Lecture 37: Patient with Jaundice: Viral Hepatitis Flashcards
A 45 year old Korean man presents to the general medical clinic after being told he has abnormal blood tests. He has been feeling ‘run-down’ for some time. He thinks he has lost some weight and his friends remark that he is yellow. Recently his legs and abdomen have become swollen and he seems to bruise easily.
What dos “yellow mean?” What are the reasons for being yellow?
Yellow means patient is jaundiced.
- This is due to i_ncreased bilirubin_ caused by decreased conjugation or removal, increased production, decreased excretion.
- This could be i_ssues within liver itself (_decreased conjugation), or before liver (increased production, i.e. haemolysis), or after liver (decreased excretion, e.g. gallstone block common bile duct results in cholangitis/cholecystitis, back pressure so bile leak into circulation, therefore jaundice).
A 45 year old Korean man presents to the general medical clinic after being told he has abnormal blood tests. He has been feeling ‘run-down’ for some time. He thinks he has lost some weight and his friends remark that he is yellow. Recently his legs and abdomen have become swollen and he seems to bruise easily.
What is the most likely reason for his symptoms?
a) Acute hepatitis
b) Choledocholithiasis
c) Chronic liver disease
d) Heart Failure
e) Nephrotic syndrome
a) Acute hepatitis
* Could be, but c is more likely.
b) Choledocholithiasis
c) Chronic liver disease
- Most likely- due to swelling and bruising.
d) Heart Failure - If somone is Jaundiced due to HF, this will be end stage. So unlikely.
e) Nephrotic syndrome - Unlikely
A 45 year old Korean man presents to the general medical clinic after being told he has abnormal blood tests. He has been feeling ‘run-down’ for some time. He thinks he has lost some weight and his friends remark that he is yellow. Recently his legs and abdomen have become swollen and he seems to bruise easily.
Why is he swollen?
The patient is swollen due to reduced plasma proteins.
This is caused by impaired production due to liver disease (hypoproteinemia or hypoalbuminemia). Reduced plasma proteins leads to reduced oncotic capillary pressure, so there is net movement of fluid into extravascular space, therefore oedema.
A 45 year old Korean man presents to the general medical clinic after being told he has abnormal blood tests. He has been feeling ‘run-down’ for some time. He thinks he has lost some weight and his friends remark that he is yellow. Recently his legs and abdomen have become swollen and he seems to bruise easily.
Why is he bruising?
There is r_educed production of clotting factors by liver._
This can be caused by liver disease, or vitamin K deficiency.
Liver disease is more likely given his history, symptoms and signs.
A 45 year old Korean man presents to the general medical clinic after being told he has abnormal blood tests. He has been feeling ‘run-down’ for some time. He thinks he has lost some weight and his friends remark that he is yellow. Recently his legs and abdomen have become swollen and he seems to bruise easily.
What are other clinical signs are there with Advanced Liver Disease?
- Hepatomegaly;
- Splenomegaly (if portal hypertension);
- Pruritis (itch due to bilirubin);
- Ascites;
- Oesophageal, abdominal (caput medusa) and rectal varices (due to increased blood flow through portacaval anastomoses);
- Gynaecomastia and testicular atrophy in males (due to imbalance in sex steroid hormones)
What are the different causes of Hepatitis?
Drugs
Toxic and drug-induced hepatitis are the most common cause.
- Commonest cause is alcoholism (excess alcohol intake). Safe limits of alcohol consumption for 12 (female) or 15 (male) standard drinks per week.
Viruses
Viral hepatitis can be caused by:
- Hepatitis viruses (viruses that specifically and exclusively cause hepatitis, which liver is main site of replication);
- Or other viruses such as Epstein-Barr virus (glandular fever/infectious mononucleosis), cytomegalovirus, HIV, mumps virus, yellow fever virus.
Bacteria
Bacterial hepatitis commonly results from pyogenic liver abscesses, acute or chronic hepatitis.
- Pyogenic abscesses commonly involve enteric bacteria such as Escherichia coli and Klebsiella pneumoniae, (usually polymicrobial, infected via sepsis).
- Acute hepatitis is caused by Neisseria meningitidis, Neisseria gonorrhoeae, salmonella, campylobacter species.
- Chronic (granulomatous) hepatitis is caused by mycobacteria species, rickettsia species.
Autoimmune
Autoimmune (lupoid hepatitis) is chronic autoimmune disease of liver.
- Presentation of HLA class II on surface of liver cells (possibly due to genetic predisposition or acute infection) causes a cell-mediated immune response against own liver cells.
Ischaemia
Ischemic hepatitis is acute liver injury due to insufficient blood flow (perfusion) to liver.
- This can be caused by shock or low blood pressure.
- In addition, ischemia can also be due to local causes involving thrombosis (clot) of hepatic artery.
A 45 year old Korean man presents to the general medical clinic after being told he has abnormal blood tests. He has been feeling ‘run-down’ for some time. He thinks he has lost some weight and his friends remark that he is yellow. Recently his legs and abdomen have become swollen and he seems to bruise easily.
A liver ultrasound (fibroscan) shows that he has cirrhosis
What is the most likely cause?
- Paracetamol overdose
- Viral heaptitis
- Autoimmune hepatitis
- Non-alcoholic stretohepatitis
- Chornic alcohol overuse
Stiff liver suggests that this is chronic not acute.
Answer is 2 or 5
- Paracetamol overdose
-
Viral heaptitis
- There are higher rates of Hepatitis in Korea than in NZ
- Autoimmune hepatitis
- Non-alcoholic stretohepatitis
-
Chronic alcohol overuse
- This is the most common cause of chronic liver disease in NZ.
Hepatitis viruses……
Are unrelated viruses that are hepatotropic
Describe Hep B virus
1) Structure
2) Route of infection
3) Diseases it causes
HBV surface antigen protein.
Hepatitis B virus (HBV) belongs to hepadnaviridae family. It is partially double-stranded hepatotropic DNA virus (enveloped).
The spread of HBV is blood-borne route (blood-to-blood contact, e.g. intercourse, IVDU, vertical transmission via mother).
- HBV causes acute hepatitis in children and adults.
- HBV causes chronic hepatitis mainly in newborns and infants (90%). It is unlikely (although possible) to develop chronic hepatitis with HBV in adulthood (<5%).
- HBV can cause fulminant hepatitis (0.5%).
Infections in childhood are mostly asymptomatic (>90%), Infections in adulthood are less likely to be asymptomatic (20-70%).
Describe the Mechanism (life cycle) of Hep B.
Mechanisms (Life Cycle)
HBV is partially double-stranded DNA virus that contains polymerase enzyme in its capsid. Capsid is surrounded by an envelope. Embedded in envelope, there is hepatitis B surface antigen (HBsAg).
- HBsAg enables HBV to interact with hepatocyte via unknown receptors (and co-receptors).
- After HBV enters hepatocytes, cellular enzymes break down viral envelope, so capsid is released into cytoplasm.
- Viral DNA with polymerase (reverse transcriptase) is transported to nucleus and complementary RNA strands are made. Ultimately two sets of RNA are produced.
- mRNA is transported to ribosomes where HBsAg is synthesised efficiently.
- Other set of RNA represents HBV complete genome, which is transported out of nucleus into cytoplasm. This is then translated very slowly (inefficiently!) to package and produce new viruses.
- Therefore, there is massive imbalance between HBsAg and other HBV proteins. Proteins synthesis (e.g. capsid) is very inefficient, whereas HBsAg synthesis is very efficient.
- After infection, HBV produces excess HBsAg than needed.
- Excess HBsAg allows HBV to clump together and form rod-shaped particles (visualized in hepatocytes).
- HBV produces so much HBsAg that it spills out into blood, thus allow (acute or chronic) hepatitis B diagnosis when detect HBsAg in the blood. If no HBsAg in patient’s blood, then no infection since there is no replication.
In HBV genome, X gene turns on cellular machinery inside hepatocyte (to speed up processes required by HBV). Therefore, X gene acts as an oncogene, and HBV is commonly associated with hepatic cancer.
Describe the Prevention and Treatment of Hep B
There is effective HBV vaccine. HBsAg is found in HBV vaccine, which is recombinantly made by E coli and then purified. Therefore, vaccinated patient has antibodies against HBsAg (but not infected with HBV).
There is only suppressive treatment for HBV (inhibit virus replication). HBV cannot be completely removed from patients.
Describe Hep A virus
1) Structure
2) Route of infection
3) Diseases
Hepatitis A virus (HAV) belongs to picornoviridae family.
It is positive sense RNA virus (non-enveloped) with icosahedral capsid.
The spread of HAV is _faecal-oral route (_excreted in faeces, caught by ingesting contaminated food or drink)
- HAV primarily causes acute hepatitis. Patient can become sick, jaundiced, vomit, abdominal pain in right upper quadrant, but patient will recover fully and thereafter become immune.
- HAV d_oes not cause chronic hepatitis._
- HAV can cause f_ulminant hepatiti_s (<1%) (sudden severe hepatitis with high mortality rate).
- Very very rare
Infections in childhood are relatively asymptomatic (60-90%). Infections in adulthood are less likely to be asymptomatic (30%).
Describe the Prevention and Treatment of Hep A
Prevention and Treatment
- There is effective HAV vaccine.
- There is no active treatment for HAV, since it is self-limiting (patients clear their own infection then recovers).
Describe Hep C virus
1) Structure
2) Route of infection
3) Diseases
Hepatitis C virus (HCV) belongs to flaviviridae family. It is single-stranded positive sense RNA virus (spherical and enveloped).
The spread of HCV is blood-borne route (blood-to-blood contact, e.g. intercourse, IVDU, vertical transmission via mother). Prior to 1988, it was called non-A non-B hepatitis.
- HCV can cause acute hepatitis (mild jaundice).
- HCV mainly cause chronic hepatitis (50-85%).
- HCV rarely cause fulminant hepatitis (only in Japan).
Infections in adulthood are mostly asymptomatic (>80%).
Describe the Prevention and Treatment of Hep C
Prevention and Treatment
There is no effective HCV vaccine.
There is curative treatment for HCV (removes HCV from liver completely).
- If antiviral drugs are given, and HCV becomes resistant, then drugs can be removed for a brief period of time. In this way, HCV will lose its resistance and antiviral drugs can be used again.
- It is possible for patient to become re-infected after initial treatment, since treatment doesn’t confer lifelong immunity.
There is no vaccine against HCV at present. Therefore, curative treatment is essential to prevent transmission.
In addition, introduction of a needle exchange programme can reduce needle sharing and HCV transmission, since IVDU is main risk factor for hepatitis C infection.
Regarding infection with Hep B Virus….
Answer: A huge excess of particles consisiting solely of HB surface antigen (HBSAg) are foremd which spill into the blood stream.
Regarding infection with Hep C virus…
Non-structural proteins form viral polymerase enzymes that are the targets of very effective drugs
In NZ which of the following patients is most likely to have chronic HBV in NZ?
A is the correct answer
Is effective 95% of the time in almost all people
