What is the comprehensive treatment approach for decompensated chronic liver disease, including management of ascites, hepatic encephalopathy, variceal bleeding prophylaxis, hepatorenal syndrome, coagulopathy, supportive care, and transplant evaluation?

Treatment of Decompensated Chronic Liver Disease

Immediately initiate treatment of the underlying liver disease while simultaneously managing acute complications—this is the single most important intervention to reduce further decompensation and improve survival. 1, 2

1. Etiological Treatment (First Priority)

Treating the root cause directly lowers mortality and morbidity, with effectiveness varying by disease severity at intervention. 1, 3

Viral Hepatitis B

• Start antiviral therapy immediately when HBV DNA is detectable by PCR, regardless of ALT level or viral load 3, 2
• Use entecavir 1 mg daily (not 0.5 mg) or tenofovir monotherapy as first-line agents due to potent antiviral activity and high genetic barrier to resistance 3, 2
• Entecavir achieves HBV DNA suppression in 57% of patients at week 48 and improves Child-Pugh class in nearly 50% of treatment-naïve individuals 3
• Peginterferon-α is absolutely contraindicated in decompensated disease due to risk of hepatic failure, severe infection, and death 3
• Clinical improvement typically requires 3–6 months of therapy 3
• Monitor HBV DNA (real-time PCR) and HBeAg status every 2–6 months 3

Viral Hepatitis C

• Initiate direct-acting antivirals immediately, as they improve liver function, reduce portal hypertension, and likely improve outcomes 2

Alcohol-Related Cirrhosis

• Mandate complete and permanent alcohol cessation, which can lead to "re-compensation" with excellent long-term outcomes in some patients 3, 2

Autoimmune Hepatitis

• Start immunosuppressive therapy, which shows clear beneficial effects even in decompensated disease 3, 2

2. Ascites Management

Initial Assessment and Grading

• Perform diagnostic paracentesis without delay in any cirrhotic patient admitted with ascites or showing clinical deterioration (fever, abdominal pain, encephalopathy, renal impairment, unexplained leukocytosis) 1, 3
• Obtain ascitic fluid for cell count with differential, culture, albumin, and total protein 4
• Paracentesis is safe even with coagulopathy; severe hemorrhage occurs in only 0.2–2.2% of procedures 1
• Use the left lower-quadrant as the preferred puncture site 1

Medical Therapy by Grade

• Grade 1 ascites (detectable only by imaging): Sodium restriction to <5 g/day (≈88 mmol/day) 1, 3
• Grade 2 ascites (moderate, visible): Sodium restriction plus spironolactone 100 mg once daily as first-line monotherapy 1, 3, 2
• Grade 3 ascites (massive/tense): Perform therapeutic paracentesis first, then initiate sodium restriction and diuretic therapy 1, 3, 2

Diuretic Regimen

• Start spironolactone 100 mg/day for first episode of ascites 1, 3
• If weight loss is <2 kg/week, increase spironolactone by 100 mg every 72 hours up to maximum 400 mg/day 1, 3
• Add furosemide 40 mg/day when spironolactone alone is insufficient or hyperkalemia develops (K+ >5.5 mmol/L); titrate in 40-mg increments to maximum 160 mg/day 1, 3
• Target weight loss of 0.5 kg/day without peripheral edema or 1 kg/day with edema 1
• Check serum creatinine, sodium, and potassium at least weekly during the first month of diuretic treatment 1, 3

Sodium and Fluid Management

• Restrict dietary sodium to <5 g/day (≈88 mmol/day); stricter restriction worsens malnutrition and is not advised 1, 3, 2
• Fluid restriction is unnecessary unless serum sodium falls below 120–125 mmol/L 1, 3, 2
• Temporarily stop diuretics if serum sodium drops below 120–125 mmol/L 1

Large-Volume Paracentesis

• Administer 8 g albumin per liter of ascites removed when extracting >5 L (≈100 mL of 20% albumin for every 3 L) 3
• For <5 L removed, synthetic plasma expander (150–200 mL gelofusine or Haemaccel) is sufficient 3

Refractory Ascites

• Defined as ascites recurring ≥3 times within 12 months despite optimal sodium restriction and maximal tolerated diuretics 3
• Options include serial large-volume paracentesis, transjugular intrahepatic portosystemic shunt (TIPS), or liver transplantation 1, 3
• Patients requiring paracenteses more frequently than every 2 weeks likely have poor dietary compliance 1

3. Spontaneous Bacterial Peritonitis (SBP)

Diagnosis

• Ascitic neutrophil count >250 cells/mm³ confirms SBP 1, 3
• Inoculate ≥10 mL ascitic fluid into blood-culture bottles at bedside to improve pathogen detection 3

Treatment

• Initiate immediate empirical antibiotic therapy determined by context, severity, and local resistance patterns 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 with GI bleeding and ascites should receive prophylactic antibiotics such as ceftriaxone 1 g/24h for up to 7 days in decompensated cirrhosis or quinolone-resistant settings, or oral norfloxacin 400 mg twice daily in remaining patients 4, 3
• After recovering from SBP, give continuous oral norfloxacin 400 mg daily (or ciprofloxacin 500 mg daily) for secondary prophylaxis 3
• All patients with SBP should be evaluated for liver transplantation 3

4. Hepatic Encephalopathy (HE)

Diagnosis

• HE remains a clinical diagnosis based on mental status, vigilance, attention, and spatial-temporal orientation 1
• Animal Naming Test (<20 animals in 1 minute) suggests covert HE 1, 3
• Measure blood ammonia only when HE is uncertain; a normal value argues against HE, whereas an elevated value does not confirm it 1
• Proper ammonia sampling requires fasting patient, avoidance of venous stasis, collection in EDTA tube, and transport on ice within 60–90 minutes 1
• Obtain brain imaging (CT or MRI) during the first HE episode to exclude intracranial hemorrhage, which is more common in cirrhotic patients 1

Treatment

• Identify and treat precipitating factors (GI bleeding, infection, dehydration, constipation, electrolyte disturbances) 1, 2
• Serum sodium <130 mmol/L is an independent risk factor for HE and predicts poor response to lactulose 1
• Discontinue benzodiazepines immediately; they are contraindicated in decompensated cirrhosis 1
• Limit proton-pump inhibitor use to validated indications only 1
• Initiate lactulose as first-line therapy for HE, as it reduces mortality and prevents recurrent overt hepatic encephalopathy 1, 2
• Add rifaximin for persistent or recurrent HE episodes 1, 5

5. Variceal Bleeding Prophylaxis and Management

Primary Prophylaxis

• Non-selective beta-blockers (propranolol or carvedilol) decrease the risk of ascites, hepatorenal syndrome, SBP, and hepatic encephalopathy beyond variceal bleeding prevention, specifically in patients who achieve marked portal pressure reduction 1, 2
• In patients with clinically significant portal hypertension (HVPG ≥10 mmHg) without high-risk varices, NSBBs reduce the composite outcome of decompensation or death from 27% to 16% 3
• Screening endoscopy is recommended for all compensated cirrhotics; if large varices are present, start NSBB therapy or endoscopic band ligation 3
• Use NSBBs with caution in patients with severe or refractory ascites; reduce or stop if mean arterial pressure falls <65 mmHg or if acute/progressive renal dysfunction develops 3

Acute Variceal Bleeding

• Initiate vasoactive drugs immediately upon suspicion of variceal bleeding, even before endoscopic confirmation 4, 1, 2
• Antibiotic prophylaxis is mandatory in cirrhotic patients with GI bleeding 4, 1
• Use a restrictive transfusion strategy with hemoglobin threshold of 7 g/dL, target 7–9 g/dL 3
• Endoscopic band ligation should be performed 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

Terlipressin Contraindications

• Terlipressin use is contraindicated in patients with hypoxemia and in patients with ongoing coronary, peripheral, or mesenteric ischemia, and should be used with caution in patients with acute-on-chronic liver failure grade 3 4
• Benefits may not outweigh risks in patients with serum creatinine >5 mg/dL and in patients listed for transplantation with MELD ≥35 4

6. Hepatorenal Syndrome (HRS)

Prevention

• Avoid nephrotoxic drugs (NSAIDs, aminoglycosides), large-volume paracentesis without albumin replacement, and hypotensive medications 4, 2

Treatment

• Terlipressin currently appears to be the best medical therapy available for patients with type 1 HRS 6
• Addition of albumin to terlipressin appears to decrease mortality in patients with type 1 HRS 6

7. Medications to Absolutely Avoid

• NSAIDs are absolutely contraindicated in cirrhosis because they reduce urinary sodium excretion, precipitate renal dysfunction, and can convert diuretic-responsive ascites into refractory ascites 1, 3, 2
• Metformin is contraindicated in decompensated cirrhosis due to lactic acidosis risk 3
• Sulfonylureas should be avoided in hepatic decompensation because of hypoglycemia risk 3

8. Diabetes Management in Decompensated Cirrhosis

• Screen all patients with decompensated cirrhosis for diabetes given high prevalence 3
• Insulin therapy is the only evidence-based option for treating type 2 diabetes in decompensated cirrhosis 4, 3, 2
• Do not use HbA1c for diagnosis or monitoring glycemic control in patients with decompensated cirrhosis 3

9. Nutritional Management

• Perform rapid nutritional screening in all patients, assuming high risk for malnutrition if BMI <18.5 kg/m² or Child-Pugh C 1, 2
• Assess sarcopenia using CT scan, anthropometry, DEXA, or BIA 3
• Evaluate muscle function with handgrip strength and/or short physical performance battery 3
• Bed rest is discouraged; prolonged inactivity contributes to muscle atrophy and sarcopenia 3

10. Anticoagulation Considerations

• Anticoagulation with enoxaparin may delay hepatic decompensation and improve survival in patients with Child-Pugh scores 7–10 by preventing portal vein thrombosis and reducing intestinal barrier damage 1, 2

11. Liver Transplantation

• Early referral for liver transplantation evaluation is essential for appropriate candidates, as decompensation significantly worsens prognosis 1, 2
• All patients with decompensated cirrhosis should be evaluated for liver transplantation 3, 2
• Mean pulmonary arterial pressure ≥45 mmHg is an absolute contraindication to liver transplantation 2
• Refer to gastroenterology promptly for any decompensation event, refractory ascites, or when TIPS evaluation is considered 1, 3

12. Monitoring and Follow-Up

• Liver function tests should be obtained every 1–3 months 3
• Remote monitoring technologies (Bluetooth-linked weighing scales, smartphone apps) may enable early intervention for weight changes, potentially improving outcomes and reducing hospital readmissions 1, 2
• Heart rate variability monitoring may identify patients at risk of further decompensation 1, 2

Common Pitfalls to Avoid

• Do not impose routine fluid restriction; restrict fluids only when serum sodium is severely low (<120–125 mmol/L) 1, 3
• Do not rely on ammonia levels to diagnose or monitor HE; HE remains a clinical diagnosis of exclusion 1
• Do not continue NSBBs in refractory ascites if mean arterial pressure falls <65 mmHg or renal dysfunction develops 3
• Do not use peginterferon-α in decompensated viral hepatitis due to risk of hepatic failure 3
• Do not restrict protein intake in hepatic encephalopathy; this outdated practice worsens malnutrition 7