Liver Cirrhosis: Management
Management of PLWH with cirrhosis should be done in collaboration with experts in liver diseases. More general management guidance is described below
For dosage adjustement 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, if otherwise indicated, also provides net benefit to cirrhotic persons. See Diagnosis Management of Hepatorenal Syndrome (HRS)
Management
Hypervolaemic Hyponatraemia
- Fluid restriction: 1000-1500 mL/ day (consumption of bouillon as required / directed by physician)
- If fluid restriction is ineffective, consider use of oral tolvaptan
- To be started in hospital at 15 mg/day for 3-5 days, then titrated to 30-60 mg/day until normal s-Na; duration of treatment unknown (efficacy/safety only established in short-term studies (1 month))
- S-Na should be monitored closely, particularly after initiation, dose modification or if clinical status changes
- Rapid increases in s-Na concentration (> 8 mmoL/day) should be avoided to prevent osmotic demyelination syndrome
- Persons may be discharged after s-Na levels are stable and without need to further adjust dose
Hepatic Encephalopathy (HE)
General management
- Identify and treat precipitating factor (GI haemorrhage, infection, pre-renal azotaemia, constipation, sedatives)
- Short-term (< 72 hours) protein restriction may be considered if HE is severe
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 PLWH 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) Perosns 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. Liberalise 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
- 25-30 Kcal/kg/day of normal body weight
Protein requirements
- Protein restriction is not recommended (see above for exception if HE)
- Type: rich in branched chain (nonaromatic) amino acids
- Some studies support that parenteral proteins carry less risk of encephalopathy since not converted by colonic bacteria into NH3
Micronutrients
- Mg and Zn
Analgesia in PLWH 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 HBV or HCV co-infected PLWH (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 PLWH with F3 fibrosis is uncertain, surveillance may be considered based on an individual risk assessment https://easl.eu/publication/easl-clinical-practice-guidelines-management-of-hepatocellular-carcinoma/
- In HBV-positive non-cirrhotics, HCC screening should follow current EASL guidelines. Risk factors for HCC in this population include family history of HCC, ethnicity (Asians, Africans), HDV and age > 45 years. EASL guidelines propose using the PAGE-B score in Caucasians to assess the HCC risk, however this score has not been validated in PLWH, see Assessment of PLWH at Initial & Subsequent Visits, Cancer: Screening Methods, and Clinical Management and Treatment of Viral Hepatitis Co-infections in PLWH. 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, see Solid Organ Transplantation (SOT)
- = MELD score 12 (listing at 15)
- Decompensated cirrhosis (at least one of the following complications)
- Ascites
- Hepatic encephalopathy
- Variceal bleeding
- Spontaneous bacterial peritonitis
- Hepatorenal syndrome
- Hepatopulmonary syndrome
- NASH cirrhosis(ii)
- HCC
- 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 - Particularly with metabolic decompensations