This document discusses various liver diseases that can occur during pregnancy. It covers physiologic liver changes in pregnancy, diseases induced by pregnancy like acute fatty liver of pregnancy (AFLP) and intrahepatic cholestasis of pregnancy (ICP), and preexisting liver diseases. It also discusses liver-related conditions in pregnancy like preeclampsia/eclampsia and HELLP syndrome. Management of various conditions is also summarized.

2. Liver disease in pregnancy
DR RESHAM ALI
GYNAE OBS U-1

3. INTRODUCTION
 Liver disease in pregnancy encompasses a
spectrum of diseases encountered during
gestation and the postpartum period that
result in abnormal liver function tests,
hepatobiliary dysfunction, or both. It
occurs in 3% to 10% of all pregnancies.

4. Physiologic Changes During
Pregnancy

5. Physiologic Changes In LIVER During Pregnancy
 Total blood flow to the liver increases
after 28th week driven by the increased
flow to the portal vein. Histology of the
liver remains essentially normal during
pregnancy.

7.  Several disorders contribute to liver disease in
pregnancy
 These include diseases induced by the
pregnancy such as acute fatty liver of pregnancy
(AFLP) and intrahepatic cholestasis of pregnancy
(IHCP),
 diseases that existed before pregnancy that
could potentially flare during pregnancy such as
autoimmune hepatitis and Wilson’s disease,
 and diseases not related to the pregnancy but
that could affect the pregnant woman at any
time during gestation such as viral hepatitis.

8.  Several disorders contribute to liver disease in
pregnancy
LIVER DISES IN
PREGNANCY
Diseases induced by
Pregnancy.
Preexisting Liver
Disease
Liver Diseases
Coincidental
with Pregnancy
HEG,HELLP Syndrome
Pre-eclampsia/eclampsia
AFLP, IHCP,
Autoimmune hepatitis
Wilson’s disease,
Cirrhosis and
Portal Hypertension
viral hepatitis
Hep:A,B,C & E,
H.SIMPLEX,CMV

9. NTRAHEPATIC CHOLESTASIS OF
PREGNANCY

10. NTRAHEPATIC CHOLESTASIS OF PREGNANCY
 Intrahepatic cholestasis of pregnancy
(ICP) is a reversible condition of
cholestasis that happens usually in the
third trimester. Findings such as pruritus,
high serum bile acids levels, and abnormal
liver function tests usually resolve after
delivery.

11. Pathogenesis
 Genetic predisposition and hormonal
factors have been implicated in the
pathogenesis of ICP.

12. Clinical presentation
 pruritus.
 steatorrhea,
 malabsorption of fat-soluble vitamins, and
 weight loss.
 ICP seems also to increase the incidence
of gallstones and cholecystitis.

13.  Although ICP is a benign condition for the
mother, poor fetal outcomes can occur.
 In some studies ICP resulted in
premature births up to 60%.
 Other complications such as fetal distress
and
 intrauterine fetal death were reported at
61% and 1.6% respectively.
 The onset of pruritus and
 higher maternal fasting serum bile acids
were associated with higher risk for
premature delivery.

14.  Elevated serum bile acids level confirms
the diagnosis.
 Aminotransferases can be elevated as
well up to 2-10 folds.
 Alkaline phosphatase levels might not be
helpful due to higher physiological levels
in late pregnancy.
 Clinical jaundice is detected in 10%-15%
of the cases only and bilirubin levels rarely
exceed 100 μmol/L.

15.  As in all cholestatic patients, women with
ICP tend to have higher low-density
lipoprotein cholesterol and triglycerides.
 Liver biopsy can reveal bland cholestasis
(intrahepatic cholestasis without
parenchymal inflammation). Liver biopsy is
usually not indicated.

16. Management
 Ursodeoxycholic acid (UDCA) is the first line
therapy for ICP. UDCA has shown significant
decrease in serum bile acids, serum
aspartate aminotransferase and alanine
aminotransferase, serum bilirubin, and was
effective for pruritus.
 Bile acids sequestrants such as
cholestyramine, antihistamines and opioid
antagonists have been used to alleviate the
pruritus.

17.  Cholestyramine does not improve
biochemical parameters or fetal outcomes
in ICP.
 Some studies suggested 40 μmol/L as a
cut off level of bile acids, after that fetal
complications may happen. No evidence is
strong enough to recommend early
delivery (at 37 wk of gestation) for
mothers with high bile acids levels,
although this strategy is still used in some
practices.

18. ACUTE FATTY LIVER OF
PREGNANCY

19. ACUTE FATTY LIVER OF PREGNANCY
 Acute fatty liver of pregnancy (AFLP) is a
rare but a serious condition that is unique
to pregnancy and happens in the third
trimester.
 AFLP can lead to significant maternal and
fetal morbidity and mortality.
 Although rare, incidence of 1 per 7270 to
13000 deliveries, outcomes can be grave
with acute liver failure and death.

20. Pathogenesis
 Until recently the pathogenesis of AFLP
was unknown and still has not been fully
elucidated. However, molecular advances
over the past decade suggest that AFLP
may result from mitochondrial
dysfunction. Defects in fetal mitochondrial
fatty acid β-oxidation have been linked to
development of maternal AFLP,
particularly fetal defects in LCHAD, which
is part of the mitochondrial trifunctional
protein (MTP) complex

21. Clinical presentation
 nausea,
 vomiting,
 headache, and
 fatigue can be the initial presentation.
 Right upper quadrant pain or epigastric pain.
 jaundice
 hypoglycemia,
 renal failure,
 coagulopathy,
 ascites, and
 Encephalopathy
 Hypertension/

22.  AFLP is a medical and obstetric emergency and
diagnosis relying on clinical and laboratory
findings should be prompt.
 Liver biopsy can be helpful in early and mild
cases of AFLP especially if diagnosis is not clear.
 Liver biopsy is not necessarily needed and
should be avoided in more severe cases were
the risk of bleeding is high and prompt
therapeutic intervention is needed.
 Alkaline phosphatase is usually elevated.
 Other findings such as leukocytosis,
 thrombocytopenia,
 disseminated intravascular coagulopathy (DIC),
 abnormal prothrombin time, partial
thromboplastin time, and normal fibrinogen can
occur.

23.  Ketonuria and proteinuria can be present.
 Elevated blood urea nitrogen and creatinine
indicate renal insufficiency.
 Low serum albumin and hypoglycemia can
occur.
 Uric acid and ammonia levels can be increased.
 Hyperuricemia can be an early indicator and
develop before hyperbilirubinemia.
 Liver biopsy usually displays microvesicular
steatosis.
 Electron microscopy can show mitochondrial
disruption.
 Imaging studies can be useful to exclude other
pathologies; but have limited utility in the
diagnosis of AFLP.

24. Management
 Stabilization of the mother and early
recognition and delivery are the keys for
successful management.
 Close monitoring and management of
associated complications is necessary to
improve outcomes.
 Plasmapheresis was used in few series in
severe cases with reported success

25. PREECLAMPSIA/ECLAMPSIA

26. PREECLAMPSIA/ECLAMPSIA
 Preeclampsia is a disorder defined by
the triad of hypertension, edema,
and proteinuria.
 It affects about 5%-10% of all
pregnant women and usually occurs
late in the second trimester or in the
third trimester.
 Eclampsia involves all features of
preeclampsia and includes neurologic
symptoms such as headaches, visual
disturbances, and seizures or coma.

27.  10- to 20-fold elevation in
aminotransferases,
 elevations in alkaline phosphatase levels
 bilirubin elevations of less than 5 mg/dL.
 Liver histology generally shows hepatic
sinusoidal deposition of fibrin along with
periportal hemorrhage, liver cell necrosis,
and in severe cases, infarction; these
changes are likely due to vasoconstriction
of hepatic vasculature.

28.  The only effective treatment for
preeclampsia is delivery of the
fetus and placenta.
 However, if evident before 36 wk
g estation, one may consider
expectant management with
intensive monitoring.
 antihypertensives such as
calcium channel blockers.
Methyldopa
 Magnesium sulfate may be
administered if eclampsia
develops.

29. HEMOLYSIS, ELEVATED LIVER TESTS
AND LOW PLATELETS

30. HEMOLYSIS, ELEVATED LIVER TESTS
AND LOW PLATELETS
 HELLP syndrome is a multisystemic disorder of
pregnancy involving hemolysis, elevated liver
tests, and low platelets.
 About 70% of cases occur antenatally, and most
cases occur during the last trimester of
pregnancy.
 The pathogenesis of HELLP is thought to
involve alterations in platelet activation,
increases in proinflammatory cytokines, and
segmental vasospasm with vascular endothelial
damage.

31.  Most patients present with
 right upper quadrant abdominal pain,
 nausea,
 vomiting,
 malaise, and
 edema with significant weight gain.
 Less commonly associated conditions include renal failure (with
increased uric acid),
 diabetes insipidus, and
 antiphospholipid syndrome.
 Other late findings include disseminated intravascular coagulopathy
(DIC),
 pulmonar y edema,
 placental abruption, and
 retinal detachment.
 Hypertension and proteinuria may be seen, but in 20% of patients,
hypertension is absent[19].

32.  Laboratory findings include hemolysis with
increased bilirubin levels (usually less than
5 mg/dL) and
 lactate dehydrogenase (LDH) levels
greater than 600 IU/L,
 moderately elevated aspartate
aminotransferase (AST) and ALT levels
(200 IU/L to 700 IU/L), and
 thrombocytopenia (less than 100 000/mL).

33.  In early stages, prothrombin time and
activated partial thromboplastin time are
normal, but in later phases it will be de-
ranged,

34.  The reported maternal mortality from
HELLP is 1%, and the perinatal
mortality rate ranges from 7%-22%
and may be due to premature
detachment of placenta,
 intrauterine asphyxia, and
 prematurity
 acute renal failure,
 adult respiratory distress syndrome,
 pulmonary edema,
 stroke,
 liver failure, and
 hepatic infarction.

35.  The only definitive treatment for HELLP
syndrome is delivery. If the pregnant woman is
greater than 34 wk gestation, immediate
induction is recommended.
 If gestational age is between 24 wk and 34 wk,
corticosteroids are administered to accelerate
fetal lung maturity in preparation for delivery 48
h later.
 After delivery, close monitoring of the mother
should continue,
 For patients with ongoing or newly developing
postpartum symptoms of HELLP, modalities such
as antithrombotic agents,
 plasmapheresis, and
 dialysis may be employed.

36.  Preexisting Liver Disease

37. Preexisting Liver Disease and Pregnancy
 The outcome of a pregnancy is greatly
affected by the medical condition of the
liver before conception. Diagnosis and
treatment of a liver disorder before
conception will minimize potential
exacerbations that could lead to liver
failure and fetal loss.

38. Cirrhosis and Portal Hypertension
 The prevalence of cirrhosis in reproductive-age
women approximates 0.45 cases per 1000.
 Etiology of cirrhosis in pregnancy is similar to
that in the nonpregnant state and commonly
includes alcohol and viral hepatitis C and B.
 Patients with cirrhosis and noncirrhotic portal
hypertension are at high risk for premature
deliveries.
 .

39.  Hepatic decompensation with jaundice, bleeding
from esophageal varices, ascites, and fulminant
liver failure can occur.
 In general, diuretics and spironolactone, are
not advisable during pregnancy or lactation
because of the potential for teratogenicity.
 Banding of bleeding esophageal varices and
octreotide are safe during pregnancy.
 Meperidine (Demerol) and midazolam (Versed)
safe to use during endoscopy.

40. Wilson’s Disease
 Wilson’s disease is an inherited autosomal recessive
defect of copper transport.
 Fertility in Wilson’s disease is decreased but can
improve with therapy.
 Treatment should be initiated before conception and
should not be interrupted during pregnancy, because of
the risk of fulminant liver failure.
 The treatment of choice in pregnancy is zinc sulfate
50 mg three times daily, because of its efficacy and
safety for the fetus.
 Patients who are treated with d-penicillamine or trientin
before pregnancy require a dose reduction by 25% to
50% of that in the pre-pregnancy state especially during
the last trimester, to promote better wound healing if a
cesarean section is to be performed.

41. Autoimmune Hepatitis
 Autoimmune hepatitis is a progressive liver disease that
predominantly affects women of all ages and can
manifest at any time during gestation and the
postpartum period.
 The disease activity of autoimmune hepatitis is usually
attenuated during pregnancy, and dosages of medication
can be decreased because of the state of immune
tolerance induced by the pregnancy.
 There is an increased risk of prematurity, low-birth-
weight infants, and fetal loss.
 Pregnancy does not contraindicate immunosuppressive
therapy. Both prednisone and azathioprine ( at dosages
<100 mg/day) are considered safe during pregnancy
and lactation.
 In one meta-analysis, prednisone given during the first
trimester was linked to a marginal risk of oral cleft defect
in the newborn.

42. Liver Diseases Coincidental with
Pregnancy

43. Viral Hepatitis
 Acute viral hepatitis is the most common
cause of jaundice in pregnancy, with an
incidence of approximately 1 to 2 per
1000. The outcome is usually benign,
except in viral hepatitis E and herpes
simplex virus (HSV) hepatitis.

44. Viral Hepatitis
 Acute viral hepatitis E is transmitted via
the fecal-oral route and is associated with
high morbidity and a maternal mortality
rate of 30%.
 Vertical transmission of HEV to the
newborn occurs in 50% of cases if the
mother is viremic at the time of delivery.
 Treatment is supportive, and judicious
hand washing prevents contamination.

45. Herpes Simplex Hepatitis
 Approximately 2% of women acquire HSV
during pregnancy.
 HSV hepatitis is a rare condition but may
be devastating when primary infection
occurs in pregnancy because it is
associated with a 40% risk for fulminant
liver failure and death.
 Treatment of choice for severe primary
HSV infection is intravenous acyclovir .

46. Acute Viral Hepatitis A
 Acute hepatitis A virus (HAV) infection is
usually self-limited during pregnancy.
 Transmission to the newborn can occur
when delivery takes place during the
incubation period because of viral
shedding and contamination during
vaginal delivery.
 Treatment of the mother is supportive.
 Passive immunoprophylaxis should be
given to the newborn.

47. Viral Hepatitis B
 Acute and chronic HBV infections during
pregnancy do not seem to affect the
course of pregnancy but are associated
with an increased risk of transmission to
the newborn.
 The risk of vertical transmission of HBV is
minimal if the infection is acquired and
resolves in the first trimester.

48.  The risk is high, ranging from 60% to
90% if the infection is acquired during the
third trimester or if the infected mother is
positive for the envelope antigen (eAg)
and the viral DNA count is elevated.
 Therefore, active and passive
immunoprophylaxis should be
administered to newborns of HBV-infected
mothers.

49. Viral Hepatitis C
 The prevalence of hepatitis C virus (HCV)
infection in women of childbearing age in the
United States is approximately 1%.
 Treatment of HCV infection is contraindicated in
pregnancy because of the teratogenicity of the
drugs used.
 There is a 3.8% rate of vertical transmission to
infants born to mothers who are viremic at the
time of delivery.
 Breast-feeding should not be discouraged and
the indication for cesarean section should be
based on obstetrical reasons.

50. Summary
 Signs and symptoms of liver disease in pregnancy are
not specific, but the underlying disorder can have
significant morbidity and mortality effects on the mother
and fetus. Early recognition can be lifesaving.
 Acute viral hepatitis is the most common cause of
jaundice in pregnancy. The outcome is usually benign.
Intervention might not be required except in cases of
viral hepatitis E and herpes simplex hepatitis.

51.  Women with well-compensated cirrhosis and
noncirrhotic portal hypertension may become
pregnant. Preconception care and management
of pregnant women with portal hypertension
should be similar to that for nonpregnant
women.
 Fertility may be restored after liver
transplantation and pregnancy might have a
good outcome.
 Vigilance in recognizing liver disorders in
pregnancy and early coordinated management
among the primary care physician, obstetrician,
liver specialist, and transplant surgeon are
essential for promoting good maternal and fetal
outcomes.