inflammation of liver presence of inflammatory cells in organ tissue Pathogenesis Immune response Acute Viral Hepatitis symptoms last less than 6 months Chronic Hepatitis Inflammation of liver for at least 6 months ID: 915430
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Slide1
Acute Viral Hepatitis
Slide2Hepatitis
: inflammation of liver; presence of inflammatory cells in organ tissue.
Pathogenesis: Immune response.Acute Viral Hepatitis: symptoms last less than 6 monthsChronic Hepatitis: Inflammation of liver for at least 6 monthsFulminant Hepatitis: severe impairment of hepatic functions or severe necrosis of hepatocytes in the absence of preexisting liver disease
Clinical Terms
Slide3Term is reserved for hepatitis virus
All are RNA viruses except HBV
All types produce clinically similar illnessRanges from asymptomatic to fulminant and fatal acute infection
Slide4Classic presentation:
infectious hepatitis
Phase 1 - Viral replication; Patients are asymptomatic during this phase.Phase 2 – Prodromal Phase 3 - Icteric phasePhase 4 - Convalescent phase; symptoms and icterus resolve. Liver enzymes return to normal.
Slide5Viral Hepatitis
Feco
-oral: Hepatitis A, EParentral : Hepatitis B, C, G, D
Slide6Virus
A
E
Virus
Non-enveloped RNA
Enterovirus
72
Non-enveloped RNA,
Calcivirus
Transmission
Feco
-oral
Feco
-oral
Age group
Children
Young adults
Secondary attack rates
10-20%
2-4%
Incubation period
2-6 wks
2-8wks
Chronicity
No
No
Fulminant
hepatitis
rare
Pregnant females
Virus isolation
Possible , MRC-5 cell lines
Not possible
Diagnosis
Immunofluorescense
, ELISA
ELISA, Viral RNA
Case fatality
0.5-1%
4%
Prevention
Immunoglobulin, Vaccination
Safe water cleaning
Slide7Slide8Prevention:
High risk
Travellers: vaccinations; passive immunoglobins given to those exposedhygienic measurespassive immunization ( gives <6months immunity to those at risk)
active immunization
(killed vaccine)
Two doses IM
Slide9Hepatitis: B
Slide10HBV is a DNA virus -------
hepadnavirus
familyIncomplete DNAEnvelopedP geneC geneS geneDane particlesEight genotypes of HBV identified and re-labeled A through H.
Slide11AT Risk Groups
IV drug users
People receiving multiple blood transfusionsBlood and blood products (0.00001%)Sexual promiscuityPeople in contact with HBV carriersMother to childHealth Care Workers
Slide12High
Moderate
Low/Not
Detectable
blood
semen
urine
serum
vaginal fluid
feces
wound exudates
saliva
sweat
tears
Breast milk
Concentration of Hepatitis B Virus
in Various Body Fluids
Slide13Pathophysiology
Transmission 3 main ways:
Parenterally/percutaneous route----IV Drug Users, needle sticks, Hemodialysis patientsSexuallyVertical/ Perinatal route
Slide14Clinical features
IP- 1-6
mthsPreicteric, icteric and convalescent phase90-95% recover in 2 mthsMortality 0.5 -2%1% with delta virus infection develop fulminant infection1- 10% will go into chronicityVaccine preventable cancerNo animal reservior
Slide15Clinical Presentation
Acute Hepatitis B
- less than 6 months; Based on significant aminotransferase activity due to necro inflammatory injury Symptoms are often non-specific symptoms such as myalgia, malaise , nausea, fatigue , pruritus, abdominal pain, RUQ, jaundiceChronic Hepatitis B - greater than 6 months; Based on grade, stage, and etiology. Fibrosis and
Necroinflammatory
processes; can last for decades
Immune tolerant--High viral replication, NL liver enzymes, low inflammation and fibrosis. Seen in children or those affected early in life.
Immune active--High Liver enzymes and High HBV DNA and
HBeAg
, Active Replication
Carrier State with low replication
Seroconversion
from
HBeAg
to
HBeAB
Low HBV levels, NL liver enzymes, Reduced Liver inflammation
Low risk for developing of HCC
Slide16Carriers > 6mths
More common in neonates and children
Super carrierSimple carrier
Slide17Slide18Diagnosis of HBV infection
Serological assays
HBsAg Early indicator, appear as early as 14 days. Usually disappears 12 to 20 week after onset of symptoms.
Presence after 6 M indicate chronic carrier.
If Absent diagnosis will depend up on
HBc-Ab
total (chronic carriers)
HBc-Ab
IgM
(acute hepatitis).
Anti-
HBsAg
(
Hbs
Ab
)
Presence > 10mU/ml without detectable
HbsAg
indicate immunity, recovery from HBV or previous vaccination.
HBc-Ab
total
1st antibody to appear 4 – 10 weeks after infection and persist for life.
Used with
HbsAg
to screen all blood donors as it detects virtually all persons who have previously infected with HBV.
Slide19Diagnosis of HBV infection
Serological assays
HBc-Ab IgM The only serologic marker that diagnose serological window (disappearance of HBsAg and
HBeAg
without appearance of their corresponding Abs).
Useful in diagnosis of acute cases and sub-clinical infections(< 6M)
HBe
-Ag
Marker of active HBV replication in the liver.
Is present only in
viraemic
patients and can be used as surrogate marker for HBV-DNA assay.
HBe-Ab
Appear after
HBe
-Ag disappear and remains for years.
Indicate decreasing infectivity.
Slide20Diagnosis
Serology
Liver Chemistry testsAST, ALT, ALP, and total BilirubinHistology--Immunoperoxidase stainingHBV Viral DNA--Most accurate marker of viral DNA and detected by PCR
Liver Biopsy--to determine grade(Inflammation) and stage(Fibrosis) in chronic Hepatitis
Screening of blood donors
Slide21Chronic infection
Slide22Treatment
Interferon therapy – First Line
Method of action is the inhibition of viral replication of cells thus assisting the immune systemInterferon alpha: TX: SUB-Q 5 million units q D or 10 million units 3x weekly Sub-QSide effects: "Flulike Symptoms", alopecia, rash, diarrheapINF-alpha(pegylated interferon-alpha): 180ug q weekly SUB-QBetter Choice than IFN-Alpha--Greater Bioavailability, Longer half life, Better treatment schedule
Slide23Treatment cont.
3) Nucleotide analogues
Method of action is the inhibition of viral reverse transcriptaseTenovirDose: 300mg qdHighly effective with low resistanceWell toleratedAdefovir – 1st line Dose: 10mg dailyResistance less than TenovirSide effect: nephrotoxicity and lactic acid
Slide24Prophylaxis
Screening of donors
Use of disposable itemsManagement of spillsPassive vaccination (Mother to child)Active vaccinationAntibody titre
Slide25Prophylaxis
HBV Vaccine
Indicated for everyone and especially those in high risk groupsIM injection at 0,1,6 months in infants and adultsResponse greater than 90% after 3rd doseHBV Pregnant MothersGive 1st dose of Hip B vaccine and Hip B Immunoglobulin(HBIG) o.5 ml within 12 hours of birth.2nd dose at 1 month, 3rd at 6 monthsRecheck at 12 months for active infection95% lifetime immunityNot Done---leads to 90% chronic HBV
Transmitted through birth canal during birth or through umbilical cord.
Others i.e. those receiving a needle stick
Should receive 0.04 to 0.7 ml/kg of HBIG and 1st dose vaccine within 48 and no later than a week.
Slide26Hepatitis C
Spherical, enveloped, single-stranded RNA virus (
Flavivirus genus)6 genotypesEach genotype has several subtypes170 million infected worldwideParenteral Transmission: IV drug usersMost common indication for liver transplantation
Slide27Hepatitis C
ACUTE CHRONIC
50-80%first 6 months after infection more than 6 months 60-70% asymptomatic often asymptomaticmost patients develop chronic 1/3 progress to cirrhosis in 20y HCV
I
nfects 3-4 million people per year
Slide28Hepatitis C
Incubation period: 7-8
wksUsually clinically mild, does not cause significant acute illness75% are subclinical infectionsCase fatality is 1%Fluctuating elevations of AST & ALT50-80% likelihood of developing chronic hepatitis
Slide29Hep C Transmission
Spread by blood to blood contact:
IV drug useMother to child transmissionCan be sexually transmitted but less commonFor most, acute infection leads to chronic infection There is no vaccine for Hepatitis C
Slide30.
Slide31Diagnosis: HCV
HCV:
Anti-HCV; cannot distinguish acute from chronic infectionEIA: antibodies against core protein and nonstructural proteins; may appear 3 – 5 months after infectionPCR: used to detect viral RNA HCV80% of cases: patients are asymptomatic and do not develop icterus.
Treatment: Interferon alpha, Ribavirin; PEG-IFNs (better sustained absorption, a slower rate of clearance, and a longer half-life than those of unmodified IFN)
Slide32Treatment of Chronic Hepatitis C
Genotype 1 (4-6)
Genotype 2,3
PEG-interferon alpha
+
Ribavirin
for
48 weeks
PEG-interferon alpha
+
Ribavirin
for
24 weeks
Chronic hepatitis C
Slide33HEPATITIS D
Defective satellite virus
Ss RNA, sphericalRequires outer envelope of HBsAG for replication and transmissionCan progress to chronic diseaseIncubation Period 30to 150 daysTransmissionAs co-infection with acute HBV ( serious and fulminant course) or superinfection in chronic HBV carrier (deterioration of chronic illness)
Slide34Hepatitis D
Subviral satellite
because it can propagate only in the presence of hepatitis B coinfection superinfectionTransmission: parenteral (intravenous drug use mostly)> 60% develop cirrhosis
Slide35Diagnosis
Immunoflurescence
SerologyHepatitis D antibody (Anti-HDV)Indicates HDV superinfectionRNA by hybridizationRisk Factors - Same high risk groups as those for Hip B Prevention - Avoidance of Hip B and/or Hip B vaccine DX - HDV antigen in serum or finding Ab to HDV antigenTX:IFN-alpha
Slide36Hepatitis G
Newly discovered virus
In pts with chronic hepatitis , hemophiliacs, iv drug abusers, blood donorsSs RNA virusTransmission parentrally, sexually and perinatalDetected by RT-PCR
Slide37Recommended PEP for Hepatitis B Virus
Vaccination/Ab response status of exposed patient
Treatment when source patient is:
HBsAg positive
HBsAg
negative
Source unknown or not available for testing
Unvaccinated/
non-immune
HBIG ×1; initiate HB vaccine series
Initiate HB vaccine series
Initiate HB vaccine series
Previously
vaccinated, known responder
No treatment
No treatment
No treatment
Previously
vaccinated,
known non-responder
HBIG ×1 and initiate revaccination or HBIG ×2
No treatment
No treatment unless high-risk source; if high-risk source, treat as if source were HBsAg positive
Previously
vaccinated,
response unknown
Single vaccine booster dose
No treatment
No treatment unless high-risk source; if high-risk source, treat as if source were HBsAg positive
Still undergoing vaccinated
HBIG ×1; complete series
Complete series
Complete series