This document provides information on the clinical presentation and progression of viral hepatitis. It describes the prodromal symptoms including fatigue, nausea and low grade fever. Onset of jaundice is characterized by diminishing constitutional symptoms and liver tenderness. Various clinical syndromes can develop after viral exposure including acute, fulminant or chronic hepatitis. The morphologic lesions are similar between virus types and include lobular inflammation and necrosis. Serologic testing can identify exposure to hepatitis A, B, C and E viruses.

3.  Prodromal symptoms
constitutional symptoms:
› -anorexia -athralgias
› - nausea and vomiting -myalgias
› -fatigue -headache
› -malaise -pharyngitis
› -cough
› Low grade fever (38-39 C)- HAV and HEV
› Dark urine and clay-colored stools- 1-5 days
before the onset of clinical jaundice.

4.  Onset of jaundice
› Constitutional symptoms diminish
› -in some patients, mild weight loss (2.5-5 kg)
› -liver is enlarged and tender
› -Right upper quadrant pain and discomfort
Recovery/post-icteric phase
-constitutionalsymptoms disappear
-2-12 weeks (more prolonged in HBV and HCV)
-some liver enlargement and biochemical test
abnormalities are still evident
-complete clinical and biochemical recovery:
1-2 months

5.  A number of clinical syndromes
may develop after exposure to
hepatitis viruses:
› Acute hepatitis
› Fulminant hepatitis
› Chronic hepatitis
› Chronic carrier state

6.  The typical morphologic lesions of all
types of viral hepatitis are similar :
› Panlobular infiltration with mononuclear cells
› Hepatic cell necrosis
› Hyperplasia of Kupffer cells
› Variable degrees of cholestasis

7. SGOT
SGPT
BILIRUBIN
PT

9.  Enterovirus 72
 Family: Picornavirus
 Genus: Hepatovirus
 nonenveloped 27 –nm, heat, acid, and
ether resistant RNA virus
Inactivation by:
a. boiling for 1 min
b. contact with
formaldehyde
c. Chlorine
d. ultraviolet radiation

10.  Incubation period:
4 weeks/ 15-45
days
 Replication:
limited in the liver
 Late incubation
period: virus is
present in the liver,
bile, stools and
blood.
 Period of
communicability:
before to after
symptoms appear

11.  Fecal-oral route

13. Serology
• IgM anti-HAV : acute HAV infection
• IgG anti-HAV : resolution or previous infection

14.  Prophylaxis with immune serum globulin
given before or early in the incubation
period ( 80% to 90% effective in preventing
clinical illness
 Post-exposure: administration of 0.02 mL/kg
 • Active immunization recommended for:
 • Travellers to developing countries:
 <3 months travel : 0.02 mL/kg
longer travels: 0.06 mL/kg every 4-6 months
 • Children 2 – 18 years old

15.  Formalin-inactivated vaccines
 -made from strains of HAV attenuated
 in tissue culture have been shown to be
safe, immunogenic, and effective in
preventing hepatitis A.
 -Hepatitis A vaccination provides long-
lasting protection (protective levels of
anti -HA V should last 20 years after
vaccination)

27.  Major cause of liver disease worldwide
 Most common chronic blood-borne
infection
 Most common cause of chronic liver
disease.

28. PARENTERAL

29. According to the 2008 data from the USA
Centers for Disease Control, the most
common risk factors for HCV are:
 Intravenous drug abuse (54%)
 Multiple sex partners (36%)
 Having had surgery within the past 6
months (16%)
 Needle stick injury (10%)
 Multiple contacts with an HCV-infected
person (10%)
 Employment in medical and dental
fields (1.5%)
 Unknown (32%)

30.  HVC
 Single-stranded positive sense RNA Virus
• Belongs to the FLAVIRIDAE FAMILY
• Sole member of the genus Hepacivirus
 The genome of HCV contains
approximately 9600 nucleotides with
open reading frame (ORF) that encodes
one large viral polypeptide precursor of
3008 to 3033 amino acids

31. HEPATOCYTE- Major site of viral replication
 In the cytosol,the 5’ UTR directs the RNA to its
docking site on the endoplasmic reticulum and
directs cap-independent internal initiation of
HCV polyprotein translation by recruiting both
cellular proteins, including eukaryotic initiation
factors (eIF) 2 and 3, and viral proteins.
 HCV- small enveloped, single-stranded RNA
virus with 9.6-kilobase that codes for a single
polyprotein with one open reading frame,
which is processed into functional proteins

33.  The 5’ untranslated region and the C
region are highly conserved among
isolates, while envelope domain E2
contains hypervariable region.
 P7 – Adjacent to the structural proteins, a
membrane protein that functions as ion
channel.

34.  3’ end are six nonstructural (NS) regions,
 NS2, which code for cyteinprotease
 NS3, which code for serine protease and
an RNA helicase
 NS4 and NS4B, NSA5A and NSA5B, which
code for RNA dependent RNA
polymerase

35.  Viral Genotype
 first division used to describe genetic
heterogeneity of HCV
 Refers to genetically distinct groups of HCV
isolates that have arisen during the evolution of
the virus
 The sequence cluster into 6 major
genotypes (designed by numbers), and
more than 70 subtypes (desined by lower
case letter) within these major genotypes

36. The incubation period for HCV ranges
from 6 to 26 days. HCV RNA is detectable in
the blood for 1-3 weeks, with elevation in
serum transaminases.

41.  Presence of anti-HCV in high titer in
serum (generally an enzyme immuno
assay greater than 9)
 Indicates exposure to virus
 Serologic Assays
 Used for diagnosis
 Virologic Assays
 For confirming infection, monitoring
response to treatment, and evalauting
immunocompromised patients.

42.  EIAs detect antibodies against HCV
antigens
 Three generations of EIAs are developed:
Third Generation –latest generation, EIAs
detect antibodies against HCV core, NS3,
NS4, NS5 antigens as early as 7-8 weeks after
infection, with sensitivity and specificity rates
of 99%

43.  Qualitative HCV RNA
nucleic acid test
(NAT)
 Only report whether
HCV is found in serum
 not and do not
quantitate the
amount of HCV RNA
 Used only for
screening purposes
now (eg. Screening
of blood donated to
the blood bank)
 Quantitative HCV
RNA test
 Essential for
monitoring the
response to antiviral
therapy

44.  Disposable equipment, and rigorous
sterilization of reusable medical and
surgical equipment have reduced
nosocomial HCV infection
 Avoidance of having sexual intercourse
to multiple partners.

45.  Exclusion of commercial blood donors and reliance
on volunteer blood supply
 Screening donor blood with surrogate markers such
as ALT and Anti-HBc,
-markers that identify segments of blood donor
population with an increased risk of blood borne
infection
 Exclusion of blood donors in high risk groups for
AIDS and the introduction of anti-HIV screening test
 Progressively sensitive serologic and virologic
screening test for HCV infection.

46.  Eradication of the Virus
**Primary goal of therapy for HCV
infections
 Sustained Virologic Response (SVR)
**Absence of detectable virus in blood
24 hrs after completion of therapy –
excellent marker for the resolution of
HCV infection.

48. HEPATITIS D VIRUS
-Discovered in 1977
-Only member of Deltavirus
-HDV is a defective RNA
virus that co-infects with
and requires the helper
function of HBV for its
replication and expression.

49. LARGE DELTA ANTIGEN
-214-amino-acid species
-It suppress replication but
its required for assembly of
the antigen into virions
SMALL DELTA ANTIGEN
-195-amino-acid species
-It plays a role in facilitating
HDV RNA replication

51. •HDV will bind
to RNA
polymerase II
REPLICATION
•Hepatocytes
via RNA-
directed RNA
synthesis
TRANSCRIPTION
• Genomic RNA to
complementary
antigenomic RNA
HDsAg

53. CO-INFECTION
-HDV can either
infect a person
simultaneously with
HBV
SUPERINFECTION
-Superinfect a
person already
infected with HBV

54.  It is clinically
indistinguishable from
other forms of viral
hepatitis
 90% of patients are
asymptomatic
 Incubation period is 21-45
days but maybe shorter in
cases of superinfection

55.  Vaccinating susceptible
person with hepatitis B
vaccine
 No products available for
immunoprophylaxis to prevent
HBsAg carriers
 Avoidance of percutaneous
exposure and limitation of
intimate contact with person
who have HDV infection

57.  Enterically transmitted virus that occurs
primarily in India, Asia, Africa and Central
America
 In these places, Hepatitis E virus (HEV) is the
most common cause of acute hepatitis
 It has 3 open reading frames (ORF) genes;
ORF1, ORF2 and ORF3

58.  ORF1 – encodes non-structural protein
involved in virus replication; Largest
among the three
 ORF2 – middle-sized; encodes the
nucleocapsid protein
 ORF3 – smallest; encodes stuctural
protein with function undetermined
 All HEV isolates belongs to a single
serotype and five genotypes
 HEV is detected in stool, bile and liver
 IgM and IgG anti-HEV are both detected
but rapidly fall after acute infection

59.  Resembles Hepatitis A virus (HAV) in its
primarily enteric mode of spread.
 Commonly on contaminated water
 Rare person-to-person spread
 Infections arise in those population that
are immune in HAV and mostly young
adults

61.  Philippine Cancer Society – Manila
Cancer Registry
 Department of Health
 World Health Organization
 Sleisenger and Fordtran’s Gastrointestinal
and Liver Disease, 9th edition
 Robbin’s and Cotran Pathologic Basis of
Disease, 8th edition
 Harrison’s Principle of Internal Medicine,
18th edition