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Liver Disease in Pregnancy
Bibleclass 23.09.2015
Felix Brunner
General Considerations
Bibleclass 23.09.2015, Brunner 2
General Considerations
Bibleclass 23.09.2015, Brunner 2
Intrahepatic
Cholestasis of
Pregnancy
HELLP
Pre-existing Liver
Cirrhosis
Bile Stone
Disease
General Considerations
Bibleclass 23.09.2015, Brunner 2
Intrahepatic
Cholestasis of
Pregnancy
HELLP
Pre-existing Liver
Cirrhosis
Bile Stone
Disease
Acute Fatty Liver
of Pregnancy
General Considerations
Bibleclass 23.09.2015, Brunner 2
Intrahepatic
Cholestasis of
Pregnancy
HELLP
Pre-existing Liver
Cirrhosis
Bile Stone
Disease
Acute Fatty Liver
of Pregnancy
Hepatitis B
Physiological Changes in
Pregnancy
Bibleclass 23.09.2015, Brunner 3
Cardiovascular Endocrinological
Biliary
Lab Parameter
Physiological Changes in
Pregnancy
Bibleclass 23.09.2015, Brunner 3
Cardiovascular
• Heart Rate,
Cardiac output ⬆• Blood pressure,
vascular
resistance ⬇• 50% blood
volume
Endocrinological
Biliary
Lab Parameter
Physiological Changes in
Pregnancy
Bibleclass 23.09.2015, Brunner 3
Cardiovascular
• Heart Rate,
Cardiac output ⬆• Blood pressure,
vascular
resistance ⬇• 50% blood
volume
Endocrinological
Biliary
Lab Parameter
• Alk. Phosph⬆• Albumin ⬇
Physiological Changes in
Pregnancy
Bibleclass 23.09.2015, Brunner 3
Cardiovascular
• Heart Rate,
Cardiac output ⬆• Blood pressure,
vascular
resistance ⬇• 50% blood
volume
Endocrinological
• Hyperestrogenic
state
Spider Nävi
Palmar
erythema
Biliary
Lab Parameter
• Alk. Phosph⬆• Albumin ⬇
Physiological Changes in
Pregnancy
Bibleclass 23.09.2015, Brunner 3
Cardiovascular
• Heart Rate,
Cardiac output ⬆• Blood pressure,
vascular
resistance ⬇• 50% blood
volume
Endocrinological
• Hyperestrogenic
state
Spider Nävi
Palmar
erythema
Biliary
• Gallbladder
Motility ⬇
Lab Parameter
• Alk. Phosph⬆• Albumin ⬇
Overview
• Hyperemesis Gravidarum
• Intrahepatic Cholestasis of
Pregnancy
• Pre-Eclampsia & Eclampsia
• HELLP-Syndrom
• Acute Fatty Liver in Pregnancy
• HBV Transmission
4Bibleclass 29.04.2015, Brunner
Hyperemesis Gravidarum
Bibleclass 23.09.2015, Brunner 5
Hyperemesis Gravidarum
Trimester: 1-2
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Hyperemesis Gravidarum
Trimester: 1-2
Symptoms: Intractable Vomitus
Ketosis
Bibleclass 23.09.2015, Brunner 5
Hyperemesis Gravidarum
Trimester: 1-2
Symptoms: Intractable Vomitus
Ketosis
5% Weight loss
Bibleclass 23.09.2015, Brunner 5
Hyperemesis Gravidarum
Trimester: 1-2
Symptoms: Intractable Vomitus
Ketosis
5% Weight loss
Epidemiology: 0.3-2% of all Pregnancies
Bibleclass 23.09.2015, Brunner 5
Hyperemesis Gravidarum
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Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Bibleclass 23.09.2015, Brunner 6
Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Risk Factors: ⬆ BMI
Bibleclass 23.09.2015, Brunner 6
Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Risk Factors: ⬆ BMI
Psychiatric Disorders,
Bibleclass 23.09.2015, Brunner 6
Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Risk Factors: ⬆ BMI
Psychiatric Disorders,
Diabetes mellitus
Bibleclass 23.09.2015, Brunner 6
Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Risk Factors: ⬆ BMI
Psychiatric Disorders,
Diabetes mellitus
Multiple Pregnancies
Bibleclass 23.09.2015, Brunner 6
Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Risk Factors: ⬆ BMI
Psychiatric Disorders,
Diabetes mellitus
Multiple Pregnancies
Positive Family History
Bibleclass 23.09.2015, Brunner 6
Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Risk Factors: ⬆ BMI
Psychiatric Disorders,
Diabetes mellitus
Multiple Pregnancies
Positive Family History
Bibleclass 23.09.2015, Brunner 6
Hyperemesis Gravidarum
Mechanism: Mixed (Motility, Hormonal, ANS)
Risk Factors: ⬆ BMI
Psychiatric Disorders,
Diabetes mellitus
Multiple Pregnancies
Positive Family History
Lab: Aminotransferases ≤ 20xULN
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Hyperemesis Gravidarum
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Hyperemesis Gravidarum
Complications:
Mother: Dehydration, AKI, Weight ⬇Wernicke Encephalopathy
Foetus: Low Birth Weight
Preterm Delivery
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Hyperemesis Gravidarum
Complications:
Mother: Dehydration, AKI, Weight ⬇Wernicke Encephalopathy
Foetus: Low Birth Weight
Preterm Delivery
Therapy: Rehydration
Bibleclass 23.09.2015, Brunner 7
Hyperemesis Gravidarum
Complications:
Mother: Dehydration, AKI, Weight ⬇Wernicke Encephalopathy
Foetus: Low Birth Weight
Preterm Delivery
Therapy: Rehydration
Antiemetics
Bibleclass 23.09.2015, Brunner 7
Hyperemesis Gravidarum
Complications:
Mother: Dehydration, AKI, Weight ⬇Wernicke Encephalopathy
Foetus: Low Birth Weight
Preterm Delivery
Therapy: Rehydration
Antiemetics
Vitamin Supp. (e.g. B1!!)
Bibleclass 23.09.2015, Brunner 7
Intrahepatic Cholestasis of
Pregnancy
Bibleclass 23.09.2015, Brunner 8
Intrahepatic Cholestasis of
Pregnancy
Trimester: 2nd Half of Pregnancy
Bibleclass 23.09.2015, Brunner 8
Intrahepatic Cholestasis of
Pregnancy
Trimester: 2nd Half of Pregnancy
Symptoms: Pruritus (particularly Soles & Palms)
Diarrhoea
Bibleclass 23.09.2015, Brunner 8
Intrahepatic Cholestasis of
Pregnancy
Trimester: 2nd Half of Pregnancy
Symptoms: Pruritus (particularly Soles & Palms)
Diarrhoea
Jaundice
Bibleclass 23.09.2015, Brunner 8
Intrahepatic Cholestasis of
Pregnancy
Trimester: 2nd Half of Pregnancy
Symptoms: Pruritus (particularly Soles & Palms)
Diarrhoea
Jaundice
Epidemiology: 0.1-1.5% all Pregnancies
Bibleclass 23.09.2015, Brunner 8
Intrahepatic Cholestasis of
Pregnancy
Trimester: 2nd Half of Pregnancy
Symptoms: Pruritus (particularly Soles & Palms)
Diarrhoea
Jaundice
Epidemiology: 0.1-1.5% all Pregnancies
(Scandinavia & South America ⬆)
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ICP - Pathogenesis
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Joshi, Lancet 2010
• 15% Mutation
MDR3 gene
(10 identified)
• Female
Hormones
Inhibit Bile Salt
Export Pumps
ICP
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ICP
Risk Factors: Intrahepatic Cholestasis due to
Bibleclass 23.09.2015, Brunner 10
ICP
Risk Factors: Intrahepatic Cholestasis due to
Contraceptive Drugs,
Bibleclass 23.09.2015, Brunner 10
ICP
Risk Factors: Intrahepatic Cholestasis due to
Contraceptive Drugs,
Positive Family History
Bibleclass 23.09.2015, Brunner 10
ICP
Risk Factors: Intrahepatic Cholestasis due to
Contraceptive Drugs,
Positive Family History
Bibleclass 23.09.2015, Brunner 10
ICP
Risk Factors: Intrahepatic Cholestasis due to
Contraceptive Drugs,
Positive Family History
Lab: Aminotransferases ≤ 20xULN
Bibleclass 23.09.2015, Brunner 10
ICP
Risk Factors: Intrahepatic Cholestasis due to
Contraceptive Drugs,
Positive Family History
Lab: Aminotransferases ≤ 20xULN
Bile Acids > 10 µmol/L
Bibleclass 23.09.2015, Brunner 10
ICP
Risk Factors: Intrahepatic Cholestasis due to
Contraceptive Drugs,
Positive Family History
Lab: Aminotransferases ≤ 20xULN
Bile Acids > 10 µmol/L
Bibleclass 23.09.2015, Brunner 10
ICP
Bibleclass 23.09.2015, Brunner 11
ICP
Complications:
Mother: Risk of Biliary &
Autoimmune Disease in the
Future
Foetus: Anoxia, Prematurity, Stillbirth,
Perinatal Death
Bibleclass 23.09.2015, Brunner 11
ICP
Complications:
Mother: Risk of Biliary &
Autoimmune Disease in the
Future
Foetus: Anoxia, Prematurity, Stillbirth,
Perinatal Death
Therapy: Ursodeoxycholicacid
Bibleclass 23.09.2015, Brunner 11
ICP
Complications:
Mother: Risk of Biliary &
Autoimmune Disease in the
Future
Foetus: Anoxia, Prematurity, Stillbirth,
Perinatal Death
Therapy: Ursodeoxycholicacid
10-15mg/kg
Bibleclass 23.09.2015, Brunner 11
ICP
Complications:
Mother: Risk of Biliary &
Autoimmune Disease in the
Future
Foetus: Anoxia, Prematurity, Stillbirth,
Perinatal Death
Therapy: Ursodeoxycholicacid
10-15mg/kg
Early Delivery Week (36)-38
Bibleclass 23.09.2015, Brunner 11
Pre-Eclampsia & Eclampsia
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Pre-Eclampsia & Eclampsia
Trimester: 2nd Half of Pregancy
Bibleclass 23.09.2015, Brunner 12
Pre-Eclampsia & Eclampsia
Trimester: 2nd Half of Pregancy
Definition: Pre-Eclampsia = AHT +
Proteinuria
Bibleclass 23.09.2015, Brunner 12
Pre-Eclampsia & Eclampsia
Trimester: 2nd Half of Pregancy
Definition: Pre-Eclampsia = AHT +
Proteinuria
Eclampsia = Pre-Eclampsia
+ Seizures
Bibleclass 23.09.2015, Brunner 12
Pre-Eclampsia & Eclampsia
Trimester: 2nd Half of Pregancy
Definition: Pre-Eclampsia = AHT +
Proteinuria
Eclampsia = Pre-Eclampsia
+ Seizures
Epidemiology: 5-10% all pregnancies
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Pre-Eclampsia & Eclampsia
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Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
& Coagulation Activation
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
& Coagulation Activation
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
& Coagulation Activation
Risk Factors: Age <16 or >45 years
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
& Coagulation Activation
Risk Factors: Age <16 or >45 years
Primiparity
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
& Coagulation Activation
Risk Factors: Age <16 or >45 years
Primiparity
Pre-existing AHT
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
& Coagulation Activation
Risk Factors: Age <16 or >45 years
Primiparity
Pre-existing AHT
pos. Family History
Occurrence previous Pregnancy
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
Mechanism: Placenta Ischemia
➡ Endothelial Dysfunction
& Coagulation Activation
Risk Factors: Age <16 or >45 years
Primiparity
Pre-existing AHT
pos. Family History
Occurrence previous Pregnancy
Bibleclass 23.09.2015, Brunner 13
Pre-Eclampsia & Eclampsia
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Pre-Eclampsia & Eclampsia
Complications:
Mother: Hypertensive Crises
Renal Dysfunction
Hepatic Rupture or InfarctionSeizures
Increased Morbidity & Mortality
Bibleclass 23.09.2015, Brunner 14
Pre-Eclampsia & Eclampsia
Complications:
Mother: Hypertensive Crises
Renal Dysfunction
Hepatic Rupture or InfarctionSeizures
Increased Morbidity & Mortality
Therapy: Early Delivery, Magnesiumsulfate
Bibleclass 23.09.2015, Brunner 14
HELLP
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HELLP
Trimester: 2nd Half of Pregancy
Bibleclass 23.09.2015, Brunner 15
HELLP
Trimester: 2nd Half of Pregancy
Definition: Hemolysis
Bibleclass 23.09.2015, Brunner 15
HELLP
Trimester: 2nd Half of Pregancy
Definition: Hemolysis
Elevated Liver Enzymes
Bibleclass 23.09.2015, Brunner 15
HELLP
Trimester: 2nd Half of Pregancy
Definition: Hemolysis
Elevated Liver Enzymes
Low Platelets
Bibleclass 23.09.2015, Brunner 15
HELLP
Trimester: 2nd Half of Pregancy
Definition: Hemolysis
Elevated Liver Enzymes
Low Platelets
Bibleclass 23.09.2015, Brunner 15
HELLP
Trimester: 2nd Half of Pregancy
Definition: Hemolysis
Elevated Liver Enzymes
Low Platelets
Epidemiology: 0.6 % all Pregnancies
Bibleclass 23.09.2015, Brunner 15
HELLP
Trimester: 2nd Half of Pregancy
Definition: Hemolysis
Elevated Liver Enzymes
Low Platelets
Epidemiology: 0.6 % all Pregnancies
5-10% Pre-Eclampsia
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HELLP
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HELLP
Mechanism: Not Clear
Bibleclass 23.09.2015, Brunner 16
HELLP
Mechanism: Not Clear
Severe Form of Pre-Eclampsia?
Bibleclass 23.09.2015, Brunner 16
HELLP
Mechanism: Not Clear
Severe Form of Pre-Eclampsia?
Bibleclass 23.09.2015, Brunner 16
HELLP
Mechanism: Not Clear
Severe Form of Pre-Eclampsia?
Risk Factors: Advanced Maternal Age
Multiparity
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HELLP
Mechanism: Not Clear
Severe Form of Pre-Eclampsia?
Risk Factors: Advanced Maternal Age
Multiparity
Caucasian Ethnicity
Bibleclass 23.09.2015, Brunner 16
HELLP
Mechanism: Not Clear
Severe Form of Pre-Eclampsia?
Risk Factors: Advanced Maternal Age
Multiparity
Caucasian Ethnicity
Lab: Hemolysis, Platelets ⬇
Bibleclass 23.09.2015, Brunner 16
HELLP
Mechanism: Not Clear
Severe Form of Pre-Eclampsia?
Risk Factors: Advanced Maternal Age
Multiparity
Caucasian Ethnicity
Lab: Hemolysis, Platelets ⬇
Aminotransferases & Bilirubin ⬆
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HELLP
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HELLP
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HELLP
Complications:
Mother: Hepatic Encephalopathy
Renal Failure
Hepatic Hematoma & Rupture
Hepatic Infarction
Child: Prematurity ➡ 6-70% mortality
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HELLP
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HELLP
Therapy: Early delivery (≥ week 34)
Bibleclass 23.09.2015, Brunner 19
HELLP
Therapy: Early delivery (≥ week 34)
ICU
Bibleclass 23.09.2015, Brunner 19
HELLP
Therapy: Early delivery (≥ week 34)
ICU
Antihypertensive Therapy
(Labetalolol, Hydralazin,
Nifedipin)
Bibleclass 23.09.2015, Brunner 19
HELLP
Therapy: Early delivery (≥ week 34)
ICU
Antihypertensive Therapy
(Labetalolol, Hydralazin,
Nifedipin)
OLT in case of Liver Failure
Bibleclass 23.09.2015, Brunner 19
Acute Fatty Liver of Pregnancy
Bibleclass 23.09.2015, Brunner 20
Acute Fatty Liver of Pregnancy
Trimester: 3rd.
Bibleclass 23.09.2015, Brunner 20
Acute Fatty Liver of Pregnancy
Trimester: 3rd.
Symptoms: Vomiting, Jaundice,
Hypoglycemia,
Bibleclass 23.09.2015, Brunner 20
Acute Fatty Liver of Pregnancy
Trimester: 3rd.
Symptoms: Vomiting, Jaundice,
Hypoglycemia,
Lactacidosis,
Bibleclass 23.09.2015, Brunner 20
Acute Fatty Liver of Pregnancy
Trimester: 3rd.
Symptoms: Vomiting, Jaundice,
Hypoglycemia,
Lactacidosis,
Hyperammonaemia
Bibleclass 23.09.2015, Brunner 20
Acute Fatty Liver of Pregnancy
Trimester: 3rd.
Symptoms: Vomiting, Jaundice,
Hypoglycemia,
Lactacidosis,
Hyperammonaemia
Epidemiology: 5/100’000 pregnancies
Bibleclass 23.09.2015, Brunner 20
Acute Fatty Liver of Pregnancy
Trimester: 3rd.
Symptoms: Vomiting, Jaundice,
Hypoglycemia,
Lactacidosis,
Hyperammonaemia
Epidemiology: 5/100’000 pregnancies
Bibleclass 23.09.2015, Brunner 20
Acute Fatty Liver of Pregnancy
Bibleclass 23.09.2015, Brunner 21
Mechanism:
• Mitochondrial
Cytopathy
• The Fetus has a defect
Fatty acid β oxidation
• Deficient long-chain 3-
hydoxyacyl coenzyme A
dehydrogenase
Mother
Acute Fatty Liver of Pregnancy
Bibleclass 23.09.2015, Brunner 22
Acute Fatty Liver of Pregnancy
Complications:
Mother: Risk factor for development
of biliary & autoimmune
disease in the future
Foetus: Anoxia, prematurity, stillbirth,
perinatal death
Bibleclass 23.09.2015, Brunner 22
Acute Fatty Liver of Pregnancy
Complications:
Mother: Risk factor for development
of biliary & autoimmune
disease in the future
Foetus: Anoxia, prematurity, stillbirth,
perinatal death
Therapy: Ursodeoxycholicacid
Bibleclass 23.09.2015, Brunner 22
Acute Fatty Liver of Pregnancy
Complications:
Mother: Risk factor for development
of biliary & autoimmune
disease in the future
Foetus: Anoxia, prematurity, stillbirth,
perinatal death
Therapy: Ursodeoxycholicacid
10-15mg/kg
Bibleclass 23.09.2015, Brunner 22
Acute Fatty Liver of Pregnancy
Complications:
Mother: Risk factor for development
of biliary & autoimmune
disease in the future
Foetus: Anoxia, prematurity, stillbirth,
perinatal death
Therapy: Ursodeoxycholicacid
10-15mg/kg
Early delivery week (36)-38
Bibleclass 23.09.2015, Brunner 22
Acute Fatty Liver of PregnancySwansea Diagnostic
Criteria Risk Factors:
• Twin pregnancy
• Nulliparity
• Inverse Relation
between BMI & AFLP
Bibleclass 23.09.2015, Brunner 23
Acute Fatty Liver of Pregnancy
Bibleclass 23.09.2015, Brunner 24
Acute Fatty Liver of Pregnancy
Complications:
Mother: Hepatic Encephalopathy
Liver Failure, Liver Rupture
Renal Failure
Maternal Mortality 1-20%
Child: Features associated
with defect fatty acid oxidation:
Hypoglycaemia, Hepatic failure,
MyopathyBibleclass 23.09.2015, Brunner 24
HBV Transmission
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HBV Transmission
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HBV Transmission
Background:
• Switzerland:
0.5% of Pregnant Women
HBs-Antigene positive
• Mother-to-Child-Transmission:- HBe-Ag positive: 70-90%
- HBe-Ag negative: 10-40%
- Acute Hepatitis B in Pregnancy: 40-60%
Bibleclass 23.09.2015, Brunner 27
HBV Transmission
Background:
• Postnatal Hepatitis B Immunoglobulin
& HBV Vaccine reduces Transmission to 5-10%
• Predictive for Immunoprophylaxis Failure
HBe-Antigen positive
HBV DNA > 200‘000 IU/ml
Bibleclass 23.09.2015, Brunner 28
HBV Transmission
Bibleclass 23.09.2015, Brunner 29Bleich, J Clin Gastr 2014
Bibleclass 23.09.2015, Brunner 30
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