Liver Disease and Multimorbidity

What are the main functions of the liver?

Exocrine (digestive) Functions
Metabolism

Cholesterol metabolism
Plasma proteins
Clotting factors
Endocrine functions
Iron and B12 Storage
Macrophage storage

Describe the Exocrine (digestive) Functions of the liver?

• synthesis and the secretion of bile for the adequate digestion and absorption of fats

• Secretes bile into a bicarbonate rich solution that helps to neutralize acid in the duodenum

• Absorption of fat-soluble ADEK vitamins

What are the metabolism functions of the liver?

• Converts plasma glucose to glycogen and triglycerides

• Converts plasma amino acids to fatty acids

• Synthesizes triglycerides and secretes them as lipoproteins

• Produces glucose from glycogen (glyconeogenesis)

• Converts fatty acids to ketones during fasting

• Produces urea – major end product of amino acid (protein) catabolism and releases into the blood

What is the Cholesterol metabolism function of the liver?

• Synthesizes cholesterol and releases into the blood

• Secretes cholesterol into bile

• Covers plasma cholesterol into bile salts

What is the plasma protein function of the liver?

Synthesizes and secretes proteins including plasma albumin, acute phase proteins, binding proteins for a variety of hormones and lipoproteins

What is the clotting factor function of the liver?

• Produces many of the plasma clotting factors including prothrombin an fibrinogen (see blood lectures)

• Bile salts – essential for the absorption of fat soluble vitamin K that is required for the formation of clotting factors in the liver

What are the endocrine function of the liver?

Secretes insulin-like growth factor 1 (IGF-1) in response to growth hormone. This promotes cell division in a number of tissues including bone

What is the main cause of liver impairment?

Alcohol 60%

What are some other causes of liver impairment?

• Alcohol consumption (60%)

• MASLD fatty liver disease – Obesity, metabolic disease

• Viral Infection

• Autoimmune Hepatitis

• Cholestatic Disorders

• Metabolic Disorders i.e. Wilson’s Disease

• Toxins

What percentage of liver impairment is preventable?

90% of liver disease is due to alcohol, obesity and viral hepatitis which are all preventable

What are cirrhotic patients monitored for every 6 months?

Hepatocellular carcinoma → cancer
3-10% will develop

How is liver disease diagnosed?

Symptoms and History
Deranged Liver (Function) Tests give an indication of liver injury
Need a few techniques

Which LFTs indicate Impaired Biliary Secretion or Cholestasis?

Bilirubin
ALP
GGT

How will ALP show in liver disease?

Elevated
Less specific to liver disease

• bones,

• kidneys,

• intestine

• placenta.

Half life 1-7 days

Define cholestasis (reduced flow of bile),?

the slowing or stalling of bile flow through your biliary system. It can be a problem in your liver or in your bile ducts.

Define hepatic infiltration

a metabolic complication where excessive neutral fat (triglycerides) accumulates within the cytoplasm of the hepatocytes

How does Bilirubin show in liver disease?

Breakdown product of haemoglobin, excreted in bile
Elevated

Which LFTs indicates Impaired synthetic and detoxifying functions?

Albumin
Ammonia
INR/prothrombin time

How does albumin show liver disease?

plasma protein produced by the liver,
reduced levels
Changes in response to inflammation as well

How does ammonia show liver disease?

Reduced ability to detoxify the blood then ammonia levels rise

Can cause encephalopathy

Define Encephalopathy?

• A syndrome of overall brain dysfunction

• Confused, agitated or not like yourself

How does INR and/or Prothrombin Time: show liver disease?

• Vitamin K dependent.

• Elevated values

• Suggest reduction in clotting factors

What is the BMJ diagnostic approach?

• AST/ALT ?acute

• Cholestatic pattern →Likely cholangitis or cholestatic diseases, including gallstones, carcinomas, or pancreatic cancers.

• Infiltrative pattern → Raised ALP then raised bilirubin. Might be TB.

What is the Child-Pugh score?

Assessment of chronic liver disease

What is the MELD Score?

validated as a predictor of survival in patients with
Cirrhosis

• Alcoholic hepatitis

• Acute liver failure

• Acute hepatitis

What is the MELD score used for?

prioritization of liver transplantation.

What is the Fib 4 score used for?

predict fibrosis risk and need for biopsy
Not used in isolation
Must use 2 or more methods

What is the ELF score used for?

predipredict fibrosis risk and need for biopsy
Not used in isolation
Must use 2 or more methods

What are the 2 main points of clinical management of liver disease?

Treat the underlying cause where possible
Address all signs, symptoms and associated conditions

What needs to be considered when treating the underlying cause of liver disease?

• Assess if condition is treatable

• Evaluate potential for reversal

• Implement measures to prevent disease progression

How to treat liver disease?

Treat Hep B/C
Abstinence from alcohol

Healthy diet and exercise

Management of metabolic risks

Immunosuppression for autoimmune hepatitis

Cholestatic liver disease (PBC)Transplant

Possible Future options

What is ascites?

• Fluid retention caused

What can ascites be caused by?

• reduced albumin – reduced oncotic pressure – fluid movement

• Increased aldosterone (reduced metabolism) –

  • acts on the kidney to increase sodium and water retention

• Fluid outside of circulation –

  • underfilling (low BP)

• Pre renal AKI

What are the treatment options for Ascites?

Paracentesis with albumin cover
Salt restriction in diet (and medicines)
Diuretics:
TIPS
Monitor for Spontaneous Bacterial Peritonitis (SBP)

Describe Paracentesis with albumin cover?

• Drain off the fluid

  • Inserting a tap

Which diuretics are used in ascites?

Spironolactone → potassium sparing
Then a loop

Can become resistant to diuretics

What is Spontaneous Bacterial Peritonitis (SBP) and how it managed?

infection of ascitic fluid without an apparent source.

• Diagnosis is by examination of ascitic fluid.

• Treatment is antibiotics

• May give patient prophylaxis

When would TIPS be used?

in diuretic –resistant/ intolerant (renal dysfunction) ascites

Summary of Oesophageal Varices?

Blood flow through liver impaired diverted through the GI system mainly stomach and oesophagus
High pressure can cause them to burst
GI bleeding in liver patients needs to be investigated

How is oesophageal varies surgically managed?

endoscopic management e.g. band ligation

TIPSS (intra-hepatic shunt) to divert blood reducing pressure

What are people prescribed in oesophageal varies?

Terlipressin → IV short term
Prophylactic Antibiotics
Non selective beta blocker

What non selective beta blockers are used in oesophageal varices?

Carvedilol 1st line
Nadolol used some times

Why is a PPI not recommended in oesophageal varices?

not recommended in absence of Peptic ulcer disease
Bleeding not caused by ulcer
associated with an increased risk of SBP

What is Pruritis itch caused by?

Reduced metabolism of bilirubin – bilirubin/bile salts deposits in skin but unclear mechanism for itch

What is the management for Pruritis (itch)?

Treat obstruction in (ERCP/MRCP)
Topical therapies
Cholestyramine sachets
Antihistamines
Rifampicin
Opioid antagonist
Sertraline

Which topical therapies are used in Pruritis (itch)?

Emollients or menthol in aqueous

What are the cautions around Cholestyramine Sachets?

• medication timings!

• Questran – binds bile acids but can be poorly tolerated
  Diarrhoea, constipation malabsorption

Which antihistamines are used in Pruritis (itch)?

frequently used but not usually effective. Non sedating preferred to avoid precipitating encephalopathy

How is rifampicin used in Pruritis (itch)?

• enzyme inducer leading to improved biliary flow but drug interactions, antimicrobial resistance

  • i.e. apixaban, anticoagulants

Which opioid antagonists are used in Pruritis (itch)?

Naltrexone

What is Wernicke’s Encephalopathy caused by?

due to deficiency in thiamine

What is hepatic Encephalopathy caused by?

Reduced ability of the liver to clear and metabolise toxins
Increasing ammonia in circulation

How to treat Wernicke’s Encephalopathy?

• Pabrinex then thiamine only,

  • IV Thiamine then PO 100mg TDS

Magnesium levels in range important co factor

How to treat Hepatic Encephalopathy?

Treatment focuses on increasing clearance of ammonia – laxatives, primarily lactulose
usually lactulose aiming for 2-3 soft stools per day.
Rifaximin to stop recurrence destroy toxins in gute

What can be a differential diagnosis in Encephalopathy?

Low sodium and low glucose common in chronic liver disease

What is done in elevated INR?

• Replace vitamin K – IV 10mg OD for 3 days or 3 doses (12 hours apart)

  • Hopefully bring INR back down to 1

What will be used to treat Hepato-renal syndrome

• Vasopressin (vasoconstrictor) – ITU/ICU

• Terlipressin titrated to effect- Ward

• Albumin

• Need to check renal function and excretion of medications

What is Hepato-renal syndrome?

renal failure caused by intrarenal vasoconstriction

How is absorption affected by liver impairment?

Decrease hepatic blood flow
Decrease first pass metabolism
increase bio-availability,

increase in half life

How is metabolism of drugs affected by liver impairment?

Accumulation of pro-drugs, drugs and/or metabolites
Active drugs increase → toxicity

Pro drugs decrease → no therapeutic

How is VD affected by liver impairment?

Increase volume of distribution in water-soluble drugs
Hypo-albuminaemia→ increase in active protein bound drugs

How is elimination affected by liver impairment?

decrease in elimination of drugs excreted in bile decrease in enterohepatic circulation

What are the key considerations when handing drugs in liver impairment?

Reduced hepatic function = Reduced ability to metabolise drugs
Reduced plasma proteins = Increase free fraction of protein-bound drugs
Be aware of and avoid hepatotoxic drugs
Avoid constipating, sedating, or highly anticholinergic drugs.
Be alert for drug side effects → Dose reductions may be necessary

Statins in liver dysfunction?

Abnormal LFTs are not a contraindication to statin therapy

How do ALT levels influence statins?

• ALT < 100 – start the statin and monitor LFTs after 6 weeks

• ALT 100-150 – start the statin and monitor at week 2, 6 and 12

• ALT > 150 – seek advice from hepatology

Which analgesia should be avoided in liver impairment?

• NSAIDs – altered PK, increased risk of AKI-HRS and GI bleed – avoid

• Opiates (particularly tramadol) increased half life, constipation, sedation