PREGNANCY RELATED LIVER DISEASES

1. LIVER DISEASES WITH
PREGNANCY
Dr. Mohammed Abdallah

2. physiology
• Spider angioma and palmar erythema, which are typical clinical
markers of liver disease, are commonly seen during pregnancy as a
consequence of the hyperestrogenic state.
• Gall bladder motility is decreased, increasing the incidence of
cholelithiasis in pregnant women
• decreased albumin in all trimesters due to hemodilution, and the
decline in albumin levels becomes more pronounced as pregnancy
advances.
• Alkaline phosphatase (ALP) is increased in the third trimester, but it
is of placental origin due to fetal bone development.
• Alpha fetoprotein (AFP) levels also increase because it is produced
by the fetal liver.
• In contrast, other liver biochemical tests, remain within the normal
range during normal pregnancy. such as total bile acids
concentration, serum alanine transaminase (ALT or SGPT) aspartate
transaminase, (AST or SGOT) gamma-glutamyl transpeptidase
(GGT), and bilirubin,

3. • Pregnancy is a pro-coagulant state in which clotting
factors (I, II, V, VII, X, and XII) and fibrinogen are
increased .
• whereas the ranges for prothrombin time (PT) and
activated partial thromboplastin (APT) time are
within normal values .
physiology

5. LIVER FUNCTION TESTS
• Alanine aminotransferase (ALT) – an enzyme found mainly in the liver; best test to
detect hepatitis
• Alkaline phosphatase (ALP) – an enzyme related to the bile ducts; often increased if ducts are
blocked
• Aspartate aminotransferase (AST) – an enzyme found in the liver and a few other places,
particularly the heart and other muscles
• Gamma-glutamyl transferase (GGT) – an enzyme found mainly in the liver; very sensitive to
changes in liver status, especially when bile ducts are blocked
• Total bilirubin – measures all of the bilirubin in the blood; levels are increased with many liver
diseases and other conditions, such as hemolysis, that lead to increased production of bilirubin
• Direct bilirubin – measures a form of bilirubin that is conjugated (combined with another
compound) in the liver; only increased in liver disease
• Albumin – measures albumin, the main protein made by the liver, and tells how well the liver is
making it
• Total protein – measures albumin and all other proteins in blood, including antibodies present
to help fight off infections (antibodies are not made in the liver)
• Lactate dehydrogenase (LD or LDH) – an enzyme released with tissue damage; may be elevated
with acute liver disease

6. physiology
• aspartate aminotransferase (AST)
• and alanine aminotransferase (ALT)
evaluate Liver cell injury or necrosis
• albumin level
• prothrombin time
evaluate liver synthetic function (are depressed in cirrhosis or
severe acute liver disease)
• alkaline phosphatase,
• bilirubin,
• gamma glutamyl transpeptidase
evaluate Cholestasis and biliary obstruction

7. Liver diseases with pregnancy
coincidental liver disease
• hepatitis
• Gallstones
• Drug toxicity .
underlying chronic liver
disease.
pregnancy-related
1. The preeclampsia-
associated liver diseases
• (HELLP) syndrome
• (AFLP) acute fatty liver of
pregnancy
2. Not preeclampsia-
associated liver diseases
• Hyperemesis gravdarum
• (ICP) intrahepatic
cholestasis of pregnancy

9. Hyperemesis gravidarum
• is intractable, dehydrating vomiting in the first trimester
of pregnancy; 50% of patients with this condition have
abnormal liver test
have been shown to be risk factors for HG development
• Multiple gestations
• increased body mass index (BMI)
• pre-existing diabetes
• psychiatric illness
• and HG in a previous pregnancy
.

10. • Elevations in serum aminotransferases usually go up to 200
U/L and this is the most common abnormal liver test result.
• In pregnant women presenting with abnormal liver enzymes
with or without HG in the first trimester, other causes of
abnormal liver enzymes must be ruled out .
Hyperemesis gravidarum

11. • Initial management is conservative
• The only FDA-approved drug for treating nausea and
vomiting in pregnancy is doxylamine/pyridoxine ( VIT B6) .
• Ginger may be used as a nonpharmacologic option, as it
has had some beneficial effects in the treatment of
nausea and vomiting of pregnancy.
• However, antihistamines, antiemetics of the
phenothiazine class, and promotility agents (eg,
metoclopramide) are used
• In refractory cases, ondansetron ( zofran) and steroids
may be considered
Hyperemesis gravidarum

13. • Obstetric cholestasis is diagnosed when otherwise
unexplained pruritus occurs in pregnancy and abnormal liver
function tests (LFTs) and/or raised bile acids occur in the
pregnant woman and both resolve after delivery.
• Pruritus that involves the palms and soles of the feet is
particularly suggestive
• Other evidence of cholestasis should be sought, including pale
stool, dark urine and jaundice, and other risk factors identified
such as a personal or family history of obstetric cholestasis,
multiple pregnancy, carriage of hepatitis C and presence of
gallstones.
Intrahepatic cholestasis of pregnancy

14. • ICP is the most common cause of jaundice during pregnancy
characterized by a reversible cholestatic condition that usually
occurs during the late second and third trimester, when
serum concentrations of estrogen reach their peak; it has a
higher incidence in twin pregnancies, which have higher
estrogen levels, and resolves after delivery, when sex
hormone levels fall
• ICP has rapid postnatal resolution, with signs and symptoms
usually disappearing spontaneously within 6 weeks of
delivery.
Intrahepatic cholestasis of pregnancy

15. • The main symptom of ICP is pruritus, which typically predominates
on the palms and soles of the feet and worsens at night.
• Pruritus often develops after 25 weeks of gestation, with 80% of cases
occurring after the 30th week.
• Other symptoms of ICP can include steatorrhea, malabsorption of fat-
soluble vitamins, and weight loss due to cholestasis .
• Jaundice has an incidence of 14–25% and may develop 1 to 4 weeks
after the onset of pruritus, with dark urine and pale feces in some women.
• The most important biochemical test in the context of ICP is total bile
acids concentration, greater than 10 μmol /L which can be the first, and
sometimes only, laboratory abnormality
• Serum bile acid values may fluctuate and increase with advancing
pregnancy; therefore, it is advisable to check it weekly in women with ICP
• >40 μmol serum bile acids in severe ICP is currently considered to be
associated with adverse pregnancy outcomes
Intrahepatic cholestasis of pregnancy

16. • Ursodeoxycholic acid improves clinical symptoms and liver
parameters in a number of cholestatic liver disorders.
• UDCA at a daily dose ranging from 600-2000 mg or 15 mg/kg per day was
effective at reducing pruritus, decreasing the total serum bile acid levels,
ALT values, and bilirubin levels and allowing delivery closer to term
• Antihistamines are commonly administered in conjunction with UDCA to
alleviate pruritus symptoms.
• Dexamethasone should not be first-line therapy for treatment of obstetric
cholestasis,
• Other medications, such as cholestyramine and S-adenosyl-methionine,
have not had satisfactory results
Intrahepatic cholestasis of pregnancy

17. • where the prothrombin time is prolonged, the use of water-
soluble vitamin K (menadiol sodium phosphate) in doses of
5–10 mg daily is indicated.
• when prothrombin time is normal, water-soluble vitamin K
(menadiol sodium phosphate) in low doses should be used .
Intrahepatic cholestasis of pregnancy

18. Mortality/Morbidity
• From a maternal viewpoint, the main consideration is
intense pruritus, It is characterized by profound itching
often beginning with the palms of the hands and soles of
the feet without evidence of a rash which may become so
intolerable that delivery is considered as early as 35-37
weeks
• The fetal viewpoint is more concerning, as even with
modern treatment the risk for fetal demise can range from
2-11 %. One of the more worrisome aspects of ICP is the
possibility of sudden fetal death, sometimes within hours of
normal fetal heart rate tracings
Intrahepatic cholestasis of pregnancy

19. • Poor outcome cannot currently be predicted by biochemical
results and delivery decisions should not be based on results
alone.
• No specific method of antenatal fetal monitoring for the
prediction of fetal death can be recommended.
• Ultrasound and cardiotocography are not reliable methods for
preventing fetal death in obstetric cholestasis
Intrahepatic cholestasis of pregnancy

20. Delivery is commonly recommended at 37 weeks’ without an amniocentesis
for fetal lung maturity due to increased risk of fetal mortality and morbidity .
• A discussion should take place with women regarding induction of labour
after 37+0 weeks of gestation.
• Women should be informed of the increased risk of perinatal morbidity
from early intervention (after 37+0 weeks of gestation).
• Women should be informed that the case for intervention (after 37+0
weeks of gestation) may be stronger in those with more severe
biochemical abnormality (transaminases and bile acids).
• Women should be informed of the increased risk of maternal morbidity
from intervention at 37+0 weeks of gestation.
• Women should be informed of the inability to predict stillbirth if the
pregnancy continues.
Intrahepatic cholestasis of pregnancy

22. • AFLP is a microvesicular fatty infiltration of hepatocytes due to Defect in beta-
oxidation of fatty acids in mitochondria, leads to fat droplets formation in
hepatocyte that is also known as acute yellow atrophy or acute fatty
metamorphosis .
• AFLP is a medical and obstetric emergency because it can be fatal for both the
mother and fetus in the absence of early recognition and appropriate
management .
• AFLP is a rare condition, usually occurring in the third trimester, with an
approximate incidence of 1: 7000 to 1: 16000 and is commonly associated
(or complicated ) with preeclampsia (50 to 100 percent).
Acute fatty liver of pregnancy

23. • AFLP usually occurs in the third trimester, rarely before the
30th gestational week, but up to 20% of cases present
postnatally .
• Clinical presentation is variable and includes non-specific
symptoms such as nausea, vomiting, abdominal pain,
headache, and malaise.
• The clinical course can rapidly progress to acute liver failure
and its complications, such as encephalopathy, jaundice, and
coagulopathy
Acute fatty liver of pregnancy

24. • Laboratory tests can show abnormal liver values, including:
 elevated aminotransferase levels (from mild elevation to 1000 IU/L, but
usually 300–500 IU/mL) .
 hyperbilirubinemia (frequently >5 mg/dL).
 leukocytosis, normochromic anemia, and thrombocytopenia are present,
as well as hypoalbuminemia, elevated uric acid, renal dysfunction,
metabolic acidosis, hyperammonemia, and biochemical pancreatitis.
Ketonuria and proteinuria can be present.
 Hypoglycemia is characteristic and predicts a poor prognosis.
 In severe cases, prolonged PT and reduced fibrinogen levels may be found,
whereas disseminated intravascular coagulation (DIK) is seen in
approximately 10% of patients with AFLP.
Acute fatty liver of pregnancy

25. Fifteen years ago, Ch’ng et al.published a study in which they
proposed diagnostic criteria, known as the Swansea
criteria, for the diagnosis of AFLP.
Acute fatty liver of pregnancy

26. Swansea criteria
he presence of ≥6 abnormal variables had positive predictive value of 85 percent and
negative predictive value of 100 percent for finding microvesicular steatosis
●Vomiting
●Abdominal pain
●Polydipsia/polyuria
●Encephalopathy
●Elevated bilirubin (>0.8 mg/dL or >14 micromol/L)
●Hypoglycemia (<72 mg/dL or <4 mmol/L)
●Leukocytosis (>11,000 cells/microL)
●Elevated transaminases (AST or ALT) (>42 international unit/L)
●Elevated ammonia (>47 micromol/L)
●Elevated uric acid (5.7 mg/dL or >340 micromol/L)
●Acute kidney injury, or creatinine 1.7 mg/dL or >150 micromol/L
●Coagulopathy or prothrombin time >14 seconds
●Ascites or bright liver on ultrasound scan
●Microvesicular steatosis on liver biopsy
The criteria are intended for use in women without hemolysis, elevated liver enzymes, and a
low platelet count syndrome or preeclampsia, which limits their clinical utility

27. • The main differential diagnosis is HELLP syndrome due to the great overlap
between AFLP and HELLP syndrome. Thus, distinguishing between these 2
disorders is often very difficult, potentially delaying diagnosis.
• Early recognition of the disease and delivery of the fetus regardless of
gestational age are the keys to successful management,
Acute fatty liver of pregnancy

29. • itself is the commonest cause of hepatic tenderness
and liver dysfunction in pregnancy, and 2%-12% of
cases are further complicated by hemolysis (H),
elevated liver tests (EL), and low platelet count (LP)-
• the HELLP syndrome. Immediate delivery is the only
definitive therapy, but many maternal complications
can occur, including abruptio placentae, renal failure,
subcapsular hematomas, and hepatic rupture.
SEVER PREECLAMPSIA
“ HELLP ”

30. • preeclampsia is a multisystem disorder defined by de
novo hypertension after the 20th week of pregnancy with
blood pressure (BP) ≥140/90 mmHg and proteinuria of >300
mg/day in association with other organ dysfunction of the
mother, such as renal impairment, liver involvement,
neurological or hematological complications, and
uteroplacental dysfunction, as well as fetal growth restriction .
• The main feature that distinguishes eclampsia from
preeclampsia is the presence of seizures
SEVER PREECLAMPSIA
“ HELLP ”

31. • The diagnosis of HELLP syndrome is based mainly on clinical features.
Women often present with fluctuating colic-like pain in the upper
abdomen, usually epigastric or in the right upper quadrant. In addition,
non-specific symptoms such as nausea, vomiting, and malaise are often
present.
• Arterial hypertension and proteinuria are noted in most women. Due to
microangiopathic hemolytic anemia,
• unconjugated bilirubin and LDH are increased,
• whereas liver enzymes are moderately elevated (ALT 2–30 fold). Low
haptoglobin may be used as another parameter for the diagnosis of
hemolysis.
SEVER PREECLAMPSIA
“ HELLP ”

32. there are 2 classifications of HELLP
syndrome: the Tennessee , and
Mississippi classifications,
SEVER PREECLAMPSIA
“ HELLP ”

33. The Tennessee classification of HELLP
The Tennessee classification describes HELLP as either complete or
partial.
Complete HELLP syndrome is characterized by the following:
• Platelet count of 100,000/μL or less
• AST or ALT levels of 70 IU/L or more
• LDH (or bilirubin) (with hemolysis as evidenced on abnormal
peripheral smear) levels of 600 IU/L (≥0.2 mg/dL) or more
Partial HELLP syndrome is characterized by severe preeclampsia plus
one of the following:
• ELLP: Elevated liver enzyme levels, thrombocytopenia, no hemolysis
• EL: Mildly elevated liver enzyme levels, no thrombocytopenia, no
hemolysis
• LP: Thrombocytopenia, no hemolysis, normal liver enzyme levels
• HEL: Hemolysis, liver dysfunction, no thrombocytopenia

34. The Mississippi classification OF HELLP
The Mississippi classification divides HELLP syndrome into 3 classes
based on platelet count, AST or ALT levels, and LDH levels.
 Class 1, which has an approximately 13% incidence of bleeding, is
associated with the highest maternal morbidity and mortality rates
and longest recovery time. Patients in this class have a platelet
count less than 50,000/µL, liver dysfunction with AST or ALT levels
greater than 70 IU/L, and hemolysis as evidenced by an LDH level
greater than 600 IU/L.
 Class 2 includes platelet counts from 50,000-100,000/µL with AST,
ALT, and LDH levels similar to those in class 1. Class 2 has an 8%
incidence of bleeding.
 class 3 The mild form of HELLP has a platelet count from 100,000-
150,000/µL, AST and ALT greater than 40 IU/L, and LDH greater
than 600 IU/L, with no increased risk of bleeding.

35. The Mississippi classification OF HELLP

36. Abdominal imaging methods, such as ultrasonography, CT, and
MRI, should be performed in all women with HELLP syndrome in
order to investigate liver complications, such as liver infarction,
intraparenchymal hemorrhage, subcapsular hematoma, and
hepatic rupture
SEVER PREECLAMPSIA
“ HELLP ”

37. As mentioned, HELLP syndrome and AFLP share similar presentations. The
differential diagnosis among AFLP and HELLP syndrome is shown in Table

38. • A pregnant patient presenting with abnormal liver tests should undergo
standard workup as with any non-pregnant individual .
• Imaging in pregnancy Ultrasound is safe and the preferred imaging
modality used in assessment of abnormal liver tests suggestive of biliary
tract disease
• Magnetic resonance imaging without gadolinium can be used in the
second and third trimester .
• Computed tomography scans carry a risk of teratogenesis and childhood
hematologic malignancies but may be used judiciously with minimized
radiation protocols (2–5 rads).
• Endoscopy in pregnancy Endoscopy is safe in pregnancy but should be
deferred until the second trimester if possible .
• Meperidine and propofol can be used for endoscopic.
Take home

39. • Active–passive immunoprophylaxis with hepatitis B immunoglobulin and
the HBV vaccination series should be administered to all infants born to
HBV-infected mothers to prevent perinatal transmission .
• Women chronically infected with HBV and high viral load (>10 6 log
copies/ml (200,000 IU/ml) and higher) should be offered antiviral
medication with tenofovir or telbivudine in the third trimester to reduce
perinatal transmission of HBV
• C-section should not be performed electively in HBV-positive mothers to
prevent fetal infection .
• Women chronically infected with HBV should be allowed to breastfeed as
recommended for infant health
Take home

40. Take home
All pregnancy related liver diseases that occur in late
second trimester or third trimester either preeclampsia
associated ( HELLP or AFLP ) OR not preeclampsia
associated ( ICP) necessitate termination of pregnancy ,
irrespective of fetal maturity in HELLP , AFLP and in ICP
if bile acids level is > 40 micromole/ L