Liver Disease Case 1

 Answer the questions at the bottom of the page when all data has been reviewed

History & Examination

A 37 year old housewife is brought to ER/ED by a neighbor who is also her friend. The patient had been found partially clothed, confused and disorientated on the suburban street where she lives. Her friend reports that the patient, Lucy, has a habit of drinking alcohol when alone in her home. Indeed, on checking the house while waiting for the ambulance, she had found several empty wine bottles. The neighbor is distressed and embarrassed as she had not seen her friend since a ‘silly’ argument some days earlier. She reports that Lucy had suffered from depression in the past and had been very down since the death of her father one year previously. Her husband does his best but was away from home that week due to work commitments. There is no other significant past medical history.

On examination, she was jaundiced and appeared to be dehydrated. She was disorientated in time and place but sufficiently cooperative for asterixis to be demonstrated. On abdominal palpation, she had definite tenderness in the right upper quadrant with no gaurding. There were no stigmata of chronic liver disease. Chest and cardiovascular examination were normal. there was no neck stiffness or photophobia. She had bilateral down-going planters with no evidence of raised intracranial pressure.

The nursing staff report self-limiting episodes of possible seizure activity while she was in the resuscitation area.



Lucy Jodan ECG anon

Report: Normal AP chest radiograph


Lucy Obs anon

Lucy Fluids anon


Q1. What pattern of enzyme abnormalities are present on her liver function tests (LFTs)?

Q2. What additional tests (name 5) must be carried out immediately at presentation ?

Q3. What abnormalities are present on her ABG (shown below)?

case1 abgCSi

Q4. Her INR is 6.8 at presentation. What is the likely diagnosis at presentation?


Q1. What pattern of enzyme abnormalities are present on her liver function tests (LFTs)?

Her AST and ALT are grossly elevated. Her gGT and Alakaline phosphatase levels are mildly elevated. This is a ‘hepatitic pattern’ of LFT derangement. You can learn about abnormalities of liver enzyme levels in the article below.

Q2. What additional tests (name 5) must be carried out immediately at presentation ?

Excellent answers: Arterial Blood Gas (ABG), Plasma Glucose: Result, INR: 6.8, Paracetamol (acetaminophen) level: 80 mg/l, CT Brain: normal. Good answers: Salicylate level, Toxicology screen, Liver ultrasound

Q3. What abnormalities are present on her ABG (shown below)?

case1 abgCSi

Undergraduate analysis

Looking at this ABG result, there is an acidosis present (a low pH). This cannot be a respiratory acidosis as ‘respiratory acid’ (CO2) is not elevated. The low level of metabolic base (bicarbonate, HCO3-) is consistent with the presence of a metabolic acidosis. The pCO2 is low consistent with partial (the pH has not returned to normal) respiratory compensation. This is what we would expect to see in a person with fulminant liver failure. Her anion gap ([Na+] less [Cl-] + [HCO3-]) (128 – 98 = 30) is elevated (normal range < 18), so this metabolic acidosis is likely due to the addition of ‘fixed acid’ to the extracellular fluid.

ABG interpretation: raised anion gap metabolic acidosis with partial respiratory compensation.

Postgraduate analysis

Taking the analysis a little further. Applying Winter’s formula, the pCO2 is somewhat lower than expected.

Predicted pCO2 = 1.5[HCO3-] + 8 (+/- 2) = 22 – 24 (mmHg)

Observed pCO2 = 18 mmHg  (18/7.5 = 2.4 kPa)

This suggests a degree of coexistent respiratory alkalosis (something pushing respiratory acid down further than predicted on the basis of compensation alone). Respiratory alkalosis is often seen in liver patients and is of undetermined aetiology. We should also remember that a mixed pattern of metabolic acidosis with co-existent respiratory alkalosis is seen in salicylate poisoning. The salicylic acid acts both as a fixed acid and stimulates respiration via CNS centers. In this woman’s case, salicylate was not detected on testing.

We note from her observation chart that the ABG was taken on room air. She is hyperventilating (low pCO2) to compensate for the metabolic acidosis with an additional respiratory alkalosis secondary to her liver disease. These factors explain her high pO2. Her A-a gradient is normal.

Q4. Her INR is 6.8 at presentation. What is the likely diagnosis at presentation?

Acute fulminant liver failure secondary to paracetamol (acetaminophen) overdose taken at some time in the preceding days. Paracetamol toxicity will be aggravated by her alcohol consumption. Her LFTs are consistent with this, showing a ‘transaminitis’ (markedly raised AST and ALT). Her INR (‘the one true liver function test’) is also elevated consistent with failure of the liver to synthesis clotting factors due to significant liver damage. The liver plays a key role in acid-base balance. In fulminant liver failure we expect to see a metabolic acidosis on the patient’s ABG. Our patient has clear evidence of severe metabolic acidosis. The liver plays a role in controlling plasma glucose and liver disease may be associated with hypoglycemia. She has paracetamol (acetaminophen) in her system. The level is not particularly high but is at least consistent with an overdose taken at some time point (or repeatedly) during recent days. This would explain her liver failure.

The AST and ALT were grossly elevated in the case under discussion secondary to drug induced necrosis of hepatocytes. However, note that there was also a rise (less pronounced) in the biliary enzyme ALP. This is readily explained. Destruction of hepatocytes results in inflammation and swelling in the organ with partial obstruction of small ducts and bystander damage to cells in the biliary tree. Hence, the detectable rise in ALP. Equally, damage to the ducts with impaired bile drainage, for example secondary to gallstones, may result in some damage to hepatocytes with leaking of hepatitic enzymes into the blood. For these reasons, in practice, the pattern of liver enzyme rise is often mixed with the one predominating reflecting the underlying cause.

You will release, of course, that the liver enzyme levels in the blood provide no information whatsoever about how well or otherwise the liver is functioning. For this reason, a lot of people refer to the term liver function tests as a misnomer. In terms of assessing the actual degree of functional impairment of the liver in disease, we use indirect markers. The liver plays the central role in the production of the clotting factors of the extrinsic pathway and in the production of the major blood protein albumin. We can look for evidence of derangedliver synthetic function by looking for elevation of the INR or a fall in serum albumin levels. It must be borne in mind that both the INR and albumin levels are influenced by factors other than liver function. They are relatively non-specific. For example, albumin levels may be low due to nephrotic renal disease or in the case we have just studied, due to poor nutritional status. As you know, multiple pathologies extrinsic to the liver may affect the INR. In reality we have no true specific liver function test available to us. However, in the correct clinical context, the INR and albumin can give us some idea of the level of liver functional impairment. In the context of liver disease, a raised INR or low albumin implies a very substantial loss of liver synthetic function and advanced liver damage.

Our patient has clinical evidence of hepatic encephalopathy (confusion and asterixis in combination with jaundice) A CT brain must be carried out to exclude unsuspected intracranial pathology. In most cases of hepatic enecephalopathy, as in this case, CT brain is normal. The abnormality is functional and of unknown aetiology. Advanced cases may develop cerebral edema.

Subsequent Course

St Agnes

Despite appropriate treatment, the patient’s condition deteriorated on ICU in the 24 hours post admission with worsening liver indices and persistent acidosis. She was listed for liver transplantation. In the week following transplantation, she regained consciousness and made peace with her friend. She apologised to her husband for her actions and was able to embrace her children. However, her actions had been deliberate and she still wanted to die. Intractable organ rejection developed in the third week post transplantation associated with renal failure, bone marrow failure and sepsis. Following a decision to adopt palliative measures she died peacefully.



Liver function tests help us identify liver and/or biliary tract damage in a patient and may give us a clue as to the nature of the damaging pathology. ‘Liver enzymes’ fall into two categories. AST and ALT are present in the hepatocytes. Therefore, when pathology damages hepatocytes, these enzymes leak into the blood stream and their levels rise on our blood tests. The LFTs are deranged with a hepatiticpattern of enzyme rise. In contrast, gGT and alkaline phosphatase (ALP) are present in the cells lining the bilary tree. Pathology focused on the biliary tree (eg stones, cholecystitis, primary biliary cirrhosis) tends to result in elevation of the level of these enzymes in the blood (anobstructive or biliary pattern).


In this diagram, bile (dark green) from hepatocytes (grey cells) is shown draining into a bile canaliculus. The hepatocytes contain large quantities of transaminases (AST: aspartate transaminase and ALT: alanine transaminase). Therefore, pathologies which damage the integrity of hepatocytes tend to lead to release of these enzymes into the adjacent vasculature (black arrows). We can detect the rise in level of these enzymes in the blood and this provides evidence of hepatocyte damage. Elevated transaminase levels are sometimes referred to as a ‘transaminitis’ indicating that diverse pathologies can cause hepatocyte damage. It is then up to us to identify the offending agent.

In contrast, the cells lining the biliary tract are rich in the enzymes alkaline phosphatase (ALP) and gamma glutamyl transferase (gGT). When these cells are damaged, these enzymes appear in the blood (red arrows).