0226 - Viral Hepatitis

Question 1

What are the hepatitis viruses?

Answer 1

Viruses for which the liver is the predominant site of replication, and that cause inflammation and hepatocyte injury (acute hepatitis).
HBV, HCV, and HDV can evade immune clearance and become chronic, leading to cirrhosis, and hepatocellular carcinoma.

Question 2

Describe the enteral hepatitis viruses (stay acute)

Answer 2

HAV - RNA virus, non-enveloped

HEV - RNA virus, calicivirus

Question 3

Describe the blood-borne hepatitis viruses (can become chronic)

Answer 3

HBV - DNA virus, enveloped (hepadnavirus)
HCV - RNA virus, enveloped, flavivirus (hepacivirus)
HDV - RNA virus, incomplete (viroid)

Question 4

Name at least 5 signs and symptoms of acute hepatitis.

Answer 4

Anorexia
Nausea
Vomiting
Bilirubinuria
Jaundice
Tender, soft liver (RUQ pain rare)
Malaise and fatigue
NOT fever, rigors, and sore throat

Question 5

What are the differences between acute and chronic hepatitis

Answer 5

Acute hepatitis is generally self-limiting.
Chronic hepatitis may present with no signs or symptoms and normal LFTs if well-compensated (otherwise look for stigmata of chronic liver disease). Acute hepatitis presents with signs and symptoms, ALT >500, and serology results.

Question 6

Name 4 differential diagnoses for acute hepatitis

Answer 6

Other viruses (EBV, CMV, H. Simplex, HIV, Parvo)
Hepatotoxicity (paracetamol/adverse drug reaction)
Other inflammation (Acute cholecystitis, cholangitis, liver abscess (pain, fever/rigor, leukocytosis)
Ischaemic hepatitis (heart failure/shock - ALT >>1,000)

Question 7

Which liver diseases are usually chronic but may present with acute symptoms?

Answer 7

Hepatitis B (flare - potentially lethal)
Alcoholic hepatitis (history, stigmata)
Non-alcoholic steatohepatitis (NASH)
Autoimmune hepatitis 
Wilson’s disease (children/young adults)

Question 8

Name two clinical outcomes of chronic hepatitis

Answer 8

Cirrhosis
Hepatocellular Carcinoma
Death

Question 9

Briefly outline HAV infection

Answer 9

Simple enteric viral infection, incubation 3-6 weeks.
Faeces not infectious 7-10 days after onset of jaundice
Often asymptomatic, but can present with significant acute signs and symptoms
Severity increases with age.

Question 10

How is HAV infection diagnosed?

Answer 10

IgM anti-HAV

Question 11

Outline the HAV vaccination

Answer 11

Live, attenuated virus, given as 2 injections over 6 months.
Safe, but expensive, so not generally cost effective (except for community outbreaks)
Can be combined with HBV vaccine

Question 12

Briefly outline the virology of HBV

Answer 12

DNA virus that replicates via RNA template (reverse transcriptase).
Causes acute or chronic hepatitis
Infected liver elaborates HBsAg
Many different genotypes

Question 13

How can HBsAG and HBV DNA diagnose HBV?

Answer 13

HBsAg most useful for acute hepatitis - it’s the surface antigen
HBV DNA essential to assess chronic HBV - it gives an indication of viral load.

Question 14

Briefly outline the epidemiology of HBV

Answer 14

350 million chronic worldwide - Africa, Asia, Arctic America
9th leading cause of death (HCC)
In Australia, 90-150,000, 75% Asian

Question 15

What are some risk factors for HBV?

Answer 15

Multiple sexual partners
Healthcare workers
Newborns of HBsAg+ mothers
Young children in contact with HBsAg
Injecting drug users

Question 16

How can HBV be prevented?

Answer 16

HBV vaccine - contains HBsAg
96% humoral immunity
>90% reduction in acute HBV
Universal infant vaccination

Question 17

What is the clinical spectrum of HBV?

Answer 17

From silent to death.
40-50% die of cirrhosis or HCC (~25%) - unpredictable course
Risk correlates with serum HBV DNA >2,000 (Key test)
Can flare lethally and with rapid progression

Question 18

How can HBV be treated?

Answer 18

Antivirals - Entecavir and Tenofovir to suppress replication.
Aim for life-long suppression of HBV replication, reversing fibrosis, preventing cirrhosis and HCC.
Effective treatment prevents decompensation of cirrhosis, and lowers risk of HCC by >50%

Question 19

How can you tell if someone has been vaccinated or infected by HBV?

Answer 19

Test for HBcAg - core antigen.

Vaccine only contains HBsAg.

Question 20

Key learning points [CRS]

Answer 20

HAV and HEV are enteric, cause acute hepatitis (HEV geographically restricted)
HBV and HCV are blood-borne (+ sexual for HBV)
Acute Hepatitis is generally self-limiting, acute liver failure rare (increased risk with age and HBV)
HBV and HCV can cause chronic hepatitis, leading to cirrhosis and liver cancer
HAV, HBV are vaccine-preventable
Preventing blood contamination is most important for HCV prevention
Chronic HBV and HCV are both treatable
Treating chronic viral hepatitis can prevent liver related death from cirrhosis and HCC

Question 21

Key learning points for treating HBV [HLP]

Answer 21

Entecavir and tenofovir now commonly used
Both suppress viral replication by median 5 log (from 10^7 to <100)
ALT normalises 3-6 months
Drug resistance rare
Surveillance for HCC (6 monthly ultrasound, AFP).