liver disease in obstetrics

Question 1

How do LFTs change in a normal pregnancy

What is the effect on liver metabolism

Answer 1

Reduction: in serum protein, AST ALT(normal 30 in T3)
Increased: fibrinogen, ALP, carrier molecules eg caeruloplasmin(carries Cu) transferrin, thyroid binding globulin, corticosteroid binding globulin.
Liver metabolism increases

Question 2

ALP
What is it?
What if it is over 1000

Answer 2

Alkaline phosphatase is a group of enzymes that catalyzes the hydrolysis of phosphate esters in a basic environment to aid transport across cell membranes.
Probably placental but can do isoenzymes to exclude a bone (pagets, mets, #) or liver source

Question 3

Causes of viral hepatitis

Answer 3

Hep A B C D E

CMV EBV HSV

Question 4

Hepatitis A
Transmission
Progress + rate of chronic infection
Vertical transmission +management of neonate

Answer 4

Hep A is transmitted by the faecal oral route
It is acute, self limiting and does not result in chronic infection. Maternal fetal transmission is rare
If at or around delivery - baby should be given immunoglobulin at birth

Question 5

Hep B screening and prevention (generally and in pregnancy)

What is the incubation time

Answer 5

Screen on booking bloods for HBsAg

Immunization in national scheme at Infanrix- hexa 6/52 3/12 5/12
Health care workers immunized + blood and bodily fluid precautions
Immunisation of children, house hold contacts and sexual partners of Hep B +

Treat Hep B in pregnancy to reduce the risk of vertical transmission

Incubation 1-6 months

Question 6

Infanrix hexa - given when? what is in it?

Answer 6

Diptheria, tetanus, pertussis, polio, hep B, haemophilis influenzae B 6/52 3/12 5/12

Question 7

Hep B - what are the risks of vertical transmission
what are the risk factors
When does it occur
what procedures increase the risk

Answer 7

Invasive procedures increase the risk (CVS amnio)
Recommend NIPT, if needs, then amnio better - avoid transplacental amnio
Increased in abruption, PTL Threatened miscarriage
Risks increased if HBV viral load high + HBsAg
+ HBsAg 70-90%
-ve HBsAg 10-40%
5% transmission AN 95% Intrapartum

Question 8

If a woman has a positive screening on her booking bloods what other Ix need to be requested

Answer 8

HbeAg (hep B e antigen) 
Anti HBe 
HBV viral load
LFTs liver USS 
Prothrombin time

Question 9

What is the risk of disease progression of Hep B in pregnancy

Answer 9

1% woman have AN hepatic flares

25% PN hepatic flares - need close monitoring

Question 10

When do we treat mums withHep B in pregnancy and with what

How effective is it

Answer 10

AN Tx at 30-32 weeks with tenofovir 300 mg daily until 6/52 PP if HBV viral load is over 200000 IU/ml
Reduces neonatal infection 18% to 5%
Ensure referral to gastro enter for monitoring
(lamivudine - resistance)

Question 11

Intrapartum management of Hep B in pregnancy

Answer 11

Np FSE or FBS LSCS for normal indications

Question 12

How do we treat newborns to reduce the risk of hep B transmission

Answer 12

Wash the baby before IM immunisations
If HBsAg + mother then for Immunoglobulin at birth and first immunisation within 12 hours of del
then to have Infanrix hexa 6/52 3/12 5/12
For testing at 5/12 (can be weakly positive due to immunoglobulin given at birth - if so immunize at 6/12 + 7/12 and retest at 8/12
Treating babies as above 85-95% protective

Question 13

Can hep B + mums breastfeed

Answer 13

if vaccinated and had IG then yes - HBV is present in the breast milk but if treated then protective
Take car with cracked and bleeding nipples

Question 14

How common is hep B in NZ

How is it transmitted

Answer 14

1-2 % of the population
50% of cases are vertical transmission
Otherwise blood/ bodiy fluid exposure,

Question 15

Progress of hep B (not in pregnancy )
chronic transmission
mortality

Answer 15

Chronic carriers have a 25 % chance of dying from hep B
neonates have a 90% risk of becoming chronic carriers
adults with acute hep B 5 % conversion

Question 16

Out of pregnancy - who gets treatment and rates of success?

Answer 16

Out of pregnancy interferon sustains remission in 30% HBeAg + and 15% HBeAg -ve
Oral antivirals are lifelong therapy and achieve suppression in most people

Question 17

Obstetric outcomes associated with hep B

Answer 17

No increase in BW PTB Delivery perinatal mortality

But if cirrhosis then associated with IUGR PTB IUD INteruterine infection

Question 18

Rate of hepatitis C in fertile woman

Answer 18

1%

Question 19

Should we and when should we test for Hep C

Answer 19

RANZCOG considers that all pregnant
women should be screened for Hepatitis C so that risk stratification can be performed and measures taken to both reduce perinatal transmission and minimise occupational exposure
Ideally pre preg so treatment can occur

Question 20

Hep C positive - what other tests should be done and why

Answer 20

PCR for HCV Viral load as this affects the risk of vertical transmission
LFTS including PTB
HIV as coinfection increases the rate of vertical transmission

Question 21

What increases the risk of HCV vertical transmission

What is the rate of vertical transmission

Answer 21

VT around 5% (20% if coinfected with HIV)

FBS FSE
HIV coinfection 
High viral load 
PROM 
LSCS not recommended as a means of reducing transmission

Question 22

How do you manage neonates born to hep C + mums

Answer 22

bath the baby before IM injections (VITK)
No imunogloblin no vaccine
All infants of HCV positive mothers should be screened following delivery to determine whether they have been infected. Care should be taken to ensure the
appropriate interval has passed for the neonate to become PCR+/- antibody positive. - 2 samples 3 months apart or +ve after 18 months

Question 23

Can Hep C infected mums breastfeed

Answer 23

HCV infection is not a contraindication to breastfeeding except in the presence of cracked or bleeding nipples. In this instance, expression and discarding of the
milk is advised whilst waiting for healing of the cracked nipple

Question 24

Treatment of hep C around pregnancy
what is the guidance ?
What is the cure rates

Answer 24

Pre preg screening to treat any + HCV woman
cure up to 95%
Treatment for HCV eg ribavirin not recommended
during pregnancy or breast feeding. In particular ribavirin is teratogenic (Category X).
For all women and male partners receiving Ribaviran, reliable contraception must be used during treatment and for 6 months after completion of treatment.
combo ribaviran and interferon

Question 25

Risk of hep C Mortality What are the rates of chronic infection What is the risk of pregnancy on hep C

Answer 25

5% of chronically infected Hepatitis C patients will die of their disease, due to liver failure or hepatocellular carcinoma 80% develop chronic infection - 20% of those get cirrhosis Pregnancy does not cause deterioration in hep C No change to obstetric outcomes Increase in obstetric cholestasis

Question 26

how is hep C transmitted

Answer 26

Blood products (15%) IVDU (50-90% IVDU are hep C +ve) Sexual transmission unusual <5%

Question 27

what is hepatitis E | Transmission

Answer 27

Hep E is transmitted via the faecal oral route from contaminated water mild self limiting illness usually but mortality rate (5%) associated with pregnant woman - hepatic encephalopathy and liver failure (20%)

Question 28

Obstetric cholestasis | epidemiology

Answer 28

0.5 - 1% pregnancy higher in Indian and Pakistani woman

Question 29

Obstetric cholestasis Clinical presentation Sx, Ix, progress pathogenesis

Answer 29

Sx - puritis limbs and trunk, particulrly palms and soles, 80% after 30 weeks, insomnia, malaise, no rash, Abnormal LFTs, dark urine, anorexia, malabsorption, steatorrhoea, (if hep C +ve often onset earlier - mean 29 weeks vs 34 weeks) Rapid PN recovery within 48 hours LFTs can take 4-6 weeks to recover LFTs: moderate increase in transaminases, Raised ALP, 20% cases raised GGT, mild elevation in bilirubin, increase bile acids, Puritis may preceed abnormal LFTs,

Question 30

Obstetric cholestasis genetics pathogenesis

Answer 30

Increase in circulating oestrogens - affect sulphation of bile acids, - affect bile acid acid transports within the hepatocytes, - decrease in hepatocyte membrane fluiditiy This occurs by a defect in methylation of the membrane phospholipids and a modification in the cholesterol to phospholipid ratio 35% +ve FH autosomal dominant sex linked inheritance

Question 31

If a woman has +ve tests for obstetric cholestasis what other Ix need to be performed

Answer 31

Liver USS - GS Viral serology - Hep B,C, A E EBV and CMV Liver autoantibodies - anti smooth muscle antibody, chronic active hepatitis (CAH) anti mitochondrial antibodies, primary biliary cirrhosis

Question 32

Obstetric cholestasis Risks to mum Risks to baby

Answer 32

Mum: Vit K deficiency - PPH Baby: Intrapartum FD 22%, Mec 25-50%, PTB 25%, Fetal IC Haemorrhage + IUD 1.5% (2.5X increase) IUD does not correlate with Sx or LFTs. perhaps with bile acids - bile acids are vasocontrictors and may affect placental perfusion, bile acids may cause arrhythmia. Bile acids are in high concentraion in fetal blood + amniotic fluid Falling perinatal mortality due to intervention now 0-2% when del pre 38 weeks

Question 33

How to monitor + manage maternal and fetal wellbeing with obstetric cholestasis

Answer 33

``` No correlation with dopplers / CTGs LFTs and Bile acids weekly PT pre delivery del 37-38 weeks (no increase in LSCS) Neonatal Vit K close labour monitoring ```

Question 34

Treatment for obstetric cholestasis + why / how we use them

Answer 34

Prolonged PT then vit K 10 mg orally daily (water soluable form) UDCA - endogenous hydrophilic bile acid reducing the proportion of hydrophobic, hepatotoxic acids 1000-1500mg daily in 2-3 divided doses improves Sx and BA For Sx chlorpheniramine 4mg tds or promethazine 25 mg nocte dexamethasone is not recommended - suppresses oestrogen production in the placenta rifampicin - anecdotal data only cholestyramine - chelation - worsens VitK def

Question 35

recurrence obstetric cholestasis

Answer 35

90 % recurrence Avoid OCP with oestrogen - POP has risk too so if used then should monitor LFTs HRT is ok as replacing physiological levels

Question 36

Acute fatty liver of pregnancy | epidemiology and mortality

Answer 36

rare 1/10000 Primip Male fetus 3:1, multiple pregnancy 20% of cases 2% maternal mortality and 10 % fetal mortality

Question 37

Acute fatty liver of pregnancy | clinical presentation

Answer 37

``` After 30 weeks - ofter 35+ Gradual onset N and V - severe V 60% pain 60% often mild PET Jaundice and ascites within 2 weeks Abn LFTs Coagulopathy90% (+/-normal platelets) AKI Lactic acidosis develop fulminant liver failure and encephalopathy Hypoglycaemia 70% hyperuricaemia 90% Features diabetes insipitus ``` Imaging - hepatic steatosis

Question 38

Genetic predisposition to HELLP + AFLP

Answer 38

woman - heterozygous for long chain 3-hydroxy- acyl-coenzyme A dehydrogenase LCHAD - disorder of mitochondrial fatty acid oxidation Baby may be homozygous for BFatty acid oxidation disorders

Question 39

how does a liver biopsy differ between HELLP and AFLP

Answer 39

HELLP - hepatic cell necrosis and subcapsular haemorrhage | AFLP - microvesicular fatty infiltrates no increased inflammation

Question 40

Management AFLP

Answer 40

``` Deliver Coagulopathy - FFP and VIt K (10mg IV) Hypoglycaemia 10 or 50% glucose Antibiotics as often associated with sepsis DI - desmopressin ``` Severity: PT, Gluose, pH, lactate, encephalopathy