Portopulmonary Hypertension Presence of pulmonary arterial hypertension in a patient with portal hypertension No other obvious causes (chronic lung disease, left heart disease, thromboembolism) 1) SCREEN - Transthoracic echocardiogram • Right ventricular systolic pressure (RVSP) - Estimates pulmonary artery pressure via tricuspid regurgitant velocity using Bernoulli principle. No consensus on definite cutoff - Previous studies suggested >50mmHg correlated with moderate (or worse) PPHTN • Peak tricuspid regurgitation velocity (TRV) - Cutoff > 2.8 m/s • Other signs: Right ventricular size, Right atrial pressure, Pulmonary artery diameter, Flattening of ventricular septum 2) DIAGNOSE - Right heart catheterization Needed for definitive diagnosis Diagnostic criteria: mPAP > 25mmHg, PVR > 3 Woods units, PA wedge pressure < 15mmHg TREATMENT: Endothelin receptor antagonists: - Mechanism: competitive antagonism of endothelin receptors, blocking the vasoconstricting effect of endothelin - Effect: improves functional class, exercise capacity, and cardiopulmonary hemodynamics Phosphodiesterase-5 inhibitors: - Mechanism: facilitates the vasodilatory effects of nitric oxide through reduced cGMP metabolism - Effect: improves functional class and cardiopulmonary hemodynamics Prostacyclin analogues: - Mechanism: causes vasodilation and reduced vascular smooth muscle proliferation - Effect: shown to improve cardiopulmonary hemodynamics Soluble guanylate cylase stimulators: - Mechanism: sensitizes soluble guanylate cyclase (sGC) to nitric oxide (NO) and directly stimualtes sGC receptors independent of NO - Effect: PATENT-1 study showed improved functional status and hemodynamics Liver transplantation: Consider in those who respond to medical therapy Lizzie Aby, MD @LizzieAbyMD #Portopulmonary #Hypertension #diagnosis #management #hepatology

Hepatopulmonary Syndrome - Diagnosis and Management Summary A defect in arterial oxygenation due to a gas exchange disorder occurring in the setting of liver disease and in the absence of intrinsic lung disease Caused by intrapulmonary vascular dilation (IVPD) either due to a diffusion-perfusion defect (Type 1) or anatomic shunt (Type 2) Clinical Presentation: • Dyspnea - Common but not specific to HPS alone • Platypnea - Dyspnea worse when sitting upright compared to lying supine • Orthopnea - PaO2 ↓ by ≥ 5% or ≥ 4mmHg from supine to upright position • Hypoxemia - V/Q mismatch and restricted diffusion from IPVDs Diagnostic Testing: • Pulse oximetry - Non-invasive initial screening tool using cutoff SpO2 < 96% detects severe HPS with 100% sens, 88% spec • Contrast-enhanced echocardiography - Assess for IPVD using peripherally injected agitated saline during echocardiography - Microbubbles appear in left heart 3-6 cardiac cycles after right atrial passage • Arterial blood gas (ABC) analysis - Quantifies degree of hypoxemia. Should be performed on room air in seated position after 10 minutes of rest HPS Diagnostic Criteria: • Underlying liver disease - Portal hypertension with or without cirrhosis • Intra-pulmonary vascular dilation - Positive findings on contrast-enhanced TTE. Can also be seen on radioactive lung perfusion scanning or pulmonary angiography (in select patients) • Oxygenation defect - PaO2 < 80mmHg or A-a gradient ≥ 15mmHg (≥ 20mmHg in patients aged 65 and older) on room air Treatment: • There is no established medical therapy for HPS. Supportive care with supplemental oxygen if PaO2 < 60mmHg, goal SpO2 > 88% • Management of underlying portal hypertension • Liver transplantation: results in almost uniform resolution of HPS features - Complete resolution of symptoms may take months after transplant - Lizzie Aby, MD @LizzieAbyMD #hepatopulmonary #syndrome #diagnosis #management #treatment #hepatology

Hepatic Encephalopathy - Diagnosis and Management Summary Definition: • Alteration in brain function manifested by neuropsychiatric symptoms • Caused by liver insufficiency and/or portosystemic shunting • * Diagnosis of exclusion: always rule out other causes of neurologic/cognitive impairment Prevalence: At cirrhosis diagnosis: 10-14%. If decompensated: 16-21% Incidence: Occurs in 30-40% over course of disease Recurrence: Up to 40% over a 30-day period Precipitants: Infection, GI bleeding, Diuretic overdose, Electrolyte imbalances, Constipation, Alcohol binge, Malnutrition, TIPS West Haven Criteria: • Grade 1: Trivial lack of awareness, Altered sleep, Shortened attention span, Impaired addition • Grade 2: Lethargy, apathy, Personality change, Asterixis, Inappropriate behavior, Disorientation to time, place • Grade 3: Somnolence (but responsive), Confusion, Gross disorientation • Grade 4: Coma (unresponsive to verbal or noxious stimuli) TREATMENT Initiate empiric treatment while identifying and addressing any precipitating factors Lactulose: non-absorbable disaccharide that is metabolized to lactic acid by colonic bacteria, acidifying the lumen and promoting NH3 -> NH4+ (which is trapped in lumen and excreted) • Titrate to maintain 2-3 bowel movements per day • Beware of dehydration, electrolyte abnormalities • Polyethylene glycol can be used in cases of lactulose intolerance Rifaximin: non-absorbable antibiotic, thought to reduce ammonia-producing colonic bacteria • Guidelines recommend using as add-on to lactulose to prevent recurrence Other therapies to consider: Zinc supplementation, IV L-ornithine L-aspartate (LOLA), oral branched chain amino acids *Supporting data is limited Diet: protein restriction is detrimental! • Skeletal muscle metabolizes ammonia important to avoid malnutrition and promote building muscle mass - Lizzie Aby, MD @LizzieAbyMD #Hepatic #Encephalopathy #Grading #Classification #Diagnosis #Management #treatment #hepatology