 γ-GT↑
 TBil↑
 cholesterin (cholesterol)↑
 PTA>40%
59
Hepatocirrhosis:
 Hepatocirrhosis is characterized by
hepatic necrosis, regeneration (formation
of regenerative nodules), fibrosis, and
architectural distortion.
60
 Hepatocirrhosis is clinically
divided into:
 Compensatory hepatocirrhosis
 Decompensatory hepatocirrhosis
61
 Compensatory hepatocirrhosis:
 symptoms and signs:
 fatigue
 symptoms of alimentary tract
 jaundice
 hepatic facies
 hepatic palm
 spider angioma
 splenomegaly
 light esophagus varix
62
 Compensatory hepatocirrhosis:
 laboratory tests:
 ALT increased frequently but always light
 AST/ALT>1
 Globulin
compensatory
 prognosis: decompensatory
liver cancer
63
 Decompensatory hepatocirrhosis:
 Clinical manifestations of decompensatory
hepatocirrhosis can be divided into two parts: one is
related with the decreased liver function(similar to
those in compensatory hepatocirrhosis ), another
characterized by the following three is related with the
increased portal pressure:
 Splenomegaly
 Esophagus varix: hematemesis (or hematochezia)
 Ascites
64
Laboratory tests
 Liver function:
 ALT, AST
 γ-GT, AKP
 TP, A, G
 SBil
 Urine bilirubin
 Urobilinogen:
 PT
 PTA
 Serum àmmonia 65
Laboratory tests
 Laborstory test:
 HAV-IgM
 HBV-Marks
 HBV-DNA test
 HCV-IgM/G
 HEV-IgM/G
 Biopsy of the liver tissue
 Blood routine test
 Urine routine test 66
Assistant examinations
 Assistantexaminations:
 Ultrasonic examination is very useful to
the diagnosis of fulminant hepatitis,
chronic hepatitis, liver cirrhosis, and liver
cancer.
67
Diagnosis
 Epidemiology:
 Symptoms and signs:
 Laboratory tests:
68
Differential diagnosis
 Jaundice caused by other reasons:

 Hemolytic jaundice
 Extrahepatic obstructive jaundice
69
Differential diagnosis
 Hepatitis caused by other reasons:
 1. Hepatitis caused by other virus (but not always
called viral hepatitis): Epstein-Barr virus and CMV
 2. Hepatitis caused by nonviral infection disease
 3. drug-related hepatitis
 4. Alcoholic liver disease
 6. Wilson’s disease
 7. Budd-chiari syndrome
70
Treatment
 Principleof treatment:
 Give priority to rest and alimentation
 Use drugs as supplement
 No drinking and not being tired
 Avoid drugs that may do harm to the liver
71
Treatment
 Acute hepatitis A:
 Acute hepatitis C:
 Use interferon-α early
 3 M.U. i.H. q.o.d. 3~6 months
 Ribavirin 800~1200mg/d
 Aim: seroconversion of HCV RNA
72
Treatment
 Liver protection therapy:
73
Treatment
 Anti-virus therapy(1. interferon):
 Indications:
 ① Active replication of HBV
 ② Active hepatitis (80U/L<ALT
<200U/L)
 ③ HBV DNA: low concentration in blood
 ④ HBc-IgM positive
74
Treatment
 Anti-virus therapy (1. interferon)
 Contraindications:
 Age: too young or too old (beyond 10~60y)
 Decompensatory hepatocirrhosis
 Organ function failure: heart failure, renal
failure, liver failure
75
Treatment
 Anti-virus therapy in chronic hepatitis B:
 1. Interferon:
 Dose and method: 3 M.U~6 M.U. i.H. q.o.d.
 Period of treatment: 6 months~1 year
 Target: Inhibition of HBV replication
 HBeAg and HBV DNA turn negative
(seroconversion)
 It is difficult to turn HBsAg from positive to
negative.
76
Treatment
 Anti-viral therapy in chronic hepatitis B:
 2.Lamivudine (`Nucleoside ànalogues):
 Lamivudine has been approved by the
FDA for treating HIV and chronic hepatitis B.
 It has potent activity as a reverse
transcriptase inhibitor (as an RNA chain
terminator in HBV reverse transcription) of
both HIV and HBV.
77
Treatment
 Anti-viral therapy in chronic hepatitis:
 2.Lamivudine (Nucleoside analogues):
 ① Active replication of HBV
 ② Active hepatitis with increased ALT(﹥
200u/l )
 ③ Positive HBeAg and HBV DNA:
 ④ HBeAg negative, anti-HBe & HBV DNA
positive (mutation of Pre-C gene)
 ⑤ TBil < 50μmol/L
 ⑥ Older than 16 years 78
Treatment
 Anti-viraltherapy in chronic hepatitis:
 2. Lamivudine (Nucleoside analogues):
 Dose and method:
 100mg/d. p.o.
 period of treatment: 1 ~3 years
 Serum HBV DNA decreases more than 90%
within about 2 weeks. And the rate of HBV DNA
seroconversion may be 70~90% 2 months later.
79
Treatment
 Immunity modulation therapy in chronic
hepatitis B
 Thymosin
 IL-2
80
Treatment
 General and supporting therapy:
 bed rest
 low-protein diet (20 to 30 g/day)
 the administration of enemas to cleanse the
bowel
 the use of oral lactulose (30 to 60 ml every 2 to
6 hours until loose stools are achieved)
 treatment with all sedatives is contraindicated
81
Treatment
 Fresh-frozen plasma for coagulation defects
 Monitored and treated carefully for
gastrointestinal bleeding:
 cimetidine
 omeprazole
 somatostatin: octreotide
82
Treatment
 Careful attention to all details of "routine"
medical management is most important, such as
fluid and electrolyte balance, acid-base balance.
83
Treatment
 Anti-infectiontherapy
 Management of acute renal failure
 Promote liver cell regenesis: PHGF
 Liver transplantation
84
Treatment
Carriers:
85
Prevention
 There are only vaccinations of HAV and
HBV.
86
87
Class is over
88

Viral Hepatitis

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Viral Hepatitis

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Viral Hepatitis

The First Teaching Hospital of

pathogens routes of clinical

 HCV RNA flaviviridae blood / body fluid

(7nm) lipid no infectivity

(42nm) core HBV DNA (circular and partly doubled)

 Only human beings and orang are susceptible to

 HCV-Ab will not transfer from positive

 3. Susceptibility and immunity:

 low area 0.2~0.5% north America, west Europe,

 Distribution of HBV infection:

 HAV→digestive tract →blood→liver→bile→stool

Acute Hepatitis: (mainly hepatitis A and E,

 Chronic hepatitis: (Hepatitis B, C and D)

 Chronic fulminant hepatitis:

 Jaundice caused by other reasons:

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