2. HISTORY
• LURMANN-1885 observed outbreak of jaundice 2-8 mths after people received
smallpox vaccine
• In 1937 larger outbreak after yellow fever vaccine
• Vaccines were then prepared from human lymph
• 1965- surface protein of HBV accidently discovered by BLUMBERG while
searching for polymorphic serum protein in Australian Aborigine & was called
Australian Antigen
• 1967- Acc. between Australian Ag & Se. Hepatitis recognised
• 1970- Dane & colleagues detected Dane particles, the surface of which cross-
reacted with antibodies against Australian Ag.
3. EPIDEMIOLOGY
• 50% of world’s population have had contact with HBV & about 10% of these
have developed persistent infection
• HBV carriers have high risk of developing HCC
• Mortality from acute is < 1% but much higher in chronic hep-B
• Lower socio-economic condition is often connected with higher prevalence
• Most healthy adults (90%) who are infected will recover and develop
protective antibodies against future hepatitis B infections
• 90% of infants and up to 50% of young children infected with hepatitis B will
develop chronic infections.
4. Hepatitis B In the World
• 2 billion people have been infected (1 out of 3 people).
• 400 million people are chronically infected.
• 10-30 million will become infected each year.
• An estimated 1 million people die each year from hepatitis B and its
complications.
• Approximately 2 people die each minute from hepatitis B.
5. .
It is a DNA virus
It belongs to the
Family: Hepadnaviridae
Genera: Orthohepadnaviridae
Other members of
Orthohepadnaviridae are
Woodchuck hepatitis virus
Ground squirrel hepatitis virus
GENOTYPE A-H
A1 & D in INDIA
6. .
• Surface of virions consists of possibly 240 subunits comprising of 3
different polypeptides termed Large, middle, small surface(HBs) proteins
• Both virion & the surface Ag particles are assembled at the ER
• The lipid in the outer protein shell or the HBs particles is derived from an
intracellular compartment & not the plasma membrane
8. . GENE REGIONS ANTIGEN
S
( Having three regions S,
Pre-S1 and Pre-S2)
S
S+ Pre S2
S+ Pre S1 & S2
Small Protein (S) Surface antigen
Middle Protein (M) HBsAg
Large protein(L)- present only in virion
C
( Having regions C and
Pre-C)
C
C+ Pre-C
Core antigen
HBeAg
P DNA Polymerase
X HBxAg (nonparticulate antigen which leads
to enhanced replication of HBV)
9. The Genome
• HBV is a small (3.2-kilobase [kb]) virus with a DNA genome that has a relaxed,
circular, partially double-stranded configuration.
• The genome is composed of 4 open reading frames
(ORFs) and has a compact design in which several genes overlap and use the
same DNA to encode different viral proteins.
• The 4 viral genes components include the core, surface,
X, and polymerase genes.
• The core gene encodes the core nucleocapsid protein, which is important in viral
packaging and production of HBeAg.
• The surface gene encodes the pre-S1, pre-S2, and S proteins (comprising the
large [L], middle [M], and small [S] surface proteins).
• The X gene encodes the X protein, which has transactivating properties and may
be important in hepatic carcinogenesis,
•The polymerase gene has a large ORF ( ≈800 AA). It encodes a large protein with functions that are critical for packaging and DNA replication
(including priming, RNA- and DNA-dependent DNA polymerase, and RNase activities).
10. Life cycle
• sodium taurocholate cotransporting polypeptide is likely to be the
receptor for binding the pre-S1 HBsAg protein (10-36)
• There is actin independence & microtubule dependence of viral entry
• Nucleocapsids bind to the NPC(nuclear pore complex), following the
classical pathway of karyophilic proteins, which is mediated by
cellular proteins importin α & β
• Formation of cccDNA from rc DNA
• removal of 5’ terminal redundancies frm –ve strand & covalently bound
polymerase
• Removal of RNA primer
• Completion of + DNA strand
• Linkage of 5’ & 3’ ends of each strand by DNA ligase
11. .
• Short +ve strand extended & -ve strand repaired forming cccDNA
• RNA polymerase II produces 3 subgenomic RNA & 1 pregenome RNA
• Viral transcripts are formed for the hepatitis B surface antigen
(HBsAg), DNA polymerase, X protein, and RNA pregenome; the
pregenome and polymerase are incorporated into the maturing
nucleocapsid and removed after translation.
• The surface protein enveloping process occurs in the endoplasmic
reticulum.
• Some of the nonenveloped nucleocapsid recirculates back to the
nucleus, and the cycle begins again.
• Excess tubular and spherical forms of HBsAg are secreted in great
abundance and outnumber complete virions in serum by a factor of
10,000 or more.
13. ANTIGENIC STRUCTURE
HBsAg ( Hepatitis B surface antigen)
• It is an envelope protein
• It carries a group specific antigen ‘a’ and two types of specific antigens
d or y and w or r
• Thus there are 4 antigenic types of HBsAg-
adw, adr, ayw and ayr
• HALF LIFE- >8 days
14. ANTIGENIC TYPES OF HBsAg
ANTIGENIC TYPES
adw 2 GP A
4 GP B
adr GP C
ayw 1 GP D
ayr
DISTRIBUTION
• Worldwide
• Asia ( South and East India)
• Africa, India, Russia
• Rare; Africa, India, Russia
15. MODES OF TRANSMISSION
• Three important modes of transmission-
• Parenteral
• Perinatal
• Sexual
16. High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
Concentration of Hepatitis B Virus
in Various Body Fluids
17. .
Parenteral Transmission:
It results from accidental inoculation of minute amount of blood, Blood products or
fluids containing HBV during medical, surgical or dental procedure.
As little as 0.00001 ml of infected blood or other material can be
infectious.
18. .
Perinatal Transmission:
• Congenital or Vertical transmission is quite common from carrier mothers
• The risk to babies is high if the mother is HBeAg positive (60-90%) and low if Negative (
5-15%)
• True congenital infection is rare
• Infection is usually acquired during birth by contact of maternal blood with the skin and
mucosa of the fetus or in the immediate postnatal period.
• Infection by ingestion has also been reported.
19. .
SEXUAL TRANSMISSION:
• HBV is present in body fluids such as semen and vaginal secretions of infected individual.
• So it can be transmitted by sexual contact
• Male homosexuals are at higher risk of acquiring infection
• The risk of transmission increases with the number of partners and duration of such
relationships.
• HBV infection has occurred after artificial insemination also.
20. HIGH RISK GROUP
• Medical and paramedical personnel
• Staff of blood banks, Dialysis units, medical laboratories, mental health
institutions
• Barbers
• Sex workers
• People from endemic regions
• Babies of mothers with chronic HBV
• Intravenous drug abusers
• Hemophiliacs and other patients requiring blood and blood product
treatment
21. CLINICAL FEATURES
• Onset is slow, usually insidious but severe
• Incubation period– 6 weeks to 6 months
• Fever is less common and of low grade.
• Jaundice is rarely seen in children
22. Acute HBV infection
• The course of acute HBV infection can be divided into three phases
1.Preicteric phase:
Malaise, anorexia, nausea and vomiting
Some develop arthralgia, serum sickness, polyarteritis nodosa and
glomerulonephritis
2. Icteric phase
Jaundice, pale stools and dark urine
3.Convalescent phase:
Malaise and fatigue
10-20% shows serum sickness type syndrome( joint pain, urticaria,
maculopapular rash).PAN & membranous GN due to vasculitis.
23. HEPATITISB CARRIERS
• Two types of Hepatitis B Carriers-
• Super Carriers:
• Blood contains high titres of HBsAg
• Also contains HBV, HBeAg and DNA polymerase
• They are highly infectious.
• Simple Carriers:
• Blood contains low level of HBsAg
• HBeAg, HBV and DNA polymerase are absent
24. IMMUNERESPONSE
1.Humoral response: ( Antibody to HBV )
i)Antibody to HBsAg:
-It is associated with resistance to infection
-Useful indicator of past infection or recent immunity
ii)Antibody to HBcAg:
-It rises rapidly following infection
-It is not protective
-It appears to be related to the amount and duration of replication of the virus
-Persistent HBsAg carriers contain Highest titre of antibody.
iii) Antibody to HBeAg:
-It is found in sera of patients with low infectivity.
2.Cell Mediated Immunity:
-Defective function of T-Cell may favour the development of Chronic liver damage.
25. LABORATORY DIAGNOSIS
1. Detection of Viral markers:
i) HBsAg:
-Specific marker for HBV infection
-First marker to appear in blood after infection
-Peak levels are seen in the Pre-icteric phase(2-6 wks b4 onset of symp) of
illness.
-It remains in circulation throughout the icteric or symptomatic course of the
disease(2 mths)
-Disappears with recovery from clinical disease but may persist for years in
carriers.
Antibody to HBsAg appears within weeks after the disappearance of HBsAg
and persists for very long periods
26. .
ii) HBeAg :
-Appears in the serum at the same time as HBsAg
-HBeAg containing sera are highly infectious and those with anti HBeAg of little
infectivity.
-It is an indicator of active intrahepatic viral replication and the presence in
blood of HBV DNA, virions and DNA polymerase.
-The presence of HBeAg is an adverse prognostic sign.
-Disappears within a few weeks
-Disappearance of HBeAg is followed by appearance of anti-HBe.
27. .iii HBcAg:
-Not detectable in the serum.
-Can be demonstrated in hepatocytes by immunofluorescence.
-Anti-HBc antibody usually appears in serum 1-2 weeks after the appearance
of HBsAg.
-Anti-HBc antibody is the earliest antibody to appear in the blood.
-It remains lifelong and thus serves as a useful indicator of prior infection with
HBV.
28. .
2. Viral DNA Polymerase:
It appears transiently in serum during preicteric phase.
3. Polymerase Chain Reaction:
-HBV DNA level can be detected in serum by PCR.
-It is a highly sensitive test.
-It is an indicator of viral replication in the liver.
-It helps to assess the progress of patients under antiviral treatment.
4. BIOCHEMICAL TESTS:
-Elevation of serum transaminase levels (SGOT, SGPT)
-Serum bilirubin levels may be elevated.
29. Course of acute hepatitis B virus (HBV) infection
Incubation period: The incubation period of the hepatitis B virus is 75 days on
average, but can vary from 45 to 160 days.
32. Natural history chronic HBV infection in patients
with early-life (A) and adult (B) acquisition of the
infection
In patients infected early in life, the fist phase is that of
immune tolerance. After decades of normal (NL) serum
ALT and high HBV DNA levels, this immune-tolerant
phase evolves to a (HBeAg)-positive immune active
phase of variable duration. Ultimately, patients enter a
spontaneous or therapeutically-induced inactive carrier
state, which can last indefinitely. At the time of HBeAg
seroconversion, however, immunologic pressure may
select for a viral mutant (precore, core promoter, or
both), which is incapable of producing HBeAg antigen.
Viral and serum ALT levels typically fluctuate during this
stage (HBeAg-negative hepatitis). If the patient is not
treated, late disease complications often occur.
B, Persons who acquire the infection in adulthood do
not enter into an immunetolerant phase. Otherwise, the
serologic and laboratory features are the same as those
for persons who acquire HBV infection early
in life. Because of the compressed time scale of events,
however, HBeAg-negative chronic hepatitis B and late-
stage complications are observed less frequently
33.
34. TREATMENT
• HBV replicates by protein primed Reverse Transciptase. The product is a 3
kb RC-DNA.Upon infection it converts to ccc DNA which is refractory to
current Anti-HBV treatment.
• Current antiviral agents can control but not eliminate HBV
• LAMIVUDINE & ENTACAVIR do not have any effect on cccDNA
• IFN-α reduces 80% ccc DNA after 10 days
• New drugs designed on basis of degradation of cccDNA by host enzyme
cytidine deaminase.
35. Severe Acute Hepatitis
• Because of the high rate ( >95%) of complete immunologic recovery from acute hepatitis B, definitive
recommendations can’t be made.
• experts recommend nucleos(t)ide analog therapy when HBeAg remains detectable in serum for
more than 10 to 12 weeks because of the high likelihood of evolution to chronic HBV infection
without treatment.
• persons with acute viral hepatitis complicated by an increase in the INR
above 1.5 and deep jaundice persisting for more than 4 weeks should receive antiviral therapy.
• Antiviral treatment of patients with hepatitis B–induced acute liver failure is recommended in the
practice guidelines because of the safety of nucleos(t)ide analog therapy and the need for liver
transplantation in many of these patients.
• It has been recommended that therapy continue for 3 months after HBsAg seroconversion or at
least 12 months after HBeAg seroconversion if HBsAg loss does not occur
37. NON-INVASIVE ASSESSMENT OF LIVER DISEASE STAGE AT BASELINE
AND DURING FOLLOW UP
• APRI (aspartate aminotransferase [AST]-to-platelet ratio index) is recommended as the
preferred non-invasive test (NIT) to assess for the presence of cirrhosis(APRI score >2 in
adults) in resource-limited settings.
• Transient elastography (e.g. FibroScan) or FibroTest may be the preferred NITs in settings
where they are available and cost is not a major constraint
• The FibroTest score is calculated from the results of a six-parameter blood test, combining six serum
markers with the age and gender of the patient: Alpha-2-macroglobulin, Haptoglobin, Apolipoprotein
A1, Gamma-glutamyl transpeptidase (GGT), Total bilirubin, and Alanine transaminase (ALT). ALT is used
in a second assessment called ActiTest that is part of FibroTest.
38. WHO TO TREAT AND WHO NOT TO TREAT IN PERSONS WITH CHRONIC
HEPATITIS B
•patient with CHB and clinical APRI score >2 , regardless of ALT levels, HBeAg status or HBV DNA levels.
• patient with CHB &APRI score<2 , but are aged more than 30 years, & have persistently abnormal ALT levels
and evidence of high level HBV replication (HBV DNA >20 000 IU/mL), regardless of HBeAg status.
• Where HBV DNA testing is not available: Treatment may be considered based on persistently abnormal ALT
levels alone, regardless of HBeAg status.
•Treatment was not recommended in persons with minimal liver disease or fibrosis, and at low risk of progression to
cirrhosis and HCC on the basis of persistently normal ALT levels and low levels of HBV replication (<2000 IU/mL), and an
APRI score ≤2, as the potential harms of long-term antiviral therapy outweigh the benefits
39. Recommendation for HBV/HIV coinfected persons:
•ART should be initiated in all those with evidence of severe chronic liver
disease, regardless of CD4 count
• Those with a CD4 count <500 cells/cumm, regardless of stage of liver
disease.
40. FIRST-LINE ANTIVIRAL THERAPIES FOR CHRONIC
HEPATITIS B
• In 12 years or older in whom antiviral therapy is indicated, the nucleos(t)ide
analogues (NAs) which have a high barrier to drug resistance (tenofovir or
entecavir) are recommended.
• Entecavir is recommended in children aged 2–11 years.
• NAs with a low barrier to resistance (lamivudine, adefovir or telbivudine)
can lead to drug resistance and are not recommended.
• In HBV/HIV-coinfected adults, adolescents and children aged 3 years or
older, tenofovir + lamivudine (or emtricitabine) + efavirenz as a fixed-dose
combination is recommended as the preferred option to initiate ART.
43. Other drugs used for the treatment of CHB
and their doses in adults
44. SECOND-LINE ANTIVIRAL THERAPIES FOR
THE MANAGEMENT OF TREATMENT FAILURE
• In persons with confirmed or suspected antiviral
resistance (i.e. history of prior exposure or primary
non-response) to lamivudine, entecavir, adefovir or
telbivudine, a switch to tenofovir is recommended.
45. WHEN TO STOP TREATMENT
• All persons with cirrhosis based on clinical evidence (or APRI score >2 in
adults) require lifelong treatment with nucleos(t)ide analogues (NAs), and
should not discontinue antiviral therapy because of the risk of reactivation,
which can cause severe acute-on-chronic liver injury.
46. Discontinuation of treatment
Persons without clinical evidence of cirrhosis (or based on APRI score≤2 in adults);
- and who can be followed carefully long term for reactivation;
- and if there is evidence of HBeAg loss and seroconversion to anti-HBe
(in persons initially HBeAg positive) and after completion of at least one additional year of treatment;
- and in association with persistently normal ALT levels and persistently undetectable HBV DNA levels (where HBV DNA testing is
available).
Where HBV DNA testing is not available: Discontinuation of NA therapy may be considered in persons who have evidence of
persistent HBsAg loss and after completion of at least one additional year of treatment, regardless of prior HBeAg status.
47. MONITORING
• It is recommended that the following be monitored at least annually:
• - ALT level (and AST for APRI), HBsAg, HBeAg, and HBV DNA levels
- Non-invasive tests (APRI score or FibroScan) to assess for the
presence of cirrhosis, in those without cirrhosis at baseline
- If on treatment, adherence should be monitored regularly and at
each visit.
48.
49. Monitoring for hepatocellular carcinoma
• Routine surveillance for HCC with abdominal ultrasound and alpha-fetoprotein testing
every six months is recommended for:
- persons with cirrhosis, regardless of age or other risk factors
- persons with a family history of HCC
- persons aged over 40 years (lower age may apply according to regional incidence of
HCC), without clinical evidence of cirrhosis (or based on APRI score 2), and with HBV
DNA level >2000 IU/mL
51. Prophylaxis
General Preventive Measures:
-Health education
-Improvement of personal hygiene
-Strict attention to sterility.
-Screening for HBsAg and HBeAg in blood donors.
-Avoiding use of Unsterile needles, syringes and other materials.
53. .
Active immunization:
Plasma derived vaccine:
- Vaccine is prepared by purifying 22 nm particle of HBsAg from the plasma of healthy
carriers.
-Formaldehyde inactivated.
-Immunogenic and safe.
Recombinant Yeast Hepatitis B vaccine.
-Produced by a recombinant DNA in Yeast in which a plasmid containing the
gene of HBsAg has been incorporated.
- Particles of HBsAg are non-glycosylated.
54. ACTIVE IMMUNIZATION
• The plasma-derived vaccine, and later with the yeast-derived(Hansenula polymorpha),
recombinant vaccines against HBV infection used
• After proper immunization with recombinant, S-containing vaccine, adults would
respond in ~97% and children in 98.5% of cases.
• The synthesis of anti-HBs antibodies at a protective level: ≥10 IU/L and ≥100 IU/L &
sufficient cellular immunity should be achieved after successful immunization of a child
or an adult against HBV.
• protective immunity lasts at least 15 yrs
55. Characteristics of the currently used, commercial
second-generation vaccines;
Name Producer Doses
Engerix B Glaxo Smith Kline, 10 and 20 μg
Gen-H-B-Vax Merck Sharp Dohme, USA 2.5, 5 and 10 μg
H-B-Vax II Merck Sharp Dohme, USA 5, 10, 40 μg
H-B-Vax PRO Merck Sharp Dohme, USA 5, 10, 40 μg
GenHevac B Pasteur Merieux 20 μg
Recombivax Merck Sharp Dohme 2.5 – 40 μg
Hepavax-Gene Green Cross Vaccine, Korea 10 and 20 μg
Euvax B Ikson Factory LG Chem, Korea 10 and 20 μg
56. Vaccine in INDIA
• 20 mcg of purified Hepatitis B surface antigen
• Adsorbed on Aluminium hydroxide (Al+++) 1.25 mg
• Preservative: Thiomersal 0.01%
57. vaccine
Third generation vaccines (surface Ag S + pre S1 + pre S2 peptides)
Hepimmune Berna Biotech Switzerland
Bio-Hep-B (Sci-B-Vac) Biotechnology General Rehovot, Israel
Hepa Gene 3 Exogene / Hexal Biotech Germany
Hepacare Medeva Gt. Britain
58. .
• protective immunity lasts at least 15 yrs in healthy responders to
HBV vaccine
• The highest rate of nonresponsiveness represents patients with
leukemia, lymphoma and/or solid tumors
• A full 4-dose scheme is usually applied (0/1/2/6 months;
0/1/2/12/months) and the dose of the vaccine could be doubled.
• The use of third generation vaccine, i.e. containing all surface
proteins pre-S1, pre-S2 and S should be an almost ideal solution to
immunize such difficult groups of children and adults.
59. .
.
Recombinant Chinese Hamster
Ovary (CHO) cell hepatitis vaccine
-CHO cells have been used for
vaccine preparation.
-First vaccine using mammalian cell
expression system.
Synthetic peptide vaccine:
-Chemically synthesised
polypeptide vaccines.
-Still under experimental stage.
.
60. .
DNA – based vaccine
• These are the next generation preparations. It was shown
• in laboratory animals that DNA vaccination appeared an effective
method to induce protective immunity
• HBsAg-DNA can be introduced into the host by I.M or I.D route.
• An alternative is using genegun, Biolistic®, PowderJectTM, Accell®, or
particle-mediated DNA delivery
• The first human studies were performed between 1999-2001,
showing very good safety, and no local or systemic side effects, except
for little or no pain at the site of vaccination
61. .
Plant-based HBV vaccines
• Incorporating preS-S genes of HBV into edible plants will enable us to
profit from the enormous potential of(GALT) of laboratory animals, as
well as humans, for the synthesis of humoral and cellular immunity
against HBV .
• cholera toxin was added as mucosal adjuvant in order to obtain
maximum antibody response
• The following genetically modified plants were tried in these
procedures: lettuce,carrot, potato, cherry, tomato,maize and tobacco.
• Experimental studies in this field were performed in countries such as
Poland, USA, Egypt, India, China and USA
62. Passive immunization
• Special immunoglobulin is produced from donors who are naturally
immune and boosted with plasma-derived vaccine
• Anti HBc negative donors who have high titers after vaccination
• HBIG 15% of HBIG must contain 200 IU/ml--- I.M
5% of HBIG must contain 50 IU/ml----- I.V
• HBIG should be administered as early as possible after exposure, preferably within 48 hours.
• A second dose is usually given at an interval of 4 weeks after the first dose.
• It may not prevent infection but protects against illness and the development of
carrier state.
• Dose: 300-500 IU( Intramuscularly administered)
63. Infant and neonatal hepatitis B vaccination
• All infants should receive their fist dose of hepatitis B vaccine as soon as
possible after birth, preferably within 24 hours, followed by two or three
doses.
Prevention of mother-to-child HBV transmission using antiviral therapy
• In HBV-mono infected pregnant women, the indications for treatment are the
same as for other adults, and tenofovir is recommended. No recommendation
was made on the routine use of antiviral therapy to prevent mother-to-child
HBV transmission.
64. PRE & POST TESTING
• If high probability of HBV infection shld be tested for HBs Ag, even if
negative for HBc Ag.
• An HBs Ag positive person shouldn’t be vaccinated
• Immune response should be controlled by a quantitative anti-HBs test
1 mth after 3rd dose anyone who is at greater than average risk
• 10 IU/l is marker of protection
• Low or non responders with <100 IU/lshld be revaccinated after 1
year
• Non responders after 4 doses can take more dose
65. Escape mutants
• HBs Ag appears in spite of protective level of Anti HBs in few due to
escape variants
• It is described in various genotype except genotype A
• Mutation in glycine 145 of the S protein to arginine
• Most vaccine have genotype A2 or HBsAg adw2
66. Algorithm for the treatment of
hepatitis B surface antigen
(HBsAg)-positive mothers during
pregnancy.
The choice of anti viral agent is
less important if treatment of the
mother is not needed
long term. In the event that the
treatment needs to be continued
after delivery, the patient should
be started on a high–genetic
barrier drug initially or switched
to one immediately after delivery.
69. TYPE C HEPATITIS
• It was discovered while trying to identify the group of ҅non-A non-B’
viruses by experimental infection in chimpanzees .
• Commonest cause of post-transfusion hepatitis in developed countries.
• The virus has not been grown in culture, but has been cloned in
Escherichia coli.
• It is a 50-60 nm virus with a linear, single stranded RNA genome, enclosed
within a core and surrounded by an envelope, carrying glycoprotein
spikes.
70. • HCV resembles flavivirus in structure and organization, and has been
classified as a new genus Hepacivirus in the family Flaviviridae.
• HCV shows considerable genetic and antigenic diversity.
• At least six different genotypes and many subtypes have been identified
indicating high mutability.
-Some genotypes are seen worldwide, while others are localized.
- Because of diversity there is little heterologous or even homologous
post infection immunity in hepatitis C.
71. EPIDEMIOLOGY
• HCV infection is seen only in humans.
• Source of infection is the large number of carriers, estimated to be about
200 million worldwide.
• Infection is mainly by blood transfusion and other modes of contact with
infected blood or blood products.
• High risk groups- Injectible drug abusers.
Transplant recipients and
Immunocompromised persons.
• Sexual transmission- Less important
• Vertical transmission- Possible.
• HCV infection occurs throughout the world.
• Carrier rates verying 1-20%
• A quarter of all chronic hepatitis cases in India is believed to be due to
HCV infection.
72. CLINICAL FEATURES
• Incubation period- 15 -160 days, with a mean of 50 days .
• Acute illness is usually mild or anicteric.
• Overt jaundice is seen in about 5% of patients only.
• Important part in type C hepatitis is its chronic illness.
• About 50-80% of patients progress to chronic hepatitis with some
developing cirrhosis and hepatocellular carcinoma.
73. LABORATORY DIAGNOSIS
• The most sensitive and Gold standard test in establishing diagnosis is assay for
HCV RNA by
Polymerase chain reaction ( PCR )
Transcription mediated amplification (TMA )
Branched chain complementary DNAhybridization ( b DNA hybridization)
• Standard method of diagnosis is the antibody detection by ELISA. It may show
nonspecific reactions and so confirmation by immunoblot assay is
recommended.
74. PROPHYLAXIS:
• Only general prophylaxis , such as blood screening is possible.
• No specific active or passive immunizing agent is available.
TREATMENT:
Prolonged treatment with Interferon α, either alone or in combination with
antiviral agents like RIBAVIRIN is indicated.
Vaccination: currently no vaccine
Problem : high variability among strains & fast mutation
Phase I/II human trial vaccine
• Syncon:
• Inovio : synthetic multi antigen DNA vaccine of gene 1a &1b & targeting the Ag Ns3/4A &
NS4B/5A
75. Treatment of acute hepatitis C
• Based on existing data, PegIFN-α monotherapy ----PegIFN-α2a, 180 µg/week or PegIFN-α2b, 1.5
µg/kg/week) for 12 weeks can be used in patients with acute hepatitis C
• PegIFN-α (PegIFN-α2a, 180 µg/week or PegIFN-α2b 1.5 µg/kg/week) should be combined with daily
weight based ribavirin (1000 or 1200 mg in patients <75 kg or ≥75 kg, respectively) for 24 weeks in
patients with acute
hepatitis C who are HIV-coinfected
• There is no indication for antiviral therapy as postexposure prophylaxis in the absence of documented
HCV transmission
