Liver diseases in pregnancy Lisa McKnight, MD, FRCPC

Liver diseases in pregnancy
Lisa McKnight, MD, FRCPC
Hin Hin Ko, MD, FRCPC
CDDW 2013
• Both speakers have no relevant financial
disclosures
CDDW/CASL Meeting Session:
CanMEDS Roles Covered in this Session:

Medical Expert (as Medical Experts, physicians integrate all of the CanMEDS Roles,
applying medical knowledge, clinical skills, and professional attitudes in their provision of
patient-centered care. Medical Expert is the central physician Role in the CanMEDS
framework.)
Communicator (as Communicators, physicians effectively facilitate the doctor-patient
relationship and the dynamic exchanges that occur before, during, and after the medical
encounter.)

Collaborator (as Collaborators, physicians effectively work within a healthcare team to
achieve optimal patient care.)
Manager (as Managers, physicians are integral participants in healthcare organizations,
organizing sustainable practices, making decisions about allocating resources, and
contributing to the effectiveness of the healthcare system.)
Health Advocate (as Health Advocates, physicians responsibly use their expertise and
influence to advance the health and well-being of individual patients, communities, and
populations.)

Scholar (as Scholars, physicians demonstrate a lifelong commitment to reflective learning,
as well as the creation, dissemination, application and translation of medical knowledge.)
Professional (as Professionals, physicians are committed to the health and well-being of
individuals and society through ethical practice, profession-led regulation, and high personal
standards of behaviour.)
At the end of this session,
participants should be able:
• To recognize normal physiologic changes
associated with pregnancy.
• To have a systematic approach to liver
diseases in pregnancy.
• To recognize and manage intrahepatic
cholestasis of pregnancy.
• To recognize acute fatty liver of
pregnancy and HELLP syndrome.
Liver Disease in Pregnancy
• Normal physiologic changes
• Liver disease specific to pregnancy
– ICP, AFLP
• Multisystem dx unique to pregnancy
• Intercurrent liver disease in
pregnancy (Viral hep)
• Chronic liver diseases
• Pregnancy as predisposing factor
Liver during normal pregnancy
• Size and appearance of liver unchanged
• Blood flow to liver unchanged despite
increased maternal blood flow



Hct
Albumin
Bilirubin
GGT (late)
transferrin
AST/ALT
PT
Bile Acids
ALP (2nd/3rd)
Cholesterol (Total
Chol + TGs )
Hepatol 1996;23(5):1030
Physical Examination
• Spider angiomata 60-70%
• Palmar erythema (63%
white, 39% black women)
• Liver is not palpable
• Jaundice is NOT normal
Cardinal Features of Disease
•
•
•
•
•
Jaundice
Pruritus
Abdominal pain
Nausea/Vomiting
Liver biochemical abnormalities
Case
• 25 yo medical student, G2P1, 35 weeks
GA, singleton with intractable itching.
• Primarily palms and soles, prevents
sleep
• Elevated ALT/AST, ALP, Bili
• Will Urso help with the itch?
• What is optimal timing of delivery?
Intrahepatic Cholestasis of Pregnancy
Prevalence:
• Geographic variation
• 1-2% pregnancies in US/Europe; 5% Latinos
Timing:
• Late 2nd to 3rd trimester (between 28-30 wk
gestation)
• Recurs in 2/3 of subsequent pregnancies
• 5x more frequent with multiple gestations
ICP Pathogenesis
• Genetic
• More common if family history
• Assn with MDR-3 gene defect
• Hormonal
• Sensitivity to cholestatic effect of estrogen
• Administration of estrogen may precipitate
• Environmental
• More common in colder months
• Selenium exposure
ICP Clinical Presentation
• Intense pruritus in palms
and soles
• Pruritus worse at night
• Excoriations due to
scratching
• Jaundice (10%) starts 1-4
wks after pruritus
• Nausea and vomiting 575%
• Abdominal pain 9-24%
ICP Laboratory findings
• Cholestatic picture
• Total bilirubin rarely > 85umol/L
• GGT either normal or only modestly
elevated
• AST/ALT elevated 2-10x; normal in 20-60%
• PT can be elevated
– Vit K deficiency
• Elevated bile acids
– do not correlate with severity
ICP Management
• Vitamin K before delivery
• Ursodeoxycholic acid (500mg BID until delivery
or 15mg/kg/d)
• Cholestyramine (8-16g per day)
• Hydroxyzine (25-50mg per day)
• Fetal Complications:
–
–
–
–
Premature labor – 30-40%
Meconium-stained amniotic fluid 27%
Fetal distress 18%
Stillbirth 3%
World J Gastro 2009 15(17):2049
ICP Management
ICP Management
ICP Management
• Urso:
– Reduced itching by -16mm on visual scale
– Statistically significant
– Did not meet clinically significant threshold (-30
mm)
– 32% women met clinically significant criteria
(NNT=6)
– RR meconium in fluid 0.39
• Early delivery vs. expectant
– 88% maternity units in UK induce at 37-38 wks GA
– Expectant: 63% had early intervention
– Early not assn with ↑C-section
Conclusions
• First trial to report quantified reduction in itching
• Urso significantly reduces pruritus but size of
benefit may be too small for doctors/women to
agree to it.
• Pregnancy risk B
• Unclear benefit to early delivery, but most
women/physicians currently practice
Hyperemesis Gravidarum
Prevalence:
•“morning sickness” in > 50%
•hyperemesis gravidarum
complicates 0.35% - 0.8% of pregnancies
Timing:
•1st trimester (4-10wk); resolves by 20 wk GA
Hyperemesis Gravidarum
Presentation:
• Severe, persistent nausea and vomiting,
wt loss > 5% or pre-preg BW or
vomiting >3x/d with wt loss >3kg +
ketonuria
• Mild jaundice, pruritus
Hyperemesis Gravidarum
Blood work:
• 50% have  LFTs (2-3x normal) seen 1-3 wk
after onset
• ALT > AST; usually 100s, rarely as high as
1000s
• Hyperbilirubinemia can occur, but rarely
>4mg/dL
• Electrolyte imbalances
Treatment:
• Gut rest, IV fluids
• Resolves rapidly with cessation of emesis
• Negligible mortality
HELLP Syndrome
• Severe, life-threatening complication of
preeclampsia
Incidence:
• 1-2/1,000 pregnancies
• 10-20% of women with preeclampsia/eclampsia
Timing:
• Mostly in 3rd trimester (28 -36 wk GA)
• 2nd trimester and post-partum are possible
Etiology:
• ? Imbalance between vasoconstrictive and
vasodilative forces causing endothelial dysfunction
and platelet aggregation
HELLP Syndrome
• Clinical Presentation:
– Mean age: 25 years
– Abdo pain (RUQ; mid-epigastrium) 70-90%
– Nausea, vomiting & malaise common
– Headache 25%
– Visual changes 15-30%
HELLP Syndrome
• Physical exam:
– Hypertension (>140/90 mmHg) 85%
– Proteinuria 85%
– Generalized edema 50-67%
– Ascites 8-10%
– Jaundice 5%
H EL LP
• Lab Abnormalities
– emolysis,
( AST/ALT), (low platelets)
– Blood smear - schistocytes
– Low haptoglobin level in 95%
– Bilirubin elevation 47-62%
– Low platelets (<100) 50%
– AST/ALT elevation (3x above normal)
HELLP Syndrome
• Maternal complications
–
–
–
–
–
–
–
–
–
DIC 4-38%
Placental abruption 10-16%
Acute renal failure 1-8%
Severe ascites 5-8%
Pulmonary edema 2-10%
ARDS 1%
Hepatic infarction / rupture/hematoma 1%
1.1%; stroke, cardiac arrest
Mortality 8%
HELLP Syndrome
• Management
– Stabilize mother; assess fetal condition;
decide whether prompt delivery is needed
– Consult MFM
– Glucocorticosteroids; anti-hypertensive; IV
Mg sulphate
– Prompt delivery is indicated:
• >34 wk GA
• Non-reassuring fetal status
• Presence of severe maternal disease
Acute Fatty Liver of Pregnancy
Epidemiology:
•Rare; 1/7000 – 1/20,000 deliveries
•More common with primiparas, male & multiple
gestations
Time:
•Typically in 3rd trimester
•Can recur in subsequent pregnancies
Etiology:
•? Decreased mitochondrial oxidation of fatty acids
with elevated estrogen levels
•LCHAD deficiency identified in 20%
Acute Fatty Liver of Pregnancy
Presentation:
• Nausea, vomiting 75%
• Abdominal pain (epigastric) 50%
• Anorexia
• Jaundice
• Preeclampsia (HTN, proteinuria) seen in > 50%
• Other: asterixis, encephalopathy, ascites
• Rare: transient polyuria & polydipsia due to
central diabetes insipidus; pancreatitis
AFLP Laboratory findings
•
•
•
•
•
•
AST / ALT elevated (up to 1000 IU/L)
Elevated Bili
PT may be prolonged
Leukocytosis with neutrophilic left shift
Thrombocytopenia in 90%
Renal failure, hypoglycemia,
hyperuricemia
Liver Biopsy
• NOT indicated
– Overall architecture is
not altered
– Microvesicular fatty
infiltration of
hepatocytes
– Droplets are minute,
surround central
nuclei
Acute Fatty Liver of Pregnancy
• Maternal Complications
– Upper GI bleed 30-40%
– Renal dysfunction 70%
– DIC 56%
– Pancreatitis 30%
– Severe hypoglycemia 25-50%
– Mortality > 90% before 1970; now < 10% for
mother, baby 36%
Acute Fatty Liver of Pregnancy
Management:
•Medical and obstetric emergency!!
•Treatment – deliver baby ASAP after
maternal stabilization
At the end of this session,
participants should be able:
• To recognize normal physiologic changes
associated with pregnancy.
• To have a systematic approach to liver
diseases in pregnancy.
• To recognize and manage intrahepatic
cholestasis of pregnancy.
• To recognize acute fatty liver of
pregnancy and HELLP syndrome.
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