Cirrhosis and Portal Hypertension

in Pregnancy
Michelle A. Russell and Sabrina D. Craigo

Cirrhosis and portal hypertension infrequently coincide with pregnancy but increase maternal and
fetal morbidity and mortality when present. Chronic liver disease and portal hypertension are not
contraindications to pregnancy but necessitate intensive monitoring throughout pregnancy. The complications of liver disease are numerous and pose additional risks. Management of complications
arising during pregnancy is similar to management in the nonpregnant patient. Provision of optimal
care for mother and fetus can require the skills of multiple specialities such as maternal fetal
medicine, gastroenterology, nutrition, and surgery. This report provides guidelines for the management of cirrhosis and portal hypertension in pregnancy.

Copyright 9 1998 by W.B. Saunders Company

irrhosis and portal hypertension can com-

C plicate pregnancy and increase maternal

and neonatal morbidity. Because of the historically high maternal mortality, pregnancy was discouraged in patients with cirrhosis or portal hypertension. With current therapy and intensive
monitoring, these medically complicated pregnancies can have favorable outcomes. This report describes the effects o f cirrhosis and portal
hypertension on pregnancy and the managem e n t of these disorders from preconception
through the postpartum period.

Portal Hypertension

Cirrhosis
Cirrhosis is an irreversible, progressive disease
characterized by diffuse damage to hepatic parenchyma cells, fibrosis, and nodular regeneration that leads to alteration of the normal liver
architecture and compromised organ function.
Cirrhosis results from destruction and regeneration o f hepatocytes, an increase in inflammatory
cells and mediators, and an altered collagen production. A shift in the ratio of collagen synthesis
from type II to type I p r e d o m i n a n c e eventually
leads to encasement of parenchyma tissue and
prohibits parenchyma cell regeneration. T h e
structural alteration in collagenous and noncollagenous tissues forms a barrier between hepatoFrom the Department of Obstetricsand Gynecology, Tufts University
School of Medicine, New England Medical Center, Boston, MA.
Address reprint requests to Sabrina D. Craigo, MD, New England
Medical Center, 750 Washington St, Box 360, Boston, MA 02111.
Copyright 9 1998 by W.B. Saunders Company
0146-0005/98/2202-0009508.00/0

156

cytes and sinusoids. T h e fibrotic barrier causes

shunting of hepatic blood, extrahepatic collateral formation, and elevated blood pressure in
the portal venous system. 1 Changes in hepatic
blood flow through the structurally distorted organ can cause elevated pressures in the portal
vascular system and subsequent portal hypertension. These changes lead to deficiencies in the
metabolism and excretion of substances normally cleared by the liver with subsequent systemic exposure to toxins.

In the United States, portal hypertension most

commonly results from cirrhosis. Noncirrhotic
portal hypertension can be seen in patients without evidence of liver disease. Noncirrhotic causes
of hypertension in the portal system include extrahepatic venous obstruction in childhood as a
result o f omphalitis, cholangitis, severe burns, or
appendicitis. In the adult it may be attributed
to veno-occlusive disease, infection, malignancy,
pancreatitis, or myeloproliferative disorders, or
it may be idiopathic.
Portal hypertension is characterized by hyperdynamic circulation and an elevation of blood
pressure in the normally low-pressure portal venous system. As a result of intrahepatic fibrosis,
paracrine h o r m o n e s and cytokines derived from
the gastrointestinal tract, extrahepatic collateral
blood flow develops from the portal vein to the
inferior and superior vena cava system. T h e normal portal pressure in the n o n p r e g n a n t state is
4 to 8 mm Hg. 2 T h e normal pressure gradient

Seminars in Perinatolog3, Vol 22, No 2 (April), 1998: pp 156-165

Cirrhosis and Portal Hypertension

between the portal vein and the vena cava is

usually 1 to 4 m m Hg. A 12 to 17-mm Hg pressure gradient can cause collateral formation in
patients with cirrhosis.~ The consequences o f collateralization include the loss of liver filtration
of toxins and bacteria from the blood, ascites,
and potential h e m o r r h a g e from tortuous collateral vessels t h r o u g h o u t the gastrointestinal tract.

Incidence
In 1990, cirrhosis was the ninth leading cause o f
death in the United States. a T e n percent to 40%
of people remain asymptomatic until the latest
stages of the disease. 3 A nutrition survey in 1980
f o u n d the prevalence o f cirrhosis to be about 3.6
cases per 1,000 persons in the United States. 3
T h e prevalence in reproductive-aged women is
approximately 0.45 cases per 1,000 persons. 4 Historically, pregnancy in women with cirrhosis has
been u n c o m m o n because the final stage of
chronic liver disease occurs after the reproductive years and because the abnormalities of hormonal metabolism result in anovulation and infertility. W o m e n with noncirrhotic portal
hypertension have normal fertility rates. Over
the last three decades several case reports, small
series, and reviews have appeared in the literature suggesting that improvements in therapy for
chronic liver diseases and portal hypertension
may parallel higher conception rates and successful pregnancy outcomes. 5q9

Etiology
The most c o m m o n cause o f cirrhosis in the weste m world is heavy alcohol consumption, accounting for 65% o f cases. W o m e n are more
susceptible to alcoholic liver damage than men,
and lower daily alcohol consumption over a
shorter duration can lead to irreversible injury.
Additionally, women with alcohol-related liver
damage have a worse prognosis than men. 3 Viral
hepatitis B and C infections are estimated to be
responsible for 10% and 15% of cases o f cirrhosis, respectively. Exposure to hepatotoxins accounts for 2% o f cases. Congenital, autoimmune, and metabolic diseases are less c o m m o n
risk factors for chronic liver dysfunction (Table

157

Table 1. Causes of Cirrhosis

Medications
Methyldopa
Methotrexate
Isoniazid
Amiodarone
Acetaminophen
Aspirin
Sulfonamides
Propylthiouracil
Nitrofurantoin
Vitamin A
Toxins
Carbon tetrachloride
Metabolic disorders
Wilson's disease
Hemochromatosis
Porphyria
Antitrypsin deficiency
Gaucher's disease
Autoimmune hepatitis
Types I, II, III
Sarcoidosis

Infections
Hepatitis B, C, D
Syphilis
Schistosomiasis
Biliary obstruction
Carcinoma
Chronic pancreatitis
Gallstones
Strictures
Cystic fibrosis
Atresia
Sclerosing cholangitis
Alcohol
Vascular disorders
Budd-Chiari syndrome
Congestive heart
failure
Veno-occlusive disease
Jejunal-ileal bypass
Chronic active hepatitis
Primary biliary cirrhosis
Cryptogenic/posmecrotie

1). In developing countries infection accounts

for more cases including schistosomiasis, toxoplasmosis, brucellosis, and tuberculosis. Postnecrotic cirrhosis accounts for a majority o f cases
e n c o u n t e r e d during pregnancy. 7 Alcohol-related cirrhosis is less frequently associated with
pregnancy, and these patients fare worse than
those with o t h e r forms o f cirrhosisfl~ Portal
hypertension can be a sequela o f advanced liver
disease but can occur in patients who do not
have evidence of cirrhosis (Table 2).
Diagnosis
T h e preliminary diagnosis o f cirrhosis is often
made by history, physical examination, and laboratory study findings, but liver biopsy may be
required when the diagnosis is uncertain. A cordprehensive history may show a cause of cirrhosis
such as alcohol or intravenous drug abuse, prior
transfusion, exposure to hepatotoxins, or a systemic a u t o i m m u n e disorder. Evidence on physical examination o f a patient with cirrhosis may
be absent, subtle, or may include obvious spider
angiomas, ascites, liver nodularity, splenomegaly, p r o m i n e n t abdominal wall vessels, or encephalopathy. Initial laboratory studies should
include aminotransferases, bilirubin, alkaline
phosphatase, total protein, albumin, blood urea

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Russell and Craigo

Table 2. Causes of Portal Hypertension

Cirrhosis
Congenital hepatic fibrosis
Partial nodular transformation
Nodular regenerative hyperplasia
Pliosis hepatis
Hepatoportal sclerosis
Idiopathic portal hypertension
Acute fatty liver of pregnancy
Polycystic disease
Sarcoidosis
Schistosomiasis
Tuberculosis
Amyloidosis
Intraperitoneal infection
Neonatal omphalitis
Veno-occlusive disease
Hepatic vein occlusion
Portal vein occlusion
Splenic vein occlusion
Inferior vena cava thrombosis
Congestive heart failure
Constrictive pericarditis
Splenomegaly
Metastatic carcinoma
Mastocytosis

nitrogen, creatinine, prothrombin time, complete blood count, and platelet count. The laboratory picture in cirrhosis is variable, but often
hypoalbuminemia, a prolonged prothrombin
time, and thrombocytopenia are present. The
histological findings of a liver biopsy in a patient
with cirrhosis can show nodules surrounded by
connective tissue septa, inflammatory cells, proliferating bile ductules, and vascular channelsfl 2
Ultrasonography, computerized tomography,
and radionucleofide imaging have been used to
support the diagnosis of cirrhosis but are not
reliable screening tools. 4

Management
Actual data pertaining to the m a n a g e m e n t of
cirrhosis and portal hypertension during pregnancy are limited. The present recommendations are based on small series and reviews, and
on extrapolation from treatment of nonpregnant patients.

Preconception Counseling
A mother with severe cirrhosis has only a 10%
chance of rearing her child to adulthood and may

die when the child is still very young, is'z3 During

preconceptual counseling the obstetrician should
first evaluate the severity of disease. Advanced
stages of liver disease are associated with a higher
frequency of complications and worse maternal
and fetal outcomes. 24 The initial evaluation
should include a complete history and physical
examination, as well as laboratory studies of liver,
renal, and coagulation function. In the presence
of portal hypertension, endoscopic evaluation
and medical treatment for esophageal varices is
warranted before conception. 6'~4 The absence of
varices on evaluation of the esophagus does not
preclude the possibility of variceal hemorrhage
during pregnancy, but makes this life-threatening
complication less likely.
Pregnancy should be planned when the disease process is stable, and reliable contraception
should be encouraged until conception is desired. If liver transplantation is an option, child
bearing should be delayed until transplant is
completed.
Medical regimens must be tailored to optimize maternal and fetal outcome. Medications
should be reviewed for potential teratogenicity
with subsequent dosage or medication modifications made before conception when possible.
Prednisone and azothioprine are used frequently in the care of patients with autoimmune
hepatitis, and cyclosporine is used in many liver
transplant recipients. These immunosupressant
medications need to be continued, but adjustments should be made to the lowest effective
dosage because of their association with intrauterine growth restriction and neonatal immunosuppression. 2~27 Spironolactone is associated
with genital malformations in the fetus, therefore discontinuation is r e c o m m e n d e d except in
patients with severe ascites. Histamine receptor
type II blocking agents are safe in pregnancy and
reduce esophagifis and gastritis that aggravate
hematemesis. Beta-adrenergic blocking agents
such as propranolol can be continued to medically control the complications of portal hypertension. Beta-adrenergic blocking agents have
been associated with fetal growth restriction but
potential benefits may outweigh this risk. 2s Interferon-alpha is used in the treatment of compensated chronic active viral hepatitis and early cirrhosis; in animal studies it is an abortifacient
with unclear teratogenicity and should be used
only if the patient accepts the unknown risks. 29

Cirrhosis and Portal Hypertension

Pregnancy probably does not increase the risk

of bleeding from varices. 9 Controversy exists regarding whether a history of preconceptual variceal hemorrhage predicts an increased risk of
bleeding during pregnancy or during labor and
delivery. One review suggests that there is no
association between an individual's prior bleeding history and the risk of recurrent bleeding
during pregnancy, 9 but several other investigators have reported an association. 6
Prophylactic surgery or sclerotherapy are generally not recommended because patients have
an unpredictable risk of bleeding; conservative
management can be effective:~ Sclerotherapy in
the nonpregnant population eradicates varices,
but they eventually recur, and 48% to 58% of
patients treated will have further episodes of
bleeding. Prophylactic sclerotherapy does not
appear to improve overall survival, a~ If sclerotherapy has been initiated before pregnancy it
should be continued, bearing in mind that the
safety of many sclerosing agents has not been
well established. Prophylactic portosystemic
shunt surgery does not prolong life in patients
with cirrhosis and portal hypertension, and
should be reserved to treat refractory life-threatening hemorrhage only.
The obstetrician should identify infectious or
hereditary causes of cirrhosis that may be transmittable to the fetus and offer appropriate neonatal immunization and genetic screening. If any
questions exist, viral serological studies should
be obtained to counsel the patient appropriately
on risks of fetal transmission. Women with positive hepatitis B surface antigen screening should
be advised that early neonatal administration of
recombinant immunoglobin and immunization
with hepatitis B vaccine can prevent 90% of neonatal transmission of the hepatitis B virus.
Women who are infected with the hepatitis C
virus should be counseled of the vertical transmission risks. Neonatal prophylaxis and immunization are not available at this time.
When the cause of liver injury is identified to
be alcohol, the patient should be counseled of
the risks of fetal alcohol syndrome if consumption persists during pregnancy. Patients should
have access to detoxification and rehabilitation
facilities as required to maintain sobriety. Alcoholic cirrhosis has a worse prognosis than liver
damage of other etiology. Abstinence from further alcohol consumption in the setting of pre-

159

existing alcohol-related hepatic injury is associated with a significantly lower morbidity than if
consumption continues:
Pregnancy
Maternal prognosis during pregnancy correlates
with her underl)dng liver disease. In the nonpregnant populaOon, the prognostic factors for
an increased rate of mortality in patients with
alcohol-related liver injury include encephalopathy, spider angiomas, ascites, renal failure,
marked elevation of serum biUrubin, and a prolonged prothrombin time of greater than 50%
above control, s~ Early termination of pregnancy
should be considered if there is evidence of severe hepatic decompensation such as ascites, encephalopathy, or liver failure: ~ In most cases,
cirrhosis is not a contraindication to continuing
pregnancy because pregnancy usually has no deleterious effects on well-compensated cirrhosis
and mild portal' hypertension. 24"a~ Pregnancy
outcome with regard to hepatic function is not
predictive of hepatic function in subsequent
pregnancies. 7.9.sl
Antenatal management requires close monitoring of the maternal and fetal condition. Surveillance of liver and hematologic function
should be performed at 2- to 4-week intervals
unless change in status warrants more frequent
evaluation. Serum albumin and prothrombin
time can be followed to assess liver synthetic
function. Renal function should be reassessed
particularly if there are signs of hepatic failure.
Maternal stool guiac tests should be performed
to screen for occult bleeding, ss
Ultrasonographic evaluation of fetal growth
may be useful during the third trimester in patients with recurrent hematemesis or in patients
on immunosuppressive agents. Immunosuppressive medications and beta agonist blocking
agents have been associated with intrauterine fetal growth restriction. There appears to be an
association between gastrointestinal bleeding
and intrauterine growth restriction. Up to 50%
of pregnancies complicated by gastrointestinal
hemorrhage are associated with restricted
growth of the fetus.
Fetal nonstress tests should be performed at
least weekly starting around 28 weeks' gestation
in patients who are medically stable and more
frequently if there is deterioration in maternal
condition or suspected fetal growth restriction.

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Mothers with portal hypertension and varices

should be instructed to modify their activities to
avoid straining and valsalva, which may aggravate
variceal bleeding. Valsalva maneuver has been
shown to increase the pressure in esophageal
varices. ~4
Maternal complications arise in nearly half of
cirrhosis-affected pregnancies. 8 The potential
maternal complications of cirrhosis are numerous: portal hypertension, variceal hemorrhage,
liver failure, splenic artery aneurysm rupture,
gastropathy, encephalopathy, renal failure, malnutrition, diabetes, infection, and carcinoma.
The complications of cirrhosis occurring during
pregnancy are managed in nearly the same manner as complications in nonpregnant patients
with cirrhosis and will be reviewed in detail. 1The
maternal mortality rate has been estimated at
10% to 61%. 5'8'9'33This is not an accurate estimation of the current rate given the availability of
emergent endoscopy, new medical therapies, improved access to blood products, and advances
in intensive care treatment of the obstetrical patient.

Labor and Delivery

Pregnancy can be allowed to proceed to term or
until fetal lung maturity is documented if maternal cirrhosis is well compensated. Delivery
should be accomplished if life-threatening maternal deterioration occurs at any point in pregnancy. If fetal jeopardy is observed, delivery
should be emergent. When maternal and fetal
condition permits, corticosteroids can be administered to enhance fetal lung maturation before
anticipated delivery at less than 34 weeks.
Cesarean sections should only be performed
for obstetric indications or for rapid deterioration in maternal hemodynamic status. 35'8 The
morbidity of laparotomy is significantly increased in patients with cirrhosis and portal hypertension. 36 Collaterals can be encountered as
aberrant dilated vessels in the abdominal wall
increasing the risk of hemorrhagic complications. Assisted vaginal delivery is recommended
by some investigators to avoid an elevation of
intraabdominal pressure and shorten the second
stage of labor. 36
Liver, renal, coagulation, and blood group
studies should be obtained when the patient arrives in the labor and delivery unit. Blood product availability must be assured before labor and

delivery because of the risk of variceal bleeding

and increased risk of postpartum hemorrhage.
The patient should be evaluated for the presence
of coagulopathy. Transfusion of platelets, cryoprecipitate, and fresh frozen plasma should be
performed as needed.
Intrapartum care requires careful management of fluid and electrolyte replacement, preparation for hemorrhagic conditions, and administration of analgesia. A Sengstaken-Blakemore
tube and a person experienced in its placement
should be available for abatement of massive
bleeding from esophageal varices. Complications from balloon tamponade occur in 5% to
30% of attempts and are attributable to airway
obstruction, aspiration pneumonitis, or perforation of the esophagus. Given the decreased gastric emptying of obstetric patients, the risk of
aspiration may be higher. A gastroenterologist
should be consulted regarding the possible need
for an emergent endoscopic procedure in patients with known varices.
Early epidural anesthesia is preferred to avoid
an increase in intrabdominal pressure and varices related to the valsalva maneuver and pain.
Spinal and general anesthesia should be avoided
because of the potential for hypotension and risk
of precipitating hepatic encephalopathy.36 Vascular engorgement occurs in normal pregnant
patients and is pronounced with portal hypertension and collateral formation. The extradural sinuses, lumbar, paraspinal, and azygous veins are
often abnormally engorged, increasing the risk
of systemic absorption of local anesthetic agents.
Severe thrombocytopenia may contraindicate
any form of regional anesthesia.

Postpartum
The postpartum treatment of patients with cirrhosis and portal hypertension varies from routine postpartum care to the need to closely monitor hepatic and coagulation status in an intensive
care setting. There is a 16% to 26% risk of postpartum hemorrhage as a result of thrombocytopenia, poor synthesis of coagulation factors V
and VII, and vitamin K deficiency.6 The incidence of puerperal infection is greatly increased
especially after cesarean section. 6 Puerperal fevers should be investigated and the patient
treated with antibiotics as appropriate. In general, lactation will occur normally, and breast
feeding can be encouraged in women with

Cirrhosis and Portal Hypertension

chronic liver disease if the etiology is not infectious viral hepatitis and the medications are compatible with nursing. 9
A reliable m e t h o d of contraception must be
provided to avoid unplanned pregnancies. The
indications for p e r m a n e n t sterilization are the
same as for women without chronic liver disease.
Surgical sterilization may be more difficult to
perform in the presence of ascites or extensive collateralization, and alternative methods
should be considered. Barrier methods and intrauterine devices can be offered, but hormonal
contraceptives should be avoided because they
may aggravate cholestasis.

Complications
Variceal Hemorrhage
Gastrointesdnal hemorrhage occurs in up to
24% of gestations complicated by cirrhosis and
portal hypertension. ~'s'3z Up to 78% of patients
with varices will bleed during pregnancy. 2s Massive hemorrhage from esophageal varices has
been the most frequently reported cause of maternal death. Bleeding occurs most commonly
in the second and third trimesters related to the
time of maximal expansion of blood volume and
increased compression of the inferior vena cava
and collateral vasculature. 9 The risk of a fatal
bleeding episode during pregnancy is related to
the etiology o f the portal hypertension and the
severity of underlying liver disease. Maternal
mortality rates associated with variceal bleeding
in the perinatal period in patients with varices
and cirrhosis range from 18% to 50%, whereas
the mortality of noncirrhotic patients is only 2%

161

and with caution because it can cause arteriolar

spasm, which decreases placental perfusion and
potentiates placental abruption. Myocardial infarction, peripheral ischemia, and hypertension
are potential maternal complications of vasopressin, a7 In the fetus, vasopressin has been associated with necrosis and amputation of digits and
limbs, sa Emergent endoscopic variceal ligation
and injection sclerosis control 90% to 100% of
acute esophageal bleeding episodes in the nongravid population and improve survival.31,aT'ag'4~
A combined approach using vasoactive agents
with endoscopy may offer technical advantages
to the endoscopist by reducing the hemorrhage
and clearing the field, s7 Emergent injection
sclerotherapy appears to be safe and effective in
pregnancy, but success rates a r e u n k n o w N . 41'42
Endoscopic variceal ligation, injection sclerotherapy, variceal transection, and radiological or
surgical portasystemic shunts may prevent episodes of recurrent bleeding. Radiographic placem e n t of a transjugular intrahepatic portasystemic stent shunt has been successfully used in
nonpregnant patients with refractory variceal
bleeding: 7 No cases of this procedure during
pregnancy have been reported. Portal shunt surgery has been performed during pregnancy and
may decrease the risk of recurrent hemorrhage,
but it is associated with up to a 25% incidence
of encephalopathy: TM In the few reported cases,
splenorenal shunt procedures appear to be well
tolerated, 4s'~'47 but at least one case of fatal disruption during pregnancy has been reported. 45
All shunt procedures should be reserved for refractory life-threatening variceal bleeding after
failed medical m a n a g e m e n t and endoscopic procedures, s7

t o 6 % . 3'~'9

Acute treatment to control hemorrhage consists of hemodynamic stabilization in an intensive

care unit with transfusion of blood products, invasive monitoring, balloon tamponade, emergent endoscopic variceal ligation or injection
sclerotherapy, and intravenous vasoconstricting
agents, s70ctreotide is a somatostatin-like medication that decreases portal pressures and controis acute variceal bleeding. Outside of pregnancy octreotide has minimal side effects.
Animal studies have shown no evidence of teratogenicity, but there is little information regarding
its use in h u m a n pregnancy. Vasopressin is a vasoconstrictor that must be used as a last resort

Hepatic Failure
Acute hepatic failure occurs in up to 24% of
patients with chronic active hepatitis and cirrhosis during pregnancy and can lead to rapid
deterioration, encephalopathic coma, cerebral
edema, hypoglycemia, and coagulopathy, s3 The
mortality rate is high, and intensive care monitoring is mandatory. Hypoglycemia can be managed with 10% dextrose infusions. Transfusions
of fresh-frozen plasma and platelets may be required to correct the coagulopathy. The treatm e n t of cerebral edema may require intubation
and hyperventilation, as well as mannitol diuresis
and phenobarbital administration. A neurosur-

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Russell and Craigo

geon should be involved because placement of

an intracranial pressure monitor may be required)
Nearly one third of patients will die within 48
hours of hepatic failure. 1 The only treatment in
fulminant cases may be a liver transplant and
must be considered early. In a limited number
of cases, liver transplantation during pregnancy
has been accomplished with successful outcomes
for both mother and fetus. 4s-51The technical aspects of the transplant procedure may be more
difficult during the third trimester, but delivery
of a severely premature fetus or delivery in the
face of an uncorrectable coagulopathy may be
catastrophic. 4s Fetal ischemic complications
have occurred during transplantation. 52There is
an increased risk of pregnancy-induced hypertension, anemia, cesarean section, and preterm
delivery in liver transplant recipients. 48

constriction and the responsible agent is yet unidentified. Patients can present with oliguria and
uremic symptoms. Serum creatinine and blood
urea nitrogen levels should be assessed and are
often elevated. A urinalysis finding showing protein, cellular elements, or granular casts may indicate an alternative etiology of the deterioration
in renal function. Intravenous fluids should be
administered liberally. Placement of Swan-Ganz
invasive monitoring should be considered if the
oliguria persists. Sources of infection should be
sought and treated aggressively. Renal toxic
drugs including aminoglycosides, nonsteroidals
and diuretics should be avoided. Renal dialysis
can maintain homeostasis until the acute hepatic
event resolves or urgent liver transplantation can
be accomplished. Liver transplantation is the
only curative treatment.

Hypersplenism
Encephalopathy
Hepatic encephalopathy or coma may be precipitated in a cirrhotic patient by hypotension, hypoxia, infection, gastrointestinal hemorrhage,
high protein diet, hypoglycemia, general anesthesia, sedatives, narcotics, thiazide diuretics,
phenothiazides, and constipation. Caution
should be taken to avoid iatragenic precipitation
of encephalopathy. Required medications
should be used judiciously, and medications that
are predominantly metabolized by the liver
should be avoided. Precipitants of hepatic encephalopathy should be sought and corrected.
Hypotensive and infectious episodes in the cirrhotic patient require aggressive management to
avoid encephalopathy. A protein-restricted diet
is recommended until the acute event subsides.
Blood ammonia levels are inconsistently elevated) The mainstay of treatment is lactulose
and antibiotic therapy to diminish gut absorption of nitrogenous compounds.

Hepatorenal Syndrome
Hepatorenal syndrome is renal failure that arises
in the setting of decompensated hepatic function. The syndrome occurs more frequently with
acute fulminant viral hepatitis and chronic alcoholic cirrhosis than from other etiologies of cirrhosis. In the nonpregnant population there is a
90% mortality rate in the setting of hepatorenal
syndrome) The cause is probably renal vascular

Hypersplenism may accompany portal hypertension as a result of splenic engorgement. Splenomegaly results in sequestration of blood cells and
hematologic abnormalities affecting all cell
lines. The white blood cell counts are usually
below 4,000 and platelet counts are generally less
than 100,000. Splenectomy is rarely indicated for
hypersplenism alone unless the thrombocytopenia is profound and results in episodes of recurrent bleeding) Thrombocytopenia combined with a prolonged prothrombin time can
make bleeding complications more likely.

Splenic ArteryAnuerysm
Pregnant patients with portal hypertension have
a 2.6% risk of rupturing a splenic artery aneurysm. There tends to be a female predominance
in rupture of splenic aneurysms with 20% occurring during pregnancy. ~s When associated
with pregnancy, up to 69% occur in the third
trimester. 13'53'55There may be few warning symptoms such as left upper quadrant pain, nausea,
or syncope before acute hemorrhagic shock. A
high index of suspicion should be maintained
because the maternal mortality rate is approximately 70% and the fetal mortality rate approaches 80%. ~4 Treatment includes emergent
blood product replacement, exploratory laparotomy, aneurysm ligation, and possible splenectomy. Computerized tomographic and plain film
radiographs with a calcified annulus in the left

Cirrhosis and Portal Hypertension

upper quadrant may suggest the presence of a

splenic artery aneurysm.

163

gestation, and repeated early in the third trimester. It is unknown whether cirrhotic patients
have an increased risk of gestational diabetes.

Ascites

Ascites formation is a manifestation of portal hypertension. It is a result of hypoalbuminemia,

venous congestion in the splanchnic vessels and
organs, and derangement of sodium metabolism. Ascites rarely occurs during pregnancy because of the increased intrabdominal pressure.
Sodium restriction and diuretics can be used if
ascites is severe.
Spontaneous bacterial peritonitis is an infection of the ascitic fluid that occurs when intrahepatic shunting leads to reduced clearance of bacteria. The immune function is impaired within
the ascites-filled peritoneal cavity. Patients are
often a.febrile and minimally symptomatic. In the
nonpregnant patient the mortality rate exceeds
60% to 90% if not treated early.
Diagnosis is made by paracentesis of ascitic
fluid and evaluation of the fluid for leukocytes,
glucose, and bacteria. When spontaneous bacterial peritonitis is suspected, blood and urine cultures should be obtained. A single organism is
cultured in a majority of cases. Escherichia coli,
Klebsiella pneumoniae and Streptococcuspneumoniae
are the most frequently isolated organisms. Antibiotic coverage should be broad spectrum such
as an aminoglycoside and ampicillin or thirdgeneration cephalosporin. The clinical course
should be monitored closely with continuation
of antibiotic therapy for 7 to 10 days. Cases occurring during pregnancy have not been reported. As with other causes of peritonitis, the
risk of premature delivery and abruptio placentae will likely be increased if spontaneous bacterial peritonitis complicates pregnancy,s6
Cancer

Hepatocellular carcinoma is rare in pregnancy

and carries a poor prognosis. It may be associated with rapid tumor growth and intraperitoneal hemorrhage in the setting of chronic liver
disease. Partial hepatic resection or transplantation are often the only treatment options. 9
Diabetes

Insulin-resistant diabetes can complicate cirrhosis. Screening with fasting and postprandial serum glucose levels should be performed early in

Malnutrition

A high percentage of patients with cirrhosis have

malnutrition. The poor nutritional intake may
be related to anorexia, alcohol intake, unappetizing diets, and a prescribed low-protein diet.
The problem may also stem from abnormal digestion, absorption, or metabolism.
Lipid soluble vitamins A, D, E, and K are malabsorbed. If the prothrombin time is prolonged,
vitamin K, 10 mg daily for 3 days, may be administered and will help to differentiate coagulopathy resulting from synthetic dysfunction from deficiency of vitamin IC57 Vitamin A should be
cautiously supplemented with no more than
5,000 IU daily because of its associated teratogenicity and hepatic toxicity in the setting of alcoholic cirrhosis. 5s Additionally, abnormal metabolism of thiamine, pyridoxine, folate, riboflavin,
and trace minerals occurs. Vitamin supplementation should be initiated early in prenatal care. 57
A reduction in bile acid synthesis produces a
deficiency in absorption of long chain fatty acids
and can cause steatorrhea, but dietary fat restriction is not necessary unless significant malabsorption is evident. The medium chain fatty
acids appear to be better absorbedY
A diet high in protein may precipitate encephalopathy as a result of an altered ratio of aromatic amino acids to branched chain amino
acids. In chronic liver insufficiency, elevated levels of aromatic amino acids are available for
brain tissue metabolism and become the precursors of inhibitory and false neurotransmitters
producing the depression of sensorium seen in
encephalopathy. Ammonia, a product of amino
acid metabolism, may not be converted adequately by the hepatocytes to the excretory form,
urea, and the high levels of ammonia can interfere with oxidative metabolism exacerbating cerebral dysfunction.57
A diet enriched with branched chain amino
acids, fats, and complex carbohydrates may be
required to maintain nitrogen balance and meet
the caloric requirements of pregnancy. Sodium
restriction may be needed in patients with evidence of ascites. The goal is to provide the estimated energy requirements and protein intake
for pregnancy and to maintain nitrogen balance

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Russell and Craigo

without precipitating encephalopathy. Managem e n t may be further complicated by the presence of insulin-resistant diabetes, which is not
u n c o m m o n in patients with chronic liver disease
and portal hypertension. Consultation with a nutritionist early in gestation will help to provide
the optimal protein-calorie diet. 57'59
Fetal Complications
Prematurity and neonatal death rates are increased in pregnancies complicated by cirrhosis.
T h e fetal complications of maternal chronic liver
disease include an overall rate of pregnancy wastage of 30% to 40%, 21'24 and up to a 25% rate o f
prematurity. 6'31 The perinatal death rate may be
as high as 1 8 % . 6'23 In the past, neonatal deaths
were often a complication of prematurity, therefore, the reported mortality rates are not likely
to reflect current statistics given the use of corticosteroids and surfactant, and m o d e r n neonatal
intensive care management.

Conclusion
Cirrhosis and portal hypertension increase maternal and fetal morbidity and mortality, but
pregnancy is not necessarily contraindicated as
was once believed. Management and counseling
should be individualized based on etiology and
severity of disease. Multidisciplinary care involving specialists in maternal fetal medicine, gastroenterology, surgery, anesthesiology, and neonatology in a tertiary obstetric and neonatal
intensive care unit is likely to lead to the best
maternal and neonatal outcomes.

6.
7.
8.
9.
10.

11.

12.
13.

14.

15.

16.

17.
18.

19.
20.

21.

22.

References
1. Gitnick G: Principles and Practice of Gastroenterology
and Hepatology (ed 2). Norwalk, CT, Appleton and
Lange, 1994
2. Genecin P, Grosmann R: The biology of portal hypertension, in Arias I, Boyer L, Fausto N (eds): The Liver:
Biology and Pathology. New York, NY, Raven Press, 1994,
pp 132%1341
3. Stroup N, Dufour M, Hurwitz E, et al: Cirrhosis and
other chronic liver diseaes, in Browns R, Remington P,
Davis J (eds): Chronic Disease Epidemiology and Control. Baltimore, MD, Port City Press, 1993, pp 241-284
4. Dufour M: Chronic liver disease and cirrhosis, in EverhartJ (ed): Digestive Diseases in the United States: Epidemiology and Impact. Baltimore, MD, NIH Publication
No. 94-1447, 1994, pp 615-645
5. Schreyer P, Caspi E, Mohamad J, et al: Cirrhosis-prego

23.
24.
25.

26.

27.
28.

nancy and delivery: A review. Obstet Gynecol 37:304-312,

1982
Pajor A, Lehoczky D: Pregnancy in liver cirrhosis. Gynecol Obstet Invest 38:45-50, 1994
Borhanmanesh F, Hahighi P: Pregnancy in patients with
cirrhosis of the liver. Obstet Gynecol 36:315-324, 1970
Cheng Y: Pregnancy in liver cirrhosis and portal hypertension. Am J Obstet Gynecol 128:812-822, 1977
Britton R: Pregnancy and esophageal varices. AmJ Surg
143:421-425, 1982
Donaldson L, Plant R: Pregnancy complcated by extrahepatic portal hypertension. AmJ Obstet Gynecol 110:255263, 1971
Herman R, Esselstyn C: The potential hazard of pregnancy in extrahepatic portal hypertension. Arch Surg
95:956-959, 1967
Mackey W, Hendry W: Pregnancy and extrahepatic portal hypertension. BrJ Surg 56:909-911, 1969
Leong A: Segmental biliary ectasia and congenital hepatic fibrosis in a patient with chromosomal abnormality.
Pathology 12:275-281, 1980
McMichens T, Robichaux A, Smith J: Successful pregnancy outcome in a patient with congenital biliary atresia. Obstet Gynecol 80:492-494, 1992
Mazar M, Wiznitzer A, Pinker A, et al: Gaucher's disease
in pregnancy associated with portal hypertension. Am J
Obstet Gynecol 154:119-120, 1986
Dupont P, Iron O, Bregnian F: Pregnancy in a patient
with treated Wilson's disease. Am J Obstet Gynecol
163:1527, 1990
Nir A, Sorokin Y, Abramavici, H: Pregnancy and primary
biliary cirrhosis. IntJ Gynaecol Obstet 28:279, 1989
Whelton M, Sherlock S: Pregnancy in patients with hepatic cirrhosis: Management and outcome. Lancet 2:995998, 1968
Pajar A, Lehoczky D: Pregnancy and extrahepatic portal
hypertension. Gynecol Obstet Invest 30:193-197, 1990
Fallon H: Liver diseases, in Burrow G, Ferris T (eds):
Medical Complications During Pregnancy. Philadelphia,
PA, Saunders, 1990, pp 294-296
Lee WM: Liver Disease, in Gall SA et al (eds): Gleicher's
Principles and Practice of Medical Therapy in Pregnancy. Norwalk, CT, Appleton and Lange, 1991, pp 979980
Thung S, Gerber M: Diagnosis of cirrhosis: Definite vs
suggestive criteria, in EpsteinJ (ed): Differential Diagnosis in Pathology: Liver Disorders New York, NY, IgakuShoin, 1995, pp 72-73
Homburg R, Bayer I, Lurie B: Bleeding esophageal varices in pregnancy. J Repro Med 33:784, 1988
Lee W: Pregnancy in patients with chronic liver disease.
Gastroenterol Clin North Am 21:889-903, 1992
Reinisch J: Prenatal exposure to prednisone in humans
and animals retards intrauterine growth. Science
202:436-438, 1978
Crawford J, Johnson K, Jones K: Pregnancy outcome
after transplantation in women maintained on
cyclosporin immunosuppression. Repro Toxicol 7:156,
1993
Haagsma E: Successful pregnancy after orthoptic transplantation. Obstet Gynecol 74:442-443, 1989
Remond G: Propranolol and fetal growth retardation.
Semin Perinatol 6:142-147, 1982

Cirrhosis and Portal H ~ o n

29. Vassiladis S, Athanassalds I: Type II interferon may be a

potential hazardous theraputic agent during pregnancy.
BrJ Haematol 82:782-783, 1992
30. Yip D, Baker A: Liver diseases and pregnancy. Clin Perinatol 12:683, 1985
31. Klein N, Riley C: Liver Disease; Current Obstetric Medicine, in Mosby Year Book 1:99-124, 1991
32. GalambosJT: Alcoholic liver disease: Fatty liver, hepatitis, and cirrhosis, in BerkJE, Haubrich W, Kaiser M, et
al (eds): Bockus Gastroenterology (ed 4). Philadelphia,
PA, Saunders 1985, pp 2985-3048
33. Varma R, Michelson M, Borhowf H: Pregnancy in cirrhotic and noncirrhotic portal hypertension. Obstet
Gynecol 50:217, 1977
34. Palmer E: Effect of Valsalva maneuver on esophageal
varices. Am J Med Sci 227:661-662, 1954
35. Soto-Albor C, Rayburu W, Taylor L, et al: Portal hypertension and hypersplenism in pregnancy secondary to
chronic schistosomiasis. J Repro Med 29:345-348, 1984
36. Heriot J, Steven C, Sattin P.d Elective forceps delivery
and extradural anesthesia in a primigravida with portal
hypertension and oesophageal varices. BrJ Anes 76:325327, 1996
37. Grace ND: Diagnosis and treatment of gastrointestinal
bleeding secondary to portal hypertension. American
College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 92:1081-1091, 1997
38. DaviesJ, Robson J: Effects ofvassopressin, adrenalin and
noradrenalin on the mouse fetus. BrJ Pharmaco138:446,
1970
39. Pauzner D, Wolman I, Niv D, et al: Endoscopic sclerotherapy in extrahepatic portal hypertension in pregnancy. A m J Obstet Gynecol 164:152-154, 1991
40. Schubert T, Smith O, Kirkpatrick S: Improved survival in
variceal hemorrhage with emergent sclerotherapy. Am J
Gastroenterol 82:1134-1137, 1987
41. Kochnor R, Goenka M, Mehta S: Endoscopic sclerotherapy during pregnancy. AmJ Gastroentero185:1132-1135,
1990
42. Iwase H, Monse K, Kawase T, et al: Endoscopic sclerotherapy for esophageal varices during pregnancy. J Clin
Gastroenteroi 18:80-83, 1994
43. Vilinkas J, Joyenes R, Serlin O: Hepatic sarcoidosis and
portal hypertension. Am J Surg 120:393-399, 1970

165

44. Summerskill W: Theraputic constraints in hepatic insufficiency. Adv Int Med 18:411-424, 1972
45. Walden R, Ben-Rafael Z: Fatal disruption of a splenorenal shunt after multiple pregnancies. Gynecol Obstet
Inves 28:106-107, 1989
46. Brown H: Splenorenal shunt during pregnancy. Am Surg
37:441-443, 1971
47. Salam A, Warren D: Distal splenorenal shunt for the
treatment of variceal bleeding during pregnancy. Arch
Surg 105:643-644, 1972
48. Lalfer S, Darby M: Pregnancy and liver transplantation.
Obstet Gynecol 76:1083, 1990
49. Fair J, Klein A, Feng T: Intrapartum orthotopic liver
transplantation with successful outcome of pregnancy.
Transplantation 50:534, 1990
50. Kato T, NeryJ, MorcosJ, et al: Successful living related
transplantation in an adult with fulminant hepatic failure. Transplantation 64:415-417, 1997
51. Hamilto M, Alcock IL Magis L, et al: Liver transplantation during pregnancy. Liver Trails Proc 25:2967-2968,
1993
52. Finlay D, Foshager M, Longly D, et al: Ischemic injury
to the fetus after maternal liver transplantation. J Ultras
Med 13:145-148, 1994
53. O'Grady J, Day E, Toole A: Slenic artery aneurysm in
pregnancy. Obstet Gynecoi 50:627, 1977
54. Barrett J, Caldwell B: Association of portal hypertension
and ruptured splenic artery Aneurysm in Pregnancy. Obstet Gynecol 57:255-257, 1981
55. Brass P: Splenic artery rupture during pregnancy. Am J
Obstet Gynecol 128:228-229, 1977
56. Yaron Y, Lessing J, Peyser R: Abruptio placentae associated with perforated appendicitis and Generalized Peritonitis. A m J Obstet Gynecol 166:14-15, 1992
57. Korston M, Zieber M: Nutrition in Pancreatic and Liver
Disease. in Shills M, OlsonJ, Shike (eds): Modern Nutrition in Health and Disease. Philadelphia, PA, Lea and
Febiger, 1994, pp 1071-1073
58. Manju M: Vitamin A and its congeners. Semin Perinatol
21:135-141, 1997
59. Weinsier IL Morgan S: Nutritional Support of Special
Medical Problems, Fundamentals of Clinical Nutrition.
St- Louis, MO, Mosby Yearbook, 1993, pp 163-165