LECTURE 16 (Viruses + Hepatitis)

Question 1

What happens in Viral Hepatitis?

Answer 1

The liver is enlarged and tender + serum aminotransferase and bilirubin levels are elevated as a result of hepatic inflammation and damage

MANIFESTATIONS:
- Jaundice
- Dark urine
- Clay-coloured stools
- Fever, malaise, nausea
- Hepatomegaly
- Pain

Question 2

What is HAV?

Answer 2

Hepatitis A virus causes Hepatitis A

EPIDEMIOLOGY & TRANSMISSION:
- Transmitted by faecal-oral route, direct contact and objects handled by infected people
- Humans are the reservoir
- Virus appears in faeces 2 weeks before symptoms -> quarantine is ineffective
- Children are the most frequently infected group

PATHOGENESIS:
- Replicates in GI tract + spreads to liver via blood
- Ingestion -> replication in oropharynx/GI tracts + transported to liver -> shed in bile + transported to intestines + shed in faeces + brief viremia + cellular immune response

INCUBATION PERIOD:
14-28 days

SYMPTOMS:
- Fever, malaise, nausea
- Loss of appetite + diarrhoea
- Abdominal discomfort
- Dark-coloured urine
- Jaundice
[adult symptoms are more severe than children]

DIAGNOSIS:
- Not clinically distinguishable from other types of acute viral hepatitis (same symptoms)
- Detection of HAV-specific IgM antibodies in blood
- RT-PCR -> to detect hepatitis A virus RNA

TREATMENT:
No antiviral therapy available

PREVENTION:
Active immunisation
[2 doses + booster dose 6-12 months later]

Question 3

What is Hepatitis E (HEV)?

Answer 3

A small virus, with a positive-sense, single stranded RNA genome that causes Hepatitis E

EPIDEMIOLOGY & TRANSMISSION:
- Transmitted faecal-oral route, water + food borne transmission from ingestion of infected animal products
- Highest prevalence in East + South Asia

INCUBATION PERIOD:
2-10 weeks, an average of 5-6 weeks

SYMPTOMS:
- mild fever
- reduced appetite
- nausea, vomiting + abdominal pain
- jaundice
- dark urine + pale stools
- hepatomegaly

COMPLICATIONS:
pregnant women infected, especially in 2nd or 3rd trimester, develop FULMINANT HEPATITIS more frequently with increased risk of ACUTE LIVER FAILURE, FOETAL LOSS and MORTALITY

DIAGNOSIS:
- detection of specific IgM antibodies to the virus in a person’s blood
- RT-PCR to detect hepatitis E virus RNA in blood and/or stool

TREATMENT:
- self-limiting -> no treatment
- immunocompromised people with chronic hepatitis E benefit from using RIBAVIRIN (antiviral drug) + iNTERFERON

PREVENTION:
Vaccine

Question 4

What is Hepatitis B Virus (HBV)?

Answer 4

A life-threatening viral infection that attacks the liver and can cause both acute and chronic disease

EPIDEMIOLOGY & TRANSMISSION:
- Important occupational hazard for health workers
- Mother to child at birth
- Exposure to infected blood
- Sexual transmission
- Can survive outside the body for at least 7 days + infect unvaccinated individuals

INCUBATION PERIOD:
on average 75 days but can vary from 30-180 days
[virus can be detected within 30-60 days after infect + develop into chronic hepatitis B]

PATHOGENESIS:
After entering the blood, the virus infects hepatocytes + viral antigens are displayed on surface of cells -> cytotoxic T cells mediate an immune attack against viral antigens -> Inflammation + necrosis occur

MANIFESTATION:
- Jaundice
- Dark urine
- Extreme fatigue
- Nausea, vomiting, abdominal pain

COMPLICATIONS:
- Acute hepatitis can develop acute liver failure -> death
- Chronic liver infection -> cirrhosis or liver cancer

DIAGNOSIS:
- Many are asymptomatic + detected only by presence of antibody to HBsAg
- Serologic tests for HBsAg + IgM antibody to the core antigen

TREATMENT:
TENOFOVIR or ENTECAVIR
[suppress hepatitis B virus]

PREVENTION:
Vaccine or Hyper-immune globulin or both

Question 5

What is Hepatitis D Virus (HDV)?

Answer 5

A liver infection caused by Hepatitis D virus

EPIDEMIOLOGY & TRANSMISSION:
- same means as HBV (e.g sexually, by blood)

PATHOGENESIS:
- Can only replicate in cells also infected with HBV since HDV uses surface antigen of HBV as its envelope protein
- Occurs only simultaneously or as super-infection with HBV

MANIFESTATIONS:
- ACUTE HEPATITIS = simultaneous infection with HBV can lead to mild-to-severe or even fulminant hepatitis
[recovery is usually complete]
- SUPERINFECTION = accelerates progression to cirrhosis (despite HDV suppressing HBV replication)

DIAGNOSIS:
detecting either delta antigen or IgM antibody to delta antigen in the patient’s serum

TREATMENT:
- no specific antiviral therapy
- no vaccine
[but person immunised against HBV will not be infected by HDV]

Question 6

What is Hepatitis C Virus (HCV)?

Answer 6

A blood borne virus that causes acute and chronic hepatitis ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness

EPIDEMIOLOGY & TRANSMISSION:
- Humans are reservoir
- Blood borne virus (injection drug use, unsafe injection practices, unsafe healthcare, transfusion of unscreened blood + blood products)

INCUBATION PERIOD:
2 weeks to 6 months

SYMPTOMS:
- Jaundice
- Fatigue + nausea
- Poor appetite
- Dark urine
- Abdominal & joint pain

DIAGNOSIS:
- Detecting antibodies to HCV using ELISA
- RIBA test performed after ELISA as a confirmatory test
- If results of RIBA are +ve, PCR is used to determine if active disease exists

TREATMENT:
- A combination of Peginterferon alfa-2a (Pegasys), Ribavirin and a protease inhibitor
- Sovaldi for treatment caused by genotypes 1, 2, 3 and 4

VACCINE:
No vaccine or hyper-immune globulins available

Question 7

Describe the Hepatitis C Virus

Answer 7

• Only member of the Hepacivirus genus of the Flaviviridae family
• Positive-sense RNA genome
• Enveloped