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What is Liver Failure

Cirrhosis is the long-term process of fibrosis and scarring of the liver parenchyma. Cirrhosis is the end of a pathway of many different chronic liver diseases, and eventually will progress to liver decompensation.

Acute Liver Decompensation is defined by decompensation of the liver (onset of jaundice, coagulopathy (INR >1.5), hepatic encephalopathy, ascites) indicating it is unable to perform its normal functions. 90% of the liver parenchyma needs to be damaged before it decompensates, and symptoms occur. Acute liver failure normally occurs on top of an underlying chronic liver disease (Scarring/Fibrosis of the liver lasting > 6 months, but with no loss of function).

Hepatic Encephalopathy - Urea builds up. This is then broken down by astrocytes in brain - This process converts glutamate to glutamine. Glutamine has osmotic effect causing raised

Jaundice is a yellow discolouration of the skin, caused by an accumulation of bilirubin. Jaundice normally presents when bilirubin >35uMol and is most easily visible in the sclera.


What causes Chronic Liver Failure

Acute - Acute Viral Hepatitis (Commonly B, C), Drug Induced Hepatitis (Paracetamol Overdose), Decompensated Chronic liver disease, Ischaemia (Trauma/Shock), Budd Chiari syndrome (Clot formation in the hepatic vein)

Chronic - Alcoholic Hepatitis, Autoimmune hepatitis, Wilson's Disease (Autosomal Recessive condition where liver cannot convert copper to Caeruloplasmin, so it builds up in liver, late stage can build up in brain), Haemochromatosis, Alpha 1 anti-trypsin, Non-Alcoholic Steatohepatitis, Chronic Viral Hepatitis, Hepatocellular Carcinoma

Post Hepatic - Primary Sclerosing Cholangitis (autoimmune bile duct inflammation and stricture formation), Primary Biliary Cholangitis (granulomatous inflammation of Interlobular duct), Bile Duct Obstruction (Pancreatitis, Bile Duct Strictures, Common Bile Duct Gall Stone, Cancer of the head of the Pancreas)


What will you find in a history of Liver Failure

Chronic – Fatigue Malaise, Anorexia, Nausea, Weight Loss
Acute – Oedema, Ascites, Bleeding/Bruising, Jaundice (May also cause Pruritis), Encephalopathy, Pleural Effusion
Post Hepatic – Steatorrhea, Dark urine
Complications – Variceal Bleeds, Spontaneous Bacterial Peritonitis

Specific Questions to ask:
Jaundice - If the patient has jaundice, they may not necessarily have liver failure. There are pre-hepatic causes (Haemolytic Anaemias, Gilberts Syndrome, Heart Failure (Backs up to the liver), Trauma/Shock) and Post Hepatic (Pancreatitis, Bile Duct Strictures, Common Bile Duct Gall Stone, Cancer of the head of the Pancreas) of jaundice, as well as hepatic causes. If this is the case specifically ask about family history of blood disorders (e.g. Thalassaemia), Surgery to the hepatobiliary tract (Strictures), or a history of gallstones
Ask about past medical history of Inflammatory bowel disease - risk factor for PSC and fatty liver
If patient has had a Paracetamol Overdose - How many tablets? How long ago? Over how long? Why?
Ask about risk factors for hepatitis – Has the Patient (or sexual partner of patient) Had Hepatitis B, C or HIV, used IV drugs, been born in or travelled to Asia/Africa, had a blood transfusion pre-1985, used a sex worker, or had a tattoo from a non-licensed tattoo parlour
History of cancers – Can metastasise to the liver (Specifically Breast, Bronchus, GI cancer)
Alcohol history - Use Cage tool and assess units per week
Personal or Family history of Liver Problems/Auto immune conditions/Cancers
Patients with cirrhosis can be knocked pushed into decompensation by; Sepsis, Malignancy, Alcohol, GI Bleeding so look/ask about these


What will you find on examination of Decompensated Liver Failure

End of the bed:
Encephalopathy – Drowsiness, Confusion, Coma
Fever – May indicate infection causing decompensation
Hands – Asterixis - Encephalopathy
Jaundiced Sclera
Fetor hepaticas - Breath smelling of pear drops
Papilledema – Raised ICP
Pleural effusion
PR - may reveal evidence of GI bleeding


What are the signs of Chronic Liver Disease decompensation

End of the bed:
Pyoderma Gangrenosum - Autoimmune hepatitis
Palmar Erythema
Duputrens contracture - Alcohol abuse
Leukonychia - Whites on Nails (Hypalbuminaemia)
Parotid enlargement - Alcohol abuse
Spider Naevi
Loss of male body hair
Hepatomegaly/Shrunken Liver
Splenomegaly – Chronic Liver disease or Haemolytic anaemia
Palpable Gallbladder – A Painless gallbladder + Jaundice is not gallstones (Consider pancreatic tumour)
Caput medusa
Atrophic Testes
PR - may reveal evidence of GI bleeding


What are the Complications of liver disease

Hepatic Failure:
Coagulopathy - Less clotting factors produced
Spontaneous Bacterial Peritonitis
Increased Risk of HCC
Hepatorenal Syndrome - Redcued immune complex clearnece by kliver, causes build up in kidney (IgA Nephropathy)

Portal Systemic Hypertension:
Oesophageal Varices


What investigations will you order in liver disease?

Unless cause is known, need to undergo a Liver Screen

LFT’s – See below text
Clotting - Clotting time can be increased in decompensated in liver failure
FBC – Infection can precipitate decompensation or looking for anaemia (Due to GI bleed or Chronic Disease)
U&E - Renal Failure can be a complication of liver failure (hepatorenal syndrome), Look for a raised Urea due to upper GI bleed and signs of dehydration that could be due top shock/sepsis
Glucose – Hypoglycaemia can occur in decompensated liver failure (Liver converts glycogen to glucose)
Paracetamol levels – If overdose suspected, to assess if above the N-Acetyl Cysteine treatment line (Treat while waiting for result)
ABG – pH is a good prognostic indicator, especially in paracetamol overdose. Lactate levels can be raised in sepsis and is another prognostic indicator
Cross Match - In case of bleeds due to low clotting and varicose veins
Viral Antibody Testing - Hepatitis A, B, C, E serology, Cytomegalovirus PCR, Epstein Barr Virus PCR
Autoantibody Testing – For Autoimmune hepatitis (Antinuclear (ANA) and antismooth muscle (SMA)) and for Primary biliary cholangitis (Antimitochondrial (AMA))
Alpha 1 anti-trypsin levels
Caeruloplasmin and urinary copper if patient <40. Caeruloplasmin will be low in Wilsons
Alpha Fetoprotein – May be raised in Hepatocellular carcinoma
Total iron/total iron binding capacity/Transferrin saturation/Ferritin – Iron levels raised in Haemochromatosis
Ascitic Tap – Of any ascites (Microscopy, Culture and sensitivity)

Liver Ultrasound with Duplex - Looking for hepatic vessel thrombosis, hepatomegaly, splenomegaly, bile duct dilation (indicating bile duct obstruction)
ERCP second line imaging used for post hepatic obstruction (if US shows dilation)
Chest X-ray needed if patient is decompensating - Pleural effusion may occur
Upper GI endoscopy should be arranged for all Chronic Liver failure patients to assess for oesophageal varices

Special Tests:
Liver Biopsy used as gold standard for diagnosis unless cause is certain – Ensure clotting time is not abnormal before biopsy

Common LFT Patterns
Chronic Liver Disease (ALT>AST)
Cirrhosis (AST>ALT)
Alcoholic Liver Disease (AST>2x ALT)
Viral hepatitis (AST > 1000)
Cholestasis /Post Hepatic (Raised ALP and GGT)
Bone Disease (ALP raised alone)


What is the acute treatment of liver disease

A-E approach
Get IV Access/Give O2 to maintain sats of 94+ /Attach 12 lead ECG. Careful about fluid overload.
Assessment with AMPLE history and brief examination
A-E approach
Get IV Access/Give O2 to maintain sats of 94+ /Attach 12 lead ECG. Careful about fluid overload and use of saline
Assessment with AMPLE history and brief examination
Get help - Refer to ITU/Liver unit once any signs of decompensation
Glucose hourly and treat any drops with dextrose
Raise the patients head to limit raises in ICP
In encephalopathy may need to intubate to protect airway
Daily bloods to look for infection and twice daily electrolytes
If worsening do a liver transplant assessment - Look below for indications
Stop any sedative medications

Pruritis - Cholestyramine
Ascites - Fluid restriction (<1.5l/day), Low salt diet, Spirinolactone.
Antibiotics Prophylaxis – If patient is Ascitic and has had SBP before
Hepatic Encephalopathy – Lactulose (reduce ammonia production) and rifaximin (antibiotic). Can give mannitol if the encephalopathy has caused raised ICP. Enema to remove urea producing gut bacteria.
Bleeding - Replacement Vitamin K, platelets, and Fresh frozen plasma/transfusion as indicated
Proton-pump inhibitors - Prophylaxis against GI bleed
Paracetamol overdose - N-Acetyl Cysteine
Budd Chiari - Anticoagulation
Gallstone – ERCP removal

Liver Transplant


What is the non emergency treatment of liver disease

Ensure adequate nutrition - Calorie/vitamin/protein/iron/zinc
Stop drinking alcohol
Avoid NSAIDS, Opiates, Sedatives
Regular exercise to prevent muscle wasting
Adjust medications for liver function

Specific Treatment Regimes:
Viral Hepatitis - Antivirals (Entecavir) and Immunise sexual contact in hepatitis B
Alcoholic Fatty Liver Disease - Use MADDREY score (Based off INR) to assess if patent requires any steroids
No Alcoholic Steatohepatitis - Low fat diet/Lose Weight (no drug treatment)
Wilsons Disease - Low Copper Diet, Penicillamine, Screen Siblings
Primary Biliary Cirrhosis/Primary Sclerosing Cholangitis - Ursodeoxycholic Acid and possibly steroids, Antibiotic Prophylaxis against ascending cholangitis
Autoimmune hepatitis - Prednisolone
Haemochromatosis - Venesection 1-3 weekly, until iron reaches normal levels, will need lifelong treatment and Low iron diet
Hepatocellular Carcinoma - Resection/Chemo, May Require palliative care. Transplant may improve prognosis in primary neoplasms

Transplant may be required. Use a scoring system to work out eligibility
Complications include – Immediate (Bleeding, Poor graft function), Early (Sepsis, Anastomotic problems, Rejection - Lethargy, fever, pain, hepatomegaly and raised liver enzymes)), Late (Recurrence of underlying disease, Chronic graft rejection, Immunosuppression consequences e.g. infection)


What are the indications and contraindications for a Liver Transplant?

Acute Liver Failure: Kings College Criteria
Paracetamol induced liver failure:
Arterial pH<7.3 OR
PT>100s (or INR>6.5), serum creatinine>300micromol/l and the presence of encephalopathy (grade 3 or 4)
Liver failure, AKI and encephalopathy

Non-paracetamol liver failure:
PT>100s (or INR>6.5)
OR 3 of the following:
Age <11 or >40
Length of time from jaundice → coma took >7 days
Drug toxicity (regardless of its contribution to the liver failure)

Chronic Liver Failure:United Kingdom Model for End-Stage Liver Disease (Based off of INR, Creatinine and Bilirubin)
Indicated in Advanced cirrhosis and Hepatocellular cancer (1 nodule <5cm or 2/3 nodules less than 3cm)

Extrahepatic malignancy
Multiple tumours
Severe co-morbidity
HIV infection
Non-compliance with drug/alcohol therapy


How will you grade encephalopathy?

Grade 1 - Drowsy but coherent; mood change
Grade 2 - Drowsy, confused at times, inappropriate behaviour
Grade 3 - Very drowsy and stuporous but rousable
Grade 4 - Comatose, barely rousable


What is the scoring system used for liver failure?

Child Pugh Score

Based off of:
Hepatic Encepalopathy
Prothrombin Time