358.1 ð é«åžçç
358.1.1 Etiology (Top Causes Globally)
- Chronic HBV / HCV (declining with DAAs + vaccination)
- Alcohol (ALD)
- MASLD/MASH (rising â increasing globally)
- Autoimmune (AIH, PBC, PSC)
- Hereditary (Wilson, hemochromatosis, alpha-1 AT)
- Drug-induced
- Vascular (Budd-Chiari, congestive hepatopathy)
- Cryptogenic
358.1.2 Pathophysiology
- Chronic injury â hepatic stellate cell activation â collagen deposition
- Fibrosis â nodular regeneration â cirrhosis
- Reversibility partial early; advanced is irreversible
- Increased portal pressure
358.1.3 Stages
Compensated: - Asymptomatic - LFT may be normal or mildly abnormal - Synthetic function preserved
Decompensated: - Jaundice - Ascites - Variceal bleeding - Hepatic encephalopathy - Coagulopathy + hypoalbuminemia
358.1.4 Lab
- AST/ALT (often normalized in advanced)
- ALP, GGT (cholestatic)
- Bilirubin â
- Albumin â
- PT/INR â (synthetic)
- Platelets â (splenomegaly)
- AFP (HCC screening)
358.1.5 Imaging
- Ultrasound: nodular liver, splenomegaly, ascites, vascular changes
- CT: structural + lesions + HCC
- MRI: liver-specific contrast
- Transient elastography (FibroScan): stiffness
- MR elastography: most accurate
- Doppler: portal/hepatic vein patency
358.1.7 Child-Pugh Classification (Letter A/B/C)
Variables: - Bilirubin - Albumin - INR - Ascites - Encephalopathy
Scoring: - A (5-6): well-compensated; 5-year survival 80% - B (7-9): moderate disease; 5-year 50% - C (10-15): decompensated; 5-year 30%
358.1.8 MELD Score
- Bilirubin, INR, creatinine
- Predicts mortality (90-day)
- Transplant priority allocation
358.1.9 MELD-Na
- Adds sodium
- Better predictor for hyponatremic patients
- Used for allocation since 2016
358.1.10 MELD 3.0
- Adds female sex + albumin + creatinine adjustments
- Even better discrimination (2023)
358.1.11 Definition
- HVPG (hepatic venous pressure gradient) > 5 mmHg
- Clinically significant > 10 mmHg
- Predicts variceal bleeding > 12 mmHg
358.1.12 Causes
Pre-Hepatic: - Portal vein thrombosis - Splenic vein thrombosis (sinistral PT) - Schistosomiasis (some areas)
Intrahepatic Pre-Sinusoidal: - Schistosomiasis (eggs in portal venules) - Primary biliary cirrhosis - Sarcoidosis
Intrahepatic Sinusoidal (Most Common): - Cirrhosis (most causes) - Acute alcoholic hepatitis
Intrahepatic Post-Sinusoidal: - Sinusoidal obstruction syndrome (SOS, VOD)
Post-Hepatic: - Budd-Chiari (hepatic vein thrombosis) - IVC obstruction - Constrictive pericarditis (cardiac) - Right HF (congestive)
358.1.13 Manifestations
- Esophageal + gastric varices
- Caput medusae
- Splenomegaly + hypersplenism
- Ascites
- Hepatorenal physiology
- Encephalopathy
358.1.14 Ascites
Pathophysiology: - Portal hypertension + splanchnic vasodilation + Na retention - â Effective arterial volume - RAAS activation
Diagnosis: - US confirms - Diagnostic paracentesis: cell count + culture + chemistry + cytology + albumin - SAAG (Serum-Ascites Albumin Gradient): - ⥠1.1 = portal hypertension-related (cirrhosis, HF, BCS, etc.) - < 1.1 = non-portal (peritoneal carcinomatosis, TB, pancreatitis) - Protein: - < 2.5 = transudate - ⥠2.5 = exudate
Treatment: - Sodium restriction < 2 g/d - Diuretics: spironolactone (100 mg) + furosemide (40 mg) in 100:40 ratio; max 400:160 - Large-volume paracentesis (LVP): albumin 6-8 g/L removed (for > 5 L) - TIPS (transjugular intrahepatic portosystemic shunt): refractory ascites - Liver transplant for end-stage
358.1.15 Spontaneous Bacterial Peritonitis (SBP)
Definition: - Bacterial infection of ascitic fluid without source - Common in cirrhotic ascites
Diagnosis: - PMN > 250/mm³ in ascitic fluid - Positive culture (often single organism)
Pathogens: - E. coli (most) - Klebsiella - S. pneumoniae - Enterococcus
Treatment: - Empiric ceftriaxone 2 g daily à 5 days (community-acquired) - Albumin (1.5 g/kg day 1 + 1 g/kg day 3) â reduces HRS + mortality - Tailor per culture - Avoid β-blockers if hemodynamic instability
Prophylaxis: - Norfloxacin or ciprofloxacin (history of SBP, low ascitic protein, GI bleeding, advanced cirrhosis) - Indefinite for prior SBP
358.1.16 Variceal Bleeding
Risk: - HVPG > 12 mmHg - Large varices, red spots, severity of liver disease
Prevention (Primary): - Non-selective β-blocker (propranolol, nadolol, carvedilol) â small varices with high-risk features OR medium-large varices - Endoscopic variceal ligation (EVL) â alternative or combination
Acute Bleeding: - Resuscitation (cautious; avoid over-transfusion; target Hgb 7-8) - Vasoactive: octreotide (50 ÎŒg IV â 50 ÎŒg/h infusion) OR terlipressin (Europe; FDA 2022 US) - Antibiotics: ceftriaxone 1 g daily à 7 days (improves survival) - EGD within 12 hours: variceal banding - TIPS: refractory (rescue) or early in high-risk (PVT) - Balloon tamponade (Sengstaken-Blakemore) â bridge - Surgery rarely
Secondary Prevention: - β-blocker + EVL - TIPS for refractory
358.1.17 Hepatic Encephalopathy (HE)
Pathophysiology: - Ammonia + other toxins (mercaptans, amines, GABA) - Astrocyte swelling
Grading (West Haven): - Grade 0: minimal (subclinical, detected by tests) - Grade 1: mild (sleep changes, mood) - Grade 2: moderate (lethargy, confusion, asterixis) - Grade 3: severe (somnolence, disoriented) - Grade 4: coma
Precipitants: - Infections (SBP, UTI, pneumonia) - GI bleeding (protein load) - Constipation - Electrolytes (hyponatremia, hypokalemia, alkalosis) - Drugs (sedatives, opioids) - Dehydration - TIPS-related
Treatment: - Lactulose 25-50 mL TID-QID (target 2-3 soft BMs daily) - Rifaximin 550 mg BID â reduces recurrence - Treat precipitants - Protein NOT restricted (older advice â protein-energy malnutrition concerns)
358.1.18 Hepatorenal Syndrome (HRS)
Definition: - AKI in cirrhosis without other cause - Functional renal failure - See Ch332 for details
Types: - HRS-AKI (Type 1): rapid (days-weeks); often precipitated by SBP, GI bleed - HRS-NAKI: subacute (Type 2 historical)
Treatment: - Terlipressin + albumin (FDA 2022) â first FDA-approved for HRS - Norepinephrine + albumin (ICU alternative) - Liver transplant (curative) - Avoid: diuretics, NSAIDs
358.1.19 Hepatocellular Carcinoma (HCC)
Risk: - Cirrhosis (any cause) - Chronic HBV (even non-cirrhotic) - High-risk MASH
Surveillance: - US ± AFP every 6 months - For all cirrhotic + chronic HBV high-risk
Diagnosis: - Imaging (LI-RADS criteria) - Biopsy if uncertain
See Ch359 for treatment
358.1.20 Coagulopathy
- Decreased synthesis of clotting factors
- Decreased synthesis of natural anticoagulants
- âRebalancedâ hemostasis
- Bleeding + clotting both possible
- Manage based on clinical picture
- INR may not reflect bleeding risk
358.1.21 Hyponatremia
- Hypervolemic hyponatremia
- Common
- Treatment: fluid restriction; tolvaptan (for selected)
- AVOID rapid correction (ODS risk)
358.1.22 Hyperestrogenic State (Cirrhosis)
- Gynecomastia
- Spider angiomas
- Palmar erythema
- Testicular atrophy
- Decreased estrogen clearance
358.1.23 Other Complications
- Hepatopulmonary syndrome (HPS)
- Portopulmonary hypertension (POPH)
- Cirrhotic cardiomyopathy
- Splenomegaly + hypersplenism (thrombocytopenia)
- Sarcopenia + malnutrition
- Encephalopathy
- Bone disease (osteoporosis)
358.1.23.1 𩺠åºé鿥
- Cirrhosis äž»èŠåå : HBV, HCV, ALD, MASLD
- Child-Pugh A/B/C: bilirubin + albumin + INR + ascites + encephalopathy
- MELD-Na: transplant priority + mortality
- HVPG > 12 mmHg: variceal bleeding risk
- SAAG ⥠1.1: portal hypertension-related ascites
- SBP: PMN > 250/mm³; ceftriaxone + albumin
- Variceal bleeding: octreotide/terlipressin + ceftriaxone + EGD banding + TIPS
- HE: lactulose + rifaximin
- HRS: terlipressin + albumin (FDA 2022)
- HCC surveillance: US ± AFP every 6 mo