How should cirrhosis be evaluated and managed, including identification of etiology, disease staging, and prevention/treatment of complications?

Evaluation and Management of Cirrhosis

Cirrhosis must be classified into two distinct clinical stages—compensated versus decompensated—based on the presence or absence of overt complications (ascites, variceal hemorrhage, or hepatic encephalopathy), as this classification fundamentally determines prognosis and management strategy. 1

Initial Risk Stratification and Staging

Stage classification is critical for prognosis: Compensated cirrhosis has a median survival exceeding 12 years, while decompensated cirrhosis drops dramatically to only 1.8 years. 1

Compensated Cirrhosis Substaging

Patients with compensated cirrhosis should be further substaged based on portal hypertension severity: 1

• Mild portal hypertension: HVPG <10 mm Hg 1
• Clinically significant portal hypertension (CSPH): HVPG ≥10 mm Hg, present in 50-60% of compensated patients without varices 1
• With gastroesophageal varices: Present in 30-40% of compensated patients; by definition indicates CSPH (HVPG ≥10 mm Hg) 1

CSPH significantly increases risk of developing varices, clinical decompensation, postsurgical complications, and hepatocellular carcinoma. 1

Decompensated Cirrhosis Classification

Decompensated patients can be further stratified into: 2, 3

• Stable decompensated cirrhosis (SDC)
• Unstable decompensated cirrhosis (UDC)
• Pre-ACLF
• ACLF (grades 1-3) 2, 3

Identification of Etiology

Systematic evaluation for underlying causes is mandatory: 1, 4

Initial Workup

• Viral hepatitis serologies (HBV, HCV, HDV) 1, 4
• Ferritin and transferrin saturation (hemochromatosis) 4
• Autoimmune markers (ANA, ASMA, immunoglobulins) 1
• Alcohol consumption assessment with specific quantification 1
• Metabolic factors: Evaluate for diabetes, obesity, nonalcoholic fatty liver disease 1, 4
• Drug-induced hepatotoxicity review 1
• HIV testing 1

Abdominal Imaging

Abdominal ultrasonography should be performed initially to assess liver morphology, exclude biliary obstruction, and screen for hepatocellular carcinoma. 1, 4

Disease Severity Assessment

Non-Invasive Fibrosis Assessment

Liver biopsy is no longer required in most cases. Non-invasive methods perform well for identifying cirrhosis or excluding significant fibrosis: 1

• Transient elastography (liver stiffness measurement): Cirrhosis typically confirmed at ≥15 kPa 1, 5
• Serum biomarker panels: APRI score, FIB-4 score, FibroTest, NAFLD fibrosis score 1, 4
• Combination approaches (elastography plus biomarkers) improve accuracy and reduce need for biopsy 1

Liver biopsy remains indicated when: 1

• Non-invasive results are contradictory or indeterminate
• Mixed etiologies are suspected
• Coagulation disorders preclude elastography (transjugular approach can be used)
• Results would alter management decisions

Prognostic Scoring Systems

• Child-Turcotte-Pugh (CTP) classification: Class A indicates compensated disease; Classes B/C indicate mostly decompensated disease 1
• MELD score: Independent predictor of decompensation; transplant evaluation indicated when ≥15 1, 6
• Serum albumin: Independent predictor of decompensation even in compensated cirrhosis 1

Treatment of Underlying Etiology

Aggressive treatment of the underlying cause is the cornerstone of management and can potentially reverse early cirrhosis, prevent decompensation, and improve survival. 7, 8

Alcohol-Related Cirrhosis

Complete and permanent cessation of alcohol consumption is mandatory and may lead to "re-compensation" with excellent long-term outcomes. 7, 8

Viral Hepatitis B

For compensated cirrhosis: 7

• Initiate antiviral therapy if HBV DNA ≥2,000 IU/mL regardless of ALT levels
• First-line agents: Entecavir or tenofovir (potent efficacy, high genetic barrier to resistance)
• Long-term treatment generally required
• Peginterferon-α may be used with careful monitoring in well-preserved liver function

For decompensated cirrhosis: 7

• Treat all patients regardless of HBV DNA level
• Preferred regimens: Tenofovir plus lamivudine combination, or entecavir or tenofovir monotherapy
• Interferon-α is absolutely contraindicated due to risk of serious complications including infection and hepatic failure

Viral Hepatitis C

Direct-acting antivirals improve liver function and reduce portal hypertension, though effects are not universal. 7, 8 Continuous monitoring for complications and HCC is needed even after achieving sustained virologic response. 7

Autoimmune Hepatitis

Immunosuppressive therapy shows beneficial effects even in decompensated cirrhosis. 7

Prevention and Management of Complications

Variceal Bleeding Prevention

Primary prophylaxis in compensated cirrhosis: 7

• Screening endoscopy to assess for varices requiring prophylaxis
• Non-selective beta-blockers (carvedilol or propranolol) for patients with varices: In a 3-year trial of 201 patients with portal hypertension, reduced risk of decompensation or death (16% vs 27% with placebo) 5
• Prophylactic band ligation as standard of care for varices 7

Acute variceal bleeding management: 7

• Initiate vasoactive drugs immediately upon suspicion, even before endoscopic confirmation
• Antibiotic prophylaxis is essential: Ceftriaxone 1 g/24h for up to 7 days in decompensated cirrhosis or quinolone-resistant settings; oral norfloxacin 400 mg twice daily in remaining patients 7
• Restrictive transfusion strategy: Hemoglobin threshold of 7 g/dL, target 7-9 g/dL 7, 5
• Erythromycin 250 mg IV 30-120 minutes before endoscopy improves visibility (unless QT prolongation present) 7
• Endoscopic band ligation within 12 hours of admission once hemodynamically stable 7
• TIPS as rescue therapy for persistent bleeding or early rebleeding 7

Prognostic factors in variceal hemorrhage: Mortality differs significantly—20% 5-year mortality if isolated complication versus >80% if associated with other complications. Bacterial infections and HVPG >20 mm Hg (mostly CTP-C class) predict poor outcomes. 1

Ascites Management

Grade 1 ascites (mild): 7

• Sodium restriction to <5 g/day (but not more restrictive, as this may worsen malnutrition)
• Treatment of underlying disease
• Discontinue NSAIDs, ACE inhibitors, angiotensin receptor blockers
• Nutritional treatment and education

Grade 2 ascites (moderate): 7

• Sodium restriction
• Oral diuretics: Spironolactone (aldosterone antagonist) starting dose 50-100 mg/day, maximum 400 mg/day; add furosemide (loop diuretic) 20-40 mg/day, maximum 160 mg/day if needed
• Combination therapy superior: In trials, combination aldosterone antagonist and loop diuretics resolved ascites more effectively than sequential initiation (76% vs 56%) with lower hyperkalemia rates (4% vs 18%) 5
• Treatment of underlying disease
• Discontinue nephrotoxic agents

Grade 3 ascites (tense): 7

• Therapeutic paracentesis followed by sodium restriction and diuretic therapy
• Fluid restriction not necessary unless serum sodium <120-125 mmol/L

Refractory ascites: 7

• Serial large-volume paracentesis with albumin replacement
• TIPS placement
• Liver transplantation evaluation
• Peritoneovenous shunt or experimental medical therapy
• Palliative care referral if not transplant candidate

Common pitfall: Patients requiring paracenteses more frequently than every 2 weeks likely have poor dietary compliance. 7 Bed rest is not recommended as excessive bed rest causes muscle atrophy; outpatient management is appropriate unless complicated by bleeding, encephalopathy, infection, hypotension, or liver cancer. 7

Spontaneous Bacterial Peritonitis (SBP)

• Perform diagnostic paracentesis without delay in all cirrhotic patients with ascites on hospital admission 7
• Diagnosis: Ascitic neutrophil count >250/mm³ 7
• Immediate empirical antibiotic therapy based on context, severity, and local resistance patterns 7
• Prophylaxis: Patients with GI bleeding and ascites should receive prophylactic antibiotics (cefotaxime or based on local data) 7

Hepatic Encephalopathy

• Lactulose: Reduced mortality relative to placebo (8.5% vs 14%) in trials of 705 patients and reduced recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in trials of 1,415 patients 5
• Rifaximin as adjunctive therapy 4
• Oral non-absorbable disaccharides may prevent development of hepatic encephalopathy 7
• Lifestyle and nutritional modifications 4

Hepatorenal Syndrome

Terlipressin: In a trial of 300 patients, improved reversal rate from 18% to 39%. 5

Hepatocellular Carcinoma Surveillance

• Ultrasound screening every 6 months for all patients with cirrhosis 6, 4
• Continue surveillance even after achieving SVR in viral hepatitis 7
• CSPH increases HCC risk independent of other factors 1

Nutritional Management

Nutritional assessment is critical: 7

• Rapid nutritional screening in all patients; assume high malnutrition risk if BMI <18.5 kg/m² or Child-Pugh C
• Assess sarcopenia using CT scan, anthropometry, DEXA, or BIA
• Evaluate muscle function with handgrip strength and/or short physical performance battery
• Sodium restriction to <5 g/day for ascites control, but greater restriction not recommended due to malnutrition risk

Medications to Avoid

NSAIDs are absolutely contraindicated: They reduce urinary sodium excretion, precipitate renal dysfunction, and convert diuretic-sensitive ascites to refractory ascites. 7

Also avoid: 7

• ACE inhibitors
• Angiotensin receptor blockers
• Nephrotoxic agents
• Large volume paracentesis without albumin replacement
• Hypotensive drugs during acute variceal hemorrhage

In decompensated cirrhosis: 7

• Metformin is contraindicated due to lactic acidosis risk
• Do not use HbA1c for diabetes diagnosis or monitoring
• Insulin therapy is the only evidence-based option for type 2 diabetes

Monitoring and Follow-Up

Clinical assessment every 6 months: 6

• Laboratory tests
• Child-Pugh score calculation
• MELD score calculation
• Evaluation for cirrhosis-related complications

Emerging monitoring technologies: 7, 8

• Bluetooth-linked weighing scales and smartphone apps enable providers to monitor weight changes and intervene early
• Remote monitoring and telemedicine can improve outcomes and reduce hospital readmissions
• Heart rate variability monitoring may identify patients at risk of decompensation

Indications for Gastroenterology Referral

Immediate referral required for: 7, 2

• Development of any decompensation event (ascites, variceal bleeding, hepatic encephalopathy)
• Refractory ascites not responding to maximum diuretic therapy
• Need for TIPS placement
• MELD score ≥15
• Hepatocellular carcinoma
• Liver transplantation evaluation

All patients with decompensated cirrhosis should be managed at institutions capable of handling cirrhosis complications and require immediate liver transplantation evaluation. 2

Patient Education

Patient education about disease management is crucial for improved outcomes, including: 7

• Salt restriction adherence
• Medication compliance
• Recognition of warning signs requiring immediate medical attention
• Alcohol cessation counseling
• Obesity management strategies
• Infection prevention measures