Micro Hepatitis

Front 1

hepatitis definition

Back 1

Inflammation of the liver, causing jaundice, fatigue, nausea, vomiting, and abdominal pain

Front 2

hepatitis Non-infectious causes

Back 2

Non-infectious causes : Drugs, alcohol, ischemia, inherited diseases, toxins etc.

Front 3

hepatitis Infectious causes:

Back 3

Infectious causes: the hepatitis viruses, other viruses, many bacteria and parasites

Front 4

what are the the “Hepatotropic” viruses?

Back 4

Mainly Hepatitis viruses A – E. These 5 viruses cause hepatic damage without major involvement of other organs.
Called the “Hepatotropic” viruses (misnomer?)

Front 5

Other viruses can cause hepatitis as part of a more widespread disease

Back 5

YF, EBV, CMV

Front 6

what were the NANB (non-A non-B) viruses

Back 6

HCV and HEV previously known as NANB (non-A non-B) viruses
Enterically transmitted NANB (now mainly HEV)
Parenterally transmitted NANB (now mainly HCV)

Front 7

Hepatitis VirusesTaxonomy
Hepatitis A

Back 7

Hepatitis A - Picornavirus

Front 8

Hepatitis VirusesTaxonomy
Hepatitis B -

Back 8

Hepatitis B - Hepadnavirus

Front 9

Hepatitis VirusesTaxonomy
Hepatitis C

Back 9

Hepatitis C - Flavivirus

Front 10

Hepatitis VirusesTaxonomy
Hepatitis D

Back 10

Hepatitis D - Deltavirus

Front 11

Hepatitis VirusesTaxonomy
Hepatitis E

Back 11

Hepatitis E - Calicivirus

Front 12

Hepatitis RNA viruses:

Back 12

RNA viruses:
Hepatitis A
Hepatitis C
Hepatitis D (defective RNA virus)
Hepatitis G (single stranded)

Front 13

Hepatitis DNA viruses:

Back 13

DNA viruses
Hepatitis B
? Hepatitis F

Front 14

Hepatitis Transmission Enteric spread

Back 14

Enteric spread: HAV, HEV
(fecal-oral transmission)

Front 15

Hepatitis Transmission Parenteral spread

Back 15

Parenteral spread: HBV, HCV, HDV
(blood, vertical & sexual transmission)

Front 16

Hepatitis Commonest sexual transmission

Back 16

hbv

Front 17

Hepatitis VirusesTaxonomy
Hepatitis A

Back 17

Hepatitis A - Picornavirus

Front 18

Hepatitis VirusesTaxonomy
Hepatitis B -

Back 18

Hepatitis B - Hepadnavirus

Front 19

Hepatitis VirusesTaxonomy
Hepatitis C

Back 19

Hepatitis C - Flavivirus

Front 20

Hepatitis VirusesTaxonomy
Hepatitis D

Back 20

Hepatitis D - Deltavirus

Front 21

Hepatitis VirusesTaxonomy
Hepatitis E

Back 21

Hepatitis E - Calicivirus

Front 22

Hepatitis RNA viruses:

Back 22

RNA viruses:
Hepatitis A
Hepatitis C
Hepatitis D (defective RNA virus)
Hepatitis G (single stranded)

Front 23

Hepatitis DNA viruses:

Back 23

DNA viruses
Hepatitis B
? Hepatitis F

Front 24

Hepatitis Transmission Enteric spread

Back 24

Enteric spread: HAV, HEV
(fecal-oral transmission)

Front 25

Hepatitis Transmission Parenteral spread

Back 25

Parenteral spread: HBV, HCV, HDV
(blood, vertical & sexual transmission)

HAV maybe rarely parenterally transmitted

Front 26

Hepatitis Commonest sexual transmission

Back 26

hbv

Front 27

which hepatitis viruses are enemic in the US?

Back 27

Hepatitis A, B, C and D are endemic in US

Front 28

most common cause of acute hepatitis

Back 28

HAV - most common cause (32%) of Acute hepatitis

Front 29

most common cause of chronic hepatitis

Back 29

HCV - most common cause of Chronic

Front 30

HAV, HBV, and HCV cause more than __ of acute hepatitis in the US

Back 30

HAV, HBV, and HCV cause more than 90% of acute hepatitis in the US

Front 31

when do you see hev in the US?

Back 31

HEV may be seen in travelers returning from endemic areas.

Front 32

Viral Hepatitis markers
Simple screening test for the nonicteric patient

Back 32

Simple screening test for the nonicteric patient– urine bilirubin
Alternative is Liver enzyme panel (generally costly)

Front 33

Viral Hepatitis markers
Serum bilirubin may be

Back 33

Serum bilirubin may be elevated

Front 34

Viral Hepatitis markers
__ is usually normal, but may elevate to no higher than twice normal.

Back 34

Alk phosphatase is usually normal, but may elevate to no higher than twice normal.

Front 35

Viral Hepatitis markers
__ is a grave finding – indicates severe liver malfunction

Back 35

Prolonged Prothrombin time (PT) is a grave finding – indicates severe liver malfunction

Front 36

Viral Hepatitis markers
Impaired ___ suggest fulminant hepatitis

Back 36

Impaired Renal function tests suggest fulminant hepatitis

Front 37

Liver enzyme panel - Hepatitis

Back 37

Alkaline phosphatase - normal
γ glutamyl transferase - normal
Alanine transaminase - raised

Front 38

Liver enzyme panel - obstruction

Back 38

Alkaline phosphatase - raised
γ glutamyl transferase - raised
Alanine transaminase - normal

Front 39

Liver enzyme panel - mixed

Back 39

Alkalinγ glutamyl transferase -raised
γ glutamyl transferase - raised
Alanine transaminase - raised

Front 40

“Acute Hepatitis Panel” for Diagnosis - HAV

Back 40

Hepatitis A : IgM anti-HAV

Front 41

“Acute Hepatitis Panel” for Diagnosis - HBV

Back 41

Hepatitis B : HepBsAg*
*HepBsAg in acute hepatitis strongly suggests acute HBV infection,
but does not rule out chronic HBV with acute superinfection by another hepatitis virus
Hepatitis B : IgM anti-HepBc

Front 42

“Acute Hepatitis Panel” for Diagnosis - HCV

Back 42

HepC Ab**
**PCR is the most specific test and the earliest for HCV

Front 43

“Acute Hepatitis Panel” for Diagnosis - HDV

Back 43

HepD Ab

Front 44

“Acute Hepatitis Panel” for Diagnosis - HEV

Back 44

Hepatitis E : IgM anti-HepE

Front 45

HEPATITIS A - Transmission

Back 45

Transmission: person-to-person, fecal-oral

Front 46

HEPATITIS A - Incubation period

Back 46

Incubation period: 2 to 6 weeks

Front 47

HEPATITIS A - Risk groups:

Back 47

Risk groups:
Eating/drinking contaminated food e.g. shellfish, water
Travelers to areas of high endemicity, poor hygiene
Caregivers/contacts of acute HAV cases
Daycare centers
International travel
Secondary infection rate in households – 20%

Front 48

HEPATITIS A - high prevalence

Back 48

High prevalence in the Middle East

Front 49

HEPATITIS A - epi

Back 49

Causes a typically minor illness in childhood, with >80% of cases being asymptomatic
Adult infection is more likely to be symptomatic
Probability of Jaundice increases with age (below 10% in young children; 70-80% in adults)
Mild self-limiting disease, confers lifelong immunity
Older patients at greatest risk for severe disease
Does not progress to chronic infection

Front 50

Hepatitis A - Serum transaminases and bilirubin begin to rise _____

Back 50

Serum transaminases and bilirubin begin to rise 2 weeks after infection

Front 51

Hepatitis A When is HepA IgM present?
When IgG?

Back 51

HepA IgM (diagnostic) is present during the acute phase; IgG during convalescence
IgG confers lifelong immunity

Front 52

Hepatitis A how long shed in feces? when is risk of transmission highest?

Back 52

HAV is shed in feces for approximately 4 weeks
Risk of transmission is highest 1 to 2 weeks before onset of illness (viral shedding in feces is highest at end of incubation period)

Front 53

Hepatitis A - Clinical Outcomes

Back 53

Clinical outcomes:
- Most patients (99%) recover completely
- Asymptomatic seroconversion
- Rare cases of acute fulminant hepatitis or protracted hepatitis
- Overall mortality rate 0.01%; highest in extremes of age

Front 54

Hepatitis A - is there a chronic state?

Back 54

Recovery is associated with complete viral clearance
- No chronic carrier state
- No chronic liver disease

Front 55

HAV Passive Prevention

Back 55

Normal human immunoglobulin for prophylaxis
- exposed to person shedding virus
- traveling within 4 weeks
- below 2 years of age
- travelers allergic to vaccine component

Front 56

HAV Active Prevention

Back 56

Active: KILLED WHOLE VIRUS VACCINE
- Above 2 years of age (maternal Abs may interfere)
- 95% protection from infection
- Health care workers, day care workers, military recruits, travelers abroad, liver disease, immunocompromised patients, MSM, IDUs
- Also sewage and wastewater workers; vets working with imported nonhuman primates
?Children ? Food handlers

Front 57

Hep A Vaccines (inactivated)

Back 57

Intramuscular; give more than 1 month before travel
Approved for age 2 years and above; Overall efficacy 94 -100%
Protection upto 20 years
One dose Vaqta (Merck)
Seroconversion in 15 days 69%
1 month 94 to 97%
100% at 1 month after second dose (6 months after first)
One dose Havrix (GSK)
Seroconversion in 15 days (80-98%)
In 1 month, 96 to 100%
100% at 1 month after second dose (6 months after first)
TWINRIX (GSK)
Combined Hep A and HepB vaccine
Licensed for persons 18 years or older
3 doses – 0, 1 month, 6 months
Accelerated schedule for travelers Days 0, 7, 21 with booster at 1 year
(Note: Hep A immunoglobulin can be used if traveler intends to stay less than 3 months in endemic area)

Front 58

HAV - Prevention(other measures for the traveler)

Back 58

Improve sanitation, strict personal hygiene, handwashing
HAV is inactivated
by boiling or cooking to 85°C (185° F) for 1 minute

Adequate chlorination of water

Avoid potentially contaminated food/ drinks
e.g. uncooked shellfish, uncooked vegetables or other food handled with questionable hygiene

Front 59

Hepatitis B – global significance

Back 59

A major global public health problem
HBV is 50 -100 times more infectious than HIV
Notorious for causing chronic infection (5% of global population)
20% of the chronically infected leads to liver cirrhosis and liver cancer (highly fatal)
Estimates: 350 million carriers worldwide; 1 million deaths annually
10th leading cause of death worldwide

Front 60

Hepatitis B Virus
HBsAg -

Back 60

HBsAg - surface antigen on protein shell of virus

Front 61

Hepatitis B Virus
HBcAg –

Back 61

HBcAg – core antigen on nucleocapsid

Front 62

Hepatitis B Virus
HBeAg

Back 62

HBeAg – produced during active viral replication

Front 63

HBV - TRANSMISSION

Back 63

Transmission*: Blood-borne, sexual; vertical from mother to child; IDU; hemodialysis; transfusions; needlestick (sharp) injury
Saliva and semen also infectious (low level)
*majority of HBV cases worldwide result from perinatal transmission; in the US – 50% cases by sexual transmission

Front 64

HBV RISK GROUPS

Back 64

Risk groups:
Injection drug use
Organ transplants
Occupational exposure
Blood transfusions
Sexual exposure
Blood products
Mother to child
Hemodialysis

Front 65

HBV transmission patterns
Developed (N. America, W. Europe)

Back 65

Developed (N. America, W. Europe)
Before vaccination programs, vertical and child-to-child was predominant
After routine immunization was instituted, the majority of infections are acquired during young adulthood by sexual activity or injecting drug use.

Front 66

HBV transmission patterns
Developing

Back 66

Developing
Mostly mother-to-child, child-to-child and from reused needles etc .

Front 67

HBV INCUBATION PERIOD

Back 67

Average incubation period is 10 -12 wks

Front 68

HBV - Preicteric phase: prodrome

Back 68

Preicteric phase: prodrome
Gradual onset of Anorexia, malaise, fatigue
Liver enzymes start elevating
Some patients may have fever, arthritis, arthralgia, rash

Front 69

HBV - ICTERIC PHASE

Back 69

Icteric Phase
Tender liver, jaundice, urine may darken
Nausea, vomiting, pruritus

Front 70

WHAT % RECOVER AFTER ACUTE HBV INFECTION?

Back 70

95%

Front 71

Markers for Hepatitis B
Antigen markers

Back 71

Antigen markers
Hepatitis B surface antigen (HBsAg)
Hepatitis B core antigen (HBcAg)
Hepatitis B e antigen (HBeAg)

Front 72

Markers for Hepatitis B
Marker of recent infection:

Back 72

Marker of recent infection: HBcAg IgM

Front 73

Markers for Hepatitis B
Markers of active viral replication

Back 73

Markers of active viral replication are HBeAg and level of HBV DNA
Indicates high level of infectiousness
Causes serious liver damage

Front 74

HBV Vertical transmission
--% risk if the mother is only HBsAg +ve

Back 74

10% risk if the mother is only HBsAg +ve

Front 75

HBV Vertical transmission
Upto --% risk if she is HBeAg +ve

Back 75

Upto 90% risk if she is HBeAg +ve

Front 76

HBV Vertical transmission
If an infant is infected, --% develop chronic infections and up to --% die of chronic liver disease.

Back 76

If an infant is infected, 90% develop chronic infections and up to 25% die of chronic liver disease.

Front 77

HBV HORIZONTAL transmission

Back 77

In endemic countries, horizontal transmission between children puts even children born to HBsAg –ve mothers at risk.

Front 78

acute HBV infection with recovery typical serolgic course

Back 78

Sometimes it is difficult to establish whether the patient had a recent infection or a past one. HBsAg and HBeAg may be negative. So only HBcAg IgM can establish the diagnosis. Since core antigen is a truncated version of surface antigen and core antigen never appears in serum, presence of core IgM indicates an immune response within liver cells and is thus a specific marker for acute HBV infection.

Front 79

progression to chronic HBV - typical serologic course

Back 79

progression to chronic HBV - typical serologic course

Front 80

Interpretation of Hepatitis B Serology Panel
HBsAg - NEG
Anti-HBs - NEG
Anti-HBc - NEG
Anti-HBc IgM - nothing
?what is my interpretation?

Back 80

Susceptible

Front 81

Interpretation of Hepatitis B Serology Panel
HBsAg - NEG
Anti-HBs - POS
Anti-HBc - POS
Anti-HBc IgM - nothing
?what is my interpretation?

Back 81

Immune due to natural infection

Front 82

Interpretation of Hepatitis B Serology Panel
HBsAg - NEG
Anti-HBs - POS
Anti-HBc - NEG
Anti-HBc IgM - nothing
?what is my interpretation?

Back 82

VACCINATED

Front 83

Interpretation of Hepatitis B Serology Panel
HBsAg - POS
Anti-HBs - NEG
Anti-HBc - POS
Anti-HBc IgM - POS
?what is my interpretation?

Back 83

ACUTE INFECTION

Front 84

Interpretation of Hepatitis B Serology Panel
HBsAg - POS
Anti-HBs - NEG
Anti-HBc - POS
Anti-HBc IgM - NEG
?what is my interpretation?

Back 84

CHRONIC infecction

Front 85

Interpretation of Hepatitis B Serology Panel
HBsAg - NEG
Anti-HBs - NEG
Anti-HBc - POS
Anti-HBc IgM - nothing
?what is my interpretation?

Back 85

?susceptible with false +
?carrier with low HBsAg
?recovering from acute inf.
?distantly immune with undetectable anti-HBs

Front 86

HBV Management

Back 86

Treatment :
For chronic infections, Interferon or antivirals – costly!
Lamivudine, Adefovir Dipivoxil (ADV) etc.
Liver transplant for cirrhosis and failure
Prevention is better than cure!

Front 87

Hepatitis B Vaccine - types

Back 87

Twinrix ( as before)
Recombivax-HB (Merck) or Engerix-B (Glaxo Smith-Kline)
Engerix-B is approved in a 3 dose schedule of 0, 1 and 6 months OR a 4 dose schedule at 0, 1, 2 and 12 months
Recombivax – HB is licensed for a 3 dose schedule, 0, 1 and 6 months

Front 88

Hepatitis B Vaccine - who gets it

Back 88

All infants
Health care workers (medical, dental, laboratory etc)
Travelers who plan to reside for 6 months or more in areas with ≥2% HBsAg prevalence
For baby born to actively infected mother (HBeAg+) – HBIG + HB vaccine

Front 89

Hepatitis D (Delta) - basics

Back 89

HDV is a defective virus that uses HBsAg as a protein coat
HDV absolutely requires coinfection with HBV. Infection can be simultaneous or as superinfection.
High rates of HDV among HBV carriers in the Amazon basin, Central Africa, Southern Italy and the Middle East.
Delta hepatitis increases mortality in both acute and chronic HBV infections by causing a more severe pathology

Front 90

Delta superinfection

Back 90

Delta superinfection
Majority result in chronic delta hepatitis; since HBsAg is persistent, HDV can persist.

Front 91

Acute Delta coinfection

Back 91

Acute Delta coinfection
Majority recover; HDV disappears when HBsAg is cleared from the serum.

Front 92

HDV - Diagnosis and Management

Back 92

Anti-HDV testing is not a reliable marker for acute infection since it may appear late, be present in low titer or only for a short time.

Interferon therapy

Front 93

HCV EPI

Back 93

Global prevalence is estimated at 170 million, with 3 to 4 million new cases/yr
Major modes of transmission are blood-borne – unscreened blood transfusions, re-use of needles/ syringes
Percutaneous – body piercing, tattoing
Sexual transmission has been documented, but not established a major mode
Prevalence rates high in some African countries, Western Pacific and E. Mediterranean (where data is available)

Front 94

HCV INCIDENCE - US

Back 94

Incidence: 35,000/year

Front 95

US - HCV PREVALENCE

Back 95

Prevalence : 1.8%
Discordant couples : 2-3%
Sex workers and gay men : 4-6%
Homeless, incarcerated : 15-50%
IDU, hemophilia : 70-90%

Front 96

Hepatitis C – Natural History

Back 96

Chronic infection : 60 – 85%
Spontaneous clearance higher with young age and female sex
Cirrhosis at 20 years : 10 -15%
Risk of cirrhosis is unrelated to viral load, genotype
Increased risk in HBV coinfection, alcoholism, HIV, male gender
1/3 of hepatocellular CA cases are HCV-related

Front 97

HCV Diagnosis

Back 97

EIA – highly sensitive for chronic infections, but only 50-70% for acute
Confirmatory test – recombinant immunoblot assay (RIBA)
Nucleic acid – based tests (PCR etc.) PCR is most specific and is positive earlier than serology; also used for confirmation of serology as well as assessing response to treatment
Important to diagnose early as early treatment with interferon can stop progression to chronic disease

Front 98

HCV Treatment

Back 98

Interferon + ribavarin is recommended
Pegylated interferon has better results for genotype 1 and is now recommended
For genotype 2, both types of interferon are equally effective and either is used
Genotypes 2 and 3 respond better to therapy

Front 99

HCV Prevention

Back 99

Prevention
NO VACCINE; IMMUNOGLOBULIN IS NOT PROTECTIVE (Ig ADMIN RESULTED IN TRANSMISSION OF HCV)
Lack of a protective immune response following infection and heterogeneity of genome has impeded development of a vaccine.
Precautions like screening of blood and organ donors, virus inactivation, sterilization of equipment, heath education and counseling for high risk groups

Front 100

Hepatitis E - Epidemiology

Back 100

Most outbreaks associated with fecally contaminated drinking water
Minimal person-to-person transmission
Common in the developing world
U.S. cases usually have history of travel to HEV-endemic areas; renal dialysis
High fatality in pregnant women
Epidemics reported from India, Asia, Africa and Latin America, esp. during rainy season due to water contamination

Front 101

HEV Management & Prevention

Back 101

Protective role of antibodies unclear.
? Reduces severity of illness
? Serum from other countries may not be protective
- No durable immunity
Assure clean drinking water, especially for pregnant women.
Boiling water before use has been shown to be effective.

Front 102

Fulminant Hepatitis

Back 102

Death from viral hepatitis is usually due to fulminant hepatitis
Development of hepatic encephalopathy within 8 weeks of symptoms or 2 weeks of jaundice
Liver enzymes do not correlate with risk; the biochemical hallmark is prolonged coagulation

Risk of developing FVH
Pregnant women with HEV (15% risk)
HAV - rare, older age and pre-existing liver disease
HBV – rare in acute form; superinfection with HDV in chronic.

Front 103

WHICH HEP VIRUSES HAVE CHRONICITY?

Back 103

HBV, HCV, HDV

Front 104

WHICH HEP VIRUSES HAVE PERCUTANEOUS TRANSMISSION?

Back 104

HBV, HCV, HDV

Front 105

WHICH HEP VIRUSES HAVE SEXUAL TRANSMISSION?

Back 105

HBV, HCV?, HDV

Front 106

WHICH HEP VIRUSES HAVE VERICAL TRANSMISSION?

Back 106

HBV

Front 107

WHICH HEP VIRUSES HAVE PERINATAL TRANSMISSION?

Back 107

HCV ?

Front 108

Mean Incubation Period (range) - HAV

Back 108

30
(15-50)

Front 109

Mean Incubation Period (range) - HBV

Back 109

80
(28-160)

Front 110

Mean Incubation Period (range) - HCV

Back 110

50
(14-160)

Front 111

Mean Incubation Period (range) - HDV

Back 111

variable

Front 112

Mean Incubation Period (range) - HEV

Back 112

40
(15-45)