LIVER TRANSPLANTATION 14:1081-1091, 2008

REVIEW

Pregnancy and Cirrhosis

Jennifer Tan,1 Bijal Surti,1 and Sammy Saab1,2
Departments of 1Medicine and 2Surgery, David Geffen School of Medicine, University of California–
Los Angeles, Los Angeles, CA

As the treatment of cirrhosis improves, pregnancy in patients with cirrhosis is likely to become more common. Although
maternal and fetal mortality is expected to similarly improve, pregnant patients with cirrhosis face unique risks. These include
higher rates of spontaneous abortion and prematurity and a potential for life-threatening variceal hemorrhage, hepatic
decompensation, splenic artery aneurysm rupture, and postpartum hemorrhage. Pregnancy outcome may be influenced by the
underlying etiology of liver disease, as in viral and autoimmune hepatitis. Medications also impact the course of pregnancy, and
must be tailored appropriately during this time.Liver Transpl 14:1081-1091, 2008. © 2008 AASLD.

Received March 28, 2008; accepted May 28, 2008.

INTRODUCTION AND EPIDEMIOLOGY complications have been described in nearly half of

Pregnancy is a rare event in patients with cirrhosis. The
exact incidence is unknown, but it has traditionally
been low for 2 reasons. First, advanced liver disease
does not typically occur until well after most patients
have completed their reproductive years, with only 45
cases of cirrhosis occurring in every 100,000 women of
reproductive age. Second, cirrhosis results in metabolic
and hormonal derangements that lead to anovulation
and amenorrhea.1
Increasing numbers of case reports and case series of
pregnancy in this population, however, indicate that
improvements in the treatment of chronic liver disease
have resulted in higher conception rates and more suc-
cessful pregnancy outcomes.1 Although previously re-
ported to be as high as 10.5%,2 maternal mortality has
likely improved along with better management of
variceal hemorrhage and liver failure.
Nevertheless, morbidity and mortality likely remains
higher than that of the general pregnant population. It
is therefore important for physicians caring for preg-
nant patients with cirrhosis to understand how to ap-
proach potential complications and tailor medication
regimens appropriately.
EFFECTS OF CIRRHOSIS AND PORTAL
HYPERTENSION
Although it is difficult to distinguish the effects of preg-
nancy from the natural history of cirrhosis, maternal
pregnancies affected by cirrhosis and portal hyperten-
sion, largely as a result of variceal hemorrhage and liver
failure.3
Esophageal Varices
Esophageal variceal bleeding has been reported in 18%
to 32% of pregnant women with cirrhosis and in up to
50% of those with known portal hypertension.4,5
Among those with preexisting varices, up to 78% will
have gastrointestinal bleeding during pregnancy, with a
mortality rate of 18% to 50%.1 In contrast, pregnant
patients with noncirrhotic portal hypertension fare
much better. Their mortality rate from variceal bleeding
is between 2% to 6%.1 This disparity may be related to
the severity of their underlying liver disease, with pa-
tients with cirrhosis more likely to be coagulopathic.
Variceal bleeding most commonly occurs during the
second and third trimesters when maternal blood vol-
ume is maximally expanded and the larger fetus causes
increased compression of the inferior vena cava and
collateral vasculature.6
As in nonpregnant patients with cirrhosis, endo-
scopic band ligation remains the mainstay of therapy
for acute episodes of hemorrhage. The first case of suc-
cessful band ligation in a pregnant patient with acute
bleeding was reported in 1998 by Starkel et al.,7 but no
prospective randomized trials for this treatment cur-
rently exist. As in the nongravid population, sclerother-
apy was previously looked to as a potential alternative,8

Abbreviations: AIH, autoimmune hepatitis; ALD, alcoholic liver disease; FDA, Food and Drug Administration; PBC, primary biliary
cirrhosis; TIPS, transjugular intrahepatic portosystemic shunt; UDCA, ursodeoxycholic acid.
Address reprint requests to Sammy Saab, M.D., M.P.H., Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plaza, Suite 214, Los Angeles,
CA 90095. Telephone: 310-206-6705; FAX: 310-206-4197; E-mail: ssaab@mednet.ucla.edu
DOI 10.1002/lt.21572
Published online in Wiley InterScience (www.interscience.wiley.com).

© 2008 American Association for the Study of Liver Diseases.

1082 TAN, SURTI, AND SAAB
but it has largely been replaced by band ligation. Ex-
perts argue that band ligation should be preferred dur-
ing pregnancy because it avoids any potential risk from
chemical instillation.7
Upper endoscopy in general appears to be safe during
pregnancy, with the main risk being fetal hypoxia from
sedative drugs or positioning. No cases of premature
labor or fetal malformations have been reported in pa-
tients who have undergone endoscopy during preg-
nancy.9
Octreotide, designated as pregnancy category B by
the Food and Drug Administration, is often used to
treat acute variceal bleeding, although its safety has not
been well studied in pregnant patients.10 Given its sim-
ilarity to vasopressin, however, possible concerns in-
clude arteriolar vasospasm, which can result in de-
creased placental perfusion and an increased risk of
placental abruption, myocardial infarction, peripheral
ischemia, and hypertension.1,3
Although transjugular intrahepatic portosystemic
shunt (TIPS) placement is generally contraindicated
during pregnancy because of the risk of radiation expo-
sure to the fetus, it may be an appropriate rescue ther-
apy for failed attempts to control variceal bleeding with
band ligation or sclerotherapy.11 The risk of fetal mal-
formations from radiation is thought to be increased at
doses above 150 mGy and is considered negligible if
doses are below 50 mGy.12 Only 3 cases of TIPS place-
ment in pregnant patients with cirrhosis have been
reported thus far, with radiation dosages of 0.1, 5.2,
and 5.49 mGy used. In all 3 cases, the mothers survived
the episode of acute variceal bleeding.11,13,14 In 1 case,
the fetus ultimately died as a result of premature deliv-
ery and infant respiratory distress syndrome, but this
was not thought to be related to the TIPS procedure.11
The prophylactic treatment of varices in pregnant
women remains controversial. A case report by Zeeman
and Moise15 in 1999 reported a successful outcome for
prophylactic banding in a pregnant patient with cryp-
togenic cirrhosis and portal hypertension, but no pro-
spective, randomized trials have been performed. Ac-
cording to the American Association for the Study of
Liver Diseases practice guidelines, all patients diag-
nosed with cirrhosis should undergo screening endos-
copy for the diagnosis of gastric and esophageal vari-
ces.16 Although there are no formal guidelines for
pregnant women, most experts recommend that a
screening endoscopy be done in women with cirrhosis
either before pregnancy or in the early second trimes-
ter.
In women at high risk for bleeding, the potential ben-
efits of primary prophylaxis with nonselective beta
blockers such as propranolol and nadolol, designated
by the Food and Drug Administration as pregnancy
category C, may outweigh the risks of potential fetal
harm. The most commonly reported morbidities from
these drugs include fetal growth retardation, neonatal
hypoglycemia, and neonatal bradycardia.16
Surgical creation of splenorenal or portacaval shunts
has also been advocated on the basis of observational
studies showing that women with cirrhosis with shunts
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
have a lower risk of spontaneous abortion compared to
women without shunts17 and a 7-fold lower risk of
severe gastrointestinal hemorrhage.18 However, surgi-
cal shunt procedures are generally performed only in
the setting of a life-threatening hemorrhage that is re-
fractory to medical and endoscopic treatments.1
Another area of controversy in pregnant patients with
portal hypertension is how to approach delivery. The
risk of variceal bleeding is thought to be particularly
increased at the time of labor because of the need for
repetitive Valsalva maneuver. The resultant increased
intra-abdominal pressure is postulated to lead to in-
creased portal hypertension and thus a higher risk of
variceal rupture. As a result, many experts advocate
using elective caesarian section or forceps delivery un-
der extradural analgesia in order to decrease this
risk.3,19 Although this seems reasonable, no random-
ized controlled trials have been performed to support
this recommendation. If a prophylactic caesarian sec-
tion is performed, a vascular surgeon should be avail-
able in the event that bleeding from pelvic or abdominal
wall collaterals is encountered.6
Hepatic Decompensation
Up to 24% of pregnant patients with cirrhosis will also
experience hepatic decompensation, which can lead to
rapid clinical deterioration.3 This has been described in
all stages of pregnancy, but often occurs after episodes
of variceal bleeding.20
When fulminant hepatic failure occurs, the only
treatment available may be emergent liver transplanta-
tion. This has been performed during pregnancy in a
small number of cases, with successful outcomes for
both mother and fetus.21,22 Reported complications re-
main high, however, and have included an increased
risk of fetal ischemia, pregnancy-induced hyperten-
sion, anemia, caesarian section, and preterm deliv-
ery.23,24 Moreover, these case reports largely involved
women without underlying cirrhosis, and it is unclear
how underlying liver disease would change the out-
come.
Ascites and Spontaneous Bacterial Peritonitis
Ascites rarely occurs during pregnancy because of in-
creased intra-abdominal pressure, which acts to resist
the extravasation of fluid from splanchnic vessels and
organs. If therapy is required, however, sodium restric-
tion and diuretics can be used, as in nonpregnant pa-
tients with cirrhosis. Although cases of spontaneous
bacterial peritonitis have not been reported, other
causes of peritonitis have been known to increase the
risk of premature delivery and placental abruption. If
spontaneous bacterial peritonitis does occur, treatment
should consist of a third-generation cephalosporin.1
Hepatic Encephalopathy
Like nonpregnant patients with cirrhosis, pregnant pa-
tients with cirrhosis can develop encephalopathy if they
 PREGNANCY AND CIRRHOSIS 1083

TABLE 1. The Food and Drug Administration Pregnancy Categories

Pregnancy
Category Definition
A Controlled studies indicate no risk.
B Animal studies show no risk, and there are no human controlled studies, or animal studies
may show an adverse effect that was not reproduced in human controlled studies.
C Risk cannot be ruled out; animal studies show an adverse effect, and there are no human
controlled studies, or there are no studies available.
D Risk is evident in human studies; use may be considered if the benefit outweighs the risk.
X Risk is evident in animal and human studies and outweighs any benefit; use is
contraindicated in women who are or may be pregnant.

are given predisposing medications or experience hypo-
tension, hypoxia, infection, hypoglycemia, or gastroin-
testinal hemorrhage. Of note, spinal and general anes-
thesia should be avoided during delivery because of the
potential for hypotension and the risk of precipitating
encephalopathy. The mainstay of treatment remains
lactulose and/or antibiotic therapy.1
Splenic Artery Aneurysm Rupture
Pregnant patients with cirrhosis also have an increased
risk of splenic artery aneurysm rupture, which occurs
in 2.6%. In fact, 20% of all splenic artery aneurysm
ruptures occur during pregnancy, with 70% occurring
during the third trimester. Rapid intra-abdominal
bleeding and hypovolemic shock often ensue, resulting
in substantial maternal and fetal mortality rates of 70%
and 80%, respectively.3 The mechanism for the devel-
opment of these aneurysms is unclear but may be re-
lated to increased splenic blood flow from both preg-
nancy and portal hypertension. High estrogen levels
during pregnancy may also have effects on the elastic
tissue of the tunica media. Management options consist
of emergency splenectomy, transcatheter embolization
of the aneurysm, or stent-graft placement. The latter 2
options are usually preferred in cases of portal hyper-
tension, as an extensive collateral circulation in these
patients makes surgery more difficult.25
Postpartum Uterine Hemorrhage
Postpartum uterine hemorrhage is another potential
source of maternal morbidity and mortality, occur-
ring in 7% to 10% of pregnancies in patients with
cirrhosis. This is likely related to a higher incidence of
coagulopathy and thrombocytopenia.9 Treatment is
similar to that in patients without cirrhosis. Blood
and coagulation factors should be transfused and
administered oxytocin or other uterine contractile
agents. Surgical therapy to ligate the bleeding vessels
or hysterectomy is indicated when these measures
fail.26
Fetal Outcomes
The spontaneous abortion rate in patients with cir-
rhosis is significantly higher than that of the general
population, with a rate of 30% to 40%27 versus 15%
to 20%.28 This is not true for patients with extrahe-
patic portal obstruction unrelated to cirrhosis, in
whom the rate of spontaneous abortion is 3% to 6%.29
Moreover, patients with cirrhosis who have under-
gone portal decompressive procedures prior to con-
ception have spontaneous abortion rates comparable
to patients with extrahepatic obstruction.30 Termina-
tion of pregnancy most often occurs as a result of
maternal death, variceal hemorrhage, stillbirth, in-
trauterine growth retardation, and maternal compli-
cations during delivery.6
In those pregnancies that do result in live births,
the risk of prematurity is significantly increased, with
a rate of up to 25%.30 In contrast, the general popu-
lation, as of 2006, had a preterm birth rate of
12.8%.31 The perinatal death rate is likewise elevated
and may be as high as 18%30 versus 1.08% in the
noncirrhotic population.32 The majority of these data
are from older literature, however, and may reflect
complications of prematurity at a time when routine
measures such as corticosteroids, surfactants, and
modern neonatal intensive care management were
unavailable.1
MEDICATIONS USED IN PATIENTS WITH
LIVER DISEASE
Data regarding the use of medications commonly pre-
scribed for patients with cirrhosis during pregnancy
are scarce, with the majority of medications falling
into pregnancy category C (Tables 1 and 2). Notable
exceptions are neomycin, azathioprine, and penicil-
lamine, which have been designated pregnancy cate-
gory D because of animal studies showing a possible
risk of fetal harm (Tables 1 and 2). Octreotide, cefo-
taxime, lactulose, telbivudine, prednisone, and ur-
sodeoxycholic acid (UDCA) have been deemed preg-
nancy category B, as animal studies have shown no
harmful effects (Tables 1 and 2). Ribavirin is preg-
nancy category X, with significant teratogenic effects
in all animal studies at 0.01 times the maximum
human dose (Tables 1 and 2).

LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
1084 TAN, SURTI, AND SAAB

TABLE 2. Medications Used for Liver Disease

FDA
Pregnancy Effect on Breast-Feeding
Drug Category Conception Effect on Mother Effect on Fetus Safe? References
Furosemide C None Electrolyte Decreased uteroplacental Unknown; no 76-78
disturbances, perfusion and reports available
decreased hepatic hypovolemia, electrolyte
perfusion disturbances
Spironolactone C None Electrolyte Decreased uteroplacental Probably; 76,79
disturbances perfusion and negligible
hypovolemia, amount in
feminization of males in breast milk
rat studies
Propranolol C None Bradycardia, Intrauterine growth Probably; 80-87
bronchospasm, retardation, bradycardia, negligible
hypotension, hypoglycemia, neonatal amount in
fatigue respiratory depression breast milk
during labor
Nadolol C None Bradycardia, Unknown Possibly unsafe; 88-90
bronchospasm, concentrations
hypotension, in breast milk
fatigue can be
significant if
high doses are
used or in
younger infants
Octreotide B Unknown Gastrointestinal No teratogenic effects in Unknown 14
side effects animal models
Lactulose B None Diarrhea, No adverse effects in Unknown; no 91
electrolyte animal models reports available
disturbances,
abdominal cramps
Rifaximin C None Nausea, Teratogenic in high doses Unknown; no 92
abdominal pain in animals; no human reports available
studies
Neomycin D None Nephrotoxicity, Like other Unknown; no 93-96
ototoxicity aminoglycosides, may reports,
cause fetal ototoxicity although other
aminoglycosides
are considered
safe
Cefotaxime B None Diarrhea, No fetal harm in animal Probably; 97-101
abdominal pain studies negligible
amount in
breast milk
Ciprofloxacin C None Nausea, dyspepsia Teratogenic in animal Probably; 102-109
studies; congenital arthropathy in
anomalies reported in 1 juvenile
human study, but none animals; 1 case
in 3 other studies report of
pseudomembranous
colitis
Norfloxacin C None Nausea, dyspepsia Teratogenic in animal Probably; no 102-103,
studies; no harm in reports, 107
human observational although other
study quinolones are
considered safe
Lamivudine C Unknown Lactic acidosis, No increases in birth Unsafe; possible 110-113
pancreatitis, defects overall; reports of severe adverse
peripheral mitochondrial reactions in
neuropathy, dysfunction infant
anemia

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 PREGNANCY AND CIRRHOSIS 1085

TABLE 2. (CONTINUED)

FDA
Pregnancy Effect on Breast-Feeding
Drug Category Conception Effect on Mother Effect on Fetus Safe? References
Interferon alfa C Unknown Fatigue, mood Abortifacient in monkeys Unknown but 114, 115
2a and 2b changes, at 90 times human dose; not
pancytopenia, case reports of transient recommended;
myalgias thrombocytopenia, excretion into
intrauterine growth milk reported in
restriction, and neonatal mice
lupus
Adefovir C Unknown Nephrotoxicity, Unknown; no studies or Unknown but 116
lactic acidosis case reports in either not
women or animals recommended
Entecavir C Unknown Lactic acidosis No studies in humans; in Unsafe; secreted 117
rats, lower body weights, into milk of
tail and vertebral lactating rats
malformations, and
reduced ossification were
seen at 3100 times
human dose
Telbivudine B Unknown Lactic acidosis, No adverse effects in Possibly unsafe; 118
neutropenia, animals at doses as high found to be
thrombocytopenia as 37 times human dose excreted into the
milk of lactating
rats
Ribavirin X Unknown Pancytopenia, Embryocidal and Possibly unsafe; 119
nephrotoxicity, teratogenic in all animals unknown
myalgias studied; should also be whether it is
avoided in men whose excreted into
female partners are or milk
may become pregnant
Azathioprine D Unknown Leukopenia, 22% malformations, 45% Unsafe 120
gastrointestinal first trimester abortion
side effects
Prednisone B None Hypertension, 4% malformation rate, Safe 121
gestational adrenal insufficiency,
diabetes, premature rupture of
cushingoid membranes
appearance,
osteonecrosis,
weight gain,
dyslipidemia,
infection
Penicillamine D Unknown Anemia, Possible cutaneous Unknown 122, 123
agranulocytosis, defects
proteinuria
Trientine C Unknown Anemia, Chromosomal defects Unknown 124
neurologic
worsening,
iatrogenic copper
deficiency
Ursodeoxycholic B Unknown Headache, Effects during first Unknown 64, 66
acid dizziness, trimester unclear;
constipation presumed safe during
third trimester
Cholestyramine C None in rat Vitamin No studies in pregnant Not excreted 125
models malabsorption, humans, possible into breast milk
particularly K vitamin deficiencies
Hydroxyzine C Unknown Central nervous Neonatal withdrawal Unknown 67
system depression syndrome

Abbreviation: FDA, Food and Drug Administration.

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1086 TAN, SURTI, AND SAAB
EFFECT OF PREGNANCY ON SPECIFIC LIVER
DISEASES
Chronic Viral Hepatitis B and C
The chief potential risk posed by viral hepatitis during
pregnancy is transmission of the virus from mother to
child. In areas endemic for hepatitis B, vertical trans-
mission of the virus is responsible for the vast majority
of infections. When a mother is a hepatitis B surface
antigen carrier with viral DNA present in her serum, the
neonate has an 80% to 90% risk of also becoming a
chronic carrier.33 High levels of viremia are the most
important risk factor for infection of the infant, with
transmission rates decreasing to as low as 10% to 30%
when viral DNA is absent from the mother’s serum.34
Intraplacental transmission is the most common
means of vertical spread, although infection can also
occur during delivery and breastfeeding.35
In contrast, rates of transmission of hepatitis C from
mother to infant are typically low, ranging from 4% to
10%.35 Risk is increased by high levels of viral RNA in
the mother and by prolonged time from rupture of
membranes to delivery. Most children who acquire hep-
atitis C from their mothers do so during delivery, when
they are exposed to a high volume of their mother’s
blood and vaginal fluids. Additional risk factors for the
vertical spread of hepatitis C are genotypes 1 and 3,
elevated alanine aminotransferase levels, and coinfec-
tion with human immunodeficiency virus.35
Laboratory parameters, are expected to fluctuate
during pregnancy, although the clinical significance is
unknown. Because of the expansion of extracellular
fluid, all markers of liver function except for alkaline
phosphatase, which is produced by the placenta, tend
to decrease. This is particularly true during the second
and third trimesters.3 Hepatitis B virus DNA levels typ-
ically increase late in pregnancy or in the early postpar-
tum period, with 1 retrospective study showing a mean
increase of 0.4 log.36 Several studies have likewise
shown hepatitis C RNA levels to increase during the
second and third trimesters.37-39
Hepatitis B viral infection itself does not appear to
alter fertility, conception, or pregnancy beyond the ef-
fects of cirrhosis or liver failure.40 Case reports have
reported delivery before 34 weeks, antepartum hemor-
rhage,41 fetal distress, and meconium peritonitis,42 but
these have been isolated experiences.
In mothers affected by hepatitis C, 1 study demon-
strated an increased incidence of intrahepatic cholesta-
sis of pregnancy.43 Another suggested that pregnant
women with hepatitis C may experience worsening
necroinflammatory and fibrotic changes on liver biopsy
after pregnancy.44 Other studies, however, have shown
no adverse effects on pregnancy or neonatal outcome.45
Caesarean delivery is not advocated in order to re-
duce transmission of hepatitis B, as studies have not
shown it to significantly decrease infection rates.46
Rather, prevention of transmission is accomplished
through administration of hepatitis B vaccine and hep-
atitis B immunoglobulin within 12 hours of birth. The
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
vaccine series must then be completed according to the
standard schedule.47,48
Caesarian delivery remains controversial for mothers
with hepatitis C, with 1 multicenter European study
demonstrating no protective effect of Caesarean deliv-
ery49 and another demonstrating a significantly higher
rate of vertical transmission in vaginally delivered in-
fants.50 There are no vaccines or immunoglobulins
available at this time for hepatitis C.
According to guidelines published by the American
College of Obstetricians and Gynecologists, breastfeed-
ing is considered safe for mothers with hepatitis C.51 In
mothers with hepatitis B, breastfeeding is also encour-
aged, although mothers are advised to hold off until the
neonate receives hepatitis B immunoglobulin.52
Antiviral treatment of hepatitis B during pregnancy is
controversial. Because the rate of mother-to-child
transmission of hepatitis B is dependent on the level of
viral DNA in the mother’s serum, it has been argued
that treating mothers with lamivudine, or more re-
cently, telbivudine results in decreased rates of neona-
tal infection.53,54 Lamivudine is designated pregnancy
category C. However, extensive experience in pregnant
women with human immunodeficiency virus, as re-
ported in a national antiviral pregnancy registry, shows
the drug to be well tolerated and safe in both mothers
and infants.55 Telbivudine has been deemed category B
because animal studies have shown no increase in fetal
harm (Table 1). With no long-term studies as of yet,
however, antiviral treatment during pregnancy remains
a subjective decision between mothers and physicians.
Antiviral treatment of hepatitis C is contraindicated
during pregnancy. Although case reports of patients
who became pregnant while on interferon showed rela-
tive safety of the medication,56 ribavirin is considered
pregnancy category X. Animal studies of ribavirin have
shown a high incidence of birth defects and spontane-
ous abortion (Table 1).
Autoimmune Hepatitis (AIH)
Although earlier studies of pregnancy in patients with
AIH showed an increased risk of prematurity, low birth
weight, and fetal loss,57 recent advances in therapy
have modified the prognosis of pregnancy in these pa-
tients.
Theoretically, AIH should improve during pregnancy
because of changes in female sex hormones and cyto-
kine profiles, resulting in a shift from T helper 1 cells to
T helper 2 cells. Indeed, there are multiple reported
cases of improvement of AIH during pregnancy.58 How-
ever, in a significant number of patients, AIH may by
exacerbated by pregnancy, with a rate of intrapartum
flare of 12.5% to 21%.59,60 Postpartum flares of AIH
also occur, with exacerbation rates ranging widely, any-
where from 12.5% to 86%.58-61 This discrepancy in
data may be due to inconsistent alteration of therapy
during pregnancy, with dosing being maintained, re-
duced, or even discontinued.
Maternal and fetal complications do appear to be
slightly increased, although evidence is limited. Pa-

tients with AIH have been shown to undergo caesarian
section at higher rates than the general population,
ranging from 16.1% to 43%.60,61 The rate of serious
maternal complications was as high as 9% in 1 study,
but this may have been biased by 1 mother who died of
multiorgan failure from a septic abortion and another
who developed fulminant hepatic failure requiring
emergent liver transplantation and hysterectomy.58 Fe-
tal loss was reported to be as high as 33% in earlier
studies,57 but more recent studies have shown rates
between 14% and 24%.59,60
A recent review of pregnancy in AIH, published by
Schramm et al.60 in 2006, examined 42 pregnancies in
22 women with AIH. The spontaneous abortion rate in
this population was 17%, and the rate of preterm deliv-
ery was 17%. Twenty-one percent of patients had AIH
flares during pregnancy, and 52% suffered postpartum
AIH flares. Interestingly, the presence of anti-Ro/SSA
and anti-soluble liver antigen/liver-pancreas antibod-
ies was associated with adverse pregnancy outcomes.
Because of the risk of intrapartum and postpartum
flares, it is generally recommended that immunosuppres-
sive therapy be continued during pregnancy. A modest
decrease in immunosuppression can often be performed
after the third month of pregnancy, when liver test typi-
cally improve. However, this is usually followed by a need
for increased doses just before delivery and in the post-
partum period. Azathioprine has been used successfully
during pregnancy in patients with inflammatory bowel
disease and rheumatoid arthritis, with benefits that far
outweighing its teratogenic potential.62,63
Although successful pregnancy is possible in patients
with AIH, careful monitoring is required because of the
higher rate of maternal and fetal complications the un-
predictable course of disease during pregnancy.
Other Liver Diseases
Reports of pregnancy outcomes in patients with pri-
mary biliary cirrhosis (PBC) are rare, largely because of
the negative effect of PBC on fertility.64 It is thought
that high levels of estrogen during pregnancy may re-
sult in impaired biliary function and altered amino-
transferase levels, but the impact of these changes on
maternal and fetal outcomes is unknown.
The safety of medications commonly used to treat
PBC is also a matter of debate. Although UDCA is
thought to be safe during the third trimester, it is un-
clear whether use in the first trimester can result in
fetal harm. The American Association for the Study of
Liver Diseases recommends avoiding UDCA in women
considering pregnancy.65 Furthermore, breastfeeding
is not advised, as it is unknown whether UDCA is ex-
creted into breast milk.66
No well-controlled studies exist on the effects of bile
acid sequestrants such as cholestyramine, and caution
is advised regarding their use. Cholestyramine is par-
ticularly known to interfere with the absorption of fat-
soluble vitamins.
Hydroxyzine, often used to treat pruritus in PBC pa-
tients, is contraindicated in early pregnancy because of
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
PREGNANCY AND CIRRHOSIS 1087
animal studies showing increased fetal abnormalities
at high doses. Human studies also show an increased
risk of neonatal withdrawal symptoms.
On the other hand, continuation of therapy is advo-
cated in pregnant patients with Wilson’s disease. Ces-
sation of therapy can lead to hemolytic crisis, with pos-
sible hepatic failure and maternal death.68 Although
penicillamine is pregnancy category D, successful out-
comes have been reported in patients treated through-
out their pregnancies.69 Current guidelines recom-
mend that pregnant women be continued on
penicillamine at a reduced dose of 25% to 50% their
prepregnancy dose.70 The safety of trientine during
pregnancy is less clear, but it can also be considered at
reduced doses.
Pregnancy data in women with hemochromatosis are
exceedingly rare, given that women are generally diag-
nosed during their postmenopausal years and that
those in their reproductive years often present with
secondary amenorrhea.
Pregnancy data are also rare in women with alcoholic
liver disease (ALD), as women with ALD are often infertile.
Infants born to mothers with ALD who continue to drink
are at high risk for fetal-alcohol syndrome, which consists
of several abnormalities, including poor growth, central
nervous system defects, dysmorphic facial features, and
cognitive and behavioral impairments.71
PREGNANCY AFTER LIVER
TRANSPLANTATION
The advent of liver transplantation has further changed
the course of pregnancy in patients with liver disease.
Although rare, like pregnancy in the context of cirrho-
sis, successful pregnancy after liver transplantation is
achievable. As of January 2006, 202 pregnancies and
205 outcomes have been reported in 121 female liver
transplant recipients in the National Transplantation
Pregnancy Registry.72 Although children born to female
liver transplant recipients have a greater risk of prema-
turity (35% versus 11.0%-12.7%) and low birth weight
(34% versus 8.2%) compared to the general population,
overall outcome is similar, with no associated malfor-
mation patterns reported thus far.72 Recent data, how-
ever, indicate that mycophenolate may be associated
with first trimester pregnancy loss and an increased
risk of congenital malformations.73
Maternal complications have been shown to be in-
creased in liver transplant recipients, particularly preg-
nancy-induced hypertension (34% versus 4%-10%),
preeclampsia (22% versus 6%-8%), and caesarian sec-
tion (35% versus 20%-25%).72 The incidence of preg-
nancy-induced or exacerbated hypertension may relate
to the type of immunosuppressive regimen used, with
the highest risk posed by cyclosporine, followed by ta-
crolimus and then corticosteroids.74
The rate of acute rejection in pregnant liver recipients
is not substantially different, from that of their non-
pregnant counterparts. In a 2005 National Transplan-
tation Pregnancy Registry report evaluating 121 liver
recipients, 7% developed acute rejection during preg-
1088 TAN, SURTI, AND SAAB
nancy, and 8% suffered graft loss within 2 years of
delivery. This risk was highest in women who conceived
within 6 months of their transplant.72
Experts recommend that pregnancy be postponed for
at least 1 year post-transplant, when graft function is
optimal on lower doses of immunosuppression and the
risks of acute rejection and opportunistic infection are
lower.75 Until then, contraception is advised, preferably
using barrier methods, which confer a lower risk of
infection or potential drug interaction. Physicians
should discuss the timing of pregnancy, methods of
contraception, and safety and adverse effects of immu-
nosuppressants with all patients considering preg-
nancy as part of pretransplant counseling.
CONCLUSION
Although pregnancy in patients with cirrhosis remains
rare, recent improvements in the treatment of cirrhosis
have resulted in increased life expectancy and quality of
life, making pregnancy a more common occurrence. As
growing numbers of patients with cirrhosis become
pregnant, physicians will need to become aware of the
unique risks and complications that they face. These
include a potential for life-threatening variceal bleed-
ing, hepatic decompensation, splenic artery aneurysm
rupture, and postpartum hemorrhage. Medications
may need to be adjusted during this time period, as
several drugs commonly used for liver disease have
potential harmful effects on the fetus or may be trans-
mitted to neonates during breastfeeding. Finally, one
must consider risks specific to the underlying liver dis-
ease, as in chronic viral hepatitis and AIH.
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