- Several studies have found that older liver transplant recipients (over age 60) have similar short-term outcomes to younger recipients in terms of postoperative morbidity, mortality, and length of hospital stay. However, long-term survival is significantly lower in older recipients, largely due to non-hepatic age-related causes of death. - While patient survival is lower in older recipients, graft survival is not significantly different between older and younger groups. The increased mortality in older patients is attributed to infections, cardiac events, and neurological causes rather than hepatic causes. - Careful consideration of medical fitness and life expectancy due to comorbidities is important when evaluating older recipients for liver transplantation. While age alone should not preclude transplantation, risks

1. ……..Prognostic factors and issues for case
selection.

2. Pirsch JD, Kalayoglu M, D'Alessandro AM, Voss BJ, Armbrust MJ,
Reed A, Knechtle SJ, Sollinger HW, Belzer FO.
Orthotopic liver transplantation in patients 60 years of age and older.
Transplantation. 1991 Feb;51(2):431-3.
Probably first drew attention to the fact that:……
Liver transplant recipients over the age of 60 years have excellent patient
and graft survival and the same postoperative morbidity as recipients
who are under 60 years of age. Therefore, advanced age does not appear
to be a contraindication to orthotopic liver transplantation.

3. Transplantation. 66(4):500-506, August 27, 1998.
Zetterman, RK.; Belle, SH.; Hoofnagle, JH.; Lawlor, S; Wei, Y; Everhart,
J; Wiesner, RH; Lake, JR.
“Age and Liver Transplantation.” (n=735)
Conclusions:- Although patient survival was significantly lower among
liver transplant recipients above the age of 60 years, the excess
mortality was due to non-hepatic, largely age-related problems. The
overall success of liver transplantation and improvement in quality of
life for older recipients is excellent.
Patient survival was lower for older than for younger recipients (81%
vs. 90% at 1 year=0.004), whereas graft survival was not different (80%
vs. 85% at 1 year; P=0.163).
The excess mortality in older patients was attributable to infections
(RR=2.0), cardiac events (RR=2.8), neurological causes (RR=3.5). The
incidence of hepatic causes of death in the two groups was similar.

4. Probablity of death after liver transplantation : young (<60 yrs) vs elderly (>60)
at 1 month and at one year. (n=735; age<60 = 600, age > 60 = 135).
Higher the age at L Tx : reflected in a lower survival at 1 month as well as at 1
year after L Tx.

5. Survival after liver transplantation : less than 60 yrs age v/s elderly recipients.
(Zettermann et al. 1998.)

6. Patient survival after liver transplantation was significantly less for
older than for younger recipients . The proportion of older and
younger recipients surviving was 81% and 90% at 1 year (P = 0.004).
The major differences in survival occurred during the first 6 months
after transplantation. After the first 6 months post-transplantation,
there was no difference in subsequent patient survival between the 113
older and the 554 younger recipients who had survived for at least 180
days(P = 0.55).
A proportional hazards analysis model that controlled for important
factors(diagnosis, CTP score, UNOS score, muscle wasting, and
procuring surgeon's assessment of liver quality) revealed recipient age
to be significantly associated with mortality at 1 year after
transplantation (relative risk=1.96; 95% confidence interval=1.17 to
3.30; P=0.011).
Recipient age was significantly associated with patient mortality at 1
year among patients with hepatitis C (relative risk=3.7; 95%
confidence interval=1.3 to 10.5) but not among patients with
cholestatic liver disease(relative risk=1.4: 95% confidence interval=0.5
to 3.9).

7. Similar outcomes, morbidity, and mortality for orthotopic liver transplantation
between the very elderly and the young . S. Rudich,
and R. Busuttil
Transplantation Proceedings
Volume 31, Issues 1-2, 3 February 1999, Pages 523-525.
Our study demonstrates that there are no significant differences in
morbidity and mortality between very elderly OLT recipients and
those more than 25 years younger. The elderly do as well (or as
poorly) after complications resulting from OLT as do the much
younger.
Median length of follow-up was similar and more than 3 years in both
groups. With the exception of cardiac arrhythmias and metabolic
encephalopathy, which were more frequent in the elderly, the groups
experienced similar complications.
In addition, the elderly spent more time in the intensive care unit
post-OLT (14.7 ± 20.9 vs 8.6 ± 14.1 days, elderly and young,
respectively).

8. Firstly, the elderly who survive the ordeal of transplant surgery do not manifest
any greater degree of cardiac, vascular, or oncologic disease than the younger
recipient. Secondly, physiologic age is much more important, in terms of
transplant outcomes, than chronologic age.
Complication Elderly Young
Number % Number % P-value
Cardiac arrhythmia 15 43 2 6 0.01
Metabolic encephalopathy 13 37 7 20 0.04
Further surgery 10 29 12 34 NS
Ventilator dependence 10 29 8 23 NS
Renal failure 6 17 10 29 NS
Biliary complication 3 9 1 3 NS
Bone disease 3 9 1 3 NS
New onset diabetes 3 9 0 0 NS
Hepatic artery thrombosis 1 3 0 0 NS

9. The Elderly Liver Transplant Recipient: A Call for Caution.
MF Levy and others. (Texas)
Ann Surg. 2001 January; 233(1): 107–113.
(n=1446, less than 60=1205, older than 60=241)
Elderly patients with better-preserved hepatic synthetic function or
with lower pre-transplant serum bilirubin levels fared as well as
younger patients.
Elderly patients who had poor hepatic synthetic function or high
bilirubin levels or who were admitted to the hospital had much lower
survival rates than the sicker younger patients or the less-ill older
patients.
Recipient age 60 years or older, pre-transplant hospital admission,
and high bilirubin level were independent risk factors for poorer
outcome.
When reviewed alone, recipient age was linked significantly to both
patient and graft survival.

10. Factors evaluating transplant outcome: in terms of ability to predict
death after transplant within 3 months (top) and within 1 year
(bottom). [age, pre-transplant ICU/ in hospital, liver function]

11. Herrero JI et al.; Liver transplant recipients older than 60 years have lower
survival and higher incidence of malignancy.
Am J Transplant. 2003 Nov;3(11):1407-12.
Older age is not considered a contraindication for L Tx, but age-
related morbidity may be a cause of mortality.
Two Grps: (patients younger than 60 years, n=54; patients older than
60 years, n=57) and both groups were compared. Older patients were
more frequently transplanted for HCV (p= 0.03) and HCC (p= 0.05)
and their liver disease was less advanced (CTP and MELD scores were
lower; p=0.004 and p=0.05, resp).
After L Tx, older patients had a significantly lower survival (p=0.02).
 Higher age was independently associated with mortality (hazard ratio
for each 10-year increase: 2.1; 95% CI: 1.1- 4.0; p=0.02).
The incidence of de novo neoplasia and nonskin neoplasia were
higher in older patients (p=0.02 and p =0.007, respectively).
In conclusion, older liver transplant recipients have a significantly
lower survival than younger patients. Malignancy is responsible for
this decreased survival.

12. The indication for LTx was more frequently hepatitis C virus-related cirrhosis
and the prevalence of HCC was higher in Group II than in Group I.
Kaplan-Meier estimate of the development of post-
transplantation de novo neoplasia, basal-cell or squamous skin
cancer, and non-skin cancer in patients younger than (Group I,
n=54) or older than 60 years (Group II, n=57).

13.  Increased cancer risk after liver transplantation: a population-based study.
EB. Haagsma, et al.;
Journal of Hepatology
Volume 34, Issue 1, January 2001, Pages 84-91.
An increased risk of cancer exists after liver transplantation, for both for
skin/lip cancer, and other solid tumours. Significantly increased RRs were
observed for non-melanoma skin cancer (RR 70.0), non-skin solid cancer (RR
2.7), renal cell cancer (RR 30.0), and colon cancer (RR 12.5). Multivariate
analysis showed that an age>40 years and pre-transplant use of immuno-
suppression were significant risk factors. (sample size=174)
 Risk factors for development of de novo neoplasia after liver transplantation.
Xiol X, et al.; Liver Transpl. 2001 Nov;7(11):971-5.
Thirty de novo neoplasia appeared in 22 of 137 transplant recipients between
12 and 104 months after orthotopic liver transplantation. The only associated
risk factor for any neoplasia was age. Age and hepatoma were independent
risk factors associated with skin cancer. That hepatoma in the explanted liver
is an independent risk factor for skin cancer suggests there might be
individual susceptibility to both neoplasia.

14. Collins BH, Pirsch JD, et al..
Long-term results of liver transplantation in older patients 60 years of age and
older.
Transplantation. 2000 Sep 15;70(5):780-3.
N= 478; 387 were <60 yrs of age & 91 were >60yrs of age.
The length of hospitalization was the same for both groups, and there
were no significant differences in the incidence of rejection, infection
(surgical or opportunistic), repeat operation, readmission, or repeat
transplantation between the groups.
The only significant difference identified between the groups was
long-term survival. Five-year patient survival was 52% in the older
group and 75% in the younger group (P <0.05). Ten-year patient
survival was 35% in the older group and 60% in the younger group (P
<0.05).
The most common cause of late mortality in elderly liver recipients
was malignancy (35.0%), whereas most of the young adult deaths were
the result of infectious complications (24.2%).

15. Acute events after liver transplants in young versus old recipients reveal no
statistical difference between the two groups.
Postoperative
events
occurring in
elderly and
young adult
recipients of
primary liver
transplants

17. Outcome of Liver Transplantation in Septuagenarians: A Single-
Center Experience.
Lipschultz et al.;
Archives of Surgery. 142(8):775-784, August 2007.
Group 1 included 62 patients aged 70 years or older (average, 71.9 +/-
2.1 years). Group 2 included 864 patients aged 50 to 59 years (average,
54.3 +/- 2.9 years).
Unadjusted patient survival of group 1 at 1, 3, 5, and 10 years was
73.3%, 65.8%, 47.1%, and 39.7%, respectively.
Unadjusted patient survival of group 2 at 1, 3, 5, and 10 years was
79.4%, 71.5%, 65.3%, and 45.2%, respectively. The difference was not
statistically significant (P = .14). Multivariate analysis for factors
affecting survival demonstrated preoperative hospitalization, cold
ischemia time, and hepatitis C/ethanol as risk factors for death.
Age 70 years or more was not a strong risk factor (mortality ratio, 1.28;
P = 0.27).

18. Volume 73, Number 8; December 2006.
Grand Rounds: Update On Liver Transplantation: Indications, Organ Allocation,
and Long-Term Care.
Lopez PM, Martin P.
Peri-operative risk, survival, quality of life, as well as the presence of co-
morbidities such as renal, cardiac and overall function, all need to be
weighed in the decision to offer a liver transplant.
In the elderly, L Tx should be considered with caution, and with
special considerations to relative risks and advantages.
Consider medical fitness to tolerate major surgery in terms of
cardiovascular reserve, renal function, respiratory function and
neurological status.
Ability to withstand the stresses of surgery, and the delayed post-
operative recovery period; and also the reserve to withstand
complications, and the treatment of complications after L Tx.
Physiological age more important than chronological age.

19. Factors that need due consideration include:-
Possible effects of post LTx medications and immunosuppression, …….
 Diabetogenic potential of drugs and worsening of diabetes.
Other medications and possible drug interactions w.r.t.
immunosuppression ans associated toxicity.
Adverse effects on osteogenesis/ bone health. Detail pre-tx assessment
might be very useful for this.
Adverse effects on cardiovascular system and post transplant high
incidence of worsening of hypertension, or de-novo new onset of high
blood pressure.
Quality of life before transplant and predicted quality of life after
transplant…….. Is LDLT going to make a significant improvement?
Predicted life expectancy……. As a result of other co-morbidities, etc.
An increased risk of malignancy in the older age group; esp. lymphoid
cancers in those with past or present EBV infection, colo-rectal
cancers in those transplanted for PSC/ PBC., and other cancers whose
incidence is higher in smokers than in non-smokers.

20. And last but not the least:………
The risk of recurrence of the liver disease needs to be understood…..
Hepatitis B recurrence is quite rare with current anti-virals and
immunotherapy, though recurrence of HBV is associated more
frequently with acute hepatitis and flares.
HCV recurrence (Approximately 86% of anti-HCV-positive, 93% of
RIBA-positive, and 97% of HCV RNA-positive candidates developed
infection after transplantation. (Everhaart and others, Hepatology. 1999
Apr;29(4):1220-6.) with treatment recurrence rates are in the order of 30
– 50%, but recurrent HCV is associated with cirrhosis in 25% patients
in 3-5 years.
Recurrence of HCC;… is nearly 40% after LTx for HCC (HEPATOLOGY
Vol. 26, No. 2, 1997, MARSH ET AL.) depending on tumour variables (size,
grade, margins, etc), sex and NAC. Old age relates to limitations in
adjuvant therapy.

21. The number of both waitlist patients and liver transplant recipients
greater than 65 yr of age continues to increase at a steady pace. In
2005, 628 patients who were older than 65 years received a liver
transplant.

22. The question of quality of life…….?
Though an improvement in the quality of life in general has been
documented in terms of physical health and health related QOL.
(Health-related quality of life after liver transplantation: a meta-analysis. Liver
Transpl Surg 1999; 5: 318-331. Bravata DM);
(Assessing health-related quality of life pre- and post-liver transplantation: a
prospective multicenter study. Liver Transpl 2002; 8: 263-270; Ratcliffe J).
However this has not been examined in elderly patients undergoing
liver transplants.
Whether this is actually the case….. And is it likely to affect the
decision to perform a LDLT, since theoretically speaking, we wouldn’t
be talking about the scarcity of donors here?

23. The Ethics of it all:…….
The U.S./ world population is aging, and as transplantation
becomes more routine, older people are pushing for the better
quality of life it can offer. At the most extreme, a hospital in
Pennsylvania recently (2004) put a kidney from a cadaver into a 94-
year-old.
Even so, long before their transplanted liver wears out, many older
recipients die of the myriad afflictions that come with aging.
From a statistical standpoint, cadaveric livers are being
squandered. With living donors, is that the case? Or is it just a
question on subjecting the donor (healthy) to a certain risk?
Nearly everybody, (at least amongst the young), lives longer with a
transplant than otherwise. But the young gain the most extra years
of life. In the mathematics of transplantation, they have the
potential for the most "net lifetime survival benefit.”
Maximizing the benefit, in many respects, is a harsh calculation.

24. And,
How old is ‘too old’?

25. Thank you!