Chronic liver failure Assessment for liver transplantation

Transcription

1 Chronic liver failure Assessment for liver transplantation

2 Liver Transplantation

3 Dealing with the organ shortage Timing of listing must reflect length on waiting list Ethical issues Justice, equity, utility 50% 5 year rule Arbitrary; quality of life Deceased versus living donors Should indications and contra-indications be similar

4 Analysis based on adult recipients only Paediatrics (0-16) % patient survival Adults N year % survival % CI

5 100 Kaplan-Meier estimates by primary liver disease % patient survival % patient survival Overall N 15 year 95% CI % survival Primary biliary cirrhosis Autoimmune cirrhosis Post hepatitis B cirrhosis Sclerosing cholangitis Cryptogenic cirrhosis Alcoholic cirrhosis Post hepatitis C cirrhosis Cancer

6 UK Transplant Kaplan-Meier estimates by year of transplant % patient survival

7 UK Transplant Kaplan-Meier estimates by year of transplant Restricting dataset to patients who have survived 6 months Future patients life expectancy can be predicted from past data % patient survival % patient survival

8 Average life expectancy by primary liver disease K Population years) Life expectancy (years) ( ) 26.9 ( ) 25.1 ( ) ( ) ( ) 15.4 ( ) 12.4 ( ) 5.8 ( ) 0 Primary biliary cirrhosis Sclerosing cholangitis Cryptogenic cirrhosis Autoimmune cirrhosis Post hepatitis B cirrhosis Primary liver disease Alcoholic cirrhosis Post hepatitis C cirrhosis Cancer

9 Average life expectancy by sex, age group and primary liver disease Life expectancy (years) years years years PBC years years PBC ALD Hep C ALD Hep C 10 0 Males Females

10 Average life expectancy by age group lifeyears lost lifeyears lost Adult liver transplant recipients Equivalent UK population Life expectancy (years) ( ) 24.6 ( ) lifeyears lost ( ) 1.8 lifeyears lost ( ) 4.2 lifeyears lost ( ) Age group

11 Life-years by sex, age group and primary liver disease 20 PBC PBC years years years years years 0 Life-years ALD Hep C ALD Males Females Hep C

12 Assessment Does the patient need a transplant at this time Will the patient survive the peri-operative period Will the patient meet the 50% 5 year criterion Does the patient want a transplant and are they fully informed?

13 Prognostic models Scoring Systems Child-Turcotte-Pugh MELD Disease specific Limitations Population sensitive Wide confidence intervals

14 MELD/PELD Equations MELD =(0.957 x LN(creatinine) x LN(bilirubin) x LN(INR) ) x 10 Capped at 40 PELD= (0.436 x Age*) *)-(0.687 x log(albumin albumin))+(0.480 x log(bilirubin bilirubin))+ (1.857 x log(inr INR))+(0.667 X growth failure ) x 10 * Age < 1 year gets 1, Age >1year gets 0 growth failure =1, no growth failure =0

15 Child-Pugh Score Variable components Some are subjective Designed to assess prognosis for patients undergoing oesophageal transection Not really validated Intuitive

16 60 CTP vs MELD National Wait List MELD Score r=0.66; p< CTP Score

17 MELD vs. CTP Validation ROC Curve UNOS Waitlist 1 Sensitivity MELD CTP MELD AUC = 0.83 CTP AUC = Specificity

18 MELD Validation Hospitalized Cirrhotics Outpatient Cirrhotics PBC Outpatients Historical Cirrhotics n Deaths 3 months 3-Month Mortality (Concordance) ( ) ( ) ( ) ( ) 1-Year Mortality (Concordance) 0.85 ( ) 0.78 ( ) 0.87 ( ) 0.73 ( ) Wiesner, et al, Liver Transplantation, 2001; 7:

19 Survival (%) MELD and PELD Three Month Mortality Risks 1,230 Adult and 649 Pediatric Patients Added to Waiting List between 3/1/01 100% 80% 60% 40% 20% 0% MELD: National Waitlist and 8/15/ reeman Liver Transplantation, 2002, 8:854. Severity Score PELD: SPLIT Patients

20 Hepatocellular CA MELD Prioritization Original Current Proposed Stage I 1 tumor < 2cm 15% Risk =MELD 24 8% Risk =MELD 20 0 Risk =MELD calculated Stage II 1 tumor 2CM but < 5 cm or 2-3 tumors largest < 3 CM 30% Risk =MELD 29 15%Risk =MELD 24 15% Risk =MELD 24 Centers re-certify every 3 months. Patients continuing to meet stage I or II definition receive additional 10% mortality risk points (~5 MELD points)

21 Hepatocellular Carcinoma Imaging Study (CT or MRI) Showing Stage I or II Tumor (chest CT and bone scan) AND one of the following APF >200 Angiogram Biopsy Chemoembolization Cryoablation Radiofrequency Ablation Alcohol Ablation

22 Other Special Cases HPS (hepatopulmonary syndrome =PaO2 < 60 on RA, shunt, no COPD or other lung Dx) RRB will assign MELD points that will give reasonable chance of organ offer within 3 months in that region. FAP (familial amyloidosis) RRB review and assign MELD points Other RRB review, need experience with MELD/PELD to assess proper placement

23 6-Month Patient Survival 2/27/02-12/31/ M/P percent surviving Status Months

24 6-Month Patient Survival Calculated MELD, 2/27/02-12/31/ Percent Surviving Months M 7-15 M M M > 35

25 6-Month Patient Survival Calculated PELD, 2/27/02-12/31/ Percent Surviving Months P < 6 P 7-15 P P P > 35

26 6-Month Patient Survival 02/27/02-12/31/ Percent Suriving Months HCC Non HCC Std M/P

27 MELD of First Offer (4/1/02-7/31/03)* Offers Statu Uncapped Lab MELD 1 *Excludes offers to patients with exception scores

28 Proportion of Transplants (%) Transplant Distribution by Lab 48 4 MELD/PELD Excludes Status 1 and Exceptions < MELD/PELD PELD (N=261) MELD (N=4,219) Deceased Donor Transplants from 4/1/2002 7/31/2003

29 Mortality Rates by MELD 0000 Waitlist Transplant Rate per 1000 PY HR=1.77 P<0.01 HR=0.32 P< HR=0.07 P< HR=0.03 P< HR=2.19 P=0.01 HR=0.62 P<0.01 HR=0.12 P<0.01 HR=0.06 P<0.01 HR=0.36 P<0.01 < Status 1 MELD

30 Lessons from MELD MELD is an objective method of assessing prognosis MELD is relatively objective and since its introduction, deaths on waiting list has been reduced Accuracy may be increased by including serum sodium Those with MELD <22 but hyponatremia (serum Na <128mmol/L) may do badly MELD score <35 does not correlate with post transplant outcome

31 Indications Unacceptable quality of life (because of the liver) Anticipated survival, in the absence of liver disease, of <1 year

32 Quality of life Recurrent encephalopathy Recurrent ascites Severe lethargy Exclude treatable causes Does not always improve after transplant Intractable itching Drugs (incl. Rifampicin, naltrexone), plasmaphoresis, MARS

33 Length of life Clinical End-stage disease Malnutrition, encephalopathy; SBP; progressive hepatic osteodystophy, HCC, developing HPS Serology Falling albumin, rising PT, rising bilirubin

34 Contra-indications to transplantation Extra-hepatic cancer/metastatic disease Active sepsis Cholangiocarcinoma Advanced cardiac disease Advanced pulmonary disease Widespread vascular thrombosis HIV with AIDS and low CD4

35 Relative Contra-indications Difficult to assess How many relative contra-indications make an absolute contra-indication?

36 Age Ethical Issues Equity, justice and utility Good innings argument Age as a continuous variable Chronological age and biological age

37 Effect of age on transplant outcome Cum Survival >60 < 60 months

38 Effect of age Survival Period Cum Hazard days days 0-30 days Age (years)

39 Nutrition MAC Died Survived TSFT

40 Nutrition Does malnutrition affect outcome It makes sense to correct nutritional deficiency with oral supplements or nasogastric feeding It makes little sense to defer transplantation for malnutrition

41 Diabetic patients vs comparison group Diabetic patients vs comparison group matched for age, sex and date of transplant Comparison Diabetics p value matched for age, sex and date of transplant Comparison Diabetics p Num ber Sex Number 43 m 7835 f m 35 f Sex 43 m f 43 m 35 f Age (m ean) Age (mean) Deaths Deaths Child Pugh score 10) 5-14 (median 10) 0.2 Child Pugh scorepatients with Hepatoma 5-156(median 10) (median ) 0.2 P atients w ith H epatom Total previousa ns 0.8 Abdominal surgery T otal previous Median Duration of ns ns (hours) Abdominal surgery Total Units blood ns M edian Duration transfused of (all patients) 5 5 ns Time Ventilated postop. (median days) 3 3 ns surgery (hours) T otal U nits bloodmedian ITU stay ns ns Median Hospital stay ns transfused (all patients) Median survival T im e V entilated postop. 3 3 ns (median days) M edian IT U stay 2 3 ns M edian Hospital stay ns M edian survival value

42 Cardiac problems Ischaemic heart disease Role of exercise ECG Stress ECG Angiogram Echocardiogram Assessment of pulmonary hypertension Structural and functional abnormalities

43 Hepatopulmonary syndrome Resting arterial blood gases If low po 2 Standing and lying po 2 Gases on 100% O 2 Consider bubble echo/muga scan Risk of transplantation increases with degree of orthodeoxia

44 Pulmonary Hypertension If estimated PA pressure >30mm Hg, or ECG shows RV+, measure PA pressure If PA 25-35mm Hg and PVR dynes.s.cm -5 : mild If PA >35 and PVR >250 dynes.s.cm -5 : moderate/severe Consider prostacyclin, Bosentan

45 Alcohol Controversial Arguments not really based on fact Recidivism Definition Need

46 Alcohol and substance misuse Alcohol: Abstinence Duration of abstinence does not correlate with posttransplant outcome Markers of recidivism: single, other drug misuse Non-hepatic alcohol damage Cardiomyopathy Cerebral atrophy other

47 HCC Milan criteria Extended criteria Role of down-sizing Management on the list

48 HCC Milan criteria Small series, based on examination of explants One lesion <5cm 3 lesions < 3cm Extended criteria Role of down-sizing Management on the list

49 HCC Milan criteria Extended criteria UCSF Role of down-sizing Management on the list

50 HCC Milan criteria Extended criteria Role of down-sizing Management on the list Trans Arterial Chemo-embolisation Radio-frequency ablation Cryotherapy/ethanol injection

51 Conclusions Assessment for transplantation is relatively easy Absolute contra-indications are usually well defined Relative contra-indications are defined but assessment is a matter of clinical judgement

52 More people die from clinical judgement than from any other cause Nils Tygstrup