August 17, 2016
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Flares in HBV DNA, ALT common in pregnant, postpartum women

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Pregnant and postpartum women with chronic hepatitis B virus infection can experience severe flares in HBV DNA and alanine aminotransferase, according to recent findings.

“In our multi-center study of pregnant women with chronic hepatitis B, significant increases in hepatitis B DNA and alanine aminotransferase (ALT) were fairly common, mostly during late second trimester and after or shortly after delivery,” Mindie H. Nguyen, MD, MAS, AGAF, FAASLD, director of the hepatology fellowship and hepatology clerkship at Stanford University Medical Center, told Infectious Disease News. “Though rare, a few of these hepatitis flares led to severe hepatic decompensation.”

Nguyen and colleagues, including Christine Y. Chang, BS, division of gastroenterology and hepatology, Stanford University Medical Center, conducted a retrospective study of 113 pregnancies in 101 women with chronic HBV seen during pregnancy at two community gastroenterology clinics and two tertiary medical centers from 1997 to 2015. The researchers sought to examine the onset, severity and resolution of flares in HBV and ALT.

“In contrast to prior studies, our work included women with both low and high viral loads, and focused on maternal outcomes,” Nguyen said.

Mindie H. Nguyen, MD, MAS, AGAF, FAASLD

Mindie H. Nguyen

Women who initiated antiviral therapy for HBV during pregnancy were excluded in the analysis of postpartum flares. Nine percent of women experienced HBV DNA flares during pregnancy (eight of 90), and 4% had flares during postpartum (two of 48). ALT flares — classified as between 99 U/L (minimum 5x upper limit of normal) and 2,522 U/L — were experienced by 6% of women during pregnancy (seven of 112) and 10% of women within 3 months’ postpartum (five of 51).

Antiviral therapy was initiated in 28 pregnancies at 28 weeks of pregnancy. Of the women in both of these groups, two continued treatment during postpartum, and three discontinued treatment at delivery; they all experienced subsequent flares in ALT (between 180 U/L and 1,429 U/L) within the first 3 months’ postpartum.

The researchers noted that most of the women who had increases in HBV DNA during pregnancy and not treated during postpartum returned to baseline HBV DNA levels. Some who remained untreated or discontinued antiviral therapy at delivery, however, sustained HBV DNA levels lower vs. baseline for 3 months to 1 year after delivery.

Christine Y. Chang, BS

Christine Y. Chang

“This suggests that immunological changes during pregnancy, rather than antiviral therapy itself, may stimulate immunoseroclearance, and would support the higher-than-expected rates of HBeAg seroconversion previously reported in [chronic HBV] pregnant women,” the researchers wrote.

Univariate analysis determined that age, hepatitis B e antigen positivity, baseline HBV DNA, baseline ALT, gravida and parity were not significant predictors of flares in this patient population. Nguyen said predictive factors for flares have not been consistently identified, suggesting the need for further research.

“Close monitoring of these patients during late pregnancy and early postpartum should be performed, as flares can be symptomatic and/or warrant antiviral therapy for prevention of hepatic decompensation in mothers as well as prevention of vertical transmission of HBV to infants. Further research is needed to characterize the effects of pregnancy on hepatitis B and help physicians manage the disease during pregnancy,” Nguyen said. – by Melinda Stevens

Disclosure: Nguyen reports receiving research support from Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals and the National Cancer Institute, and serving on the advisory boards at Alnylam Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Janssen Pharmaceuticals, and Roche Laboratories. Please see the full study for a list of all other researchers’ relevant financial disclosures.