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LIVER DISEASES WITH PREGNANCY
LIVER DISEASES WITH
PREGNANCY
Dr Walid Abdalla Mohamed Obstetrics & Gynecology Dept . Faculty of Medicine Zagazig University
Dr Walid Abdalla Mohamed
Obstetrics & Gynecology Dept .
Faculty of Medicine
Zagazig University
Introduction Liver disease is a rare complication of pregnancy, but when it occurs it may do
Introduction
Liver disease
is
a
rare complication of
pregnancy, but when it occurs it may do so
in a dramatic and tragic fashion for both
mother and infant. Diseases such as acute
fatty liver of pregnancy (AFLP) may begin
gradually with mild symptoms and liver
enzyme abnormalities but, if left untreated,
can progress to jaundice, liver failure, and
death.
( Bacq & Riely , )2004
• Some of the normal physiologic changes of pregnancy can mimic abnormalities associated with liver disease.
• Some of the normal physiologic changes of
pregnancy can mimic abnormalities
associated with liver disease.
• Telangiectasia, particularly on the chest,
back, and face, and palmer erythema occur
in up to 60 percent of normal pregnant
women but disappear after delivery.
(Riely, 2001)
Anatomical, Physiological, and Biochemical changes during pregnancy.
Anatomical, Physiological, and
Biochemical changes during
pregnancy.
Anatomic Changes: • Liver weight increases during pregnancy has not been documented. Liver size is difficult
Anatomic Changes:
• Liver weight increases during pregnancy has not
been documented. Liver size is difficult to
estimate in pregnancy, but records fail to show
any substantial increase in liver weight in
comparison with nonpregnant controls.
• Therefore, detection of hepatomegaly is strong
evidence for the presence of liver disease.
(Fagan, 1986)
Summary of physiological and biochemical changes in the liver during pregnancy
Summary of physiological and biochemical changes in the
liver during pregnancy

Increased:

Alkaline phosphatase levels rise threefold or fourfold due to

placental production

Clotting factor changes create a hypercoagulable state

Decreased:

Gallbladder contractility

Uric acid levels

Albumin, total protein, and antithrombin III concentrations

No change:

Liver aminotransferase levels (aspartate aminotransferase,

alanine aminotransferase(more specific as it rises only in liver injury) ,gamma-glutamyl transferase)

Bilirubin level Prothrombin time

Spectrum of liver diseases in pregnancy (Fleming & Zein, 2005)
Spectrum of liver diseases in
pregnancy
(Fleming & Zein, 2005)
• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

Liver diseases induced by pregnancy

– First trimester • Hyperemesis gravidarum – Second and third trimesters • Intrahepatic cholestasis of pregnancy
– First trimester
• Hyperemesis gravidarum
– Second and third trimesters
• Intrahepatic cholestasis of pregnancy
• HELLP syndrome (hemolysis, elevated liver enzymes,
low platelet counts )
• Acute fatty liver of pregnancy
• Liver diseases coincidental with but not induced by pregnancy – Acute viral hepatitis and other
• Liver diseases coincidental with but not
induced by pregnancy
– Acute viral hepatitis and other viral infections
– Alcohol-related diseases
– Gallstone disease
– Budd-Chiari syndrome
• Preexistent liver diseases – Portal hypertension, cirrhosis, primary biliary cirrhosis – Autoimmune hepatitis – Wilson
• Preexistent liver diseases
– Portal hypertension, cirrhosis, primary biliary
cirrhosis
– Autoimmune hepatitis
– Wilson disease
– Chronic infection with hepatitis B or hepatitis
C virus
– Alcoholic liver disease
• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

Liver diseases induced by pregnancy

– First trimester • Hyperemesis gravidarum – Second and third trimesters • Intrahepatic cholestasis of pregnancy
– First trimester
• Hyperemesis gravidarum
– Second and third trimesters
• Intrahepatic cholestasis of pregnancy
• HELLP syndrome (hemolysis, elevated liver enzymes,
low platelet counts )
• Acute fatty liver of pregnancy
Hyperemesis gravidarum
Hyperemesis gravidarum

Def:* severe nausea and vomiting and unresponsive to simple dietary modification and anti-emetics.

* vomiting suffiecently severe to produce weight loss, dehydration ,alkalosis from loss of hydrochloric acid and hypokalemia

incidences : vary and appear to be ethnic and familial prediction and the risk increase among-obesity , nulliparity, and twin gestation.

hospitalization rate is about 0.5-0.8 % and with those have

previous history up to 20% require hospitalization.

Pregnancy-Unique Quantification of Emesis/Nausea (PUQE) index : Total score is sum of replies to each of

Pregnancy-Unique Quantification of Emesis/Nausea (PUQE) index:

Total score is sum of replies to each of the three questions. Nausea Score: Mild NVP = ≤6; Moderate NVP = 7–12; Severe NVP = ≥13

Etiology:

- High or rapid rise in serum level of pregnancy related hormones (HSG,E2, progesterone,placental growth hormone, prolactin,thyroxine and adreno-cortical

hormone)

-There is some studies implicated psychological component

- for unknown reason a female fetus

increase the risk by 1.5 folds.

There is small evidence for the association between hyperemesis and H.pylori infection.

Complications:

- Acute renal failure from dehydration , and may require 5 day dialysis when S. creatinine

reach 10.7 mg/l

-Life-threating complication of retching include

Mallory-weiss tears, rupture esophagus,

pneumothorax and pneumomediastinum

Mallory Weiss tear syndrome

Mallory Weiss tear syndrome

Thiamine deficiency will lead to Wernicke encephalopathy half of patient have the

triad of : ( confusion,ocular findings and Ataxia) and MR imaging findings , late

sequelae are common and include

blindness,convulsions and coma

Vitamin K deficiency may lead to maternal coagulopathy and fetal intracranial

hemorrhage.

• Laboratory testing demonstrates abnormal liver values in up to 50% of affected patients; the most
• Laboratory testing demonstrates abnormal
liver values in up to 50% of affected
patients; the most sensitive test is the
ALT, which may rise as high as 1000 U.
• Severely affected patients also have
elevations in bilirubin.
Antiemetic therapy is helpful rectal or oral as first line Improvement in the nausea and vomiting
Antiemetic therapy is helpful rectal or oral
as first line
Improvement in the nausea and vomiting
and resolution of the liver test abnormalities
occur when most affected patients are
given intravenous fluids and put to gut rest,
correct dehydration , ketonemia and acid
base imbalances.
. Corticosteroid therapy has been reported
with little success.however pt treated by
corticosteroids have fewer readmission

Thiamine is given 100 mg to prevent Wernicke encephalopathy

if severe unresponsive vomiting appropriate

steps should be taken to exclude underlying disease( gastroenteritis,cholecystitis,

pancreatitis,hepatitis peptic ulcer , preeclampsia and AFLP

it was found that high level of thyroxine is implicated in hyperemesis more than HCG level

If associated psychiatric and social factors improvement while hospitalization occur

but may relapse after discharge in these

situation assistance with psychosocial problem is beneficial Its important to know that

Patients affected with hyperemesis gravidarum have no increased rate of prematurity, infants with low birth weight,
Patients affected with hyperemesis gravidarum
have no increased rate of prematurity, infants
with low birth weight, or infants with birth
defects .
• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

Liver diseases induced by pregnancy

• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third
• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

First trimester

• Hyperemesis gravidarum
• Hyperemesis gravidarum
• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

Second and third trimesters

• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

Intrahepatic cholestasis of pregnancy Preeclampsia, eclampsia, and the HELLP syndrome (hemolysis, elevated liver enzymes, low platelet counts) Acute fatty liver of pregnancy

• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third
Intrahepatic Cholestasis of Pregnancy • The syndrome has been variously called recurrent jaundice of pregnancy, cholestatic
Intrahepatic Cholestasis of
Pregnancy
• The syndrome has been variously called
recurrent jaundice of pregnancy, cholestatic
jaundice of pregnancy,ictrus gravidarum,
jaundice of late pregnancy, and hepatosis of
pregnancy. ICP, however, is the preferred term,
because jaundice is inconstant in any type of
cholestatic disorder .
(Gonzalez-Peralva et al., )1996
• The frequency of ICP is clearly higher among certain ethnic groups, including Scandinavians and Chileans.
• The frequency of ICP is clearly higher
among certain ethnic groups, including
Scandinavians and Chileans. In the latter
group, ICP may appear in 2.4% or more of
pregnancies, the highest reported incidence
in the world. The incidence is quite high
(20.9%) in twin pregnancies.
• Several studies have demonstrated a
familial and genetic predisposition to the
syndrome in Sweden, Chile, and the United
States.
(Lammert, et al., 2000)

Clinical presentation

Pruritus is the dominant and initial symptom and appears in the third trimester in more than
Pruritus
is
the
dominant
and
initial
symptom and appears in the third trimester in
more than 70% of cases. Most of the
remaining
patients
date
their
onset
of
symptoms to the second trimester.some cases
reported
in
the
first
trimester
with
hyperplacentosis and a triploid fetus.

The symptom may become very severe and usually involves the trunk and the extremities, including the palms and the soles of the feet. As a result of the pruritus, insomnia, fatigue, and even mental disturbances have been reported

Many patients report the appearance of dark urine without frank jaundice shortly after the onset of
Many patients report the appearance of dark
urine without frank jaundice shortly after
the onset of pruritus. Only a minority of
patients develop obvious jaundice, and this
is usually mild.
It is notable that abdominal pain, biliary colic,
fever, anorexia, nausea, vomiting, and
arthralgias are absent.
• The improvement in both pruritus and jaundice begins to occur quite promptly after delivery, most
• The improvement in both pruritus and
jaundice begins to occur quite promptly
after delivery, most often within 24 hours.
However, jaundice may continue for
several days after delivery, and some of
the abnormal chemistry profiles persist for
as long as several months.
• Subsequent pregnancies are frequently
accompanied by recurrences of the
syndrome.
Biochemical Changes CLINICAL FEATURES BIOCHEMICAL CHANGES Pruritus Jaundice * No Anorexia or malasie 2 nd or
Biochemical Changes
CLINICAL FEATURES BIOCHEMICAL CHANGES
Pruritus
Jaundice *
No Anorexia or malasie
2 nd or 3 rd trimester onset *
Recurrent*
Familial *
Serum bile acid
Alkaline Phosphatase
5' Nucleotidase
GGTP
Bilirubin (total)
AST/ALT
Prothrombin time
Cholesterol
Triglyceride
-10to 100 fold
-7to 10 fold 
Two Folds
Normal to slight 
Normal to 5 mg/dL
 not exceed 250 U/L
Normal to twofolds
Two to Fourfolds 
Normal to twofolds 
Effects on the Mother • Although earlier reports suggested that the only effect of ICP on
Effects on the Mother
• Although earlier reports suggested that the only
effect of ICP on the mother was related to the
discomfort of pruritus, more recent studies have
suggested more serious complications. These
include an increased risk of postpartum
hemorrhage, especially in those given
cholestyramine, and an increased risk for the
development of gallstones after pregnancy.
(Glantz, et al., 2005)
Effects on the Fetus • The implications of ICP for the fetus are considerably more ominous.
Effects on the Fetus
• The implications of ICP for the fetus are
considerably more ominous. An increased
incidence of prematurity and fetal death has been
reported in several studies. Fetal distress is
reported in one third of patients, leading to
cesarean section in 30% to 60% of cases and
prematurity in over 50% in some series. Stillbirths
are recorded in more than 9%. These outcomes
are more likely if the disorder begins earlier in
pregnancy. Thus, ICP very clearly increases the
risks to the fetus .
( Glantz, et al., )2004
• Therapy is directed at alleviating pruritus in the mother. Ursodeoxycholic acid has been used successfully
Therapy is directed at alleviating pruritus in the
mother. Ursodeoxycholic acid has been used
successfully in the treatment of cholestasis.
Improvement in both liver function test results and
the symptom of pruritus has been documented in
women with ICP treated with a standard
15mg/kg/day dosage. A larger dosage, 20 to 25
mg/kg/day has been shown to be effective with no
adverse affects on either mother or baby.
(Mazella et al., 2001)

Treatment

• Phenobarbital in a dosage of 100 mg/day has been reported to be effective in approximately
• Phenobarbital in a dosage of 100 mg/day has
been reported to be effective in approximately
50% of patients.
Cholestyramine may be somewhat effective and
is usually given in a dosage of 4 g four or five
times per day.
• Cholestyramine may worsen the malabsorption of
fats and fat-soluble vitamins. Therefore, the
prothrombin time must be monitored in patients
treated with this regimen, and parenteral vitamin
K should be given before delivery.
(Eloranta et al., 2002)
• Antihistamininc and topical emollients may give some relif. • Some investigators recommend elective induction at
• Antihistamininc and topical emollients may
give some relif.
• Some investigators recommend elective
induction at 38 weeks or as early as 36
weeks in the presence of jaundice or if the
fetus's lungs have matured.
• Antihistamininc and topical emollients may give some relif. • Some investigators recommend elective induction at
• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

Liver diseases induced by pregnancy

– First trimester • Hyperemesis gravidarum – Second and third trimesters • Intrahepatic cholestasis of pregnancy
– First trimester
• Hyperemesis gravidarum
– Second and third trimesters
• Intrahepatic cholestasis of pregnancy
• HELLP syndrome (hemolysis, elevated liver enzymes,
low platelet counts )
• Acute fatty liver of pregnancy
HELLP Syndrome • The HELLP syndrome is a multi-system disease variant of severe preeclampsia that is

HELLP Syndrome

• The HELLP syndrome is a multi-system disease variant of severe preeclampsia that is characterized by
• The HELLP syndrome is a multi-system disease
variant of severe preeclampsia that is
characterized by microangiopathic hemolytic
anemia (MAH) abnormal peripheral smear,
increased bilirubin <1.2 mg/dL, and increased
lactic dehydrogenase > 600 IU/L ,;
• Elevated liver enzymes aspartate
aminotransferase )AST( ≥ 72 IU/L, lactate
dehydrogenase (LDH) > 600 IU/ ,
• Thrombocytopenia (platelet count, <100,000/
mm3(, and, in the syndrome’s most severe form,
DIC .
• HELLP syndrome is more common among older multiparous women.
• HELLP syndrome is more common among older
multiparous women.

HELLP syndrome affects up to 20% of pregnancies involving severe preeclampsia.

• Although up to 11% of the cases occur before 27 weeks of gestation, most cases
• Although up to 11% of the cases occur before
27 weeks of gestation, most cases (70%) occur
between 27 and 36 weeks of gestation and
about a third occur after delivery. Exacerbations
may occur after delivery, followed by recovery
within 72 hours.

(Martin et al., 1999)

• HELLP syndrome is more common among older multiparous women. • HELLP syndrome affects up to
• Clinical presentation: • Frequent presenting symptoms include nausea, malaise, epigastric or right upper quadrant abdominal
Clinical presentation:
• Frequent presenting symptoms include nausea,
malaise, epigastric or right upper quadrant
abdominal pain (65%–90% of cases), and
edema. In a large series, HELLP syndrome was
observed with DIC (21% of patients), abruption
placenta (16%), acute renal failure (8%), and
pulmonary edema (6%). The maternal mortality
rate is approximately 1% to 4%, and the perinatal
mortality rate ranges from 10% to 20%,
depending on gestational age and severity of the
condition at the time of delivery .
(Sibai et al., )1993
Maternal morbidity in HELLP syndrome can be classified into the following four
Maternal morbidity in HELLP syndrome can
be classified into the following four

categories (in decreasing order of frequency) Coagulation disorders associated with hemorrhagic complications, Cardiopulmonary dysfunction, Central nervous system disorder and Hepatic or gastrointestinal dysfunction. (Isler et al., 1999)

• Women with HELLP syndrome should be considered to be at increased risk for obstetrical complications
• Women with HELLP syndrome should be
considered to be at increased risk for
obstetrical complications in subsequent
pregnancies (preterm deliveries, IUGR,
abruption-placenta), and the risk for
recurrence ranges from 4% to 25% .
Infants born to mothers with HELLP
syndrome are at risk for thrombocytopenia.
(Sibai et al., 1995)
differential diagnosis of HELLP syndrome Thrombotic coagulopathies Consumptive Miscellaneous disorders Hemolytic uremic syndrome AFLP Systemic lupus
differential diagnosis of HELLP
syndrome
Thrombotic coagulopathies
Consumptive
Miscellaneous
disorders
Hemolytic uremic syndrome
AFLP
Systemic lupus
Thrombotic
Sepsis
Antiphospholipid
thrombocytopenia purpura
Drug-induced hemolytic
anemia
Sepsis
DIC
Abruptio placentae
Amniotic fluid
embolism
syndrome
Cholecystitis
Appendicitis
DIC
Laboratory investigation
Laboratory investigation
Risk factors for HELLP syndrome include the following: • • • LDH level, > 1400 IU/L
Risk factors for HELLP syndrome include the
following:
LDH level, > 1400 IU/L
AST level, > 150 IU/L
ALT level, > 100 IU/L
• Platelet count, < 50,000/mm3
Uric acid level, > 7.8 mg/dL
• Creatinine level, > 1.0
• Creatine phosphokinase level, > 200 IU/L
Liver function present with shock and hemoperitoneum. The condition also may manifest hepatic infarcts with associated
Liver function
present with shock and hemoperitoneum. The
condition also may manifest hepatic infarcts with
associated fevers, high levels of aminotranferase
(N5000 IU/L), and anemia.

Patients usually are not jaundiced. Total bilirubin concentration rarely exceeds 1 to 2 mg.

HELLP syndrome rarely leads to subcapsular hemorrhage; hepatic rupture often leads to death of the mother and fetus. Typically, these patients

(Krueger et al., 1995)

Therapy and outcome
Therapy and outcome
• The maternal morbidity rate has been reported to be as high as 24%, but it
• The maternal morbidity rate has been reported
to be as high as 24%, but it ranges between 1%
to 4% in optimal medical environments. In
patients who died, the mean gestational age
was 31 weeks, and death was attributed to
sepsis, hemorrhagic shock, intracerebral insults,
and cardiac pulmonary failure. Investigators
found 16% maternal death rate attributed to
hepatic complications.
(Martin et al., 1999)
• The neonatal mortality rate associated with HELLP syndrome (10%–20%) has been attributed to placenta ischemia
• The neonatal mortality rate associated
with HELLP syndrome (10%–20%) has
been attributed to placenta ischemia
leading to abruption, extreme prematurity,
and intrauterine asphyxia. Factors
associated with perinatal survival in
preterm pregnancies with HELLP
syndrome include achievement of a birth
weight of at least 600g, elapsed time of 48
hours after medical therapy with steroids
for perinatal lung maturity, and caesarian
delivery.
(Barton & Sibai, 1992)
• Termination of pregnancy and the removal of the chorionic villi is the only therapy that
• Termination of pregnancy and the removal
of the chorionic villi is the only therapy that
minimizes maternal and fetal compromise.
Timing of delivery depends on the severity
of the maternal condition , fetal condition,
placenta reserve, and gestational age.
• HELLP syndrome - antepartum management • assess and stabilize the maternal condition • correct coagulopathy

HELLP syndrome - antepartum management

• HELLP syndrome - antepartum management • assess and stabilize the maternal condition • correct coagulopathy
• assess and stabilize the maternal condition • correct coagulopathy if DIC is present • give
• assess and stabilize the maternal condition
• correct coagulopathy if DIC is present
• give intravenous magnesium sulfate to prevent
seizures
• provide treatment for severe hypertension to
prevent stroke
• transfer to tertiary center if appropriate
• if subcapsular hematoma of liver, computed
tomography or ultrasound of the abdomen
• HELLP syndrome - antepartum management – evaluate fetal well-being • non stress test • biophysical
• HELLP syndrome - antepartum management – evaluate fetal well-being • non stress test • biophysical

HELLP syndrome - antepartum management

• HELLP syndrome - antepartum management – evaluate fetal well-being • non stress test • biophysical
– evaluate fetal well-being • non stress test • biophysical profile – timing of delivery •
– evaluate fetal well-being
• non stress test
• biophysical profile
– timing of delivery
• if > 34 weeks gestation, deliver
• if < 34 weeks gestation, administer corticosteroids,
then deliver in 48 hours
• HELLP syndrome - management for cesarean birth – use general anesthesia if platelet count is
• HELLP syndrome - management for cesarean birth – use general anesthesia if platelet count is

HELLP syndrome - management for cesarean birth

– use general anesthesia if platelet count is < 75,000 / mm 3 – transfuse 5
– use general anesthesia if platelet count is
< 75,000 / mm 3
– transfuse 5 to 10 units of platelets before
surgery if platelet count is < 50,000 / mm 3
– leave vesicouterine peritoneum open
– install subfascial drain
• HELLP syndrome - management for cesarean birth – schedule secondary closure of skin incision or
• HELLP syndrome - management for
cesarean birth
– schedule secondary closure of skin incision
or subcutaneous drain
– administer postoperative transfusions as
needed
– perform intensive monitoring for at least 48
hours postpartum
– consider dexamethasone (10 mg IV every 12
hours) until postpartum resolution of disease
occurs
• Liver diseases induced by pregnancy – First trimester • Hyperemesis gravidarum – Second and third

Liver diseases induced by pregnancy

– First trimester • Hyperemesis gravidarum – Second and third trimesters • Intrahepatic cholestasis of pregnancy
– First trimester
• Hyperemesis gravidarum
– Second and third trimesters
• Intrahepatic cholestasis of pregnancy
• Preeclampsia, eclampsia, and the HELLP syndrome
(hemolysis, elevated liver enzymes, low platelet counts)
• Acute fatty liver of pregnancy
Acute Fatty Liver of Pregnancy
Acute Fatty Liver of Pregnancy

Sheehan, first recognized this disorder as a distinct syndrome in 1940.

• He named it Acute yellow atrophy but it is now more commonly known as acute
• He named it Acute yellow atrophy but it is
now more commonly known as acute fatly
liver of pregnancy.
(Sheehan, 1940)
• (AFLP) is rare,, with a reported incidence of 1 in 13,000 to 1 in 16,000
• (AFLP) is rare,, with a reported incidence
of 1 in 13,000 to 1 in 16,000 deliveries.
• Preeclampsia is present in 50% or more of
cases of AFLP and may play a role in its
origin.
(Vigil-De, 2001)
• Reports of occasional recurrent cases and an association with a deficiency of long- chain 3-hydroxyacyl-cocnzyme
• Reports of occasional recurrent cases and
an association with a deficiency of long-
chain 3-hydroxyacyl-cocnzyme A (LCHAD)
dehydrogenase, raise the interesting notion
that, at least in some instances, this
disease results from an inborn error of
metabolism.
Clinical Characteristics
Clinical Characteristics
• AFLP occurs in the latter half of pregnancy, usually close to term. As with HELLP
• AFLP occurs in the latter half of pregnancy,
usually close to term. As with HELLP syndrome,
affected patients may present after delivery. It is
reported to occur more commonly in a first
pregnancy and in the presence of multiple
pregnancy, also prevalent in preeclampsia.
There are reports of an association between
AFLP and gestation of a male fetus.
(Castro et al., 1999)
• Affected women have nonspecific symptoms, including, prominently, nausea and vomiting, malaise and fatigue, jaundice, thirst,
• Affected
women
have
nonspecific
symptoms, including, prominently, nausea
and vomiting, malaise and fatigue,
jaundice,
thirst,
headache,
These can
and
altered
mental status.
be signs
and
symptoms of acute hepatic failure.
• In severe cases that go untreated, there is progression over hours or days to fulminant
• In severe cases that go untreated, there is
progression
over
hours
or
days
to
fulminant
hepatic
failure,
with
hepatic
coma,
hypo-glycemia,
severe
coagulopathy with hemorrhage from the
gastrointestinal
tract
or
the
uterus
and
death.
• Most affected women have signs of coexistent preeclampsia, including modest elevations in blood pressure,odema and
• Most affected women have signs of
coexistent preeclampsia, including modest
elevations in blood pressure,odema and
protienuria .

Polydipsia

With or without polyuria, frequently is an early symptom in AFLP.

Polydipsia With or without polyuria, frequently is an early symptom in AFLP. The patient may drink
Polydipsia With or without polyuria, frequently is an early symptom in AFLP. The patient may drink

The patient may drink 2 or 3 liters of liquids overnight. it often exceeds the magnitude of vomiting. It has been interpreted as a transient

diabetes insipidus.
diabetes insipidus.

(Cammu et al., 1987)

Laboratory tests
Laboratory tests

Clinical features

Biochemical changes

Nausea, Vomiting Malaise, Fatigue Jaundice

Bilirubin (total) AST/ALT GGTP

Slight , normal normal to 1000 U Slight

Abd. Pain

Prothrombin time

Preeclampsia

Fibrinogen



Coma

Uric acid

polydipsia

Ammonia

Bleeding

Glucose

Onset in second half of gestation;

Leukocytes

postpartum onset possible

platelets

,

• Imaging may be useful; fat in the liver has been demonstrated in AFLP with ultrasonography
• Imaging may be useful; fat in the liver has
been demonstrated in AFLP with
ultrasonography and CT scanning
however none are particulary reliable with
poor sensitivity.
• Liver biopsy is not indicated for diagnosis
(Barton et al., )1998
Characteristics of HEELP syndrome and AFLP
Characteristics of HEELP syndrome and AFLP

HELLP

AFLP

Early Platelet count, 50,000-150,000/mm 3 LDH level, 600-1400 IU/L Bilirubin/PT levels, Normal

Early Platelet count, >100,000/mm 3 Uric acid abnormal LDH level, normal PT- Abnormal Bilirubin/ levels, abnormal

Late

Bilirubin/PT levels, abnormal

late

Platelet count, <50,000/mm 3 LDH level, >1400 IU/L

Platelet count, <100,000/mm 3 LDH level, < 600 IU/L Hypoglycemia PT Abnormal

Complications

Complications cerebral edema, renal failure (60%), hypoglycemia (53%),  infections (45%)  gastrointestinal hemorrhage (33%), 
cerebral edema, renal failure (60%), hypoglycemia (53%),  infections (45%)
cerebral edema,
renal failure (60%),
hypoglycemia (53%),
infections (45%)
Complications cerebral edema, renal failure (60%), hypoglycemia (53%),  infections (45%)  gastrointestinal hemorrhage (33%), 

gastrointestinal hemorrhage (33%), coagulopathy (30%), fetal death severe postpartum hemorrhage

Complications cerebral edema, renal failure (60%), hypoglycemia (53%),  infections (45%)  gastrointestinal hemorrhage (33%), 
MANAGMENT All patients should be hospitalized as soon as the diagnosis of AFLP is suspected Moderate
MANAGMENT
All patients should be hospitalized as soon as
the diagnosis of AFLP is suspected
Moderate or severely affected patients
(encephalopathic, deeply jaundiced, with a
prothrombin time less than 40% of the
control), or with any extrahepatic
complications, should be attended in
intensive care units .

it seems convenient to maintain glucose infusions . Because of the risk of a sudden hypoglycemia until a full metabolic recovery is obtained.

it seems convenient to maintain glucose infusions . Because of the risk of a sudden hypoglycemia

Treatment of AFLP begins with delivery. The route should be guided by obstetric indications. Cesarean section is not always

necessary; vaginal delivery can be accomplished.
necessary; vaginal delivery can be
accomplished.
• With delivery , resolve of hepatic dysfunctions begins, the initial sign of improvement being a
• With delivery , resolve of hepatic dysfunctions begins, the initial sign of improvement being a

With delivery ,resolve of hepatic dysfunctions begins, the initial sign of improvement being a fall in prothrombin time elevation.

• The management should include maximal support in an intensive care unit by a team that
• The management should include maximal
support in an intensive care unit by a team
that includes both obstetricians and

hepatologists. Liver transplantation for AFLP has been reported.

• With delivery , resolve of hepatic dysfunctions begins, the initial sign of improvement being a
• With delivery , resolve of hepatic dysfunctions begins, the initial sign of improvement being a

(Paternoster et al.,

)2004

There are no residua after AFLP, and complete recovery of the affected patient should be expected. Cases of recurrent AFLP, as well as cases of nonketotic hypoglycemia in the offspring, have been reported

• There are no residua after AFLP, and complete recovery of the affected patient should be
• There are no residua after AFLP, and complete recovery of the affected patient should be

There are two problems develop around these time one is DI due to elevated vasopressinase

• There are no residua after AFLP, and complete recovery of the affected patient should be
• There are no residua after AFLP, and complete recovery of the affected patient should be

cause by diminsihed production of inactivating enzyme another is acute pancreatitis.

• There are no residua after AFLP, and complete recovery of the affected patient should be
PRE-EXISTENT LIVER DISEASE
PRE-EXISTENT LIVER
DISEASE
• Preexistent liver diseases – Portal hypertension, cirrhosis, primary biliary cirrhosis – Autoimmune hepatitis – Wilson
• Preexistent liver diseases
– Portal hypertension, cirrhosis, primary biliary
cirrhosis
– Autoimmune hepatitis
– Wilson disease
– Chronic infection with hepatitis B or hepatitis
C virus
– Alcoholic liver disease
• Pregnancy is uncommon in women with established liver cirrhosis, including primary biliary cirrhosis, because they
• Pregnancy is uncommon in women with
established liver cirrhosis, including primary
biliary cirrhosis, because they tend to be past
childbearing age or infertile due to the condition.
A life-threatening complication of liver cirrhosis
is variceal bleeding associated with portal
hypertension. Treating bleeding esophageal
varices with nonselective beta-blockers, band
ligation, and octreotide is safe and effective
during pregnancy.
(Helmy &Hayes, 2001)
• Ursodeoxycholic acid (FDA category B) at doses of 10 to 13 mg/kg is treatment of
• Ursodeoxycholic acid (FDA category B) at
doses of 10 to 13 mg/kg is treatment of
choice for primary biliary cirrhosis and may
be continued during pregnancy and
breastfeeding.
(Sternlieb, 2005)
• The presence of severe portal hypertension with esophageal varices is associated with an increased risk
• The presence of severe portal hypertension with
esophageal varices is associated with an
increased risk of hemorrhage during pregnancy.
The use of sclerotherapy for bleeding varices
during pregnancy may provide a safe alternative
to portacaval anastomosis and has been
reported to be effective.
(Pauzner et al., 1991)
• Preexistent liver diseases – Portal hypertension, cirrhosis, primary biliary cirrhosis – Autoimmune hepatitis – Wilson
• Preexistent liver diseases
– Portal hypertension, cirrhosis, primary biliary
cirrhosis
– Autoimmune hepatitis
– Wilson disease
– Chronic infection with hepatitis B or hepatitis
C virus
– Alcoholic liver disease
• Women with autoimmune hepatitis can become pregnant and can still carry a successful pregnancy. The
• Women
with
autoimmune
hepatitis
can
become pregnant
and
can
still
carry
a
successful pregnancy. The course of the
disease
is
unpredictable.
Although
spontaneous remission
may
occur,
maternal
death
and
exacerbation
during
pregnancy and after delivery have been
reported.
(Heneghan et al., 2001)
Corticosteroids are the treatment of choice in autoimmune hepatitis and appear to be safe in pregnancy.
Corticosteroids are the treatment of choice in
autoimmune hepatitis and appear to be safe in
pregnancy. They seem to induce rapid remission
of autoimmune hepatitis, whether during the initial
onset or during a flare. Although azathioprine is in
FDA category D (positive evidence of risk), we
have little evidence that it is toxic in pregnancy.
Data from patients with inflammatory bowel
disease suggest it is likely to be safe in pregnancy
at dosages less than 100mg/day.
(Moskovitiz et al., 2004)
• Preexistent liver diseases – Portal hypertension, cirrhosis, primary biliary cirrhosis – Autoimmune hepatitis – Wilson
• Preexistent liver diseases
– Portal hypertension, cirrhosis, primary biliary
cirrhosis
– Autoimmune hepatitis
– Wilson disease
– Chronic infection with hepatitis B or hepatitis
C virus
– Alcoholic liver disease
Wilson disease is a rare disorder characterized by cirrhosis, neurological abnormalities, and less commonly hematological and
Wilson
disease
is
a
rare
disorder
characterized by cirrhosis, neurological
abnormalities,
and
less
commonly
hematological and renal dysfunction .
D-Penicillamine and trientine have been
used during pregnancy. However, the
dosage should be reduced to the minimum
necessary dose, which is about 25% to
50% of the dose the patient had been
taking before the pregnancy.
(Roberts & Schilsky, 2003)
• Zinc is the agent of choice for Wilson disease during pregnancy because of its safety
• Zinc is the agent of choice for Wilson
disease during pregnancy because of its
safety for the fetus. It should be
maintained throughout the pregnancy at
50 mg three times a day.
(Brewer et al., 2000)
Liver diseases coincidental with but not induced by pregnancy
Liver diseases coincidental
with but not induced by
pregnancy
Liver diseases coincidental with but not induced by pregnancy – Acute viral hepatitis and other viral
Liver diseases coincidental with but not
induced by pregnancy
– Acute viral hepatitis and other viral infections
– Alcohol-related diseases
– Gallstone disease
– Budd-Chiari syndrome
Hepatitis A Characteristics Older name Hepatitis A Infectious hepatitis Virus type Virus size Incubation period Transmission
Hepatitis A
Characteristics
Older name
Hepatitis A
Infectious hepatitis
Virus type
Virus size
Incubation period
Transmission
Vertical transmission to fetus
RNA
27 nm
15 – 50 days
Fecal – oral
Not observed
Serologic diagnosis
Hepatitis A antibody
IgM and IgG types
Maximum infectivity
Prodrome
Carrier state
None
Acute clinical forms
Asymptomatic to
fulminant
Chronic clinical forms
None
• The clinical syndrome of acute HAV infection consists of vague flu-like symptoms with fatigue, weakness,
• The clinical syndrome of acute HAV infection
consists of vague flu-like symptoms with fatigue,
weakness, nausea, and loss of appetite. The
onset is usually abrupt. A variety of extrahepatic
manifestations including myalgia, arthralgias,
arthritis, and urticaria, may occur.
• Other forms of HAV infection include cholestatic
hepatitis, with a prolonged course marked by
itching and jaundice.
(Willner, et al., 1998)
• The characteristic changes in liver function test findings include marked elevations in AST and ALT.
• The characteristic changes in liver function
test findings include marked elevations in
AST and ALT. Most often, these reach
levels of 1000 to 2000 U during the early
part of the infection. Elevations in bilirubin
and alkaline phosphatase also occur but
are more unpredictable.
(Fiore, et al., 2003)
• There is substantial evidence that pregnancy does not alter the course of HAV infection. However,
• There is substantial evidence that pregnancy does
not alter the course of HAV infection. However, a
higher incidence of fulminant disease during
pregnancy has been reported in developing
nations. Concurrent malnutrition has been a
suspected cause. If the course of HAV infection is
severe, it may precipitate premature labor in
women in the third trimester of pregnancy. There is
no evidence that HAV causes birth defects, and
there is no evidence of maternal-fetal transmission.
(Atkinson, et al., 2002)
• Clinical management of pregnant patients with HAV infection does not differ from that of those
• Clinical management of pregnant patients with
HAV infection does not differ from that of those
who are not pregnant. However, hospitalization
may be indicated, specially during the last
trimester and in the presence of severe anorexia,
nausea, and vomiting.
• In rare circumstances in which the mother has
acute HAV infection at the time of delivery,
immune serum globulin may be administered to
the infant. Even under these conditions, the risk of
transmission to the infant seems very small.
(Fiore, et al., 2003)
Hepatitis B
Hepatitis B
Hepatitis B

Characteristics

Hepatitis B

Older name

Serum hepatitis

Virus type

DNA

Virus size

42 nm

Incubation period

30 180 days

Transmission

Parentral or body fluid

Vertical transmission to fetus

Common

Serologic diagnosis

HBs Ag,

HBs Ab, IgM, and IgG

types

HBe Ag, Ab, Hepatitis B virus DNA

Maximum infectivity

Prodrome or HBe Ag Positive

Carrier state

5 10%

Acute clinical forms

Asymptomatic to fulminant

Chronic clinical forms

Chronic persistent hepatitis Chronic active hepatitis Cirrhosis

The incidence of the HBV carrier state among pregnant women is variable and depends on the
The incidence of the HBV carrier state
among pregnant women is variable and
depends on the patient group studied. The
incidence of HBV carriers is considerably
higher in populations in which drug abuse
or with high incidence of sexual
promiscuity.
(Van Zonneveld, et al., 2003)
• Evidence suggests that transmission of HBV to infants is common when mothers have acute infection
• Evidence suggests that transmission of
HBV to infants is common when mothers
have acute infection in the third trimester
or when they are chronic carriers of HBV
infection and have positive results of
serum tests for HBeAg or HBV DNA.
(Su, et al., 2004)
• In women with chronic hepatitis B infection, taking lamivudine ( nucleotide analogue used against HIV
• In women with chronic hepatitis B infection,
taking lamivudine ( nucleotide analogue
used against HIV and HBV alone or with
combination with other anti-viral) before
becoming pregnant and continuing to take it
throughout the pregnancy has been
reported to lower rates of transmission of
the virus from mother to newborn.
(Su, et al., 2004)
• The administration of hyperimmune globulin and HBV vaccine protects 90% to 95% of infants from
The
administration
of
hyperimmune
globulin and HBV vaccine protects 90% to
95% of infants from HBV infection.
It is recommended that 0.5 ml, of HBIG
be
given at birth and that three doses of HBV
vaccine be given beginning at birth.
(Sehgal, et al., 1992)
Hepatitis C
Hepatitis C
Hepatitis C

Characteristics

 

Hepatitis C

Older name

Non A non B hepatitis

Virus type

RNA

Virus size

30-60 nm

Incubation period

30

160 days

Transmission

Parentral sporadic

Vertical transmission to fetus

Uncommon

Serologic diagnosis

Hepatitis C antibody

RNA by PCR

Maximum infectivity

HIV co- infected

Carrier state

50

85%

Acute clinical forms

Asymptomatic to sever relapsing

Chronic clinical forms

Chronic persistent hepatitis Chronic active hepatitis Cirrhosis

• The rate of vertical transmission of hepatitis C is less than 5%. The risk is
• The rate of vertical transmission of hepatitis
C is less than 5%. The risk is higher if the
mother
is
co-infected
with
human
immunodeficiency
virus
(HIV),
if
she
is
viremic at
the time
of delivery,
if
her viral
DNA load is greater than 1 million copies/ml,
and
if
the
time
from
the
rupture
of
membranes to delivery is more than 6 hours.
The
mode of
delivery does
not seem
to
influence
the
rate
of
transmission from
mother to child.
(Ceci et al., 2001)
• Breastfeeding is not considered a risk factor for transmission, even though viral RNA has been
• Breastfeeding
is
not
considered
a
risk
factor for transmission, even though viral
RNA has been detected in breast
.
(Steininger et al., 2003)
• Newborns of infected mothers should be tested at 12 to 18 months of age, when
• Newborns of infected mothers should be
tested at 12 to 18 months of age, when IgG
antibodies to hepatitis C virus that may
have passively transferred from the
placenta to the fetus would have been lost,
and the persistence of hepatitis C viral RNA
would indicate infection with hepatitis C.
(Ferrero et al., 2003)
• Interferon is in FDA category C, and ribavirin is in category X. Both drugs are
• Interferon
is
in
FDA
category
C,
and
ribavirin is in category
X.
Both drugs are
contraindicated in pregnancy. If a woman
gets
pregnant
while
on combination
therapy, then both drugs should be
stopped, and she should be advised that
she has already
put
the fetus
at
risk
of

teratogenicity. (Resti et al., 2003)

Herpes simplex virus
Herpes simplex virus
Herpes simplex virus • It can cause fulminant liver failure and death if infection occurs during

It can cause fulminant liver failure and death if infection occurs during pregnancy, and the rate

of transmission to the fetus can reach 30% to 50% if the primary episode occurs at
of transmission to the fetus can reach 30% to
50% if the primary episode occurs at delivery.
• About 90% of pregnant women with this infection have abnormal liver enzyme tests and an
• About 90% of pregnant women with this
infection have abnormal liver enzyme tests
and an abnormal prothrombin time.
Acyclovir (FDA pregnancy category B) is
very effective if promptly given at doses of
400 mg three times daily for 5 to 7 days,
and early delivery is not required.
(Nigro , et al., 2003)
Cytomegalovirus • Infection may remain asymptomatic in pregnant women, and the prognosis is favorable. The risk
Cytomegalovirus
• Infection
may
remain
asymptomatic in
pregnant women, and the prognosis is
favorable. The risk of transmission to the
fetus and of congenital abnormalities
is
highest when acute infection occurs in the
first 22 weeks of pregnancy. Termination of
the pregnancy may be an option after
appropriate counseling regarding the
potential serious risks to the infected fetus.
(Benachi A, et al., 2003)
Liver diseases coincidental with but not induced by pregnancy – Acute viral hepatitis and other viral
Liver diseases coincidental with but not
induced by pregnancy
– Acute viral hepatitis and other viral infections
– Alcohol-related diseases
– Gallstone disease
– Budd-Chiari syndrome
Alcohol use • Women are two to four times more likely than men to develop alcoholic
Alcohol use
• Women are two to four times more likely
than men to develop alcoholic liver
disease for the same amount of alcohol
ingested, and they exhibit a tendency to
disease progression even with abstinence.
(Pares et al., 1986)
• Continued drinking during pregnancy may lead to miscarriage, stillbirth, prematurity, growth retardation, and the fetal
• Continued drinking during pregnancy may
lead to miscarriage, stillbirth, prematurity,
growth retardation, and the fetal alcohol
syndrome (growth retardation, behavioral
disturbances ,cardiac defects, spinal
defects, and craniofacial anomalies).
Alcohol abstinence throughout pregnancy
should be emphasized.
(Lemoine et al., )2003
Liver diseases coincidental with but not induced by pregnancy – Acute viral hepatitis and other viral
Liver diseases coincidental with but not
induced by pregnancy
– Acute viral hepatitis and other viral infections
– Alcohol-related diseases
– Gallstone disease
– Budd-Chiari syndrome
Gallstone disease • Pregnancy is a risk factor for sludge and gallstone formation. By the end
Gallstone disease
• Pregnancy is a risk factor for sludge and
gallstone formation. By the end of the third
trimester, 10% to 12% of pregnant women
have gallstones. Most gallstones disappear
spontaneously without causing symptoms.
If symptoms develop, the treatment may be
conservative or surgical, depending on the
severity of the symptoms.
• Laparoscopic surgery seems to be safe and should be considered. The optimal time for it
• Laparoscopic surgery seems to be safe
and should be considered. The optimal
time for it appears to be during the second
trimester, when fetal organogenesis is
completed and the size of the uterus does
not interfere with the surgery.
(Halpern , 1998)
Liver diseases coincidental with but not induced by pregnancy – Acute viral hepatitis and other viral
Liver diseases coincidental with but not
induced by pregnancy
– Acute viral hepatitis and other viral infections
– Alcohol-related diseases
– Gallstone disease
– Budd-Chiari syndrome
Budd-Chiari syndrome • Budd-Chiari syndrome is very rare and often insidious, manifesting after delivery. It is
Budd-Chiari syndrome
• Budd-Chiari
syndrome
is
very
rare
and
often insidious, manifesting after delivery. It
is characterized by thrombosis of the
hepatic veins and portal hypertension. Its
clinical manifestations include ascites,
hepatomegaly, and abdominal pain.
(Singh et al., 2000)
• Proper diagnosis and management require imaging studies such as Doppler ultrasonography and CT and liver
• Proper diagnosis and management require
imaging studies such as Doppler
ultrasonography and CT and liver biopsy.
Treatment with anticoagulants,
thrombolytics (warfarin is contraindicated in
pregnancy), diuretics, and portocaval
shunting may be required. Liver
transplantation is indicated when hepatic
decompensation develops.
(Deltenre et al., 2001)
Pregnancy Following Liver Transplantation
Pregnancy Following Liver
Transplantation
• Pregnancy after liver transplantation is often successful, but it must be regarded as a high
• Pregnancy after liver transplantation is
often successful, but it must be regarded as
a high risk, associated with hypertension,
preeclampsia, intrauterine growth
retardation, and prematurity. It is best
delayed until 1 to 2 years after grafting.
Pregnancy planned at least 2 years after
liver transplantation with stable allograft
function can have excellent maternal and
neonatal outcome.
(Nagy et al., 2003)
• In most female recipients studied, pregnancy does not appear to cause excessive or irreversible problems
• In most female recipients studied,
pregnancy does not appear to cause
excessive or irreversible problems in graft
function if the function of transplanted
organ is stable prior to pregnancy,
including twins if the woman has stable
hepatic function before pregnancy.
(Nagy et al., 2003)
• In female recipients in contrast to the general population, a high incidence of low birth-weight
• In female recipients in contrast to the
general population, a high incidence of low
birth-weight and prematurity has been a
consistent outcome. Immunosuppressive
agents may cause hypertension,
preeclampsia and renal dysfunction in
these recipients. However, there has been
no specific pattern of malformation in their
newborns or any apparent increase in the
incidence of small-for-gestational-age
newborns.
(Armenti et al., 2000)
• immunosuppression during pregnancy is not teratogenic and does not lead to congenital anomalies. • Nearly
• immunosuppression during pregnancy is
not teratogenic and does not lead to
congenital anomalies.
• Nearly 70% of pregnancies after systemic
administration of tacrolimus resulted in a
favourable outcome without any significant
effect on intrauterine growth.
(Jabiry et al., 2005)
Thus, during pregnancy, the female recipient may continue the immunosuppressive regimen to stabilize the transplanted liver
Thus, during pregnancy, the female recipient
may continue the immunosuppressive
regimen to stabilize the transplanted liver
function but prevent the effect on the
intrauterine growth.

Also, it was found that tacrolimus may decrease the incidence of onset of hypertension and toxemia of pregnancy.

• To the present, 37 cases of pregnancies after liver transplantation have been reported worldwide. •
• To the present, 37 cases of pregnancies
after liver transplantation have been
reported worldwide.
• In conclusion:
Under careful monitoring a childbearing age
woman with stable and adequate liver
function may have a successful pregnancy
and a delivery after liver transplantation.
(Pan et al., 2007)