The document summarizes various liver conditions that can cause jaundice in pregnancy. It discusses physiological changes in the liver during pregnancy and various causes of jaundice related and unrelated to pregnancy. These include viral hepatitis, intrahepatic cholestasis of pregnancy (ICP), preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy (AFLP). It provides details on pathogenesis, clinical presentation, management and prognosis for these conditions. Pregnancy-related liver disorders can affect both mother and fetus, so prompt diagnosis and treatment are important.

1. Jaundice in Pregnancy
Dr Anusha Rao P

2. Summary of physiological changes in the liver during pregnancy
• Increased:
• Blood volume and cardiac ouput rise by 35%–50%
• Alkaline phosphatase levels rise threefold or fourfold due to placental
production
• Clotting factor changes create a hypercoagulable state
• Decreased:
• Gallbladder contractility
• Hemoglobin
• Uric acid levels
• Albumin, total protein, and antithrombin III concentrations
• No change:
• Liver aminotransferase levels (AST, ALT, GGT)
• Bilirubin level
• Prothrombin time

4. CAUSES OF JAUNDICE IN PREGNANCY
UNRELATED TO PREGNANCY PREGNANCY SPECIFIC
HEPATIC CAUSES
• Acute viral hepatitis
• Drug induced hepatitis
• Chronic hepatitis
-viral (HBV, HCV)
-Autoimmune hepatitis
• Wilson’s disease
• Cirrhosis of liver
• Budd- chiari syndrome
PRE-HEPATIC CAUSES
• Hemolytic anemia
POST-HEPATIC CAUSES
• Common bileduct stone/ strictures
• Biliary parasitosis
• Hyperemesis gravidarum
• Intrahepatic cholestasis of pregnancy
• Pre-eclampsia/ eclampsia
• HELLP Syndrome
• Acute fatty liver of pregnancy

5. Test Non pregnant
adult
II trimester III trimester Cholestasis of
pregnancy
ALP (U/L) 33-96 25-126 38-229 Higher than in
normal
pregnancy
AST (U/L) 12-38 3-33 4-32 2-10 fold
increase above
normal
Total Bilirubin
(mg/dL)
0.3-1.3 0.1-0.8 0.1-1.1 2-5

6. features
Acute hepatits ICP HELLP AFLP
Trimester Any III III III
Presentation Fever, jaundice Pruritis HTN, N/V, pain N/V, pain
S. ALT & AST >>> > >> >>
S. ALP > > = =
Platelets = = < =
Fetal
complications
Transmission of
infection in
HBV and HCV
Prematurity
Fetal distress
IUGR
IUGR
Prematurity
Premature del.

7. Intrahepatic Cholestasis of Pregnancy
• Also called as recurrent jaundice of pregnancy,
cholestatic jaundice of pregnancy, jaundice of late
pregnancy, and hepatosis of pregnancy.
• It is a form of intrahepatic cholestasis associated with
pruritus, elevated serum bile acid levels, and the
findings of bland cholestasis on liver biopsy .

8. • 1.5 – 2% of pregnancies.
S. bile acid levels
• Mild : 10-39 umol/L
• Severe : > 40 umol/L
• Conjugated hyperbilirubinemia,
slight inc. in ALP/ GGT
• Synthetic function and architecture of liver-
unaltered.

9. Pathogenesis
Unknown
• Genetically susceptible women.
• Low plasma selenium levels .
• An enhanced sensitivity to estrogen .
• A variation in the metabolism of
progesterone(diminished secretion of sulfated
progesterone metabolites) .
• Molecular mechanism show many gene mutations that
control hepatocellular transport systems
– Multidrug resistance 3 (MDR3) gene found with progressive
familial intrahepatic cholestasis.
– Decrease canalicular transport of bile acids .

10. Clinical Presentation :
Pruritus
dominant and initial symptom
third trimester (> 70% of cases)
usually involves the trunk and the extremities, including the palms and the
soles of the feet.
 Disappears 24-48 hours postpartum (but biochemical and histological
abnormalities take longer to resolve)
• 10% to 25% patients develop obvious jaundice, and this is usually mild.
• Abdominal pain, biliary colic, fever, anorexia, nausea, vomiting, and
arthralgias are absent.

11. Effects on the Mother
• Improvement of symptoms and laboratory test results begins
with delivery of the infant .
• Is usually prompt and complete .
• No residual hepatic defect after resolution of the disorder .
• Increased risk for development of gallstones, cholecystitis,
and pancreatitis.
• 60% to 70% of patients develop cholestasis during subsequent
pregnancies

12. Effects on the Fetus
• Serious implications
• Increased incidence of prematurity and fetal death.
(intrapartum fetal distress, meconium aspiration, and neonatal
respiratory distress)
• These complications correlate with maternal bile acid levels >
40 μmol/L.
• More likely if the disorder begins earlier in pregnancy.

13. Management
Palliative
• Antihistamines and topical emollients.
• Ursodeoxycholic acid, 10-15 mg/kg/day
• Cholestyramine
– Bile acid binders
– worsens steatorrhea and resultant fat-soluble and vitamin K deficiencies,
fetal coagulopathy, intracranial hemorrhage and stillbirth
• S'-adenosyl-1.-methionine
– lead to a significant improvement in pruritus and in serum transaminase
and bilirubin levels, perhaps by reducing the negative effects of
estrogens on bile secretion.

14. Differential diagnosis:
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Benign recurrent intrahepatic cholestasis
• Viral hepatitis
• Biliary obstruction

15. LIVER DISEASE OF PREECLAMPSIA
• Preeclampsia is a form of pregnancy-related
hypertension that is associated with damage and
dysfunction of one or more maternal organs, possibly
including the liver,that may produce severe, life-
threatening complications and affect pregnancy
outcome .

16. “HELLP” SYNDROME
• Hemolysis, Elevated Liver enzymes,and Low
Platelet count (HELLP) syndrome .
• Multi-system disease variant of severe
preeclampsia that is characterized by
– Microangiopathic hemolytic anemia (MAH),
– Hepatic dysfunction (hepatic necrosis),
– Thrombocytopenia (platelet count, <100,000/ mm3),
and,
– In the syndrome’s most severe form, DIC.
– 12% of women with severe preeclampsia .

18. • CT and MRI, may be useful
– detects intrahepatic hemorrhage and infarction.
• Liver biopsy
– Periportal hemorrhage, intrasinusoidal fibrin deposition
and irregular areas of liver cell necrosis with mild
reactive hepatitis .
– There is little correlation between the severity of
liver biopsy lesions and laboratory test
abnormalities .

19. D/D of HELLP
MiscellaneousIncreased Liver
enzymes
Thrombocytopenia
Systemic lupus
Drug-induced
hemolytic anemia
Sepsis
Abruptio placenta
Amniotic fluid embolism
cholecystitis
Appendicitis
Acute viral hepatitis
Acute fatty liver of
pregnancy
Hemolytic uremic syndrome
Immune thrombocytopenic
purpura,
Thrombotic thrombocytopenic
purpura,
Anti-phospholipid antibody
syndrome
DIC

20. ACUTE FATTY LIVER OF PREGNANCY
• AFLP is a form of microvesicular fatty liver disease
unique to human gestation that presents late in
pregnancy, often as fulminant hepatic failure with
sudden onset of coagulopathy and encephalopathy in
a woman without a prior history of liver disease .
• Acute Yellow atrophy/ Acute Fatty metamorphosis
• AFLP is diagnosed in approximately 1 of 10,000
pregnancies / third trimester.
• Maternal mortality 10-15%
• Perinatal mortality 15-20%

21. Pathogenesis
Unknown
• Associated with inherited mitochondrial abnormalities
of beta oxidation of fatty acid .
• Genetic mutations .
• The most common are the G1528C and E474Q
mutations of the gene on chromosome 2 that code for
long chain-3-hydroxyacyl-CoA-dehydrogenase
(LCHAD).
• Autosomal recessive carnitine palmitoyltransferase1
(CPT1) deficiency has also been reported.

23. Clinical Characteristics
• AFLP presents late in pregnancy ;between 34 and 37
weeks of gestation .
• Rarely may present after delivery.
• Occur more commonly in first pregnancy and with
male fetus/ twins.
• Have signs of coexistant preeclampsia (50%)
• In severe cases progression over hours or days to
fulminant hepatic failure and death.

24. Clinical features
• Nonspecific symptoms like
– Nausea and vomiting,
– Malaise and fatigue,
– Jaundice,
– Thirst, headache, and
– Altered mental status.
– Pruritus (overlap with ICP )
• There can be signs and symptoms of acute hepatic
failure.

25. • The histologic hallmark is microvesicular fatty
infiltration of the liver that is most prominent in
hepatocytes surrounding central veins (zone three)
and spares those surrounding portal areas .
• Do not have the periportal hemorrhage and fibrin deposition seen in
preeclampsia and HELLP syndrome.
• Confusion
– lobular disarray suggestive of viral hepatitis and
– biliary ductular proliferation and inflammation
suggestive of cholangitis

27. Complications
 Cerebral edema,
 Renal failure (60%),
 Hypoglycemia (53%),
 Infections and sepsis (45%)
 Gastrointestinal hemorrhage (33%),
 Coagulopathy (30%),
 Fetal death
 Severe postpartum hemorrhage

28. Course
• Patients with undiagnosed AFLP
– Have unpredictable course and often within short time course,
to fulminant hepatic failure and death for both mother and
fetus.
• Survival of patients with AFLP has been reported to be
about 100% with prompt diagnosis, delivery of the infant,
and intensive care.
• Recurrence of AFLP has been documented more likely if
the woman has a homozygous enzyme- deficient fetus.

29. Management
 Early diagnosis, prompt delivery and supportive
care are the cornerstones in the management
Spontaneous resolution .
 Treated in intensive care units.
Transfusions with whole blood or packed red
cells, along with FFP, cryoprecipitate, and
platelets .
Mechanical ventilation , hemodialyisis and
antibiotics
 Hepatic encephalopathy is treated by measures intended to evacuate
feces and bacteria from the colon.
 Infusion of concentrated glucose solution may be required to treat or
prevent hypoglycemia .

30.  Prompt delivery
 The route should be guided by obstetric indications. Cesarean
section is not always necessary; vaginal delivery can be
accomplished .
• Two associated conditions .
– Transient diabetes insipidus. This presumably is due to
elevated vasopressinase concentrations caused by
diminished hepatic production of its inactivating enzyme.
Trt – Vasopressin .
– Acute pancreatitis, which develops in up to half of women.
 Liver transplantation has rarely been performed for AFLP .

31. USUAL HEPATIC DISORDERS
AND PREGNANCY
• 1.VIRAL HEPATITIS
• 2. CHRONIC LIVER DISEASE AND PORTAL
HYPERTENSION
• 3. AUTOIMMUNE LIVER DISEASES
• 4. BUDD-CHIARI SYNDROME
• 5. HEPATIC NEOPLASIA AND MASS LESIONS

32. Viral hepatitis
Hepatitis A
• It does not appear to alter the normal course
of pregnancy, nor does pregnancy appear to
influence the natural history of hepatitis A.

33. Hepatitis E (non enveloped ss RNA)
• an epidemic disease during the monsoon season in
central and south Asia and India.
• during the third trimester of pregnancy is a cause of
fulminant hepatic failure and has a mortality rate of up
to 20% .
• Associated with intrauterine fetal death .
• Maternal fetal transmission of hepatitis E resulting in
symptomatic neonatal hepatitis .
• No known therapy prevents vertical transmission of
this virus

34. Hepatitis B
• As a rule, maternal hepatitis B virus infection
does not influence the course of pregnancy, nor
does pregnancy alter the natural history of
maternal hepatitis B infection.
• Most women of childbearing age with chronic
hepatitis B are healthy virus carriers with a very
low risk of developing complications of their
disease.
• Vertical transmission is 10%(second tri.) and
90%(third tri. Infections)

36. HBsAg Anti HBc IgM- Anti HBc Anti-HBs Interpretation
- - - - Never infected
- + - + Immune due to
natural infection
- - - + Immune due to
vaccination
+ + + - Acute infection
+ + - - Chronic infection
- + - - • Past infection
• Low level chr.
Infection
• Passive
transfer to the
infant
• False positive
anti HBc

37. • Without treatment, vertical transmission is 90% in the
infants born to both HBsAg and HBeAg positive and
10% in the infants born to HbsAg postive mothers .
• Antivirals to given to those mothers who are HBeAg
positive and whose HBV DNA is > 109 copies
• The infants of mothers with a reactive serum test for
hepatitis B surface antigen should
– receive HBIG and first dose of Hep B vaccine (0, 1, 6
mnths) within 12 hrs at birth .

38. Antiviral therapy
• Based on the severity of disease (hepatic activity
and fibrosis)
• Interferon therapy C/I during pregnancy .
• Oral agents
– Telbivudine and tenofovir are pregnancy category B
drugs and are preferred.
– Lamivudine is a pregnancy category C drug, but is
thought to be associated with a low risk of
complications .
– Other drugs insufficient data .

39. D/D in the III trimester
Disorder AST Bilirubin
Cholestasis of pregnancy <200 1-5
Acute fatty liver of
pregnancy
200-800 4-10
Hepatitis >2000 5-20

40. Budd Chiari Syndrome
• Pregnancy is a predisposing factor for the
development of venous thrombosis.
• Hepatic vein thrombosis may occur in association
with HELLP syndrome and with preeclampsia in
women who have antiphospholipid antibody.
• Should be evaluated for the presence of
antiphospholipid antibody and and other
circulating procoagulants( factor V Leiden )

41. Autoimmune hepatitis
• 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.

42. • 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.
• Azathioprine
– FDA category D (positive evidence of risk),
– However data from patients with IBD suggest it is likely
to be safe in pregnancy at dosages less than 100mg/day.

43. CHRONIC LIVER DISEASE AND PORTAL
HYPERTENSION
• 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
• Portal hypertension, ascites, and compensatory
dilation of submucosal esophageal veins
connecting the portal circulation and the azygos
vein can occur in pregnant women with
noncirrhotic portal hypertension aggravated by
increased circulating blood volume .

44. • Even in the absence of pathologic causes of portal
hypertension, these esophageal venous collaterals may become
engorged during gestation due to increased blood flow and
compression of the inferior vena cava by the enlarging uterus .
• Treating bleeding esophageal varices with nonselective beta-
blockers, band ligation, sclerotherapy and octreotide is safe
and effective during pregnancy.

45. Pregnancy and liver transplantation
• With advances in transplantation, and
immunosuppression, it is unnecessary to discourage
pregnancy of most female liver transplant recipients at
reproductive age.
• The first report of successful pregnancy after liver
transplantation was published in 1978.
• 37 cases of pregnancies after liver transplantation have
been reported worldwide.

46. • Pregnancy planned at least 2 years after liver transplantation
with stable allograft function can have excellent maternal and
neonatal outcome.
• Transplant patients should continue immunosuppressive
therapy during gestation .
• Treatment regimens (esp Tacrolimus ) used to prevent graft
rejection have not been associated with teratogenicity.
• Adverse effects of these medications,however, including
hypertension and hyperglycemia, may increase the incidence of
fetal distress and preeclampsia .

47. THANK YOU