Investigations before OLT, Immunosuppression and rejection, Follow up after OLT andrea.degottardi@insel.ch
When is liver transplantation indicated?
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
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 10-12 mmhg > 12 mmhg Biology Fibrogenesis/A ngiogenesis Scar Scar/ Microthrombosis Carcinogenesis Elastography 8-14 KPa 14-75 KPa modif. after Garcia-Tsao, Hepatology, 2010
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, 2000. D Amico, Gastroenterology, 2001. Stokkeland, Hepatology, 2006
When is liver transplantation indicated? Hernandez-Gea, Am J Gastro, 2012
MELD Score Model for End-Stage Liver Disease 6-40 9.57xlog creatinine + 3.78xlog bilirubin + 11.12xlog INR + 6.4
3-Month survival MELD R Wiesner et al, Gastroenterology 2003;124:91-96
How to select the right time point for OLT listing
How to select the right time point for OLT listing
How to select the right time point for OLT listing
How to select the right time point for OLT listing The exception with HCC
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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 %
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 < 7.30 - INR > 3.5 - Creatinine > 300 um - Bili > 300 um - Age < 10 or > 40 years - Jaundice to HE time > 7 days
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
IMMUNOSUPPRESSION Commonly used drugs Follow up visits 2-4 W 2/W 1-2 Mo 1/W after 3 Mo every 4-6 W
Wirkungsmechanismen
IMMUNOSUPPRESSION Main side effects PRED CYS TAC MMF mtor
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
Early Follow up after OLT Early complications
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
Rejection Acute rejection 1. 4-14 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
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
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
CMV 1. 23-85% 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
HBV 1. <10% with HBIg + Lamivudin 2. Hepatect or Zutectra HCV 1. 100% 2. Treatment lergely possible with new antivirals, for example Sofosbuvir/Ledipasvir
HCC-relapse (<10%) 1. Switch IS to mtor inhibitors 2. Surgical resection 3. TAE 4. RFA 5. Radiation therapy 6. Sorafenib
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)
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)
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
Kidney insufficiency
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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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