liver disease 2 - management of complications

• complications of liver disease;

  Severe liver disease;

  • Ascites
  • Varices
  • Encephalopathy
• what are ascites?

  Accumulation of fluid in the peritoneal cavity, leading to swollen (or expanded) abdomen - "abdominal distension"

  Can be uncomfortable, and may affect breathing and eating.
• when does abdominal distension occur?

  when substances, such as air or fluid accumulate in the abdomen causing it to expand
• what is the treatment for ascites?

  Diuretics. Spironolactone (an aldosterone antagonist) +/- furosemide (loop diuretic).
• what is the rationale for using spironolactone and furosemide?

  Diuresis - induces negative fluid balance and reduction in the amount of ascites.

  Spironolactone is useful as it is an aldosterone antagonist. Liver patients have high-circulating levels of aldosterone.
• what's an alternative to spironolactone for ascites?

  Amiloride. Can be used if spironolactone is not well tolerated e.g. due to side-effects such as gynaecomastia.
• how can you monitor the working effect of spironolactone and furosemide?

  Weight loss.
• what needs to be monitored when taking spironolactone and furosemide?

  • Daily weight
  • Renal function, urea, electrolytes - especially sodium, potassium and creatinine.
  • Side effects and tolerability.
• what is spontaneous bacterial peritonitis (SBP)?

  Infection of the ascitic fluid. It can be caused by gram-negative or positive bacteria.
• symptoms and signs of spontaneous bacterial peritonitis;

  patients may have severe abdominal pain, raised temperature and erased white-cell count
• diagnosis of SBP;

  Take a sample of ascitic fluid. SBP if the neutrophil count > 250 cells per mm^3
• what is the treatment for SBP?

  • Initially treat with a broad spectrum intravenous (IV) antibiotic e.g.
  • 3rd generation cephalosporins such as ceftazidime
  • Piperacillin with tazobactam
  • Treatment for 5 days and review to see if infection resolved
  • Ciprofloxacin or co-trimoxazole may be required longer term as prophylaxis (preventative therapy)
• What is hepatic encephalopathy?

  Changes in the brain – can be changes in mood & behaviour, confusion, delirium and coma

  Four grades dependent on clinical signs (grade 1 – 4)
• symptoms of hepatic encephalopathy;

  • Confusion
  • Forgetfulness
  • Changes in mood/personality
  • Poor concentration
  • Hepatic “flap”, worsening handwriting
  • Seizure
  • Tremors
  • Coma
• precipitants for hepatic encephalopathy;

  • A build-up of toxins and chemical mediators e.g. ammonia
  • Dehydration
  • Constipation
  • Infection
  • Medication
• what is the treatment for hepatic encephalopathy?

  Strategies for avoiding precipitants and lowering ammonia levels.

  Changing the pH gut reduces the absorption of ammonia into the bloodstream by preventing the growth ammonia producing bacteria in the gut. This change also favours the growth of non-ammonia-producing bacteria.
• what is a medication used to treat hepatic encephalopathy?

  Lactulose - 20-30 mls 2-3 times a day

  or Phosphate enema once or twice daily
• what is the rationale for using lactulose?

  Inhibits intestinal ammonia production by several mechanisms including changing the pH of the gut lumen and reducing colonic bacterial load.

  Helps to reduce/prevent episodes of hepatic encephalopathy.
• what needs monitoring when using lactose for treatment?

  number of soft stools per day - should aim for 2-3
• what else other than laxatives can be used to help treat hepatic encephalopathy?

  antibiotics - Rifaxamin tablets 550mg twice daily

  and L-ornithine L-aspartate sachets (unlicensed)
• rationale for using rifaxamin;

  low systemic absorption, and high levels in faeces. Kills gut bacteria to reduce ammonia levels (gut bacteria produce ammonia)
• rationale for L-ornithine L-aspartate sachets

  increases removal of ammonia
• what is portal hypertension and varices?

  Portal hypertension = increased blood pressure around the liver - portal vein.

  When the liver becomes severely scarred, it's harder for blood to move through it. Leading to an increase in pressure of blood around the intestine.

  Varices - dilated, tortuous veins that develop in response to increased pressure.
• what can cause the increased resistance to blood flow? (portal hypertension)

  This can be due to:

  • disruption of hepatic architecture
  • compression of hepatic venules by regulating nodules
• what can occur when there's an increase in resistance to blood flow?

  Collateral vessels (varices) form - enable blood to bypass the liver. These blood vessels are very weak and can split and bleed. This can cause massive bleeding and be life-threatening.
• where does the portal vein carry blood?

  carries blood from bowel and spleen to the liver
• symptoms of portal hypertension and varices;

  may include:

  • vomiting blood
  • passing blood in stool
  • medical emergency
• Management of portal hypertension and varices;

  Resuscitation - fluid, blood transfusion

  Endoscopy - banding or injection sclerotherapy (glue) of varices.
• Initial medication for portal hypertension;

  • Terlipressin (potent vasoconstriction)
  • Antibiotics – infection common. IV broad spectrum antibiotic e.g. piperacillin and tazobactam
  • Proton-pump inhibitor e.g. omeprazole
• secondary prophylaxis (prevention) of portal hypertension/varices;

  • Propranolol tablets
  • Non-selective beta-blocker (NSBB) – antagonist of beta-1 and beta-2 receptors
  • Beta-2 blockade - splanchnic (gut) vasoconstriction
  • Beta-1 blockade - decreased heart and cardiac index
  • Results in reduced portal flow and decreased portal pressure
  • Beta-blockers prevent re-bleeding and increase survival
  • Nadolol or Carvedilol can also be used as have action on beta-1 and beta-2 receptors and is often better tolerated in terms of side effects
• what is pruritus?

  Itching. Due to cholestasis which can lead to the build-up of bile acids in the blood and under the skin. It can affect anywhere in the body.
• what are the treatment options for pruritus?

  Topical treatments - like calamine lotion, and menthol 2% in aqueous cream.

  Oral medications

  • Colestyramine
  • Ursodeoxycholic acid
  • Antihistamines - e.g chlorpheniramine are often prescribed but thought to be ineffective
• how does colestyramine help treat pruritus?

  It is an anion-exchange resin - that binds to bile acids in the small intestine which reduces the circulating and reabsorption of bile acids in the bloodstream. But it can also affect the absorption of other medicines and fat-soluble vitamins.
• how does Ursodeoxycholic acid treat pruritus?

  A type of bile acid and so increases the proportion of 'watery' bile acids and helps bile acids to flow better.
• symptoms of alcohol withdrawal can range from mild - severe;

  • Delirium, marked tremor
  • Fear and delusions, restlessness and agitation
  • Fever
  • Rapid pulse
  • Dehydration
  • Seizures
• treatment for alcohol withdrawal;

  Benzodiazepines - Chlordiazepoxide (usually first-line), lorazapam (shorter-acting)
• rationale for using Benzodiazepine e.g. chlordiazepoxide for alcohol withdrawal?

  Prevents withdrawal symptoms such as agitation and alcohol withdrawal seizures (sedative and anti-convulsant properties)
• mechanism of benzodiazepines;

  Benzodiazepines are cross-tolerant with alcohol and modulate anxiolysis by stimulating GABA-A receptors. During withdrawal from one agent, the other may serve as a substitute
• why use chlordiazepoxide?

  • Long half-life and slower onset action – less abuse potential
  • Low potency
• what is the detoxification regime?

  Structured treatment plan aimed at gradually tapering and discontinuing the use of a medication that someone becomes dependant on.