Investigations before OLT, Immunosuppression and rejection, Follow up after OLT.

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1 Investigations before OLT, Immunosuppression and rejection, Follow up after OLT

2 When is liver transplantation indicated?

3 When is liver transplantation indicated? Frequent: CIRRHOSIS a) Viral Hepatitis HCV HBV HDV b) ALD c) NASH HCC Rare a) Autoimmune PBC AIH PSC b) Cryptogenic c) Metabolic diseases Hemochromatosis Alpha-1-AT deficiency Wilsons disease e) others Budd-Chiari Policystic liver disease Amyloidosis

4 When is liver transplantation indicated? Histology F1-F3 F4 (cirrhosis) Clinical Non cirrhotic Stable Stable Decompensated Symptoms None None Jaundice/Varices Complications Gradient < 6 mmhg 6-10 mmhg mmhg > 12 mmhg Biology Fibrogenesis/A ngiogenesis Scar Scar/ Microthrombosis Carcinogenesis Elastography 8-14 KPa KPa modif. after Garcia-Tsao, Hepatology, 2010

5 decompensated compensated When is liver transplantation indicated? NO VARICES NO ASCITES VARICES NO ASCITES 7% 7% 1% 3-5% median survival 12 years 1-year mortality ASCITES +/- VARICES VARICEAL BLEEDING+/- ASCITES 8% 15-20% 40-60% median survival 2-3 years El Serag, Am J Gastro, D Amico, Gastroenterology, Stokkeland, Hepatology, 2006

6 When is liver transplantation indicated? Hernandez-Gea, Am J Gastro, 2012

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8 MELD Score Model for End-Stage Liver Disease xlog creatinine xlog bilirubin xlog INR + 6.4

9 3-Month survival MELD R Wiesner et al, Gastroenterology 2003;124:91-96

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13 How to select the right time point for OLT listing

14 How to select the right time point for OLT listing

15 How to select the right time point for OLT listing

16 How to select the right time point for OLT listing The exception with HCC

17 Question

18 Acute liver failure 1) Drug or alimentary toxicity (mushrooms) 2) Viral hepatitis: HBV, Herpes, HEV 3) Budd-Chiari syndrome Clichy criteria: presence of hepatic encephalopathy + factor V level <20% (age < 30) or <30 %

19 Acute liver failure Clichy criteria: presence of hepatic encephalopathy + factor V level <20% (age < 30) or <30 % King s College criteria: - paracetamol induced or other - art. ph < INR > Creatinine > 300 um - Bili > 300 um - Age < 10 or > 40 years - Jaundice to HE time > 7 days

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21 Essential investigations before OLT Laboratory: Liver and kidney function Serologies (CMV!) Blood group Radiology: Anatomy of the liver, vessels, HCC Staging (CT, MRI) Interdisciplinary evaluation: - ID - anesthesia - psychiatry Endoscopy: Upper and lower GI Heart and lungs: stress-ecg LUFU

22 IMMUNOSUPPRESSION Commonly used drugs Follow up visits 2-4 W 2/W 1-2 Mo 1/W after 3 Mo every 4-6 W

23 Wirkungsmechanismen

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25 IMMUNOSUPPRESSION Main side effects PRED CYS TAC MMF mtor

26 Early Follow up after OLT Early complications 1. Primary non function 2. Thrombosis or stenosis of the hepatic art. 3. Portal vein thrombosis 4. Biliary leakage or anastomosis stricture

27 Early Follow up after OLT Early complications

28 Long term follow up: complications 1. Rejection 2. Infections 3. HCC relapse 4. arterial hypertension 5. Osteoporosis 6. Kidney dysfunction/insufficiency 7. (skin-) Tumors Liver Transplantation; Martin ed.; in Clinics in Liver Disease; 11, 2, 2007 Medical Care of the Liver Transplant Patient; Kilemberg & Clavien eds; Blackwell Science, 1997

29 Rejection Acute rejection days after OLT 2. no specific symptoms 3. Lab: cholestasis 4. biopsy needed for diagnosis 5. treatment with steroids Chronic rejection 1. first 6 months after OLT 2. obstruction of small arteries and ductopenia 3. jaundice 4. biopsy needed for diagnosis 5. treatment with steroids and increased IS

30 Infections 1. Frequent in the first 12 months 2. Bacterial infections 3. Viral infections CMV HZV HSV 4. fungi Candida Albicans Aspergillus Fumigatus Criptococcus Neoformans 5. Protozoa Pneumocistis Carinii

31 Bacterial infections 1. Most frequent during the first 8 weeks after OLT 2. Clinical manifestations Abdominal (Peritonitis, Cholangitis, Abscess) Pneumonia Wound infections Becteremia of unknown origin 3. Bacteria intestinal Enterokokken Escherichia Coli other S. Aureus Klebsiella Pneumoniae Pneumokokken Legionellen Nocardia

32 CMV % 2. 50% asymptomatic 3. Viral origin Transplanted organ Blood transfusions Reactivation 4. Symptoms cold pneumonia GI (nausea, vomiting, diarrhea) Hepatitis 5. Diagnosis: PCR, liver biopsy, coloscopy with biopsies

33 HBV 1. <10% with HBIg + Lamivudin 2. Hepatect or Zutectra HCV % 2. Treatment lergely possible with new antivirals, for example Sofosbuvir/Ledipasvir

34 HCC-relapse (<10%) 1. Switch IS to mtor inhibitors 2. Surgical resection 3. TAE 4. RFA 5. Radiation therapy 6. Sorafenib

35 Arterial hypertension 1. Prevalence >70% 2. Etiology: IS, in particular Prednisone, Ciclosporine or Tacrolimus 3. Therapy: ACE inhibitor Hyper-K with IS Leucopenia mit MMF Calcium antagonists (Amlodipine)

36 Diabetes and overweight 1. Very frequent! 2. Therapy like in the non transplanted population, based on adequate diet and physical activity Lipid metabolism 1. Increaed cholesterol with mtor inhibitors 2. Treatment using Statins (Pravastatin, Atorvastatin)

37 Kidney insufficiency 1. Frequent! Up to 20 % after 5 years 2. Aetiology: Ciclosporine (CSA) Tacrolimus (FK) Scarring of the parenchyma Microthromboses Tubular atrophy 3. Treatment Immunosuppression low dose (Plasmalevels) Switch to mtor inhibitors

38 Kidney insufficiency

39 Neoplasia 1. Affects long-term mortality 2. incidence: 2-26% 3. Maily skin tumors (Basalioma, Melanoma) and Lymphomas (PTLD) 4. Risk factors: age smoke alcohol High immunosuppression EBV (de novo/reactivation) 5. Screening is important! - Dermatology

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41 Question

42 Family planning Contraception: Oral contraceptive pill has no CI. If older than 35 consider other possibilities. Avoid smoking. Pregnancy. Possible one year after OLT. Monitoring is important because of premature birth