Chronic liver disease Flashcards
What is the long term outcome of chronic liver disease?
Progression to cirrhosis
How long is liver disease present for it to be chronic?
> 6 months.
Can be subclinical and acute presentation but the process has been going on for > 6 months
What is the overall pathology of chronic liver disease?
Recurrent inflammation and repiar with fibrosis and regeneration. Balance
What are the capillaries in the liver called and why?
Hepatic sinusoids- much more leaky than normal capillaries to allow proteins to move in and out
What is found in the hepatic triad?
Hepatic portal vein, Hepatic artery and Bile duct
Which cells in the liver are responsible for inflammation and laying down of scar tissue?
Quiescent hepatic stellate cells which once activated become a hepatic myofibroblast and lay down collagen
What can activate hepatic stellate cells?
Hepatocyte kupffer cell (inflammatory cell)
Inflammatory cytokines
Products of damaged cells
What are the consequences of activated hepatic stellate cells?
Increased: Number of HSCs (hepatic stellate cells) TIMPs (tissue inhibators of metaloprotiases) Matrix Decreased: MMPs (matrix metaloproteases)
What normally causes resolution in the liver after acute injury?
The hepatic stellate cells are inactivated and become apoptotic and die.
What leads to chronic liver disease?
If the hepatic stellate cells continue to be activated by tissue inhibatorsof metaloproteases
What are the causes of chronic liver disease? Most common first?
Alcohol NAFLD Hep C Primary bilary cholangitis Autoimmune hepatitis Hep B Haemochromatosis Primary sclerosisng cholangitis Wilsons Disease Alpha 1 anti-trypsin Budd-Chiari Methotraxate
Lots of chronic disease can affect the liver eg Amyloid or sarcoid, but these are not chronic liver disease. Why?
They do not lead to cirrhosis
What is the most common chronic liver disease?
NAFLD- non-alcoholic fatty liver disease.
30% of general population.
What can NAFLD progress to?
NASH- non alcoholic steatosis hepatitis.
Inflammation on top of the fat
What causes NAFLD?
Obesity (60% of obese individuals have NAFLD), metabolic syndrome, Type 2 diabetes
How is NAFLD treated?
Lose weigh and improve diet
What are the similarities between NAFLD and alcoholic fatty liver disease?
Histology is identical.
Hep C can also look similar
Which inflammatory cell is associted with fatty liver disease?
Neutrophils
What causes the progression from NAFLD (steatosis- bigign biuld up of triglycerides) to NASH?
1) Oxidative stress (most important) and lipid peroxidation
2) Pro inflammatory cytokine release- TNF alpha generated by hepatocytes
3) Lipopolysaccharide
How is NAFLD (simple steatosis) diagnosed and treated?
USS diagnosis
Treatment = weight loss and exercise.
What are the health consequences of NAFLD?
No liver outcomes
Increased CV risk
How is NASH diagnosed and treated?
Diagnosis = liver biopsy Treatment = weight loss and exercise and other experimental treatments
What are the health consequences of NASH?
Risk of progression to Cirrhosis.
But if addressed with weight loss is reversible
What are the autoimmune liver diseases?
Primary Biliary cholangitis
Auto-immune hepatitis
Primary sclerosing cholangitis
(Alcohol related liver disease and drug reactions have some auto-immune features)
What is Primary biliary cholangitis?
Autoimmune disease due to antimicrobial antibodies. CD4+ T cell mediated which are reactive to M2 target. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis.
What is the presentation of Primary biliary cholangitis?
Middle aged women.
Usually incidental finding.
Symptoms = fatigue, itch without rash, xamthalasma and xanthomas (hypercholesterolaemia is a consequence as the liver is not using cholesterol for bile salts)
How is Primary bilary cholangitis diagnosed?
Need 2 of the following:
Positive antimitochondrial antibody (blood test)
Cholestatic LFTs
Liver biopsy
What is the treatment for Primary bilary cholangitis?
Urseo deoxycholic acid- which promotes bile flow through the liver and slows the progression of the disease.
What are the common outcomes for primary biliary cholagitis patients?
Most will not develop symptoms/liver failure
Itch can be problematic.
Those who do develop liver failure will be unfit for transplant because too old but still the 3rd most common cause of transplantation in the UK
How many types of auto immune hepatitis and which demographic is common for each one?
Type 1: Adults (10-20 and 45-70 (>females)
Type 2: Children and young adults (>female)
What is type 1 autoimmune hepatitis associated with?
Autoimmune thyroidits, graves diease and chronic UC
Occasionally with Rheumatiods, systemic sclerosis, SLE, pernicious anaemia
How do type 1 autoimmune hepatitis patients present?
Acute onset of symptoms similar to acute viral hepatitis with jaundice (40%) Hepatomegaly Jaundice Stigmata of chronic liver disease Splenomegaly Elevated AST and ALT Elevated PT Non specific symptoms
How is Type 1 Autoimmune hepatitis diagnosed?
Elevated AST and ALT. Elevated IgG Rule out all other liver disease Presence of autoimmune antibodies Liver Biopsy is needed to confirm diagnosis
What is the hallmark finding of Autoimmune hepatitis?
Interface hepatitis.
Piecemeal necrosis is defined as the appearance of destroyed hepatocytes and lymphocytic infiltration at the interface between the limiting plate of periportal hepatocyte, parenchymal cells and portal tracts
What is the pathogenesis of auto immune hepatitis?
Unknown mechanism. Genetically predisposed (HLA genes) and then environmental triggers ( viruses, toxins and drugs (Nitrofurantoin, diclofenac, statins, oxyphenisatin)
How is autoimmune hepatitis treated?
Corticosteriods
Azithioprine (steroid sparing agent)
If you don’t take steroid you will DIE.
What are the outcomes with autoimmune hepatitis?
40% will develop cirrhosis
=> oesophageal varacies, ascites, encephalopathy.
Up to 20% spontaneous resolution
If you survive the first 2 years your long tem survival is good
What is primary sclerosing cholangitis?
Autoimmune destructive disease of the Large and medium sized bile ducts.
What is the demographic for primary slerosing cholangitis?
More males than females and many also have UC
How is Primary sclerosing cholangitis diagnosed?
Imaging of billary tree
ERCP or MRCP.
See strictuing and dialitation
What is the treatment for primary sclerosing cholangitis?
Maintain bile flow, monitor for cholangiocarcinoma and colorectal cancer
How does primary sclerosing cholangitis present?
Recurrent cholangitis
What is Haemochromatosis?
Genetic iron overload syndrome.
Monogenetic autosomal recesive disease.
How common is Haemochromatosis?
1 in 200 have gene but it has partial penitrance so clinically far fewer present
What is the presentation of haemachromatosis?
Cirrhosis, cardiomyopathy, pancreatic failure.
Bronzed diabetic
How is haeochromatosis treated?
Venesection. Donate blood every week until you have been iron off loaded
What does the body use iron for?
Producing Haem for muscles and RBCs,
Neutrophil burst is iron dependent
What is WIlsons disease?
Mono- genetic autosomal recessive disease. => Loss of function or loss of protein caeruloplasmin. This is the copper binding protein => loss of copper regulation and tissue disorbtion of copper.
WHat are the clinical signs of wilsons disease?
Neurological
Hepatic- cirrhosis
What are Kaiser Fleisher rings?
Dark rings around the iris of the eye which are due to copper deposition
How is Wilsons disease treated?
Copper chelatio drugs to bind the copper and then excrete
Aviod copper in diet (nuts and chocolate)
What is an Alpha 1 anti trypsin deficiency?
Mutations in the A1AT genes => protein function loss and excess trypsin activity (breakdown of proteins)
What is the clinical presentation of Alpha 1 anti-trypsin deficiency?
Lung emphysema because the protin is broken down. This proetin is then deposited in the liver => cirrhosis
What is the treatment for Alpha 1 anti trypsin deficiency?
Supportive management
What is Budd-Chiari?
Thrombosis of hepatic veins due to congenital webs in the veins or a thrombotic tendency (protein S or C deficiency.
What is the clinical presentation of Budd-Chiari?
Acute = jaundice and tender hepatomegaly Chronic = ascities
How is Budd Chiari diagnosed?
USS of hepaic veins
How is Budd Chiari treated?
Recanulisation or TIPSS
What is methotrexate used to treat and what are the liver consequences?
Used to treat rheumatoid arthritis and psoriasis.
Causes progressive liver fibrosis. Must monitor for fibrosis and be prepared to stop the drug
What is Cardiac Cirrhosis?
Cirrhosis secondary to increased right heart pressures (valvular disease, congenital, rheumatic fever, constrictive pericarditis)
Uncommon in UK
How does cardiac cirrhosis present?
CCF with ascites and liver impairment. Look for a raised JVP. Treated by treating the cardiac cause
Where does the portal vein carry outflow from?
Spleen, oesophagus, stomach, pancreas and small and large intestine
How much blood flows through the liver every minute?
1.5-2 Litres.
75% is from the portal vein
What is the hepatic vein pressure and the portal vein pressure normally?
Hepatic vein =4mmHg
Portal vein =7mmHg
Hepatic artery =100mmHg- drivves flow.
Where are the 4 Portalcaval anastamosis?
Oesophagus,
Umbilicus
Retroperitoneal
Rectum
What is portal hypertension?
Portal pressure > 8mmHg. This creates a greater pressure gradient from portal vein to hepatic vein
What are the causes of portal hypertension??
Cirrhosis (post sinusoidal), schistosomiasis (presinusoidal) and portal thrombosis (prehepatic).
Increased resistance to flow and increased portal flow
Most common demographic of portal thrombosis?
Pre term babies as they had umbilical vein cauterisation.
Why does cirrhosis put you at increased risk of HCC?
Recurrent hepatocyte death and regeneration (recurrent DNA copying)
Inflammation (DNA damage ROS/RNS)
Hepatitis B genome integration into human genome.
Cirrhosis is the 5th most common cause of death. WHat are the most common causes of cirrhosis?
Alcohol,
Hep C
NASH
Is compensated cirrhosis usually and incidental finding?
Yes, patients are normally assyptomatic
What are the 2 types of decompensated cirrhosis or liver failure?
1) Acute on chronic (usually infection or insult) potentially reversible.
2) End stage liver disease. Irreversible
What are the signs of decompensated cirrhosis?
Stigmata of lliver disease + Jaundice Ascites Encephalopathy Easy bruising
What are the stigmata of liver disease?
Spider neavi (blanch) Plamar erythema Clubbing Gynaecomastia Leukonykia Hepatomegaly/Splenomegaly
What are the complications of cirrhosis?
PORTAL HYPERTENTION
=> Ascites, varaceal bleeding and encephalopathy
What is the nutrition advice for those with liver failure?
Energy intake of 35-40kcal/kg and a high protein diet
Small frequent meals and snacks as this reduces fasting gluconeugenesis and muscle catabolis.
?Night feeding or slow release carbs before bed.
Vitamin B, D and calcium suplementation
? fat soluble vitamin deficiency
How does ascites occur?
1) Cirrhosis => portal hypertension.
2) Hepatocellular dysfunction and portosystemic shunting
3) Increased production of vasodilators
4) Arteriolar vasodilation (Decreased SVR and MAP)
5) Activation of arterial baroreceptors (increased heart rate and CO)
6) Activation of RAAS and sympathetics
7) Renal vasoconstriction and sodiuma dn water retention
How is ascites treated?
1) Spirolactone + stop NSAID and reduce salt intake
2) Furusemide
3) Paracentesis
4) TIPSS
5) Transplant
NB: Always look for infection (Spontaneous bacterial peritonitis)
How can you check that the patient is excreting enough sodium and not retaining it?
24 hours urinary sodium excretion (need to excrete >80mmol/day) or a urine spot test where the Na+>K+ as this suggests excretion of >80mmol a day
What type fo drug is spiralactone and why is it used first line?
Aldosterone antagonist. Used because the RAAS system is very active in ascites
What are the risks and benefits of paracentesis?
+ Rapid relief
- Riak of infection/encephalopathy
- Hypovolaemia can result and you must give albumin to replace this in the circulation
How effective is TIPSS in treaing ascites?
60% have no ascites and no diuretics
30% have ascites controlled by diuretics
10% no improvement
What does TIPSS stand for?
Trans-jugular Intra-hepatic PortoSystemic Shunt
What is spontaneous bacterial peritonitis?
Translocated bacteria from the gut cause infection in ascites
How is a spontaneous bacterial peritonitis diagnosed?
Tap and neutrophil count >250 cells
What is the treatment for spontaneous bacterial peritonitis ?
Antibiotics and alba,
Telepressin
Maintain renal perfusion.
What is a complication of Spontaneous Bacterial Peritonitis?
Hepatorenal syndrome
Poor prognosis
When patients with cirrhosis are admitted to hospital, are they all given antibiotics?
Yes to prevent spontaneous bacterial peritonitis
What causes encephalopathy?
Ammonia from dietary intake is shunted from intestine to systemic circulation (due to cirrhosis), bypassing liver which causes disturbances in neurotransmitter trafficking.
Ammonia glutamate/glutamine shuttle
What are the signs of encephalopathy?
Liver flap and confusion.
Beware alcohol with drawl has a fine tremour- not a flap
What is the treatment for enephalopathy?
Look for a cause. Treat with lactulose to clear gut and reduce the transit time (Rifaxamin) Reversible. Keep the small meals up. If spontaneous, consider transplant
How much blood is usually in the oesophageal anastamosis and how much with varacies?
Normal = 2-3ml a minute Varacies = 1.5 L a minute
What is the primary prophylaxis to prevent oesophageal varaceal bleed?
Beta blocker (propranolol) to reduce systemic and portal BP. Elective banding
If you perform a TIPSS procedure, what is the risk of encephalopathy afterwards?
10% because you are forming a shunt past the liver so ammonium from the diet is effecting the brain rather then being metabolised to urea
What happens to prothrombin time in liver failure?
Increases- the patient appears to be anticoagulated.
But they have reduced anticoagulent AND procoagulant factors.
Should all in-patients with cirrhosis get heparin for clots?
Yes unless they have had a varaceal bleed
Why would you consider liver transplant?
1) Event based: Ascites or varaceal bleeds (recurrent)
2) Liver function based: Bilirubin,albumin and PT time (UKELD score)
3) QoL based: itch, lethargy, spontaneous encephalopathy.
What is measured in the UKELD score for liver transplant consideration?
International normalised ratio
Creatinine
Bilirubin
Sodium
What is the general prognosis for liver transplant?
If you can survive the first year, where there is a 10-20% mortality then your long term survival is good
Why is a UKELD score of 49 used?
Because this is the score at which you have a greater chance of death from liver disease than death due to transplant complications.
Can chronic liver patients be on the urgent transplant list?
No- this is only for acute liver failure
When is a UKELD score >49 NOT needed to be listed for elective transplant?
HCC Varient syndromes (Diuretic resistant ascites, Hepatopulmonary syndrome, Chronic hepatic encephalopathy, Polycyctic liver disease, Familial amyloidosis, Primary hyperlipidaemia)
When may you get a synchronous liver and kindey transplant?
Familial amyloidosis as the amyloid produced by the liver damages the kidneys
