Liver Disease in Pregnancy - Mucosal Immunology · General Considerations Bibleclass 23.09.2015, Brunner 2 Intrahepatic Cholestasis of Pregnancy HELLP Pre-existing Liver Cirrhosis

Liver Disease in Pregnancy

Bibleclass 23.09.2015

Felix Brunner

General Considerations

Bibleclass 23.09.2015, Brunner 2



Intrahepatic

Cholestasis of

Pregnancy

HELLP

Pre-existing Liver

Cirrhosis

Bile Stone

Disease



Intrahepatic

Cholestasis of

Pregnancy

HELLP

Pre-existing Liver

Cirrhosis

Bile Stone

Disease

Acute Fatty Liver

of Pregnancy



Intrahepatic

Cholestasis of

Pregnancy

HELLP

Pre-existing Liver

Cirrhosis

Bile Stone

Disease

Acute Fatty Liver

of Pregnancy

Hepatitis B

Physiological Changes in

Pregnancy


Cardiovascular Endocrinological

Biliary

Lab Parameter


Pregnancy


Cardiovascular

• Heart Rate,

Cardiac output ⬆• Blood pressure,

vascular

resistance ⬇• 50% blood

volume

Endocrinological

Biliary

Lab Parameter


Pregnancy


Cardiovascular

• Heart Rate,


vascular


volume

Endocrinological

Biliary

Lab Parameter

• Alk. Phosph⬆• Albumin ⬇


Pregnancy


Cardiovascular

• Heart Rate,


vascular


volume

Endocrinological

• Hyperestrogenic

state

Spider Nävi

Palmar

erythema

Biliary

Lab Parameter



Pregnancy


Cardiovascular

• Heart Rate,


vascular


volume

Endocrinological

• Hyperestrogenic

state

Spider Nävi

Palmar

erythema

Biliary

• Gallbladder

Motility ⬇

Lab Parameter


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



Trimester: 1-2



Trimester: 1-2

Symptoms: Intractable Vomitus

Ketosis



Trimester: 1-2


Ketosis

5% Weight loss



Trimester: 1-2


Ketosis

5% Weight loss

Epidemiology: 0.3-2% of all Pregnancies





Mechanism: Mixed (Motility, Hormonal, ANS)




Risk Factors: ⬆ BMI





Psychiatric Disorders,






Diabetes mellitus






Diabetes mellitus

Multiple Pregnancies






Diabetes mellitus


Positive Family History






Diabetes mellitus








Diabetes mellitus



Lab: Aminotransferases ≤ 20xULN





Complications:

Mother: Dehydration, AKI, Weight ⬇Wernicke Encephalopathy

Foetus: Low Birth Weight

Preterm Delivery



Complications:



Preterm Delivery

Therapy: Rehydration



Complications:



Preterm Delivery


Antiemetics



Complications:



Preterm Delivery


Antiemetics

Vitamin Supp. (e.g. B1!!)


Intrahepatic Cholestasis of

Pregnancy



Pregnancy

Trimester: 2nd Half of Pregnancy



Pregnancy


Symptoms: Pruritus (particularly Soles & Palms)

Diarrhoea



Pregnancy



Diarrhoea

Jaundice



Pregnancy



Diarrhoea

Jaundice

Epidemiology: 0.1-1.5% all Pregnancies



Pregnancy



Diarrhoea

Jaundice

Epidemiology: 0.1-1.5% all Pregnancies

(Scandinavia & South America ⬆)


ICP - Pathogenesis


Joshi, Lancet 2010

• 15% Mutation

MDR3 gene

(10 identified)

• Female

Hormones

Inhibit Bile Salt

Export Pumps

ICP


ICP

Risk Factors: Intrahepatic Cholestasis due to


ICP


Contraceptive Drugs,


ICP





ICP





ICP






ICP





Bile Acids > 10 µmol/L


ICP





Bile Acids > 10 µmol/L


ICP


ICP

Complications:

Mother: Risk of Biliary &

Autoimmune Disease in the

Future

Foetus: Anoxia, Prematurity, Stillbirth,

Perinatal Death


ICP

Complications:



Future


Perinatal Death

Therapy: Ursodeoxycholicacid


ICP

Complications:



Future


Perinatal Death


10-15mg/kg


ICP

Complications:



Future


Perinatal Death


10-15mg/kg

Early Delivery Week (36)-38


Pre-Eclampsia & Eclampsia



Trimester: 2nd Half of Pregancy




Definition: Pre-Eclampsia = AHT +

Proteinuria





Proteinuria

Eclampsia = Pre-Eclampsia

+ Seizures





Proteinuria

Eclampsia = Pre-Eclampsia

+ Seizures

Epidemiology: 5-10% all pregnancies





Mechanism: Placenta Ischemia




➡ Endothelial Dysfunction





& Coagulation Activation











Risk Factors: Age <16 or >45 years







Primiparity







Primiparity

Pre-existing AHT







Primiparity

Pre-existing AHT

pos. Family History

Occurrence previous Pregnancy







Primiparity

Pre-existing AHT

pos. Family History

Occurrence previous Pregnancy





Complications:

Mother: Hypertensive Crises

Renal Dysfunction

Hepatic Rupture or InfarctionSeizures

Increased Morbidity & Mortality



Complications:

Mother: Hypertensive Crises

Renal Dysfunction

Hepatic Rupture or InfarctionSeizures

Increased Morbidity & Mortality

Therapy: Early Delivery, Magnesiumsulfate


HELLP


HELLP



HELLP


Definition: Hemolysis


HELLP



Elevated Liver Enzymes


HELLP




Low Platelets


HELLP




Low Platelets


HELLP




Low Platelets

Epidemiology: 0.6 % all Pregnancies


HELLP




Low Platelets

Epidemiology: 0.6 % all Pregnancies

5-10% Pre-Eclampsia


HELLP


HELLP

Mechanism: Not Clear


HELLP


Severe Form of Pre-Eclampsia?


HELLP




HELLP



Risk Factors: Advanced Maternal Age

Multiparity


HELLP




Multiparity

Caucasian Ethnicity


HELLP




Multiparity

Caucasian Ethnicity

Lab: Hemolysis, Platelets ⬇


HELLP




Multiparity

Caucasian Ethnicity

Lab: Hemolysis, Platelets ⬇

Aminotransferases & Bilirubin ⬆


HELLP


HELLP


HELLP

Complications:

Mother: Hepatic Encephalopathy

Renal Failure

Hepatic Hematoma & Rupture

Hepatic Infarction

Child: Prematurity ➡ 6-70% mortality


HELLP


HELLP

Therapy: Early delivery (≥ week 34)


HELLP


ICU


HELLP


ICU

Antihypertensive Therapy

(Labetalolol, Hydralazin,

Nifedipin)


HELLP


ICU

Antihypertensive Therapy

(Labetalolol, Hydralazin,

Nifedipin)

OLT in case of Liver Failure


Acute Fatty Liver of Pregnancy



Trimester: 3rd.



Trimester: 3rd.

Symptoms: Vomiting, Jaundice,

Hypoglycemia,



Trimester: 3rd.


Hypoglycemia,

Lactacidosis,



Trimester: 3rd.


Hypoglycemia,

Lactacidosis,

Hyperammonaemia



Trimester: 3rd.


Hypoglycemia,

Lactacidosis,

Hyperammonaemia

Epidemiology: 5/100’000 pregnancies



Trimester: 3rd.


Hypoglycemia,

Lactacidosis,

Hyperammonaemia

Epidemiology: 5/100’000 pregnancies




Mechanism:

• Mitochondrial

Cytopathy

• The Fetus has a defect

Fatty acid β oxidation

• Deficient long-chain 3-

hydoxyacyl coenzyme A

dehydrogenase

Mother




Complications:

Mother: Risk factor for development

of biliary & autoimmune

disease in the future

Foetus: Anoxia, prematurity, stillbirth,

perinatal death



Complications:





perinatal death




Complications:





perinatal death


10-15mg/kg



Complications:





perinatal death


10-15mg/kg

Early delivery week (36)-38


Acute Fatty Liver of PregnancySwansea Diagnostic

Criteria Risk Factors:

• Twin pregnancy

• Nulliparity

• Inverse Relation

between BMI & AFLP





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


HBV Transmission


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%


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


HBV Transmission

Bibleclass 23.09.2015, Brunner 29Bleich, J Clin Gastr 2014


Documents

Liver Disease in Pregnancy - Mucosal Immunology · General Considerations Bibleclass 23.09.2015, Brunner 2 Intrahepatic Cholestasis of Pregnancy HELLP Pre-existing Liver Cirrhosis