Liver failure

Hepatic encephalopathy

• Chronic encephalopathy warrants treatment when it interferes with lifestyle – one of the earliest signs is excessive wakefulness at night, followed by forgetfulness, and then the more overt signs (foetor, flap, asterixis).
• Eliminate benzodiazepines or other sedating medication if possible
• Beware of dehydration – if on a diuretic, consider stopping it until the encephalopathy is controlled.
• Reduce protein load if this is excessive, but very low protein diets are detrimental to nutrition.
• Give lactulose¹ 10 ml 3x/d, titrated to achieve relief of symptoms. (May need 20-30 ml 3x/d)

Perspective – lactulose, neomycin and metronidazole.

Although neomycin has been recommended for 40 years for this condition, evidence of efficacy is lacking. The only readily identifiable placebo controlled RCT of neomycin² failed to demonstrate superiority over placebo in the mean time from therapy initiation to reaching Grade 0 encephalopathy. (39 hours in the neomycin group versus 49 hours in the placebo group) However the trial was small (20 active, 19 placebo) and so is underpowered to convincingly demonstrate lack of benefit. Metronidazole is touted as a safer and more effective alternative to neomycin, however the evidence for this is not much better, and it has been described as causing an encephalopathy in its own right.

Lactulose seems to have a beneficial effect on mortality (absolute risk reduction in mortality about 4% in a group with a baseline mortality rate of 8%) when evaluated in a group of trials including other non-absorbable disaccharides and patients with varying degrees of morbidity.³ The evidence for low protein diets is less clear.⁴

Renal impairment in liver disease.

• Iatrogenic dehydration in someone with liver disease is common, and the remedy is simple – don’t worry about a bit of ascites and leg swelling, but keep the kidneys going. Stop diuretics and stop aminoglycosides.
• Sepsis is often overlooked, particularly primary bacterial peritonitis. Think of it, diagnose it and treat it.
• Hypotension related to over-enthusiastic ascitic tapping may lead to an ATN type situation.
• The ‘true’ renal failure associated with liver failure in fact gives urinary indices highly suggestive of ATN.

Hypoglycaemia in liver disease.

Keep on NGT caloric supplements, plus I.V. 10% dextrose infusion as necessary but beware of hyponatraemia. This is an eminently preventable cause of deterioration. Don’t forget to give thiamine in anyone with borderline nutrition given dextrose.

Bleeding varices

Check and correct INR, consider metoclopramide I.V. 10 mg 3x/d, and insert a Sengstaken tube, then once resuscitated organise transfer to an endoscopy service where injection or ligation can be performed.

Sengstaken – method.

Place 250 ml of air in the gastric balloon, and then pull it back up against the OG junction. If this doesn’t stop the bleeding, then place 40 ml of air into the oesophageal balloon. Suction regularly above the balloon (either via a separate NG tube, or the third lumen of the tube if there is one). Try to remove the tube in less than 24 hours.

Prophylaxis of variceal bleeding

It is reasonable to add carvedilol 6.25 mg for Child Pugh B and C (and 12.5 mg 12 hourly for Child Pugh A.)

Perspective – bleeding in liver disease.

There is often an endeavour to correct the coagulation defect in liver disease with parenteral vitamin K, but if a procedure is planned (e.g. biopsy) then INR correction with FFP is quicker and more likely to be successful. The defect is usually in clotting factor synthesis, not because of vitamin K deficiency. There may be a case to be made for the use of parenteral vitamin K in patients with cholestasis, where there is possibly reduced vitamin K absorption.

Infection in patients with liver disease.

Look for this when patients present with deterioration in encephalopathy – pneumonia, urinary tract infections and primary peritonitis are the usual causes, although a primary gram-negative septicaemia with no obvious portal of entry may also occur.

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1. Weber FL. Effects of lactulose on nitrogen metabolism. Scandinavian J Gastroenterol. 1997;222:83-87 ↩

2. Strauss E, Tramote R, Silva EP, et al. Double-blind randomised clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology. 1992;.39:542-5 ↩

3. Gluud LL, Vilstrup H, Morgan MY. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2016 May 6;2016(5):CD003044. doi: 10.1002/14651858.CD003044.pub4. PMID: 27153247; PMCID: PMC7004252. ↩

4. Shawcross D, Jalan R. Dispelling myths in the treatment of hepatic encephalopathy. Lancet. 2005;365:431-3 ↩

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