Liver Transplantation Evaluation: Essential Work-Up Curtis K. Argo, MD, MS VGS/ACG Regional Postgraduate Course Williamsburg, VA September 13, 2015 Objectives Discuss determining readiness for transplantation when is the right time to refer for transplantation evaluation? Describe the key aspects of liver transplantation medical evaluation 1
Confirm cirrhosis Clinical diagnosis Imaging (nodular liver and/or splenomegaly + presence of varices on EGD or varices/ascites on imaging + thrombocytopenia Biopsy-proven Nice but often not necessary unless mixed signals Likely to survive without a transplant? Child s class/ctp score CTP class: A = 5-6, B = 7-9, C = 10-15 2
Likely to survive without a transplant? No: Child s classc=ctp>10 CTP 30-35% mortality in 1 year Probably: Child s class B = CTP 7-9 20% mortality in 5 years Yes: Child s class A = CTP 5-6 90% survival for 5 years Likely to survive without a transplant? MELD score Wiesner R et al. Gastroenterology 2003. 3
Likely to survive long-term without a transplant? No: MELD > 20 >10% mortality in 3 months Unlikely: MELD = 15-19 5-10% mortality in 3 months Possibly: MELD = 10-12 <5% mortality in 3 months Yes: MELD < 10 Likely to survive without a transplant? MELD score vs. CTP score MELD appears to be more oesensitive st ethan CTP in predicting mortality Wiesner R et al. Gastroenterology 2003. 4
Likely to survive without a transplant? Presence of portal hypertensive complications Variceal bleeding Ascites without good control Hepatic encephalopathy requiring ED/admission Spontaneous bacterial peritonitis 50-60% 1 year survival Hepatorenal syndrome Median survival = 2 weeks Andreu M et al. Gastroenterology 1993. Better off with a transplant? 1 year survival Merion RM et al AJT 2005. 5
Better off with a transplant? Transplant benefit appears to occur on a 5-year time horizon at MELD of 10 Schaubel DE et al AJT 2006 Appropriate time to refer for transplant evaluation? MELD score 15 Waiting time still a factor with MELD < 20 CTP 8 Life-threatening portal HTN complication Hepatocellular carcinoma MELD exception to 22 points in selected cases that meet Milan criteria AASLD guideline 2005 6
Basic but Important Questions Can the patient survive the operation and the immediate postoperative period? Nutrition Comorbidities Functional status Age Can the patient be expected to comply with the complex post-transplant p medical regimen? Past behavior predicts future behavior Addiction Does the patient have other comorbidities that could severely compromise graft function or patient survival futile? AASLD guideline 2005 Age No specific age limitation Patients age >70 have had reduced long-term posttransplant survival, mainly due to death from malignancies or perioperative complications Coronary Artery Disease RFs: smoker, age>50, DM, personal or FmHx Increased perioperative mortality in CAD pts Stress echo is best studied, but there is no consensus on best risk stratifying test Catheterization is indicated in any positive test 7
High risk features for transplant in NASH/cryptogenic cirrhosis 60 years old BMI 30 Pre-transplant Diabetes + Pre-transplant HTN + Dilemma: 50% 1-year mortality risk in largest retrospective cohort of transplanted NASH cirrhosis pts (n=98) in patients with all 4 of these risk factors (n=18) Malik SM et al, AJT 2009 Substance abuse/addiction Use vs. Abuse Abuse: demonstration of dependence through continued substance use despite negative effects on health, family, job, or legal status Use: intermittent use of substance that does not have the above negative ramifications and is remediable with relatively conservative measures UVA s policy We do not condone use of any illegal, illicit drug in any transplant candidate Alcoholic abstinence of at least 6 consecutive months is required prior to listing for liver transplant 8
Obesity BMI > 40 is strongly associated with reduced 30-day, 1-yr, and 2-yr post-transplant survival BMI > 35 is associated with reduced 5-yr survival Our cutoff for transplant listing at UVA is BMI 40 Underweight BMI < 18 is strongly associated with poor posttransplant outcome Nair S, et al, Hepatology 2002 Extrahepatic Malignancies High risk for recurrent disease due to immunosuppression A waiting period is standard after cure/remission of a malignancy Waiting period varies by the type, grade, and extent of the extrahepatic malignancy UVA utilizes a cancer consultation service (Israel Penn) to aid in determining appropriate waiting period and risk of recurrence 9
HIV infection HIV is a chronic infection thanks to HAART Patients can undergo transplant if they have HIV Control of infection with present HAART is required with undetectable HIV viral load CD4 count > 250 HCV and renal failure is a relative contraindication Significant drug interactions between calcineurin inhibitors (tacrolimus, cyclosporine) and certain protease inhibitors (use integrase inhibitors?) Hepatopulmonary Syndrome (HPS) Chronic liver disease, hypoxemia, widespread intrapulmonary vasodilation Not pathophysiologically compatible to have both HPS and pulmonary HTN (vasoconstriction) More likely hypoxemia with pulmonary HTN is portopulmonary HTN Workup ABG for po2 higher MELD if po2< 60 Transthoracic echocardiogram with bubble study Exclude intracardiac shunting and confirm pulm shunting Macroaggregated albumin scan to quantify intrapulmonary shunting if po2 and echo fit 10
Portopulmonary HTN Idiopathic pulmonary HTN in cirrhotic patient with no history of underlying lung disease Mild and moderate pulmonary HTN not contraindication to transplantation and pulm HTN usually resolves in 4-6 months Severe e e pulmonary HTN = mean PA pressure e 35 mm Hg Contraindication to transplantation due to possibility of poor graft function related to passive congestion May use vasodilator medications to correct to under this limit Vascular anatomy MR angiogram g is our study of choice although CT angiogram can be adequate with careful contrast protocol Require suitable portal inflow and hepatic arterial and venous anatomy Portal vein thrombosis s is not a contraindication ca o Portal system atrophy/complete occlusion is a CI Imaging also helpful in assessing liver volume General rule: liver mass to be transplanted should be 1-2% of total body mass of recipient 11
Hepatocellular carcinoma (HCC or hepatoma) Transplantation ti is curative in selected candidates Can consider resection but need to be free of portal HTN IR or Rad Onc supplies valuable services in preventing patients from progressing outside of criteria as well as downstaging to meet criteria TACE, RFA, XRT, Y-90 microspheres Sorafenib s role pre- and post-transplant is unclear AASLD Guidelines for HCC Diagnosis < 1 cm 1-2 cm > 2cm Low likelihood of HCC If characteristic on US q 3 months 2 dynamic images arterial No growth in 1-2 yrs enhancement + washout (CT, MRI, contrast Enhanced US) Resume q 6 month US Treat as HCC If characteristic on 1 dynamic imaging or AFP > 200 ng/ml Treat as HCC False negative 30% If not typical on imaging, biopsy lesion If not typical on imaging, biopsy lesion Bruix J et al. Hepatology 2005;42:1208-1236 12
Milan Criteria 1 lesion < 5 cm No evidence of extrahepatic spread Based on pre-transplant imaging 4 year survival - 74% 3 lesions, none > 3 cm Recurrence rate - <10% Validated in several studies with > 1000 patients 5 yr survival >70% Recurrence < 15% Mazzoferro et al N Engl J Med 1996;334(11):693-9 Acute liver failure (ALF) If the patient is a viable liver transplant candidate from psychosocial perspective, then tertiary referral is recommended for critical care management and urgent evaluation Remember King s criteria in acetaminophen overdose ph< 7.3, INR > 6.5, Creatinine > 3.4, grade III/IV encephalopathy Low phosphorous is good prognostic sign Utilize N-acetylcysteine IV in both acetaminophen and non-acetaminophen ALF Aggressively treat encephalopathy and renal failure but there is no role for correcting coagulopathy unless acute bleeding occurring 13
Thanks for your attention! Curtis Argo, MD, MS cka3d@virginia.edu 14