Jaundice and pregnancy

Lessons from practice

A 25‐year‐old woman presented with jaundice, vomiting and weight loss. She was 13 weeks’ pregnant (gravida 2, para 1) and had lost 20 kg (from 85 kg to 65 kg) over the course of the pregnancy. She had first noticed the jaundice 3 weeks earlier. She denied abdominal pain and pruritus. In a previous pregnancy she had hyperemesis gravidarum and lost 30 kg during the first trimester. She denied any other medical history. She was taking ondansetron as required for her nausea but denied taking any other medications, herbal remedies or over‐the‐counter products. She did not drink alcohol. Her vital signs at presentation were: blood pressure in the sitting position 109/70 mmHg, blood pressure in the standing position 90/68 mmHg, respiratory rate 18 breaths per minute and oxygen saturation 98%, and she was afebrile. She was clinically dehydrated, as evidenced by postural hypotension and dry mucous membranes, which was further supported by ketones present on bedside urinalysis. She was visually jaundiced but, notably, her abdomen was soft and non‐tender, and there was no evidence of hepatosplenomegaly or peripheral stigmata of chronic liver disease. Pertinent blood test results are shown in Box 1.

A viral, autoimmune, thyroid, coeliac and haemolysis screen was unremarkable (Box 2).

An abdominal ultrasound showed that the gallbladder was filled with thick, immobile and echogenic sludge (Box 3, arrow). There was no evidence of acute cholecystitis or biliary duct dilatation.

Her liver dysfunction was suspected to be related to hyperemesis gravidarum and she was managed with antiemetics, rehydration, correction of electrolyte abnormalities and supplemental nasogastric feeding under the supervision of a dietitian. Follow‐up in hepatology clinic a week later revealed that she was gaining weight and her nausea was controlled. Her blood test results showed bilirubin 26 μmol/L (reference range [RR], < 20 μmol/L), alanine aminotransferase 109 U/L (RR, < 34 U/L), aspartate aminotransferase 40 U/L (RR, < 31 U/L), γ‐glutamyl transferase 31 U/L (RR, < 38 U/L), and alkaline phosphatase 63 U/L (RR, 30–110 U/L). Blood tests repeated one month later had normalised.

Discussion

Pregnancy‐related liver disease tends to be reserved for patients after 20 weeks’ gestation. These disorders can be life‐threating if not identified and managed correctly. They include acute fatty liver of pregnancy, pre‐eclampsia, HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome, and cholestasis of pregnancy. During the first trimester, few pregnancy‐related liver conditions exist, but one well described is related to hyperemesis gravidarum.

Hyperemesis gravidarum is characterised by nausea, vomiting and typically mild to moderate elevations in serum aminotransferases and bilirubin. It usually manifests in the first trimester and abates by 20 weeks’ gestation. If left untreated, complications of micronutrient deficiency (Wernicke encephalopathy from vitamin B1 deficiency, bleeding from vitamin K deficiency), dehydration (renal injury, electrolyte disturbance) and malnutrition (immunosuppression, muscle wasting) may manifest.

The pathophysiology of jaundice in hyperemesis gravidarum is not well understood. The condition produces a state of ketosis that is known to cause slowing of biliary drainage, which is thought to be in part related to the contraction of the sphincter of Oddi. Pregnancy itself results in delayed gastric emptying, which promotes cholestasis. Histology typically shows evidence of cholestasis and the occasional necrotic hepatocyte.1 More recently, an association has been described between jaundice in hyperemesis gravidarum and the presence of biliary sludge, as evident in our case.2 Formation of biliary sludge has been hypothesised to result from a combination of the above described mechanisms, with the addition of dehydration. Intermittent movement of sludge within the biliary tree causing blockage of bile flow is a possible mechanism contributing to jaundice formation.

Management includes fluids to restore euvolaemia, replacement of electrolytes, supplemental nutrition (enteral and, in severe intractable cases, parenteral) and antiemetics. Medications need to be safe for mother and fetus, and typically ondansetron intravenously followed by glucocorticoid therapy are indicated for intractable cases. Outcomes tend to be favourable for both mother and fetus when patients are managed promptly.3 Recurrence in subsequent pregnancies is common and, as such, patients should be closely monitored to allow early intervention in future pregnancies.

When approaching jaundice in pregnancy, it is important not to overlook exacerbation of existing liver diseases and common causes for liver injury, including viral infections, alcohol, drugs (most commonly antibiotics such as erythromycin, amoxicillin or clavulanic acid), toxins, and biliary pathology. It is important to be systematic and consider pre‐hepatic (haemolytic anaemia), hepatic (intrinsic liver disease) and post‐hepatic (stones, biliary pathology) causes in addition to pregnancy‐specific liver conditions.

Box 3 – Abdominal ultrasound showing the gallbladder filled with thick, immobile and echogenic sludge (arrow)

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