Liver & Biliary Overview Flashcards
B - non-alcoholic steatohepatitis
- she has type II diabetes, is obese and consumes alcohol regularly
- these are all risk factors
- simvastatin can be hepatotoxic, but she has only been taking this for 2 years so it is unlikely
A - full recovery
-
HBsAg shows that they have a current infection
- this could be acute or chronic
- Anti-HBcAg IgM (IgM core antibody) shows that they must currently have an acute infection
- someone with an acute hep b infection is most likely to make a full recovery
D - IV cefotaxmine and oral lactulose
- the patient has encephalopathy
- they also have spontaneous bacterial peritonitis
- fever
- worsening abdominal tenderness / distenstion
- high neutrophil count
- IV cefotaxime is an antibiotic that will treat the SBP
- lactulose reduces ammonia production in the gut to prevent encephalopathy from getting worse
What is the underlying cause of jaundice?
it is caused by an increased concentration of bilirubin in the blood
(hyperbilirubinaemia)
What are the steps involved in the bilirubin metabolism pathway?
- old RBCs are broken down in the spleen
- the haemoglobin from RBCs produces iron** and **unconjugated bilirubin
- the unconjugated bilirubin travels in the blood, bound to albumin, to the liver
- in the liver it is conjugated by UDPGT enzyme
- conjugated bilirubin then enters the biliary system and forms part of the bile
- conjugated bilirubin enters the duodenum in the bile via the common bile duct
- here it is converted to urobilinogen and stercobilinogen
- urobilinogen is excreted in the urine
- stercobilinogen is excreted in the faeces and gives them a dark colour
What causes pre-hepatic jaundice?
What type of hyperbilirubinaemia is present?
- caused by excessive RBC breakdown
- or impaired uptake of RBCs by the liver
- this overwhelms the liver’s ability to conjugate bilirubin
- there is an unconjugated hyperbilirubinaemia
- any bilirubin that is conjugated will be excreted normally, but the excess unconjugated bilirubin will remain in the bloodstream to cause jaundice
What are the 2 major causes of pre-hepatic jaundice?
Why do these lead to jaundice?
Haemolysis:
- increased RBC breakdown leads to an increase in unconjugated bilirubin concentration
- the liver cannot conjugate the bilirubin fast enough, leading to an increase in unconjugated bilirubin in the blood
- there is nothing wrong with the liver, there is just a massive excess of bilirubin
Gilbert’s Syndrome:
- this is a deficiency of the UDPGT enzyme
- UDPGT enzyme is not working as well as it would in a healthy person, so when this individual becomes stressed / gets an infection they can appear jaundiced
What causes hepatocellular (intrahepatic) jaundice?
What type of hyperbilirubinaemia is produced here?
- caused by dysfunction of the hepatic cells
- the liver loses some of its ability to conjugate bilirubin, however this is not the main problem
- if the liver becomes cirrhotic, it compresses the intra-hepatic portions of the biliary tree to cause a degree of obstruction
- the conjugated bilirubin cannot get into the biliary system
- this produces a mixed conjugated and unconjugated hyperbilirubinaemia
- it is mainly conjugated hyperbilirubinaemia
What are the main causes of hepatocellular jaundice?
Caused by anything that damages the hepatocytes:
- alcoholic liver disease / cirrhosis
- hepatitis
- viral, autoimmune
- hepatocellular carcinoma / liver mass
- haemochromatosis
- iatrogenic e.g. medication
What causes post-hepatic jaundice?
What type of hyperbilirubinaemia is produced?
- this is jaundice caused by obstruction of biliary drainage
- the liver is still functioning and conjugating bilirubin as normal
- the conjugated bilirubin cannot get into the duodenum, so it enters the bloodstream instead
- this produces a conjugated hyperbilirubinaemia
How can the causes of post-hepatic jaundice be divided into 3 categories?
Intra-luminal causes:
- gallstones
Mural causes:
- strictures
- cholangiocarcinoma
- drug-induced cholestasis
- PSC / PBS
Extra-mural causes:
- pancreatic cancer
- abdominal masses (e.g. lymphomas)
How can looking at the urine determine what kind of hyperbilirubinaemia might be present?
- conjugated bilirubin is water soluble and so can be excreted in the urine
- unconjugated bilirubin cannot be excreted in the urine
-
dark (“coca-cola”) urine occurs in conjugated or mixed hyperbilirubinaemia
- hepatocellular or post-hepatic jaundice
-
normal urine is seen in unconjugated hyperbilirubinaemia
- pre-hepatic jaundice
In what type of jaundice do the stools appear different?
Why does this occur?
- in post-hepatic jaundice the stools will appear paler
- this occurs when there is an obstructive picture as there are reduced levels of stercobilin entering the GI tract
- this normally colours the stool
- there will also be dark urine and pruritis
- itching is caused by bile salts, as the blockage affects the drainage of bile salts into the duodenum
What blood tests should anyone presenting with jaundice have?
- liver function tests
- coagulation studies
- prothrombin time can be used as a marker of liver synthetic function
- FBC
- anaemia, raised MCV and thrombocytopenia can all be seen in liver disease
- U&Es
What tests are included in a liver screen?
What does each of these things measure?
Bilirubin:
- quantifies the degree of suspected jaundice
Albumin:
- marker of liver synthetic function
Transaminases - ALT & AST:
- markers of hepatocellular injury
- AST : ALT ratio > 2 means likely alcoholic liver disease
- AST : ALT ratio = 1 means viral hepatitis more likely
Alkaline phosphatase (ALP):
- raised in biliary obstruction
- as well as during pregnancy, bone disease and certain malignancies
Gamma-GT:
- more specific for biliary obstruction than ALP
What results would you expect to see for each type of jaundice on LFTs?
Pre-hepatic:
- raised bilirubin only
Hepatocellular:
- there is damage to hepatocytes so you would expect to see raised AST & ALT
Post-hepatic:
- there is an obstruction / bile duct damage so you would expect to see raised ALP / GGT
What is meant by hepatitis?
What are the possible causes of this?
- hepatitis is inflammation of the liver
- it presents with raised AST and ALT
- causes can be acute or chronic and include:
- alcoholic hepatitis
- non-alcoholic steatohepatitis (NASH)
- viruses
- drugs
- autoimmune
How does hepatitis tend to present?
- all types of hepatitis tend to present with similar symptoms
- RUQ pain
- jaundice (hepatocellular)
- hepatomegaly
- joint pain
- nausea
- fatigue
- dark urine
How long does hepatitis have to persist for to become chronic?
What are the possible outcomes of acute and chronic hepatitis?
- acute hepatitis resolves within 6 months
- it becomes chronic if it lasts for longer than 6 months
- acute hepatitis can resolve on its own, progress to chronic hepatitis or (rarely) result in acute liver failure
- chronic hepatitis may progress to cirrhosis, liver failure and hepatocellular carcinoma
What are the 3 conditions that make up the spectrum of alcoholic liver disease?
-
steatosis occurs after a few days of heavy drinking
- this is completely reversible
-
alcoholic hepatitis (inflammation) occurs after long term alcohol use (not a binge)
- this is reversible, especially if mild
- if alcohol consumption is continued this can cause cirrhosis
- this is IRREVERSIBLE as it involves scarring of the liver
What are the symptoms of mild and severe alcoholic hepatitis?
Mild:
- nausea
- anorexia
- weight loss
- hepatomegaly
Severe:
- fever
- jaundice
- tachycardia
- tender hepatomegaly
- bruising
- encephalopathy
- ascites
What causes the inflammation associated with alcoholic hepatitis?
- alcohol metabolism requires NAD+
- when there is excessive alcohol consumption, there is not enough NAD+ available for glycolysis
- this promotes fatty infiltration into the liver, leading to inflammation
What would a full blood count show in someone with chronic high alcohol intake?
macrocytic anaemia
- this presents as low haemoglobin and high mean cell volume (MCV)
What would liver function tests show in someone with chronic high alcohol consumption?
-
AST : ALT ratio > 2
- remember “alcohol then toAST”
- increased bilirubin
- decreased albumin
- ALP may be normal or raised
-
GGT is raised in someone who drinks a lot of alcohol over long periods of time
- raised GGT indicates biliary damage, but also chronic alcohol consumption
What would a clotting screen show in someone with chronic alcohol consumption?
- clotting screen is a functional assessment that tells you how well the liver is working
- the liver makes clotting factors, so clotting time increases when the liver is damaged
- increased prothrombin time is a sensitive marker of significant liver damage
What imaging is performed in alcoholic liver disease?
What would a liver biopsy show?
- hepatic ultrasound scan is performed
- liver biopsy is diagnostic, but rarely needed
the presence of Mallory bodies indicates hepatitis
- these are damaged intermediate filaments within the hepatocytes
there may also be ballooning degeneration of hepatocytes
- this is a form of liver parenchymal cell death
What is involved in the management of alcoholic liver disease?
- alcohol abstinence
-
diazepam may be given in hospital to manage alcohol withdrawal
- this prevents withdrawal symptoms and seizures
-
nutrition
- enteral preferred - calories and vitamins - alcoholics are often malnourished
- weight loss / smoking cessation
- steroids are given in severe alcoholic hepatitis
What is meant by non-alcoholic fatty liver disease (NAFLD) and how can this progress?
- the presence of a fatty liver in those who do not consume alcohol in amounts generally considered harmful to the liver
- steatosis is completely reversible
- this progresses to steatohepatitis (NASH), which involves inflammation
- this is reversible, especially if it is mild
- this progresses to cirrhosis, which is irreversible
What are the risk factors associated with NAFLD?
- obesity (truncal)
- insulin resistance / type II diabetes
- hyperlipidaemia
- hypertension
- metabolic syndrome
- short bowel syndrome
- total parenteral nutrition (TPN)
What additional symptoms may someone with NAFLD present with?
- they may have signs of insulin resistance
- polyuria
- polydipsia
- acanthosis nigricans
What are the investigations involved in NAFLD?
- LFTs
- AST : ALT ratio < 1
- GGT / ALP may also be raised
- blood glucose to check for diabetes / how well controlled it is
What is involved in the management of NAFLD?
- diet and exercise
- controlling risk factors
- statins for hypercholesterolaemia
- good blood sugar control in diabetes
- metformin for diabetics
What is the difference between steatosis and non-alcoholic steatohepatitis (NASH)?
-
steatosis involves fatty accumulation in the liver
- a liver can remain fatty without disturbing liver function
- by various mechanisms and insults to the liver, steatosis can progress to non-alcoholic steatohepatitis (NASH)
- NASH involves steatosis combined with inflammation and sometimes fibrosis
How does someone with NAFLD usually present?
- usually no noticeable symptoms and is only detected during routine blood tests or unrelated abdominal imaging
- may have some symptoms related to liver dysfunction
- fatigue
- malaise
- dull RUQ abdominal discomfort
What type of infection is usually caused by viral hepatitis A & E?
What are the exceptions to this?
- hep A & E usually cause acute hepatitis, which very rarely progresses to chronic hepatitis
- when you think of A&E - think of ACUTE problems
- hepatitis A&E can become chronic in immunosuppressed individuals
- hepatitis E can cause severe liver failure in pregnant women
How are hepatitis A & E spread?
What is the management for this infection?
- they are spread via the fAEco-oral route
- this is via contaminated water or sex
- management is supportive as this infection is acute and will regress on its own
- paracetamol and alcohol should be avoided
What does the presence of IgM and IgG in Hep A / E serology tell you?
-
IgM tells you that the infection is acute
- they currently have the infection
- IgG tells you that they have had the infection, but have now cleared it
- IgM = now*
- IgG = gone*
Do hepatitis B and C tend to be acute or chronic?
What is the risk associated if an infection can become chronic?
- Hep B & C can be acute or chronic
- Hep C** most commonly becomes _C_hronic**
- Hep B usually stays acute (80-90% cases)
- as they can become chronic, there is a risk of cirrhosis / hepatocellular carcinoma
- this risk is greater with Hep C infection as it is more likely to become chronic
Under what circumstances can Hep D infection occur?
What is the associated risk?
- Hep D is a coinfection / superinfection of Hep B
- it can only occur if someone is already infected with Hep B
- Hep D infection increases the risk of liver failure in someone with Hep B infection
What is the treatment for acute Hep B infection?
- it does not require treatment as the infection is cleared naturally in 90% cases
- if Hep B persists for > 6 months then antiviral treatment is required
What is the treatment for chronic Hep B infection?
What is the problem with this treatment?
- antiviral treatment suppresses HBV DNA replication
- it is NOT curative, so drug withdrawal leads to relapse
- if the liver is working well (i.e. no decompensated cirrhosis) then peginterferon-a-2a is given
- if the liver is functioining poorly (i.e. decompensated cirrhosis), then give tenofovir or entecavir
What is the treatment for hep B when there is a co-existing hep D infection?
peginterferon-a-2a AND tenofovir/entecavir
What is the treatment for hepatitis C infection?
- this needs to be treated with antivirals as infection is likely to become chronic
- treat with sofosbuvir or ledipasvir
What are the 2 antigens associated with the hepatitis B virus?
Which one can be useful in detecting Hep B infection?
Surface antigen:
- HBsAg is on the outside of the molecule
- if HBsAg is present, there is a current active Hep B infection
Core antigen:
- HBcAg is in the middle of the virus and is not detectable in the blood
- this is not useful in telling whether there is a current active infection
What are the 2 antibodies that are associated with Hep B infection?
What does their presence tell you about current infection?
Surface antibody:
- HBsAb tells you that the person has cleared a Hep B infection
- they had the infection in the past, but do not have it currently
- OR they have been vaccinated against Hep B
Core antibody:
- this is only derived from natural infection
- if IgM is present, there is an acute infection
- if IgG is present, this person may have a chronic infection
Complete the table
What are the main symptoms associated with haemochromatosis?
What can this progress to?
- 75% of cases are asymptomatic
- hepatomegaly
- diabetes mellitus onset
- bronze skin
- arthralgia
- male impotence / testicular atrophy
What are the investigations involved in haemochromatosis?
- first line investigation is transferrin saturation and serum ferritin
- transferrin saturation will be raised
- serum ferritin will be raised (this is non-specific as it is an acute phase protein)
- gene typing of HFE
- gold standard is liver biopsy to see iron deposits
What are the clinical features of Wilson’s disease?
- characterised by hepatitis + dementia + parkinsonism in a young person
- hepatosplenomegaly
- abdominal pain
- jaundice
- ascites
- portal hypertension
- Kayser-Fleischer rings
What is meant by cirrhosis?
Does the liver still function if it is cirrhotic?
- normal liver is replaced by fibrosis and nodules of regenerating hepatocytes
- it can be stable or decompensated (liver failure)
- the liver still functions when it is cirrhotic, but cirrhosis can eventually lead to liver failure, which can be life-threatening
- there is also increased risk of HCC
What are the most common causes of cirrhosis?
What type of cirrhosis is seen in viral causes and alcoholic causes?
- alcohol misuse
- viral hepatitis (B / C)
- autoimmune hepatitis
- haemochromatosis
- NASH
- chronic biliary disease
- viral hepatitis leads to macronodular cirrhosis (nodules > 3mm)
- chronic alcohol abuse leads to a micronodular cirrhosis (nodules < 3mm)
What are the most common stigmata of chronic liver disease?
- clubbing
- spider naevi
- Dupuytren’s contracture
- palmar erythema
- gynaecomastia
- increased bruising
- a patient can be clincally well with hepatitis or cirrhosis, with signs of chronic stable liver disease
What is the normal portal circulation?
What is the purpose of this?
- blood from the spleen (splenic vein) and bowels (inferior and superior mesenteric veins) travels through the liver via the portal vein
- this blood is full of ingested toxins / pathogens
- the blood passes through the liver to be detoxified and then becomes part of the systemic circulation via the inferior vena cava
What is meant by portal hypertension?
Why does it occur?
- an increased pressure in the portal vein due to cirrhosis (of any cause)
- it occurs due to a blockage in the liver (e.g. due to cirrhosis) leads to a backlog of blood into the portal system
- this raises pressure within the portal vein
Why does decompensated cirrhosis / liver failure lead to encephalopathy?
- the liver functions to remove gut products from the blood
- these arrive via the portal vein, and are removed before the blood returns to systemic circulation
- in decompensated cirrhosis, the hepatocytes are damaged and less functional and there is scar tissue in the liver
- the liver is less effective at removing gut products from the blood, so they make their way into the systemic circulation (intrahepatic shunting)
- some blood from the gut bypasses the liver due to raised portal pressure at the sites of porto-systemic anastomoses
- gut products in systemic circulation then impact on neurotransmission in the brain, causing encephalopathy
- in this case, it is caused by ammonia
What is spontaneous bacterial perionitis?
How is it diagnosed?
- this is the development of a bacterial infection in the peritoneum
- it occurs when the ascitic fluid (i.e. an increased volume of peritoneal fluid) becomes infected without an apparent source
- it is diagnosed using paracentesis (needle aspiration of ascitic fluid)
- SBP is diagnosed when neutrophil count of the aspirate is > 250 cells per mm3 in the absence of another reason for this
What is the management for ruptured varices when there is haematemesis?
- start with ABCDE approach then IV fluids and/or blood
- need to replace blood when Hb < 7 g/dL or patient could bleed to death
- fluids will replace volume, but not clotting factors
- then give terlipressin + antibiotics
- terlipressin reduces blood flow to the gut, which reduces pressure on the portal system
-
EVL is performed after resuscitation when the patient is haemodynamically stable
- this involves placing bands over the varices to stop bleeding
What is cholelithiasis?
What is biliary colic and why does it occur?
- cholelithiasis refers to a gallstone in the gallbladder
- biliary colic refers to presence of cholelithiasis + pain
- the stone in the gallbladder moves into the cystic duct and obstructs the flow of bile moving into the common bile duct
- the gallbladder contracts vigorously against the stone, which causes pain
- this is worse after a fatty meal as this stimulates the gallbladder to contract (release of bile helps emulsification of fats)
What is meant by choledocholithiasis?
What if there is also pain present?
- choledocholelithiasis refers to a gallstone in the common bile duct
- if there is choledocholelithiasis + pain then this is biliary colic
- this term means presence of pain due to gallstones
What is the management for choledocholelithiasis and biliary colic?
- for both analgesia + ERCP + lap chole
- in cholelithiasis, you do not remove the gallbladder if there is no pain
- in choledocholelithiasis, remove the gallbladder even if there is no pain
- the stone in the CBD will go on to cause complications, including pancreatitis and ascending cholangitis
What happens in primary biliary cirrhosis?
What bile ducts are affected and who tends to be affected more?
- only affects intrahepatic ducts
- more common in females
- autoimmune condition in which the intrahepatic bile ducts are slowly destroyed
- this leads to a build-up of bile and other toxins in the liver (cholestasis)
What other conditions is PBC associated with?
How is it diagnosed?
- it is associated with other autoimmune conditions including Sjorgen’s syndrome and rheumatoid arthritis
- raised antimitochondrial antibodies are usually diagnostic
- a “florid duct lesion” will be present on histology
- this is a granulomatous destruction of bile ducts
What is primary sclerosing cholangitis?
Which ducts are affected and which gender is affected more often?
a long-term progressive disease of the liver and bile ducts characterised by inflammation and scarring of the bile ducts that usually allow bile to drain from the liver
- affects both intra- and extra- hepatic ducts
- affects males more than females
How is PSC diagnosed?
What would it look like on histology?
- it is diagnosed with MRCP
- this shows a beaded appearance - segmental fibrosis with saccular dilation
- histology will show “concentric onion skin fibrosis”
- many antibodies, including pANCA, may be raised
What are the 2 main symptoms of pancreatic cancer?
What is the main form of pancreatic cancer?
- pancreatic cancer presents with painless jaundice and a palpable gallbladder
- pancreatic cancers are mostly adenocarcinomas from exocrine tissue
- 75% are found in the head of the pancreas
What are the 2 different categories of malignant liver tumours?
Primary tumours:
- these originate in the liver
- 90% are hepatocellular carcinomas
- these occur in people who have had cirrhosis for a long time
- cholangiocarcinomas are cancer of the bile ducts
Secondary tumours (most common):
- these are liver tumours that have metastasised from elsewhere
- common sites are:
- bowel
- breast
- oesophagus
- stomach
- pancreas
What are the signs and symptoms of hepatocellular carcinoma?
- malaise
- anorexia
- weight loss
- RUQ pain
- jaundice
- ascites (due to chronic liver disease)
- cachexia
- hepatomegaly
What is cholangiocarcinoma?
Where does it arise from?
- they are usually adenomas of the bile duct epithelium
- can arise from intra- or extra-hepatic ducts or the gallbladder
