Controversies in Management of Portal Hypertension and Cirrhosis Complications in the Transplant Candidate Patrick Northup, MD, FAASLD, FACG Medical Director, Liver Transplantation University of Virginia
Disclosures Financial: None Off label indications: None
Overview General Cirrhosis Considerations Malnutrition, sarcopenia, frailty Portal vein thrombosis Ascites and Edema HRS, beta-blocker use, midodrine, albumin infusions Variceal Bleeding When to TIPS Encephalopathy Dietary restriction, ammonia levels, minimal HE
Progression of Cirrhosis Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases, Volume: 65, Issue: 1, Pages: 310-335.
Sarcopenia, malnutrition, frailty
Sarcopenia, malnutrition, frailty
Sarcopenia in cirrhosis It s not just malnutrition, can happen in the morbidly obese Loss of skeletal muscle mass More typical in patients with severe ascites and edema Leads to poor functional status which is a strong predictor of transplant (and non-transplant) outcomes
Sarcopenia in cirrhosis after an overnight fast the caloric requirements of patients with alcoholic cirrhosis are normal, but the nature of fuels oxidized are similar to normal humans undergoing 2-3 d of total starvation. Thus, patients with alcoholic cirrhosis develop the catabolic state of starvation more rapidly than do normal humans Owen OE, et al, J Clin Invest 1983; 72(5): 1821-32.
Sarcopenia eventually leads to frailty
Sarcopenia and Liver Transplantation
Six minute walk is a good starting point
Six minute walk is a good starting point
How can we help with sarcopenia and frailty Prehabilitation, or increased muscle mass and activity level has shown benefit for liver transplant recipients Not clear whether this is a self fulfilling prophecy : those able to prehab might have done well anyway Developing data on BCAA enriched evening snack Reasonable to supplement with 300-400 kcal at 11 pm
Portal vein thrombosis Occlusive main trunk PVT Cavernoma
Importance of PVT: transplant survival 148 occlusive PVT 3147 no or non occlusive PVT Hazard ratio by Cox multiple regression analysis Englesbe Liver Transplant 2010;16:83-90
How to Treat: Anticoagulation, Low Molecular Weight Heparins Once varices are controlled, overall bleeding rates appear similar or modestly higher than noncirrhosis patients. Severe bleeding is rare. Adapted from Intagliata, et al, Clinical Liver Disease; 28 June 2016
How to Treat: Anticoagulation Direct-acting Oral Anticoagulants (DOAC) in Cirrhosis Patients Intagliata, et al, Dig Dis Sci 2016; 61: 1721-7
Pearls about PVT and Transplant Must rule out malignant thrombus, HCC spreads to the PV frequently Eradicate EV s as per practice guidelines before starting therapy Not an indication for hospital admission or ED visit if the patient is asymptomatic but should be treated within 6-8 weeks for best chance IR approaches have shown benefit but require a skilled hand and experience
Issues in ascites and edema management
Ascites management notes Remember, it s sodium balance that affects fluid balance, sodium restriction to less than 2000 mg daily is the key for fluid control Overall fluid restriction is not recommended unless sodium is less than 125 mmol/l Runyon, et al. Hepatology 2013; 57(4): 1651 Spironolactone monotherapy is superior to furosemide monotherapy, best when used together in proportional doses however Perez-Ayuso, et al. Gastroenterology 1983; 84:961-8
Midodrine for refractory ascites J Hepatol 2012; 56:348-354
Stop beta-blockers? When? Why? Hepatology 2010; 52(3): 1017-23
Stop beta-blockers? When? Why? The risks versus benefits of beta blockers must be carefully weighed in each patient with refractory ascites. Systemic hypotension often complicates their use. Consideration should be given to discontinuing or not initiating these drugs in this setting. (Class III, Level B) Hepatology 2010; 52(3): 1017-23
Albumin infusions for ascites? 20% albumin infusion 40 g twice weekly for 2 weeks and then once weekly thereafter for 18 months in patients with persistent ascites after failing to completely respond to high dose diuretics Lancet 2018 June; 391: 2417-29
Albumin infusions for ascites? Lancet 2018 June; 391: 2417-29
Terlipressin for HRS: Finally? Journal of Hepatology 200O; 33: 43-48
Variceal Bleeding
Early TIPS for EV bleeding? NEJM 2010; 362(25): 2370-79
Early TIPS for EV bleeding? The trial had many exclusion criteria, including CTP class A, CTP class B without active bleeding at endoscopy, CTP C patients with a score of 14 and 15 points, age > 75 years, HCC outside Milan criteria, a creatinine level greater than 3 mg/dl, previous combination pharmacological plus endoscopic treatment to prevent rebleeding, bleeding from isolated gastric or ectopic varices, total PVT, and heart failure. Patients included in the study constituted <20% of those admitted for VH. Notably, observational studies have not confirmed the effect of early TIPS on survival and further studies are necessary Garcia-Tsao, et al, Hepatology 2017; 65(1): 310-35
Hepatic Encephalopathy
Encephalopathy notes It s not all ammonia. In fact, ammonia is unlikely to be the sole pathogenic force in most HE HE level and activity have little to do with dietary protein intake in the vast majority of patients Sarcopenia and frailty are deadly consequences of advanced decompensated cirrhosis and dietary restriction may contribute to malnutrition and harm
Please stop following ammonia levels Patients without evidence of hepatic encephalopathy (grade 0) frequently had ammonia levels above 47 mmol/l, for example, 69% (20/29) of the patients without signs or symptoms of encephalopathy had total arterial ammonia levels greater than that threshold Ong, et al, Am J Medicine 2003;114:188-93 High blood-ammonia levels alone do not add any diagnostic, staging, or prognostic value in HE patients with CLD Vilstrup, et al, Hepatology 2014; 60(2): 715-735.
Minimal and Covert HE Subtle or often subclinical confusion or slowed mentation. Frequently noted only by the patient s family members. Diagnosis should not be made with ammonia testing Must be diagnosed with neuropsychological tests and psychometric tests and performed by experienced examiners Cannot be diagnosed in the setting of confounding factors Vilstrup, et al, Hepatology 2014; 60(2): 715-735.
It s generally a bad idea to restrict dietary protein and it has no effect on hepatic encephalopathy incidence or severity. Daily protein intake should be 1.2-1.5 g/kg/d Cordoba, et al, J Hepatol 2004; 41(1): 38-43.
Summary General Cirrhosis Considerations Malnutrition, sarcopenia, frailty are important Portal vein thrombosis can be treated Ascites and Edema beta-blocker use, midodrine, albumin infusions all may have an impact Variceal Bleeding Early TIPS might have a survival benefit for a some Encephalopathy Dietary restriction, ammonia levels should not be used Covert HE can be diagnosed with advanced testing
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