Acute Liver Disease Flashcards
What is acute liver failure defined as?
Less than 26 weeks with encephalopathy and impaired function in the absence of cirrhosis or pre-existing liver disease
What are the common causes of acute liver failure?
- Viral hepatitis (A and E)
- Drug-induced hepatitis (acetaminophen)
- Hypoxia-induced liver injury
- Pregnancy-related acute fatty infiltration
- Acute Budd-Chiari syndrome
- Veno-occlusive disease
- Wilson disease
- Right-sided heart failure
- Autoimmune hepatitis
- Mushroom ingestion
- Sepsis
- Heatstroke
What is the most common cause of acute liver failure worldwide?
viral hepatitis A and E
What is the most common cause of acute liver failure in the UK?
Drug induced acetaminophen
What is PT time in the context of liver failure?
One of the best indicators of severity of liver failure For coagulaopathy of vitamin A, D, E and K
List some complications of acute liver failure.
- Encephalopathy
- Coagulopathy
- Hypoglycaemia
- Increased infection risk
What are the symptoms of hepatic encephalopathy?
Arises from high levels of ammonia that can cause:
* Confusion
* Extreme tiredness
* Insomnia/hypersomnia
* Bradykinesia
* Asterixis
* Slurred speech
* Ataxia
* Hyperactive deep tendon reflexes
What are the complications of hepatic encephalopathy?
Cerebral oedema from high ICP
Acute renal failure
Coagulopathy
Metabolic derangement
Haemodynamic changes with peripheral vasodilation, increased heart rate and cardiac output and reduced mean arterial pressure.
What causes exacerbation of hepatic encephalopathy?
GI bleeds
Spontaneous bacterial peritonitis
Renal failure
How is coagulopathy assessed in patients with acute liver failure?
Poor platelet function due to reduced levels of Factor II, VII, IX, and X, protein C and S will cause mucocutanoeus bleeding in gums and teeth and intracranial haemorrhage. This will leads to high PT and INR.
Which prophylactic medication should be initiated for coagulopathy?
PPIs for prophylaxis of GI bleeding
Which complications arise from acute liver failure?
->Sepsis
->Renal failure
->Metabolic disorders with hypoglycaemia
->Cerebral oedema, due to high arterial ammonia, with triggers including hypoxia, systemic hypotension and decreased cerebral perfusion pressure
-> Increaased infection risk due to loss of Kuppfer cell function
What are the features of paracetomol overdose?
Paracetomol overdose can be asymptomatic but develop vomiting and right upper quadrant pain with Janice and encephalopathy from liver damage, and eventually acute kidney injury.
What is the pathophysiology of paracetomol overdose?
With paracetomol overdose, paracetomol is detoxified by gucuronide and sulphate conjugates to be excreted in the urine and a small amount metabolised to form the intermediate NAPQI. However,, in paracetomol overdose, there will be a buildup of NAPQI which can cause hepatocytes cell death.
What is the management for paracetamol overdose?
- GI decontamination with activated charcoal
- IV infusion of acetylcysteine with Glucose infusion
What is the mechanism of action of acetylcysteine?
acetylcysteine is an antioxidant which replenishes cysteine for glutathione synthesis to enable metabolism of paracetomol. This should be followed by glucose infusion.
-> rash is a common side effect so. Treat with chlorphenamine, an anti histamine
What are the features of salicylate poisoning?
Clinical features of salicylate poisoning appear early such as:
- Vomiting
- Dehydration
- Hyperventilation
- Tinnitus
- Vertigo
- Sweating
Patients present initially with respiratory alkalosis due to direct stimulation of central respiratory centres and then develop metabolic acidosis.
What is the management for salicylate poisoning?
*Management is to correct dehydration and provide activated charcoal within an hour of presentation. Bezoar formation of charcoal can slow down release.
*Correct acidosis with IV sodium bicarbonate and monitor for serum hypokalemia
*Dialysis may be required for salicylate level above 500mg, with AKI and heart failure
What investigations are performed for acute liver failure?
- FBC for autoantibodies
- U&Es for paracetamol level and ammonia
- LFTs will show high AST/ALT ratio indicating hepatocellular injury
- PT and INR
- Glucose
- Arterial blood gas for plasma ammonia
*CT head scan to assess for intracranial bleeding and cerebral oedema
What is INR?
INR is the international normalised ratio between Patient PT and the control PT, it should be 1.1 or below.
What does a high INR indicate?
An INR of 2 to 3 indicates reduced clotting time and is normal for those taking warfarin. High INR can be caused by anticoagulants and antiplatelets, liver conditions
What does low INR indicate?
Low INR causes fast clotting and can be caused by high intake of vitamin K rich foods liver, broccoli, chickpeas, green tea, kale, turnip greens
What are the general treatments for acute liver failure?
aggressive fluid resuscitation to prevent renal failure and vasopressor therapy with noradrenaline or dopamine. Broad spectrum antibiotics,
Vitamin K and FFP to treat coaugulopathy
Dextrose solution for hypoglycaemia, Hypoglycaemia is a risk for patients due to impaired glycogen production and gluconeogenesis.
Lactulose diuretic for hepatic encpehalopathy
How is hepatic encephalopathy managed?
Encephalopathy managed with lactulose osmotic diuretic that increases lactic acid production by bacteria which will drive conversion of ammonia -> ammonium and rifaximin antibiotic
What is jaundice?
Hyperbilirubinaemia, visible at levels above 3mg/dl, causing yellow discolouration, however long-standing jaundice can cause a green colour due to biliverdin.
What are the indicators of jaundice?
Jaundice is indicated by:
* bilirubin level greater than 100 micromol/L.
* Has an abnormal clotting profile or shows signs of coagulopathy.
* Has abnormal renal function.
* Is suspected of having taken a paracetamol overdose.
Is frail or has significant co-morbidities.
What causes pre-hepatic jaundice?
Pre-hepatic jaundice is caused by high levels of unconjugated bilirubin, where there are normal ALT/AST levels and ALP/GGT caused by:
* Haemolytic anaemia
* Gilbert’s syndrome
* Crigler-Najjar syndrome
What is Critter-Najjar syndrome?
Inherited autosomal recessive disorder from an absence or decreased activity of UDP-glucuronosyltransferase (UGT) required for Glucoronidation of unconjugated bilirubin in the liver and it allows it to be excreted into bile.
It can cross the blood brain barrier as free bilirubin can easily cross compared to albumin bound and cause neural deficits.
What is the management of Critter-Najjar syndrome?
Management is with phototherapy, plasmapheresis to remove excesss unconjugated bilirubin but the definitive management is liver transplantation
What should be assessed in jaundice?
Clinical presentation includes pruritus and yellow discolouration of the skin. Physical examination includes evaluating body, where a history of arthralgias and myalgias before yellowing indicates hepatitis, either due to drugs or viral infections.
Patient should be questioned about recent blood transfusions, IV drug use, body piercings, tattoos, sexual activity, recent travel abroad and alcohol histotrophic.
What are the causes of hepatocellular jaundice?
High levels of conjugated bilirubin and will have absence of urobilinogen in faeces
- Alcoholic liver disease
- Viral hepatitis
- Iatrogenic medication
- Hereditary haemochromatosis
- Wilson’s disease
*Budd-Chiari syndrome - Hepatocellular carcinoma
What are the features of jaundice with hepatocellular cancer?
With hepatocellular cancer, there may be evidence of decompensation like ascites, variceal bleeding and hepatic encephalopathy
What is post-hepatic jaundice associated with?
Abdominal pain and nausea, arising from gallstones or obstructions, or abdominal masses like lymphomas
Mural causes like cholangiocarcinoma, strictres or drug-induced cholestasis
What are the common signs of decompensated liver function?
- Ascites
- Jaundice
- Encephalopathy
- UGI bleed
What are the red flags indicating severe liver dysfunction?
- Confusion
- Poor coordination
- Asterixis
- Nystagmus
- Bruising
- Purpura
- Petechia
What is the management for jaundice due to gallstones?
Removal through ERCP or stenting
What is the process of bilirubin metabolism?
Bilirubin methanol is begins from breakdown of RBC to release haem -> porphyria to -> unconjugated bilirubin. This is sent to the liver for conjugation by glucoronic acid by UDPGT. Bilirubin Glucoronidation enters the bile and becomes part of the intestinal circulation and is converted by the gut bacteria to urobilinogen to be excreted by the kidneys or -> Stercobilin to form part of faeces and give it the characteristic brown colour.
What causes jaundice in previously stable patients with cirrhosis?
Sepsis, GI bleeding, malignancy from hepatocellular caricnoma and alcohol and drugs.
Which drugs can induce jaundice?
Anti malarias
Paracetomol overdose
Sodium valproate
Statins
Sulphonylureas
Steroids
Fusidic acid
Monoamine oxidase inhibitor
Isoniazid, rifampicin and pyrazinamide
What investigations in the FBC for jaundice?
Full blood count to indetify Haemolysis or infection markers like CRP
-> if ferritin is raised, screen for hereditary haemochromatosis
-> Caeruloplasmin in people under 40 indicates metabolic liver disease
-> alpha-1 antitrypsn can indicate metabolic disease
-> very high ALT over 10000 indicates acute liver injury from drugs, ischaemia or viruses
Coomb’s test for antibodies on surface of RBC indicating haemolytic anaemia
What does raised bilirubin in absence ofc anaemia or haemolytsis?
indicates Gilbert’s syndrome
What LFTs indicate cholestasis?
Cholestasis is indicated by raised ALP, due to primary biliary or sclerosing cholangitis or biliary obstruction.
Hepatitis is indicated by raised ALT and AST, from hepatocellular liver injury, where AST is greater than ALT. Mixed picture may indicate cholestasis and hepatocytes damage. Low serum albumin indicates chronic liver disease
What is the management of jaundice?
*Removal of gallstone through ERCP or stenting
*Treating coauglopathy with *Vitamin K supplementation or fresh frozen plasma infusion
*Treatment of decompensating chronic liver disease with laxatives or rifaximin to reduce amount of ammonia producing bacteria in the bowel which worsens levels of bilirubin
*Mild pruritis treatment with warm or oatmeal baths or antihistamines
Bile acid sequestrants ike cholestyrmaine
What characterizes autoimmune hepatitis?
Chronic and progressive autoimmune mediated inflammation of the liver, more common in young and middle-aged women. It is associated with other inflammatory autoimmune conditions and has an idiopathic aetiology.
Common associations with autoimmune hepatitis is thyoriditis, rheumatoid arthritis, sjogren syndrome and ulcerative colitis .
What is type 1autoimmune hepatitis?
- Type 1: bimodal presentation with specific antibodies, betweeen 10-25 years old and 45-70 years old. Antibodies will be anti-smooth muscle antibodies, ANA and anti-systemic lupus antibodies or LP antibodies
What is Type 2 autoimmune hepatits?
juvenile onset in children under 15 years old. Antibodies are anti-LC1, and anti-LKMI (anti liver kidney microsome type 1)
What is Type 3 autoimmune hepatits?
antibodies directed against soluble liver-kidney antigen
What are the features of autoimmune hepatitis?
Autoantibodies are targeted to liver tissue with lymphoplasmacystic interface hepatitis hwoever this is non specific as it is also present in viral hepatitis. AST and ALT will be high, GGT and total IgG will be raised.
What is the clinical presentation of autoimmune hepatitis?
Fatigue, nausea, weight loss, jaundice, ascites and pruritis
What is autoimmune hepatitis associated with?
Thyroiditis, rheumatoid arthritis, sjogren syndrome and ulcerative colitis .
What is the diagnosis of autoimmune hepatits?
FBC including LFTS, U&Es and antibody screen
-> shows IgG predominant hypergammaglobulinaemia
Liver biospy
What is the investigation of choice in autoimmune hepatitis?
investigation of choice which includes liver ultrasound and FBC.
What is the management of autoimmune hepatitis?
Management is steroid treatment which will cause complete remission. There is an induction high dose of steroid and eventual maintenance dose of steroids and azathriopine immunosuppressant
What is the definitive management for untreated autoimmune hepatitis?
Liver transplantation as there is a risk of liver cirrhosis and death without steroid management
What is the common laboratory finding in autoimmune hepatitis?
IgG predominant hypergammaglobulinaemia
What is the role of lactulose in managing encephalopathy?
It increases lactic acid production by bacteria, converting ammonia to ammonium
What is the significance of an INR above 1.1?
Indicates reduced clotting time
What can cause high serum bilirubin in the absence of hemolysis?
Gilbert’s syndrome
What is the first-line imaging for jaundice?
Ultrasound abdomen
What is the management for pruritus in jaundice?
Warm or oatmeal baths or antihistamines
What is the clinical presentation of Wilson’s disease?
High levels of copper leading to liver damage, neurological symptoms, and psychiatric issues
What is AST and where is it produced?
Aspartate aminotransferase is produced in the liver, heart, and skeletal muscles.
What is the normal range for AST?
Normal range is between 8 to 50 with higher end of range in men.
How does the normal range of AST differ between genders?
AST levels are higher in men than women.
What is ALT and its primary site of production?
Alanine Aminotransferase is produced primarily in the liver.
What is the normal range for ALT?
Normal range is 4 to 36. It may rise with intense exercise, pancreatitis, liver ischaemia and coeliac disease.
What indicates a high AST to ALT ratio?
A high AST to ALT ratio is greater than 2:1.
What is the De Ritis ratio?
The AST/ALT ratio, which increases with alcoholic liver disease, NAFLD, Hepatitis C, alcoholic liver disease, alpha 1 antitrypsin deficiency, haemochromatosis, Wilson disease, Budd-CHiari and vascular disease.
List conditions associated with an increased AST/ALT ratio.
- Alcoholic liver disease
- NAFLD
- Hepatitis C
- Alpha 1 antitrypsin deficiency
- Haemochromatosis
- Wilson disease
- Budd-Chiari syndrome
- Vascular disease
What causes minor elevation of AST/ALT?
- Chronic hepatitis C
- NAFLD
- Statin use
- Haemochromatosis
- Alcohol
What is indicated by major elevation of AST/ALT?
- Ischaemia
- Autoimmune hepatitis
- Fulminant hepatitis
- Flare of chronic hepatitis B
- Biliary obstruction
What does chronic elevation of AST/ALT indicate?
Chronic metabolic disease, cirrhosis, and viruses like Hepatitis C.
What can cause a high AST/ALT ratio unrelated to liver disease?
dermatomoysitis with enzymes are not highly specific to liver synthesizing ability.
What happens to AST and ALP in intrahepatic cholestasis?
AST will be high initially before a rise in ALP.
What is ALP and when is it typically elevated?
ALP is high in third trimester pregnancy and produced from placenta, bone, and liver.
What does GGT indicate when elevated?
GGT rise occurs with alcoholic liver disease or NAFLD.
What components are included in a liver function test?
- Serum bilirubin
- ALT
- AST
- ALP
- GGT
- INR
- Serum albumin
What is the most common drug causing drug-induced liver injury?
Co-amoxiclav, formed of amoxicillin and clavulanic acid. Cl Avila IC acid prevents bacteria breaking down amoxicillin.
Which factors indicate hepatic function?
- Albumin
- PT and INR
- Bilirubin
What vascular dysfunction occurs with ischaemic hepatitis?
Ischaemic hepatitis occurs due to shock
Venous congestion with right sided heart failure and Budd Chiari syndrome
List causes of parenchyma injury in the liver.
- Drug-induced
- Wilson’s disease
- Haemochromatosis
- Alpha 1 antitrypsin deficiency
- NAFLD
What is cholestasis disease characterized by?
Increase in bilirubin, leading to increased expression of ALP and GGT.
What conditions are linked to intrahepatic cholestasis?
- Third trimester pregnancy
- Oral contraceptives
- Primary biliary cholangitis
- Infiltrative diseases like sarcoidosis
Which conditions are linked to extrahepatic cholestasis?
Extrahepatic cholestasis from primary sclerosing cholangitis, choledocholithiasis and pancreatic carcinoma
What indicates unconjugated hyperbilirubinaemia?
Haemolytic anaemia with reduction in haptoglobin (which binds to free RBCs), high levels of LDH nad schistocystes.
What does mixed hyperbilirubinaemia indicate?
Intrahepatic jaundice from hepatocellular injury with an associated ALT and AST rise linked to conditions like autoimmune hepatitis Budd CHiai, fulminant hepatitis or metabolic
What does conjugated hyperbilirubinaemia indicate?
Issues with bile excretion due to cholestasis. There will be a reduction in urobilinogen and Stercobilin so there will be pale stools and dark urine.
What are the drugs linked to hepatic injury?
- Co-amoxiclav
- Paracetamol
- Aspirin
- Tricyclic antidepressants
What is the effect of acute liver disease on urea synthesis?
Impaired urea synthesis leads to a build-up of urea and ammonia.
What is leukocytosis associated with in liver disease?
Infection/inflammation like cholangitis and alcoholic hepatitis.
What is the cause of leukocytopenia in liver disease?
hypersplenism, malnutrition and portal hypertension
What is the significance of PT in acute liver failure?
PT rises quickly in acute liver failure.
What is the role of Vitamin K in liver dysfunction?
Reverses thrombocytopenia only if cholestasis causes malabsorption.
What is the typical management of thrombocytopenia?
Platelet transfusion and TPO injection.
What is fulminant hepatitis characterized by?
Rapid onset of encephalopathy with hepatic synthetic failure.
What precipitates fulminant hepatitis?
Infection, hypokalemia, sedatives, increased protein intake, renal failure.
What is the acronym for fulminant hepatitis?
DAVES:
Drugs like paracetomol and illicit drugs
Alcohol
Hepatitis A, B, C,D E
Epstein Barr virus
Herpes simplex virs
What are precipitating factors for fulminant hepatitis?
- Infection
- Hypokalemia
- Sedatives
- Increased protein intake
- Renal failure
What investigations are included for fulminant hepatitis?
- Urine and serum toxicology screen
- Hepatitis serology
- Ceruloplasmin
- Antinuclear antibodies
- Smooth-muscle antibodies
- Serum protein electrophoresis
- CMV and EBV serology
What are the management strategies for fulminant hepatitis?
- Aggressive fluid resuscitation
- Mechanical ventilation
- Monitoring for intracranial hypertension
What does the King’s College criteria assess?
Need for transplantation in non-fulminant hepatic failure.
What are the aspects of the King’s college criteria?
INR > 6.5 (PT > 100s) or any 3 of the following variables:
age < 10 or > 40 yrs
aetiology – non A, non B hepatitis, halothane hepatitis, idiosyncratic drug reactions
duration of jaundice before encephalopathy > 7 days
INR > 3.5 (PT > 50s)
bilirubin > 300micromol
What is the management for paracetamol overdose?
- Correct dehydration
- Provide activated charcoal within an hour
- Monitor for serum hypokalemia
- bezoar formation of charcoal to slow release
*Correct acidosis with IV sodium bicarbonate and monitor for serum hypokalemia
*Salt restriction and diuretics to decrease ascites
*Frequent glucose monitoring
*Dialysis may be required for salicylate level above 500mg, with AKI and heart failure
What are the acetylcysteine dosage guidelines for paracetamol?
Maximum dose is 4g in 24 hours, with less than 50kg body weight at risk of toxicity. 10g is a toxic dose for everyone heavier than 50kg and risk of hepatic injury.
What are the types of paracetamol overdose?
- Staggered is paracetomol ingested over more than an hour, squally in the context of self harm
- Single acute is excessive amounts of paracetomol ingested over an hour
What is the management for unknown ingestion time of paracetamol?
Start acetylcysteine until history is obtained or hepatic transaminases are less than 50.
What should be done if presenting between 8-24 hours post-ingestion of paracetamol?
Commence NAC infusion and measure paracetamol and ALT/AST levels.
What is the management of single ingestion over 24 hours?
They are at risk of hepatitis injury so immediately start acetylcysteine and check ALT/AST levels and continue infusion for those with persistently high paracetomol concentration over 10mg or ALT is over 50.
How to manage paracetomol concentration double of the Nonogram?
increase the dose of acetylcysyteine
What is post-hepatic jaundice characterised by?
abdominal pain and nausea, arises from gallstonesobstructions from pancreatic cancer or abdominal masses like lymphomas
Mural causes like cholangiocarcinoma, strictres or drug =0nduced cholestasis
What is the clinical presentation of jaundice?
Presentation includes pruritus and yellow discolouration of the skin
Physical examination includes evaluating body, where a history of arthralgias and myalgias before yellowing indicates hepatitis, either due to drugs or viral infections.
Patient should be questioned about recent blood transfusions, IV drug use, body piercings, tattoos, sexual activity, recent travel abroad and alcohol histotrophic.
What is the cycle of bilirubin metabolism?
Bilirubin methanol is begins from breakdown of RBC to release haem -> porphyria to -> unconjugated bilirubin. This is sent to the liver for conjugation by glucoronic acid by UDPGT. Bilirubin Glucoronidation enters the bile and becomes part of the intestinal circulation and is converted by the gut bacteria to urobilinogen to be excreted by the kidneys or -> Stercobilin to form part of faeces and give it the characteristic brown colour.
What is the cause of jaundice in previously stable patinets with cirrhosis?
Sepsis, GI bleeding, malignancy from hepatocellular caricnoma and alcohol and drugs.
What are the signs of decompensated liver failure?
ascites, jaundice, encephalopathy and UGI bleed.
What is acute fatty liver of pregnancy?
An obstetric emergency due to defects in fatty acid metabolism to support faetoplacental growth, but accumulate in hepatocytes to cause cellular damage. There is increased risk with preeclampsia and HELLP syndrome and having a male foetus
What are symptoms of acute fatty liver of pregnancy?
- Nausea
- Vomiting
- Anorexia
- Abdominal pain
- Jaundice
- Ascites
- Coagulation disorders
What is HELLP syndrome?
Severe pre-eclampsia with haemolysis, elevated liver enzymes, and low platelet count.
What is the pathophysiology of HELLP syndrome?
Occurs in third trimester or shortly after childbirth, with increased risk for Oder age and multi parity. There is an ischaemic reperfusion injury triggering inflammatory response due to failure of spiral artery remodelling.
There will be microangiopathic haemolytic anaemia and abnromal oxidation of fatty acids by foetus and release of metabolic intermediates causes liver dysfunction.
How do patients present with HELLP syndrome?
colicky mid-epigastric and/or right upper quadrant pain associated with nausea, vomiting, and fatigue. Associated features may include jaundice, increasing abdominal girth, leg swelling, headache, and visual changes.
Patients may present with severe bleeding, placental abruption, acute kidney injury, liver hematoma, or retinal detachment.
What are the clinical signs of HELPP syndrome?
Patients have hypertensionc with a blood pressure >140/90 mmHg and may have ascites or pedal edema. Right upper quadrant or epigastric tenderness is noted. Icterus may be present.
What virus can cause acute liver failure in immunocompromised individuals?
Herpes simplex virus result in acute liver failure in immunocompromised individuals/pregnant women and neonates.
Presentation includes malaise, fever, pharyngitis and oral/genital ulcers with hepatomegaly and increased levels of ALT and AST showing a hepatitic picture. Treat with antiviral Aciclovir via IV infusion
What is yellow fever?
A mosquito-borne virus causing hepatocyte damage, anpotposis and necrosis of the liver and acute liver failure.
What symptoms are associated with cytomegalovirus infection?
Double stranded DNA virus affecting immunocompromised individuals. There will be Infectious mononucleosis symptoms, fulminant hepatitis, and cholestasis jaundice.
What is infectious mononucleosis syndrome caused by?
Epstein Barr virus characterised by extreme tiredness, fever and sore throat in young people, spread by oral secretion exchange with an incubation period of sitz weeks. It can result in autoimmune haemolytic anaemia of infected hepatocytes and causes a cholestasis pattern of liver injury with an acute onset
