ALT Flares Are Infrequent During the Course of Pregnancy: Prospective Study from the Hepatitis B Research Network (HBRN) Adult Cohort Study

Abstract

Background: Studies of disease activity during pregnancy in chronic hepatitis b are few and limited to small retrospective case series. Therefore, it remains unclear how often to monitor patients during pregnancy. Aims: To prospectively investigate the serum ALT and hepatitis B virus (HBV) DNA levels during pregnancy and post-partum. Methods:Women enrolled into the NIDDK-funded HBRN adult cohort study, who were either pregnant when enrolled or became pregnant are included. Since treatment can affect natural history, data collected after the start of treatment are excluded. Pregnancy stages are defined as: pre-delivery <28 weeks and ≥28 weeks, and post-partum ≤16 weeks and >16 weeks. A disease flare is defined as serum ALT>200 U/L. The evolutions of ALT and log10 IU/mL HBV DNA levels over time were modeled by a mixed effect model. Pregnancy stage, HBeAg and their interaction were included as covariates. Results: From 1/1/2011 to 3/18/2013, 82 pregnant women with chronic HBV were enrolled or became pregnant after enrollment. There were 8 (10%) White, 11 (13%) Black, 62 (76%) Asian and 1 (1%) mixed/other. Characteristics when first known to be pregnant included: median age of 32 years (range 18-50 years), 43% of 70 with known status were HBeAg+ (medians: ALT 26 U/L, HBV DNA 8.3 log10 IU/mL) and 57% were HBeAg- (medians: ALT 24 U/L, HBV DNA 2.6 log10 IU/mL). There were 43 with pregnancy outcomes available: 39 live births, 3 miscarriages and 1 termination. Model estimates suggest ALT increases early post-delivery among both HBeAg+ and HBeAg- women (p<0.001), particularly among HBeAg+ women (see table). In contrast, DNA levels are relatively stable over time (NS for both HBeAg+ and HBeAgwomen). Only 2 (2.4%) women had a flare. One pre-delivery ≥28 weeks, HBeAg- with peak ALT 225 U/L, the other <16 weeks post-delivery, HBeAg+ with peak ALT 205 U/L. Conclusion: Serum ALT levels increase post-delivery, particularly among HBeAg+ women with chronic HBV, but remain within normal range in most participants. Flares have been infrequent and mild thus far, and not associated with changes in HBV DNA levels or development of jaundice. On-going assessment in participants will help determine recommended monitoring guidelines for future participants.