Faculty Bibliography

Backgrounds: Despite the use of timely immunoprophylaxis, vertical transmission (VT) occurs in 10% infants born to highly viremic mothers with chronic hepatitis B. We evaluated if lamivudine use in the 2nd trimester (2T) vs. 3rd trimester (3T) improves the VT rate in treatment naive HBeAg+ mothers with HBV DNA > 6 log₁₀copies/mL. Methods: HBV mono-infected mothers with lamivudine use (100 mg/day) at the 2T or 3T during 5/2008-1/2013 were retrospectively enrolled and compared to cases with similar maternal baseline from untreated mothers. All infants received appropriate immunoprophylaxis. Infants' HBsAg and HBV DNA status at 28 weeks was used to determine VT rate. Results: 155 consecutive mothers treated with lamivudine (2T/3T=61/94) and 89 match cases selected from untreated mothers were enrolled with comparable maternal baseline values (Table 1). Prior to delivery, maternal HBV DNA mean (SD) levels were 4.15 (0.98), 4.68 (0.90), 7.16 (0.52) log₁₀ copies/mL in the 2T, 3T and control group, respectively (F=327.207, p< 0.001). At birth, HBsAg positivity from venous blood was found in 21.31% (13/61), 31.91% (30/94), and 32.58% (29/89) [p=0.268] of newborns in the 2T, 3T and control group, respectively. At the age of 28 weeks, infants with HBsAg+ or detectable HBV DNA were 0% (0/61 and 0/94) in the 2T and 3T groups vs. 5.62% (5/89) in the control group (p=0.012); all infants in lamivudine-treated groups seroconverted to anti-HBs with undetectable DNA (< 500 copies/mL). There was no significantly difference in VT rates between the groups of lamivudine initiated in the 2T and 3T. 126 lamivudine-treated mothers discontinued therapy at week 4 postpartum. ALT flares during pregnancy (5 x ULN) were observed 6.45% (10/155) and 1.12% (1/89) in lamivudine and control arms respectively (p=0.054), but severe hepatitis exacerbation (ALT>10XULN) was uncommon (lamivudine:control=1/126:5/45, p=0.001). No lamivudine discontinuations from adverse events or genotypic resistance were reported. !

BACKGROUND & AIMS: Despite appropriate passive and active immunization, perinatal transmission of hepatitis B virus (HBV) still occurs in 5%-10% of infants born to women with high levels of viremia who test positive for the hepatitis B e antigen (HBeAg). We evaluated the effects of cesarean section delivery on perinatal transmission of HBV from women who tested positive for the hepatitis B surface antigen (HBsAg). METHODS: We analyzed data from 1409 infants born to HBsAg-positive mothers through vaginal delivery (VD) (n = 673), elective caesarean section (ECS) (n = 496), or urgent cesarean section (UCS) (n = 240) who completed appropriate immunization against HBV. The prevention was assumed to have failed for infants who were HBsAg positive when they were 7-12 months old; this information was used to assess transmission rates. RESULTS: HBV infection was transmitted to a smaller percentage of infants born by ECS (1.4%) than by VD (3.4%, P < .032) or UCS (4.2%, P < .020). UCS had no effect on vertical transmission, compared with VD (4.2% vs 3.4%, P = .593). Infants born by ECS had a significantly lower rate of vertical transmission than those born by non-ECS (1.4% vs 3.6%, P = .017). Women with HBV DNA levels <1,000,000 copies/mL did not transmit the infection to their infants, regardless of method of delivery. There were no differences in maternal or infant morbidity and mortality among the groups. CONCLUSIONS: There is a significantly lower rate of vertical transmission of HBV infection to infants delivered by ECS, compared with those delivered vaginally or by UCS. Elective cesarean sections for HBeAg-positive mothers with pre-delivery levels of HBV DNA >/=1,000,000 copies/mL could reduce vertical transmission.

BACKGROUND & AIMS: Many foreign-born persons in the US are at high risk of chronic hepatitis B (HBV) and C (HCV) infections, yet are not aware of their infection, and lack healthcare coverage or linkage to care. METHODS: A unique partnership, the Hepatitis Outreach Network, combines the expertise and resources of the Mount Sinai School of Medicine, the NYC Department of Health and Mental Hygiene, and community-based organizations, to provide education, screening and link to care in communities with high prevalence of chronic viral hepatitis. Comprehensive HBV and HCV screening identifies infected patients, who then receive further evaluation from either local or Mount Sinai physicians, combined with patient-navigators who organize follow-up visits. RESULTS: Of 1603 persons screened, 76 had HBV and 75 had HCV. Importantly, screening for HCV based on traditional risk factors would have missed 67% of those who tested positive. Of the 76 persons with HCV infection, 49 (64%) received a medical evaluation (26 with local providers and 23 at Mount Sinai). Of the 49 HCV-infected persons evaluated, treatment was recommended in 11 and begun in 8 (73%). Of the 76 persons with HBV infection, 43 (57%) received a medical evaluation (31 with local providers and 12 at Mount Sinai). Of the 43 HBV-infected persons evaluated, treatment was recommended and begun in 5 (100%). CONCLUSIONS: Hepatitis Outreach Network has successfully established novel proof of concept for identifying HBV and HCV infections in foreign-born persons through use of several unique elements that effectively link them to care.

The management of chronic hepatitis B (CHB) during pregnancy remains a challenge and involves various aspects of maternal-fetal care. Despite the standard immunoprophylaxis, a significant portion of infants born to highly viremic mothers remain infected with hepatitis B virus (HBV). Emerging data suggest that antiviral therapy in the third trimester can prevent immunoprophylaxis failure. To minimize fetal exposure to antiviral agents, antiviral therapy during pregnancy should be reserved for mothers with advanced disease or who are at risk for hepatic decompensation. Current safety data suggest that lamivudine, telbivudine, or tenofovir may be used during pregnancy. However, the timing in initiating antiviral therapy requires careful assessment of risks and benefit. The authors provide a systematic review of the features of HBV during pregnancy, risk factors for vertical transmission, and evidence-based data on antiviral use during pregnancy. They propose an algorithm to assess the need of antiviral treatment and monitor mothers with CHB.

Of the estimated 400 million patients with chronic hepatitis B (CHB) globally, around 75% are Asians, representing a clinically important sub-group with a higher risk of cirrhosis and hepatocellular carcinoma than Caucasian patients. This review summarizes recent data from clinical long-term and real-life studies of entecavir and tenofovir, the recommended first-line oral therapies for treating CHB, in nucleos(t)ide-naive Asian CHB patients with compensated or decompensated liver disease. Long-term treatment with entecavir or tenofovir achieved profound and durable virological suppression, and led to improved liver histology and function. The data presented in this review will help physicians in making evidence-based decisions choices regarding first-line antiviral therapy and long-term management in Asian CHB patients.

In infants born to hepatitis B surface antigen (HBsAg)-positive mothers, failure after passive-active immunization still occurs. The role of maternal hepatitis B DNA level and other risk factors in this setting remains unclear. This study retrospectively evaluated virologic and other risk factors associated with immunoprophylaxis failure in infants born to HBsAg-positive mothers. Between January 2007 and March 2010, we reviewed the clinical and virologic tests in 869 mother-infant pairs. All infants received the identical passive-active immunization schedule after birth. The failure infants (HBsAg positive at 7-12 months of age) were compared to infants who were HBsAg negative when tested during this time period. Among 869 infants, 27 (3.1%) infants were immunoprophylaxis failures and the other 842 (96.9%) infants remained HBsAg negative. When mothers' pre-delivery HBV DNA levels were stratified to <6, 6-6.99, 7-7.99 and >/= 8 log(10) copies/mL, the corresponding rates of immunoprophylaxis failure were 0%, 3.2% (3/95), 6.7% (19/282) and 7.6% (5/66), respectively (P < 0.001 for the trend). All failure infants were born to hepatitis B e antigen (HBeAg)-positive mothers. Multivariate logistic regression analysis identified maternal HBV DNA levels [odds ratio (OR) = 1.88, 95% confidence interval (CI): 1.07-3.30] and detectable HBV DNA in the cord blood (OR = 39.67, 95% CI: 14.22-110.64) as independent risk factors for immunoprophylaxis failure. All failure infants were born to HBeAg-positive mothers with HBV DNA levels >/= 6 log(10) copies/mL. The presence of HBV DNA in cord blood predicted failure to passive-active immunization.