A high maternal viral load is the most important factor affecting immunoprophylaxis against mother-infant transmission of HBV. The application of antiviral drugs in pregnant women with a high serum HBV DNA level (>10(6)~10(7) IU/ml) during the second and third trimesters can reduce the prenatal serum HBV DNA level and significantly increase the success rate of blocking mother-infant transmission in neonates. This article interprets the contents related to antiviral therapy for pregnant women carrying HBV with the purpose of blocking mother-infant transmission of HBV in the guidelines published by Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, National Institute for Health and Care Excellence, Korean Association for the Study of the Liver, and World Health Organization.
Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B ; drug therapy ; prevention & control ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Practice Guidelines as Topic ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Viral Load

Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.
Antiviral Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/etiology ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon-alpha/adverse effects/therapeutic use ; Liver Cirrhosis/complications ; Liver Neoplasms/etiology ; Nucleotides/adverse effects/chemistry/therapeutic use ; Risk Factors

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Prognosis

BACKGROUND/AIMS: This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients. METHODS: CHB patients treated with TDF monotherapy (300 mg/day) for > or =12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks. RESULTS: In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naive, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9+/-2.3 log IU/mL (mean+/-SD), and was higher in the NA-naive group than in the NA-exp and LAM-R groups (5.9+/-2.0 log IU/mL vs 3.9+/-2.0 log IU/mL vs 4.2+/-1.7 log IU/mL, P<0.01). The complete virological response (CVR) rate at week 48 in the NA-naive group (71.4%) did not differ significantly from those in the NA-exp (71.3%) and LAM-R (66.1%) groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898), while the CVR rate did not differ with the NA experience. CONCLUSIONS: TDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.
Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Resistance, Viral ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Liver Cirrhosis/etiology ; Male ; Middle Aged ; Nucleotides/*chemistry/therapeutic use ; Retrospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; virology ; Hepatitis B virus ; Humans ; Liver Neoplasms ; drug therapy ; virology ; Nucleotides ; therapeutic use

PURPOSE: This study aimed to assess the role of thiopurine S-methyltransferase (TPMT) and 6-thioguanine nucleotide (6-TGN) as predictors of clinical response and side effects to azathioprine (AZA), and estimate the optimal AZA dose in Korean pediatric inflammatory bowel disease (IBD) patients. MATERIALS AND METHODS: One hundred and nine pediatric IBD patients in whom AZA treatment was required were enrolled. Thiopurine metabolites were monitored since September 2010. Among them, 83 patients who had prescribed AZA for at least 3 months prior to September 2010 were enrolled and followed until October 2011 to evaluate optimal AZA dose, adverse effects and disease activity before and after thiopurine metabolite monitoring. RESULTS: The result of the TPMT genotype was that 102 patients were *1/*1 (wild type), four were *1/*3C, one was *1/*6, one was *1/*16 (heterozygote) and one was *3C/*3C (homozygote). Adverse effects happened in 31 patients pre-metabolite monitoring and in only nine patients post-metabolite monitoring. AZA dose was 1.4+/-0.31 mg/kg/day before monitoring and 1.1+/-0.46 mg/kg/day after monitoring (p<0.001). However, there were no statistical differences in disease activity during metabolite monitoring period (p=0.34). Adverse effects noticeably decreased although reduction of the AZA dose since monitoring. CONCLUSION: TPMT genotype and thiopurine metabolite monitoring could be helpful to examine TPMT genotypes before administering AZA and to measure 6-TGN concentrations during prescribing AZA in IBD patients.
Adolescent ; Adult ; Azathioprine/*adverse effects/therapeutic use ; Child ; Child, Preschool ; Female ; Genotype ; Guanine Nucleotides/metabolism ; Humans ; Inflammatory Bowel Diseases/*drug therapy/metabolism ; Male ; Methyltransferases/genetics/metabolism ; Republic of Korea ; Risk Factors ; Thionucleotides/metabolism ; Treatment Outcome

OBJECTIVETo analyze the dynamic changes in hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B (CHB) patients following treatment by antiviral nucleotide drugs over a 5-year follow-up period and to assess the clinical significance of quarterly and annual quantitative measurements.

METHODSOne-hundred-and-ten patients with CHB were enrolled in the study and administered on-going standard mono-therapy with various antiviral nucleotide drugs. Over a 5-year period, the HBV DNA level was measured by quantitative PCR every three months and the HBsAg levels were measured by chemiluminescence once a year. The dynamic changes in HBV DNA and HBsAg levels were assessed by Chi-squared test and ANOVA.

RESULTSOnly 90 of the CHB patients completed the 5-year follow-up and were included in the analysis. The patients who showed HBeAg-positivity at baseline (study start) had higher levels of HBV DNA and HBsAg than the patients showing HBeAg-negativity. In general, the antiviral nucleotide drug therapy induced downward trends in HBsAg and HBV DNA level over time (F = 17.1, 151.53, all P less than 0.05). However, the most robust reduction in HBV DNA occurred during the first year. The HBsAg level followed an opposite trend, with the most robust reductions occurring in the 3rd, 4th and 5th years of treatment.

CONCLUSIONLong-term antiviral nucleotide mono-therapies induced decreases in HBV DNA and HBsAg levels in CHB patients, with the former being most reduced in the short-term and the latter in the long-term.

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Follow-Up Studies ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Nucleotides ; therapeutic use ; Treatment Outcome ; Young Adult

Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Nucleotides ; therapeutic use ; Polyethylene Glycols

OBJECTIVETo investigate the ability of Fuzhenghuayu capsule to improve markers of liver fibrosis when provided as supplemental therapy in patients with chronic hepatitis B (CHB) who achieved complete virological response but unsatisfactory resolution of fibrosis markers with nucleos(t)ide analog (NAs) monotherapy.

METHODSOne-hundred-and-ten patients with CHB-related liver fibrosis who had received NA for more than or equal to 2 years and achieved sustained virological response (SVR) but no improvement in liver fibrosis index were randomly divided into two equal groups: experimental group, continued oral NAs (one tablet, 1 time/day) with simultaneous Fuzhenghuayu capsule (1.5 g, 3 times/day) for 48 weeks; control group, continued oral NAs only for 48 weeks. Serum fibrosis markers (hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III procollagen (PIIIP) and IV collagen (IV-C)), liver fibrosis stages, B ultrasonic wave, and liver function were observed before (baseline) and after treatment and compared by statistical analysis.

RESULTSThe baseline levels of fibrosis markers were not significantly different between the experimental and control groups. After treatment, the levels of all of the fibrosis markers were lower in the experimental group (P less than 0.05 vs. control group; HA t = 19.548, LN t = 2.264, PIIIP t = 2.230, and IV-C t = 6.649) and lower than the baseline levels (P less than 0.01; HA t = 12.458, LN t = 7.402, PIIIP t = 4.620, IV-C t = 8.937). The control group also showed a significant reduction in HA and LN levels after treatment (P less than 0.01 vs. baseline; t = 5.202 and 3.444), but PIIIP and IV-C were unaffected. The baseline liver fibrosis stages were not significantly different between the experimental and control groups. After treatment, only the experimental group showed significant improvement in liver fibrosis stages (P less than 0.01). The rates of excellent therapeutic outcome, effectiveness, and non-effectiveness were significantly different between the experimental group (11.3%, 43.4%, and 45.3%) and the control group (1.0%, 22.2%, and 75.6%) (x2 = 9.408, P less than 0.01). Similar trends were observed for improvements in B ultrasonic wave for liver and spleen and in markers of liver function. Finally, neither treatment group experienced adverse effects.

CONCLUSIONFor CHB patients who achieve SVR by antiviral treatment with NAs, but unsatifactory improvement in liver fibrosis indices, administration of supplemental Fuzhenghuayu capsule with continued NAs therapy may represent a safe and effective treatment.

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver ; pathology ; Liver Cirrhosis ; drug therapy ; metabolism ; Male ; Middle Aged ; Nucleotides ; therapeutic use ; Phytotherapy ; Prospective Studies ; Treatment Outcome

OBJECTIVETo conduct a meta-analysis to study the effect of antiviral therapy on the prognosis of patients with chronic hepatitis B (CHB)-related cirrhosis.

METHODSPubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese Biomedical Database, Chinese Journals Full-text Database, and Wan Fang Digital Journal Full-text Database were searched for studies on nucleoside analogues antiviral treatment outcome of patients with CHB-related cirrhosis (vs. controls without antiviral therapy) published between January 1998 and March 2012. Data extraction and quality assessment was performed by two independent investigators. Heterogeneity was assessed by the I2 index. In the case of homogeneity the random-effects model was applied, and in the case of heterogeneity the fixed-effects model was applied. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

RESULTSSeven studies were included in the meta-analysis: one high-quality randomized-controlled trial (RCT) study, four prospective cohort studies, and two case-control studies. Compared to the control group, the group treated with antiviral therapy showed a significantly lower incidence of hepatocellular carcinoma (11.2%, 76/680 vs. 6.7%, 75/1116; OR = 0.56, 95% CI: 0.40 to 0.79, P = 0.001) and lower mortality (23.6%, 78/331 vs. 10.8%, 43/398; OR = 0.36, 95% CI: 0.23 to 0.55, P = 0.000).

CONCLUSIONAntiviral therapy with nucleoside analogues significantly reduces the incidence of hepatocellular carcinoma and mortality in patients with CHB-related cirrhosis.

Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; complications ; diagnosis ; drug therapy ; Humans ; Liver Cirrhosis ; diagnosis ; drug therapy ; etiology ; Nucleotides ; therapeutic use ; Prognosis