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Antiviral therapy for CHB during pregnancy remains a challenge as the safety data is limited. We evaluated the safety use of TDF for the entire pregnancy in managing mothers with elevated ALT. Methods: Mothers with active CHB who started or switched to TDF at the first trimester and mothers who preferred no treatment during pregnancy were enrolled. Patients were prospectively followed until postpartum week 28. Primary endpoints were safety of mothers and infants. Secondary end points were HBV DNA suppression with ALT normalization throughout the pregnancy and vertical transmission rates. Results: Among 139 mothers screened, 85 were enrolled with 39 mothers who received TDF and 46 mothers who were untreated. Their baseline values are shown in table 1. The mean (range) duration of TDF exposure for the treated group was 38 (28-41) weeks. TDF was well tolerated without significant adverse events (>grade II). Prior to the delivery, mean (SD) serum creatine levels were 52.92 (+8.36) mmol/L in the TDF group vs. 50.55 (+9.89) mmol/L in the untreated group (p=0.242); The serum phosphorus levels were similar between the treated and untreated groups (1.07 vs. 1.06 mmol/L, p=0.763); a complete virologic response (HBV DNA<500 copies/mL) was achieved in 38/39 (97.4%) patients on TDF treated vs. 2.2 % in the untreated group (p<0.001); ALT normalization was observed in 97.4% in the TDF group vs. 56.5% in the untreated group (p<0.001). The birth defect/congenital malformation rates were similar when comparing infants in the treated vs. untreated group (2.6% vs. 2.2%, p=1.000). The infant baselines are also shown in table 1. Both infant groups received appropriate immunoprophylaxis and completed the follow ups. At the age 28 weeks, lower percentage of infants with HBsAg+ was observed in the TDF group vs. those in the untreated group (0% vs. 6.5%, p=0.246). Conclusion: TDF treatment for entire pregnancy was safe for both mothers and infants. TDF therapy suppressed maternal viremia with normalization of ALT and ma!

Despite decreasing prevalence, new cases of hepatitis C in China are increasing recently with growing percentage of patients who are with advanced disease, aging, or not eligible for interferon-based treatments. Hepatitis C infection represents a serious public health burden. This review was based on expert's consensus during a medical forum on hepatitis sponsored by the Beijing Wu Jie-Ping Medical Foundation. The literature searches were conducted in PubMed and critical publications in Chinese journals. Data on hepatitis C prevalence, risk factors, viral or host features, and treatment modalities were extracted and reviewed. Recent large-scale surveys reported reducing prevalence of hepatitis C to approximately 0.4% in China, partly because of regulation changes to safer medical practices and illegalizing commercial blood donations. Patient demographics evolved from being dominated by former paid blood donors to include intravenous drug users and others. Although hepatitis C genotype 1 is the most common, other genotypes are emerging in prevalence. The current standard of care is interferon-based without direct acting antivirals. However, many patients failed therapy because of high treatment costs, substantial needs to manage side effects, difficulties with treatment monitoring in the rural areas, and growing populations of elderly and cirrhotic patients. The lack of high efficacy therapies with good safety profile and low disease awareness in China resulted in increasing public burden of advanced hepatitis C disease. Despite significant reduction of hepatitis C prevalence, iatrogenic, nosocomial, and community transmissions are still significant. In addition to promoting disease awareness, interferon-free regimens are needed to reduce the public health burden.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother-to-child transmission (MTCT) in real-world settings. During the period of January 2009 to March 2011, we enrolled hepatitis B e antigen-positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx=252/51/345) completed the 52-week study with 661 infants (LdT/LAM/NTx=257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention-to-treat analysis indicated 2.2% (95% confidence [CI]: 0.6-3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9-10.3) in the NTx group (P50.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups(1.9% vs. 3.7%; P=0.758). On-treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the NTx group (P=0.002). There were no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups. CONCLUSIONS: LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. The treatment was well tolerated with no safety concerns identified.

Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.

BACKGROUND AND AIM: The modified normal alanine aminotransferase (ALT) value (i.e., males <30 and females <19 IU/L) is a better criteria associated with histological activity in chronic hepatitis B (CHB). This study was aimed to assess if the modified ALT criteria could be better associated with disease phases in a cohort of Asian Americans (AsAm) with CHB. METHODS: This two-center retrospective study evaluated 198 non-treated AsAm with CHB and a mean follow-up of 21 months. Both conventional and modified ALT criteria were used to determine the differences and clinical value using modified ALT criteria in classifying CHB phases. RESULTS: Among HBeAg (+) patients (29.3 %), HBV pre-core (PC) and basal core promoter (BCP) mutations were detected in 24.4 % and 31.3 %, respectively. Using baseline conventional ALT criteria, 97/153 (63.4 %) patients could be categorized into CHB phases 1 to 4, whereas 56/153 (36.6 %) were indeterminate. Using the modified ALT criteria, 43 (28.1 %) patients had phase changes of which 31/43 (72.1 %) were moved from phase 1 and indeterminate to phases 2 and 4, more active CHB phases. In 13/31 of these patients with liver biopsy, 6 (19.4 %) reported stage 2-4 fibrosis and 10 (32.3 %) reported grade 1-2 inflammation. Using modified ALT criteria to evaluate 48/153 patients with full data at baseline and the end of 1-year follow-up, we observed that 19/48 (39.6 %) changed their CHB phases; 5/48 (10.4 %) moved from phases 1 and 3 to phases 2 and 4; 2/48 (4.2 %) remained in the active phases; 10/48 (20.8 %) became indeterminate. CONCLUSIONS: HBV PC and BCP mutations were detectable in 24.4 % and 31.3 % of HBeAg (+) AsAm patients, respectively. Compared with conventional ALT criteria, modified ALT criteria is more sensitive in identifying CHB patients in active phases.

BACKGROUND & AIMS: Despite appropriate immunoprophylaxis, HBV vertical transmission (VT) occurs in 5-10% of infants born to HBs-antigen (HBsAg)+ mothers. We investigated whether amniocentesis increases the risk of transmission. METHODS: We performed a case-control study on infants who were born to HBsAg+ mothers without antiviral exposure and completed appropriate immunization. Infants born to mothers with amniocentesis were compared to those without amniocentesis to assess VT rates, which were defined by the percentage of infants with HBsAg positivity when they were 7-12months old. RESULTS: Of the 642 consecutive infants enrolled, 63 infants with amniocentesis were compared with 198 matched infants selected from the remaining 579 infants without amniocentesis. There was a higher VT rate in infants with amniocentesis than in those without amniocentesis (6.35% vs. 2.53%; p=0.226). Maternal HBV DNA levels before amniocentesis were further stratified to <500 copies/ml, 500-6.99log10copies/ml, and 7log10copies/ml for subset analyses. There were no significant differences in the VT rates between the amniocentesis group and the control group if the maternal HBV DNA levels were <6.99log10copies/ml. However, a significantly higher VT rate was observed in the amniocentesis group vs. the control group if the maternal HBV DNA levels were 7log10copies/ml (50% vs. 4.5%, respectively, p=0.006). According to baseline value risk analyses, performing amniocentesis on highly viremic mothers was a risk factor for HBV transmission (OR=21.3, 95% CI: 2.960-153.775). CONCLUSIONS: Amniocentesis performed on HBsAg+ mothers with HBV DNA 7log10copies/ml significantly increased the frequency of VT. HBsAg+ women who plan to have amniocentesis should be evaluated for the risk of VT and stratified according to their HBV DNA levels. Further prospective studies are warranted to verify our findings.