Liver and GI Flashcards
Liver physiology in pregnancy
Pregnancy is associated with increased liver metabolism
Symptoms and signs of normal pregnancy can mimic GI and liver disease
- Nausea and vomiting
- Spider naevi and palmar erythema (due to high estrogen levels) can be normal
Increase: fibrinogen, ALP (2-4 fold increase, max 400 U/L)
Decreased total serum protein, albumin, GGT
Fall in upper limit of ALT/AST
No change in bilirubin
Progesterone also reduces gallbladder emptying –> predisposes to gallstone formation
HELLP incidence
Lab changes
Affects 5-10% of PET pregnancies
Up to 1/3 of women with HELLP will not have HTN or proteinuria
LDH - Increase - can be indicative of haemolysis (as can schizocytes on peripheral smear, elevated bilirubin)
Low platelets
Mild increase ALT/AST, urate, WCC
Complications of HELLP
Eclampsia Maternal mortality - ~1% (pending recourse settings) Perinatal mortality 7-60% Placental abruption Liver subcapsular haematoma - Liver infarction, rupture or necrosis Acute renal failure
Recurrence of HELLP
Up to 25%
Risk of recurrence for any type of PET / eclampsia is 45%
Management of HELLP
If antenatal - Prompt delivery - AN steroids for fetal lung maturity MDT - ICU support - Haematology - General surgeon - If liver complication Monitor - Monitor and treat HTN, thrombocytopenia and coagulopathy Vitamin K and FFP if coagulopathic Fluid balance Consider platelets at time of delivery MgSO4 - if at risk of eclampsia Steroids - some evidence for use of steroids for women who develop postnatal HELLP Imaging - Consider abdomen / liver imaging if abdominal pain, shoulder tip pain, or hypotension
Liver complications of HELLP
Hepatic bleeding or swelling –> liver rupture
~1% of subcapsular haematoma
Involve liver trauma surgeon
If haematoma contained, treat conservatively
Options:
- Packing
- Drainage
- Hepatic artery ligation
- Resection of affected areas
Percutaneous embolisation of hepatic arteries is reasonable 1st line therapy if haemodynamically stable
Obstetric cholestasis incidence
NZ / Au - 1%
- Increased risk in Indian and Pakistani women
Earlier presentation if HCV
Obstetric cholestasis - key points of presentation
Diagnosed when otherwise unexplained pruritus occurs in pregnancy and abnormal LFTs and/or raised bile acids occur in pregnant woman and both resolve after delivery
Usually presents >28/40
Bilirubin - not usually raised
Most sensitive and specific marker for the diagnosis of OC
Normal bile salt levels do not exclude the diagnosis
If persistent pruritus and normal LFTs, then repeat every 1-2 weeks
Investigations in OC
Exclude other causes of LFT derangement:
- Hepatitis A, B, C
- EBV
- CMV
- Liver autoimmune screen for chronic active hepatitis and primary biliary cirrhosis (e.g. anti-smooth muscle and antimitochondrial antibodies)
- Liver ultrasound
PET screen
Glucose
Risk factors of OC
Personal Hx of OC FHx of OC Multiple pregnancy Carriage of hepatitis C Presence of gallstones IVF Advanced maternal age Indian / Pakistan
Pathophysiology of OC
Exact cause is unknown
Thought to be secondary to the cholestatic effects of oestrogen and progesterone in genetically susceptible women –> affect the sulfation and transport of bile acids in the liver –> cholestatic effect causing regurg of bile salts into the circulation and damaging surrounding hepatocytes
Elevated bile salts –> itch, insomnia
35% have positive FHX
Geographical and season variation exists
Risks to pregnancy with OC (fetal)
Spontaneous PTB - at most only slightly increased from the general population (4-12%)
Iatrogenic PTB
Fetal death
- The current additional risk of stillbirth in obstetric cholestasis above that of the general population has not been determined but is likely to be small (RCOG)
- Some authors suggest risk is low if <40micromol/l. Older studies suggest some risk of >40
- Only women with total bile acids >100micromol/l at any point in their pregnancy had stillbirth rates statistically significantly higher than the pooled national stillbirth rate (UTD, Lancet meta-analysis 2019). In this meta-analysis, no increase in stillbirth rate at bile acid level <100 but majority of babies were born by 39/40.
- Fetal death is usually sudden. There is no evidence of placental insufficiency
Meconium passage
NICU admission
Increased risk of RDS - appears to be associated with bile acids entering the lungs
Risks to pregnancy with OC (Maternal)
Maternal - morbidity in association with intense pruritis and consequent sleep deprivation
CS rate ? Related to OC, IOL, obstetrician / patient anxiety
PPH ?
Vitamin K deficiency from malabsorbtion of fat soluble vitamins
Antenatal management of OC
Weekly LFTs until delivery
- Along with general review, BP, urinalysis (to exclude other pathology)
- Increase frequency of monitoring if deterioration in LFTs and consider other diagnoses, also check coags
Fetal monitoring - No specific method can be recommended
- Offer continuous fetal monitoring in labour
Predicting fetal outcome is difficult
- Deliver in hospital with NICU support (as increased risk of NICU admission)
Medical management of OC
There is no evidence that any specific treatment improves fetal or neonatal outcomes
Topical emollients - Topical aqueous cream with 1-2% menthol
- Safe, but efficacy is unknown
Antihistamines
- May provide some sedation at night
Ursodeoxycholic acid (UDCA)
- Improves pruritus (in up to 75%) and liver function in women with OC
- Inform women of lack of robust safety data concerning protection against stillbirth and safety to the fetus or neonate
- Mechanism of action unclear
Rifampicin if refractory to UCDA
If prothrombin time (PT) is prolonged, 5-10mg vitamin K recommended
Timing of delivery in OC
Offer IOL from 36-40 weeks after counselling
CDHB:
- Bile salts >100 or ALT >200 - timing of delivery to be individualised, offer for 36/40
- Bile salts >40 or worsening LFTs - offer IOL at 38/40
- Bile salts <40 - offer IOL at 40/40
RCT - no increased CS with IOL 37-38 weeks but increased neonatal RDS
Postnatal management of OC
Check symptoms and LFTs normalised
- Check LFTs >10 days PN (in normal pregnancy, LFTs may increase in the first 10 days)
- Return to normal usually within 4-6 weeks
Reassurance about the lack of long-term sequelae for mother and baby
High recurrence rate (45-90%)
Contraception
- Avoid oestrogen-containing methods
- May be an increased risk of recurrent cholestasis with COCP (rare)
Increased incidence of obstetric cholestasis in family members
AFLP incidence
1 in 7,000 to 1 in 20,000 pregnancies
Newer data - maternal mortality 2%, fetal mortality 11%
AFLP risk factors
Primigravida (not as marked as with PET) Older mothers Male fetus (3:1) Multiple pregnancy (20% of cases) Fetal long-chain 3-hydroxyacyl dehydrogenase deficiency PMHx of AFLP Low BMI
AFLP pathogenesis
May be a variant of PET
Defects in fatty acid metabolism –> microvesicular fatty infiltrates of the liver –> damage to hepatocytes and liver failure
Subgroup of women who are susceptible have LCHAD deficiency
