What are the current guideline recommendations for managing adult patients with liver cirrhosis?

Management of Liver Cirrhosis

The cornerstone of cirrhosis management is aggressive treatment of the underlying liver disease—complete alcohol abstinence for alcoholic cirrhosis, antiviral therapy for viral hepatitis, or immunosuppression for autoimmune hepatitis—as this directly prevents decompensation, potentially reverses early fibrosis, and improves survival more than any other intervention. 1, 2, 3

Immediate Etiologic Treatment

The management paradigm has shifted from reactive treatment of complications to proactive prevention of disease progression while patients remain compensated. 3

Viral Hepatitis B

• Initiate antiviral therapy immediately if HBV DNA ≥2,000 IU/mL, regardless of ALT levels, using entecavir (1 mg daily, not 0.5 mg) or tenofovir as first-line agents due to their potent antiviral efficacy and high genetic barrier to resistance. 3
• In decompensated cirrhosis, treat all patients regardless of HBV DNA level. 3
• Peginterferon-α is absolutely contraindicated in decompensated cirrhosis due to risk of hepatic failure, severe infection, and death. 3
• Entecavir achieves HBV DNA suppression in 57% of patients at week 48 (versus 20% with adefovir) and improves Child-Pugh scores in nearly 50% of treatment-naïve patients. 3

Viral Hepatitis C

• Direct-acting antivirals (such as ledipasvir/sofosbuvir) improve liver function and reduce portal hypertension in both compensated and decompensated cirrhosis. 2, 3

Alcoholic Cirrhosis

• Complete and permanent alcohol abstinence is mandatory and can lead to "re-compensation" with excellent long-term outcomes in some patients, though disease progression may continue in others despite abstinence. 2, 3

Autoimmune Hepatitis

• Immunosuppressive therapy yields clear benefits even in decompensated disease. 3

Surveillance and Screening

Hepatocellular Carcinoma (HCC)

• Perform six-monthly abdominal ultrasound with serum alpha-fetoprotein (AFP) for HCC surveillance in all patients with cirrhosis. 1, 2
• For HCC within accepted criteria (solitary ≤5 cm or up to three lesions ≤3 cm), liver transplantation is the recommended first-line treatment for patients with decompensated cirrhosis. 1
• Surgical resection is preferred for HCC in non-cirrhotic liver and is first-line for solitary HCC in cirrhotic liver when liver function is maintained (Child-Pugh A). 1
• Thermal ablation (radiofrequency or microwave) is first-line for solitary <2 cm HCC in compensated cirrhosis, with choice between ablation and resection based on tumor location, liver function, and portal hypertension severity. 1

Esophageal Varices

• Perform upper endoscopy at diagnosis to screen for esophageal varices. 2
• Liver stiffness ≥20 kPa or platelet count <150 ×10⁹/L warrants upper endoscopy to assess for varices. 3
• In patients with clinically significant portal hypertension (HVPG ≥10 mmHg) without high-risk varices, non-selective beta-blockers (carvedilol or propranolol) reduce the composite outcome of decompensation or death from 27% to 16%. 3, 4
• If large varices are present, start non-selective beta-blocker therapy or endoscopic band ligation. 3

Nutritional Management

• Restrict dietary sodium to <5 g/day (≈88 mmol/day or 2000 mg/day); stricter restriction worsens malnutrition and is not recommended. 2, 3
• Provide adequate protein intake of 1.2-1.5 g/kg/day, carbohydrate intake of 2-3 g/kg/day, and total calories of 35-40 kcal/kg/day. 2
• In patients with sarcopenia, sarcopenic obesity, or decompensated cirrhosis, provide high-protein diet and a late-evening snack. 1
• Bed rest is not recommended, as excessive bed rest causes muscle atrophy; patients should remain active unless complicated by bleeding, encephalopathy, infection, hypotension, or liver cancer. 3

Management of Ascites

Initial Treatment by Grade

• Grade 1 ascites (detectable only by imaging): Sodium restriction to <5 g/day, treat underlying disease, discontinue NSAIDs, ACE inhibitors, or angiotensin receptor blockers. 3
• Grade 2 ascites (moderate, visible): Add spironolactone 100 mg once daily as first-line monotherapy plus sodium restriction. 2, 3
• Grade 3 ascites (massive/tense): Perform therapeutic paracentesis first, then initiate sodium restriction and diuretic therapy. 2, 3

Diuretic Regimen

• Start spironolactone 100 mg once daily; if weight loss is <2 kg/week, increase by 100 mg every 72 hours up to maximum 400 mg/day. 2, 3
• Add furosemide 40 mg/day when spironolactone alone is insufficient or hyperkalemia develops (potassium >5.5 mmol/L); titrate in 40-mg increments to maximum 160 mg/day. 2, 3
• For recurrent or long-standing ascites, begin combination therapy (spironolactone + furosemide) from the outset to achieve faster natriuresis and lower hyperkalemia risk. 2
• Target weight loss of 0.5 kg/day without peripheral edema or 1 kg/day with edema. 3

Monitoring During Diuretic Therapy

• Check serum creatinine, sodium, and potassium at least weekly during the first month of diuretic treatment. 2, 3
• Temporarily stop diuretics if serum sodium drops below 120-125 mmol/L. 2, 3

Fluid Restriction

• Fluid restriction is unnecessary unless serum sodium falls below 120-125 mmol/L. 2, 3

Large-Volume Paracentesis

• For large-volume paracentesis, administer 8 g of albumin per liter of ascites removed (≈100 mL of 20% albumin for every 3 L of fluid). 3
• When removing <5 L, albumin is not required; a synthetic plasma expander (150-200 mL of gelofusine or Haemaccel) is sufficient. 3

Refractory Ascites

• Refractory ascites is defined as ascites that recurs ≥3 times within 12 months despite optimal sodium restriction and maximal tolerated diuretic doses. 3
• Options include serial large-volume paracentesis every 2-3 weeks with albumin replacement, transjugular intrahepatic portosystemic shunt (TIPS), or liver transplantation. 2, 3
• TIPS should be considered only in highly selected cirrhotic patients; contraindications include age >70 years, bilirubin >50 µmol/L, platelets <75 ×10⁹/L, MELD ≥18, active hepatic encephalopathy, infection, hepatorenal syndrome, and malignant ascites. 5, 3
• Palliative care referral should be offered to patients with refractory ascites who are not transplant candidates. 3

Management of Spontaneous Bacterial Peritonitis (SBP)

Diagnosis

• Perform diagnostic paracentesis without delay in all cirrhotic patients with ascites on hospital admission or with any clinical deterioration (fever, abdominal pain, altered mental status, unexplained deterioration, new encephalopathy, renal impairment, or unexplained leukocytosis). 5, 3
• Inoculate ascitic fluid into blood-culture bottles at bedside to improve pathogen detection. 3
• Ascitic neutrophil count >250 cells/mm³ confirms SBP. 5, 3
• Obtain ascitic fluid for cell count with differential, culture, albumin, and total protein. 5

Treatment

• Initiate immediate empirical antibiotic therapy; in decompensated cirrhosis or quinolone-resistant settings, use ceftriaxone 1 g/24h for up to 7 days; in remaining patients, use oral norfloxacin 400 mg twice daily. 3
• Administer albumin 1.5 g/kg within 6 hours of diagnosis, followed by 1 g/kg on day 3, especially when serum creatinine is rising or already elevated. 3

Prophylaxis

• Patients recovering from an SBP episode should receive continuous oral norfloxacin 400 mg daily (or ciprofloxacin 500 mg daily) for secondary prophylaxis. 3
• Patients with gastrointestinal bleeding and ascites should receive prophylactic antibiotics (ceftriaxone 1 g daily for up to 7 days or oral norfloxacin 400 mg twice daily). 3

Management of Hepatic Encephalopathy (HE)

Diagnosis

• Diagnose HE clinically based on mental status, vigilance, attention, and spatial-temporal orientation; the Animal Naming Test (<20 animals in 1 minute) suggests covert HE. 5, 3
• Blood ammonia should be measured only when HE is uncertain; a normal value argues against HE, whereas an elevated value does not confirm it. 5
• Obtain brain imaging (CT or MRI) during the first HE episode to exclude intracranial hemorrhage, which is more common in cirrhotic patients. 5

Treatment

• Identify and treat precipitating factors: gastrointestinal bleeding, infection, dehydration, constipation, electrolyte disturbances, and medication noncompliance. 5, 3
• Serum sodium <130 mmol/L is an independent risk factor for HE and predicts poor response to lactulose. 5
• Discontinue benzodiazepines immediately; they are contraindicated in decompensated cirrhosis. 5
• Limit proton-pump inhibitor use to validated indications only. 5
• Initiate lactulose as first-line therapy; in meta-analyses of 705 patients, lactulose reduced mortality from 14% to 8.5% compared to placebo. 4
• Add rifaximin for persistent or recurrent HE episodes; in trials of 1,415 patients, rifaximin reduced recurrent overt HE from 46.8% to 25.5%. 4
• Oral non-absorbable disaccharides may prevent the development of hepatic encephalopathy. 3

Management of Acute Variceal Bleeding

• Initiate vasoactive drugs (terlipressin, octreotide) immediately upon suspicion of variceal bleeding, even before endoscopic confirmation. 3
• Terlipressin should not be used in patients with hypoxemia or active coronary, peripheral, or mesenteric ischemia, and should be used with caution in acute-on-chronic liver failure grade 3. 3
• Antibiotic prophylaxis is essential in all cirrhotic patients with gastrointestinal bleeding. 3
• Use a restrictive transfusion strategy with a hemoglobin threshold of 7 g/dL, target 7-9 g/dL. 3
• Administer erythromycin 250 mg IV 30-120 minutes before endoscopy to improve visibility, unless QT prolongation is present. 3
• Perform endoscopic band ligation within 12 hours of admission once hemodynamic stability is achieved. 3
• TIPS should be used as rescue therapy for persistent bleeding or early rebleeding. 3
• Avoid nephrotoxic drugs, large volume paracentesis without albumin replacement, and hypotensive drugs during acute variceal hemorrhage. 3

Management of Hepatorenal Syndrome (HRS)

• To prevent HRS, avoid nephrotoxic drugs (NSAIDs, aminoglycosides), large-volume paracentesis without albumin replacement, and medications that may cause hypotension. 3
• In a randomized trial of 300 patients, terlipressin improved the rate of reversal of HRS from 18% to 39%. 4

Medications to Avoid

• NSAIDs are absolutely contraindicated in cirrhosis because they reduce urinary sodium excretion, induce azotemia, precipitate renal dysfunction, and can convert diuretic-sensitive ascites to refractory ascites. 2, 3
• Metformin is contraindicated in decompensated cirrhosis due to lactic acidosis risk; it may be used in compensated cirrhosis with estimated GFR >30 mL/min. 1, 3
• Sulfonylureas should be avoided in hepatic decompensation because of hypoglycemia risk. 1, 3

Medications Safe with Caution

Diabetes Management

• Compensated cirrhosis (Child-Pugh A): GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) and SGLT2 inhibitors (empagliflozin, dapagliflozin) are acceptable. 1
• Child-Pugh B: SGLT2 inhibitors may be used. 1
• Decompensated cirrhosis: Insulin therapy is the only evidence-based option for treating type 2 diabetes. 3

Cardiovascular Medications

• Statins can be prescribed in compensated cirrhosis according to cardiovascular-risk guidelines; they may also lower portal pressure and improve survival, though further validation is needed. 3

Non-Selective Beta-Blockers in Refractory Ascites

• Non-selective beta-blockers are not an absolute contraindication in refractory ascites; continue with close monitoring. 3
• Reduce or stop non-selective beta-blockers if mean arterial pressure falls <65 mmHg or if acute/progressive renal dysfunction develops. 3

Monitoring Schedule

• Monitor serum electrolytes, creatinine, and weight within 1 week of diuretic initiation or dose changes. 5
• Calculate Child-Pugh and MELD scores every 6 months for prognostic assessment. 2
• Liver function tests should be obtained every 1-3 months. 3
• In HBV-related disease, measure serum HBV DNA (real-time PCR) and HBeAg status every 2-6 months. 3

Liver Transplantation Evaluation

• Refer all patients with newly diagnosed cirrhosis for liver transplantation evaluation, as development of ascites carries a 20% one-year mortality. 2
• All patients with decompensated cirrhosis should be evaluated for liver transplantation. 2, 3
• Evaluation for liver transplantation is indicated for patients with a MELD score of 15 or greater, complications of cirrhosis, or hepatocellular carcinoma. 6
• All patients with SBP should be evaluated for liver transplantation as part of definitive management. 3

Gastroenterology Referral Indications

• Development of any decompensation events (ascites, variceal bleeding, hepatic encephalopathy) requires referral to gastroenterology. 3
• Refractory ascites not responding to maximum diuretic therapy requires referral. 3
• Need for TIPS placement for refractory ascites or recurrent variceal bleeding requires referral. 3

Common Pitfalls

• Do not restrict fluids routinely; fluid restriction is only indicated for severe hyponatremia (<120-125 mmol/L) and may worsen effective hypovolemia. 5, 2
• Do not use intravenous diuretics; oral administration is standard and IV use can cause acute kidney injury from rapid fluid shifts. 5
• Do not rely on ammonia levels to diagnose or monitor HE; HE remains a clinical diagnosis of exclusion. 5
• Proper ammonia sampling requires a fasting patient, avoidance of venous stasis, collection in an EDTA tube, and transport on ice within 60-90 minutes. 5
• Severely elevated ammonia (>100 µmol/L) in the setting of minimal liver dysfunction should prompt evaluation for inherited metabolic disorders. 5