Pregnancy and liver disease

Three possibilities need to be borne in mind

when faced with pregnant women with a liver
disease or abnormality
1-this may represent a worsening of pre-existing
diagnosed or undiagnosed chronic liver disease
or biliary disease
2-This may represents a genuine first presentation
of liver disease which is not related to pregnancy
(Intercurrent liver disease )
3-Pregnancy-associated liver disease
conditions only occur during pregnancy, may recur
in subsequent pregnancies and resolve after
delivery of the baby
Physiologic Changes During Pregnancy That may contribute
to liver disease in pregnancy
Increases
Blood volume, heart rate, and cardiac output rise by 35% to 50%, peak at 32 weeks' gestation;
further increase by 20% in twin pregnancies
Alkaline phosphatase levels rise three- to fourfold because of placental production
Clotting factors I, II, V, VII, VIII, X, and XII
Ceruloplasmin level
Transferrin level
Decreases
Gallbladder contractility
Hemoglobin level (because of volume expansion)
Uric acid level
Albumin and total protein levels
Antithrombin III and protein S level
Systemic vascular resistance
Modest decline in blood pressure
No Changes
Liver transaminase levels (aspartate aminotransferase, alanine aminotransferase)
γ-Glutamyl transferase (GGT) level
Bilirubin level
Prothrombin time
Platelet count (or slight decline)
Approximately 3% of pregnant women are
affected by some form of liver disease during
pregnancy. Some of these conditions can be
fatal for both the mother and child. So Causes
may be consequential to, or independent of,
the pregnancy

In general, the earlier the pregnancy the more

likely it is represent pre-existing liver disease
or non-pregnancy related acute liver disease
(and most common due to viral hepatitis.)
When elevated serum transaminases are present,
acute viral hepatitis and drug causes need to be
excluded like..
*Acute hepatitis A (has no effect on the fetus).
*Chronic hepatitis B has long-term health
implications for the mother and the effectiveness
of perinatal vaccination (with or without pre-
delivery maternal antiviral therapy)
*Maternal transmission of hepatitis C occurs in 1%
*Hepatitis E is reported to progress to acute liver
failure more commonly in pregnancy, with a 20%
maternal mortality.

*Newly acquired primary herpes simplex hepatitis

can cause fulminant liver failure, premature
delivery, and stillbirths. On the other hand,
pregnancy can induce eclampsia and AFLP with a
potential for liver failure and death.
Pregnancy may be associated with both worsening
and improvement of autoimmune liver disease
(e.g. autoimmune hepatitis). Cirrhosis often
leads to infertility, but full-term delivery can
occur. Complications of portal hypertension may
be a particular issue in the second and third
trimesters.
Gallstones are more common during pregnancy,
and may present with cholecystitis or biliary
obstruction. ERCP can be safely performed, but
lead protection for the fetus is essential and X-
ray screening must be kept to an absolute
minimum.
 Pregnancy-associated liver disease

These conditions can present a challenge for health

care providers, only occur during pregnancy ,
(mid and 3rd trimester)may recur in subsequent
pregnancies and resolve after delivery of the
baby. which include ;
hyperemesis gravidarum, acute fatty liver of
pregnancy, intrahepatic cholestasis of pregnancy,
and hemolysis and elevated liver enzymes and
low platelets (HELLP) syndrome.
 1.Hyperemesis Gravidarum
HG is defined as nausea and intractable vomiting that
results in dehydration, ketosis, and weight loss >5%
of body weight. HG complicates 0.3–2.0% of
pregnancies during the first trimester. usually
between 4-10 weeks of gestation, but may occur as
late as 20 weeks' gestation. Risk factors for HG
include past history of the disease, hyperthyroidism,
psychiatric illness, molar pregnancy, preexisting
diabetes, multiple gestations, multiparity, increased
body mass index, high daily intake of saturated fat
before pregnancy. The cause remains unknown
psychologic predisposition, harmful foods , Certain
hormone levels also seem to play a role,
Symptoms
Symptoms include severe nausea and vomiting, at times
requiring hospitalization. Patients often present with
dehydration and may show evidence of malnutrition with poor
weight gain. The diagnosis is based upon the clinical
presentation. Although no standard diagnostic criteria exist,
some commonly used ones include persistent vomiting with no
other cause, evidence of acute starvation (usually with
ketonuria), and evidence of acute weight loss . Up to half of the
hospitalized patients have abnormal liver enzymes.
Aminotransferase levels may rise up to 200 IU/L but are
generally less than 300 IU/L, and alkaline phosphatase may
rise to twice the normal value. Both direct and indirect bilirubin
values may rise to 4 mg/dL, and serum amylase and lipase
may rise up to 5 times normal values. a liver biopsy may be
performed. The biopsy often reveals a normal histologic
appearance or bland cholestasis.
Treatment
Treatment of hyperemesis gravidarum consists of non-
pharmacologic and pharmacologic interventions.
Nonpharmacologic interventions include avoiding
nausea inducing triggers such as odors from
perfume, smoke, cooking foods, and chemicals.
Other triggers that may stimulate nausea include
eating certain foods, especially spicy, salty, or fatty
ones; therefore low fat, frequent, small meals may
help to improve symptoms. Another treatment option
that has proven successful is multivitamin use at the
time of conception, so any patient with a history of
hyperemesis should be encouraged to start taking
multivitamins prior to conception.
Pharmacologic treatment
vitamin B6 given 3-4 times per day is the initial
treatment of choice. It may also be used in
conjunction with doxylamine, an H1 receptor blocker,
This combination has demonstrated great success
and has proven safe to take in pregnancy.
If these 2 medications prove insufficient, the next step
is to add promethazine 12.5 mg orally or rectally
every 4 hours, or another H1 blocker,
dimenhydramine, 50-100 mg orally or rectally every
4-6 hours. If dehydration is not evident,
metaclopramide I.M. or orally every 8 hours;
promethazine can be added.If dehydration is present,
intravenous fluids should be started
metoclopramide ,promethazine iv may be given .
Finally, if all of the above are insufficient,
methylprednisolone orally or intravenously for 3
days followed by a 2-week taper or ondansetron
8 mg intravenously every 12 hours can be
added. Admission to the hospital should be
considered if a patient has persistent vomiting
and cannot tolerate any liquids. In addition, any
patient with change in vital signs, mental status
changes, or continued weight loss should be
admitted, vitamins, especially thiamine, should
be given for patients who cannot tolerate liquids
for a prolonged period of time or have evidence
of dehydration..
2-Intrahepatic cholestasis of pregnancy

This accounts for 20% of cases of jaundice in

pregnancy; it usually occurs in the third
trimester of pregnancy but can occur earlier is
associated with intrauterine growth retardation
and premature birth.The condition presents
with itching and cholestatic LFTs; however
bilirubin may be normal and liver biochemistry
hepatitic.
Delivery leads to resolution of disease
recurrence of cholestasis occurs in 60% of
future pregnancies.
Pathogenesis: is due to an estrogen sensitivity effect and
exhibits a familial tendency. It is frequently recurrent
specially if the women is prescribed oral contraceptives.

Effect of Cholestasis on pregnancy:

⚫ Postpartum hemorrhage (reduced vitamin K absorption)
⚫ Premature labour (30%)
⚫ Stillbirth.

Other causes of jaundice should be excluded,

cholestyramine resin is effective for pruritus,
Induction of labour is indicated at 37-38 weeks or earlier
if there is fetal compromise.
The condition resolves rapidly after delivery.
3-Acute fatty liver of pregnancy
it occurs in 1 in 14 000 pregnancies in the USA.
Acute fatty liver of pregnancy (AFLP) is a rare and
serious condition that typically presents in the third
trimester with vomiting, abdominal pain, jaundice
and other symptoms . It is more common in first
pregnancies and multiple pregnancies, and is
associated with male fetuses. Rarely, fulminant
liver failure may occur.
The diagnosis can usually be made on the basis of
the clinical features, abnormal liver function
tests (LFTs) and the appearances of fatty liver on
ultrasound. A liver biopsy is rarely needed to make
the diagnosis but shows microvascular steatosis.
Management is with supportive care and by
delivery of the fetus. The development of AFLP
has been linked in some cases with an inherited
deficiency of the enzyme long-chain acyl-CoA
dehydrogenase (LCHAD)
in the baby
Criteria for diagnosis of acute fatty liver of pregnancy
ancy
Extremely uncommon before late second trimester
It may follow intravenous tetracycline or prolonged
vomiting
Differentiation from toxaemia of pregnancy (which is
more common) can be achieved by the finding of
high s.uric acid and the absence of haemolysis.
Overlap between acute fatty liver of pregnancy,
HELLP and toxaemia of pregnancy can occur.
Early diagnosis, specialist care and delivery of the
fetus have led to a fall in maternal and perinatal
mortality to 1% and 7% respectively.
Management of AFL:
⚫ Intensive Unit Care
⚫ Adequate intravenous fluids
⚫ Albumin, glucose and vitamin K
⚫ Correction of coagulation defects
⚫ The pregnancy should be terminated, usually
by CS.
4-The HELLP syndrome (haemolysis, elevated liver
enzymes and low platelets) is thought to be part of
the spectrum of pre-eclampsia.
tends to affect multiparous women. Usually at 27-
36 weeks of pregnancy with hypertension,
proteinuria and fluid retention. Jaundice occurs in
5% of cases. It usually presents antenatally but
can also appear for the first time in the postnatal
period.
Diagnosis by
⚫ Careful history and examination
⚫ Biochemical test
⚫ Ultrasound
Blood tests may show low haemoglobin, with
fragmented red cells, markedly elevated
serum transaminases and raised D-dimers.

Maternal complications include DIC and

placental abruption. Maternal mortality is 1%
and perinatal mortality can be up to 30%.

Delivery usually leads to prompt resolution,

and disease recurs in < 5% of subsequent
pregnancies
Thank you