4. Liver Transplantation History
• 1958 Research programs on liver
replacement at Northwestern and Harvard
• 1963 First liver transplant (Univ. of CO)
• 1967 First long survival
• 1979 Cyclosporine
• 1987 Univ. of WI solution for improved
organ preservation
• 1989 FK 506
• 1999 Living donor liver transplantation
5. Liver Transplantation
Liver transplantation is the OPTIMAL
treatment for end stage liver disease
(ESLD)
ESLD has 2 forms: Acute and Chronic
- Acute = Fulminant Hepatic Failure
- Chronic = Cirrhosis
6. Fulminant Hepatic Failure (FHF)
Synonymous with Acute Liver Failure
Definition: Development of encephalopathy
within about 8 weeks of the onset of
symptoms or within about 2 weeks of the
onset of jaundice
Pathology: Pan-lobular or Sub-massive
necrosis
Classically seen in Paracetamol poisoning.
In India – commonest cause is HEV, HAV
and drug induced.
7. Criteria for transplantation of acute
liver failure
KING’S COLLEGE CRITERIA
• Acetaminophen toxicity
ph < 7.30 (after hydration and regardless of degree of encephalopathy)
or
INR >6.5
creatinine >3mg/dl
Encephalopathy III-IV
• Non-acetaminophen etiology
•INR >6.5 irrespective of degree of encephalopathy
or 3 of the following five criteria
Age<10, >40
Etiology: nonA-E hepatitis, drugs
Duration of jaundice before encephalopathy >7 days
INR >3.5
Serum bilirubin >17.5 mg%.
CLICHY CRITERIA
• Factor V <20% (age <30 years) or 30% (age >30 years)
• Confusion and/or coma
8. Acute Liver failure (PGIMER criteria –
Clinical prognostic Indicators)
age ≥50 yr,
JEI >7 days,
grade 3 or 4 encephalopathy,
presence of cerebral edema,
prothrombin time ≥35 seconds, and
creatinine ≥1.5 mg/dL.
Presence of any 3 of 6 CPI was optimum in
identifying survivors and nonsurvivors
9. Chronic Liver disease : Cirrhosis
All patients with cirrhosis do not qualify for liver
transplantation.
Transplantation is generally considered when a
patient has suffered from either a complication of
portal hypertension.
The onset of decompensation is associated with
significantly impaired survival.
The development of hepatorenal syndrome is an
ominous marker that signals the need for
immediate transplant evaluation.
10. Chronic Liver Disease — Signs of
decompensation
Ascites
Encephalopathy
Portal Hypertensive Bleeding
Hepatocellular Carcinoma in the setting of
Cirrhosis
11. Chronic Liver Disease—Indications for
Transplantation
Ascites
Ascites has a two-year mortality of 50%
SBP has a two-year mortality of 80%
Hepato-Renal Syndrome :
- 2 types, type 1 has very poor prognosis,
>50% mortality at 2 weeks, and type 2 has 50%
mortality at 1 year.
Variceal bleed and hepatic encephalopathy:
difficult to quantify the effect on mortality as they
are a mechanical result of portal hypertension
12. When?
Quality of life issues
– Severe lethargy
– Intractable itching
– Recurrent bile duct infections
– Intractable ascites
– Severe bone thinning
– Pain
14. When….?
Patients who are too well should not be
transplanted.
Likewise, transplantation of patients who are
too sick is associated with poor outcomes.
The goal of transplantation is to prolong
survival.
Thus, liver transplantation should be
performed at the time point when the patient
is expected to have greater survival with a
liver transplant than without.
15. Prognostication
Survival of a patient with ‘‘Child’s C cirrhosis’’ is
about 20–30% at 1 year and less than 5% at 5
years.
In contrast, the survival rate after transplantation
is 85–90% at 1 year and over 70% at 5 years.
By the time the patient has evidence of advanced
clinical liver disease (Child’s C cirrhosis), the
patient may not survive long enough to get a
transplant.
16. MELD score
• MELD -- Model for End-Stage Liver Disease
Scoring System – MELD Score
= 0.957 x Loge(creatinine mg/dl)
+ 0.378 x Loge(bilirubin mg/dl)
+ 1.120 x Loge(INR)
+ 0.643
• MELD score depends upon kidney function,
bilirubin level and clotting factor levels
17. MELD score
Introduced in Feb 2002.
The MELD score originally was developed and
validated to assess the short-term prognosis of
patients with cirrhosis undergoing TIPS.
Developed by the Mayo Clinic.
Using the MELD model, patients are assigned
a score from 6 to 40.
Estimated 3-month survival for a score of 6 is
90%, and for a score of 40 is 7%.
18. Chronic Liver Disease—Indications for
Transplantation
Ultimately, the decision to transplant is based
upon the patient’s likelihood of survival
Survival with transplantation:
One-year ~85-90%
Two-year ~80-88%
Five-year ~65-75%
Usually a patient will be listed for liver tx at a
MELD of 10 or more, when the expected 3
month survival is less than 90%.
20. Guidelines for Organ Allocation
Organs should be allocated to transplant
candidates in the order of medical urgency
The role of waiting times in determining
allocation order should be minimized
Every attempt should be made to promote
efficient use of donor organs
21. Requirements for Transplantation
End stage liver disease
Physiologic ability to tolerate surgery: Cardiac,
pulmonary, renal, cerebral function
Anatomy – status of vessels (PV/HA/HV)
Social support/ psychological support
No extra-hepatic infection or malignancy
Alcohol abstinence for 6 months/ no substance
abuse
22. Contra-indications
Cardiopulmonary disease that cannot be corrected and is a
prohibitive risk for surgery.
Malignancy outside of the liver within five years of
evaluation (not including superficial skin cancers) or not
meeting oncologic criteria for cure.
Active alcohol and drug use. Minimum period of abstinence
of at least six months (+/- participation in a structured
rehabilitation program) may be needed.
Advanced age and AIDS are examples of relative
contraindications.
Liver transplantation can be performed in those older than
65 provided that there has been a comprehensive search
made for co-morbidities
23. Liver Transplantation
Evaluation
Determine cause of liver disease
Document severity of liver disease
Determine survival and functional ability
Concomitant medical problems
Psychiatric evaluation
Social Evaluation
24. LTx Evaluation
• Medical history
– Symptoms such as fatigue, itching, swelling,
changes in mental status and GI bleeding
– Other medical problems
– Medications
– Includes alcohol use and drug use history
• Physical examination
• Blood tests
– Determine underlying cause of liver disease
– Determine current functional status of the liver
25. LTx Evaluation
Liver Ultrasound/CT scan/MRI
Liver biopsy
ERCP/ MRCP – Cholangiogram – examines
bile ducts if cirrhosis is otherwise
unexplained
PET scan and other inv for cancer
26. Evaluation of psychosocial support for
LTx
Psychosocial evaluation
– Support systems
– Compliance with post transplant
immunosuppression medication protocol
after transplantation
Social and family support around the
transplant
27. Limitations of MELD
• Patients with liver cancer
• Bile duct infections
• Itching
• Disabling mental status changes (hepatic
encephalopathy)
• ? Criteria for living donors
Other conditions like : HPS, metabolic diseases,
congenital errors of metabolism, fulminant
liver failure, graft non-function, etc
28. Surgical perspective
Immediate function of a transplanted liver is essential.
Unlike in kidney, pancreas, or, to some extent, heart
transplantation, there is no effective artificial support
for a hepatic patient in the event of graft failure.
A complex surgical exercise in a severely physiologically
compromised patient –
- major surgery
- blood loss – portal hypertension
- immunosuppression
- risk of infection
- necessity of liver function
29. Donor selection
Cadaveric/ living donor.
Blood group match. (HLA not
required/ cross matching not
required).
Size match.
Marginal donors.
Split liver.
30. Organ harvesting/ procurement
HTK solution (custodiol)
UW (Viaspan)
Goal: Cool the organs and
perfuse with preservative
solution while
exsanguinating the
organs.
Aortic canulation
Portal canulation
34. Anesthesia
Physiological processes, biological function, and drug
disposition, renal function, RBF
Interpretation of liver function study results
Portal hypertension and complications: variceal hemorrhage,
SBP, sepsis, ascites, hepatorenal syndrome, encephalopathy
Cardiac and circulatory effects: hyperdynamic circulation,
vasodilatation.
Portopulmonary hypertension
Coagulopathy
Cholestasis, jaundice
Impact of anesthesia on liver function
Limited functional reserve
Hepatic blood flow
Drug clearance
Anesthesia-induced hepatitis
Postoperative jaundice
Risk factors for decompensation in patients with cirrhosis
35. Implantation of the new liver.
Orthotopic/ auxillary
begins with a controlled
recipient hepatectomy
formidable task in individuals
with severe portal
hypertension and extensive
collateral
Role of temporary porta-caval
shunt..
Engraftment with venous,
arterial and then biliary
anastomoses.
Classic v/s piggy back
implantation.
37. Classical v/s piggy back technique
Classical or cava
replacement
Piggy-back technique
38. Graft function
Helpful signs of hepatic function in the
immediate postoperative period
1. Hemodynamic stability
2. Awakening from anesthesia
3. Clearance of lactate
4. Resolution of hypoglycemia
5. Normalization of coagulation profile
6. Resolution of elevated transaminases
7. Bile of sufficient quantity and golden brown in
color
41. Immediate outcome
What factors:
Organ harvesting.
Organ preservation.
Warm and cold ischemia times.
Graft selection/ graft quality.
Donor-recipient matching.
Surgical problems.
Medical issues.
42. Post-op monitoring
Monitor hemodynamics, vitals, and blood tests.
Blood tests: LFTs, lactate, ABG, CBC, and coagulation
parameters.
Monitor immunosuppression.
rising transaminases and bilirubin in the 48 h immediately
after transplantation may not be ominous signs as long as
the prothrombin time, serum lactate, bile production, or
other measures of hepatic function are stable or improving
Usually anesthesia is not reversed and patients are kept
intubated for upto 48 hours.
Doppler examination of the transplanted liver.
Medication: immunosuppression, antibiotics, antiplatelets,
analgesics, and PPIs.
44. Complications
Immediate, early and late.
Immediate – post-op.
- Bleeding (commonest – 12-15%)
- Graft non-function (PNF) [5%] or
delayed graft function [6-7%].
- Vascular complications: HAT, PVT and
venous thrombosis.
- Renal dysfunction.
- complications related to prolonged and
major surgery, blood transfusion.
- Infections – viral and bacterial.
46. Complications
Late complications:
- Usually late, after more than a year.
- Recurrent disease
- Medication adverse effects
- Chronic rejection
- Infections
- Metabolic problems
- Recidivism
48. Waiting for a liver
Management of Ascites.
Management of portal hypertension
Renal function
Hepatic encephalopathy
General health and activity
Treatment of viral disease
Vaccination
Prevention of infection.
49. If waiting is not possible….,
getting too late….
LDLT: living donor liver transplant.
India: only related/ approved by a ethical committee.
Advantages:
- elective surgery.
- healthy known donor
- short cold ischemia times
- reduced waiting time
Disadvantages:
- risk to donor
- cost and more resources
- higher risk of biliary ad vascular complications
- reduced size liver
52. Essential Concepts for Using
Living Donors
• No conflict of interest
• No coercion
• Minimize donor risks
• Donors must be given every opportunity to
change their minds
• Emphasize alternatives
53. How Much Liver Do You Need?
• Liver = 2% body weight
• Optimal: > 1% liver weight/body weight ratio
• 70 kg recipient needs at least 700 cc (gm)
• Cannot go below 0.7 - 0.8%
- GRWR.
- Graft/ SLV ratio
- Usually right lobe.
- Recently the use of dual grafts has been done
successfully.
54. LDLT problems
Risk to donor: 0.2 – 0.3% risk of death
- 2-4% risk of major complications
- About 15-25% risk of minor complications.
Higher incidence of biliary problems
Higher incidence of vascular problems
Small for size syndrome
Ethical issues
Initially had poorer graft survival, but recently
has been equal to DDLT.
55. Diagnoses indicating potential candidacy for LT include the following:
* 070 Viral hepatitis
* 1550-1552 Malignant neoplasm of liver and intrahepatic bile ducts
* 2115 Benign neoplasm of liver and biliary passages
* 2308 Carcinoma of liver and biliary system
* 2353 Neoplasm of uncertain behavior in liver and biliary passages
* 2390 Neoplasm of unspecified nature in digestive system
* 2710 Glycogenesis
* 2720 Pure hypercholesterolemia
* 2727 Lipidoses
* 2751 Disorders of copper metabolism
* 2770-2776 Cystic fibrosis, disorders of porphyrin metabolism, other disorders of purine and pyrimidine
metabolism, amyloidosis, disorders of bilirubin excretion (like EHBA as well as Criggler Najar syndrome),
mucopolysaccharidosis, other deficiencies of circulating enzymes including urea cycle disorders, an dother metabolic
disorders.
* 2860 Congenital factor VIII disorder
* 2861 Congenital factor IX disorder
* 4530 Budd-Chiari syndrome
* 570 Acute and subacute necrosis of liver
* 5710 Alcoholic fatty liver
* 5712 Alcoholic cirrhosis of liver
* 5714 Chronic hepatitis
* 5715 Cirrhosis of liver without mention of alcohol
* 5716 Biliary cirrhosis
* 5718 Other chronic nonalcoholic liver disease
* 5719 Unspecified liver disease without mention of alcohol
* 5728 Other sequelae of chronic liver disease
* 5758 Other specified disorders of gallbladder
* 5761,5762 Cholangitis, obstruction of bile duct
* 75161,75169 Biliary atresia, other anomalies of gallbladder, bile ducts, and liver
* 7744 Perinatal jaundice due to hepatocellular damage
* 7778 Other specified perinatal disorders of digestive system
* 864 Injury to liver
* 3483 Encephalopathy, unspecified
* 452 Portal vein thrombosis.