What is the best treatment approach for a patient with a Model for End-Stage Liver Disease (MELD) score of 23, who is a liver transplant candidate and experiencing ongoing issues with hepatic encephalopathy?

Management of Hepatic Encephalopathy in a Transplant Candidate with MELD 23

This patient requires urgent liver transplantation evaluation as the definitive treatment, combined with immediate dual therapy of lactulose plus rifaximin for hepatic encephalopathy management. 1, 2

Immediate Transplant Referral is Critical

Patients with end-stage liver disease (MELD 23) and recurrent or persistent hepatic encephalopathy not responding to other treatments should be assessed for liver transplantation—this is a strong recommendation with 100% consensus. 1, 2

• A first episode of overt hepatic encephalopathy should prompt referral to a transplant center, and this patient has ongoing (recurrent/persistent) disease requiring immediate evaluation 1, 2
• Recurrent or persistent hepatic encephalopathy in a patient with MELD 23 dramatically worsens survival, with expected mortality exceeding 50% within 90 days without transplantation 2
• Overall survival after an episode of overt hepatic encephalopathy is only 42% at 1 year and 23% at 3 years without transplantation 2
• Liver transplantation represents the ultimate and only definitive treatment for hepatic encephalopathy in this clinical context 1

Medical Management Strategy

Dual Therapy is Required

Initiate combination therapy with lactulose PLUS rifaximin immediately—this is the standard of care for recurrent/persistent hepatic encephalopathy. 1, 2

• Lactulose: Titrate to achieve 2-3 soft bowel movements per day (strong recommendation, 96% consensus) 1
• Rifaximin 550 mg twice daily: Add rifaximin as an adjunct to lactulose for patients with recurrent episodes (strong recommendation, 92% consensus) 1
• The landmark trial showed rifaximin plus lactulose reduced hepatic encephalopathy recurrence from 45.9% to 22.1% (hazard ratio 0.42, p<0.001) and reduced hospitalizations from 22.6% to 13.6% 3
• Over 91% of patients in rifaximin trials were using concomitant lactulose therapy 1, 4
• Combination therapy showed complete reversal of hepatic encephalopathy in 76% versus 50.8% with lactulose alone (p<0.004), with significantly reduced mortality (23.8% vs 49.1%, p<0.05) 5

Critical Precipitating Factor Management

Systematically identify and correct precipitating factors—this resolves up to 90% of hepatic encephalopathy cases. 6, 7

Common precipitants to address:

• Infections (most common—check for spontaneous bacterial peritonitis, urinary tract infection, pneumonia) 1, 6, 7
• Gastrointestinal bleeding (requires rapid blood removal from GI tract with lactulose or mannitol by nasogastric tube) 1
• Constipation (ensure adequate bowel movements) 6, 7
• Dehydration and electrolyte disturbances (correct hypokalemia, hyponatremia) 1, 6
• Sedative medications (discontinue all psychoactive drugs—they are absolute contraindications) 7, 2
• Acute kidney injury (monitor closely given MELD 23) 7

Monitoring and ICU Considerations

• ICU admission is indicated for MELD >20, especially with organ failures like renal dysfunction 2
• Patients with grade 3-4 hepatic encephalopathy are at aspiration risk and require intensive monitoring 1, 2
• Perform frequent mental status checks with transfer to ICU if level of consciousness declines 6
• Follow closely for metabolic abnormalities including glucose, potassium, magnesium, and phosphate levels 6

Critical Contraindications to Avoid

TIPS (transjugular intrahepatic portosystemic shunt) is absolutely contraindicated in this patient. 2

• Overt recurrent/chronic hepatic encephalopathy is an absolute contraindication to TIPS 2
• Three-month mortality with TIPS for MELD ≥25 is 66% 2
• Benzodiazepines are absolutely contraindicated in decompensated cirrhosis 2

Important Limitations of Rifaximin

Rifaximin has not been studied in patients with MELD scores >25, and only 8.6% of patients in controlled trials had MELD scores over 19. 4

• There is increased systemic exposure in patients with more severe hepatic dysfunction 4
• However, rifaximin remains FDA-approved for reduction in risk of overt hepatic encephalopathy recurrence in adults, with 91% of trial patients using concomitant lactulose 4

Nutritional Support

• Address malnutrition present in approximately 75% of patients with hepatic encephalopathy 6
• Provide moderate hyperalimentation with small, frequent meals throughout the day, including a late-night snack 6
• Multivitamin supplementation is generally recommended 6
• Consider replacement of animal protein with vegetable and dairy protein, provided overall protein intake is not compromised 1

Quality of Life Considerations

• Development of hepatic encephalopathy in cirrhosis is associated with markedly reduced quality of life beyond the mortality impact 2
• Recurrent hospitalizations for hepatic encephalopathy episodes severely impair daily functioning and autonomy 2
• Patients who have had an episode of overt hepatic encephalopathy should be provided with information on the risks associated with driving and appropriateness of formal driving assessment 1

Common Pitfalls to Avoid

• Do not fail to seek precipitating factors—they cause 90% of cases 6, 7
• Do not rely exclusively on ammonia levels for diagnosis—isolated blood ammonia determination does not provide diagnostic, prognostic, or staging value 6
• Do not confuse hepatic encephalopathy with other causes of altered mental status—this is a diagnosis of exclusion requiring thorough investigation 7
• Do not delay transplant evaluation—this patient's MELD score and recurrent hepatic encephalopathy mandate urgent assessment 1, 2
• Do not use rifaximin monotherapy—it should always be combined with lactulose in this clinical context 1