Obstetric Cholestasis
Obstetric Cholestasis – Summary of GTG 43 + Excerpts from the related TOG article
Diagnosis of Obstetric Cholestasis /Intrahepatic Cholestasis of Pregnancy ( OC/ICP) –
According to the RCOG Guideline- OC is diagnosed when there is
- Otherwise unexplained pruritus in pregnancy
and abnormal liver function tests (LFTs)
and/or raised bile acids occur in the pregnant woman
and both resolve after delivery.
Pruritus that involves the palms and soles of the feet is particularly suggestive.
(According to this definition, Raised Bile Acids are NOT MANDATORY to make a diagnosis)
- OC is Associated with an increased risk of adverse perinatal outcome. ( Stillbirth rate 1.5 % in OC as compared to 0.5% in normal population) .
- Perinatal risks associated with OC are -spontaneous preterm birth, iatrogenic preterm birth and fetal death. Increased likelihood of meconium passage.
- The risk appears to be greater for women with severe disease (Bile acid concentration > 40 micromoles/litre) Though Bile acid elevation is not needed to diagnose OC, it has prognostic significance .
The Physiological Changes in Liver Function during pregnancy are as follows-
AST and ALT | Evaluates liver cell injury or necrosis. ALT is more specific to the liver than AST. Normal pregnancy level of AST and ALT are 20% less than non pregnant levels. | Marked ALT elevation is often seen in Viral Hepatitis. Moderate elevation of ALT may be present in HELLP< Hyperemesis, Acute fatty liver of pregnancy, cholelithisis, drug induced hepatotoxicity |
| Albumin | Evaluates liver synthetic function | Decreased by 20 to 40% in pregnancy ( partly due to dilution) Reduced in cirrhosis or severe acute liver disease. |
| Prothrombin | Evaluates liver synthetic function | Reduced in cirrhosis or severe acute liver disease. |
| Alkaline Phosphatase | Rises in pregnancy( 2 to4 fold) due to production by placenta. Also produced by bone. Therefore not reliable in pregnancy. | Maximum level is 400 IU /l in the third trimester. If very high level, special labs can test for isoenzymes ( to check for synthesis from bone or liver) |
| GGT | Reduced in pregnancy  | |
| Bile acids | Specific marker in Obstetric Cholestasis, with Diagnostic and prognostic value. | Fetal Risk is low at level less than 40 micromol/L. There is 1–2% increase in risk for every 1 micromol/l increase in bile acid level. |
If a woman presents with pruritus in pregnancy, without any rash ( especially pruritus over palms and soles) –
- Clinical history should be taken ( Gallstones, Hepatitis C carriage, Personal or family history of OC, Multiple pregnancy- are all risk factors for OC) ; History of pale stool, dark urine and Jaundice ( supports diagnosis of OC)
- Clinical examination to rule out liver disease should also be done.
- Initial testing should be done by LFT and Bile acid level.
- Because symptoms may precede Lab abnormalities by several weeks, retesting should be done every 1 to 2 weeks, if symptoms persist after initial normal lab findings.
Of GGT, ALT and AST , only one may be raised at the initial raised Bile Acid Level ( NOT the first visit with itching). ALT , AST and GGT may be raised in 50%, 37% and 13 % of women at the initial raised bile acid level respectively.
Serum Bilirubin is usually normal in OC.
Bile acid elevation in pregnancy is diagnostic of OC and may have prognostic value.
Ideally Bile acids should be checked in fasting state( because they are lower in fasting state) ,but in general, this is not done and guideline recommendations are based on ‘random’ bile acid levels.
If LFT is abnormal- look for other causes of abnormal liver function-
- viral screen for hepatitis A, B, and C, Epstein Barr and cytomegalovirus
- liver autoimmune screen for chronic active hepatitis and primary biliary cirrhosis (anti-smooth muscle and antimitochondrial antibodies)
- liver ultrasound
- Coagulation profile
- Consider pre-eclampsia or Acute fatty liver of pregnancy as possible differential diagnoses.
( The presence of autoantibodies should point to presence of Autoimmune causes.
In such cases , there is usually the presence of other Autoimmune Disorders.
The antibodies pointing to specific autoimmune disorders are as follows–
AMA, ANA- Primary biliary cirrhosis.
ANA, aSMA- Primary sclerosing cholangitis .
ANA, aSMA, LKM1, Anti-soluble liver antigen Anti-liver pancreas antibodies –Autoimmune hepatitis.
( AMA = anti-mitochondrial antibodies; ANA = anti-nuclear antibodies; pANCA = perinuclear anti-neutrophil cytoplasmic antibodies; aSMA = anti-smooth muscle antibodies;
LKM1 = anti-liver kidney microsomal antibodies.)
Treatment
Drug of choice– Ursodeoxycholic acid ( UDCA)
Antihistamines
Topical treatment
Second line treatment- Rifampicin ( Source TOG 2016;18:273–81. DOI: 10.1111/tog.12308)
( Rifampicin with UDCA has been shown to be useful in Primary Biliary Cirrhosis ) A 2015 study reported beneficial effect with UDCA and Rifampicin. However, more studies are needed. Before commencing Rifampicin- make sure the Liver Transaminase are not markedly raised. Patient should be informed that Rifampicin causes discoloration of urine and sweat.
Vitamin K – When Prothrombin time is prolonged- menadiol sodium phosphate 5–10 mg daily.
Oil soluble preparation of Vit K should not be used.
Where Prothrombin time is normal, there may still be benefit by way of reduction of PPH risk
( 12 % PPH in women who took oral vitamin K versus 45% in women who did not take) .
However the British National Formulary( BNF) , based on 1955 data recommends against use of Vitamin K in late pregnancy and labor because of risk of haemolytic anaemia, hyperbilirubinaemia and kernicterus in the newborn- This data likely needs revision, and many hospitals do not follow this advice by the BNF.
Postnatal Vitamin K should be offered to the baby in the usual way.
Elective delivery–
Discuss Induction of labor from 37 weeks (GTG) . The TOG article mentions a study according to which immediate delivery at 36 weeks of gestation without fetal lung maturity testing or steroids was found to be optimal.
Place of birth- book under consultant-led, team based care. Delivery in a hospital unit.
Continuous intrapartum fetal monitoring.
Postnatal–
defer LFT testing to at least 10 days( LFTs may increase in the first 10 days of the
Puerperium ).
Discussion in Postnatal visit- Make sure that Pruritus has resolved and LFT have returned to normal.
Implications for future- No long term sequelae.
Recurrence rate 45 to 90%.
Avoid estrogen containing contraceptives( may cause recurrence of symptoms) .
Increased incidence of OC in Family members.
Support groups- Obstetric Cholestasis Patient Support Group (http://www.ocsupport.org.uk/).
QUICK RECAP
OC- Take history to rule out other causes.
Examination- look for rash, rule out other causes.
LFT, Bile acid→ if raised→ rule out other causes of liver disease.
Repeat labs 1-2 weeks.
Ursodeoxycholic acid, Antihistaminics, Emmollients. ??Rifampicin.
Vitamin K if Prothrombin is high.
Induction of labor at 37 weeks. Continuous intrapartum CTG.
Postnatal – Repeat LFT at 6 weeks ( defer for at least 10 days postpartum) . Make sure symptoms resolve.
Future- recurrence risk
Contraception- avoid estrogen containing contraception.