Complication of Portal Hypertension: should the patients in the waiting list be treated differently?

Transcription

1 Wilma Debernardi Venon Gastroepatologia, Az. Osp. San Giovanni Battista ditorino Complication of Portal Hypertension: should the patients in the waiting list be treated differently? Il sottoscritto dichiara di non aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione e che la presentazione contiene discussione di farmaci ad uso off-label

2 16 th AISF Pre-Meeting Course INDICATIONS TO LIVER TRANSPLANTATION AND MANAGEMENT OF PATIENTS IN THE WAITING LIST Rome, February 19 Complication of Portal Hypertension: should the patients in the waiting list be treated differently? Wilma Debernardi Venon Gastroepatologia Az. Osp. San Giovanni Battista Torino

3 Portal Hypertension and Liver Transplantation Pre-transplant Organ allocation Post-transplant status MELD MELDNa outcome PSH Quality of life Gastroesophageal Bleeding PBS Rebleeding Renal failure Sepsis Temporary withdrawal from the list Ascites Refractory HRS Iposodiemia Renal Failure Sepsis Portal thrombosis Variceal bleeding Heparin PNF Sepsis Dialysis Renal Failure PVT Waiting Time

4 Portal Hypertension and Liver Transplantation Optimize pre-transplant status 1. Prevention mortality in waiting list 2. Close monitoring 3. Prompt diagnosis 4. Aggressive management post-transplant good outcome Liver Transplant Center

5 Management of SBP in patients awaiting for Liver Transplantation Primary prophylaxis Criticisms: Peritoneal fluid examination Multiresistant bacteria Renal failure Recurrence:70% Temporary withdrawl from the list (2 weeks) GI haemorrage SBP bacteraemia rebleeding crea >1.2 SBP Child >9 HRS Na < 130 meq/l mortality Ascitic fluid protein <15 g/l Recommendations Third generation cephalosporins Albumin 1.5 g/kg 1 g/kg at 48h PMN control Long term oral norfloxacin 400 mg/d Fernandez J. Gastroenterology 2007,Cardenas A & Gines P. Gut 2011

6 VARICEAL BLEEDING in patients waiting for LT Criticisms: High MELD Portal thrombosis Tolerance or contraindication to B blockers Impact on prognosis PBS HRS Upper endoscopy: every 12 months Primary prophylaxis Acute variceal bleeding Current guidelines Prevention of rebleeding

7 Primary prophylaxis of variceal bleeding in patients waiting for LT Small varices + red signs Child C Non selective B blockers Medium or large varices Non selective B blockers Endoscopic banding Criticisms: Contraindication to BB Non responders to BB Treatment discontinuation side effects HRS HVPG? Carvedilol Endoscopic banding 40%

8 Primary prophylaxis of variceal bleeding in patients waiting for LT HVPG Non responders to propranolol Effects of Carvedilol, a vasodilating B blocker, compared with propranolol for Portal Ipertension in cirrhosis 5 RCT, 175 patients MAP reduction: Carv > Pro Proposal: Child A 12.5 mg twice day Child B/C low dose normal renal function Adverse events:ns Sinagra E & D Amico G.Alim Pharm Ther 2013, Tripati D. Alim Pharm Ther 2002

9 Primary prophylaxis of variceal bleeding in patients waiting for LT HVPG Non responders to propranolol Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodinamic non response to propranolol 104 patients 37 (36%) R to PRO 67 NR 38 (56%) R to CARV 29 ( 21%) EBL Decompensation: 32% vs 55% (BB/EBL) Reiberger T. Gut 2013 Carvedilol vs variceal band ligation for the prevention of the first variceal bleed 152 pts Thipati D. Hepatology 2009

10 Primary prophylaxis of variceal bleeding in patients waiting for LT A randomized study comparing ligation with propranolol for primary prophylaxis of variceal bleeding in candidates for liver transplantation 62 pts, 31EBL bleeding Ns versus BB deaths 1 fatal ulcer bleeding Norberto L.Liver Transplatation 2007

11 Primary prophylaxis of variceal bleeding in patients waiting for LT Endoscopic variceal ligation for primary prophylaxis of esophageal variceal hemorrhage in pre liver transplant patients Lim EJ Liver Transplantation pts, 101 EBL mean MELD: 20 bleeding: 2% side effects: 1.2% death or failed LT: 0 70 Endoscopic follow up 3 vs 6 months after esophageal variceal eradication by band ligation in cirrhosis: a prospective randomized trial % 41% 96 EBL 3% 0 Debernardi W. Eur J Gastr Hepat submitted primary P awaiting LT side effects death Primary prophylaxis Waiting LT Side effects death Randomized Study Comparing banding and propranolol to prevent initial variceal haemorrhage in cirrhotics with high-risk esophageal varices Jutabha R.Gastroenterology 2005

12 Primary prophylaxis of variceal bleeding in patients waiting for LT Proposal: B Blockers Child A carvedilol Child B/C propranolol carvedilol low dose waiting time endoscopic experience Low risk High risk Banding portal thrombosis HRS intolerance/contraindication BB HVPG Banding

13 Meta-analysis: Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis Bleeding Mortality Gonzales R. Ann Intern Medicine 2012

14 Prevention of variceal rebleeding and Liver Transplantation Patients whose first episode of bleeding occurs while taking a B blocker have high long term risks of rebleeding and death 89 pts, 34 bleed with BB Early use of TIPS in patients with acute variceal bleeding and high risk for treatment failure 63 pts, 32 early TIPS Garcia Pagan JC. NEJM 2010, Ribeiro de Souza A.Clin Gastr and Hepatology 2012, Garcia Pagan JC.J Hepatology 2013

15 Prevention of variceal rebleeding in patients waiting for LT Proposal: Combination therapy early vasoactive drugs prophylactic antibiotics endoscopic treatment high risk of rebleeding Child C 13 MELD 16 Child B with active bleeding early TIPS HVPG >20 mmhg Portal thrombosis Recurrent gastric variceal

16 Moderate ascites identifies patients with low model for end-stage liver disease scores awaiting liver transplantation who have a high mortality risk 18,124 patients listed for LT MELD < 21 Fever, bleeding, HPS, abdominal pain paracentesis + US Somsouk Ma.Alim Pharm Therap 2009, Cardenas A.Gut 2011, Liver transplantation 2011

17 Refractory ascites and liver transplantation HRS type II Survival < 6months Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis. D Amico G.Gastroenterology 2005

18 Refractory ascites in patients waiting for liver transplantation TIPS or large volume paracentesis? Timing for LT < 1 month > 1 month Large volume TIPS paracentesis Diuretics HRS type II waiting time, transplants, etiology of cirrhosis, liver function Somsouk Ma.Alim Pharm Therap 2009, Cardenas A.Gut 2011

19 Hyponatremia and mortality among patients on the LT waiting list Advanced cirrhosis + Na <130 meq/l: 22% Advanced cirrhosis + Na < 130 meq/l + refractory ascites:50% 1 year survival 25% OLT rapid correction of Naemia osmotic demielination syndrome Kim WR. NEJM 2018, Planas R.Clin Gastr Hepat 2006, Angeli P.Hepatology 2006

20 Impact of PreTransplant Hyponatremia on outcome following LT 2,175 patients Naemia < 130 meq/l: 31% Stay in ICU CPM: 8/10 pts 251 patients Naemia < 130 meq/l: 8% Neurological disorders Renal failure Infections HR=2-4 Yun BC.Hepatology 2009 Londoňo MC. Gastroenterology 2006

21 TOLVAPTAN, an oral vasopressin antagonist, in the treatment of hyponatraemia in cirrhosis Tolvaptan, 63 patients vs placebo, mg/d mg/d Duration therapy: 30 days Na < 130 meq/l: 56% of patients Child B/C:80% Na 5.6±5.1 vs 0.8±4.1, p<0.001 egfr 5.1± 4.0 vs1.7 ±4.5, p< Recurrence Side effects: HF, HE Marked iponatraemia < 125 meq/l Low oral dose: 15 mg/d Short time: 7 days To avoid rapide increase of serum sodium To ill to be transplant? Liver transplantation High priority on the list? Cardenas A. J Hepatology 2012, Boyer TD.Ther Adv Gastroenterology 2012

22 Hepatorenal syndrome: prognosis and pretransplant management Prevention: infections PBS: norfloxacin + albumin postparacentesis volume expansion adequate use of diuretics Rapid diagnosis Early treatment Martin-Llahi M. Gastroenterology 2011

23 Treatment of Hepatorenal syndrome as bridge to liver transplantation Terlipressin + Albumin Responders (40-60%) Impact of LT on the survival of patients treated for HRS type 1 Renal failure in cirrhotic patients: role of terlipressin in the clinical approach to HRS type 2 99 pts, 47 treated Transplants 16 pts, 11 HRS HRS reversal HRS not reversal Boyer TD.Liver ttasnplantation 2011, Alessandria C & Marzano A. Eur J Gast Hep 2002

24 Treatment of Hepatorenal syndrome as bridge to liver transplantation Terlipressin + Albumin Relapser (15%) long term treatment (> 30 days) Care Unit + Priority to LT Piano. J Hepatol 2011, Caraceni P. DLD 2011

25 Hepatorenal syndrome reversal and allocation priority to LT Responders HRS type 1 baseline MELD MELD-Na Allocation system Transplant Center HRS type 2 baseline MELD MELD-Na MELD MELD before HRS no priority TIPS high MELD priority LT (< 3 m) Prognostic Formulae used in the calculation of the probability of death according to MELD score Angeli P. J Hepatol 2012, Martin-Llahi M.Gastroenterology 2011

26 Hepatorenal syndrome non-responders and allocation priority to LT Non Responders HRS ATN Dialysis Onset HRS type 1 LT: mean interval 4-6 weeks ARF resolution UNOS recommendation for combined liver-kidney transplantation Marik PE.Nephrol Dial Transplant XU X. Transplantation 2009 Angeli P.J Hepatology 2012

27 Portal vein thrombosis in patients waiting for LT Incidence: 7-30% Outcome after LT PVT Primary non function Renal failure and dialysis Surgical time Blood Transfusion US doppler every 3 months PVT 5% 6.6% 20% 6h 10U Non PVT 1.1% 1.4% 9.4% 5h 5U p < < Liver transplantation 2000, Gut 2005 portal vein splenic vein mesenteric vein Aim of the therapy!

28 Portal vein thrombosis in patients waiting for LT Recanalization:40-75%,Reversal by FFP, No impact on blood loss or surgical time Con: monitoring, bleeding, complete thrombosis Con: misplacement, high MELD, HE Feasibility: %, Recanalization if complete PT, Low risk of dysfunction

29 Portal vein thrombosis in patients waiting for LT Organ allocation NO Predictor of waiting list mortality MELD exception Post-transplant anticoagulation NO anatomical portal anastomosis (?) long term treatment High risk of portal thrombosis Yes MELD calculated before anticoagulation MELD XI (?) YES prothrombotic state reno-portal anastomosis or caval transposition Francoz C. J Hepatology 2012 Enoxaparin prevents PVT and decompensation in patients with advanced cirrhosis Villa E. Gastroenterology 2012