Hepatitis B is a serious disease that is endemic in many parts of the world. A significant proportion of patients with chronic hepatitis B (CHB) are infected with a variant form of the hepatitis B virus (HBV) which decreases or abolishes the production of hepatitis B e-antigen (HBeAg). The purpose of this literature review is to describe the epidemiology of HBeAg-negative CHB (e-CHB) worldwide. A literature search was conducted to identify studies pertaining to e-CHB and underlying variants (precore and core promoter). Fifty studies were included in our analysis. The median prevalence of e-CHB among patients with chronic HBV infection was 33% in the Mediterranean, 15% in Asia Pacific, and 14% in the USA and Northern Europe. The pre core stop codon variant was detected in a median of 60% (range 0-100%) of HBeAg-negative patients overall, 92% in the Mediterranean, 50% in Asia Pacific and 24% in the USA and Northern Europe. There were very few data on the prevalence of core promoter variants outside Asia where the median prevalence among HBeAg-negative patients was 77%. This literature review revealed that e-CHB is more common than previously suspected and that it is present worldwide with marked variations in the prevalence of associated HBV variants across different geographical regions. Additional research using population based samples of adequate size based on a consensus definition of e-CHB and using standardized HBV DNA assays is needed to better estimate the true prevalence of e-CHB and its associated HBV variants.

Objective To estimate the strength of association between first-trimester bleeding and miscarriage, setting aside the bleeding at time of loss. Methods Women enrolled in a community-based pregnancy cohort study before or during early pregnancy. Detailed, first-trimester bleeding data were collected by telephone interview. Bleeding episodes proximal to miscarriage (within 4 days) were excluded. We used discrete-time hazard models to evaluate the association between bleeding and miscarriage. Models were adjusted for maternal age, prior miscarriage, and smoking. Exploratory regression tree analysis was used to evaluate the relative importance of other bleeding characteristics (duration, associated pain, color, timing). Results Of the 4510 participants, 1204 (27%) reported some first-trimester vaginal bleeding or spotting, and 517 miscarriages were observed. Eight percent of those with bleeding reported heavy bleeding episodes. When we evaluated any bleeding, including episodes of only spotting, the unadjusted relative odds (OR) of miscarriage for women with bleeding (n=1204) was 1.1 (95% confidence interval [CI] 0.9–1.3). However, women who reported heavy bleeding (n=97)had nearly three times the risk of miscarriage compared to women without bleeding during the first trimester (OR 3.0, 95% CI 1.9–4.6). Adjustment for covariates had little effect on estimates. Further analyses suggested that women with heavy bleeding accompanied by pain were the group accounting for most of the elevated risk. Conclusion Heavy bleeding in the first trimester, particularly when accompanied by pain, is associated with higher risk of miscarriage. Spotting and light episodes are not, especially if only lasting 1–2 days..

Purpose-Although first-trimester vaginal bleeding is an alarming symptom, few studies have investigated the prevalence and predictors of early bleeding. This study characterizes first trimester bleeding, setting aside bleeding that occurs at time of miscarriage.Methods-Participants (n=4539) were women ages 18-45 enrolled in Right From the Start, a community-based pregnancy study (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008). Bleeding information included timing, heaviness, duration, color, and associated pain, as well as recurrence risk in subsequent pregnancies. Life table analyses were used to describe gestational timing of bleeding. Factors associated with bleeding were investigated using multiple logistic regression, with multiple imputation for missing data.Results-Approximately one-fourth of participants (n=1207) reported bleeding (n=1656 episodes), but only 8% of women with bleeding reported heavy bleeding. Of the spotting and light bleeding episodes (n=1555), 28% were associated with pain. Among heavy episodes (n=100), 54% were associated with pain. Most episodes lasted less than 3 days, and most occurred between gestational weeks 5-8. Twelve percent of women with bleeding and 13% of those without experienced miscarriage. Maternal characteristics associated with bleeding included fibroids and prior miscarriage.Conclusions-Consistent with the hypothesis that bleeding is a marker for placental dysfunction, bleeding is most likely to be seen around the time of the luteal-placental shift.