Alcoholic Liver Disease as First Indication

Transcription

1 Alcoholic Liver Disease as First Indication Patrizia Burra Multivisceral Transplant Unit Gastroenterology Department of Surgery, Oncology and Gastroenterology Padua University Hospital, Padua, Italy

2 Patrizia Burra, MD, PhD UOSD Trapianto Multiviscerale, Azienda Ospedaliera Universita Padova Il sottoscritto dichiara di non aver avuto/di aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione e che la presentazione non contiene/contiene discussione di farmaci in studio o ad uso off-label

3 Percentage of liver transplants in the US by etiology of liver disease, Blue=Virus Yellow=Alcohol Red= Goldeberg D, et al. Gastroenterology 2017

4 Percentage of liver transplants for HCC in the US by etiology of liver disease, Blue=Virus Yellow=Alcohol Red= Goldeberg D, et al. Gastroenterology 2017

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7 Liver Transplantation for : Padua experience ( ) TOT Average in 15 years = 22.3% *Jan-Sept 2017

8 Number of liver transplants performed in Europe according to Countries ELTR data on liver transplantation for alcoholic liver disease France UK Spain Germany Italy Neuberger J Hepatol 2002;36: from European Liver Transplant Registry

9 Alcoholic cirrhosis as indication to liver transplantation in Spain Legaz et al. Alcohol Clin Exp Res. 2016

10 Trends on main indications for liver transplantation In Spain Legaz et al. Alcohol Clin Exp Res. 2016

11 Survival curves according to main indications for liver transplant in Spain in the short and long term Legaz et al. Alcohol Clin Exp Res. 2016

12 Number of liver transplants for alcoholic liver disease overtime according to recipient gender in Europe 1200 Male Female Burra WIH 2017

13 Changes in indications to liver transplantation overtime in male patients 100% ALF AIH PBC PSC HCC Metabolic Other 90% 80% 70% 60% 50% 40% 30% 20% HCC 10% 0%

14 Changes in indications to liver transplantation overtime in female patients 100% ALF AIH PBC PSC HCC Metabolic Other 90% 80% 70% 60% 50% 40% 30% HCC 20% 10% 0%

15 Indications to liver transplantation in Europe Male Female 29 % ALF AIH PBC PSC HCC Metab. Other Germani, EASL 2016

16 Indications to liver transplantation in Europe Male Female 29 % 13 All p< ALF AIH PBC PSC HCC Metab. Other Germani, EASL 2016

17 Indications to liver transplantation in Europe Male Female 29 % all p< ALF AIH PBC PSC HCC Metab. Other Germani, EASL 2016

18 RECIPIENT AGE Changes over time in recipients transplanted for alcoholic liver disease in Europe < >60 < >60 % Germani, EASL 2016

19 DONOR AGE Changes overtime of donor age in recipients transplanted for alcoholic liver disease in Europe < >60 < >60 % Germani, EASL 2016

20 Effect of donor/recipient matching on the outcome of liver transplantation Marino Hepatology 1995

21 Changes in donor/recipient gender matching overtime in patients transplanted for alcoholic liver disease in Europe M/M F/M F/F M/F Linear (F/M) %

22 LT WL rate per 100,000 US population Waiting list for liver transplant in the era of DAAs patients, UNOS database The rate for decompensated cirrhosis has decreased by 32%, for has increased by 41%, for HCC has increased in both and. Annual Standardized Incidence Rates (ASIR) of LT Wait-Listing per 100,000 US Population Overall Decompensated cirrhosis HCC 10 IFN PI DAA 6 IFN PI DAA 5 IFN PI DAA Year of wait-list registration Flemming JA, et al. Hepatology 2017;65:804 12

23 AD AD AD % Trajectories in Waiting List Registration over time Padua University Hospital p=0.01 Decompensated Cirrhosis 20 p= *Delisting after DAAs: 0% to 5,6% Ferrarese, Transplantation submitted

24 % AD AD AD % Trajectories in Waiting List Registration over time Padua University Hospital p=0.01 Decompensated Cirrhosis 20 p= *Delisting after DAAs: 0% to 5,6% HCC p= Ferrarese, Transplantation submitted

25 % AD AD AD % Trajectories in Waiting List Registration over time Padua University Hospital p=0.01 Decompensated Cirrhosis 20 p= *Delisting after DAAs: 0% to 5,6% HCC p= Ferrarese, Transplantation submitted

26 AD AD AD % Trajectories in Liver Transplantation over time Padua University Hospital p=0.02 Decompensated Cirrhosis Ferrarese, Transplantation submitted

27 % AD AD AD % Trajectories in Liver Transplantation over time Padua University Hospital p= HCC Ferrarese, Transplantation submitted Decompensated Cirrhosis

28 % AD AD AD % Trajectories in Liver Transplantation over time Padua University Hospital p= HCC Ferrarese, Transplantation submitted Decompensated Cirrhosis

29 Alcoholic Liver Disease as First Indication: does it really matter? Ethical issues (Germani) Abstinence before transplant (Pageaux) Neoplastic risk HCC development Metabolic alterations Neurological abnormalities Prevention of relapse (Addolorato) Outcome (Toniutto) Early transplant for severe acute alcoholic hepatitis (Germani)

30 Evaluation of the candidate with alcoholic liver disease for liver transplantation Medical Severity of liver disease (CPT, MELD, other ) Co-morbidities

31 Evaluation of the candidate with alcoholic liver disease for liver transplantation Medical Severity of liver disease (CPT, MELD, other ) Co-morbidities Psychological/Psychiatric/Toxicologic/Social Alcohol abuse or dependence Polydrug abuse Amount and duration of alcohol consumption Alcohol abstinence Previous alcohol rehabilitation Social stability and family relationship Admission of alcoholism

32 Alcohol Abuse and Risk of Upper Aero Digestive Tract Cancer Jiménez-Romero et al. WJG Ursic-Bedoya J et al. WJG. 2015

33 Multivariate analysis of the risk factors for solid organ malignancy Risk Factors for Solid Organ Malignancy: Multivariate Analysis Risk factor HR (95%CI) P value Age by decade 1.33 ( ) Smoking history 1.72 ( ) ( ) PSC 2.62 ( ) Watt K. Gastroenterology 2009

34 Evaluation of smoking habits in candidates to liver transplantation with alcoholic liver disease Alcohol and tobacco use commonly co-occur, with at least 90% of those with an alcohol problem also using tobacco. More than 40% are smoking across all time periods after transplant. Alcoholic liver disease recipients resume smoking early post-transplant, increase their consumption over time. DiMartini LT 2005

35 Alcoholic liver disease () and solid tumors after liver transplantation italian liver transplant recipients 186 cancers 32 head and neck cancers 9 esophageal cancer 10-year cumulative risk for head, neck and esophageal cancer was 2.53% Piselli, Burra & Serraino TI 2015

36 Alcoholic liver disease () and solid tumors after liver transplantation Head and neck cancers SIR 11.8 in liver transplant for (tongue 23, laryns 13.7) SIR 1.8 in liver transplant for non Esophageal cancer SIR 23.7 in liver transplant for SIR 2.9 in liver transplant for non SIR Standardized Incidence Ratios Piselli, Burra & Serraino TI 2015

37 Natural history of chronic liver disease Pellicoro A Nature Reviews Immunology 2014

38 Genetic risk markers in alcoholrelated development of HCC Ethanol metabolism Oxidative stress Inflammation process Iron or lipid metabolism Nahon P & Nault JC Liv Int 2017

39 Cumulative incidence of HCC according to Geography and Etiology of Cirrhosis Alcohol 1.7 x 100 person-years Fattovich G Gastroenterology 2004

40 HCC and alcohol consumption With viral hepatitis in sharpe decline in EU, excessive alcohol consumption will become the main cause of HCC. Alcohol and Digestive Cancers Across Europe: Time fo Change UEG EU Affairs 2017

41 Common and unique features of and NAFLD in HCC Goossens & Yoshida, Gastroenterology 2016 Courtesy of Svegliati Baroni

42 Predictors of Metabolic syndrome after liver transplantation Predictors of MetS OR 95% CI Shorter time from LT Older age Alcoholic liver disease BMI >25 before LT Reduction of physical activity as cause of weight gain after LT Reduced calcium intake Anastacio LR, Nutrition 2011

43 SPECT to evaluate cerebral blood flow alterations in patients with alcoholic liver disease Burra, EJGH 2004

44 Regional brain activity after liver transplantation by etiology of liver disease Senzolo & Burra Transplant International 2009

45 Senzolo & Burra, Transplantation 2002

46 Adherence to medical regimen in patients with alcohol-related liver disease Germani G, AASLD 2009 To medical treatment No Yes To outpatient clinics No Yes To blood tests No Yes Alcohol Non Alcohol (n=67) (n=67) (%) (%) p n.s. n.s. n.s.

47 Patient survival after liver transplantation according to liver disease in Europe (ELTR-ELITA data) Burra P. Am J Transpl 2010

48 Take home messages Alcohol-related liver disease represents up to one third of indications to liver transplantation. Stringent evaluation of co-morbidities and risk of tumors should be performed in candidates to liver transplant. Overall, alcohol-related liver disease represents a favourable indication to liver transplantation.

49 Consensus Conference Venice 15 February 2018 ILTS Annual Congress Lisbon May