End-stage liver fibrosis with portal hypertension; ascites, varices, and encephalopathy define decompensation.
Also known as: cirrhosis, decompensated cirrhosis, ascites, hepatic encephalopathy, portal hypertension
Overview
Diffuse hepatic fibrosis with regenerative nodules, representing the end stage of chronic liver injury from any cause. Compensated cirrhosis is asymptomatic; decompensated cirrhosis is defined by ascites, variceal bleeding, hepatic encephalopathy, or jaundice.
Epidemiology
Affects ~600,000 US adults; 12th leading cause of death. Common etiologies in US: MASLD/MASH, alcohol-associated liver disease, chronic HCV (declining with DAAs), chronic HBV. Mortality dependent on Child-Pugh and MELD scores; 1-yr mortality 1-3% compensated, 20-60% decompensated.
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Peritoneal carcinomatosis or TB peritonitis — Ascites with elevated SAAG <1.1; cytology, ADA, AFB
Protein-losing enteropathy — Hypoalbuminemia without liver dysfunction; alpha-1 antitrypsin clearance
Diagnostic workup
Diagnostic criteria
Histologic gold standard but rarely needed; clinical, biochemical, and imaging features are usually sufficient. Compensated vs decompensated cirrhosis based on presence of ascites, variceal bleeding, hepatic encephalopathy, or jaundice.
Labs
LFTs — AST/ALT often mildly elevated or even normal; AST > ALT and AST:ALT >2:1 suggests alcohol; alk phos and GGT cholestatic
Bilirubin, albumin, INR (synthetic function — used for Child-Pugh and MELD)
Triphasic CT or MRI with contrast for HCC surveillance and characterization
Upper endoscopy at diagnosis to screen for varices (or non-invasive criteria — Baveno VI/VII: liver stiffness <20 kPa + platelets >150,000 allows deferral)
MELD/Child-Pugh scoring for prognostication and transplant evaluation
Diagnostic algorithm
Child-Pugh Variable
1 point
2 points
3 points
Bilirubin (mg/dL)
<2
2-3
>3
Albumin (g/dL)
>3.5
2.8-3.5
<2.8
INR
<1.7
1.7-2.3
>2.3
Ascites
None
Mild (diuretic responsive)
Moderate-severe (refractory)
Encephalopathy
None
Grade 1-2
Grade 3-4
Class A
5-6 points; 1-yr survival ~100%
Class B
7-9 points; 1-yr survival ~80%
Class C
10-15 points; 1-yr survival ~45%
Child-Pugh score for cirrhosis severity. MELD-Na is used for transplant allocation but Child-Pugh remains useful clinically.
Treatment
First-line
Treat underlying cause: alcohol cessation, antiviral therapy (HBV nucleoside analogues, HCV DAAs), weight loss for MASH, immunosuppression for autoimmune hepatitis, phlebotomy for hemochromatosis, chelation for Wilson
Vaccinate against HAV, HBV, pneumococcus, influenza, COVID-19
Nutritional support — late-evening snack to reduce muscle catabolism; protein 1.2-1.5 g/kg/day; supplementation of B12, folate, thiamine, vitamin D
HCC surveillance: ultrasound ± AFP every 6 months
Variceal screening EGD (or non-invasive criteria)
Ascites
Sodium restriction <2 g/day
Diuretics: spironolactone (start 100 mg) + furosemide (start 40 mg) in 100:40 ratio; titrate to maintain ratio
Therapeutic large-volume paracentesis (>5 L) — give albumin 6-8 g/L removed
Refractory ascites: TIPS (avoid in encephalopathy, EF<60%, advanced age, decompensated MELD); serial paracenteses; liver transplantation
SBP prophylaxis: norfloxacin or ciprofloxacin daily if ascitic protein <1.5 g/dL plus poor liver function or prior SBP
SBP treatment: ceftriaxone 2 g/day × 5-7 days + albumin 1.5 g/kg day 1, 1 g/kg day 3 (reduces hepatorenal syndrome and mortality)
Esophageal varices
Primary prophylaxis for medium/large varices: non-selective beta-blocker (propranolol, nadolol, carvedilol) titrated to HR 55-60 OR serial EVL (band ligation)
Acute variceal bleed: octreotide infusion + ceftriaxone 1 g + EGD with EVL within 12 h + restrictive transfusion (Hgb ~7); early TIPS for high-risk patients
Secondary prophylaxis after bleed: NSBB + serial EVL until eradication
Coagulopathy (decreased synthesis of factors; balanced — not as protective as INR suggests; balance rebalances toward thrombosis with portal vein thrombosis risk)
Sarcopenia, malnutrition
Sepsis, immune dysfunction
Cardiopulmonary: cirrhotic cardiomyopathy
Endocrine: hypogonadism, glucose intolerance
PANCE pearls
SAAG (serum-ascites albumin gradient) ≥1.1 g/dL = portal hypertension as cause of ascites; <1.1 = other (carcinomatosis, TB, pancreatic, nephrotic).
Spontaneous bacterial peritonitis: ascitic PMN ≥250/mm³ regardless of culture — start empiric ceftriaxone and albumin immediately.
Albumin in SBP (1.5 g/kg day 1, 1 g/kg day 3) reduces hepatorenal syndrome and mortality (Sort, NEJM 1999).
Restrictive transfusion (Hgb ~7) in variceal bleed reduces rebleed and mortality vs liberal (Villanueva, NEJM 2013).
Early TIPS within 72 h of variceal bleed for high-risk patients (Child-Pugh C <14, or B with active bleed at EGD) reduces mortality (García-Pagán, NEJM 2010).
Lactulose first-line for hepatic encephalopathy; add rifaximin for recurrence (Bass NM, NEJM 2010 RFHE3001 trial).
Do NOT restrict protein in cirrhosis — worsens sarcopenia and outcomes.
INR overestimates bleeding risk in cirrhosis; coagulopathy is REBALANCED — thrombosis risk is real.
MELD-Na is the standard score for transplant allocation; Child-Pugh remains useful at the bedside.
Acute kidney injury in cirrhosis differential: pre-renal (volume depletion, response to albumin), HRS (no response to albumin, no other cause), ATN, drug-induced — albumin challenge differentiates.
Avoid NSAIDs (renal failure), aminoglycosides, ACEi/ARBs in advanced cirrhosis.
References
AASLD 2021 Ascites — Biggins SW et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the AASLD. Hepatology 2021;74:1014-1048
AASLD 2014 HE — Vilstrup H et al. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by AASLD and EASL. Hepatology 2014;60:715-735
Baveno VII — de Franchis R et al. Baveno VII — Renewing consensus in portal hypertension. J Hepatol 2022;76:959-974
RFHE3001 (Rifaximin HE) — Bass NM et al. Rifaximin Treatment in Hepatic Encephalopathy. NEJM 2010;362:1071-1081
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