Liver Failure Flashcards
7 key functions of the liver
Synthesis of clotting factors (except factor 8)
Glucose homeostasis (gluconeogenesis, glycogen storage)
Albumin synthesis
Conjugation and clearance of bilirubin
NH3 metabolism (the urea cycle)
Drug metabolism and clearance
Immune (dealing with gut-derived bacteria and bacterial products)
Sequelae of liver failure by system
Brain: hepatic encephalopathy, cerebral oedema, intracranial HTN
Lungs: acute lung injury, ARDS
Heart: high output state, frequent subclinical myocardial injury
Pancreas: pancreatitis (particularly in acetaminophen-related disease)
Adrenal gland: inadequate glucocorticoid production contributing to hypotension
Kidney: frequent dysfunction or failure
Bone marrow: frequent suppression (esp in viral and seronegative disease)
Liver: loss of metabolic function (decreased gluconeogenesis causing hypoglycaemia, decreased lactate clearance causing lactic acidosis, decreased ammonia clearance causing hyperammonaemia, loss synthetic capacity causing coagulopathy), portal HTN
Systemic inflammatory response: high energy expenditure or rate of catabolism
What findings are seen on routine liver function tests (including coags) in liver failure?
Elevated bilirubin (mostly conjugated, as the liver has very high capacity for conjugation)
Liver enzyme patterns: hepatocellular injury or necrosis, intra- or extra-hepatic cholestasis, or mixed picture
Decreased albumin (but half life is 20 days so level can be normal in acute injury)
Clotting profile: INR affected more by liver disease than APTT
Why is INR affected more by liver disease than APTT?
Liver disease results in abnormal coagulation because of a loss of synthetic function (clotting factor production) AND vitamin K deficiency in cholestasis due to poor absorption of fat soluble vitamins
What pattern is seen on LFT in hepatocellular injury or necrosis, and in what pathological processes is this seen?
ALT and AST elevation (ALT predominantly from liver, AST from many sites)
Very high ALTs seen in acute viral hepatitis, acute drug toxicity, ischaemia
What pattern is seen on LFT in intra- or extra-hepatic cholestasis, and in what pathological processes is this seen?
Elevation of ALP (also produced in other tissues, esp bone), elevation of GGT
High ALP, GGT with minor elevation of transaminases typical of biliary obstruction, liver infiltration, cholestatic reactions to drugs
In what pathological processes is a mixed picture seen on LFTs?
Many forms of liver disease including alcoholic liver disease, fatty liver disease
Mrs EH, 45 year old non-smoker and mother of 4 children, employed full-time
PHx: menorrhagia and dysmenorrhoea from fibroids, treated with total abdominal hysterectomy (TAH)
Presented with intermittent abdominal pain post-surgery and admitted for suspected subacute bowel obstruction 4/52 post-TAH; settled with conservative Mx
Presents to ED again 7/52 post-TAH with increasing abdominal pain over 2 days, vomiting, obstipation, anorexia and LOW (10kg over 7/52)
Rx: paracetamol PRN, Mylanta PRN
Allergies: codeine
O/E: not unwell looking, BMI 22, haemodynamically stable, soft non-tender but distended abdomen
Ix: normal FBE, UEC shows K+ 3.3mmol/L, normal LFTs, AXR sows incomplete mid to distal SBO (Gastrografin follow-through requested)
Dx: recurrent subacute bowel obstruction secondary to adhesions from previous TAH
Mx: initially conservative (NGT, IVF and electrolyte replacement, NBM, analgesia in the form of paracetamol 1g QID strict)
Progress: day 1 - refused NGT and Gastrografin follow-through, day 2-4 - vomiting small quantities, accepted NGT, intermittent abdominal pain requiring PO and PR paracetamol, day 5 - laparoscopic division of adhesion, Pfannenstiel incision reopened for division of adhesion to free bowel, day 6-8 - NBM, ongoing post-op pain requiring tramadol and paracetamol 1g QID “strict”, day 9-10 0 haematuria and refused heparin, displaying odd behaviour, oliguria and CP, MET called, increasingly confused and drowsy, LOC, admitted to ICU unconscious and anuric (intubated, ventilated, CVC, CVVH, IDC, IV Abx)
O/E after day 10: jaundice, no signs of CLD, encephalopathic
Ix after day 10: elevated creatinine and lactate, acidotic, increased INR, CXR shows LLL connsolidatio but CTB normal
What do these findings suggest?
Further Ix?
What is the likely cause of Mrs EH’s illness?
Mx?
An acute liver injury
Further Ix: paracetamol levels (elevated), HAV/HBV/HCV (all negative except IgG anti-HAV and HBsAb) serology, liver U/S (normal)
Likely Dx: fulminant hepatic failure secondary to accidental paracetamol poisoning, with associated acute renal failure and HAP
Mx: n-acetylcysteine (NAC) loading dose, coagulation factors, continuous veno-venous haemofiltration (CVVH), IV Abx, sedated with morphine and midazolam, transfer to Austin ICU
What are the 7 most common causes of acute hepatitis?
Acute viral hepatitis
Drug-related
Ischaemic hepatitis
AI
Acute Budd Chiari
Wilson’s disease
Idiopathic
What is CVVH?
Continuous veno-venous haemofiltration is a temporary treatment for patients with acute renal failure who are unable to tolerate haemodialysis and are unstable
What are the criteria for transferring a patient to a liver transplant unit?
Avoid late referral and transfer of unstable patients
Criteria for transfer:
INR >1.5 and rising (except paracetamol overdose)
Any encephalopathy
Poor prognosis
Mrs EH’s progress:
Day 11 - transferred to Austin Hospital ICU for NAC infusion, correction of coagulopathy, paralysed and ventilated, mannitol infusion, CVVH (lactate free), hypernatraemia target (145-155mmol/L), develops hypothermia, referred to neurosurgery for intracranial pressure monitor insertion, urgently assessed and listed for liver transplantation
Day 12 - deterioration overnight (fixed dilated pupils, absent brainstem reflexes, ongoing sepsis with increasing NA requirements, persistent lactic acidosis), donor organ becomes available but patient assessed as too unstable for transplant, family meeting comes to decision to limit treatment and patient dies at 10:15
Post-mortem histology shows massive panlobular necrosis with relative preservation of portal tracts and hepatic necrosis with mild fatty changes; post-mortem findings include a) multi-system organ failure, b) fulminant hepatocellular necrosis and c) evidence of paracetamol toxicity
Pathologist comment: “ingestion of 10 or more standard tablets may result in fulminant hepatic failure resulting in death within 5-7/7 if unchecked”
When should the daily dose of paracetamol be reduced?
People who are fasting
Heavy EtOH users
Patients taking medications that induce cytochrome p450
Prolonged starvation (depleted hepatic glutathione stores)
Histopathology: describe the findings
Massive panlobular necrosis with relative preservation of portal tracts
Hepatic necrosis with mild fatty changes
What can increase susceptibility to paracetamol poisoning?
Prolonged starvation including fasting (depletes hepatic glutathione stores)
Heavy alcohol use
Patients taking medications that induce cytochrome p450
What is usually found on testing in the setting of paracetamol poisoning?
Large rises in serum transaminases
Define acute liver failure
Rapid deteriorating of liver function in previously normal liver
Jaundice to encephalopathy generally occurs within 8 weeks
What are the guidelines for acute liver failure?
INR >1.5
Any encephalopathy
Duration of illness (jaundice) up to 26 weeks
What % of liver transplants does acute liver failure account for?
5-8%
How common is ALF?
Rare
What is the prognosis of ALF?
>80% died in pre-transplant era
Survival now >70% in most leading centres
45% survival without transplant (probably reflects both availability of transplant as rescue therapy and improved medical Mx)
Outcome highly dependent on aetiology and rate of progression
Describe the common aetiologies of acute liver failure
Viral hepatitis
Paracetamol
Other drugs
What are King’s college criteria for early indices of poor prognosis in acute liver failure (non-paracetamol)?
Platelets >100 (INR >6.5), irrespective of hepatic encephalopathy (HE) grade
Or any 3 out the 5 following:
Unfavourable aetiology (seronegative hepatitis, Wilson’s disease, idiosyncratic drug reaction, halothane)
Age less than 10 or >40
Jaundice to encephalopathy interval >7 days
Platelets >50 (INR >3.5)
Bilirubin >300 umol/L
Describe the interventions and their benefit in 6 common causes of acute liver failure
List 6 causes of acute liver failure in order of best to worst prognosis (measured by % survival)
Paracetamol OD
Hepatitis A and E
Hepatitis B
Non A-non B hepatitis
Drug reactions
Wilson’s disease
What is the role of biopsy in acute liver failure?
Quantify extent of liver injury
Establish aetiology
Guide to treatment
What are the 2 general guidelines for liver transplantation in fulminant hepatic failure?
Timing is critical:
Select and list patients with poor prognosis as early as possible to optimise chance of obtaining donor liver
Do not transplant those in whom survival or neurological recovery is unlikely
What is King’s College Criteria best for?
Identifying FHF patients with poor prognosis who need transplantation
Outline the King’s College Criteria for liver transplantation in FHF
- Paracetamol OD
- pH less than 7.30 (irrespective of grade of encephalopathy) after fluid resuscitation
OR
- PT time >100 secs, and serum creatinine >300 umol/L
- In patients with grade III or IV encephalopathy
What is a toxic dose of paracetamol?
200 mg/kg or 10g, whichever is less
What is the antidote for paracetamol OD? How effective is it?
N-acetylcysteine (NAC)
100% effective if given within 8/24 of ingestion, regardless of dose ingested
Describe the epidemiology of paracetamol-induced FHF
Occurs generally in the young
Female predominance
Accidental OD is not uncommon (significantly higher grade of encephalopathy in the accidental group)
Association with alcohol and starvation
May occur in the hospital setting
How does paracetamol OD commonly occur in the hospital setting?
Prolonged courses in fasting individuals (at therapeutic doses)
Supra-therapeutic doses (often in short courses), esp in alcoholics
What % of paracetamol ODs are accidental?
10-20%
What are the most common drug classes in OD?
Analgesics (e.g. paracetamol)
Antipsychotics (e.g. quetiapine)
Antidepressants
Sedatives
Drugs of abuse
Describe normal paracetamol metabolism
How does NAC act as an antidote for paracetamol OD?
Acts as glutathione donor and reduces the production of toxic metabolite NAPQI
Describe paracetamol metabolism in the setting of glutathione depletion
Describe the principles of Mx of paracetamol OD
Prevention of absorption: administer activated charcoal within 60 mins of ingestion
Symptomatic care: anti-emetics
Risk assessment: dose based/plasma paracetamol concentration
Specific care: NAC
Other activities: psychological assessment following deliberate self-poisoning, toxicovigilance, chronic/occupational poisonings, follow local and regional guidelines, ensure antidote is stocked, assay advice
What doses of paracetamol can result in OD if ingestion is staggered?
24 hrs: 200 mg/kg or 10g, whichever is less
48 hrs: 150 mg/kg or 6kg per day, whichever is less
>48 hrs: 100 mg/kg or 4g per day, whichever is less
Describe the acute Mx of paracetamol OD
Describe Mx of repeated supratherapeutic ingestion of paracetamol
45 year old male, married with 3 school-age kids, electronic engineer with telstra, on no medications
Presents feeling tired with swollen ankles
O/E: obese (BMI 32), firm hepatomegaly, spider naevi, icterus
What further Hx is important?
Alcohol Hx
Hx of transfusions, vaccinations, unprotected sex (including high risk)
Drug Hx (including IVDU)
45 year old male, married with 3 school-age kids, electronic engineer with telstra, on no medications
Presents feeling tired with swollen ankles
O/E: obese (BMI 32), firm hepatomegaly, spider naevi, icterus
Alcohol Hx: drinks 6 cans beer/night with additional bottle of wine on weekends, loss of licence for drunk driving twice
Blood transfusion after MVA 1994 (no other RFs for viral hepatitis)
Rx: takes multivitamins, no prescribed medication
What baseline tests are used to confirm the Dx?
Abdominal U/S
FBE, LFTs, coagulation profile
45 year old male, married with 3 school-age kids, electronic engineer with telstra, on no medications
Presents feeling tired with swollen ankles
O/E: obese (BMI 32), firm hepatomegaly, spider naevi, icterus
Abdominal U/S: liver demonstrates coarsened echotexture and nodular surface, main portal vein is large at 1.6 cm but does demonstrate antegrade flow, no filling defects were identified within the portal vein, mid-portion of bile duct was identified which measures approximately 3 mm, no free fluid seen, spleen grossly enlarged at 15 cm, no patent para-umbilical vein and no varices identified, gallbladder is collapsed but there is an apparent polyp within the fundal region
Summarise these findings
Nodular coarse liver in keeping with cirrhosis + splenomegaly
Large portal vein with no apparent filling defect
45 year old male, married with 3 school-age kids, electronic engineer with telstra, on no medications
Presents feeling tired with swollen ankles
O/E: obese (BMI 32), firm hepatomegaly, spider naevi, icterus
Abdominal U/S: nodular coarse liver in keeping with cirrhosis + splenomegaly, large portal vein with no apparent filling defect
What findings would you expect on FBE, LFTs and coags?
Decreased platelets
May be mildly decreased Hb, WCC
Decreased albumin
Elevated bilirubin
Elevated ALP
Elevated GGT (alcohol is an inducer)
Mildly elevated serum transaminases
Increased INR
45 year old male, married with 3 school-age kids, electronic engineer with telstra, on no medications
Presents feeling tired with swollen ankles
O/E: obese (BMI 32), firm hepatomegaly, spider naevi, icterus
Abdominal U/S: nodular coarse liver in keeping with cirrhosis + splenomegaly, large portal vein with no apparent filling defect
What other Ix are required for this patient’s work-up?
Viral hepatitis: HCV Ab, HBsAg, HBcAb, HBsAb
Caeruloplasmin (Wilson’s)
a1-AT
Iron studies
AI screen: ANA, SMA, AMA, IgG
45 year old male, married with 3 school-age kids, electronic engineer with telstra, on no medications
Presents feeling tired with swollen ankles
Hx of alcohol abuse
O/E: obese (BMI 32), firm hepatomegaly, spider naevi, icterus
Abdominal U/S: nodular coarse liver in keeping with cirrhosis + splenomegaly, large portal vein with no apparent filling defect
Dx? Is a liver biopsy needed to confirm?
Cirrhosis secondary to alcohol (with possible component from NASH)
Liver biopsy may help to confirm if cause unclear; but remember that once the liver is cirrhotic it is usually not apparent what the underlying cause is
What are the most common causes of chronic liver disease?
Rules of 3s:
Most common: alcohol(/non-alcohol increasingly), HBV, HCV
Genetic: Wilson’s, haemochromatosis, a1-AT deficiency
AI: PBC, PSC, AI hepatitis
Other: NASH, drugs, Budd Chiari syndrome
What are the potential complications of chronic liver failure and what Mx is indicated?
Hepatoma: screening indicated
Variceal bleeding: screening indicated
Ascites: prophylactic Abx indicated
45 year old male, married with 3 school-age kids, electronic engineer with telstra, recently diagnosed with cirrhosis secondary to alcohol + NASH
Patient keeps drinking and 3/12 later presents more unwell
O/E: disoriented, swollen abdomen, distended abdominal wall veins, spontaneous bruising on arms
Pathophysiology of these signs?
Disoriented: hepatic encephalopathy
Swollen abdomen: ascites (synthetic failure leading to decreased oncotic pressure +/- increased hydrostatic pressure due to portal congestion)
Distended abdominal wall veins: recanalisation of paraumbilical veins due to portal HTN
Spontaneous bruising: synthetic failure leading to decreased production of clotting factors, platelet sequestration in spleen and decreased TPO
