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Total Alanine Aminotransferase (ALT) Flares in Pregnant North American Women With Chronic Hepatitis B Infection

Results From a Prospective Observational Study

Bzowej, Natalie H. MD, PhD1; Tran, Tram T. MD2; Li, Ruosha PhD3; Belle, Steven H. PhD4; Smith, Coleman I. MD5; Khalili, Mandana MD6; Chung, Ray MD7; Tsai, Naoky MD8; Terrault, Norah MD, MPH9 for the Hepatitis B Research Network (HBRN)

American Journal of Gastroenterology: May 01, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.14309/ajg.0000000000000221

INTRODUCTION: Alterations in the immune system can result in alanine aminotransferase (ALT) flares either during pregnancy or after delivery in women with chronic hepatitis B virus (HBV) infection. The aim of this study was to prospectively assess changes in serum biochemical and virological markers of HBV infection during and after pregnancy in a large North American cohort of pregnant women with chronic HBV.

METHODS: Adult pregnant women enrolled in the Hepatitis B Research Network between 2011 and 2016 were included. Serum ALT values and HBV DNA viral levels were obtained at <28 weeks and >28 weeks of gestation and <16 weeks, 16–31 weeks, and 32–48 weeks postpartum. Outcomes of ALT flares included severity, duration, and initiation of antiviral therapy.

RESULTS: Among the 158 pregnant women with chronic HBV, the median age was 33 years, 73% were Asian, and 63% were hepatitis B e antigen (HBeAg) negative. The median HBV DNA level was substantially higher in the HBeAg-positive vs HBeAg-negative women (1.3 × 108 vs 343 IU/mL), but serum ALT levels at their first study visit were similar. Among untreated pregnant women, there was a very mild increase in serum ALT postpartum among both HBeAg-positive and HBeAg-negative women (P < 0.001). Serum ALT flares (range 107–513 U/L) developed in 3.4% (5/149) during pregnancy and in 4.3% (4/92) after delivery. Twenty-two percent were initiated on antiviral therapy. After withdrawal of prophylactic anti-HBV therapy, 17.2% (5/29) developed serum ALT flares (range 107–208 U/L) within 14 weeks of drug discontinuation, and 3 additional women had flares despite continuous anti-HBV therapy during pregnancy or postpartum. Many ALT flares were not associated with significant changes in HBV DNA levels. No flares were severe with elevations of bilirubin or clinical decompensation.

DISCUSSION: Spontaneous ALT flares in untreated pregnant women with chronic HBV are infrequent, mild, and self-limited both prepartum and postpartum. Although flares after the withdrawal of antiviral therapy postpartum are more common, they were also mild and self-limited. Further studies of the immunopathogenesis of pregnancy-related flares are needed, as well as effects on long-term outcome of the mother and infant.

1Ochsner Medical Center, New Orleans, Louisiana, USA;

2Cedar Sinai Medical Center, Los Angeles, California, USA;

3University of Texas Health Science Center, Houston, Texas, USA;

4University of Pittsburgh, Pittsburgh, Pennsylvania, USA;

5Georgetown University Hospital, Washington, District of Columbia, USA;

6University of California San Francisco, San Francisco, California, USA;

7Massachusetts General Hospital, Boston, Massachusetts, USA;

8University of Hawaii, Honolulu, Hawaii;

9University of California, San Francisco, San Francisco, California, USA.

Correspondence: Natalie H. Bzowej. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received September 17, 2018

Accepted February 22, 2019

© The American College of Gastroenterology 2019. All Rights Reserved.
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