BEMS UNIVERSITY OF POONCH AJ&K

1. Today We Will
Define hepatitis, viral hepatitis &
the liver
Learn about the 5 different
types of viral hepatitis

2. What Is Hepatitis?
Hepatitis means inflammation of the liver
◦ Hepat (liver) + itis (inflammation)= Hepatitis
Viral hepatitis means there is a specific
virus that is causing your liver to inflame
(swell or become larger than normal)

3. The Liver
Is located in the upper right quadrant of
the abdomen
•Cleans the blood
•Regulates hormones
•Helps with blood clotting
•Produces bile
•Produces important proteins
•Maintains blood sugar levels
•And much, much, more
• The liver is essential
for life !

4. Inflammation
Walls of
scar
tissue
begin to Healthy liver cells
form become trapped
by a wall of scar
tissue

5. Viral Hepatitis
5 types:
A: fecal-oral transmission
B: sexual fluids & blood to blood
C: blood to blood
D: travels with B Vaccine
E: fecal–oral transmission Preventable
Adapted from Corneil, 2003

6. Hepatitis A
Ca used by hepatitis A virus
Ca
Humans as their reservoir
SOC: Infected feces, HAV-contaminated food
POC: 1–2 weeks before the
onset of symptoms until about 7 days
after the patient becomes jaundiced.
Fecal oral contamination
Oral anal sexual activity contamination,
shellfish from contaminated water
Incubation 18 – 45 days
Immune globulin within two weeks of exposure

7. Etiology
Hepatitis A virus (HAV)
 HAV is one kind of picornavirus and used to be
classified as enterovirus type72, but recently, it is
considered to be classified as heparnavirus
 Hepatitis A virion is a naked spherical particle,
diameter 27nm
 Consists of a genome of linear, single-stranded RNA,
7.5kb. The genome may be divided into 3 coding
region: P1 region (encoding structural protein), P2 and
P3 regions (encoding non-structure protein)
 During acute stage of infection, HAV can be found in
blood and feces of infected human and primates
 Marmoset and chimpanzee are susceptible animals

8. Etiology
Hepatitis A virus (HAV)
 HAV can not cause cytopathy, replicate within
cytoplasma of hepatocytes and via bill are discharged
with feces
 7 genetypes, 1, 2, 3, 7 types from humanbody
 Only one antigen-antibody system. Anti-HAV IgM is
diagnostic evidence of recent infection, IgG is
protective antibody.
 Resistance of HAV: 56°C, 30 min, usually temperature
1 week, dry feces at 25°C 30 days, fresh water, sea
water ,shellfish or soil for several months. 70% alcohol
at 25°C , 3 min, 100°C, 5 min and ultraviolet, 1 min

9. HAV

10. HEV

11. Pathogenesis:
Hepatitis A, E
Inoculation of the pathogen (entrance gate –
small intestine).
Viremia.
Viral fixation on hepatocytes, intracellular
localization.
Primary replication of the virus.
Excretion with a goal to intestine.
Part of the viruses caused viremia (prodromal
period of the disease).
Activation of immune system, that causes
cytolysis, mesenchimal inflammation and
cholestasis.
Immune response, elimination of the virus.

12. Hepatitis A
SIGNS AND SYMPTOMS
•Most are anicteric and
asymptomatic
•Flu-like URTI with low-grade fever
•Anorexia
•Indigestion
•nausea
•Aversion to cigarette smoke and
other strong odors
•May or may not be jaundiced

13. Hepatitis E
Hepatitis E Virus (HEV)

Reservoir: Infected Humans and Animals: wild and domestic esp. swine
Incubation: 14-60 days
Period of Communicability:
-Not known.
- Hepa-E virus has been detected in stools 14 days after the
onset of jaundice and approximately 4 weeks after ingestion of
contaminated food or
water and persists for about 2 weeks.
Source of infection:
- Contaminated water in areas of poor sanitation
-household member,sex partners, shared injection
equipment
S/S: JAUNDICE is almost always present

14. Epidemiology
Source of infection
Hepatitis A and E: patients
with acute hepatitis and
person with sublinical infection
Route of transmission
Hepatitis A and E:
fecal-oral route
predominantly

15. pathogenesis
Hepatitis A:
HAV invade into human body by mouth
and cause viremia.After one week,the
HAV reach liver cells replicate within.Then
enter intestien with bill and appear in
feces.someone believe that damage of
liver cells maybe caused by immune
response.Due to:
◦ HAV does not cause cytopathy

16. ◦ After HAV replicating and discharging,liver
cells damage begin
◦ Animal experiment proved that immune
complex may attend the pathogenesis of HA
◦ Complement level reduce the pathogenesis
maybe following:activated T cell secrete γ-
INF that promote the representation of HLA-
Ⅰantigen on the liver cells,CTL may kill the
target cell infected with HAV

17. Pathology
◦ Degeneration
◦ Necrosis
◦ Regeneration
◦ Infiltration of inflammatory cells
◦ Hyperplasia of interstitial cells

18. Clinical picture
1. Preicetric stage or prodromal stage:3 – 9 days
 Sudden onset of influenza like picture: fever -
headache – malaise – muscular pain
 Anorexia is marked with nausea – vomiting –
distension
 Pain in Rt hypochondrium & epigastrium
 Dark urine – pale stool
 Transient itching
 Examination: fever with relative bradycardia +
enlarged tender liver

19. Clinical picture
 Icteric stage: 2-4 w
 Jaundice with fever & improvement of general
condition
 Anorexia nausea & vomiting diminish or disappear
 Urine is dark brown & frothy
 Stool are clay in color – bulky – offensive – greasy
 Examination:
 Soft tender enlarged liver Spleen is enlarged in 20
%
 L N 10% generalized lymph adenopathy with LN
of post. Triangle of neck

20. Clinical picture
Convalescence stage:
 Signs & symptoms gradually disappear
 Jaundice may persist for some times due to
affinity of bile pigment to elastic tissue
 Complete recovery of liver may take up to 6
months

21. Investigation:
L FT:
1. serum bilirubin : total, direct and indirect
2. ALT – AST : from 500 – 2000 IU/L ALT > AST
3. Alkaline phosphatase – 5’nucleotidase – GGT:
Blood :
 Leucopenia with relative lymphocytosis, ESR

22. Urine :
 Early bilirubin appearance
 Bile salt : granular casts – frothy urine - +ve hay
sulfur test
Stool:
 Pale – clay with stetorrhea
Serology
Acute stage Chronic stage others
Hepatitis A Anti HAV IgM Anti HAV IgG Fecal
HAV
Hepatitis D Anti HDV IgM Anti HDV IgG
Hepatitis E Anti HEV IgM Anti HEV IgG

23. Susceptibility and immunity of
population
 Hepatitis A
Most adult has anti-HAV due to covert
infection. Infant under 6 month acquired
antibody from mother. Young children is
susceptible
 Hepatitis E
Common susceptible. Children appear
covert infection, adult show overt infection

25. Etiology
 Hepatitis B virus (HBV)
HBV is a kind of hepadnovirus
Three particles in serum:
spherical particles and tubular particles with
a diameter of 20 nm, composed of HBsAg
large particles with a diameter of 42 nm,
named Dane particle. It consists of an outer
protein shell (envelope, contain HBsAg) and an
inner body ( core, contain HBcAg, HBeAg, HBV-
DNA and DNAP )

26. Etiology
 Hepatitis B virus (HBV)
Hepatitis B viron genome is a small
circular, partially double stranded DNA
with 3200 nucleotides long. HBV DNA is
asymmetry in length of two strands:
minus strand (long strand, L) has full
length. Four open reading frames (ORF)
coded on the minus strand: C, S, X, and P
region

27. 大球形
颗粒
管
形
颗
小球形
粒
颗粒
HBV

28. Etiology
 Hepatitis B virus (HBV)
 Four open reading frames (ORF)
S region: include pre-s1, pre-s2 and S gene,
encoded pre-s1 protein, pre-s2 protein and HBsAg.
Pre-s1 protein + pre-s2 protein + HBsAg—large
protein
Pre-s2 protein + HBsAg—middle protein
HBsAg—major protein
C region included pre-c and C gene, encode HBeAg
and
HBcAg
X region encoded HBxAg
P region encoded DNA polymerase

29. Etiology
HBcAg—anti-HBc system
 HBcAg can be found in the nuclei of liver cells, no
free HBcAg in serum
 HBcAg is the marker of replication of HBV
 The stage called window phase
 Anti-HBc IgM is a marker of acute infection and
acute attack of chronic infection of HBV. Anti-HBc
IgG is the marker of past infection, high titer
means low level replication of HBV

30. Etiology
HBSAg
Related to chronocity, activity of
hepatitis B or liver cancer
Resistance
Resistant to heating and common
disinfections. Chimpanzee is susceptible to
HBV

31. Hepatitis B
Hepatitis B Virus (HBV)
Reservoir: Humans
Source of infection:
-infected individuals
- receipt of blood transfusion or
other blood products
- use of shared needles
- history of tattooing, ear or body
piercing, or acupuncture
Incubation: 30-180 days
Period of communicability:
-1-2 months before and after the onset of
symptoms
Mode of transmission: Heterosexual
transmission, contact with blood and body
fluids

32. Hepatitis B
SIGNS AND SYMPTOMS
•Loss of appetite,
•dyspepsia,
•abdominal pain
•Gen. aching malaise and weakness
•Jaundice
•Ligh-colored stools and dark urine
•Hepatomegaly and splenomegaly
•Enlarged posterior cervical lymph
nodes

33. Pathogenesis:
Hepatitis B
Inoculation of the pathogen.
Viremia.
Viral integration and replication in
hepatocytes, also may be in blood cells, bone
marrow, lymph nodes, spleen.
Activation of immune system, that causes
cytolysis, mesenchimal inflammation and
cholestasis.
Immune response, elimination or persistence
of the virus.

34. Hepatitis B marker:
antigen Significance Corresponding significance
Ab
HBsAg Appear after 6 week Anti HBs Appear after 3 m
(surface) Acute infection, remain Reflecting recovery
for 3 ms & immunity
Chronic infection if >6
ms
HBcAg Detected on Liver Anti HBc Appear after 2 m
(core) Biopsy only (not serum) Reflecting sever
acute & chronic form
HBeAg Reflect ongoing viral Anti HBe Appear after 2.5 m
(envolop) replication (chronicity) Non replicating
virus
HBV DNA Most sensitive indication for viral replication & chronicity (Dan
particle)
It is detected by PCR

35. •Serological gap:
It is a window last several weeks between
disappearing of HBs Ag & appearance of
Anti Hbs. Anti HBc Ab may represent
serological evidence of recent HBV
infection
Blood free from Hbs Ag & Anti Hbs (but
containing anti – HBC) is the major cause
of trasfusion HBV infection

37. Etiology
 Hepatitis C virus (HCV)
 HCV is a member of flavivirus family.
 HCV genome is a single stranded positive-sense RNA
and contains 9.4kb
 The genome contains 5’-non coding region, C region, E
region and NS region
 HCV genome may be divided into many types and
subtypes.
 Resistance
 Antigen-antibody system
 The concentration of HCV in blood is low, HCV Ag has not be
detected, anti-HCV is the indicator of infection and the
marker of infectivity
 HCV-RNA
HCV-RNA may be detected from blood or liver tissue, it’s
the direct evidence of infectivity

38. HCV

39. • Hepatitis C
– Is similar to that of HB. CTL and
some cytokines play an important
action
– The chronicity is related to the
variability of gene
– HCV infection is related to HCC
closely but HCV does not integrate to
liver cells, so from HCV infection to
HCC may be related to chronic
inflammation and cirrhosis

40. Natural History of Hep C
20%
Only 20% will Clear the
show symptoms Virus
Initially !
Healthy Acute Chronic
Liver Infection Infection
80% Virus
Continues
to Damage
Liver
Adapted from Lauer and Walker, NEJM 2001

41. Natural History Con’t
Chronic Cirrhosis Liver
Hepatitis 20-30% Cancer
1-4%/year
Most symptoms begin to show only when liver is more severely damaged

42. Epidemiology
 Route of transmission
 Hepatitis B, C, and D:
humoral transmission (parenteral
transmission)
Mather to infent transmission(vertical
transmission)
Sexual contact transmission
Insect transmission

43. Hepatitis C
Hepatitis C Virus (HCV)
Source of infection:
-Parenteral drug, needlestick injuries, Blood transfusion
-High-risk sexual contact (multiple partners, history of other
STDs, anal sex, etc.)
Incubation: 15-160 days
Contact with blood and body fluids: transfusion of blood and blood
products
Period of communicability:
-one or more weeks before onset of symptoms and persists in
most persons

44. Hepatitis C
SIGNS AND SYMPTOMS
•Asymptomatic or experience mild
symptoms
•Fatigue
•Abdominal pain and poor appetite
•Jaundice
•Headaches
•joint aches
•muscle aches
•nausea

45. Hepatitis D
Hepatitis D Virus (HDV)
Reservoir: humans
Animals: chimpanzee and pigs
Source of infection: same as Hepa-B
Incubation: 30-180 days
Period of communicability: not been yet determined,
but virus excretion in stool has been demonstrated up to 14
days after onset of illness
Co-infects with hepatitis B, close personal contact

46. Pathogenesis:
Hepatitis D
Need virus hepatitis B for its replication,
develops only in infected HBV patients

47. Hepatitis D
SIGNS AND SYMPTOMS
•Similar to those with hepatitis B
•May progress to chronic active hepatitis
and cirrhosis
•always associated with a coexistent
hepatitis B virus infection, either
simultaneous new infections (co- infection)
or a chronic hepatitis B infection
(superinfection)

48. Pathogenesis
Initial
viremia, with inflammation of GIT
mucosa.
Intrahepatic localization lead to
A- diffuse centrilobular necrosis, with cellular infiltration
around portal tracts
B- intrahepatic cholestasis due to cellualar edema &
inspissation of bile
Other organ: splenomegaly –
lymphoadenopathy
Hypoplasia of BM