Block 5: liver Flashcards
(50 cards)
1
Q
Liver disease most common cause
A
Commonest cause of liver disease in non-alcoholic fatty liver disease (NAFLD). Most common cause of death in lifer disease is alcohol related
2
Q
Diseases alcohol can cause
A
- Mouth, throat, stomach, liver and breast cancer
- Cirrhosis of the liver
- Heart disease
- Depression
- Stroke
- Pancreatitis
- Liver disease
3
Q
Recommended alcohol units and measures to reduce alcohol consumption
A
Recommended: men and women 14 units a week, spread over several days
Measures to reduce alcohol consumption:
- Brief interventions: use of AUDIT-C questionnaire, CQUINN target in hospital
- Public health campaigns around counting units
- Minimum unit pricing: 50p per unit
4
Q
Risk factors for NAFLD
A
Other factors associated with increasing mortality rates in liver disease: obesity (increases NAFLD), chronic viral hepatitis
Risk factors for NAFLD:
- Obesity/overweight: central/visceral, 80% of those with a BMI >30 have NAFLD
- T2DM/Insulin resistance: 70% of those with T2DM have NAFLD
- Metabolic syndrome
- Increasing age
- Males>females
- Sedentary individuals
5
Q
Chronic viral hepatitis
A
- Hepatitis C is rare in the UK
- Approx 30% will develop cirrhosis after 20-30 years
- Have increased risk of liver cancer and cirrhosis if untreated
- Increased prevalence of hepatitis B due to immigration: can get cancer without being cirrhotis
6
Q
How does liver disease present
A
- Often asymptomatic
- Incidental findings: abnormal LFT’s, Hepatosplenomegaly/ incidental finding on imaging, Raised MCV, abnormal clotting, low platelets
- Screening for NAFLD in T2DM and screening for hepatitis viruses
- Non-specific symptoms: anorexia, weight loss, lethargy
- Specific liver symptoms: jaundice, pruritis, bleeding varices, ascites/oedema, encephalopathy
7
Q
Causes of chronic liver disease
A
- Alcohol
- NAFLD
- Viral hepatitis
- Genetic- haemochromatosis, Wilsons
- Autoimmune: autoimmune hepatitis, primary sclerosis cholangitis, primary biliary cholangitis
- Alpha 1 antitrypsin liver disease
8
Q
Liver disease: what to ask about in a history
A
- Alcohol (ARLD)
- Weight/T2DM (NAFLD)
- Previous jaundice (viral hep/gallstones)
- Transfusion/injections (Hepatitis B and C)
- Family history (Haemochromatosis, Wilson’s disease, Haemolysis)
- Travel history (Viral hepatitis, Schistosomiasis)
- Previous surgery (Biliary stricture, retained stones, hepatic metastases)
- Drugs: methotrexate, nitrofurantoin
- Sexual orientation/contacts: Hep B, HIV
- Occupation: ARLD (pubs), toxins, viral hep, health care
- Sport: anabolic steroids
9
Q
Symptoms connected with different disorders in liver disease
A
- Abdo pain, fever, rigors: biliary colic, cholangitis
- Pruritis: cholestatic disease
- Arthritis/Arthralgia: Haemochromatosis, autoimmune hepatitis, Hepatitis B
- Pigmentation: PBC, Haemochromatosis
- Bloody diarrhoea: PSC (IBD patients)
- Weight loss: malignancy/end stage cirrhosis
- SOB, emphysema: AAT deficiency
- Dry eyes/mouth: PBC
10
Q
Causes of acute liver failure
A
- paracetamol overdose- biggest cause in the UK
- Statins, NSAID’s, chemotherapy, mushroom poisoning
- alcohol
- viral hepatitis (usually A or B)- biggest cause worldwide
- acute fatty liver of pregnancy, HELLP, Pre-eclamptic liver rupture
- Other: Wilsons disease, autoimmune lymphoma, malignancy
- Vascular: budd-chiari syndrome, hypoxic hepatitis
11
Q
Features of acute liver failure
A
- Jaundice
- coagulopathy: raised prothrombin time
- hypoalbuminaemia
- hepatic encephalopathy
- renal failure is common (‘hepatorenal syndrome’)
12
Q
What is acute liver failure
A
- No underlying chronic liver disease
- Biochemical evidence of liver injury/damage
- Impaired liver function: high bilirubin, jaundice
- AND hepatic encephalopathy within 8 weeks of symptom onset
- A potentially reversible condition due to severe liver injury
- Without encephalopathy its acute liver injury
13
Q
Hepatic encephalopathy grade 1
A
- Conscious level: sleep reversal, restless
- Personality: forgetful, agitated, irritable
- Neurological signs: Tremor, apraxia, incoordination, impaired handwriting
- EEG: Triphasic waves (5Hz)
14
Q
Hepatic encephalopathy grade 2
A
- Conscious level: Lethargy, slowed
- Personality: disorientated, loss of inhibition, inappropriate behaviour
- Neurological signs: asterixis (liver flap), dysarthria, ataxia, hyporeflexes
- EEG: Triphasic waves (5Hz)
15
Q
HE grade 3
A
- Conscious level: sleepy, confused
- Personality: disorientated, aggressive
- Neurological signs: Asterixis, muscular rigidity, extensor planters, hyperreactive reflexes
- EEG: triphasic waves (5Hz)
16
Q
Hepatic encephalopathy grade 4
A
- Conscious level: coma
- Personality: none
- Neurological signs: Decerebration
- EEG: delta slow waves
17
Q
Acute liver failure progression
A
- Elevated transaminases, asymptomatic
- Acute liver injury: Progressive jaundice, elevated transaminases, coagulopathy (INR >1.5)
- Hepatic encephalopathy, acute liver failure
- Multi-system failure
- Death
Categories in ALF: hyper-acute, acute and subacute
18
Q
Hyperacute LF
A
- A jaundice to HE time of <=7 days, classically paracetamol overdose, greater chance of transplant free survival
- Bloods: significant rise in ALT, low/moderate rise in bilirubin, marked prolongation in PT
19
Q
Acute LF
A
- Jaundice to hepatic encephalopathy time 8-28 days
- Classically due to Hep B
- Typically more jaundiced than hyperacute with a moderate chance of transplant free survival
20
Q
Subacute LF
A
- J to HE time typically from 4-8 weeks, can be up to 28. Beyond 28 weeks suggests chronic liver disease
- Characterized by deep jaundice, low transaminases and less marked coagulopathy.
- May have splenomegaly, ascites and shrinking liver volume so hard to differentiate from cirrhosis.
- Very poor non-transplant survival rate, classically caused by Drug induced liver injury or non A-E hepatitis
21
Q
Paretamol toxicity
A
- Hyperacute course of ALF with ALT >1000, raised lactate with increased risk of kidney injury and cerebral oedema. Best rates if transplant free survival
- A paracetamol level and Tox screen should be check on admission for acute liver injury/failure
- About 10-15gm of paracetamol is enough to cause hepatotoxicity due to metabolic activation of paracetamol
- N-acetylcysteine (NAC) is an effective antidote within the therapeutic window
- Why overdose on paracetamol: its cheap, easy to get and effective in overdose
22
Q
Paracetamol metabolism
A
- Paracetamol is metabolised by cytochrome P450 to the toxic metabolite is N-acetyl-p-denzoquinoneimine
- NAPQI: causes direct oxidative stress, mitochondrial dysfunction and an immune reaction
- Glutathione binds NAPQI and limits toxicity, in overdose Glutathione is depleted which can cause massive hepatocyte necrosis
23
Q
Presentation of paracetamol overdose
A
- Early <8 hours: vague symptoms i.e. N+V, metabolic acidosis/coma if paracetamol levels >800mg
- 12-36 hours: no sx, present for tx, have abdo pain
- 24-72 hours: hepatic failure: coagulopathy, deranged LFT’s, hypoglycaemia, RUQ pain, jaundice, N&V, renal failure
- Complications: loss of hepatocyte metabolic function, coagulopathy, lactic acidosis, hypoglycaemia, HE, massive systemic inflammatory response, multi-organ failure
24
Q
Outcomes in paracetamol overdose
A
Patients presenting with an unintentional paracetamol overdose: Tend to have poorer outcomes in terms of transplant free survival as its often staggered. Tend to be older, abuse alcohol and present with significant kidney injury, More likely to develop encephalopathy
25
Non paracetamol drug induced ALF
- Currently a diagnosis of exclusion- no blood tests that can confirm diagnosis
- Drug history over the last 6 months: prescribed, OTC, herbal and illicit
- HEV can mimic DILI- routinely check HEV IgM in routine acute liver screen
- <10% progress to ALF but 80% die or require transplantation
26
Drugs that cause non paracetamol drug induced ALF
- Cautions: antituberculosis drugs, antibiotics (nitrofurantoin), co-amoxiclav, Flucloxacillin, antiepileptics (phenytoin and valproate), NSAID’s
- Cocaine and MDMA can cause acute ischaemic injury and hypoperfusion
27
Viral hepatitis: HAV and HBV
- HAV: <1% will develop ALF. A hyperacute or acute course. More common in elderly
- HBV: new infection, delta superinfection or reactivation. <4% of HBV cases will develop ALF. Mortality higher than in other viral causes
28
Viral hepatitis: HEV and other
- HEV: more common in those who have travelled to endemic areas i.e. India than those with autochthonous infection. Hyperacute/acute presentation. And have genotype 1 or two infection. High mortality rate in pregnancy. The genotypes in the UK (3 or 4) are more likely to cause chronic infection especially in the immunosuppressed
- Other: HSV1, HSV2, VZV, CMV, EBV
29
Indeterminate ALF
- Acute/subacute phenotype
- 20% transplant free survival rate
- Proposed causes: exposure to drug/toxin, viral agent, autoimmune, paracetamol toxicity. Unlikely to be one cause
- When no known cause
- Have small shrunken livers and signs of portal hypertension
- Second most common cause of ALF
- No found cause
30
Autoimmune hepatitis
- Less common cause of ALF
- Consider if presence of other autoimmune disease and if female
- Typically elevated IgG and positive autoantibodies but can be absent (anti-nuclear, anti-smooth muscle)
- Liver biopsy may be required
31
Pregnancy related acute liver failure
- Flare of known liver disease, co-incidental onset of liver disease in pregnancy or pregnancy related liver disease. Can cause ALF
- Pregnancy related liver disease: Hyperemesis gravidarum, Pre-eclampsia and eclampsia (with hepatic rupture), HELLP syndrome, acute fatty liver of pregnancy (AFLP)
- Hyperemesis gravidarum- can cause raised transaminases, synthetic liver failure does not occur so ALI or ALF does not rise
- AFLP: occurs in third trimester in genetically predisposed women with mitochondrial defects, causes significant perinatal and maternal mortality
- HELLP occurs in third trimester resulting in hepatic ischaemia
32
Ischaemic hepatitis and malignant infiltration of the liver
- Ischaemic hepatitis: most common cause of acute transaminitis in hospital but rarely progresses to ALF
- Malignant infiltration of the liver: i.e. in breast cancer can cause ALF. Treatment options are limited and transplantation is not an option
33
Miscellaneous causes of acute liver failure 2
- Toxins: causing ALF include cocaine, ectasy, herbal remedies and mushroom poisoning
- Budd-Chiari syndrome: presents with ALF with previous hepatic vein thrombosis and thrombosis of the patent hepatic vein
- Wilson disease: rare cause of ALF. Consider in young patients with low/normal ALP, haemolytic anaemia and possibly neuro-psychiatric features
34
Initial investigations in ALF: assess disease severity
- PT or INR: on admission and every 6 hours
- Liver blood tests: sone every 6 hours, important to look at bilirubin
- Renal function: urine output (hourly), urea, creatinine. Renal dysfunction is a marker of poor prognosis
- Arterial blood gas and lactate
- Arterial ammonia: shows what patients with encephalopathy are at higher risk of cerebral oedema, intracranial hypertension, cerebral herniation and death
35
Investigations in ALF: causes
- Paracetamol serum level
- Toxicology screen in urine
- Virology: HBsAg, anti-HBc IgM, HDV if positive for HBV
- anti HAV IgM, anti HEV IgM, anti-HSV IgM, anti-VZV IgM, CMV, HSV, EBV, parvovirus and VZV PCR
- Autoimmune markers: anti-smooth muscle, anti-nuclear
- Abdominal imaging: Ultrasound
Tests for complications: Lipase or amylase to show pancreatitis
36
Conditions that may affect decisions in emergency liver transplants
- History of chronic liver disease
- Active and dependent alcohol or substance misuse
- History of cancer in recent past
- Severe congestive heart disease or respiratory co-morbidity
37
Immediate management of ALF at presentation
- Screen intensively for hepatic encephalopathy: shows rapid progression of disease (ALF)
- Assess suitability for liver transplant
- Transfer to tertiary liver/transplant centre even if contraindications
- Transfer to specialised unit early: if the patient has an INR >1.5 and onset of hepatic encephalopathy or other poor prognostic features
38
Initial treatment in ALF
- Manage in critical care environment
- N-acetyl cysteine in paracetamol overdose: continue until PT <20 or up to 5 days
- Aggressive fluid resus
- Glucose (10-20%) infusions for hypoglycaemia
- Intubation and ventilation for encephalopathy that is threatening their airway- reduces cerebral oedema risk
- Avoid hepatoxic and sedative drugs
- Broad spectrum antibiotics and antifungals
- Inotropes and if hypotensive despite resuscitation
- Early CVVH (continuous veno-venous hemofiltration) to control acidosis/ammonia
- Stress ulcer prophylaxis
39
Complications of acute liver failure
- Metabolic: hypoglycaemia, hyponatraemia, hypophospataemia, Hypokalaemia
- Pulmonary: Pneumopathy, acute respiratory distress syndrome, pulmonary overload
- Haemodynamic: Hyperkinetic syndrome, Arrhythmia
- Infection: Bacterial, fungal, pneumopathy, septicaemia, urinary infection
- Renal: low threshold for RRT
- Coagulation/haemostasis: unbalanced haemostasis, thrombocytopenia (low platelet count and prolonged PT)
- Neurological: cerebral oedema, cranial hypertension, brain death
40
Brain in ALF
- Worst complication is intracranial hypertension due to HE which can cause coning and brainstem death
- Brain oedema-induced ICH is a classic complication of HE in ALF
- Due to astrocyte swelling associated with hyperammonaemia
- Incidence of ICH has decreased recently
- More likely to affect patients with Grade 3 or 4 HE
- Risk of ICH is highest in patients with: hyperacute or acute phenotype, younger age, renal impairement, need for inotropic support, persistent elevation of arterial ammonia >150-200
41
N-acetylcysteine in ALF
- Only effective antidote to paracetamol overdose by minimising hepatocyte injury
- Prevents glutathione depletion
- Virtually complete protection if given <8-10 hours post overdose
- Start without delay in staggered overdose
- Side effects are common: treat with antihistamine and slowing rate of infusion
- Can be effective in mushroom poisoning and DILI
42
Specific management for different causes of ALF 1
- Paracetamol toxicity: N-acetylcysteine
- Ischaemic/hypoxic: circulatory support, statin, transplant often not an option
- Pregnancy related (HELLP, AFLP): early delivery, transplant in post partum deterioration
- Hepatitis B: Nucleotide analogues
43
Specific management for different causes of ALF 2
- Hepatitis E: Ribavirin
- HSV/VZV: Aciclovir
- Wilsons disease: transplant, no other treatment
- Autoimmune hepatitis: steroids if no HE otherwise transplant
- DILI: withdraw offending drug, steroids if DRESS
- Budd-Chiari syndrome: TIPSS, hepatic vein stenting, thrombolysis
44
Paracetamol and hyperacute criteria for referral to transplant centres- more likely to survive without transplant:
- Arterial pH <7.30 or HCO3 <18
- INR >3.0 day 2 or >4.0 thereafter
- Oliguria and/or elevated creatinine, renal failure
- Altered level of consciousness
- Hypoglycaemia
- Elevated lactate unresponsive to fluid resuscitation
45
Non-paracetamol criteria for referral to a transplant centre
- pH <7.30 or HCO3 <18
- INR >1.8
- Oliguria/renal failure or Na <130 mmol/l
- Encephalopathy, hypoglycaemia or
- Bilirubin >300 μmol/l (17.6 mg/dl)
- Shrinking liver size
46
Selection for LTx depends on
- 1 year survival following emergency LTx for ALF is now 80%
- Accurate prediction of survival without transplant
- Consideration of the survival potential after LTx
- Consideration of whether a patient is too sick to transplant
47
Kings college criteria for liver transplant: ALF due to paracetamol
- Arterial pH <7.3 after resuscitation and >24 hours since ingestion
- Lactate >3 mmol/L or
- The 3 following criteria: HE >Grade 3, Serum creatinine >300 µmol/L, INR >6.5
- Patients can be put on the super urgent transplant list
48
Kings college criteria for liver transplant: ALF not due to paracetamol
- INR >6.5 or
- 3 out of 5 following criteria: Aetiology: indeterminate aetiology, hepatitis, drug-induced hepatitis, Age <10 years or >40 years, Interval between jaundice and encephalopathy >7 days, Bilirubin >300 µmol/L, INR >3.5
- Patients can be put on the supe urgent transplant list
49
Medical contraindication to liver transplantations
- Untreated or progressive infection
- Clinically apparent extrahepatic or metastatic malignancy: any malignancy in the last 5 years
- Progressive hypotension, resistant to vasopressor support
- Clinically significant ARDS, FiO2 > 0.8
- Fixed dilated pupils > 1 hour in the absence of thiopentone
- Severe coexistent cardiopulmonary disease
- HIV- relative contraindication
50
Psychiatric contraindications to liver transplant
- Multiple episodes of self harm (>5) with an established pattern of behaviour esp if non drug methods used
- Consistently stated wish to die in the absence of an established mental illness
- Chronic refractory schizophrenia or other mental ilness, resistant to therapy
- Incapacitating dementia or mental retardation
- Active IV drug abuse or oral polydrug use
- Alcohol dependence or abuse
- Established pattern of non-compliance with treatment
