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THAI TRANSPLANT CARE (TTC)

LIVER

Thai Transplantation Society

April 2015

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THAI TRANSPLANT CARE (TTC) LIVER

1
2558

2
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10310
. 02-716-6181-4
02-716-6183
www.transplantthai.org

42

500

3/3 49 10110
. 0-2258-7954, 0-2662-4347
0-2258-7954
E-mail : bkkmed@gmail.com

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............................................................................................
.............................
(indication) (criteria)
.............................................................
(contraindication) .......................
.................................
(indication) (criteria) ..
(contraindication) ...........................
.........................................................................................
.......................................................
.........................................................................................
......................................
................................................................................ 26,
acute rejection ................................
chronic rejection ............................
.........................................................................................

9
10
11
13
14
15
16
16
17
20
21
30
34
40
41

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(Glossary)
ACR
ALT
AST
APC
ALP
ATG
CMV
CNI
CR
CKD
GFR
EBV
INR
IL2
MMF
MPA
mTOR
PTLD
RAI
TCR

Acute cellular rejection

Alanine aminotransferase
Aspartate aminotransferase
Antigen presenting cell
Alkaline phosphatase
Antithymocyte globulin
Cytomegalovirus
Calcineurin inhibitors
Chronic rejection
Chronic kidney disease
Glomerular filtration rate
Ebstein-Barr
International ratio
Interleukin 2 (IL-2)
Mycophenolatemofetil
Mycophenolic acid
Mammalian Target of Rapamycin
Post-transplant lymphoproliferative disorders
Rejection activity index
T cell receptors

10

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1. autoimmune
hepatitis
2. primary biliary cirrhosis, sclerosing cholangitis, biliary atresia
3. metabolic liver disorders hemochromatosis, Wilsons disease,
tyrosinemia, glycogen storage disease
4. (fulminant hepatic failure)

5. (hepatocellular carcinoma)
6. hepatoblastoma, hepatic hemangioendothelioma, polycystic liver disease, Budd-Chiari syndrome

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(indication) (criteria)

(decompensated cirrhosis)
1
90 Child-Pugh B (Child-Pugh score >7) ChildPugh C (Child-Pugh score >9)
(ascites), (spontaneous bacterial peritonitis), (hepatic encephalopathy),
(variceal hemorrhage), hepatorenal syndrome
MELD score#
15 6

MELD score = (0.957loge (Cr.-mg/dl) + 0.378loge (Bili-mg/dl) + 1.12loge (INR) +

0.643)*10
(hepatocellular carcinoma)
5 70

5 . 1 1
3 3 .(
Milan criteria)
(portal vein)
Milan criteria

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(fulminant hepatic failure)

Kings College criteria 1

1 Kings College criteria

Acetaminophen overdose

Non-acetaminophen causes

Arterial pH < 7.3

3

Prothrombin time > 100 (INR > 6.5)

3 5

1. Prothrombin time > 100

( INR > 7.7)
2. Creatinine > 3.4 ./.
3. Grade III IV hepatic
encephalopathy

1. < 10 > 40
2. : non-A, non-B

3. Jaundice > 7 encephalopathy

4. Prothrombin time > 50 (INR > 3.5)
5. Bilirubin > 17.5 ./.

chronic
cholestasis, hepatopulmonary syndrome

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(contraindication)
1.
2. (uncontrolled sepsis)
3. human immunodeficiency virus (HIV)
4.

5.
6.
7.

8.

14

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(indication) (criteria)

1. biliary atresia, sclerosing cholangitis
2. progressive familial intrahepatic cholestasis, Alagilles syndrome
3. Metabolic liver disorders Wilsons disease, tyrosinemia, CriglerNajjar syndrome, disorder of urea cycle, inborn error of bile acid metabolism
4. (fulminant hepatic failure)
5. primary liver tumor, cystic fibrosis, total parenteral
nutrition-induced cholestasis

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(indication) (criteria)
1. (cirrhosis)

1.1
- Total bilirubin > 9 ./.
- Prothrombin time 5 INR
> 1.4
- Serum albumin< 3.5 /.
1.2
- Hepatic encephalopathy
- Refractory ascites
- Spontaneous bacterial peritonitis
- Recurrent variceal bleeding
- Intractable pruritus
- Hepatopulmonary syndrome
- Growth failure ( nutritional support )
2. Acute liver failure (fulminant hepatic failure)
Kings College criteria ( 1)
grade III - IV hepatic encephalopathy
AST ALT
coagulogram
3. Metabolic liver disorders
tyrosinemia, Crigler-Najjar type I, organic acidemia, primary oxalosis, Wilsons
disease
4.
Milan criteria

16

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(contraindication)
1. HIV
2. (uncontrolled sepsis)
3.

4.

5.
6.

1. Murray KF, Carithers RL Jr, AASLD. AASLD practice guidelines: Evaluation of

the patient for liver transplantation. Hepatology 2005;41:1407-32.
2. Martin P, DiMartini A, Feng S, Brown R Jr, Fallon M. Evaluation for liver
transplantation in adults: 2013 practice guideline by the American Association
for the Study of Liver Diseases and the American Society of Transplantation.
Hepatology 2014;59:1144-65.
3. Kelly D, Mayer D. Liver transplantation. In: Kelly D, editor. Diseases of Liver
and Biliary System in Children. 3rd ed. West Sussex: Blackwell publishing;
2008. p. 503-530.

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Immunological pathway of organ transplantation

.. 2506


alloantigen
steroid azathioprine




recipient
donor immune tolerance

Recipient donor alloantigen

(innate
and adaptive immune response) antigen presenting
cell (APC) T helper cell (TH)
interleukin 2 (IL-2)
IL-2 IL-2 receptor
specific T cell
( 1)

18

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1 allograft rejection antigen presenting cells (APC) alloantigen express MHC class II T cell
receptor (TCR) specific T cell

TH ( 2)
APC bile duct vascular endothelium
acute rejection
endotheliitis bile duct
APC
antigen MHC class II
molecule TH antigen
T cell receptors (TCR) complex co-receptor
CD3 TCR co-stimulatory receptor:
CD28 [ APC B7 (CD80, CD86)], TCR
antigen MHC class II

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calcineurin
nuclear factor of activated T cell (NFAT) transcription factor
IL-2 IL-2
IL-2

IL-2/IL-2 receptor
molecular target of rapamycin
mTOR TCR co-receptor: CD28

2 IL-2 signaling molecules

allograft rejection

20

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( anergy), NF-KB transcription factor

cyclin dependent kinase (CDK)

nucleic acid
purine pyrimidine DNA

acute rejection
IL-2 specific T cell

( 2)

1. Starzl TE, Klintmalm GB, Porter KA, Iwatsuki S, Schroter GP. Liver transplantation with use of cyclosporina and prednisone. N Engl J Med 1981;305:266-9.
2. John Devlin, Peter Donaldson, Roger Williams. Type of rejection and immunosuppression. In: Williams R, Portmann B, Tan K-C, eds. The Practice of Liver
Transplantation. London: Churchill Livingstone, 1995. p. 183-89.

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Corticosteroids
T-cell
antigen-derived cytokine expression IL-1, IL-2, IL-3 IL-6
500-1000 .
corticosteroids
3-6

Calcineurin inhibitors (CNI) cyclosporine tacrolimus

Cyclosporine tacrolimus
cyclosporine cyclophilin tacrolimus FK-binding
protein calcineurin transcription
activation cytokine genes IL-2, TNF-alpha, IL-3, IL-4,
T cell activation proliferation
Tacrolimus CYP3A4 CYP3A5 90
tacrolimus tacrolimus
(trough level) 5-15
/. 4-6 trough level
5-7 /. 0.050.1 ././ 2
0.03-0.05 ././

cyclosporine trough
level 250-350 /. 1

22

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trough level 150-250 /. 6

100-200 /.
5 ././ 2
trough level cyclosporine 2
C2 (
) C2 850-1400
/.
cyclosporine C2 tacrolimus
cyclosporine C2
troughlevel

Antiproliferativedrug mycophenolatemofetil (MMF),

mycophenolic acid (MPA) azathioprine
MMF MPA purine nucleotides T B lymphocytes MMF
immediate release MPA delayedrelease MMF
2-3 / 30-40 ./
./ 600 ./ (..)/ 2-3 /
MPA 720-1440 ./ 2
MPA
azathioprine purine synthesis
inhibition azathioprine 1-3 ././

mTOR Inhibitor
FK506-binding protein mammalian
targets of rapamycin T-cell proliferation sirolimus

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0.1 ./. 5 . 2 ./
(trough level)
5-10 /. everolimus 1
. trough level 3-8 /.
CNI CNI
sirolimus
tacrolimus cyclosporine graft
survival hepatic artery thrombosis

Antibody therapy 2
Lymphocyte depleting antibody antithymocyte globulin (ATG)
polyclonal antilymphocyte antibody T cell
apoptosis antibody-mediated cytolysis 1.5-5 ./. 4-6
. 3-5
Non-lymphocyte depleting antibody IL-2 receptor antibody
basiliximab IL-2 -chain competitive antagonism
IL2-induced T cell proliferation 20 .
20 . 4
35 . 10 ./



2

24

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Tacrolimus

Hypertension, headache, infection, hyperglycemia, insulin dependence, tremor, chronic renal failure, PTLD
Cyclosporine
Hypertension, infection, hyperglycemia, chronic renal failure, hirsutism, gingival hyperplasia, PTLD
Sirolimus
Hypercholesterolemia, infection, edema, proteinuria,
PTLD,delayed wound healing, may be associated with
hepatic artery thrombosis when use early post liver transplantation
Corticosteroid
Hypertension, increased appetite, Cushing syndrome, acne,
gastritis, hyperglycemia, delayed wound healing, osteoporosis, delayed linear growth
MycophenolateIntestinal hypermotility, cramping, diarrhea, leukopenia,
mofetil (MMF)
anemia, thrombocytopenia, PTLD
Antithymocyte globulin Fever, chills, rash, anemia, thrombocytopenia, serum sickness, nephritis, CMV infection and PTLD
IL-2 receptor antibody Rare infusion reaction, less opportunistic infection and
PTLD

2 induction maintenance
1. Induction immunosuppression: 3
corticosteroid, CNI antimetabolite
corticosteroid
IL-2 receptor antibody antithymocyte globulin (ATG)

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Steroid induction methylprednisolone 500 . 1

Antibody induction IL-2R antibody lymphocytedepleting

antibody
rejection
acute cellular rejection
antibody induction UNOS
antibody induction 25
antibody induction
rejection
1 antibody induction

antibody induction
renal toxicity CNI antibody induction CNI
/ CNI (delayed introduction of CNI)
IL-2 receptor antibody

antibody induction

1. hepatorenal syndrome
2.
3. CKD stage 3 CKD stage 2 with acute kidney
injury
4. extended criteria donor
5. rejection post-operative renal
impairment

26

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Antibody IL-2R receptorantibody (

basiliximab) lymphocyte depleting antibody thymoglobulin
anti-thymocyteglobulin
Basiliximab
20 .
(

) 4
Thymoglobulin anti-thymocyte globulin
1.5 ././ 5-7 (
pre-medication rejection)

1. Tchervenkov J, Flemming C, Guttmann RD, des Gachons G. Use of

thymoglobulin induction therapy in the prevention of acute graft rejection episodes following liver transplantation. Transplant Proc 1997;29:13S-5S.
2. Emre S, Gondolesi G, Polat K, Ben-Haim M, Artis T, Fishbein TM, et al. Use of
daclizumab as initial immunosuppression in liver transplant recipients with
impaired renal function. Liver Transpl 2001;7:220-5.
3. Neuhaus P, Clavien PA, Kittur D, Salizzoni M, Rimola A, Abeywickrama K, et
al. Improved treatment response with basiliximabimmunoprophylaxis after liver
transplantation: results from a double-blind randomized placebo-controlled trial.
Liver Transpl 2002;8:132-42.
4. Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic
renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;
349:931-40.

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5. Yoshida EM, Marotta PJ, Greig PD, Kneteman NM, Marleau D, Cantarovich M,
et al. Evaluation of renal function in liver transplant recipients receiving daclizumab
(Zenapax), mycophenolatemofetil, and a delayed, low-dose tacrolimus regimen
vs. a standard-dose tacrolimus and mycophenolatemofetil regimen: a multicenter
randomized clinical trial. Liver Transpl 2005;11:1064-72.
6. Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, et al.
Short-term induction therapy with anti-thymocyte globulin and delayed use of
calcineurin inhibitors in orthotopic liver transplantation. Liver Transpl 2007;
13:1039-44.
7. Bajjoka I, Hsaiky L, Brown K, Abouljoud M. Preserving renal function in liver
transplant recipients with rabbit anti-thymocyte globulin and delayed initiation
of calcineurin inhibitors. Liver Transpl 2008;14:66-72.
8. Neuberger JM, Mamelok RD, Neuhaus P, Pirenne J, Samuel D, Isoniemi H, et
al. Delayed introduction of reduced-dose tacrolimus, and renal function in liver
transplantation: the ReSpECT study. Am J Transplant 2009;9:327-36.
9. Boillot O, Seket B, Dumortier J, Pittau G, Boucaud C, Bouffard Y, et al.
Thymoglobulin induction in liver transplant recipients with a tacrolimus,
mycophenolatemofetil, and steroid immunosuppressive regimen: a five-year
randomized prospective study. Liver Transpl 2009;15:1426-34.
10. Wang XF, Li JD, Peng Y, Dai Y, Shi G, Xu W. Interleukin-2 receptor antagonists in liver transplantation: a meta-analysis of randomized trials. Transplant
Proc 2010;42:4567-72.
11. Benitez CE, Puig-Pey I, Lopez M, Martinez-Llordella M, Lozano JJ, Bohne F, et
al. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized
controlled trial in liver transplantation. Am J Transplant 2010;10:2296-304.
12. http://www.fda.gov/safety/medwatch/safetyinformation/ucm187076.htm

28

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. . . .
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2. Maintenance immunosuppression:
corticosteroid
corticosteroid 3-6 (
autoimmune hepatitis) (monotherapy)
2 (double therapy) CNI antiproliferative drug mTOR-inhibitor

meta-analysis tacrolimus
acute rejection cyclosporine
tacrolimus cyclosporine
(monotherapy)
anti-proliferative mTOR-inhibitor
CNI cyclosporine
PTLD EBV IgG (+)
EBV IgG (-)
tacrolimus

(
)

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CNI

1. CNI (early minimization) CNI

(early withdrawal CNI)
CNI ( target level CNI
50-70 ) MMF
rejection CNI
PROTECT study CNI
everolimus glomerular filtration rate (GFR)
CNI
2. CNI CNI (CNI switching)
CNI MMF
6
antiproliferative drug

rejection
5
3. CNI (CNI-free regimen)
rejection
CNI

cyclosporine
cyclosporine

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. . .. .. . . .

cyclosporine
tacrolimus
(hepatocellular carcinoma)
sirolimus everolimus
sirolimus
everolimus mammalian target of rapamycin (m-TOR)
pathway
meta-analysis 2 sirolimus

sirolimus

(combined liver kidney transplantation - CLKT)

GFR CLKT
50 CNI
antiproliferative

1. Zarrinpar A, Busuttil RW. Immunomodulating options for liver transplant patients. Expert Rev Clin Immunol 2012;8:565-78.
2. Post DJ, Douglas DD, Mulligan DC. Immunosuppression in liver transplantation. Liver Transpl 2005;11:1307-14.
3. Shenoy S, Hardinger KL, Crippin J, Korenblat K, Lisker-Melman M, Lowell JA,
et al. A randomized, prospective, pharmacoeconomic trial of neoral 2-hour
postdose concentration monitoring versus tacrolimus trough concentration

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4.
5.
6.

7.

8.

9.

10.

11.

12.

13.

monitoring in de novo liver transplant recipients. Liver Transpl 2008;14:173-80.

Levitsky J. Next level of immunosuppression: drug/immune monitoring. Liver
Transpl 2011;17Suppl 3:S60-5.
Wiesner RH, Fung JJ. Present state of immunosuppressive therapy in liver
transplant recipients. Liver Transpl 2011;17Suppl 3:S1-9.
McAlister VC, Haddad E, Renouf E, Malthaner RA, Kjaer MS, Gluud LL.
Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation: a meta-analysis. Am J Transplant 2006;6:1578-85.
OGrady JG, Burroughs A, Hardy P, Elbourne D, Truesdale A, Uk, et al. Tacrolimus
versus microemulsifiedciclosporin in liver transplantation: the TMC randomised
controlled trial. Lancet 2002;360:1119-25.
A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression
in liver transplantation. The U.S. Multicenter FK506 Liver Study Group. N Engl
J Med 1994;331:1110-5.
Boudjema K, Camus C, Saliba F, Calmus Y, Salame E, Pageaux G, et al.
Reduced-dose tacrolimus with mycophenolatemofetil vs. standard-dose
tacrolimus in liver transplantation: a randomized study. Am J Transplant
2011;11:965-76.
Pageaux GP, Rostaing L, Calmus Y, Duvoux C, Vanlemmens C, Hardgwissen
J, et al. Mycophenolatemofetil in combination with reduction of calcineurin
inhibitors for chronic renal dysfunction after liver transplantation. Liver Transpl
2006;12:1755-60.
Schmeding M, Kiessling A, Neuhaus R, Heidenhain C, Bahra M, Neuhaus P, et
al. Mycophenolatemofetilmonotherapy in liver transplantation: 5-year follow-up
of a prospective randomized trial. Transplantation 2011;92:923-9.
Fischer L, Klempnauer J, Beckebaum S, Metselaar HJ, Neuhaus P, Schemmer
P, et al. A randomized, controlled study to assess the conversion from calcineurininhibitors to everolimus after liver transplantation-PROTECT. Am J Transplant
2012;12:1855-65.
Abdelmalek MF, Humar A, Stickel F, Andreone P, Pascher A, Barroso E, et al.

32

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. . .
. . . .
. . .. .. . . .

14.

15.

16.

17.

18.

19.

20.
21.
22.

Sirolimus conversion regimen versus continued calcineurin inhibitors in liver

allograft recipients: a randomized trial. Am J Transplant 2012;12:694-705.
Goralczyk AD, Schnitzbauer A, Tsui TY, Ramadori G, Lorf T, Obed A. A therapeutic exploratory study to determine the efficacy and safety of calcineurininhibitor-free de-novo immunosuppression after liver transplantation: CILT. BMC
Surg 2010;10:15.
Sgourakis G, Radtke A, Fouzas I, Mylona S, Goumas K, Gockel I, et al. Corticosteroid-free immunosuppression in liver transplantation: a meta-analysis and
meta-regression of outcomes. Transpl Int 2009;22:892-905.
Firpi RJ, Zhu H, Morelli G, Abdelmalek MF, Soldevila-Pico C, Machicao VI, et
al. Cyclosporine suppresses hepatitis C virus in vitro and increases the chance
of a sustained virological response after liver transplantation. Liver Transpl
2006;12:51-7.
Rabie R, Mumtaz K, Renner EL. Efficacy of antiviral therapy for hepatitis C
after liver transplantation with cyclosporine and tacrolimus: a systematic review and meta-analysis. Liver Transpl 2013;19:36-48.
Menon KV, Hakeem AR, Heaton ND. Meta-analysis: recurrence and survival
following the use of sirolimus in liver transplantation for hepatocellular carcinoma. Aliment Pharmacol Ther 2013;37:411-9.
Liang W, Wang D, Ling X, Kao AA, Kong Y, Shang Y, et al. Sirolimus-based
immunosuppression in liver transplantation for hepatocellular carcinoma: a metaanalysis. Liver Transpl 2012;18:62-9.
Spada M, Riva S, Maggiore G, Cintorino D, Gridelli B. Pediatric liver transplantation. World J Gastroenterol 2009;15:648-74.
Dell-Olio D, Kelly DA. Calcineurin inhibitor minimization in pediatric liver allograft recipients. Pediatr Transplant 2009;13:670-81.
Kelly DA, Bucuvalas JC, Alonso EM, Karpen SJ, Allen U, Green M, et al. Longterm medical management of the pediatric patient after liver transplantation:
2013 practice guideline by the American Association for the Study of Liver

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Diseases and the American Society of Transplantation. Liver Transpl 2013;19:
798-825.
23. Farkas SA, Schnitzbauer AA, Kirchner G, Obed A, Banas B, Schlitt HJ. Calcineurin
inhibitor minimization protocols in liver transplantation. Transpl Int 2009;22:4960.

34

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. . .
. . . .
. . .. .. . . .

acute rejection


allograft rejection graft fibrosis liver
allograft rejection late graft deterioration graft failure
solid organ allograft liver allograft tolerogenic properties

Acute cellular rejection (ACR)

ACR
(1) early ACR ( 90 )

(2) late ACR ( 90 )

chronic rejection

SPLIT study 461 5

50 ACR 60 ACR
5 20 early ACR late-onset ACR
1-5 ACR 1
late graft loss 2

ACR

(irritability)

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AST, ALT, ALP, GGT, bilirubin

ACR
( CMV, herpes simplex virus, hepatitis E), recurrent hepatitis B C, steatohepatitis, drug-induced
liver injury, biliary complications hepatic artery thrombosis /
/

ACR
(1) mixed, but predominantly mononuclear inflammatory cells infiltrate in the portal triad; (2) bile duct inflammation/damage; (3)
endotheliitis ACR rejection
activity index (RAI) International Banff Schema 1997 3
(0-9 )
0-2 = no rejection
3 = borderline
4-5 = mild rejection
6-7 = moderate rejection
8-9 = severe rejection
ACR
(drug compliance) (immunosuppression)

36

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. . .
. . . .
. . .. .. . . .

3 Rejection activity index (RAI): Banff Schema for Grading Liver Allograft
Rejection: An International Consensus (Hepatology 1997;25:658-63)
Category
Portal
inflammation

Criteria
Score
Mostly lymphocytic inflammation involving, but not
1
noticeably expanding, a minority of the triads
Expansion of most or all of the triads, by a mixed infil2
trate containing lymphocytes with occasional blasts, neutrophils and eosinophils
Marked expansion of most or all of the triads by a mixed
3
infiltrate containing numerous blasts and eosinophils with
inflammatory spillover into the periportal parenchyma
A minority of the ducts are cuffed and infiltrated by
Bile duct
1
inflammation/ inflammatory cells and show only mild reactive changes
such as increased nuclear: cytoplamic ratio of the
damage
epithelial cells
Most or all of the ducts infiltrated by inflammatory cells.
2
More than an occasional duct shows degenerative changes
such as nuclear pleomorphism, disordered polarity and
cytoplasmic vacuolization of the epithelium
As above for 2, with most or all of the ducts showing
3
degenerative changes or focal lumenal disruption
1
Venous endo- Subendothelial lymphocytic infiltration involving some, but
thelial inflam- not a majority of the portal and/or hepatic venules
2
Subendothelial infiltration involving most or all of the
mation
portal and/or hepatic venules
3
As above for 2, with moderate or severe perivenular
inflammation that extends into the perivenular parenchyma
and is associated with perivenular hepatocyte necrosis

NOTE: Total Score = Sum of Components. Criteria that can be used to score liver allograft biopsies
with acute rejection, as defined by the World Gastroenterology Consensus Document.

.THAI
. . . TRANSPLANT
. . . . . . . . . .CARE
. . . . (TTC)
. . . . LIVER
. . . . 37

ACR ( 3)

3 acute cellular rejection (ACR)

RAI 4-5 baseline immunosuppression corticosteroid

( ), MMF mTOR inhibitor
RAI 6 > 4
methylprednisolone 250-1000
./( methylprednisolone 10 ././ 1 )

38

. . . . . . . .
. . .
. . . .
. . .. .. . . .

1-3
5-10

ACR methylprednisolone 250-1000 ./ ( 10 ././)
1-3 5-10
ACR corticosteroid
2-5
ACR methylprednisolone
(
) methylprednisolone 250-1000 ./
( 10 ././) 3-7
ATG 1.5 ././
4-6 4-7 (maximum cumulative dose 21 ././course)
ATG pre-medication acetaminophen 500-1000
. ( 10 ./.) , diphenhydramine 25-100 .
(1 ./.) methylprednisolone
50-100 . ( 2 ./.)
infusion-related reaction, ,
ATG

baseline immunosuppression, methylprednisolone / ATG cotrimoxazole / antifungal

.THAI
. . . TRANSPLANT
. . . . . . . . . .CARE
. . . . (TTC)
. . . . LIVER
. . . . 39
methylprednisolone ATG
CMV reactivation/infection
2 (1) ganciclovir prophylaxis; (2) CMV viral load
3-6
ACR tacrolimus 8-15 /
. / corticosteroid (
), MMF mTOR inhibitor
refractory rejection recurrent rejection
MMF 1-2 / ( 5
./. 2 10-20 ./
. 1 )
mTOR inhibitor

40

. . . . . . . .
. . .
. . . .
. . .. .. . . .

chronic rejection
Chronic rejection
graft dysfunction graft loss 2
ductopenic rejection late-onset cellular rejection 10
tacrolimus
medication non-compliance
CR CR acute rejection
12 rejection
non-compliance
late rejection CR graft dysfunction
fibrosis

/
CR /
graft failure
ALP, GGT, AST, ALT, bilirubin

CR
( International Banff Schema
2000) , biliary complications,
recurrent primary sclerosing cholangitis/primary biliary cirrhosis drug-induced
liver injury /

.THAI
. . . TRANSPLANT
. . . . . . . . . .CARE
. . . . (TTC)
. . . . LIVER
. . . . 41

CR
baseline immunosuppression,
( MMF / mTOR inhibitors), cyclosporine-based immunosuppression tacrolimus-based
graft failure

1. Importance of liver biopsy findings in immunosuppression management:

biopsy monitoring and working criteria for patients with operational tolerance.
Liver Transpl 2012;18:1154-70.
2. McDiarmid SV, Anand R, Lindblad AS. Development of a pediatric end-stage
liver disease score to predict poor outcome in children awaiting liver transplantation. Transplantation 2002;74:173-81.
3. Lucey MR, Terrault N, Ojo L, Hay JE, Neuberger J, Blumberg E, Teperman
LW. Long-term management of the successful adult liver transplant: 2012
practice guideline by the American Association for the Study of Liver Diseases
and the American Society of Transplantation. Liver Transpl 2013;19:3-26.
4. Wiesner RH, Fung JJ. Present state of immunosuppressive therapy in liver
transplant recipients. Liver Transpl 2011;17 Suppl 3:S1-9.
5. Kelly DA, Bucuvalas JC, Alonso EM, Karpen SJ, Allen U, Green M, Farmer D,
et al. Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study
of Liver Diseases and the American Society of Transplantation. Liver Transpl
2013;19:798-825.
6. Banff schema for grading liver allograft rejection: an international consensus

42

. . . . . . . .
. . .
. . . .
. . .. .. . . .

7.

8.
9.

10.

11.

12.

document. Hepatology 1997;25:658-63.

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