Acute glycogenic hepatopathy in pregnancy: a case report and literature review

Case presentation

A 46 year-old gravida 4 para 2 presented to L&D at 30 weeks gestation complaining of one week of blurred vision, persistent headache and excessive urination. She had failed to follow up on a glucose challenge test (GCT) result of 222 mg/dL at 15 weeks gestation. A pregnancy 8 years earlier was complicated by diet treated gestational diabetes mellitus (GDM) and culminated in vaginal delivery after labor induction at 33 weeks for preeclampsia with severe features and postpartum Intensive Care Unit (ICU) admission for blood pressure control. She did not test for diabetes postpartum or at any time thereafter. She also had mild asthma since childhood. Her admission body mass index (BMI) was 36 kg/m² and blood pressure (BP) was 185/90 mmHg. Preeclampsia with severe features was diagnosed, intravenous Hydralazine 5 mg and Labetalol 300 mg orally were given immediately, intravenous magnesium sulfate infusion was started, and Betamethasone 12 mg IM was given in anticipation of preterm delivery.

Pertinent admission results were HbA_1c – 12.5%, serum glucose – 626 mg/dL, anion gap – 31, serum bicarbonate – 12 mmol/L, beta-hydroxybutyrate – 7.9 mmol/L, serum creatinine – 1.21 mg/dL, ALT – 24 IU/L, AST – 22 IU/L, and negative urine toxicology. She refused ABG. Liver function tests, platelet count, lactate dehydrogenase (LDH), and urine protein were normal and anti-islet cell antibodies were negative. Diabetic ketoacidosis (DKA) was diagnosed, and an insulin drip, fluid infusion and electrolyte repletion were started.

The second dose of betamethasone was withheld because of hyperglycemia detected on admission. DKA resolved within 24 h of admission. NPH insulin was initiated after DKA resolved but was discontinued 24 h later because she developed a generalized allergic-type rash that was suspected to be drug-induced. Insulin glargine and Insulin lispro were started for basal-bolus therapy and adjusted according to fasting and postprandial blood glucose measurements to maintain blood glucose levels between 70 and 140 mg/dL. Diabetes self-management and nutrition education were provided. Labetalol, which had been initiated on admission at 300 mg BID, was discontinued approximately 36 h later due to persistent maternal mild hypotension. Antihypertensive therapy was never required for the pregnancy duration and postpartum. Maternal echocardiogram was normal. Ophthalmology and podiatry evaluations were unremarkable. The blurred vision (suspected to be due to hyperglycemia-induced intra-lenticular sorbitol accumulation) improved after hyperglycemia resolved, as expected. Fetal assessment was normal throughout the hospitalization.

ALT and AST levels were normal on admission but began to rise two days after DKA resolved (Figure 1). Amylase and lipase levels were found to be slightly elevated on hospital day 4 (107 IU/L and 384 IU/L, respectively) but normalized over the next week. She denied abdominal pain, nausea or vomiting throughout the hospitalization and tolerated a full diet; therefore, acute pancreatitis was considered very unlikely. An extensive gastroenterology evaluation (hepatitis A IgM, hepatitis B sAg, hepatitis B cAb total, hepatitis E, HCV PCR, antinuclear antibody, anti-neutrophil cytoplasmic antibody, autoimmune hepatitis IgG, anti-mitochondrial antibodies, alpha-1 antitrypsin, urinalysis, urine toxicology screen, thyroid function test and anti-thyroid antibodies, anti-tissue transglutaminase antibody, anti-endomysial antibodies, ferritin, total iron-binding capacity (TIBC), and iron, serum ceruloplasmin level) was normal.

Figure 1:

Graph illustrating liver transaminase trends during hospital course. Arrow indicates delivery date.

Right upper quadrant ultrasound revealed moderate hepatomegaly (liver length of 18.7 cm) and increased echogenicity, but no cholelithiasis, acute cholecystitis or ductal dilatation (Figure 2). She declined magnetic resonance cholangiopancreatography (MRCP) and diagnostic liver biopsy. She first developed generalized itching twelve days after admission and serum bile acid level was 20 mg/dL. Ursodiol was started for presumed developing intrahepatic cholestasis of pregnancy. She left the hospital against medical advice on hospital day fourteen despite persistent itching and still elevated ALT and AST. She followed up outpatient for daily ALT/AST measurements, three times per week biophysical profiles (BPP), and weekly high risk obstetric clinic visits.

Figure 2:

Right upper quadrant sonogram showing hepatomegaly.

She agreed to return to the hospital at 33 weeks gestation and remain till delivery because of continued itching and persistently elevated ALT and AST despite Ursodiol 1,200 mg daily. Serum bile acids on this admission were 62 mmol/L. Readmission systolic BP ranged from 125 to 146 mmHg and diastolic BP ranged from 61 to 76 mmHg with +1 proteinuria. Preeclampsia with severe features was suspected initially, and a rescue course of betamethasone was administered. Intravenous magnesium infusion was started for seizure prophylaxis but was discontinued after twenty-four hours because her blood pressure remained normal. Her outpatient insulin regimen of insulin glargine 50 units qhs and insulin lispro 5 units before meals continued in hospital. Serum ALT and AST level peaked approximately fourteen days after she first presented in DKA and began to decrease spontaneously (Figure 1). Labor was induced at 34 weeks (ten days after the ALT, AST started decreasing) because of patient’s discomfort from persistent itching.

A male infant was delivered by emergency cesarean following a prolonged fetal bradycardia in the second stage of labor. APGAR scores were 3 and 8 at one and 5 min, respectively. The neonate was intubated for the first day of life because of poor respiratory effort, however he did well thereafter and did not experience hypoglycemia. Patient’s post-operative course was uncomplicated. The ALT and AST continued to trend down till discharge (Figure 1). Postoperative glucose control was excellent; therefore, insulin was replaced with metformin 1,000 mg BID. Patient consented to have her case reported in a medical journal.

Take home message

AGH is rare during pregnancy. Acute glycogenic hepatopathy, like other diseases seen more frequently during pregnancy, for example, preeclampsia with severe features, causes elevated serum transaminases. Expectant management of acute glycogenic hepatopathy during pregnancy may avoid iatrogenic preterm birth.