1) Liver transplantation involves replacing a diseased liver with a healthy donor liver. It has improved survival rates from 30% to over 90% due to advances like immunosuppressive drugs. 2) There are various indications for liver transplantation in both adults and children, including cirrhosis, liver cancer, and genetic liver diseases. Recipients are selected based on factors like MELD score and disease severity. 3) The surgery requires connecting the donor liver's blood vessels and bile duct. Post-operatively, patients are closely monitored and given immunosuppressants to prevent rejection while managing side effects.

1. LIVER TRANSPLANT
PRESENTER: DR. DHILEEBAN MAHARAJAN
MODERATOR: DR. ROMEO SINGH

2. INTRODUCTION
• Thomas Starzl 1960
• Orthotopic (rarely heterotopic)
• One year survival from 30% to >90%
• Improved operative technique, immunosuppressive therapy
• Cadaver organ transplantation

3. Trend of liver transplant in India

4. • Orthotopic graft : Graft placed in its normal anatomical site
• Heterotopic graft : Graft placed in a site different from normal location
• Allograft : From one individual to another
• Xenograft: Between different species

5. MAJOR INDICATIONS
 Decompensated cirrhosis
 Acute liver failure
 Unresectable primary hepatic malignancy

6. INDICATIONS
CHILDREN
• Biliary atresia
• Neonatal Hepatitis
• Congenital hepatic fibrosis
• α1 Antitrypsin deficiency
• Inherited disorder
• Glycogen storage disorder
• Lysosomal storage disorder
• Wilson’s disease
• Tyrosinemia
• Protoporphyria
• Crigler- Najjar disease Type I
• Primary hyperoxaluria Type I
• Hemophilia
ADULTS
• 10 & 20 biliary cirrhosis
• Primary sclerosing cholangitis
• Autoimmune hepatitis
• Caroli’s disease
• Cryptogenic cirrhosis
• Chronic hepatitis with cirrhosis
• Hepatic vein thrombosis
• Fulminant hepatitis
• Alcoholic cirrhosis
• Chronic viral hepatitis
• Primary hepatocellular malignancies
• Hepatic adenomas
• NASH
• Familial amyloid polyneuropathy

7. Proportion of liver transplants
performed for specific indications

8. CONTRAINDICATIONS
ABSOLUTE
• Uncontrolled extrahepatobiliary infection
• Active sepsis
• Uncorrectable life limiting congenital
anomalies
• Active alcohol abuse
• Advanced cardiopulmonary disease
• Extrahepatobiliary malignancy
• Liver metastasis
• Cholangiocarcinoma
• AIDS
• Life threatening systemic diseases
RELATIVE
• Age> 70
• Prior extensive hepatobiliary surgery
• Portal vein thrombosis
• Renal failure (not related to liver)
• Previous extrahepatic malignancy
• Severe obesity
• Severe malnutrition
• Medical noncompliance
• HIV with CD4 <100/µL
• Intrahepatic sepsis

9. SELECTION CRITERIA
• MELD Score: 0.957* loge (creatinine) + loge (total bilirubin) +1.120*
loge (INR) + 0.643
• Child Pugh score
• Utility Models
• Transplant benefit models

10. MELD SCORE
• The MELD score assigns points that reflect the severity of liver
disease
• A patient’s priority on the waiting list is based on the medical
status as determined by MELD score
• The score is based on a formula that considers bilirubin, INR,
Creatinine

12. • Score : 6 in healthy person to 40 in severe ESLD
• Score < 15 should not undergo liver transplantation
• Preference – Sickest patient as per MELD score
• Significant decrease in the rate of death of potential recipients on the
waiting list because it allows livers to be directed to the sickest patients.
• The scoring used in pediatric patients is referred to as the pediatric end-
stage liver disease (PELD) score.
• Pediatric donors are distributed to pediatric patients preferentially.

13. 1. Fulminant hepatic failure
2. Primary graft nonfunction
3. Portopulmonary hypertension
4. Hepatopulmonary syndrome
5. Familial amyloid polyneuropathy
6. Primary hyperoxaluria
7. Cytic Fibrosis liver disease
8. HCC
Disease specific MELD exceptions:

14. KING’S COLLEGE CRITERIA
Acetaminophen induced ALF
o Ph- <7.3 or
o INR- >6.5 and
o S. creat- >3.4mg/dl
Non- acetaminophen induced ALF
o INR> 6.5 or
Any three of the following
o Age- <10 or >40
o Time of onset of jaundice
to development of coma of >7 days
o INR- >3.5
o S.Bilirubin - >17mg/dl

16. CADAVER DONOR SELECTION
• Acceptable Criteria
• Brain dead
• Hemodynamic stability
• Adequate oxygenation
• Absence of infections
• No abdominal trauma
• No hepatic dysfunction
• HBV, HCV HIV sero-negative
• Most important factors
• Organ size
• ABO compatibility
* HLA matching not mandatory*

17. LIVING DONOR TRANSPLANTATION
Requirements:
i. 18 – 60 years old
ii. Compatible blood type
iii. No chronic diseases
iv. No major abdominal surgery
v. Related genetically or emotionally

19. Aim
- Preserve the functional integrity of the organs
- Careful monitoring and management of fluid balance.
Warm ischaemia - Time between the diagnosis of death (cardiorespiratory arrest)
and cold perfusion of the organ(up to 45 minutes is acceptable)
Storage time- Liver - <12hrs(Optimal) , 18hrs(Max. time
Organ recovery from deceased donors

20. SURGICAL TECHNIQUE
• Removal of native liver complicated by Coagulopathy and portal hypertension
• Lead to large blood product transfusion
• Portal vein  Intra & suprahepatic IVC  Hepatic artery  Bile duct
• Anhepatic phase ( coagulopathy, hypoglycemia, hypocalcemia, hypothermia)
• Donor liver inserted
• Caval  Portal Vein  Hepatic artery  Bile duct

22. POST OPERATIVE MONITORING
-- Invasive monitoring (arterial and venous)
-- T tube  Dark copious bile
-- Routine antimicrobials
Bowel decontamination
Systemic Broad spec. antibiotics
Antifungal
Antiviral

23. Good signs:
-- Aminotransferase downward trend
-- Improvement in coagulopathy
-- Falling serum bilirubin level
Bad Signs
-- Scanty pale bile
-- Metabolic acidosis
-- Depressed mentation
-- Continued vasopressor support
-- Worsening liver parameters

24. IMMUNOSUPPRESSIVE THERAPY
 Cyclosporin
 Tacrolimus
 Prednisone
 Mycophenolic acid
 Antithymocyte globulin
 OKT 3 (Muromonab)
 Sirolimus or Everolimus
 Basiliximab, Alemtuzumab
 Azathioprine

25. Initial
Maintenance
Immunosuppression
To prevent graft rejection while avoiding
morbidity due to its side effects
AIM

26. CYCLOSPORIN
• 1980
• Calcineurin inhibitor
• Blocks early activation of T cells
• Nephro-toxicity ( dose dependent)
• Reversible
• other adverse effects
•Hypertension
•Tremor
•Hirsutism
•Glucose intolerance
•Gingival hyperplasia

27. TACROLIMUS
• Macrolide lactone antibiotic
• Streptomyces tsukubaensis
• 10- 100 time more potent
• Rescue therapy
• Reducing the likelihood of bacterial and CMV infections
• Good oral absorption
• Metabolized by cyt P450
• Adverse effects:
• Nephrotoxicity and neurotoxicity
• Diabetes mellitus

28. MYCOPHENOLIC ACID
• Non-nucleoside purine metabolism inhibitor
• Penicillium species
• Bone marrow suppression

29. OKT 3 (MUROMONAB)
• Monoclonal antibodies to T cells
• Mainly in renal dysfunction patients
• Reversing acute rejection
• Adverse effects:
• Fever and chills
• Diarrhea
• pulmonary edema
• opportunistic infections

30. SIROLIMUS & EVEROLIMUS
• mTOR inhibitor (blocks later events in T cell activaton)
• Complication - Hepatic artery thrombosis
• Everolimus – hydroxyethyl derivative of sirolimus
• Used in kidney transplantation
• Not accepted for liver transplantation

31. NON-HEPATIC COMPLICATIONS
• Cardiovascular instability
•Arrhythmias
•CCF
•Cardiomyopathy
•Pulmonary compromise
•Pneumonia
•Fluid overload
•Renal Dysfunction
•Prerenal azotemia
•ATN
•Drug nephrotoxicity
•Malignancy:
•B-cell lymphoma
•De nova neoplasm
• Hematologic:
• Anemia
• Thrombocytopenia
• Infection:
• Bacterial
• Fungal/Parasitic
• Viral
• Neuro-psychiatric:
• Seizures
• Metabolic encephalopathy
• Depression
• Diseases of donor:
• Infection
• Malignancy

33. HEPATIC COMPLICATIONS
• Prehepatic:
• Pigment load
• Hemolysis
• Blood Collections
• Intra-hepatic:
• Hepato-toxic drugs
• Hypoperfusion
• Benign postoperative cholestasis
• Intra-hepatic:
• Transfusion associated hepatitis
• Exacerbation of primary hepatic disease
• Posthepatic:
• Biliary obstruction
• renal dysfuction

34. HEPATIC DYSFUNCTION CONT..
1. Primary graft non dysfunction
2. Rejection
3. Recurrent primary hepatic disease
4. Vascular compromise
I. Portal vein obstruction
II. Hepatic artery thrombosis
III. Anastamotic leak
IV. Bile duct disorder:
I. Stenosis
II. Obstruction
III. leak

35. ACUTE CELLULAR REJECTION
-- one week after surgery
-- impaired LFT
-- LIVER BIOPSY
1. Bile duct injury
2. Partial inflammation with eosinophils
3. Endothelitis
-- High dose steroids
-- if not improved add OKT-3
Mimic Acute rejection:
1. Slowly resolving reperfusion injury
2. Biliary tract obstruction
3. Cholestasis related to sepsis

36. ACUTE REJECTION HISTOPATHOLOGY

38. CMV HEPATITIS

39. CHRONIC REJECTION
• Due to repeated bouts of acute rejection
• Liver Biopsy:
1. Progressive cholestasis
2. Focal parenchymal necrosis
3. Mononuclear infiltration
4. Vascular lesion
5. Ductopenia
Treatment: Retransplantation

40. • Previous episodes of acute rejection
• Long warm ischaemia time
• Cytomegalovirus (CMV) infection
• Raised blood lipids
• Inadequate immunosuppression (including poor compliance)
Risk factors for chronic rejection

42. POST-TRANSPLANTATION
IMMUNOPROLIFERATIVE DISORDER
-- Low grade to aggressive neoplasm
-- Uncontrolled proliferation of B cell after LT
-- Typically in primary EBV infection
-- Monoclonal or polyclonal
-- More in pediatric LT
-- Mostly due to immunosuppressive therapy
Clinical features:
1. Lymphadenopathy
2. unexplained fever
3. Extranodal masses

43. • WHO GRADING
I. Benign polyclonal lympho-proliferative disorder
II. Polymorphic PTLD
III. Monomorphic PTLD
iv. Classic non-Hodgkins like PTLD
• Treatment includes
 Reduction in immunosuppressive therapy
 Antiviral against EBV
 Systemic chemotherapy (Rituximab)

44. MAJOR CHALLENGES
Shortage of donor organ
 Threat of recurrence
 Morbidity due to immunosuppressives

45. RECENT RESEARCH
• Using expanded criteria graft
• Good graft flow by segmental hepatic veins
• Limiting antibiotic usage
• Optimizing immunosuppression
• Minimizing donor morbidity

46. THANK YOU