PREGNANCY OUTCOME

AFTER LIVER
TRANSPLANT
Gen.Dr Amgad .M.G. Moustafa , MSc,FRCOG.
Head of Obstetrics and Gynecology department
International Medical Center

When we have to manage a liver

problem with pregnancy ?

IS IT BAD
NEWS ?

HELLP syndrome
HELLP syndrome was named by Dr. Louis Weinstein in 1982 after its
characteristics:
H(hemolysis, which is the breaking down of red blood cells)
EL(elevated liver enzymes)
LP(low platelet count)
The global mortality rate of HELLP syndrome has been reported to be as high
as 25%.

Acute fatty liver of pregnancy (AFLP)

is a rare, potentially fatal
complication that occurs in the third
trimester or early postpartum period
The mortality from AFLP is approximately 18%
and deaths are usually secondary to sepsis, renal
failure, circulatory collapse, pancreatitis or
gastrointestinal bleeding

Viral hepatitis with pregnancy

virus A,B,C,D,E

Acute viral hepatitis ( Virus E ) during pregnancy

is associated with 20-30 % mortality .

Child-Pugh classification(ChildTurcotte-Pugh score)

Measure

1 point

2 points

3 points

Total bilirubin, mol/l

(mg/dl)

<34 (<2)

34-50 (2-3)

>50 (>3)

Serum albumin, g/dl

>3.5

2.8-3.5

<2.8

Prothrombin time,
prolongation (secs)

<4.0

4.0-6.0

> 6.0

Ascites

None

Hepatic encephalopath None

y

Mild

Moderate to Severe

Grade I-II (or

suppressed with
medication)

Grade III-IV (or

refractory)

Points

Class

One year survival

Two year survival

5-6

100%

85%

7-9

81%

57%

10-15

45%

35%

Child-Pugh classification(ChildTurcotte-Pugh score)

Mortality rates for patients undergoing surgery
were

10% for those with Child class A,

30% for those with Child class B, and
7682% for those with Child class C cirrhosis

Liver Transplantation and Pregnancy

FIRST REPORTED 1960s
Liver transplant is the treatment of choice for end-stage liver
disease.
Advances in surgical technique and immunosuppressive
therapy have helped to increase the number of women in the
child bearing age who undergo LIVER TRANSPLANT each year.
IN 1987,
First successful pregnancy in a liver transplant recipient was
reported.

Liver Transplantation and

Pregnancy
In U.S.A. ,approximately 14,000 women of
reproductive age are currently living after liver
transplantation, and another 500 undergo LT
each year.
IN EGYPT ?
IN International medical center
2 females ( age reproductive period) out of 200

Liver Transplantation and Pregnancy

Many times , a transplanted liver normalizes a
womans hormone imbalance and restores
fertility.

How are we going to manage a young lady?

( female liver transplant recipients )
Preconception counselling ?
Contraception After Transplant ?
Management during
pregnancy ?
Immunosuppression during
pregnancy ?
Mode of delivery ?
Postpartum and Breast feeding ?
What is the outcome ?

Preconception counselling ?
A woman of childbearing age who receives a
transplant is typically advised to avoid
pregnancy for at least 1 year after
transplantation, based on data that show an
increased risk of potential graft dysfunction,
rejection, or loss, and adversely affect fetal well
being.
The American Society of Transplantation (AST)
National Transplantation Pregnancy Registry (NTPR).

Preconception counselling ?
The American Society of Transplantation (AST)
recommends that pregnancy is allowable if there has
been:
1. No rejection within the past year.
2. There is adequate and stable graft function
3. No acute infections that may impact fetal growth and
well-being particularly cytomegalovirus infection
4. Maintenance immunosuppression is at stable dosing.

Contraception After Transplant ?

Ovulatory cycles may begin as soon as 1 month after
transplantation. Thus, prior to transplantation,
gynecologists and transplant professionals should
counsel women on potential methods of
contraception to avoid unplanned pregnancy.
But what method of contraception are we going to
use?
What are the advantages and disadvantages of each
method?

There is limited evidence regarding

the safest and most effective
method of contraception following
liver transplantation for prevention
of an unplanned pregnancy:
Barrier methods:
Lowest risk but probably lowest effectiveness

Combined hormonal methods (estrogen +

progestin):
contraindicated in women with active liver
disease.
In addition, combined oral contraceptives are
relatively contraindicated in women with
hypertension, (especially in combination).
They may also increase the blood levels of
immunosuppressants such as corticosteroids,
cyclosporine, tacrolimus, and sirolimus. Thus,
blood levels of immunosuppressants must be
monitored to ensure safety.

Intrauterine devices (IUDs)

Perhaps the best contraceptive option for the transplant
population
It is long-acting reversible contraception.
No drug interaction, are highly efficacious, are reversible,
and have minimal risk to the recipient.
Furthermore, recent studies have shown that they are safe
to use in immunocompetent and immunocompromised
patients.
Although the American Society of Transplantation
recommends against offering IUDs as first-line contraceptive
therapy in this population, this remains an area of debate
because IUDs have been reported to be an effective
approach in some patients?

Management during pregnancy ?

Routine monitoring of pregnancy and careful ultrasound
examination to diagnose congenital malformations and
growth restriction.
Liver transplant recipients often have comorbidities,
such as hypertension and diabetes, which add additional
risk to a pregnancy.
Aggressive management of hypertension: The drug of
choice is methyldopa.

In cases of acute rejection, steroids are the preferred

drugs

Immunosuppression during
pregnancy ?
Overview and management of
immunosuppression in liver transplanted female
candidates for pregnancy need expertise to
balance the risk of rejection and maternal and
fetal complications.

Immunosuppression during
pregnancy ?
Corticosteroids:
If the patient is maintained on a low dose of
corticosteroids due to the underlying liver
disease etiology, like autoimmune disease, or
because she has experienced episodes of
rejection, there might be a need for an increased
dose of steroid during pregnancy.

Immunosuppression during pregnancy ?

Corticosteroids:

The Maternal Risk :

Gestational hypertension and gestational diabetes
mellitus (GDM) and increased rates of premature
rupture of membranes.
THE FETAL RISK:
The overall fetal- neonatal complication is low.
Increased cleft-palate and lip in animal studies.
Rare reports of fetal adrenal insufficiency.
In summary,
Prednisone is classified as a category B medication

Immunosuppression during pregnancy ?

Calcineurin inhibitors cyclosporine and
tacrolimus
Calcineurin inhibitors suppress T cell function
through inhibition of cytokines such as
interleukin-2.

Immunosuppression during
pregnancy ?
Calcineurin inhibitors cyclosporine and tacrolimus
Maternal Risk :
hypertension, diabetes, renal insufficiency and neurotoxicity.
FETAL RISK :
There are also reports of an increased incidence of transient
neonatal hyperkalemia.
In summary :
Cyclosporine and tacrolimus are classified as United States Food
and Drug Administration (US FDA) category C medications and,
overall, deemed as safe to use during pregnancy.

Immunosuppression during pregnancy ?

Azathioprine
It inhibits purine metabolism, resulting
in suppression of cell-mediated
immunity.

Immunosuppression during pregnancy ?

Azathioprine

Maternal Risk :
Preterm delivery
FETAL RISK :
There are also reports of fetal anemia,
thrombocytopenia, neonatal infection and sepsis, and
low birth weight
In summary :
Azathioprine is classified as a US FDA category D
medication, based mainly on reports of animal studies
with teratogenic effects, but this has not been

Immunosuppression during pregnancy ?

Mycophenolate mofetil
Mycophenolate mofetil (MMF) is a purine biosynthesis
inhibitor that works by inhibiting B and T cell function.
In the first trimester, MMF has been associated with
pregnancy loss ranging from 33% to 45%.
There is multiple malformation reported that involve
cleft lip and palate, microtia and the absence of auditory
canals.
In summary:
As a result of this significant teratogenic risk, MMF is
classified as a US FDA category D medication and should
not be used during pregnancy.

Immunosuppression during
pregnancy ?

Sirolimus
It acts through blocking signal 3 of cell activation
from IL-2 receptors in T-cells and B-cells.
It has been considered a non-nephrotoxic
immunosuppressant agent that might replace
Calcineurin inhibitors in liver recipients with
renal dysfunction.
Data on the safety of sirolimus during pregnancy
and its teratogenicity is limited, although no
significant fetal malformation has been reported.

Mode of delivery ?
Vaginal delivery (preferred):
Usually delayed until labor onset unless maternal/fetal
indications for induction exist
Cesarean delivery:
It is only indicated for obstetric reasons.
Antibiotic prophylaxis for all surgical procedures.
Increased steroid dose at labor onset to overcome the stress of labor
and prevent postpartum transplant rejection.

Postpartum and Breast feeding ?

Immunosuppressive drug levels should be
monitored, as blood levels will vary due to
changing gastrointestinal function and
absorption, loss of effects of fetal liver
metabolism , and reconstitution of the maternal
immune system.
It is essential to continue monitoring organ
function for potential graft rejection.

Postpartum and Breast feeding ?

Breastfeeding by transplant recipient mothers remains
a controversial issue requiring further investigation.
Although recent reports have been supportive of the
practice. The national transplantation pregnancy
registry (NTPR) has reports from 98 recipients who
have breastfed their 126 children while taking a variety
of immunosuppressive agents and regimens. There
were no specific problems reported in the children
related to breastfeeding.
It is advisable to check the infants blood level of the
maternal medications for which levels are available-a

What is the outcome ?

Reports show a good success rate of pregnancy in liver
transplant recipients compared to general population :
Live birth rate reported to be 77%
Miscarriage rate reported to be 17%
However , complications were at higher rate compared
to general population
Preeclampsia reported to be 22%
C.S. rate 45%
Preterm delivery 39%

Conclusion
Successful pregnancy is becoming an expectation for
both the patient and their care providers.
Return of menstrual function is common in the months
after transplantation and, thus, preconception
counselling is an essential part of pregnancy planning
in the liver transplant recipient of childbearing age.
A multidisciplinary team should be involved in the
management of the transplant recipient before, during,
and after pregnancy. obstetrician ( high risk Pregnancy
, fetal medicine in conjunction with their transplant

Conclusion

A woman of childbearing age who receives a transplant is

typically advised to avoid pregnancy for at least 1 year after
transplantation.
Perhaps the best contraceptive option for the transplant
population is long-acting reversible contraception, more
specifically, intrauterine devices. However individualization is
important.
Most immunosuppressive medications are considered relatively
safe as they have not been shown to cause either an increase in
the incidence of or a pattern of birth defects. These relatively safe
medications include prednisone, azathioprine, the calcineurin
inhibitors, cyclosporine, and tacrolimus. Mycophenolate mofetil
(MMF) should not be used during pregnancy.