Viral Hepatitis

Question 1

What is hepatitis E virus?

Answer 1

• HEV is RNA virus that is found worldwide but more common in LMIC
• HEV genotypes 1 and 2 are found in humans
• HEV genotypes 3 and 4 are zoonotic diseases with reservoirs in both humans and animals
  e.g. pigs, monkeys, dogs

Question 2

How is hepatitis E virus transmitted?

Answer 2

1. Via contaminated food and water
   e.g. poor sanitation and water purification
2. Many animals have been identified as viral reservoirs
   e.g. pig, shellfish, rodents, deer, cow
3. Transmission via blood transfusion may occur
4. Perinatal transmission is rare and controversial

Question 3

How to prevent hepatitis E virus transmission?

Answer 3

Cooking food and boiling water inactivates the virus

Question 4

Incubation of HEV?

Answer 4

Incubation of 15-60 days

Question 5

Clinical features of HEV?

Answer 5

Most are asymptomatic or mildly symptomatic

Question 6

Liver pathology of HEV?

Answer 6

1. acute hepatitis, usually self-limited
2. Liver failure in a small proportion (1-5%)
   - more common in pregnant women, people with malnutrition, and those with pre-existing liver disease.
3. Cholestatic jaundice may linger for >3 months

Question 7

Extrahepatic manifestations of HEV infection?

Answer 7

1. pancreatitis
2. hematological abnormalities
3. neuro syndromes
   e.g. GBS, aseptic meningitis, others

Question 8

HEV diagnosis?

Answer 8

1. anti-HEV IgM antibodies - active infection
2. anti-HEV IgG antibodies - past infection
3. PCR - can detect HEV RNA in stool and serum samples
4. anti-HEV IgG assays
   - suffer from low specificity so if the clinical picture does not fit, a positive may be a false positive
5. liver biopsy

Question 9

Prevention of HEV?

Answer 9

General WASH measures
- Water Sanitation Hygiene

Question 10

What is hepatitis C?

Answer 10

• RNA virus discovered in the mid/late 1980s.
• 6 genotypes (1 to 6)

Question 11

Epidemiology of HCV?

Answer 11

Uncommon in Malawi and most of Southern Africa but worldwide causes infection in 150 million.

Question 12

Transmission of HCV?

Answer 12

1. via percutaneous exposure
   - IV drugs
   - blood transfusions
   - needlestick injury
   - exposure to contaminated medical equipment or supplies
   - dialysis
   NB: People who inject drugs are a key pop
2. organ transplantation
3. Rare: mother-to-child, sexual

Question 13

Risk factors for HCV infection?

Answer 13

1. injection drug use
   - past or current, esp. long term
2. HBV or HIV positive
3. hx of incarceration

Question 14

HCV natural history?

Answer 14

• Acute and chronic phases of infection
• 30-60% progress from acute to chronic while the rest self-resolve.
• In chronic HCV, liver inflammation occurs slowly over several decades, and leads progressively to liver fibrosis and then cirrhosis.
• Once cirrhosis sets in there is risk of Hepatocellular carcinoma (HCC)
• Death is due to cirrhosis and/or HCC

Question 15

Acute vs chronic HCV?

Answer 15

1. acute - HCV infection that develops during the first 6 months following the exposure
2. chronic - HCV infection that persists beyond 6 months following the exposure

Question 16

Incubation period of HCV?

Answer 16

2 weeks to 6 months

Question 17

3 stages of acute inflammation of the liver due to hepatitis virus infection?

Answer 17

1. prodromal stage
   - fever, malaise, anorexia, nausea, vomiting, RUQ pain and tender hepatomegaly
2. icteric phase
   - jaundice, dark urine, pruritis
3. resolution of symptoms
   - usually within 4 weeks in HAV and HEV infection, can become chronic in HBV and HCV infection

Question 18

HCV tests?

Answer 18

1. anti-HCV antibodies (EIA/ELISA immunoassay)
2. HCV RNA (qualitative PCR)
   - if anti-HCV antibody test is positive

Question 19

HCV diagnosis?

Answer 19

1. Diagnosis is based on detection of HCV RNA in blood
   - Usually in thousands to hundred thousand IU/ml
2. To reduce cost, we first do HCV antibody test
   - If positive, confirm infection with HCV RNA.

Question 20

HCV Ab-positive and HCV RNA-negative explained?

Answer 20

1. the patient resolved after acute infection
2. s/he was cured with medications, and
3. the antibody was a false positive.
   In low prevalence settings
   - is very common because the antibody assays are not very accurate
   Note: In Malawi, it could be that most of the HCV-antibody-positive patients are HCV RNA negative

Question 21

When to do a HCV RNA test first?

Answer 21

1. prior HCV infection
2. immunocompromised

Question 22

How long do the HCV tests take?

Answer 22

1. anti-HCV antibodies - may take as long as 6 weeks after HCV exposure to be detectable on tests
2. HCV RNA - may take as long as 2-3 weeks after viral exposure to be detectable on tests

Question 23

Old HCV treatment?

Answer 23

Interferon alpha weekly subcutaneous injections plus ribavirin for 6 months

Question 24

Side effects of interferons?

Answer 24

1. flu-like syndrome
2. neuropsychiatric effects (fatigue, depression, suicidal ideations)
3. autoimmune disorders
4. hematologic problems (pancytopenia)

Question 25

Side effects of Ribavirin?

Answer 25

1. teratogenic 2. can cause hemolytic anemia, cardiac events

Question 26

Who is prioritized in treatment of HCV?

Answer 26

Treatment is universal, but patients with advanced liver disease and those with HIV are prioritized

Question 27

Was the old treatment for HCV effective?

Answer 27

In the old way, many dropped out and only around 40% were cured

Question 28

New treatment of HCV?

Answer 28

- Direct-acting antivirals (DAA) were developed in past 10 years - DAAs are very well tolerated and achieve cure >90% of the time with 8-12-week course of daily pills - If no cirrhosis, shorter (as little as 8 weeks), and if cirrhosis, you treat for 12-24 weeks.

Question 29

What is hepatitis A?

Answer 29

RNA virus - Very common in Malawi and other LMIC

Question 30

Transmission of HAV?

Answer 30

fecal-orally, usually via contaminated food - Outbreaks can occur, when the person preparing the food is shedding the virus and not using good hygiene

Question 31

Incubation period for HAV?

Answer 31

Incubation period about 21 days.

Question 32

Clinical features of HAV?

Answer 32

1. Some are asymptomatic but perhaps ~70% get acute symptoms of hepatitis. 2. The illness self-resolves over a period of 2-4 months. 3. <1% develop fulminant liver failure 4. Liver failure is most likely if the person already has chronic HCV or HBV.

Question 33

Diagnosis of HAV?

Answer 33

1. HAV IgM - positive 2. HAV IgG - positive is less helpful when the prevalence is high in the population - unless you have excluded other types of viral hepatitis.

Question 34

HAV treatment?

Answer 34

supportive care

Question 35

HAV prevention?

Answer 35

1. WASH measures 2. A very effective and safe vaccine exists; however, not widely used in many LMIC. - Patients with chronic HBV (HBsAg-positive) and chronic HCV (HCV RNA-positive) should be prioritized for HAV vaccine