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
AFLP clinical features
Usually >30/40
Non-specific symptoms –> severe vomiting (60%), abdominal pain (60%), jaundice, ascites
Often co-existing mild PET (20-40%)
Abnormal LFTs - 3-10 fold increase in transaminases
Hypoglycaemia
- Unable to store or produce glucagon as liver failing
Coagulopathy due to DIC (90%)
AKI
May be lactic acidosis and raised ammonia
May develop fulminant liver failure and hepatic encephalopathy –> liver flap
Diabetes insipidus - hepatic metabolism of placenta vasopressin is impaired in AFLP –> inappropriate clearance of ADH
Distinguishing features between AFLP and HELLP
Distinct features (compared to HELLP):
- Profound hypoglycaemia (70%)
- Marked hyperuricaemia (90%)
- Coagulopathy (90%) in the absence of thrombocytopenia
Liver biopsy with special stains for fatty change or electron microscopy = gold standard
- Not usually practical with coagulopathy
Management of AFLP
Expeditious delivery
- Regardless of fetal age as delivery initiates resolution of life-threatening disease
MDT
- ICU
- Liaison with regional liver unit
Treat coagulopathy with FFP and vitamin K (10mg iv) prior to delivery
Treat hypoglycaemia aggressively
Most women improve quickly post-delivery so management is usually conservative and support
Low threshold for antibiotics
- Significant risk of sepsis
- Gentamicin contraindicated as high risk of AKI
N-acetyl cysteine and plasmapheresis are sometimes used
Consider liver transplant
Baby should be screened for LCHAD deficiency
Recurrence risk is ~25%, more likely if heterozygous for LCHAD deficiency
Completely recovery is the norm if survives
Autoimmune chronic active hepatitis
Associated with anti-smooth muscle antibodies and raised IgG levels
Usually treated with prednisolone +/- azathioprine
Continue in pregnancy
Primary biliary cirrhosis
Usually presents with pruritis
Raised ALP and GGT
Diagnosis confirmed with anti-mitochondrial antibodies
Pruritis may worsen in pregnancy, UCDA can be continued or added
Liver cirrhosis
If severe often infertile
Liver disease may decompensate during pregnancy, therefore discourage pregnancy in women with severe impairment of hepatic function
Bleeding from oesophageal varices is a rise if portal HTN, especially in second and third trimester
- Stabilise on beta blockers, continue throughout pregnancy
Liver transplant
Fertility may return to normal after transplant
- Should have contraception arranged
Postpone pregnancy for >18/12 to stabilise and reduce drugs post-op
Usually on tacrolimus, prednisone and azathioprine
- All safe in pregnancy
92% LBR
Graft function and survival do not appear to be affected by pregnancy
Increased risk of PET, IUGR, PTB, GDM
Gallbladder disease in pregnancy
1/3 of women with gallstones become symptomatic when pregnancy
Oestrogen —> increased cholesterol production
Pregnancy improves gallbladder contractility –> forms sludge and gallstones
Gallstones are more common in multip
Acute cholecystitis occurs in 0.1% of pregnancies
Management - As for non-pregnancy - Conservative management - NBM, NG, IVF, antibiotics, analgesia (resolution in 3/4) - Surgery best done in second trimester ERCP - risk of pancreatitis
Pathophysiology of HG
Unknown, likely multifactorial
Primarily thought to be a/w rising levels of hCG
- Conditions with higher levels of hCG a/w increased severity of NVP
- Also HCG peaks in the first trimester when HG is normally seen
- However high HCG levels are not consistently a/w n/v
Elevated serum concentrations of oestrogen and progesterone
- Relax smooth muscle –> slow GI transit time, may alter gastric emptying
- However these levels peak in third trimester when NVP or HG has usually resolved
H. pylori may play a role in some women
- H. pylori infection a/w increased likelihood of HG during pregnancy
Genetic factors - increased risk of developing HG among relatives of women previously affected
Incidence of HG
SOMANZ – any nausea or vomiting 69%
1.1%
Typically starts between 4th and 7th week
Peaks ~9/40
Resolves by 20/40 in 90%
Nausea and vomiting of pregnancy vs. HG
Nausea and vomiting of pregnancy (NVP)
- Diagnose when onset of symptoms (nausea, vomiting, dry retching) in the first trimester and other causes of n/v excluded
Hyperemesis gravidarum (HG) - Nausea and/or vomiting caused by pregnancy leading to significant reduction of oral intake and weight loss of >5% compared with pre-pregnancy, with or without dehydration and/or electrolyte abnormalities
Obesity in pregnancy
~50% of women who become pregnant are either overweight or obese
BMI >30 pre-pregnancy or at booking visit
Risks of obesity
- antenatal
Miscarriage GDM Fetal congenital abnormalities Stillbirth PET - If BMI >35 Thromboembolism - Risk of PE > DVT Abnormalities in fetal growth Obstructive sleep apnoea Preterm birth Maternal death
Risks of obesity
- intrapartum
IOL, prolonged labour and failure to progress Rate of instrumental delivery Failed instrumental delivery Shoulder dystocia Caesarean section - BMI >40 = 52% of CS Difficulties with fetal heart rate monitoring PPH Peripartum death
Risks of obesity
- anaesthetic
Difficulties with labour analgesia
- Correct siting within the epidural space
- Increased risk of dislodgement
Use of GA
Difficultly maintaining an adequate airway, failed intubation
Increased risk of need for ICU care post-op
Difficult IV access
Risks of obesity
- post-partum
Delayed wound healing and infection
Thromboembolic disease
Greater likelihood of needing support with breastfeeding establishment and continuation
Postnatal depression - Up to 40%
Long term neonatal consequences
- Neonatal body composition
- Infant weight gain
- Obesity
Guidelines on weight gain during pregnancy
Normal weight - 11.5 to 16kg
Obese (includes all classes) - 5 to 9.1kg
Losing weight during pregnancy is not recommended
- Increased risk of low birth weight baby
Low gestational weight gain is associated with:
- PTB
- Increased risk of SGA
Obesity
- Prepregnancy care
Discuss impact of obesity on fertility and pregnancy outcomes
Medications or surgery for weight management are not recommended around the time of conception
High dose (5mg) folate is recommend if BMI >30
Address psychosocial concerns
Offer contraception to allow time for weight optimisation
Weight loss between pregnancies:
- Reduces the risk of: stillbirth, hypertensive complications, fetal macrosomia
- Increases the chances of successful VBAC
Obesity antenatal care
MDT
Nutritional supplementation:
- 5mg folic acid and 150mcg iodine
- Obese women are at increased risk of iron and vitamin D deficiency
Flu vaccination - increased risk of major maternal morbidity with influenza during pregnancy
At subsequent follow up appointments check BP (with correct size cuff) and urinalysis
Offer early OGTT, with repeat at 28/40 if the early test was normal
Anaesthetic assessment
Consider aspirin to lower risk of PET from 12/40
FHx PET, multiple pregnancy
Consider VTE risk
Ultrasound
- Anatomy scan less accurate (fat –> scatter effect)
- BMI>35 should have serial USS
Obesity
- intrapartum
Check guidelines for local unit
- Ensure appropriate equipment available
Less likely to have a successful VBAC
- Operative and anaesthetic risks of emergency CS are higher
Timing of birth
- No universal consensus
- Observational data comparing outcomes before and after a protocol of delivery by 40/40 found a significant reduction in the risk of CS for obese women
IV line on admission to labour ward
May need to confirm presentation with USS
FSE for monitoring
Active management 3rd stage
Increased dose of IV antibiotics for CS (e.g. 3g cefazolin)
Awareness of increased risk of shoulder dystocia and PPH
Operating theatre staff need to be altered regarding increased weight (usually >120kg)
Obesity - postpartum management
BMI >40 –> 50% wound infection
Breastfeeding support
Consider VTE prophylaxis
Weight management postpartum
Screen for post-natal depression
Consider appropriate contraception
Previous bariatric surgery
Should be on lifelong vitamin supplementation
Referral to dietician, especially if malabsorptive surgery - may require additional supplementation during pregnancy - vitamin B12, iron, folate, vitamin D, calcium
Avoid pregnancy for 12-24 months after surgery and during the initial weight loss phase
Require closer monitoring of their nutritional status and fetal growth
Current evidence suggests a positive outcome in reduction of maternal risks during pregnancy, such as GDM, but with an increase risk of FGR and stillbirth
Can’t have OGTT due to dumping syndrome
- HbA1c
- BSLs for 1 week
Food safety in pregnancy
TOXOPLASMOSIS Wash hands after handing raw meet Cook meet well Do not empty cat's litter tray Wash hands after touching animals
LISTERIA
Wash, cook, cover and chill all food
Do not eat leftovers
- Listeria can grow at low temp including fridge
Avoid high risk foods
- Soft and semi soft pasteurized cheese
- Raw milk cheeses and yoghurts
- Cold chicken and other processed meets
- Prepared salads
- Raw seafood
- Raw eggs
- Hummus and tahini
Clinical assessment
of HG
Typically starts between 4th and 7th week
Peaks ~9/40
Resolves by 20/40 in 90%
Typically get hyponatraemia, hypokalaemia, low serum urea, hypochloraemia, hypomagnesaemia, metabolic hypochloraemic alkalosis
If severe, metabolic acidaemia may develop
Measure TFTs in women with HG or NVP refractory to treatment, or those with Sx of thyrotoxicosis
- If TSH
Maternal complications of HG
Wernicke’s encephalopathy -Due to vitamin B1 (thiamine) deficiency
- Potentially fatal
- can be precipitated by IV dextrose
Hyponatraemia
- Both severe hyponatraemia and rapid reversal can –> central pontine demyelination
Pyridoxine (vitamin B6) deficiency
- Causes anaemia and peripheral neuropathy
Acute kidney injury Oesophageal rupture Rhabdomyolysis Mallory-Weiss tears Malnutrition PTSD Thrombosis
Basic stuff for HG
MDT IVF and fluid balance Thrombo-prophylaxis Vitamin supplementation - thiamine 100mg po OD - folic acid 5mg - Iodine 150mcg - pyridoxine
Acid suppression
- omeprazole
Psychosocial support
Manage/prevent constipation
Anti-emetics
for HG
1st
Antihistamines (H1 receptor antagonists)
- Cyclizine, Promethazine
- decreasing stimulation of the vomiting centre
Side effects: sedation, anti-cholinergic effects
Prochlorperazine
- Central and peripheral dopamine antagonists
- Chance of extrapyramidal side effects, oculogyric crises
2nd
Metoclopramide
- Dopamine and serotonin receptor antagonist
- Equal to ondansetron for nausea, but less effective for vomiting
- Chance of extrapyramidal side effects
Ondansetron
- Serotonin receptor antagonists
- Potentially a/w cleft palate, cardiac defects
3rd
Steroids
- Cochrane 2016 - no difference in days of hospital admission compared to placebo, but there was a decreased admission rate
Complementary therapies for HG
Ginger
? Improves nausea but not vomiting
- Ginger superior to placebo but less effective than metoclopramide
Acupressure and acupuncture
- Safe in pregnancy
- Acupressure may improve NVP
- Cochrane found no overall reduction in symptoms
Vitamin B6 (pyridoxine) - May improve nausea but not vomiting
Predictors of pregnancy outcome
Disease activity prior to conception
- Remission >3/12 preconception –> good prognosis
Hx of disease activity in previous pregnancy
Crohn’s tend to remit in pregnancy
UC more likely to flare in pregnancy
- In postpartum period flare is six times more common
Management of IBD in pregnancy
Encourage to conceive when in remission
Mycophenolate and methotrexate should be stopped/switched 3 months before trying to conceive.
Sulphalazine (5mg folic acid) and Mesalalazine safe to use throughout pregnancy and breastfeeding.
Azathioprine safe in pregnancy.
anti-TNF agents i.e. infliximab have growing evidence of safety
- Ideally stop in third trimester so baby can clear the drug prior to delivery
- Babies should not have live vaccines until 6 months of age if mother on infliximab
Correct any nutritional deficiencies due to malabsorption
If symptoms deteriorate:
- FBC, stool culture, CRP, flexible sigmoidoscopy
- For flares of colonic disease use corticosteroid enemas or oral prednisone.
Regular growth scans
