Liver Cirrhosis: Management

Management of persons with cirrhosis should be done in collaboration with experts in liver diseases. More general management guidance is described below. For dosage adjustment of antiretrovirals, see Dose adjustment of ARVs for impaired Hepatic function

In end-stage liver disease (ESLD), use of EFV may increase risk of CNS symptoms.
ART also provides net benefit to persons with cirrhosis.

Management

Hypervolaemic Hyponatraemia (Na⁺ concentration ≤130 mmol/L)

1. Fluid restriction: 1000-1500 mL/ day
2. Hold diuretics
3. Consider albumin infusion
4. At present, the use of vaptans should be limited to controlled clinical studies

Hepatic Encephalopathy (HE)

General management

1. Identify and treat precipitating factor (GI haemorrhage, infection, pre-renal azotaemia, constipation, sedatives)
2. In patients with severe hyper-acute disease with HE and highly elevated arterial ammonia who are at risk of cerebral oedema, nutritional protein support can be deferred for 24-48 h until hyper­ammonemia is controlled
3. Recommend enteral or parenteral nutritional support in critically ill patients

Specific therapy

• Lactulose 30 cm³ po every 1-2 hours until bowel evacuation, then adjust to a dosage resulting in 2-3 formed bowel movements per day (usually 15-30 cm³ po bid)
• Lactulose enemas (300 cm³ in 1L of water) in persons who are unable to take it po. Lactulose can be discontinued once the precipitating factor has resolved
• Rifaximin 550 mg po bid is an effective add-on therapy to lactulose for prevention of overt hepatic encephalopathy recurrence

Uncomplicated ascites

General management

• Treat ascites once other complications have been treated
• Avoid NSAIDs
  Prophylaxis (Norfloxacin 400 mg po qd) should be given to persons at high risk of spontaneous bacterial peritonitis (SBP)
  1) Persons with cirrhosis and gastrointestinal bleeding
  2) Persons who have had one or more episodes of SBP. (Recurrence rates of SBP within one year have been reported to be close to 70%)
  3) Persons in which ascitic fluid protein is < 1.5 g/dL along with
       • Impaired renal function: creatinine ≥1.2 mg/dL (106 μmol/L), blood urea nitrogen ≥ 25 mg/dL (8.9 mmoL/L), or serum sodium ≤ 130 mEq/L (130 mmoL/L)
       • Liver failure: Child-Pugh score ≥ 9 with bilirubin ≥ 3 mg/dL

Specific management

• Salt restriction: 1-2 g/day. Liberalize if restriction results in poor food intake
• Large volume paracentesis as initial therapy only in persons with tense ascites
• Administer iv albumin (= 6-8 g/L ascites removed)

Follow-up and goals

• Adjust diuretic dosage every 4-7 days
• Weigh the person at least weekly and BUN, uric acid (UA) as surrogate for volume status s-creatinine, and electrolytes measured every 1-2 weeks while adjusting dosage
• Double dosage of diuretics if: weight loss < 2 kg a week and BUN, UA, creatinine and electrolytes are stable
• Halve the dosage of diuretics or discontinue if: weight loss ≥ 0.5 kg/day or if there are abnormalities in BUN, UA, creatinine or electrolytes
• Maximum diuretic dosage: spironolactone (400 mg qd) and furosemide (160 mg qd)

Nutrition: Cirrhotic Persons

Caloric requirements

• Nonobese at least 35 kcal/kg body weight/day; obese 25-35 kcal/kg/ day if BMI 30-40, and 20-25 kcal/ kg/day if BMI>40

Protein requirements

• Protein restriction is not recommended
• Protein intake of 1.2-1.5 g/kg/day of normal body weight
• Type: rich in branched chain (nonaromatic) amino acids

Micronutrients

• Vitamin A, D, E, K; vitamin B1, B3, B6, B9, B12, C, magnesium, zinc, selenium, copper
• Micronutrient deficiencies should be assessed at least annually

Physical activity
Recommended to improve muscle contractile function and muscle mass in patients with cirrhosis. Personalized activity prescription:

• Frequency – Aerobic (4-7 d/week)
• Resistance (2-3 d/week)
• Intensity – Use the talk test (be short of breath but can still speak a full sentence); 3 sets of 10-15
• Time – Start slow and build up - Aerobic: 150 min per week - Resistance: ≥1 day per week •
• Type – aerobic, resistance, flexibility and balance

Personalized activity prescription (guided by a certified exercise physiologist or physical therapist)

Analgesia in persons with Hepatic Failure

• Acetaminophen can be used; caution on daily dose (max 2 g/day)
• NSAIDs generally avoided; predispose persons with cirrhosis to develop GI bleeding. Persons with decompensated cirrhosis are at risk for NSAID-induced renal insufficiency
• Opiate analgesics are not contraindicated but must be used with caution in persons with pre-existing hepatic encephalopathy

HCC Screening

• HCC screening is indicated in all cirrhotic persons with HBV or HCV co-infection (even if HCV infection has been cured and HBV replication is medically suppressed) in a setting where treatment for HCC is available. Although the cost-effectiveness of HCC screening in persons with F3 fibrosis is uncertain, surveillance may be considered based on an individual risk assessment easl.eu/publications/clinical-practice-guidelines/
• In HBV-positive non-cirrhotic persons, HCC screening should follow current EASL guidelines. Risk factors for HCC in this population include family history of HCC, ethnicity (Asians, Africans), HDV co-infection and age > 45 years. EASL guidelines propose using the PAGE-B score in Caucasians to assess the HCC risk, see Assessment of Initial & Subsequent Visits, Cancer: Screening Methods, and Clinical Management and Treatment of Viral Hepatitis Co-infections. Table on fibrosis cut-offs, see Cut-off Values of Non-invasive Tests for the Detection of Significant Fibrosis and Cirrhosis
• Ultrasound (US), with or without alpha-foetoprotein (AFP) every 6 months. AFP should not be used alone. AFP is a suboptimal surveillance tool because of low sensitivity and specificity

Liver Transplant Referral

Best to refer early as disease progresses rapidly

• = MELD⁽ⁱ⁾ score 12 (listing at 15)
• Decompensated cirrhosis (at least one of the following complications at its first occurrence)
• Ascites
• Hepatic encephalopathy
• Variceal bleeding
• Spontaneous bacterial peritonitis
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• NASH cirrhosis⁽ⁱⁱ⁾
• HCC

 see Solid Organ Transplantation (SOT)

1. Unit for both s-creatinine and s-bilirubin is mg/dL. MELD score = 10 {0,957 Ln (serum creatinine (mg/dL)) + 0.378 Ln (total bilirubin (mg/dL)) + 1.12 Ln (INR) + 0.643},
   see https://www.mdcalc.com/meld-score-model-end-stage-liver-disease-12-older
2. Particularly with metabolic decompensations
   
   

Consideration of malnutrition, frailty and sarcopenia in persons with cirrhosis*:

1. All persons with cirrhosis should be assessed for frailty with a standardized tool both at baseline and longitudinally.
2. Given the strong association between muscle mass and outcomes in persons with cirrhosis, objective measures of muscle loss should be considered to assess risk for poor outcomes.
3. All persons with cirrhosis (regardless of a diagnosis of malnutrition) should receive educational resources and counseling regarding the association between nutritional status and outcomes and to optimize nutritional status.

See also hepatorenal syndrome.

* Hepatology 74(3):p 1611-1644, September 2021. | DOI: 10.1002/hep.32049