Spontaneous preterm birth in women with chronic hepatitis B virus infection.

OBJECTIVE: To determine whether chronic hepatitis B virus (HBV) infection, as evidenced by serum levels of HBsAg and HBV DNA, is a risk factor for spontaneous preterm birth (SPB). METHOD: The prevalence of HBV infection and the SPB rate were prospectively investigated among 1826 pregnant women, 30.89% Albanian and the remainder of other European origins. RESULTS: Overall, 70 (3.8%) of the women were chronically infected with HBV. HBsAg status was strongly linked to SPB, which incurred to 5 (7.3%) of 64 women with circulating HBsAg compared with 28 (1.6%) of 1703 without current HBV infection (odds ratio, 5.2; P=0.007). SPB, however, was linked neither to HBsAg levels, nor to HBV DNA levels, nor to the presence or absence of viremia. CONCLUSION: Pregnant women were found to be at higher risk for SPB if they had circulating HBsAg, and the risk did not seem to be influenced by the levels of HBsAg or HBV DNA.

Serological and virological profile of chronic HBV infected women at reproductive age in Greece. A two-year single center study.

OBJECTIVE: Seroprevalence of HBsAg in 26,746 women at reproductive age in Greece and evaluation of HBeAg/anti-HBe serological status as well as serum HBV-DNA levels in a subgroup of HBsAg(+) women at labor. STUDY DESIGN: Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was calculated using a sensitive quantitative PCR assay, with a lower limit of quantification of 200 copies/ml. RESULTS: Overall, 1.53% of women were HBsAg(+) and the majority of them (64.96%) were Albanian. Among Albanian women the mean prevalence of HBsAg was 4.9%, 5.57% among Asian women, and 1.29% among women from Eastern European countries. The prevalence of HBsAg among African (0.29%) and Greek women (0.57%) was very low and significantly lower in comparison with the mean value of the studied population. Only 2.67% of HBsAg(+) women were HBeAg(+). Of a subgroup of women in labor with available serum samples 28.6% had undetectable levels of viremia (<200 copies/ml) and 15.9% had extremely low levels of viral replication (<400 copies/ml). Only 12.7% of pregnant women evaluated at labor exhibited extremely high serum HBV-DNA levels (>10,000,000 copies/ml) whereas 42.8% of them exhibited HBV-DNA levels between 1500 and 40,000 copies/ml. CONCLUSIONS: The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher among specific ethnic populations (Asian, Albanian). The HBeAg(-)/antiHBe(+) serological status is a finding observed in the vast majority of HBsAg(+) women of our study population, and a significant percentage of them (approximately 44.5%) exhibit extremely low or even undetectable levels of viral replication at labor, suggesting possibly that only a proportion of HBsAg(+) women in Greece exhibit an extremely high risk of vertical transmission of the infection.

HBeAg negative serological status and low viral replication levels characterize chronic hepatitis B virus-infected women at reproductive age in Greece: a one-year prospective single center study.

AIM: To evaluate the seroprevalence of hepatitis B surface antigen (HBsAg) in 13 581 women at reproductive age and the hepatitis B e antigen (HBeAg)/anti-HBe status as well as serum hepatitis B virus (HBV)-DNA levels in a subgroup of HBsAg(+) pregnant women at labor in Greece. METHODS: Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was determined by a sensitive quantitative PCR assay. Statistical analysis of data was based on parametric methodology. RESULTS: Overall, 1.156% of women were HBsAg(+) and the majority of them (71.3%) were Albanian. The prevalence of HBsAg was 5.1% in Albanian women, 4.2% in Asian women and 1.14% in women from Eastern European countries. The prevalence of HBsAg in African (0.36%) and Greek women (0.29%) was very low. Only 4.45% of HBsAg(+) women were also HBeAg(+) whereas the vast majority of them were HBeAg(-)/anti-HBe(+). Undetectable levels of viremia (<200 copies/mL) were observed in 32.26% of pregnant women at labor and 29.03% exhibited extremely low levels of viral replication (<400 copies/mL). Only two pregnant women exhibited extremely high serum HBV-DNA levels (>10 000 000 copies/mL), whereas 32.26% exhibited HBV-DNA levels between 1 500 and 40 000 copies/mL. CONCLUSION: The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher enough among specific populations. The HBeAg(-)/anti-HBe(+) serological status and the extremely low or even undetectable viral replicative status in the majority of HBsAg(+) women of our study population, suggest that only a small proportion of HBsAg(+) women in Greece exhibit a high risk for vertical transmission of the infection.

Relationship between serum b2-microglobulin levels and virological breakthrough in HBeAg-negative chronic hepatitis B patients, under long-term treatment schedules including lamivudine.

AIM: Predictive value of serum b2-microglobulin (b2m) levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM). METHODS: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB. RESULTS: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3+/-2.6 vs 3.8+/-3.4 mo, P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03). CONCLUSION: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment, compared to baseline ones, might be a predictor of risk for VB.

Serum beta2-microglobulin levels in hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy: relationship with virological breakthrough.

OBJECTIVES: To evaluate the predictive value of serum beta2-microglobulin (beta2m) levels for virological breakthrough in hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy. METHODS: Serum beta2m levels were calculated at baseline and every three months during lamivudine monotherapy in 25 patients with chronic hepatitis B, using microparticle enzyme immunoassay technology to investigate their association with biochemical, virological and histological outcome data. Cox proportional hazard models were used to investigate the association between serum beta2m levels and virological breakthrough. RESULTS: Seven of 25 (28%), nine of 25 (36%) and 14 of 25 (56%) chronic hepatitis B patients exhibited virological breakthrough at months 12, 24 and 36 of treatment, respectively. All chronic hepatitis B patients who did not show virological breakthrough in the follow-up period exhibited beta2m elevation in month 3 of treatment. The duration (in months) of serum beta2m elevation was significantly higher in the responders group than the nonresponders group (7.3 +/- 2.6 versus 3.8 +/- 3.4, P=0.02). In contrast to patients whose serum beta2m levels were increased at three months, patients whose beta2m levels were decreased had a 4.6 times higher risk of experiencing virological breakthrough (hazards ratio 4.6, 95% CI 1.22 to 17.36). When age, pretreatment serum alanine aminotransferase and hepatitis B virus DNA levels, and grade of liver disease were simultaneously included in the same Cox model, decreased beta2m status was still associated with increased risk of virological breakthrough (hazards ratio 12.2, 95% CI 1.28 to 116.8). CONCLUSIONS: In hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy, serum b2m levels at three months of treatment, compared with baseline levels, are good predictors of risk for virological breakthrough.

Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance.

OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.