Liver Transplant Candidate Evaluation by rub18840

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									Liver Transplant: Candidate Evaluation
                                                 il le
                                             is v
                                          o u
                                  f
                Luis S. Marsano, MD
                                    L
                          o
                     Professor of Medicine


                        y
             it
                    Director of Hepatology



         r s
     Division of Gastroenterology, Hepatology & Nutrition



        e
           University of Louisville, Jewish Hospital,



     iv
                     & Louisville VAMC




Un
                   Liver Transplantation
                                        il le
                                    is v
• First attempts: 1963
                                 o u
                             f L
• Reasonable mortality: early 1980s

                            o
   – Organ preservation


                it        y
   – Immunosuppression


              s
   – Patient selection


           er
   – Surgical technique


        iv
• Current:
 n – 1 Year Survival ≥ 85%

U  – 5 Year Survival ≥ 70%
                     Frequency & Need
                                             il le
• 1983 NIH Consensus Conference:is
                                           v
                                 o  u
                              L Centers
  Therapeutic Modality for End-Stage Liver Disease
                            f
                         o
                     ty Transplants in 2006.
• More than 100 Liver Transplant

                s  i
               r Transplant Candidates in waiting
• There were 6650 Liver

          v e
         i2006
     n
• 16,686 Liver

 Ulist in
                                Consequences
                                            il le
                                        is v
•   Longer waiting time
                                     o u
•
                               f L
    Greater “waiting-list mortality”
•
                          o
    More pressure to use “extended criteria” organs.

                        y
                 it
•   Maximal utilization of organs: split livers
•
            er s
    Need for living donors

         iv
•   Tighter selection of recipients
•
    Un
    Need for early referrals – (for problem correction)
              Liver Transplants per Year
                                                         il le
                                                     is v
18000

                                                  o u
16000


                                         f L
                                 o
14000



                               y
12000


                  it
10000


                s
                                                            Transplanted


              r
 8000                                                       Waiting




          iv e
 6000
 4000




Un
 2000
    0
        1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
                                           Deceased Donors by Type
                                                                                il le
                                                                               1997 - 2006
                   6,000

                                                                            is v
                   5,000

                                                                         o u                    5430
Number of Donors




                   4,000

                                                                 f L
                   3,000


                                                    y o
                                          it
                   2,000                                                                        1945
                   1,000


                                     er s                                                       647


                                  iv
                      0


                    n
                           1997    1998   1999   2000   2001     2002   2003   2004   2005   2006


                   U
                                                              Year

                                                        SCD      ECD      DCD
      Survival after Liver Transplant &
                          Re-Transplant
                                                 il le
                                             is v
100

                                          o u
 90


                                    f L
                            o
 80
 70
 60


                it        y
              s
 50                                             Primary LTX


            r
                                                Re-LTX


           e
 40



        iv
 30
 20



Un
 10
  0
       1 year   2 years   5 years    10 years
                                 il le
                 Balancings
                                v
                             i Needs
                         o u
                   f  L
                 o the Patient
         s i tyand
   Need to Care for

     e r to Care for the Organ
 nivNeed

U
                             il le
                         is v
                      o u
                  f L the Patient
                o
     Need to Care for

         s i ty
      er
 n iv
U
                 Indications for Liver
                     Transplantation
                                        il le
                                  is v
                              o u(91%)
                        f  L
• End Stage Chronic Liver Disease

• Extremely poor ty
                     o of Life, or Serious
• Fulminant Hepatic Failure (6%)


            r s i with Early Mortality
                 Quality

  (2-3%). e
  Metabolic Disorder

    n iv
 U
                 Etiology of Liver Disease
 Adult Liver Transplant Recipients
                                                il le
                                            is v
             3.7

                                         o u
                                      L
                                           Chronic HCV
                   4.7


                                    f
           3.8                             ALD
                           20.7


                           o
                                           Cryptogenic C
     4.4



                         y
                                           PBC



           it
     4.8                                   PSC



         s
                                           Acute Liver Failure


       r
  5.5
                                           HBV


      e
                                  17.1     AIH


   iv
   6.2
                                           ALD+HCV


 n
         8.7                               Malignancy



U
                   9.3   10.9              Metabolic
                                           Other
        Non-Disease-Specific

                                             le
       Minimal Listing Criteria

                                       v  il
           Liver Transpl Surg 1997;3:628-637




                                  u is
                               o
                            LNecrosis)
                          f
• Immediate need for Liver Transplantation
                       o < 90% in ESLD.
  (Acute & Subacute Hepatic
• Estimated 1-year y
               s it = or > 7 (Child B or C)
                   Survival
             rBleed or single episode of SBP,
• Portalve
• Child-Pugh score

     n i of Child class
         HTN

 Uirrespective
                           il le
                       is v
                    o u
                 f L
              y o
End Stage Chronic Liver Disease
        r s it
    iv e
Un
                                  Indications
                               il le
     End-Stage Chronic Liver Disease

                           is v
• Hepatocellular Disease: u
                       L o
                     f
                          Child-Pugh B (7-9) or C (10-15)

                   o
                ty
                          1               2              3


            s i
Encephalopathy Grade
Ascites
          r
                       None
                       None
                                         1-2
                                        Mild
                                                        3-4
                                                     Moderate

        e                                              ≥ 3.0
Bilirubin (mg/dL) <      1-2            2.1-3


     iv
   (Cholestasis)        (< 4)          (4-10)          (>10)

   n
Albumin (mg/dL)

 U
Protime elevation or
   (INR < )
                        ≥ 3.5
                         1-4
                       (<1.7)
                                       2.8-3.5
                                        4.1-6
                                      (1.7-2.3)
                                                       ≤ 2.7
                                                       ≥ 6.1
                                                      (> 2.3)
                          il le
                      is v
                   o u
               f L
              o
      Fulminant Hepatic Failure

          ity
            (Acute & Subacute)

     er s
 niv
U
             Fulminant Hepatic Failure
                Definitions & Incidence
                                            il le
                                        is v
                                     o u
• Classic: Development of hepatic encephalopathy

                                    L
  within 8 weeks of initiation of symptoms in a

                                  f
  patient without known chronic liver disease.

                          o
• Practical: Development of hepatic

                        y
               it
  encephalopathy and coagulopathy (INR > 1.5)

             s
  within 26 weeks from the onset of jaundice, in

          er
  patient without known chronic liver disease.

       iv
• Incidence: 2300-2800/ year in USA;

 n
  – 6% of adult transplants;

U
  – 6% of liver-related deaths;
  – 0.1% of deaths in USA.
                 Subtypes of Fulminant
                       Hepatic Failure
                                            il le
                                        is v
• Hyperacute:
                                     o u
                               L
                            100


                             f
  encephalopathy in < 8      90


                       o
  days from jaundice.        80



                     y
                             70                  Hyperac



               it
• Acute: encephalopathy      60                  ute



             s
                             50                  Acute


           r
  from 8 – 28 days.          40




       iv e
• Subacute:                  30                  Subacute
                             20


 n
  encephalopathy from        10



U
  29 days to 26 weeks         0
                                  Survival (%)
  after onset of jaundice
           Fulminant Hepatic Failure
             & Liver Transplantation
                                                      il le
                                                  is v
• Mortality: 75% with
                                               o u
                              L
                           90



                            f
  grade III-IV             80



                      o
  encephalopathy           70



                    y
                           60


               it
• Median age = 28 (vs.   % 50


             s
                                                                     FHF


           r
  44 for chronic ESLD)     40                                        ESLD




       iv e
• Mean waiting time =      30
                           20


 n
  5.3 days
                           10


U                           0       ABO
                                incompatible
                                               Patie nt
                                               Survival
                                                           O rgan
                                                          Survival
Etiology of Acute Liver Failure
                    1998-1999
                                               il le
                                           is v
                                        o u
                                    L
                                            Acetaminophen
               2.2 2
             2.2 1.1 .2


                                  f
           4.5                              Other Drug


                            o
       5.7                                  Indeterminate


                          y
                                 35.4



          it
                                            HBV
     6.2                                    AIH



      r s
                                            HAV



     e
     7.4                                    Ischemia



  iv
                                            Wilson



 n
                                            Pregnancy
                                            Malignancy


U
           17.1
                          14.8
                                            Other
                                      Indications
                 Fulminant Hepatic Failure
                                              il le
                                          is v
                                       o u
• King’s College Criteria
                               f L
                      y o
         r s it
• Acetaminophen (PPV 0.95, NPV 0.78)

     iv e
    • pH < 7.3   or



Un  • PT with INR > 6.5 + creatinine > 3.4 mg/dL
       Acetaminophen-related FHF
                                          Expected Survival
                                                            il le
                                                        is v
100                                            100

                                                     o u
                                          f L
 90



                                 o
 80
                               71
 70



                          it   y
 60          53



                        s
 50


           r
 40                                                        % Survival



          e
 30



       iv
 20


 n
 10



U
  0
      Tylenol + Brain   Tylenol + Brain   Tylenol + NO
       edema + ARF          edema         Brain edema
                                 Indications
             Fulminant Hepatic Failure
                                        il le
                                    is v
                                   u
– Non-Acetaminophen (PPV 1, NPV 0.3)
                                 o
                             L
  • Age < 30 & Factor V < 20 mg/dL, or

                           f
                     o
  • Age > 30 & Factor V < 30 mg/dL


           it      y
  • Patient with INR > 6.5, or


       r s
  • Three of the following:

      e
     – Age < 10 or > 40

   iv
     – Drug reaction or FHF of indeterminate cause


Un   – Jaundice > 7 days before encephalopathy
     – PT with INR > 3.5
     – Bilirubin > 17.6 mg/dL
      Hepatitis A- or B-related FHF
                                                           il
                                           Expected Survival  le
                                                       is v
100

                                                    o u
                                          f L
 90



                                 o
 80
 70                                            67




                          it   y
 60
                               50


                        s
 50


            r
 40                                                       % Survival



           e
             30
 30



        iv
 20


 n
 10



U
  0
      Hep A/B + Brain   Hep A/B + Brain   Hep A/B + NO
       edema + ARF          edema          Brain edema
                                                           FHF
                 Expected Survival by Etiology
                                                          il le
                                                      is v
100

                                                   o u
 90


                                          f L
                                 o
 80



                               y
 70



                      it
 60



                    s
 50


            r
                                                           % Survival



           e
 40



        iv
 30



 n
 20



U
 10
  0
      Wilson's   Cryptogenic   Idiosyncratic   Halothane
             Fulminant Wilson’s Disease

                                                 il le
                                Modified Nazer’s score

                                             is v
• Validated in children         Points

                                          o u
                                         Bili    AST INR


                                    L
  (Liver Transpl 2005;11:441-


                                  f
                                  0      <5.84   <100   <1.3


                             o
  448) & adults (Liver



                           y
  Transpl 2007;13:55-61)


                it
                                  1      5.85-   100-   1.3-
• Score =/> 11, or INR                    8.7    150    1.6


            r s
  =/> 7 needs OLTx;

           e
                                  2      8.8-
                                         11.6
                                                 151-
                                                 200
                                                        1.6-
                                                        1.9


        iv
  all other can receive
                                         11.7-   201-   1.9-


 n
  chelation therapy.              3
                                         17.5    300    2.4


U                                 4      >17.5   >300   >2.4
                             il le
                         is v
                        u Early
    Poor Quality of Lo with
                o f Life

             ty
                         Mortality

       r s i
   iv e
Un
                                             Indications
                                                    il le
                                                      Q of L

                                                is v
• Quality of Life

                                             o u
                                     f L
   – Correction of extrahepatic manifestations of metabolic

                              o
     or chronic liver disease likely to cause early mortality

                            y
                  it
      •   recurrent biliary sepsis


                s
      •   primary hyperoxaluria,



             er
      •   familial homozygous hypercholesterolemia,



          iv
      •   urea cycle defects,



 n
      •   familial amyloid polyneuropathy,



U
      •   hepatopulmonary syndrome,
      •   portopulmonary HTN, etc
                            il
             Contraindications le
                        is v
                     o u
                  f L
 • Absolute      o
        s i ty
       r
 • Relative
      e
 n iv
U
                         Contraindications:
                                  Absolute
                                              il le
                                          is v
                                       o u
• Extrahepatic Malignancy (except in Hepatic Epithelioid
  Hemangioendothelioma)
                                f L
                        y o
• Cholangiocarcinoma (unless in approved special protocol)


              s it
• Hemangiosarcoma

            r
           e
• Uncontrolled Sepsis


  n     iv
• Portopulmonary HTN with PAPm > 35 mmHg despite


 U
  therapy
  Transplant Survival in PPHTN
                                                il le
                                            is v
                                         o u
                                      L
              100




                                    f
               90




                          o
               80




                        y
               70




              it
                                      PAPm<35
               60




            s
               50                     PAPm(35-



          r
                                      50)



         e
               40
                                      PAPm>50




      iv
               30
               20



 n
               10




U
                0
                    OLTx Survival

Expected Survival less than 62% are a contraindication for OLTx
                   Contraindications:
                            Absolute
                                       il le
                                   is v
                              o uDisease
• Active Alcoholism/Substance Abuse

                         f L
• Advanced Cardiac or Pulmonary

                       o Precluding
• Inability to Comply w. Immunosuppression

                  i ty
• Anatomic Abnormality
                s
  Treatment
           e  r
       iv
• Irreversible Neurologic Complication
     n
 (ICP > 50 mmHg x 2h, or cerebral perfusion

 U
 pressure < 40 mmHg x 2h)
                              Contraindications:
                                       Absolute
                                                     il le
                                                 is v
• BMI 40 or higher

                                              o u
                                         L
• BMI 35-39.9 + [Diabetes Mellitus OR Hyperlipidemia] +
  any of the following:
   –   Macroalbuminuria
                               o       f
   –

                  it         y
       Microalbuminuria > 300 mg/L


                s
   –   Renal Insufficiency (other than HRS)
   –

             er
       Retinopathy



          iv
   –   Coronary Artery Disease



  n
   –   Peripheral Vascular Disease



 U
   –   TIA / Stroke
   –   Autonomic Neuropathy
                       Obesity and OLTx
                                         il le
                                     is v
                                  o
• 20% of OLTx recipients are obese.
                                    u
                            f L
• Obesity increase risk of HCC & other tumors

                       o
• Severe obesity: higher infections, respiratory


               it    y
  failure, systemic vascular complications, hospital

             s
  LOS, & cost.

          er
• Mortality in Obese (BMI 30-34.9) & Severely-

       iv
  Obese (BMI 35-39.9) is similar to non-obese when


Unadjusted by co-morbidities.
• Morbid-Obesity (BMI > 40) increases mortality.
                          Contraindications:
                                    Relative
                                                il le
                                            is v
•   AIDS
                                         o u
•
                                  f L
    Advanced age: well motivated and active 65-70
•   Poor social support

                          y o
                 it
•   Previous extrahepatic malignancy:

             r s
     – 2 years free in most malignancies.

            e
         iv
     – 4-5 years free in melanoma, breast ca, colon ca

     n
    – Send consult to: Israel Penn International Transplant


    U
      Tumor Registry (www.ipittr.uc.edu)
• Hepatopulmonary S with PaO2 < 50 mmHg
       Hepatopulmonary Syndrome
                                        il le
                                    is v
                                 o u
• Extra MELD points may be given (24 points) if
  PaO2 < 60mmHg
                           f L
                       o
• Worsens 5 mmHg PaO2 per year.

                     y
               it
• LTx mortality increases to 34% with PaO2 < 50

           r s
  mmHg or MAA shunt > 20%; data is not

          e
       iv
  conclusive yet.

 n
• TIPS is controversial; Coil embolization of

U
  discrete A-V fistulas may help (but is uncommon)
                      Contraindications:
                                Relative
                                         il le
                                     is v
• Prior portosystemic shunt
                                  o u
                               L
• Renal failure

                       o
   – FHF = higher mortality
                             f
               it    y
   – ESLD = if requiring dialysis or liver-kidney Tx

             s
     → higher mortality, ICU stay and cost

          er
       iv
• Obesity: more wound infections (BMI > 35)

 n
• Malnutrition: increases L.O.S., cost and mortality

U
                          il le
                      is v
                   o u
                f L
            y o
          it
     Need to Care for the Organ

     er s
 niv
U
                        Transplant Candidacy

                                        il le
                        Psychosocial Aspects
                                     s
• Non-compliance is responsible fori25%
                                       v of
                                o u
                           f L
  late deaths post organ transplant.

                       o
• Adherence has several components:

               s i
  – medication use,
                   ty     - clinic visits,


           e r
  – laboratory tests,     - self-monitoring,

       iv
  – exercise,
     n
                          - use of harmful substances.

 U
                       Transplant Candidacy
                        Psychosocial Aspects
                                                il le
                                            is v
• Factors affecting adherence:
                                         o u
  – hostility,

                                f L
                          o
  – poor caregiver-support,


                        y
  – poor friend-support,


             s it
  – lack of active coping strategies,

           r
  – use of avoidant coping strategies;


       iv e
  Risk of non-adherence:


 n
      • 0-1 factor: 30%,


U
      • 2-3 factors: 50%,
      • >/=4 factors: 80%
                                Psychosocial Aspects
                                     Social Support
                                                     il le
                                                 is v
• Should be able to provide:

                                              o u
                                        L
   – basic care,                  - transportation,


                                      f
   – medication verification,     - emotional support.


                              o
• Sources of support: family, friends, work relations, faith &

                            y
                 it
  community organizations.


               s
• More than one support person must be identify.


            er
• Must be willing to be involved during evaluation, hospital


         iv
  care, & post-operative care.

  n
• Good support correlates with: better adherence, low

 U
  recidivism, less depression, better graft survival.
                    Psychosocial Aspects
            Alcohol Abuse & Dependence
                                                       il le
                                                   is v
                                                o u
• Chronic medical problem with relapsing-remitting course.


                                          L
• Only 75% of patients transplanted for ALD have alcohol

                                        f
  dependence.

                                o
• Dependence is strong predictor for relapse.


                  it          y
• Dependence requires 3 or more within 12 mo:


                s
   –   1. Tolerance,


              r
   –   2. Withdrawal Syndrome,


             e
   –   3. Larger amount & longer use than intended,


          iv
   –   4. Persistent desire to cut down,


  n
   –   5. Excessive time using,


 U
   –   6. Important activities affected b/o use,
   –   7. Use continues despite physical/psychological problem.
                  Psychosocial Aspects
          Alcohol Abuse & Dependence
                                           il le
                                       is v
                                    o u
• Stable sobriety: if lasting > 5 years.


                             f L
• Sobriety < 6 months does not consistently predicts

                        o
  alcohol relapse.


                it    y
• Relapse rate in LTx waiting-list: up to 25%

              s
• All relapses are serious; very few can go to “social

           er
  use”: Complete abstinence (even from “non-

        iv
  alcoholic beer/wine” is recommended

  n
• Pre- & post-LTx patients should have routine

 Ualcohol screening
                   Psychosocial Aspects
           Alcohol Abuse & Dependence
                                              il le
                                          is v
• Patterns of alcohol relapse post-LTx:
                                       o u
                                  L
   – complete abstinence: 69%,


                          o     f
   – occasional (<14 units/wk & < 4 units in a day): 10%,
   – heavy (>14 units/wk or > 4 units/d for any period): 21%


                it      y
• No difference in 8-y survival among the 3 groups,

            r s
  but alcohol contributed to death in 15% of

           e
  “heavy” group.

        iv
• Any relapse post-LTx:


Un – 1 year = 8-22%;
   – 5 years = 30-50% (vs 60-80% in non-LTx alcoholics)
                   Psychosocial Aspects
           Alcohol Abuse & Dependence
                                       il le
                                  is  v
                             o u
• Predictors of post-LTx alcohol use:
  –   Alcohol dependency
                        f L
  –
                      o
      Short pre-Tx sobriety
  –
              s i ty
      Hx polysubstance abuse
  –
         e  r
      Family Hx alcoholism

      iv
  –   Previous addiction rehabilitation


 U
  –
    n Personality disorders
     Urine Tests for Drugs of Abuse
                                                         il le
                                                     is v
Test Drug       Detectability    False Positives
                                                  o u
                                           L
                duration


                                         f
Amphetamines 2-3 days            Ephedrine, Pseudoephedrine, phenylephrine,


                                  o
                                 selegiline, chlorpromazine, trazodone,



                                y
                                 bupropion, desipramine, amantadine,


                    it
                                 ranitidine



                r s
Cocaine         Light: 2-3 days; Topical anesthetics with cocaine



               e
                heavy: 8 days



            iv
Marijuana       Light: 1-7 days; Ibuprofen, naproxyn, dronabinol, efavirenz,


  n
                heavy: 1 month hemp seed oil



 U
Opiates         1-3 days         Rifampin, fluoroquinolones, poppy seeds,
                                 quinine in tonic water
Phencyclidine   7-14 days        Ketamine, dextrometorphan
                      Psychosocial Aspects
                  Prescription-Drug Abuse
                                               il le
                                           is v
                                        o u
• May be using medication to treat the wrong


                                 f L
  indication (narcotic for anxiety), or at excessive

                          o
  dose.


                it      y
• Chemical dependency program is recommended.
• Should:

           er s
        iv
   – get controlled substances from only one prescriber,


  n
   – use single pharmacy,


 U
   – be followed by psychiatrist or addiction specialist
                    Psychosocial Aspects
                 Prescription-Drug Abuse
                                          il le
                                      is v
                                   o u
• Remember that Methadone once a day is


                             f L
  appropriate for opioid dependency but not for pain

                        o
  control (q 3-6 hours for pain control)


                it    y
• Tapering Methadone in “stable methadone-


            r s
  maintained opioid addicts”, results in relapse of up

           e
  to 80%.


  n     iv
• Relapse of illicit-opioid use < 10% in “methadone

 U
  patients”, and LTx outcome and nonadherence to
  medication is similar to “non-methadone patients”.
                Psychosocial Aspects
        Mood & Personality Disorders
                                           il le
                                       is v
                                    o u
• Up to 63% of cirrhotics have depression.


                              f L
• Depression increases physical complaints & pain,

                        o
  decreases quality of life & coping skills.

                      y
                it
• Treatment of depression can help compliance

            r s
• Patients with suicidal ideation or attempt need

           e
        iv
  intense evaluation from all sources; isolated act is

  n
  not contraindication for LTx; patterns of self-

 U
  destructive behavior are contraindication for LTx.
               Psychosocial Aspects
       Mood & Personality Disorders
                                          il le
                                     is v
                                o udisorder
• Schizophrenia, schizoaffective disorder,
                             Lwith good
                          fsupport, and good
  bipolar disorder, and personality

                        o
  which are stable, controlled,
                    y
                  twith the transplant team,
                 i for LTx.
  adherence, good family
               s
             r
  working relation
           e
       iv
  are not contraindication


 U  n
                       Obesity and OLTx
                                         il le
                                     is v
                                  o
• 20% of OLTx recipients are obese.
                                    u
                            f L
• Obesity increase risk of HCC & other tumors

                       o
• Severe obesity: higher infections, respiratory


               it    y
  failure, systemic vascular complications, hospital

             s
  LOS, & cost.

          er
• Mortality in Obese (BMI 30-34.9) & Severely-

       iv
  Obese (BMI 35-39.9) is similar to non-obese when


Unadjusted by co-morbidities.
• Morbid-Obesity (BMI > 40) increases mortality.
                                     Obesity
                 Contraindications for OLTx
                                                     il le
                                                 is v
• BMI 40 or higher

                                              o u
                                         L
• BMI 35-39.9 + [Diabetes Mellitus OR Hyperlipidemia] +
  any of the following:
   –   Macroalbuminuria
                               o       f
   –

                  it         y
       Microalbuminuria > 300 mg/L


                s
   –   Renal Insufficiency (other than HRS)
   –

             er
       Retinopathy



          iv
   –   Coronary Artery Disease



  n
   –   Peripheral Vascular Disease



 U
   –   TIA / Stroke
   –   Autonomic Neuropathy
  Drug Coverage/ Medical Insurance
                                                 il le
                                             is v
• One time costs:
                                          o u
                                    L
   – Physician cost from day 0 to 90 (total):

                                  f
      • Surgeon = $ 3100   - Hepatologist = $ 570


                             o
      • Anesthesia = $     - Hospital $$$$$



                it
• Recurrent costs:
                           y
              s
   – Cost of Immunosuppressive drugs and laboratory

            r
     monitoring: $ 2000/month.

           e
        iv
   – Management of co-morbidities and anti-rejection


 n
     treatment complications.


U
   – Surveillance for organ damage (ultrasound + doppler,
     liver biopsy, ERCP, …)
                         il le
                     is v
                  o u
               f L
            y o
          it
 Deciding Transplant Priority

     er s
 niv
U
  Model for End-stage Liver Disease
    (MELD) HEPATOLOGY 2001;33:464-470
                                              il le
                                          is v
                                       o u
• Predicts 3-month & 1-year mortality for:
   – a) Hospitalized,

                               f L
                         o
   – b) Ambulatory non-cholestatic,


                       y
   – c) Ambulatory cholestatic (PBC)


              s it
• No affected by: SBP, PSE, Ascites, or Variceal

            r      bleed

        iv e
• 3.8 log(e) bili (mg/dL) + 11.2 log (e) INR + 9.6

 n
  log(e) creatinine (mg/dL)

U
• www.mayo.edu/int-med/gi/model/mayomodl.htm
                 MELD - 3500 patients
               Three-month Death Rates
                                                   il le
                                               is v
100

                                            o u
 90


                                   f L
                          o
 80
 70
 60


                 it     y
               s
 50


          r
                                                   % Death



         e
 40



      iv
 30
 20



Un
 10
  0
      <9   10 to 19   20 to 29   30 to 39   > 40

      MELD 15-17 is equivalent to surgical death-rate
 Effects of MELD implementation
                                        il le
                                    is v
                                 o u
• Current MELD score at OLTx is higher than in
  pre-MELD era.
                           f L
                      o
• Removal from list due to “death/too sick”

                    y
               it
  decreased from 25.9% to 6.7%


           r s
• Patient survival: no-change/slightly better.

          e
       iv
• OLTx for HCC has increased from 7% to 22%

 n
• Waiting time for HCC decreased from 2.3 to 0.6 y

U
                           il le
                       is v
                    o u
                f L
              o
     Correcting for Mortality not

          ity
            Measured by MELD

     er s
 niv
U
                   Factors that may Modify

                                   le
                              MELD points

                               vil
                      Liver Transpl. 12:S85-136, 2006


• Hepatocellular Carcinoma: is
                         o u
                     f L
  – single lesion > 2cm & < 5cm, OR

                   o
  – up to 3 lesions </= 3 cm each, OR

                ty
  – chronic liver disease + AFP > 500ng/mL


          r s i
        e
  – POINTS: increases the MELD to 22


   n iv
 U
                                                   le
                           MELD Exceptions
                                               vil
                            Liver Transpl. 12:S85-136, 2006



                                           uis
                                         o
• Hepatopulmonary Syndrome:


                                  f L
  – Sitting-up ABG@RA with PaO2< 60 mmHg, AND (+)


                          o
    Echo bubble study, with normal CXR & PFTs.


              it        y
  – If CXR or PFTs is abnormal, must have MAA scan


            s
    with shunting > 20%.


         er
  – POINTS:


      iv
     • PaO2 56-59 mmHg = MELD 22;


 n
     • PaO2 51-55 mmHg = MELD 24;


U
     • PaO2 = 50 mmHg = MELD 26 baseline, plus 2 points every 3
       months.
                                                   le
                            MELD Exceptions
                                               vil
                            Liver Transpl. 12:S85-136, 2006



                                           uis
                                         o
• Recurrent Bacterial Cholangitis (PSC, Caroli’s,

                                   L
  ischemic cholangiopathy, etc):

                                 f
   – =/> 2 culture (+) bacteremia over 6 months, OR

                           o
   – any septic complication not related to PTC/ERCP,


                it       y
     without stent/tube, and not suppressed despite antibiotic


              s
     therapy, in the absence of correctable lesion.


           er
        iv
   – POINTS: At Regional Review Board

 n
     discretion.     Add points to MELD

U
     equivalent to 8% death-risk now and every 3
     months.
                                                le
                          MELD Exceptions
                                            vil
                           Liver Transpl. 12:S85-136, 2006



                                        uis
                                      o
• Portopulmonary HTN:

                                    L
  – PP hypertension defined as:

                                  f
     • MPAP 26 to 35 mmHg, AND


                         o
     • PVR >240dynes/sec/cm-5, AND



               it      y
     • [MPAP-PCWP] >12mmHg



             s
  – POINTS: At Regional Review Board discretion.

           r
  – If MPAP > 35 mmHg AND 12 wks of therapy

          e
    (prostacyclin) achieve:

       iv
     • MPAP <35 mmHg AND


 n
     • PVR <400 dynes/sec/cm-5, AND


U
     • Satisfactory RV function;
  – MELD of 26, with additional points after 6 months.
                                                              le
                                   MELD Exceptions
                                                          vil
                                    Liver Transpl. 12:S85-136, 2006



                                                      uis
                                                    o
• Refractory Ascites:

                                          f L
  – Definition = massive ascites AND 2 of the

                                 o
    following:

                               y
     •   a) =/>3 therapeutic paracentesis > 2 L each in last 60 days;



                 it
     •   b) =/> 2 episodes of SBP;


               s
     •   c) Persistent despite previous TIPS;


             r
     •   d) Unresponsive to Spironolactone 400 + Furosemide 160,


            e
     •   e) =/> 2 therapeutic thoracentesis;


         iv
     •   f) Serum Na =/< 125 mEq/L


 n
  – POINTS: At the discretion of Regional Review

U
    Board.
                                        le
                         MELD Exceptions
                                   v il
                          Liver Transpl. 12:S85-136, 2006



                             u  is
                           o
• Refractory Portal HTN GI bleeding:
  – Apply if:
                       f L
                     o
     • bleeding > 6 units in 24 h, OR


               i ty
     • > 2 units/d for 3 days, OR

             s
           r
     • > 2 units/week for > 6 weeks in patient with patent


      iv e
       TIPS or in whom TIPS is contraindicated (bili > 5
       mg/dL, portal v. thrombosis, portopulmonary HTN)


 U n
  – POINTS: MELD exception according to
    Regional Review Board.
                                                le
               Other MELD Exceptions
                                            vil
                           Liver Transpl. 12:S85-136, 2006



                                        uis
                                      o
• Small-for-size syndrome

                                  L
• Cystic Fibrosis
•

                          o     f
  Familial Amyloidotic Polyneuropathy


                        y
• Primary Hyperoxaluria type 1

                it
• Hereditary Hemorrhagic Telangiectasia
•
            r s
  Polycystic Liver Disease

           e
        iv
• Cholangio Ca (for UNOS approved protocol with


     n
  neoadjuvant therapy)


    U
• Carcinoid Neuroendocrine tumors, after removal of
  primary tumor, and without extrahepatic disease.
                                                le
               Other MELD Exceptions
                                            vil
                           Liver Transpl. 12:S85-136, 2006



                                        uis
                                 L    o
• Hepatic Epithelioid Hemangioendothelioma, despite
  extrahepatic disease.

                         o     f
• Adenoma in patient with Glycogen Storage Disease


                it
• Tyrosinemia type 1
                       y
            r s
• Crigler-Najjar type 1

           e
        iv
• Homozygous Familial Hypercholesterolemia


  n
• Maple Syrup Urine Disease (domino LT)


 U
• Mitochondrial defects confined to liver
• Disorders of Fatty Acid metabolism.
                                           le
                 No MELD Exceptions
                                       vil
                      Liver Transpl. 12:S85-136, 2006



                                   uis
                                 o
•   Hepatic Encephalopathy
•
                          f
    Biliary Dysplasia in PSCL
•
                   y o
    Intractable pruritus
•
            r s it
    Budd-Chiari Syndrome
•
        iv e
    Non-carcinoid Neuroendocrine tumors
•
Un  Biliary Cystadenocarcinoma
                                            il
                                    Conclusionsle
                                        is v
                                     o u
• Liver Transplantation is a well established

                                 L
  treatment modality for Fulminant and Chronic End

                         o     f
  Stage Liver Disease, as well as some metabolic

                       y
  diseases with high mortality.

                it
• Long term survival is very good.

            r s
           e
• Shortage of organs requires strict adherence with

        iv
  principles of fair distribution, giving priority to the

  n
  sickest person who has a reasonable expectation of

 U
  survival and who is likely to take good care of the
  grafted organ.
                         il le
                     is v
                  o u
               f LQuestions ?
            y o
      r s it
  iv e
Un
                             il le
                        is v
        TreatmentLo
                      u in the
               o f “waiting list”
                   of HCV


        s i ty
     er
 niv
U
    Pre-LTx Treatment of HCV-Cirrhosis

                                        il le
                                   Candidates

                                    is v
• Best Candidates:
                                 o u
  – Child-Turcotte score =/< 7

                             f L
                        o
  – MELD =/< 18



               it     y
• Best response:

             s
  – genotype 2 & 3


          er
• Patients with Child-Turcotte 8 to 10, or

       iv
  MELD 18 to 24 are controversial.

 n
• Patients with Child-Turcotte =/> 11, or

U MELD =/> 25 are not treatment candidates.
           Effect of pre-LT Therapy on Post-OLTx

                                                         il le
               Outcome in Cirrhotics listed for LT

                                                        v
                Everson et al. Rev. Gastrointest Disord 2004;4 Suppl 1:S31-38




                                                    uis
                                                  o
100                                     100


                                           L
 90                                      90




                                o        f
 80                                      80
 70                                      70




                   it         y
 60                                      60                       Post-
 50                                      50


                 s
                                                                  OLTx
                        IFN+RBV


               r
 40                                      40                       HCV-
                        (N=102)



              e
 30                                      30                       Recurren




           iv
 20                                      20                       ce




 n
 10                                      10
  0                                       0



U
       EOT     SVR                             HCV-     HCV-
      HCV-                                    RNA(-)@ RNA(+) @
      RNA(-)                                    LT       LT
      Post OLTx HCV-Recurrence in Listed Cirrhotics


                                                 il le
                Treated with Daily IFN Monotherapy

                                                v
                           Thomas et al. Liver Transpl 2003;9:905-915




                                            uis
100


                                   L      o
                                 f
 90



                          o
80




                        y
70



                 it
60



               s
50                                              Pre-LT HCV-RNA(-)



             r
                                                Pre-LT HCV-RNA(+)


            e
40




         iv
30




 n
20
10


U
 0
            % HCV-Recurrence
                         il le
                     is v
                  o u
                  L Liver Tx
     Live-DonorfAdult
                o
         s i ty
      er
 n iv
U
               Live-Donor Adult Liver Tx
                                                        il le
                                                    is v
                                                 o u
• 5% of transplants in USA. (learning curve = 20 cases)

                                           L
• Donor: (30-45% of potential donors donate; aborted hepatectomy in 5%)
    – 30% offspring,

                                o
                           - 20% sibling,
                                         f
                              y
    – 20% parent,         - 20% unrelated,


                   it
    – 10% other relative/unknown.


               r s
• Donor age: 50% > 50 years old.

              e
           iv
• Donor risk: (14 death, 1 vegetative state, 2 LT/ 6-7000 live-donors)

  n
    – 0.4% mortality,


 U
    – 0.4-0.6% catastrophic complication, &
    – 35% morbidity
• Patient survival: equal to cadaver-donor.
            Live-Donor Adult Liver Tx
                                          il
             Disease-Specific Considerations
                                             le
• HCC: Must fulfill Milan Criteria is
                                        v
                                o u
                          f  L
• HCV: Is acceptable indication, but
                        o
  appropriate timing needs further
  investigation (noty early).

             r s it indication for emergency
                     too

          e
• FHF: Acceptable

       iv
  transplantation.
     n
 U
                  Live-Donor Adult Liver Tx
                                                 il le
                                       Donor Evaluation

                                             is v
                                          o u
• Complete history & physical with “ideal & actual body

                                     L
  weight”.

                                   f
• CBC, CMP, serologic testing, comprehensive coagulation

                            o
  profile, markers of liver disease, other tests as indicated by


                 it       y
  Hx & PE.


               s
• Psychosocial evaluation.


            er
• Radiology: liver volume & vascular anatomy; biliary


         iv
  anatomy pre-op or intra-op.


  n
• Pre-op liver Bx is controversial (do if: abnl. enzymes, or

 U
  steatosis by imaging, or BMI > 30, donor genetically
  related to patient with AIH, PSC, or PBC)
              Live-Donor Adult Liver Tx
                                         il le
                               Donor Evaluation

                                     is v
                                  o u
• Donor age-limit of 60 is considered appropriate.


                            f L
• BMI > 30 may increase risk to donor, but is not

                       o
  absolute contraindication.


               it    y
• Volumetric imaging analysis may overestimate

             s
  liver volume by 10%.

          er
• Calculated donor-remnant should be at least 30%

       iv
  of original liver volume & with complete venous


Undrainage.
• Graft-liver-volume to recipient-body-weight ratio
  (GWBWR) should be =/> 0.8%.
               Live-Donor Adult Liver Tx
                                            il le
                                  Donor Evaluation

                                        is v
• ABO compatibility is recommended.
                                     o u
• ABO incompatible only in:
                              f L
                        o
  – a) infants,


               it     y
  – b) child < 1y/o without isoagglutinins,


             s
  – c) emergency situation where no deceased-donor

           r
    available


       iv e
• Lab contraindications: HIV, HCV, HBsAg(+),

 n
  anti-HBc(+)

U
• Thromboembolism prophylaxis recommended.
• Autologous blood storage should be offered.
  “Small-for-Size” Syndrome (SFSS)
                                          il le
                                      is v
                                   o u
• Partial liver graft unable to meet functional

                                 L
  demands of recipient: poor early graft function in
  absence of ischemia.
                            o  f
                          y
• Prevention: in cirrhotic GWBWR must be =/>
  0.85%

              r s it
             e
• Manifestations:

          iv
   –   Poor bile production

 n
   –   Prolonged cholestasis

U  –
   –
       Significant ascites
       Coagulopathy
          “Small-for-Size” Syndrome
                                              il le
                                          is v
• Biochemical profile:
                                       o u
                                  L
   – Elevated Direct (& total) bili

                                f
                          o
   – Mild/moderate elevation of ALT & AST


                        y
   – Prolonged PT


              s it
• Histologic Features:

            r
           e
   – Cholestasis with “bile plugs”


        iv
   – Areas of regeneration & ischemia with patchy necrosis.

 n
• Prognosis: 50% of recipients will die of sepsis

U within 4-6 weeks.
        “Small-for-Size” Syndrome
                                         il le
                                    is  v
                               o  u
• Recipient Factors Predictive of poor-
  outcome/ SFSS
                         f  L
  – Graft mass
                      o
                 i ty
  – Poor metabolic & physical recipient condition
               s
          e  r
  – Advanced chronic liver disease & severe portal

      iv
    hypertension


 U  n
  – Impaired venous inflow and/or outflow.
                         il le
                     is v
                  o u
               f L
            y o Questions ?
      r s it
  iv e
Un
       Hepatopulmonary Syndrome
                                        il le
                                    is v
                                 o u
• Extra MELD points may be given (24 points) if
  PaO2 < 60mmHg
                           f L
                       o
• Worsens 5 mmHg PaO2 per year.

                     y
               it
• LTx mortality increases to 34% with PaO2 < 50

           r s
  mmHg or MAA shunt > 20%; data is not

          e
       iv
  conclusive yet.

 n
• TIPS is controversial; Coil embolization of

U
  discrete A-V fistulas may help (but is uncommon)
                     Caution in PPHTN
                                          il le
                                      is v
• Avoid Beta-blockers
                                   o u
                             L
                          100




                           f
• Avoid Ca channel         90




                      o
                           80
  blockers

                    y
                           70




               it
                                                PAPm<35
• Avoid Anticoagulation    60




             s
                           50                   PAPm(35-



           r
                                                50)



          e
                           40
                                                PAPm>50




       iv
                           30
                           20



 n
                           10




U
                            0
                                OLTx Survival
                              Liver Transplant
                                  Waiting List
                                                   il le
                                               is v
16000

                                            o u
14000

                                    f L
                          o
12000




                    it  y
10000



                  s
8000


            r
                                                    Number



           e
6000



        iv
4000



 n
2000


U
   0
        1994   1995   1996   1997    1998    1999
                                   Liver Transplant

                                               il le
                                       Waiting List

                                           is v
18000

                                        o u
16000


                                   f L
                            o
14000



                          y
12000



                 it
10000


               s
                                                Number


             r
 8000                                           Transplanted


            e
 6000



         iv
 4000


 n
 2000


U
    0
        1994 1995 1996 1997 1998 1999    2004
                                                                                      le
                                    Waiting List Registrations 1997-2006

                                                                                  vil             U.S.

                                                                               is
Number of Registrations




                           80,000



                                                                            o u
                                                                      L
                           70,000




                                                                    f
                           60,000



                                                       o
                           50,000




                                      it             y
                           40,000




                                    s
                           30,000




                                 er
                           20,000




                              iv
                           10,000




                           n
                               0
                                1997   1998   1999   2000    2001    2002   2003   2004   2005   2006



                          U
                                                       Year of Snapshot

                                                            Kidney      Liver
                         Liver Transplant
                       Waiting List Deaths
                                                 il le
                                             is v
                                          o
              Deaths waiting for Transplant
                                            u
                                   f L
                          o
2000




               it       y
1500

1000


          er s                                    Number



       iv
500



Un0
       1994   1995   1996   1997   1998    1999
                                 MELD
                 Three-month Death Rates
                                                         il le
                                                     is v
                        MELD Score vs Mortality
                                                  o u
                                          f L
                                   o
          100



                                 y
          80


% Death
          60


              r s it                                    Hospitalized
                                                        Amb non-cholest


             e
          40



          iv
                                                        Amb cholest
          20                                            Historical




Un         0
                </= 9    10 to
                          19
                                 20 to
                                  29
                                         30 to
                                          39
                                                 > 40
                                                         le
                                MELD Exceptions
                                                     vil
                                 Liver Transpl. 12:S85-136, 2006



                                                 uis
                                               o
• Small-for-Size Syndrome:
  – Four of 6 criteria:

                                       f L
                               o
     •   a) >5 days post-LDLT;



                             y
     •   b) Bili >10 mg/dL without obstruction/rejection;


                 it
     •   c) Bile-duct ischemia/leak;



             r s
     •   d) INR =/>1.5;


            e
     •   e) Significant ascites;



         iv
     •   f) Liver Bx with centrilobular ballooning, necrosis, and


 n
         cholestasis.



U
  – POINTS: MELP/PELD equivalent to 50% mortality,
    with increase of 10% mortality every 3 months.
                                           le
                     MELD Exceptions
                                       vil
                      Liver Transpl. 12:S85-136, 2006



                                   uis
                                 o
• Cystic Fibrosis:

                          f L
  – Liver alone: If FEV1<40%: add MELD points

                       o
    equivalent to 10% mortality now and every 3

                     y
              it
    months.

          r s
  – Liver-Lung: If FEV1<40%: 40 MELD points.

         e
 n    iv
U
                                        le
                     MELD Exceptions
                                   v il
                      Liver Transpl. 12:S85-136, 2006



                              u is
                            o
• Familial Amyloidotic Polyneuropathy:

                       f L
  – Diagnosis confirmed by TTR gene mutation by

                     o
    DNA analysis or mass spectrometry in tissue

                i ty
  – POINTS: Initial MELD of 15% mortality, then

              s
            r
    MELD increase equivalent to 10% mortality


      iv e
    every 3 months (for “domino transplant”.)


 U  n
                                                     le
                            MELD Exceptions
                                                 vil
                             Liver Transpl. 12:S85-136, 2006



                                             uis
                                           o
• Primary Hyperoxaluria type 1:


                                   f L
  – Proven deficiency of alanine:glyoxylate


                           o
    aminotransferase (AGT) by liver Bx analysis


               it        y
  – POINTS:


             s
     • a) Less than 1y/o: PELD 40;



          er
     • b) > 1y/o with ESRD on HD, for Liver-Kidney: MELD/PELD



       iv
       equivalent to 15% mortality, with increase in 10% mortality
       every 3 months;



Un   • c) OLTx before renal injury or Liver-Kidney before ESRD:
       MELD/PELD equivalent to 10% mortality, with increase in
       10% mortality every 3 months.
                                       le
                      MELD Exceptions
                                  v il
                       Liver Transpl. 12:S85-136, 2006



                             u is
                          o
• Hereditary Hemorrhagic Telangiectasia:

                      f L
  – Diagnosis: by abdominal CT with characteristic

                    o
    changes (diffuse heterogeneous enhancement &

               i ty
    enlarged hepatic artery)

           r s
  – POINTS: At Regional Review Board

         e
      iv
    discretion;

   n
    Consider MELD 40 for acute biliary necrosis,

 U
    and MELD 22 for intractable heart failure.
                                                       le
                              MELD Exceptions
                                                   vil
                               Liver Transpl. 12:S85-136, 2006



                                               uis
                                             o
• Polycystic Liver Disease:

                                       L
   – Massive PLD (cyst/parenchyma ratio > 1), AND


                             o       f
   – Have either cachexia, ascites, variceal bleeding, hepatic
     outflow obstruction, biliary obstruction, albumin <


                it         y
     2.2mg/dL, low Mid-Arm Circumference (<23.1 cm in
     females, <23.8 cm in males), cholestasis, or recurrent

            r s
     cyst infection.

           e
   – POINTS: At Regional Review Board discretion.

        iv
      • 1) Without renal insufficiency: initial MELD of 15; add 3


 n
        points every 3 months with reapplication.


U
      • 2) With renal insufficiency CrCl < 30: initial MELD 20; add 3
        points every 3 months with reapplication.
                    Re-LTX 1-year Survival
                           by UCLA Class
                                             il le
                                         is v
•   POINTS (1 each)
                                      o u
                                L
                             100



                              f
•   Age > 18                  90


                         o
                              80
•   Liver ischemia > 12 h

                       y
                              70



                 it
                              60                    1 point
•   Pre-op in ventilator

               s
                              50                    2 points


             r
                              40                    3 points


            e
•   Creatinine > 1.6 mg/dL

         iv
                              30                    4 points
•   Bilirubin > 16 mg/dL      20


     n
                              10



    U
                               0
                                   % 1-y Survival
        Predictors of Alcohol Relapse
                          (Kelly 2006)
                                          il le
                                    is  v
• Depression
                               o  u
                          f  L
• Lack of stable partner (family & friends)
• Tobacco use
• Lack of insight y
                       o
               s it (gm/day) before
  evaluation r
          e OF ABSTINENCE WAS NOT
• Amount of alcohol

       iv
 UAn
• LENGTH
    PREDICTOR

								
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