Liver disease

In today's episode of categorise or die, we're splitting the liver's numerous functions into synthesis, storage and metabolism and clearance.

Synthesis

• Albumin
• CRP
• Clotting factors
• Bile acids
• Antithrombin III
• Immunoglobulins
• Lymph

Storage

• Iron
• Vitamins
• Glycogen

Metabolism and clearance

• Carbohydrate
• Protein
• Fat
• Bilirubin
• Hormones
• Drugs

If you're answering this question as part of a CRQ, give at least one answer from each section, as sometimes they limit the number of marks awarded to each of them.

• Also referred to as fulminant liver failure
• Jaundice, coagulopathy and encephalopathy
• This has to be new onset - i.e. the liver was alright before

We use the O'Grady classification, which measures time from jaundice to encephalopathy:

• Hyperacute = <7 days
• Acute = <4 weeks
• Sub-acute = <12 weeks

• This is a much slower, grumbling process of deteroration that occurs over at least 28 weeks or 6 months depending on which source you're using
• Here there is a progressive destruction of the liver's architecture, with chronic inflammation resulting in previously healthy tissue being replaced by nodules of fibrosis
• This in turn leads to a steady decline in liver function
• Chronic liver disease is either compensated, with no symptoms and normal(ish) LFTs, or decompensated, with jaundice, variceal bleeding, ascites or encephalopathy

Frequently the journey of chronic liver disease is studded with episodes of acute functional deterioration, which we refer to as acute-on-chronic liver disease.

Acute on chronic liver failure carries high mortality with often multiple organ dysfunction.

• Viral hepatitis
• Autoimmune hepatitis
• Alcoholic liver disease
• Cryptogenic liver disease
• Primary biliary cirrhosis
• Sclerosing cholangitis
• Venous outflow obstruction
• Drugs
• Metabolic disease (Wilson's, haemochromatosis, alpha-1-antitrypsin deficiency)

This is an enormous answer, so break it down by system, and give one or two examples from each.

Cardiovascular

• Increased cardiac output and lower systemic vascular resistance (hyperdynamic circulation)
• Splanchnic vasodilatation and functional hypovolaemia
• Diastolic dysfunction, QT prolongation and poor response to stress (cirrhotic cardiomyopathy)

Respiratory

• Ascites can cause diaphragmatic splinting and reduction in FRC
• Pleural effusions (hepatic hydrothorax)
• Hepatopulmonary syndrome (due to arteriovenous shunting within the lung)
• Portopulmonary hypertension (pulmonary vasoconstriction and vascular remodelling)

Gastro

• Varices
• Splenomegaly
• Ascites
• Spontaneous Bacterial Peritonitis

Renal

• Hepatorenal syndrome

Haematological

• Anaemia
• Coagulopathy
• Hypofibrinoginaemia
• Thrombocytopenia

Neuro

• Hepatic encephalopathy (reversible encephalopathy due to accumulation of ammonia, short-chain fatty acids and mercaptans)
• Asterixis

Endocrine

• Hypoglycaemia
• Hypoalbuminaemia
• Adrenal insufficiency
• Secondary hyperaldosteronism leading to water retention and hyponatraemia

Other

• Malnutrition
• Muscle wasting
• Poor wound healing

Deranged procoagulant factors

• Hypofibrinogenaemia
• Vitamin K deficiency
• Thrombocytopenia
• Reduced thrombopoeitin
• Reduced factors 2, 5, 7, 9, 10 and 11
• Increased t-PA

Deranged anticoagulant factors

• Increased vWF
• Reduced protein C
• Reduced protein S
• Reduced antithrombin
• Reduced plasminogen

• Severity of disease
• Extrahepatic manifestations
• Evidence of decompensation
• Sepsis
• Steroids
• Ascites
• Pleural effusion

• Full blood count
• Urea, creatinine and electrolytes
• Liver function tests
• Clotting
• ECG
• Echocardiography
• CPET
• ABG
• Chest Xray
• Ultrasound abdomen to assess portal venous pressures

Patients with chronic liver disease tend to reach a strange semi-stable 'balance' in which they're not substantially more likely to clot or to bleed than other patients.

The reason they have such spectacular GI bleeds generally comes as a result of raised portal venous pressure and splanchnic congestion, rather than an inability to clot properly.

As a result, we shouldn't reflexively manage raised INRs with FFP or cryoprecipitate. Not only do these not do much below an INR of around 1.7, it doesn't seem to help anyway.

TEG or ROTEM are generally much better options to allow you to correct abnormalities on the fly.

That being said, there are several things that you can do if you're worried about coagulopathy:

• Vitamin K - will help with nutritional/bile salt deficiency, but won't do much if they've got substantial hepatic synthetic failure
• FFP - if actively bleeding with a prolonged PT
• Platelets - if less than 50 000 and actively bleeding or major surgery
• Cryoprecipitate - if you're struggling

• All your standard AAGBI monitoring - ECG, BP, Saturations, ETCO2 etc
• Urine output - catheter
• Invasive blood pressure monitoring is advised in significant liver disease
• Consider a central line in patients with a high MELD score, to facilitate electrolyte correction, but remember CVCs carry risk in this patient cohort

Big fluid shifts can take you by surprise, especially if large volumes of ascites are going to be drained, so preemptive monitoring and fluid therapy is warranted.

If you're draining lots of ascites remember the need for human albumin replacement.

• Propofol has more pronounced cardiac and respiratory depressant effects in liver disease
• Atracurium may be of benefit due to its metabolism not relying on hepatic function, although protein binding and volume of distribution changes may require a larger dose
• Rocuronium can have a prolonged elimination
• Reduced pseudocholinesterase concentrations can prolong duration of blockade with suxamethonium
• Volatile anaesthesia and TIVA are both acceptable options, however TIVA may be better as remifentanil is metabolised by red blood cell esterases, which are preserved in liver disease
• Morphine has prolonged effects due to reduced extraction ratio and hepatic blood flow, so fentanyl is preferred for postoperative pain control
• NSAIDs are generally avoided for risk of renal toxicity, platelet dysfunction and GI bleeding
• Paracetamol should be used in liver disease to reduce opioid requirements, but caution in severe hepatic dysfunction

In general it seems that anaesthetic technique doesn't matter too much, as long as you're thinking about and dealing with all the liver-related problems.

Easier said than done.

• Haemodynamic instability
• Bleeding and coagulopathy
• Drug metabolism and encephalopathy
• Oliguria and acute kidney injury
• Hypoglycemia
• Electrolyte disturbance*

*Pay particular attention to calcium if you're giving blood products.

Yeah good question.

• Severe liver disease patients seem to be both dry and overloaded at the same time
• They retain sodium like mad, and renal function can often deteriorate despite plenty of filling 
• Try and avoid hypervolaemia, and keep a close eye on potassium
• Goal directed fluid therapy targetting urine output or cardiac output monitoring parameters is probably a good idea
• One can always 'consider albumin' especially in the presence of ascites
• Vasopressors shouldn't be forgotten either, as these patients often have low systemic vascular resistance
• If you're giving blood, give it as slowly as you can get away with - to allow the tired liver to process the citrate
• Don't forget glucose

• Positive pressure ventilation and PEEP can worsen hepatic venous pressure, with knock on effects on cardiac output
• Avoid hyperventilation as hepatic blood flow is reduced by hypocarbia
• Avoid excessive airway and oesophageal instrumentation as there is risk of bleeding - nasal intubation is usually avoided
• Even fasted patients can regurgitate if they have ascites or hiatus hernia
• Viral hepatitis can pose a threat to staff via needle stick injury

Patients with liver disease have a much less effective stress response to trauma and surgery, meaning they're more likely to get any of multiple complications:

• Wound dehiscence and infection
• Bacterial peritonitis
• Respiratory tract infection
• Acute kidney injury
• Decompensated liver failure

The most pressing issue is whether the surgery and anaesthesia is going to trigger a decompensation of their liver failure, so generally patients should be monitored closely on HDU or ITU after anything other than the most minor of procedures.

The decision to remain intubated rather than extubating at the end of surgery should be guided by the following indications:

• Severity liver disease
• Duration and extent of surgery
• Known associated cardiac or pulmonary disease 
• Significant fluid or electrolyte disturbance 
• Hypothermia
• Preoperative encephalopathy
• Oxygen saturations <90% on 40% oxygen

Any signs of liver decompensation should be discussed immediately with a specialist liver centre.

• VTE needs individual assessment and management based on surgical and haematology team input
• Laxatives to avoid encephalopathy
• Careful monitoring of fluid balance and renal function, as high risk of hepatorenal syndrome
• Avoidance of both hypo and hyperglycaemia as both carry increased mortality and morbidity
• Enteral nutrition seems to be better for hepatic function than parenteral

Also called the Child-Pugh score, this uses the following parameters:

• Bilirubin
• Albumin
• INR
• Encephalopathy (how bad)
• Ascites (present or not)

It then churns out three levels - A, B and C - to give an idea of postoperative mortality and morbidity.

• 5-6 = Class A = <5% operative mortality
• 7-9 = Class B = 25%
• 10-15= Class C = >50%

It's used for both hepatic and non-hepatic surgery, and its main drawback is the degree of subjectiveness when assessing the severity of encephalopathy and ascites.

It also has rather arbitrary cut off values.

• The MELD score uses creatinin, bilirubin and INR to generate a score
• MELD score <10 is similar to CP A = consider proceding with caution
• MELD 10-15 or CP B = optimise patient then consider proceding with caution
• MELD >15 or CP C = avoid surgery wherever possible

There are multiple variations of the MELD score such as the MELDNa and UKELD scores, but they all do very similar things.

This uses the following data points to predict postoperative mortality in patients with cirrhosis:

• Age
• ASA
• Cause of cirrhosis

Doesn't get examined much, and misses a few key things like severity of portal hypertension which are quite important.

This relatively new calculator incorporates the following:

• Platelets
• Albumin
• Bilirubin
• Age
• ASA
• Obesity
• Presence of fatty liver disease
• Emergency surgery and category

This one seems to be pretty good but is still under investigation, and as always risk calculators should form part of the assessment, not guide it entirely.

• Acute hepatitis - viral or alcoholic
• Fulminant hepatic failure
• Severe chronic hepatitis
• Child Pugh C cirrhosis
• Severe uncontrolled coagulopathy
• Severe extrahepatic complications (cardiomyopathy, heart failure, renal failure)