Pregnancy and the Liver Flashcards
Jaundice in Pregnancy:
Intrahepatic Cholestasis of Pregnancy
Intrahepatic cholestasis of pregnancy
Intrahepatic cholestasis of pregnancy (also known as obstetric cholestasis) occurs in around 1% of pregnancies and is generally seen in the third trimester. It is the most common liver disease of pregnancy.
Features
pruritus, often in the palms and soles
no rash (although skin changes may be seen due to scratching)
raised bilirubin
Management
ursodeoxycholic acid is used for symptomatic relief
women are typically induced at 37 weeks
Complications include an increased rate of stillbirth. It is not generally associated with increased maternal morbidity
Jaundice in Pregnancy:
Acute Fatty Liver of Pregnancy
Acute fatty liver of pregnancy
Acute fatty liver of pregnancy is rare complication which may occur in the third trimester or the period immediately following delivery.
Features abdominal pain nausea & vomiting headache jaundice hypoglycaemia severe disease may result in pre-eclampsia
Investigations
ALT is typically elevated e.g. 500 u/l
Management
support care
once stabilised delivery is the definitive management
Other causes of Jaundice during Pregnancy
Gilbert’s and Dubin-Johnson syndrome, may be exacerbated during pregnancy
HELLP Syndrome
HELLP
Haemolysis, Elevated Liver enzymes, Low Platelets
HELLP syndrome is a severe form of pre-eclampsia whose features include: Haemolysis (H), elevated liver enzymes (EL), and low platelets (LP). A typical patient might present with malaise, nausea, vomiting, and headache. Hypertension with proteinuria is a common finding, as well as epigastric and/or upper abdominal pain.
Example Question
A 37-year-old woman who is 32 weeks pregnant presents with malaise, headaches and vomiting. She is admitted to the obstetrics ward after a routine blood pressure measurement was 190/95mmHg. Examination reveals right upper quadrant abdominal pain and brisk tendon reflexes. The following blood tests are shown:
Hb 85 g/l
WBC 6 * 109/l
Platelets 89 * 109/l
Bilirubin 2.8 µmol/l ALP 215 u/l ALT 260 u/l γGT 72 u/l LDH 846 u/I
A peripheral blood film is also taken which shows polychromasia and schistocytes.
What is the most likely diagnosis?
Obstetric cholestasis > HELLP syndrome Eclampsia Gestational hypertension Acute viral hepatitis
The patient in this scenario fulfils the criteria for HELLP syndrome.
Fatty Liver of Pregnancy: Example Question
A 38 year-old nulliparous woman, who is at 35 weeks gestation, presents with a 10-hour history of fatigues, nausea and vomiting. She has not eaten for the past 24 hours and says that she feels a little dizzy. She describes no blood in her vomit and has had no recent changes in her bowel habit. She has no past medical history of note and she does not currently take any regular medication. She has no family history of note and does not smoke or drink any alcohol.
On examination she appears to be very anxious and abdominal exam reveals right upper quadrant and epigastric pain on deep palpation. There is no organomegaly and bowel sounds are present. The baby is moving normal.
She has a temperature of 37.5oC, heart rate of 85 beats per minute, blood pressure of 135/80mmHg, oxygen saturation of 99% and a respiratory rate of 18 breaths per minute.
Blood tests reveal:
Hb 10.5 g/dL Platelets 82 * 109/l WBC 12.9 * 109/l Na+ 134 mmol/l K+ 3.9 mmol/l Urea 7.2 mmol/l Creatinine 95 µmol/l CRP 20 mg/l ESR 8 mm/hr Bilirubin 90 µmol/l ALP 140 u/l ALT 431 u/l γGT 45 u/l Albumin 30 g/l Prothrombin time (PT) 23 seconds
What is the most likely diagnosis?
Ascending cholangitis Intrahepatic cholestasis of pregnancy > Fatty liver of pregnancy Infectious gastroenteritis Hyperemesis gravidarum
The most likely diagnosis in this case is fatty liver of pregnancy. This usually presents with nausea and vomiting in combination with pain in the epigastrium and right upper quadrant of the abdomen. The normal gestational range it tends to affect is 28-42 weeks, as opposed to hyperemesis gravidarum, which affects early pregnancy.
Disseminated intravascular coagulation (DIC) is a risk of developing this condition and this patient is displaying some of the signs (low platelets and raised prothrombin time) of starting to develop DIC. Intrahepatic cholestasis of pregnancy tends to present with fatigue and itching as the two main symptoms and ascending cholangitis tends to be a triad of fever, right upper quadrant pain and jaundice. Gastroenteritis does not tend to raise liver function tests to the values displayed above.
HELLP Syndrome - Example Question
A 32-year-old primigravida at 37 weeks attends the antenatal unit complaining of abdominal pain which is worse on the right side. She has also been vomiting. Her blood pressure is 148/97 mmHg. She denies any abnormal discharge and reports that fetal movements are still present. Her blood results are shown below.
Hb 93 g/l Platelets 89 * 109/l WBC 9.0 * 109/l Urate 0.49 mmol/l Bilirubin 32 µmol/l ALP 203 u/l ALT 190 u/l AST 233 u/l
You are phoned for advice on the results. What is the most likely diagnosis?
> HELLP syndrome Obstetric cholestasis Acute fatty liver Hyperemesis gravidarum Gout
The most likely diagnosis here is HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), a serious manifestation of pre-eclampsia. The clinical features of hypertension, vomiting and abdominal pain support the diagnosis but are not pre-requisites. The abdominal pain here may be a sign of liver inflammation and resulting stretch of the liver capsule.
Obstetric cholestasis is associated with intense pruritus and the most sensitive marker is a rise in serum bile acids. Acute fatty liver is another serious condition, which also has associations with pre-eclampsia. It would typically cause greater elevations in liver enzymes and a deep jaundice. Hyperuricaemia may be a useful marker of pre-eclampsia and does not necessarily indicate an attack of gout. Urate is thought to rise due to diminished kidney function and reduced clearance. Hyperemesis gravidarum should be a diagnosis of exclusion and would be unlikely to present for the first time this late into pregnancy.
Pre-Eclampsia
Pre-eclampsia
Pre-eclampsia is a condition seen after 20 weeks gestation characterised by pregnancy-induced hypertension in association with proteinuria (> 0.3g / 24 hours). Oedema used to be third element of the classic triad but is now often not included in the definition as it is not specific
Pre-eclampsia is important as it predisposes to the following problems
fetal: prematurity, intrauterine growth retardation
eclampsia
haemorrhage: placental abruption, intra-abdominal, intra-cerebral
cardiac failure
multi-organ failure
Risk factors > 40 years old nulliparity (or new partner) multiple pregnancy body mass index > 30 kg/m^2 diabetes mellitus pregnancy interval of more than 10 years family history of pre-eclampsia previous history of pre-eclampsia pre-existing vascular disease such as hypertension or renal disease
Features of severe pre-eclampsia hypertension: typically > 170/110 mmHg and proteinuria as above proteinuria: dipstick ++/+++ headache visual disturbance papilloedema RUQ/epigastric pain hyperreflexia platelet count < 100 * 106/l, abnormal liver enzymes or HELLP syndrome
Management
consensus guidelines recommend treating blood pressure > 160/110 mmHg although many clinicians have a lower threshold
oral labetalol is now first-line following the 2010 NICE guidelines. Nifedipine and hydralazine may also be used
delivery of the baby is the most important and definitive management step. The timing depends on the individual clinical scenario
Intrahepatic Cholestasis of Pregnancy - Example Question
A 30-week pregnant woman presents with itchy palms and soles of the feet particularly at night but no rash. She is not jaundiced and has not travelled recently. Liver enzymes and serum bile acids are raised (see table). Prothrombin time is normal. Urine dipstick reveals 1+ of protein and her blood pressure is 132/80.
ALT 65 mmol/l ALP 171 mmol/l Bilirubin 40 mmol/l Bile acids 80 mmol/l Pro-thrombin time Normal Anti-nuclear Antibodies (ANA) Negative Anti-Mitochondrial antibodies Negative Urine Protein-Creatinine Ratio 14 mg/mmol/l
What is the most likely diagnosis?
Acute fatty liver of pregnancy > Intrahepatic cholestasis of pregnancy Pre-eclampsia Primary biliary cirrhosis Gallstones
This is a typical presentation for intrahepatic cholestasis of pregnancy. Pruritis affects the limbs and trunk particularly the palms and soles, developing in the second half of pregnancy. Rash and jaundice are rare features of this condition. There is a moderate elevation (less than three-fold) in transaminases and primary bile acids rise (10-100 fold). However these are not specific and other causes of deranged liver function tests in pregnancy should be excluded. There is a risk of fetal death with raising bile acids. Complete recovery occurs within 48 hours of delivery. Management is with ursodeoxycholic acid (UDCA). It has a high recurrence in future pregnancies.
Acute fatty liver of pregnancy is rare but potentially lethal for both mother and fetus. It often presents near term with severe vomiting and abdominal pain. The patient is usually jaundiced.
Pre-eclampsia is a condition associated with hypertension and proteinuria in pregnancy.
There is 1+ protein on urine dipstick so a urinary protein-creatinine ratio has been requested which is normal (>30 mg/mmol is pathological). Pre-eclampsia symptoms such as headache, blurred vision, abdominal pain and oedema are not present.
Primary biliary cirrhosis is an autoimmune liver disease associated with destruction of the intralobular ducts. Anti-Mitochondrial antibodies are highly specific to the condition (negative in this patient).
The patient does not complain of abdominal pain, which would suggest an obstructing gallstone.
Note: Pregnancy-specific reference ranges for liver function tests should be used
(~20% lower than non-pregnant ranges). Also remember that ALP is produced by the placenta and therefore not useful in pregnant women.
Intrahepatic Cholestasis of Pregnancy - Example Question
A 34 year-old primiparous woman in her third trimester of pregnancy presents with fatigue and severe itching which has been worsening over three weeks. She is otherwise well. Her only other past medical history is childhood eczema and hayfever for which she takes the occasional antihistamine for. She has no relevant family history. She does not smoke and does not drink any alcohol.
Examination reveals mildly icteric sclera and excoriations on her trunk and arms. Her cardiorespiratory, abdominal and antenatal examinations are normal.
Blood tests reveal:
Hb 11.0 g/dL Mean corpuscular volume 98 fl Platelets 390 * 109/l WBC 8.8 * 109/l Na+ 135 mmol/l K+ 3.3 mmol/l Urea 2.9 mmol/l Creatinine 59 µmol/l Bilirubin 69 µmol/l ALP 910 u/l ALT 232 u/l γGT 300 u/l Albumin 30 g/l Prothrombin time 24 seconds
Urinalysis is normal. What is the most likely diagnosis?
> Intrahepatic cholestasis of pregnancy Viral hepatitis HELLP syndrome Autoimmune hepatitis Primary sclerosing cholangitis
The most likely diagnosis is intrahepatic cholestasis of pregnancy. This is a rare condition, in which roughly half of patients experience mild jaundice and itching in the third trimester. Furthermore, there can be a prolonged prothrombin time and increased tendency to bleed. The blood tests show a classic cholestatic picture with a high ALP.
Obstetric Cholestasis
Obstetric cholestasis
Obstetric cholestasis affects around 0.7% of pregnancies in the UK
Features
pruritus - may be intense - typical worse palms, soles and abdomen
Risks
increased risk of premature birth
Management
induction of labour at 37 weeks is common practice but may not be evidence based
ursodeoxycholic acid - again widely used but evidence base not clear
vitamin K supplementation
Obstetric Cholestasis - Example Question
A 32-year-old pregnant woman presents to the GP with jaundice and itchy skin for the past 2 weeks. She claims that is a lot worse during this pregnancy compared to her last one. History reveals that she is currently 30 weeks pregnant with no complications up until presentation. On examination, the only notable findings are mild jaundice seen in the sclerae, as well as excoriations around the umbilicus and flanks. She denies any tenderness in her abdomen during the examination. Blood tests show the following:
ALT 206 U/L AST 159 U/L ALP 796 umol/l GGT 397 U/L Bilirubin (direct) 56 umol/L Bile salts 34 umol/L
Bile salts reference range 0 - 14 umol/L
What is the most likely diagnosis?
> Obstetric cholestasis Budd-Chiari syndrome Acute hepatitis HELLP syndrome Acute fatty liver of pregnancy
Obstetric cholestasis, also known as intrahepatic cholestasis of pregnancy, is a condition caused by the impaired flow of bile. This, in turn, causes a build up of bile salts which can then deposit in the skin (causing pruritus) as well as the placenta. It is thought that the aetiology of this condition is a combination of hormonal, genetic and environmental factors.
Although the pruritic symptoms can be distressing for the mother, the build up of bile salts can also be detrimental to foetal wellbeing. The combination of the immature foetal liver’s ability to cope with breaking down the excessive bile salt levels as well as the vasoconstricting effect of bile salts on human placental chorionic veins has been theorised to be the cause of sudden asphyxial events in the foetus leading to anoxia and death.
Fatty Liver of Pregnancy vs Obstetric Cholestasis vs HELLP
Fatty liver of pregnancy usually presents with nausea and vomiting in combination with pain in the epigastrium and right upper quadrant of the abdomen. The normal gestational range it tends to affect is 28-42 weeks, as opposed to hyperemesis gravidarum, which affects early pregnancy.
Disseminated intravascular coagulation (DIC) is a risk of developing this condition (low platelets and raised prothrombin time would be signs to look out for) NB Differentiated from HELLP because causes a deep jaundice with significantly elevated liver enzymes e.g. ALT >400 (much more so than HELLP)
Intrahepatic cholestasis of pregnancy tends to present with fatigue and itching (intense pruritus) as the two main symptoms. Bile acid rise is most sensitive marker.
