QuestionSBA
QuestionChoice
Ascites can develop in patients with decompensated chronic liver disease and is primarily due to portal hypertension. It presents with abdominal distension, with evidence of shifting dullness, reflecting excess fluid within the abdominal cavity. In acute liver failure these mechanisms have not taken place, so ascites is significantly less common
33335
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Ascites
QuestionChoice
Gynaecomastia develops in chronic liver disease because of impaired testosterone breakdown within the liver, leading to a rise in oestrogen levels (more testosterone is converted to oestrogen) which can stimulate breast tissue development
33334
b
Gynaecomastia
QuestionChoice
Splenomegaly can develop in chronic liver disease because of blood pooling in the spleen, secondary to portal hypertension
33337
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Splenomegaly
QuestionChoice
Tender, smooth hepatomegaly suggests an acute liver pathology, with potential causes including acute viral hepatitis, hepatic vein thrombosis (Budd Chiari syndrome) and right heart failure with portal congestion. In chronic liver disease there is usually a degree of liver cirrhosis over time, which causes a reduction in organ size because of fibrosis. The caveat to this is in cases of malignancy where they may be hepatomegaly due to presence of a mass, but this is usually irregular in nature and not classically tender
33333
a
Tender, smooth hepatomegaly
QuestionChoice
Spider naevi (sometimes also called spider angiomas) are a particular form of telangiectasia representing another manifestation of the imbalance of testosterone and oestrogen occurring in chronic liver disease. On examination, spider naevi can be identified as spider-like vessels, which fill from a central arteriole (i.e. when you apply pressure, they blanch (fade), and refill from the centre)
33336
d
Spider naevi
Concept
Chapter
# Summary

Liver failure can manifest acutely or chronically, with various causes including infections, drugs, toxins, and chronic liver diseases. Clinical features range from hepatic encephalopathy to abnormal bleeding and jaundice. In hepatic encephalopathy, cerebral oedema arises from the accumulation of ammonia, leading to neurological symptoms. Investigations involve blood tests, ultrasound, and ascitic fluid analysis. Management includes addressing the underlying cause, monitoring closely, and providing supportive care such as lactulose for encephalopathy and vitamin K for coagulopathy. Liver transplantation may be necessary in severe cases. Complications include infections, cerebral oedema, bleeding, and multi-organ failure.


# Definition

Liver failure refers to the loss of liver function and the development of complications including coagulopathy, jaundice or encephalopathy. It can occur acutely if onset of symptoms in less than 26 weeks with a previously healthy liver and subdivided into hyperacute (< 7 days), acute (8-21 days), or subacute (4-26 weeks) liver failure. Chronic liver failure occurs on a background of liver cirrhosis.

# Epidemiology

Liver failure is a significant global health concern, with varying incidence rates worldwide. In the United Kingdom, chronic liver diseases represent a substantial portion of liver failure cases, with alcohol-related liver disease and non-alcoholic fatty liver disease being prominent contributors. The incidence of acute liver failure is relatively low but can occur rapidly and unpredictably, leading to severe morbidity and mortality if not promptly managed.


# Aetiology

Acute liver failure can arise from various causes, including:

- **Viral Hepatitis:** Hepatitis A, B, and E infections can lead to acute liver failure, particularly in cases of fulminant hepatitis.
  
- **Drug-Induced Liver Injury:** Overdose or adverse reactions to medications like paracetamol (acetaminophen), halothane, isoniazid, and certain antibiotics can precipitate acute liver failure.

- **Toxic Exposures:** Exposure to hepatotoxic substances such as Amanita phalloides mushrooms or industrial chemicals like carbon tetrachloride can cause acute liver damage.

- **Vascular Disorders:** Conditions like Budd-Chiari syndrome, characterised by hepatic vein obstruction, can result in rapid liver failure.

Chronic liver failure typically develops over an extended period due to ongoing liver damage. Common causes include:

- **Alcohol Misuse:** Chronic alcohol consumption is a leading cause of liver cirrhosis and subsequent liver failure.

- **Chronic Viral Hepatitis:** Persistent infection with hepatitis B or C viruses can progress to cirrhosis and liver failure if left untreated.

- **Non-Alcoholic Fatty Liver Disease (NAFLD):** Accumulation of fat in the liver, often associated with obesity and metabolic syndrome, can lead to inflammation, fibrosis, and ultimately liver failure.

- **Autoimmune Liver Diseases:** Conditions such as autoimmune hepatitis, primary biliary cholangitis (formerly primary biliary cirrhosis), and primary sclerosing cholangitis can cause chronic inflammation and scarring of the liver.

- **Hereditary Conditions:** Genetic disorders like haemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency can result in progressive liver damage and failure over time.

# Signs and Symptoms 

- Hepatic encephalopathy
- Abnormal bleeding
- Jaundice

If the cerebral oedema is severe, raised intracranial pressure may develop. This is more common in fulminant hepatic failure and has a high mortality rate.

It is important to separate the signs of liver failure from the signs of chronic liver disease. The presence of both indicates a de-compensation of chronic liver disease.

### Pathophysiology of Hepatic Encephalopathy

- In liver failure, nitrogenous waste (ammonia) accumulates in the circulation.
- This small molecule is able to cross the blood-brain barrier, and once in the cerebral circulation it is detoxified by astrocytes which form glutamine through the amidation of glutamate.
- The excess glutamine disrupts the osmotic balance and the astrocytes begin to swell, giving rise to cerebral oedema.

### Four stages of hepatic encephalopathy

1. Altered mood and behaviour, disturbance of sleep pattern and dyspraxia
2. Drowsiness, confusion, slurring of speech and personality change
3. Incoherency, restlessness, asterixis
4. Coma

# Investigations 

- Blood tests assessing synthetic function of the liver:

- INR to look for coagulopathy and establish a diagnosis of liver failure
- Liver Function Tests including albumin to check liver enzymes, bilirubin levels and to further assess synthetic function of the liver
- Full blood count to look for leucocytosis (possible infective cause), thrombocytopaenia (in chronic liver disease) and anaemia (normocytic could indicate haemolytic anaemia as in Wilson's or a GI bleed from oesophageal varices, macrocytic could indicate B12 and folate deficiency as in alcohol excess)
- Urea and electrolytes to establish baseline renal function and to look for hepato-renal syndrome or any electrolyte abnormalities (such as hypokalaemia which can worsen encephalopathy and should be corrected)
- Tests to determine cause such as:
  - Paracetamol level (paracetamol overdose)
  - Hepatitis
  - Epstein-Barr virus
  - Cytomegalovirus serology (viral infection)
  - Iron studies (haemochromatosis)
  - α-1 anti-trypsin (α-1 antitrypsin deficiency)
  - Caeruloplasmin level (Wilson's disease)
  - Iron studies (hereditary haemochromatosis)
  - Auto-antibodies (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis)

Imaging/Invasive:

- If ascites is present, a peritoneal tap should be taken for microscopy and culture to look for spontaneous bacterial peritonitis.
- Abdominal ultrasound
- Doppler ultrasound would be of use in identifying Budd-Chiari syndrome
- OGD may be required if concerns over varices/variceal bleeding

# Management

- Treat the underlying cause if possible
- Monitor observations closely including blood glucose


- For encephalopathy:
  - Firstly, the stage of encephalopathy should be graded (see table below)
  - Lactulose is given to help nitrogenous waste loss through the bowels (reducing encephalopathy). Constipation is an important precipitant of encephalopathy in patients with chronic liver disease.
  - Rifaximin is a 2nd line antibiotic which reduces nitrogen forming micro-organisms in gut 
  - IV mannitol can be given to reduce cerebral oedema in encephalopathy


| Grade   | Symptoms                                                    |
|---------|-------------------------------------------------------------|
| Grade 1 | Altered mood and behaviour, disturbance of sleep pattern, dyspraxia |
| Grade 2 | Drowsiness, confusion, slurring of speech, personality change |
| Grade 3 | Incoherency, restlessness, asterixis                          |
| Grade 4 | Coma                                                        |

  
- For coagulopathy
  - Vitamin K may need to be given IV - helps production of coagulation factors
  - Fresh frozen plasma can be given if patient is bleeding

  
- Spontaneous bacterial peritonitis
  - Broad spectrum antibiotics - IV Piperacillin-Tazobactam is usually first-line
  
- Hepatorenal syndrome - triad of cirrhosis, ascites and renal failure
- Portal hypertension leads to release of vasoactive mediators which leads to splanchnic vasodilation, which reduces perfusion to kidneys, sensed by macula densa cells in JGA and leads to the activation of RAS.
- There are two types: 1. Rapidly progressive, often managed with terlipressin 2. Slowly progressive, usually managed with Midodrine
  - May require haemofiltration
  - If patient required fluid resuscitation, human albumin solution rather than crystalloid fluid.
-	A TIPSS procedure may be necessary but note immediately after this can worsen hepatic encephalopathy

- Liver transplantation may be necessary as this is the only definitive management for chronic liver failure - indications are set out below.

## King's College Hospital Criteria for Liver Transplant

The King's College Hospital criteria are designed to predict poor outcome in acute liver failure and are therefore an indication of patients that should be considered for urgent liver transplantation.

King's College Hospital Criteria for Liver Transplant (paracetamol induced):

The criteria for **paracetamol** induced liver failure are as follows:

- Arterial pH <7.3 24h after ingestion **OR**
  - Pro-thrombin time >100s
  - **AND** creatinine >300µmol/L
  - **AND** grade III or IV encephalopathy.

King's College Hospital Criteria for Liver Transplant (non-paracetamol liver failure):

The criteria for non-paracetamol liver failure are as follows:

- Prothrombin time >100s **OR**
- **Any three of**:
  - Drug-induced liver failure
  - Age under 10 or over 40 years
  - 1 week from 1st jaundice to encephalopathy
  - Prothrombin time >50s
  - Bilirubin ≥300µmol/L.


# Complications 

- The most common complication of acute liver failure is **infection**.

Bacterial infection occurs in up to 80% of patients, and fungal infection in around 30%. This is thought to result from decreased phagocyte action, reduced complement levels and multiple medical interventions which are often invasive. Patients often present atypically, with no fever or raised white cell count.

Other complications include:

- Cerebral oedema ± raised intracranial pressure
- Bleeding (where there is a source, for example during the introduction of intracranial pressure monitors)
- Hypoglycaemia (easily treated with glucose)
- Multi-organ failure


# NICE Guidelines

[NICE CKS - Cirrhosis](https://cks.nice.org.uk/topics/cirrhosis/)




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A 57-year-old male presents to the Emergency Department with confusion and abdominal pain. He is unable to give any information about his medical history, due to his confusion. Blood tests identify significantly deranged liver function tests.

On examination, what clinical sign may suggest that this is an acute rather than chronic form of liver disease?
a