2: Jaundice, Hepatitis, Hepatic Failure, Chronic Liver Disease Flashcards
Define jaundice
yellow discolouration of the skin and sclera
What concentration of bilirubin results in jaundice
> 50
How can the aetiology of jaundice be divided
Pre-Hepatic
Hepatic
Post-Hepatic
What are the three categories of pre-hepatic jaundice
- Haemolytic
- Crigler-Najar
- Gilbert Syndrome
What are the four causes of haemolytic anaemia
- Sickle Cell
- G6PD
- Hereditary spherocytosis
- Haemolytic disease of foetus and new-born
Which enzyme is defective in Gilberts syndrome
UGT
What is the role of the UGT enzyme
In hepatocytes UGT converts unconjugated bilirubin to conjugated bilirubin
Explain Gilbert syndrome
There is low UGT enzyme. Meaning normally individuals are able to conjugate bilirubin. However, if haemolysis increases (illness, stress, dehydration) there will be an increase in unconjugated bilirubin as it exceeds the enzymes capacity
What is Crigler-Najar syndrome
Complete absence of UGT
What does Crigler-Najar syndrome usually lead to
Bilirubin encephalopathy and kernicterus
What are 6 hepatic causes of jaundice
- Hepatitis
- Hepatocellular carcinoma
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Hereditary haemochromatosis
- Alcoholic liver disease
What are 5 causes of post-hepatic jaundice
- Gallstones
- Cholangiocarcinoma
- Pancreatic cancer
- Abdominal mass (eg. lymphoma)
- Dubin Johnson Syndromne
Which enzyme is deficient in Dupin-Johnson syndrome
Defect in MRP2
What is the function of MRP2
MRP2 is responsible for transporting conjugated bilirubin to hepatic duct
In pre-hepatic jaundice how will urine appear
Normal
In pre-hepatic jaundice how will stool appear
Normal - Dark
Why does urine appear normal and stool dark in pre-hepatic jaundice
As it is caused by an increase in physiological pathways
In hepatic jaundice how will urine appear
Dark
In hepatic jaundice how will stool appear
Clay
Explain why urine is dark and stool pale in hepatic jaundice
As there is a problem within the liver and hence conjugating bilirubin. Reduction in conjugated bilirubin reduces amount entering stool - hence causing pale stools. Unconjugated bilirubin accumulates in the circulation and hence is excreted by the kidneys.
How will urine appear in post-hepatic jaundice
Very Dark
How will stool appear in post-hepatic jaundice
Pale. Clay-coloured
Why is urine v.dark and stool pale in post-hepatic jaundice
Obstruction to outflow of bile. This means it cannot enter stool - giving stool a pale colour. Accumulating bilirubin backs-up the system enters the circulation causing dark urine.
How is bilirubin formed
From break-down of haem in RBC
Explain normal processing of bilirubin
Haem is a degradation production of RBC. Haem is converted to unconjugated bilirubin. This is conjugated at hepatocytes making it water-soluble and able to be excreted via the GI tract. Two main excretion productions are stercobillin and urobilinogen.
Explain the pathophysiology of pre-hepatic jaundice
Increase in RBC degradation. This increases unconjugated bilirubin. It is still able to be conjugated and therefore excreted in faeces. However, unconjugated bilirubin exceeds enzymes ability to conjugate causing an accumulation in the blood-stream resulting in jaundice.
Increase billirubin in bile also increases the risk of pigment stones.
Explain pathophysiology of hepatic jaundice
Liver looses ability to conjugate bilirubin, leading to excess unconjugated bilirubin. If the liver becomes cirrhotic it may obstruct bile - leading to a mixed conjugated and unconjugated hyperbilirubinaemia.
Explain post-hepatic jaundice
Obstruction of biliary drainage leads to a conjugated hyperbillirubinaemia. Pressure in the bile-duct can cause back flow through tight junctions and enter the circulation. Bile salts and cholesterol may cause pruritus. Reduced bile excretion can cause steatorrhoea.
What investigation should be ordered in jaundice
LFTs
Why is bilirubin useful in assessing jaundice
Determine extent of hyperbillirubinaemia
Why is albumin useful in assessing jaundice
Determine liver function
Why is AST and ALT useful in assessing jaundice
Liver damage
Why is ALP useful in assessing jaundice
Indicates obstruction
Why is GGT useful in assessing jaundice
Often elevated in alcoholic liver disease
If the AST: ALT ratio is more than two what does it indicate
Alcoholic liver disease
If the AST: ALT ratio is 1 what does it indicate
Viral Hepatitis
In pre-hepatic jaundice how will
a. ALT/AST present
b. ALP present
a. normal
b. normal
In hepatic jaundice how will
a. ALT/AST present
b. ALP present
a. raised
b. normal
In post-hepatic jaundice how will
a. ALT/AST present
b. ALP present
a. normal
b. raised
What is hepatitis
Inflammation of the liver
What are the two types of hepatitis
- Autoimmune
2. Viral
What is autoimmune hepatitis
inflammation of the liver caused by T cell function and autoantibodies directed against cell-surface antigens
What does the type of autoimmune hepatitis depend on
antibodies present
What 2 antibodies are present in type I autoimmune hepatitis
ANA
anti-SMA
Who does type I autoimmune hepatitis affect
adults and children
What antibodies are present in type 2 autoimmune hepatitis
anti-LKM1
Who does type II autoimmune hepatitis affect
children
What antibody is present in Type III autoimmune hepatitis
soluble liver and kidney antigen
Who does Type III autoimmune hepatitis affect
adults
Is autoimmune hepatitis more common in males or females
females (4:1)
what age-range does autoimmune hepatitis occur
10-20y and 45-70y
what three other conditions is autoimmune hepatitis associated with
Hashimotos thyroiditis
Coeliac disease
T1DM
what genes are associated with autoimmune hepatitis
HLAB8
HLADR3
how do symptoms vary in autoimmune hepatitis
Can vary from asymptomatic to liver failure
give 5 common symptoms of autoimmune hepatitis
- Lethargy
- Weight Loss
- Amenorrhoea
- Abdominal pain
- Jaundice
what will a third of patients with autoimmune liver disease develop
Acute liver failure
how will acute liver failure in autoimmune hepatitis present
- Fever
- RUQ pain
- Jaundice
what investigations may be ordered in autoimmune hepatitis
- LFTs
- Antibodies
- IgG
- Liver biopsy
how will LFTs present in autoimmune hepatitis
Raised AST and ALT
what antibodies may be present in autoimmune hepatitis
Anti-nuclear antibodies
Anti-smooth muscle antibodies
how will IgG present in autoimmune hepatitis
May be raised - hypergammaglobulinaemia
when is a liver biopsy performed in autoimmune hepatitis
If autoantibodies are positive
what is first-line management of autoimmune hepatitis
Prednisolone.
Azathioprine may be used as steroid-sparing alternative.
what is the ultimate treatment for autoimmune hepatitis
Liver transplantation - if decompensated cirrhosis or failure to respond to medical therapy.
what is hepatitis A
Infection with hepatitis A
in which countries is hepatitis A common
(The A’s!):
South America
Africa
how is hepatitis A spread and how can this be remembered
Faecal-Oral.
Hepatitis A and E are the vowels - they are spread by the bowels
what food is hepatitis A particularly associated with
Shell-Fish
what is risk factor for catching hepatitis A
Travelling
what is the incubation period of hepatitis A
1-2W
how does hepatitis A initially present
Pro-drome
what is a KEY feature of hepatitis A prodrome
RUQ pain and tender hepatomegaly
what are 4 features of hepatitis A pro-dromal phase
- Fever
- Anorexia
- N+V
- RUQ - tender hepatomegaly
what are 2 symptoms of icteral phase of hepatitis A
Jaundice
Dark Stool, Pale Urine
Pruritus
How will LFTs present in hepatitis A
Raised AST + ALT
What is the AST to ALT ratio in hepatitis A
AST:ALT = 1
What is another investigation for hepatitis A
anti- HepA IgM and IgG
what does a raised anti-hep A IgM indicate
Current Infection
what does a raised anti-hep A IgG indicate
Previous Infection
how is hepatitis A managed
Self-resolving
is there a vaccine for hepatitis A
Yes
how many vaccinations of hep A does a person need
initial vaccine, followed by a booster 6-12m later
who is given Hep A vaccines
- Travellers
- MSM, IVDU, HIV
- Chronic liver disease
- Occupational risk
does hep A cause chronic disease
No
What is hepatitis B
Infection with hepatitis b virus
In which countries is HBV more common
- Far East
- Africa
- Mediterranean
What are the three methods of HBV transmission
Vertical
Parental
Sexual
What are 5 risk factors of HBV
- MSM
- IVDU
- HIV
- Baby of HbSAg +ve mother
- Prison staff
- Haemodialysis patients
What is the incubation period of HBV
6m
In acute infection what % will be symptomatic
30%
What are some symptoms of acute-hepatitis B
- Fever
- Lethargy
- Arthralgia
- Jaundice
- RUQ pain
What defines acute-hepatitis B infection
Manifests within 6m of infection
What defines chronic hepatitis B infection
Manifests beyond 6m of infection, or longer with positive HbSAg
How do individuals with chronic Hep B present
Often asymptomatic carriers
If individual has re-activation of chronic hep B how may it present
Liver Failure
Explain pathophysiology of acute Hepatitis B
HBV infects hepatocytes, which then express it’s antigen on their surface. Lymphocytes respond to HBV antigen and are activated - causing destruction of hepatocytes and subsequent inflammation.
Explain pathophysiology of chronic hepatitis B infection
Chronic inflammation leads to necrosis resulting in cirrhosis. Also causes cell dysplasia which is a risk factor for hepatocellular carcinoma
What two investigations should be ordered for HBV patients
HBV serology
LFTs
What is the first-marker of HBV infection to appear
HbsAg
If HbsAg is present more than 6-months what does it indicate
Chronic Infection
What does HbsAg trigger
anti-HBS
If anti-HBS is present on its own what does it indicate
individual has been vaccinated against HBV
What is HbcAg
HBV core-antigen
What does anti-HBC IgM imply
current infection
What does anti-HBC IgG imply
previous infection
What does presence of HbeAg indicate
highly infectious strain of HBV
What else is included in HBV serology
anti-HBV DNA
If individual has anti-HBS only what does it indicate
previously vaccinated against HBV
If individual has
anti-HBS
anti-HBC IgG
what does it indicate
previous infection with HBV
If individual has
HbsAg
anti-HBC IgG
What does it indicate
They are a carrier of chronic HBV
If individual has
HbsAg
HbeAg
What does it indicate
Severe Infection
If individual has
HbsAg
anti-HBC IgM
HBV DNA
What does it indicate
Current Infection with HBV
How will LFTs present in HBV infection
Raised AST and ALT
What is the AST: ALT ratio in HBV infection
<1
What is first-line in managing HBV infection
Pegylated Interferon Alpha
What is second-line in managing HBV infection
Tenofovir and Entecavir
Is there a vaccine for HBV
Yes
When is the HBV vaccine given
As part of routine immunisation schedule at:
2, 3 and 4 months
When is testing for anti- HBs only recommended
Only if occupational exposure to HBV - test 4m following vaccine
What does infection with HBV predispose to
HDV Infection
What are three other complications of HBV infection
Chronic hepatitis
Fulminant hepatitis
Hepatocellular carcinoma
What is acute hepatitis C infection
infection with hepatitis C in the past 6-months
What is chronic hepatitis C infection
infection with hepatitis C more than 6-months ago
What are the three methods of transmitting hepatitis C
- Sexual
- Parental
- Vertical
What are three risk factors for hepatitis C
- IVDU
- Recipients of blood transfusions before 1992
- Prisoners
What is the incubation period of hepatitis C
6-9W
what proportion of acute hepatitis C infections are asymptomatic
80%^
what are 4 possible symptoms of hepatitis C infection
- Malaise
- RUQ pain
- Jaundice
- Tender hepatomegaly
what % of hepatitis C patients develop silent chronic infection
85%
what % of hepatitis C patients will develop cirrhosis
25%
what % of hepatitis C patients will develop hepatocellular carcinoma
4%
What are possible haematological complications of chronic cirrhosis
Cryoglobulinaemia
What are possible rheumatological complications of chronic cirrhosis
Arthalgia
Arthritis
What are possible ophthalmological complications of chronic cirrhosis
Sjogren’s
What are possible dermatological complications of chronic cirrhosis
Percutaneous Cutanea Tarda
what are liver complications of chronic hepatitis C
Cirrhosis
Hepatocellular carcinoma
what are renal complications of HCV
Membroproliferative glomerulonephritis
what is first-line investigation of HCV
ELISA
how will LFTs present in HCV
Raised AST and ALT
what will be seen on ELISA in hepatitis C
anti-HCV antibodies
what diagnostic tests are ordered for HCV
PCR for HCV RNA
if HCV RNA is positive what does it indicate
Current Infection
If anti-HCV antibodies are positive, but HCV RNA negative what does it indicate
previous infection
if HCV RNA positive what should be performed
Non-invasive elastography
What is used to manage HCV
Protease inhibitor w/wo ribavirin
Name two combination protease inhibitors
Daclatasvir and Sofosbuvir
Sofosbuvir and simeprevir
What is the aim of treatment in HCV
sustained virological response: undetectable HCV RNA at 6-months
Is there a vaccine for HCV
No
What % will develop chronic HCV
50-80%
What are three complications of HCV
- Cirrhosis
- Hepatocellular carcinoma
- Fulminant hepatitis
What does hepatitis D require for infection
Hepatitis B
What is hepatitis D co-infection
When Hep B and Hep D infect at the same time
What is hepatitis D super-infection
When a HbsAg positive individual is infected with Hep D
Explain pathophysiology of hepatitis D
Hepatitis D is a single-stranded RNA virus. It requires HbsAg to complete its replication cycle.
What is first-line investigation for HDV
ELISA:
anti-HDV antibody
When should anti-HDV antibody only be requested
If HbsAg positive
What is second line investigation for HDV
rtPCR for HDV RNA
What is first-line management for HDV
pegylated interferon-alpha
What is ultimate management for HDV
liver transplantation
How can HDV infection be prevented
vaccination with hepatitis B at 2,3 and 4 months
What are three risks of super-infection HDV
- Chronic hepatitis
- Fulminant hepatitis
- Cirrhosis
What is hepatitis E
Infection with RNA virus hepatitis E
Which countries is hepatitis E infection more common
India
China
Which countries is hepatitis A infection more common
Africa
South America
How is hepatitis E transmitted
Faecal-Oral Route
What food in particular is associated with hepatitis E
Pork
What is the incubation period of hep E
2-8W
How does hep E initially present
Pro-drome 1-2W
What is are features of pro-drome in Hep E
- RUQ pain
- Tender hepatomegaly
- Fever
- Malaise
- N+V
What are 3 symptoms of icteral hepatitis E phase
Jaundice
Pale stools, Dark Urine
Pruritus
What is first line investigation for Hep E
ELISA for anti-HEV antibodies
What does anti-HEV IgM indicate
Current Infection
What does anti-HEV IgG indicate
Previous Infection
How is HEV managed
Supportive
Is there a vaccine for hep E
No
What is a good way to remember there is no vaccines for hep C and E
vaCcinEs
C
E
= have no vaccines
in which population is hepatitis E a great risk
pregnant women
why is hepatitis E a risk to pregnant women
20% risk fulminant hepatitis
Define hepatic failure
Deterioration of liver function resulting in coagulopathy and encephalopathy
What defines coagulopathy
INR > 1.5
What is acute-liver failure
Development of encephalopathy or coagulopathy in a previously healthy liver
what time-frame defines hyper-acute liver failure
<7d
what time-frame defines acute liver failure
8-21d
what time frame defines sub-acute liver failure
4-26W
what is chronic liver failure
when liver failure develops on a background of previous liver disease
what is fulminant hepatic failure
syndrome where there is massive necrosis of liver cells causing impairment of liver function
what are the 4 etiological categories of liver failure
- Medications
- Infections
- Vascular
- Other
what infections can cause liver failure
Hepatitis
Yellow Fever
Leptospirosis
what drugs may cause liver failure
Paracetamol over-dose
Isoniazid
what vascular disease can cause liver failure
Budd-Chiari
what are other causes of liver failure
- Alcohol
- Fatty Liver Disease
- Wilson’s
- Haemochromatosis
- Autoimmune hepatitis
What are 5 symptoms of hepatic failure
- Jaundice
- Hepatic encephaloapthy
- Constructional apraxia
- Asterixis
- Fetor hepaticus
Why does hepatic encephalopathy occur
As the liver fails, ammonia accumulates in the brain.
This is cleared by astrocytes, which produce glutamine.
Glutamine causes a shift in the osmotic balance - drawing fluid into cells
what is constructional apraxia
Unable to construct a 5-point star
what is fetor hepaticus
Breath smells like pear drops
what are the four features of grade I hepatic encephalopathy
- Constructional apraxia
- Mood disturbance
- Sleep disturbance
- Poor arithmetic
what are the 5 features of grade 2 hepatic encephalopathy
- Drowsy
- Confused
- Slurred speech
- Liver Flap
- Inappropriate behaviour
what are the 4 features of grade 3 hepatic encephalopathy
Incoherent
Restlessness
Liver Flap
Stupor
what is grade 4 hepatic encephalopathy
coma
what diagnostic system is used for liver failure
Kings-College Criteria in Acute Liver Failure
According to kings college criteria in acute liver failure, if paracetamol-induced liver failure what arterial pH is required for diagnosis
pH <7.3
According to kings college criteria in acute liver failure, if individual does not have pH <7.3 what 3 other criteria must be met to make a diagnosis
- PT > 100
- Creatinine > 300
- Grade III or IV encephalopathy
According to kings college criteria in acute liver failure, if non-paracetamol acute liver failure what criteria should be met for diagnosis
Prothrombin time > 100s
According to kings college criteria in acute liver failure, if non-paracetamol acute liver failure and PT <100s what criteria should be met for diagnosis
Requires 3 out-of the following 5:
- <10 or >40-years
- Medication induced liver failure
- > 1W between jaundice and onset encephalopathy
- PT > 50s
- Bilirubin > 300
What investigations are ordered for liver failure
- LFTs
- Coagulation studies
- FBC
- Virology studies
- Ascitic tap
How may prothrombin time and INR present
- Prothrombin time = prolonged
- INR = >1.5
How may LFTs present in liver failure
- Raised billirubin
- Raised AST and ALT
- Raised/Normal ALP
How may FBC present in chronic liver failure
Chronic liver disease is associated with IDA
Why are viral serologies ordered
Check for hepatitis
If an ascitic tap is ordered and has neutrophils >250 what does this indicate
Spontaneous bacterial peritonitis (SBP)
How is liver failure treated
- Intubate if required
- NG tube
- Catheter
- 10% dextrose
- Treat cause
- Use phenytoin to treat any seizures
If individual with liver failure has ascites how is this managed
- Fluid restriction
- Low salt diet
- Diuretics
- Daily weight
If individual with liver failure is bleeding what is given
Vitamin K
FFP
Platelets
When is hypoglycaemia treatment in liver failure
<2
What two medications may be given to treat encephalopathy in liver-failure
Lactulose
Rifaximin
What is the role of lactulose
Lactulose is catabolised by gut flora where it decreases pH trapping ammonia
What is rifaximin
Non-absobable antibiotic that reduces concentration of ammonia-producing bacteria
What is cirrhosis
chronic liver damage
In which gender is cirrhosis more common
males (2:1)
What are the 3 broad etiological categories for cirrhosis
- Hepatotoxic
- Inflammation
- Metabolic
What hepatotoxic substances may cause cirrhosis
Alcohol
Medications:
- Amiodarone
- Methotrexate
What are 6 inflammatory causes of cirrhosis
- Hep B
- Hep C
- Hep D
- Primary sclerosing cholangitis
- Primary biliary cholangitis
- Autoimmune hepatitis
What are 4 metabolic causes of cirrhosis
- Wilson’s
- Haemachromatosis
- Budd-Chiari
- Non-alcoholic fatty liver disease
- a1 alpha trypsin deficiency
What is the most common cause of liver cirrhosis
Hep C
What is the second most common cause of liver cirrhosis
Alcohol
What 3 nail signs may be present in cirrhosis
- Clubbing
- Leuconychia
- Terry’s sign = telangiectasia of outer 1/3 of nail
What 2 signs on the palm may present present in cirrhosis
Dupuytrens contracture
Palmar erythema
What does enlargement of the parotid gland in cirrhosis indicate
Alcohol
Explain pathophysiology of cirrhosis
Recurrent inflammation of hepatocytes heals by fibrosis and scarring which results in decrease in function.
Cytokines also activate stellate cells to produce collagen reducing liver function
Loss of liver function leads to:
- Reduced clotting factor production = coagulopathy
- Increase ammonia = hepatic encephalopathy
- Decrease albumin = ascites
- Decrease bile acids = malabsorption fat-soluble vitamins
What 4 blood tests are ordered in cirrhosis
- LFT
- Coagulation profile
- FBC
- Viral serology
How will LFTs present in cirrhosis
Raised ALT, AST
Raised ALP
Raised GGT
How will coagulation studies present in cirrhosis
Raised INR
why may an individual with cirrhosis have a microcytic anaemia
If caused by alcoholic liver disease - may have vitamin B12 deficiency.
what is first-line imaging for cirrhosis
Fibroscan
what is a fibroscan also called
Transient elastography and acoustic radiation force impulse imaging
what should all individuals with a new diagnosis of cirrhosis be offered and why
Upper GI endoscopy to check for oeseophageal varices
How should liver cirrhosis be managed
- Good nutrition
- Alcohol abstinence
- Cholestyramine for tiching
- Ursodeoxycholic acid for hepatitis
How is ascites managed
- Fluid restriction <1.5L
- Low-salt
- Spirinolactone
What is the only definitive treatment for liver cirrhosis
Liver transplant
If individual has liver cirrhosis how often should they receive an US scan and AFP to check for hepatocellular carcinoma
Every 6-months
What scoring system is used to predict prognosis in liver cirrhosis
Child-Pugh
What is the child-pugh score based on
Ascites
Albumin
Bilirubin
PT
Encephalopathy
What are two complications of liver cirrhosis
Acute liver failure
Portal HTN
How may portal hypertension manifest
- Caput medusa
- Oesophageal varices
- Splenomegaly
- Ascites
What is spontaneous bacterial peritonitis
Type of peritonitis seen in those with ascites secondary to liver failure
how will SBP present
- Fever
- Abdominal pain
- Ascites
what is used to investigate SBP
Paracentesis
what is seen on paracentesis in SBP
Neutrophils > 250
what is used to managed SBP
IV Cefotaxime
Who is prophylactic cirpofloxacin against SBP given to
- One episode of SBP
- Serum protein <15 and one of:
- Child-pugh 9
- hepatorenal syndrome