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Mechanistic Deep Dive
Portal Hypertension Mechanism
- â Intrahepatic resistance (mechanical + functional)
- â Splanchnic blood flow (vasodilation)
- â Cardiac output
- â Systemic vascular resistance
Hyperdynamic Circulation
- Splanchnic + systemic vasodilation
- Hyperdynamic state
- Effective hypovolemia â RAAS, AVP, SNS activation
Ammonia + HE
- Astrocyte glutamine accumulation
- GABA-glutamate imbalance
- Manganese deposition (chronic)
- Inflammation contributory
Recent Trials & Updates
CONFIRM (2021) â Terlipressin HRS
- FDA approval 2022
- â HRS reversal
REVERSE Trial â Terlipressin
- Phase 3 in HRS-1
- Approved
Early TIPS (Garcia-Pagan 2010)
- Pre-emptive TIPS for high-risk
- â Rebleeding + mortality
- Practice-changing
TRIGGER (Restrictive Transfusion)
- Hgb 7 vs 9 target
- Restrictive better outcomes
- Applies to UGIB
Beta-Blockers in End-Stage
- Caution in advanced (refractory ascites, hypotension)
- May worsen prognosis
Rifaximin in Cirrhosis
- Reduces HE recurrence (PROFIT)
- Reduces SBP recurrence (some)
- Now incorporated
High-Yield Specialist Points
MELD Exception Points
- HCC within Milan criteria
- Hepatopulmonary syndrome
- Portopulmonary hypertension
- Familial amyloidotic polyneuropathy
- Cholangiocarcinoma (Mayo protocol)
- Cystic fibrosis
TIPS Indications
- Refractory ascites
- Refractory variceal bleeding
- Hepatorenal syndrome (selected, with vasoconstrictor)
- Budd-Chiari syndrome
- Hepatic hydrothorax
TIPS Contraindications
- Heart failure (right-sided)
- Severe encephalopathy
- Polycystic liver
- Severe pulmonary hypertension
- Active infection
- Coagulopathy uncorrected
TIPS Complications
- Encephalopathy (worsens)
- Stent occlusion
- Cardiac decompensation
- Hepatic injury
Hepatopulmonary Syndrome (HPS)
- Triad: liver disease + intrapulmonary vasodilation + hypoxemia
- Orthodeoxia + platypnea
- Treatment: O2 + liver transplant
Portopulmonary Hypertension (POPH)
- PAH in portal hypertension
- PAH-specific therapy
- Liver transplant in select
Hepatic Hydrothorax
- Ascites communicating with pleural space
- Usually right-sided
- Treatment similar to ascites; TIPS
Variceal Bleeding Mortality
- 15-20% at 6 weeks
- Active management critical
Sarcopenia + Cirrhosis
- Common
- Prognostic
- Nutrition + exercise
- BCAA (branched-chain amino acids) supplementation
Cirrhotic Cardiomyopathy
- Subclinical
- Stressed in surgery / pregnancy / fluid loading
- May contribute to HRS
Coagulation in Cirrhosis
- âRebalancedâ hemostasis
- INR not reliable for bleeding
- TEG / ROTEM for selected
Liver Transplant + Cirrhosis
- See Ch358
- MELD-based priority
- Many indications
Acute-on-Chronic Liver Failure (ACLF)
- Cirrhosis + acute precipitant
- Multi-organ failure
- High mortality
- ICU + liver transplant evaluation
- Different staging (CLIF-C)
Pearls
- Cirrhosis main causes: HBV, HCV, ALD, MASLD
- MELD-Na for transplant priority
- HVPG > 12 mmHg: variceal bleeding risk
- SAAG ⥠1.1: portal HTN
- SBP: PMN > 250; ceftriaxone + albumin (1.5 + 1 g/kg)
- Variceal bleeding: octreotide + ceftriaxone + banding + TIPS
- HE: lactulose + rifaximin
- HRS: terlipressin + albumin (FDA 2022)
- HCC surveillance: US ± AFP every 6 mo
- Early TIPS for high-risk variceal bleeding