The association of vitamin D with hepatitis B virus replication: Bystander rather than offender.

BACKGROUND/PURPOSE: Low vitamin D is frequent in hepatitis B virus (HBV)-infected patients and several studies show an inverse association of serum vitamin D level with HBV viral load. However, the causal relationship remains unclear. METHODS: HBV carriers receiving regular 6-month surveillance without current antiviral treatment or cirrhosis were invited to participate into this trial. The markers of HBV replication included serum HBV DNA and quantitative HBsAg (qHBsAg) levels. Those with undetectable HBV DNA or sufficient vitamin D levels, cancer or electrolyte imbalance were excluded. The eligible subjects were randomized to receive either vitamin D supplement 2000 IU per day for 2 months (vitamin D group) or none (control group). RESULTS: A total of 196 HBV carriers (93 males and 103 females; mean age 51.9 ± 10.0 years) were screened. Of them, 28 patients had undetectable serum HBV DNA levels, which is defined as spontaneous viral clearance. The vitamin D levels were not different between patients with detectable HBV DNA and those without (p = 0.18). After exclusion, 149 patients were randomized to two groups: 75 in vitamin D group and 74 in control group. After 2 months vitamin D supplement, the serum vitamin D levels were significantly higher in the vitamin D group than the control group (p < 0.001). However, the serum qHBsAg and HBV DNA levels were comparable between these two groups. CONCLUSION: There is no causal relationship between vitamin D and HBV replication. The role of liver reserve on serum vitamin D levels in patients with chronic HBV infection needs further investigation.

Assessing the Durability of Entecavir-Treated Hepatitis B Using Quantitative HBsAg.

OBJECTIVES: This study aims to assess whether quantitative HBsAg can predict durability of chronic hepatitis B (CHB) patients stopping entecavir (ETV) treatment. METHODS: We conducted a multicenter study on non-cirrhotic CHB patients who discontinued ETV treatment. The primary end points were clinical relapse and sustained viral response (SVR), which was defined as undetectable serum hepatitis B virus (HBV) DNA levels (<6 IU/ml) at 12 months off-therapy. RESULTS: A total of 117 consecutive CHB patients were enrolled. Among them, 93 patients who received more than 1-year off-therapy follow-up were included for the final analysis. The duration of off-therapy follow-up was 24.8±11.6 months. All 12 patients who did not achieve therapeutic end points had clinical relapse. In 81 patients who achieved therapeutic end points, clinical relapse and SVR were observed in 44 (54.3%) and 11 (13.6%) patients, respectively. The serum HBV DNA at 3 months and 6 months off-therapy were associated with clinical relapse over time, whereas quantitative hepatitis B surface antigen (qHBsAg) level at 6 months off-therapy had a marginal effect. Furthermore, end-of-treatment qHBsAg levels were associated with SVR (P=0.009). CONCLUSIONS: The serum qHBsAg level off-therapy can predict durability of ETV-treated CHB patients. It may guide clinicians to select which patients can maintain sustained viral suppression or need retreatment after discontinuing ETV treatment.

Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus.

UNLABELLED: The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. CONCLUSIONS: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.

SNP rs7770370 in HLA-DPB1 loci as a major genetic determinant of response to booster hepatitis B vaccination: results of a genome-wide association study.

BACKGROUND AND AIM: Hepatitis B (HB) vaccination is highly effective in reducing the risk of hepatitis B virus infection. However, breakthrough and chronic hepatitis B virus infections in vaccinated subjects raised concern about its long-term efficacy. The specific aim of the study was to explore the host genetic determinants of long-term immunological memory against HB vaccination. METHODS: We conducted a case-control study nested in a cohort of HB booster recipients who had received primary HB vaccination during infancy but failed to reside an anti-HBs titers ≥ 10 mIU/mL at the age of 15-18 years. We used a genome-wide single nucleotide polymorphism (SNP) array plate to scan autosomal chromosomes and assayed the human leukocyte antigen (HLA)-DPB1 genotype by sequence-based techniques. RESULTS: We found that 10 of the 112 candidate SNPs (P-value < 5.0 × 10(-5) ) clustered within a 47-Kb region of the HLA-DP loci. All the minor alleles of these HLA-DP candidate SNPs were correlated with lower likelihoods of nonresponse to HB vaccine. There was a significant linkage disequilibrium between these HLA-DP candidate SNPs and HLA-DPB1 protective alleles. Multivariate analyses showed that rs7770370 was the most significant genetic factor. As compared with rs7770370 GG homozygotes, adjusted odds ratios were 0.524 (95% confidence interval, 0.276-0.993) and 0.095 (95% confidence interval, 0.030-0.307) for AG heterozygotes and AA homozygotes, respectively. CONCLUSION: Our results showed that rs7770370 was the most significant genetic factor of response to HB booster. The rs7770370 and nearby SNPs may also contribute to the long-term immunological memory against HB vaccination.

Fibrosis index based on four factors better predicts advanced fibrosis or cirrhosis than aspartate aminotransferase/platelet ratio index in chronic hepatitis C patients.

BACKGROUND/PURPOSE: Liver biopsy is the gold standard to determine the severity of hepatic fibrosis despite its risk and invasiveness. The aspartate aminotransferase/platelet ratio index (APRI) could noninvasively predict the severity of hepatic fibrosis in chronic hepatitis C (CHC) patients. Whether fibrosis index based on four factors (FIB-4) could better predict the severity of hepatic fibrosis than APRI in CHC patients remains inconclusive. METHODS: This retrospective study enrolled 1473 CHC patients (784 men and 689 women) with liver biopsy and clinical data including age, aspartate aminotransferase, alanine aminotransferase, and platelet count. FIB-4 and APRI were calculated with a formula using the four clinical parameters. Hepatic fibrosis was staged using the Metavir classification system. RESULTS: The areas under the receiver operating characteristics of FIB-4 for the diagnosis of significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (F4) were 0.816 [95% confidence interval (CI), 0.795-0.836], 0.827 (95% CI, 0.806-0.849), and 0.849 (95% CI, 0.830-0.867), respectively, compared with those of APRI-0.799 (95% CI, 0.778-0.819), 0.791 (95% CI, 0.770-0.812), and 0.802 (95% CI, 0.781-0.922). In addition, the areas under the receiver operating characteristics of FIB-4 were significantly greater than those of APRI for patients with advanced fibrosis and cirrhosis, respectively (p < 0.0001). CONCLUSION: FIB-4 could predict hepatic fibrosis in CHC patients. By adding two parameters (age and alanine aminotransferase), FIB-4 better predicts advanced fibrosis and cirrhosis than APRI in CHC patients.

HBV-DNA level at 6 months of entecavir treatment predicts HBeAg loss in HBeAg-positive chronic hepatitis B patients.

BACKGROUND/PURPOSE: To evaluate whether on-treatment HBV-DNA level could predict the treatment response to entecavir in hepatitis B e antigen (HBe)-positive chronic hepatitis B (CHB) patients. METHODS: A total of 68 treatment-naïve HBeAg-positive patients (75% male, mean age at 46.6 ± 11.9 years) receiving at least 2 years of entecavir therapy were enrolled. The primary therapeutic endpoint was HBeAg loss. On-treatment complete virological response was defined as serum HBV-DNA < 63 IU/mL. RESULTS: The median baseline alanine aminotransferase (ALT) and HBV-DNA levels were 199.5 (27-1622) U/L and 7.7 (3.8-13.2) log10 IU/mL, respectively. The median treatment duration was 31.7 (24.3-69.6) months. The rate of HBeAg loss at 2 years was 30.9%. By univariate analysis, on-treatment complete virological response at Month 6 was associated with HBeAg loss at 2 years (p = 0.019). After adjustment for age, sex, cirrhosis, baseline ALT, and HBV-DNA levels, this factor remained significant in multivariate analysis (odds ratio: 4.35; 95% confidence interval: 1.24-15.24, p = 0.021). CONCLUSION: On-treatment complete virological response at Month 6 is a favorable factor predictive of HBeAg loss at 2 years of entecavir therapy. Therefore, measurement of serum HBV-DNA level at 6 months of entecavir therapy is optimal to predict HBeAg loss at 2 years of therapy in HBeAg-positive CHB patients.

Chronic hepatitis B infection in adolescents who received primary infantile vaccination.

UNLABELLED: Hepatitis B virus (HBV) infection is a global health issue. Universal infantile hepatitis B (HB) vaccination is very efficacious. However, HBV infections among those immunized subjects have been reported. The long-term efficacy of postnatal passive-active HB vaccination in high-risk subjects is not well explored. A total of 8,733 senior high school students who were born after July 1987 were assayed for hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs). The overall HBsAg and anti-HBs-positive rates were 1.9% and 48.3%, respectively. The HBsAg-positive rate was 15% in HB immunoglobulin (HBIG) recipients (adjusted odds ratio [OR]: 15.63; 95% confidence interval [CI]: 10.99-22.22). Among students who did not receive HBIG, there was a significantly negative association between HB vaccination dosage and HBsAg-positive rate (P for trend = 0.011). Adjusted ORs for those who received 4, 3, and 1 to 2 doses were 1.00, 1.52 (95% CI: 0.91-2.53), and 2.85 (95% CI: 1.39-5.81), respectively. Among HBIG recipients, the HBsAg-positive rate was significantly higher in subjects with maternal hepatitis B e antigen (HBeAg) positivity and who received HBIG off-schedule. A booster dose of HB vaccination was administered to 1974 HBsAg- and anti-HBs-negative subjects. Prebooster and a postbooster blood samples were drawn for anti-HBs quantification. The proportions of postbooster anti-HBs titer <10 mIU/mL was 27.9%. Subjects with prebooster anti-HBs titers of 1.0-9.9 mIU/mL had significantly higher postbooster anti-HBs titers than those with prebooster anti-HBs titers of <1.0 mIU/mL (P < 0.0001). CONCLUSION: Having maternal HBeAg positivity is the most important determinant for HBsAg positivity in adolescents who received postnatal passive-active HB vaccination 15 years before. A significant proportion of complete vaccinees may have lost their immunological memories against HBsAg.

Prevalence and determinants of gastroesophageal reflux symptoms in adolescents.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is common in adults, and there are increasing secular trends in adult GERD morbidity in many countries. However, population-based study on adolescent GERD was very limited. The specific aims of the study were to explore the prevalence and determinant of GERD symptoms in adolescents. METHODS: A population-based association study was performed on 1828 students aged 13-16 years from four public junior high schools in Taiwan. The presences of symptoms of GERD, asthma and food allergy, demographic characteristics, and health behaviors were obtained by structured questionnaires. RESULTS: Complete information of symptoms of GERD and asthma were available for 1745 (95.5%) students. The cumulative and 3-month prevalence rates of GERD symptoms were 20.5% and 8.9%, respectively. Multivariate-adjusted odds ratio of having experienced GERD symptoms were 1.53 (95% confidence interval [CI]: 1.18-1.98) for ever smoking, 1.52 (95% CI: 1.12-2.26) for bi-ethnicity, 1.70 (95% CI: 1.26-2.29) for food allergy, and 3.59 (95% CI: 2.69-4.82) and 2.43 (95% CI: 1.67-3.53) for having asthma attacks within or more than 1 year before, respectively. Similar results were found for 3-month prevalence. CONCLUSIONS: The study showed that GERD symptoms were frequent in junior high school students in Taiwan. Food allergy, asthma, and cigarette smoking were independently correlated with the prevalence of GERD symptoms. Psychosocial factors associated with bi-ethnic family may contribute to its development.

Baseline hepatitis B surface antigen quantitation can predict virologic response in entecavir-treated chronic hepatitis B patients.

BACKGROUND/PURPOSE: Several anti-viral drugs are approved for the treatment of hepatitis B virus (HBV) infection. However, whether quantitative hepatitis B surface antigen (qHBsAg) can predict the therapeutic response during long-term entecavir treatment remains unclear. METHODS: Fifty-five chronic hepatitis B (CHB) patients who received entecavir for more than 2 years were enrolled. The serum qHBsAg level was measured by HBsAg II quant immunoassay. A significant decline in the qHBsAg level was defined as > 1 log reduction from baseline to 6 months of entecavir treatment. RESULTS: Of the 55 patients (41 males and 14 females with a mean age of 48.3 ± 11.4 years), 23 patients were positive for hepatitis B e antigen (HBeAg). The median treatment period was 34 months, and ranged from 26 months to 43 months. A total of 288 serum samples were used to determine the qHBsAg levels. At year 3 of entecavir therapy, one (1.8%) patient had HBsAg seroclearance. A high qHBsAg level was defined as greater than 10,000 IU/mL. Patients with a high baseline qHBsAg level had a lower rate of virologic response at year 1 (37.5% vs. 89.7%, p < 0.001) and year 2 (56.2% vs. 94.9%, p = 0.001). In this study population, 14.5% had a significant decline of the qHBsAg level. A significant decline could not predict HBeAg loss in HBeAg-positive or virologic response in all patients. CONCLUSION: The baseline serum qHBsAg level can predict virologic response in entecavir-treated CHB patients. However, a significant decline in the qHBsAg level cannot predict serologic or virologic response of entecavir treatment.

Factors affecting the diagnostic accuracy of ultrasonography in assessing the severity of hepatic steatosis.

BACKGROUND/PURPOSE: Ultrasonography has long been recognized as a useful tool for detecting hepatic steatosis in clinical practice. However, whether it can assess the severity of hepatic steatosis and which factors affect its diagnostic accuracy remain unclear. METHODS: A total of 171 patients with various causes of hepatitis undergoing liver biopsies were retrospectively reviewed. The clinical, serologic data and ultrasonographical findings were recorded. Hepatic steatosis was graded as negative, mild, moderate, or severe by ultrasonography and histology. Histology was used as gold standard and the agreement rates were calculated. RESULTS: Our data showed that the agreement rate of ultrasonography was 61.4% in assessing the severity of hepatic steatosis and 74.3% in diagnosing hepatic steatosis compared with histology (crude kappa=0.46 vs. 0.46). Using univariate analyses, body mass index and histology activity index score were associated with the agreement in assessing the severity of hepatic steatosis (p=0.008 and 0.035), whereas Ishak fibrosis score had a trend association (p=0.066). Multivariate analyses indicated that age, body mass index, and Ishak fibrosis score could affect the agreement (odds ratio=0.72, 0.89, and 1.41; 95% confidence interval=0.54-0.97, 0.83-0.97, and 1.1-1.8). CONCLUSION: Ultrasonography could assess the severity of hepatic steatosis with moderate accuracy. Obese patients are difficult ultrasonographically. In addition, age and hepatic fibrosis could affect the performance of ultrasonography in assessing the severity of hepatic steatosis.

A pilot study of add-on oral hypoglycemic agents in treatment-naïve genotype-1 chronic hepatitis C patients receiving peginterferon alfa-2b plus ribavirin.

BACKGROUND/PURPOSE: Insulin resistance (IR) affects sustained virological response (SVR) to peginterferon alfa plus ribavirin (PR) in patients with chronic hepatitis C (CHC). Whether add-on oral hypoglycemic agents (OHAs) to PR improve SVR remains unclear; therefore, we conducted a prospective, randomized pilot trial on 23 consecutive patients with genotype 1 CHC and IR in Taiwan. METHODS: Patients were randomized to receive acarbose (Arm A; n = 7) or metformin (Arm B; n = 6) or pioglitazone (Arm C; n = 5) in addition to peginterferon alfa-2b (1.5 µg/kg/week) plus ribavirin (1000-1200 mg/day) or just PR (Arm D; n = 5). The primary end point was SVR, and secondary end points were viral clearance at Weeks 17, 29, and 53. There were no differences among all arms at baseline. RESULTS: Using intent-to-treat analysis, SVR was observed in 66.7% (4/6), 83.3% (5/6), 66.7% (4/6), and 60% (3/5) in Arms A, B, C, and D, respectively. SVR was higher in female patients receiving OHA [90% (9/10)] than in male patients [50% (4/8)]. Results of per protocol analysis showed that SVR was 80.0% (4/5) in Arm A, 100% (5/5) in Arm B, 66.7% (4/6) in Arm C, and 60% (3/5) in Arm D. Patients receiving OHA had a higher rapid virologic response: 11/18 (61%) versus 2/5 (40%). Complete early virologic response was comparable between patients receiving OHA and PR [15/18 (83%) vs. 4/5 (80%)]. CONCLUSION: Our preliminary data show add-on OHAs to PR might achieve better early viral kinetics and SVR. However, further larger studies are needed to confirm these findings.

Responses to booster hepatitis B vaccination are significantly correlated with genotypes of human leukocyte antigen (HLA)-DPB1 in neonatally vaccinated adolescents.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near the human leukocyte antigen (HLA)-DP loci that were significantly correlated with outcomes of hepatitis B virus (HBV) infection. We performed a case-control study nested in a well-characterized cohort of booster recipients to assess whether genetic variants of HLA-DPB1 are also associated with response to hepatitis B (HB) vaccination. The cases and controls were 171 and 510 booster recipients whose post-booster titers of antibodies against HBV surface antigen (anti-HBs) were undetectable and detectable, respectively. The HLA-DPB1 genotype was determined using sequence-based techniques. The frequencies of HLA-DPB1 alleles were significantly different between cases and controls (p = 1.7 × 10(-8)). The HLA-DPB1 05:01 and 09:01 alleles were significantly more frequent in the cases, and 02:01:02, 02:02, 03:01:01, 04:01:01, and 14:01, were significantly more frequent in the controls. The adjusted odds ratio (OR) of undetectable post-booster anti-HBs titers was significantly correlated with the number of risk alleles (p for trend = 3.8 × 10(-5)). For the number of protective alleles, the trend was significantly inversed (p for trend = 1.3 × 10(-5)). As compared with subjects with two risk alleles, adjusted OR were 0.34 (95 % confidence interval [CI] 0.21-0.55) and 0.20 (95 % CI 0.08-0.48) for subjects with 1 and 2 protective alleles, respectively. The HLA-DPB1 02:02, 04:01:01, 05:01 and 09:01 alleles were also significantly correlated with the likelihoods of undetectable pre-booster anti-HBs titers. Our results indicated that HLA-DPB1 is significantly correlated with response to booster HB vaccination in adolescent who had received postnatal active HB vaccination. HLA-DBP1 may also determine the long-term persistence of response to HB vaccination.

Viral load and alanine aminotransferase correlate with serologic response in chronic hepatitis B patients treated with entecavir.

BACKGROUND AND AIM: Although entecavir has been shown to have good efficacy and low resistance for the treatment of chronic hepatitis B (CHB), factors associated with a favorable response remain unknown. METHODS: This was a retrospective, multicenter study of 248 treatment-naïve hepatitis B e antigen (HBeAg)-positive patients (69.4% male; median age, 39.4 years) treated with entecavir for more than 1 year, and 15.7% of them had cirrhosis at baseline. The primary endpoints were HBeAg loss and/or seroconversion. RESULTS: The median baseline levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA were 201 U/L (range, 27-2415 U/L) and 7.6 log(10) IU/mL (range, 2.2-13.18), respectively. The median treatment period was 25.3 months (range, 12-69.6). The rates of ALT normalization at years 1, 2, and 3 were 83.1%, 87.9%, and 94.9%, respectively. The cumulative rates of HBeAg loss at years 1, 2, and 3 were 20.3%, 38.0%, and 48.9%, respectively. The rates of undetectable HBV-DNA at years 1, 2, and 3 were 52.1%, 78.9%, and 82.5%, respectively. Using Cox proportional hazards model, multivariate analysis showed that baseline ALT greater than five times the upper limit of normal, and viral load were independent factors associated with HBeAg loss (hazard ratio: 1.81, and 0.812; 95% confidence interval: 1.062-3.085; 0.7-0.942, respectively). CONCLUSION: Entecavir treatment for 3 years can achieve good biochemical and virologic responses in HBeAg-positive CHB patients, but has a modest effect on HBeAg loss and/or seroconversion. In addition, baseline serum ALT and HBV-DNA levels are independent factors associated with favorable treatment responses.

Male sex, hiatus hernia, and Helicobacter pylori infection associated with asymptomatic erosive esophagitis.

BACKGROUND AND AIMS: Asymptomatic erosive esophagitis (AEE) is an easily forgotten subgroup of gastroesophageal reflux disease due to its lack of warning symptoms, despite having the risk of developing complications, such as bleeding, stricture, or even esophageal adenocarcinoma. METHODS: A total of 2843 potentially eligible patients were screened at the health management center of Buddhist Tzu Chi General Hospital. A total of 1001 patients responded to the survey and gave informed consent; 998 patients who completed the reflux disease diagnostic questionnaire were enrolled. Of them, 594 patients who had no reflux symptoms were included for final analysis. The presence and severity of erosive esophagitis was graded according to the Los Angeles classification. Active infection of Helicobacter pylori (H. pylori) was determined by the Campylo-like organism (CLO) test during endoscopies. RESULTS: A total of 14.5% (86/594) of asymptomatic patients had endoscopic findings of erosive esophagitis. In the univariate analysis, male sex and hiatus hernia were significantly associated with AEE. Positive CLO tests had a trend association. Based on the multivariate analysis, male sex (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.35-3.98), hiatus hernia (OR: 4.48, 95% CI: 2.35-89.17), and positive CLO test (OR: 0.57, 95% CI: 0.34-0.95) were associated with AEE, as compared to the healthy controls. CONCLUSIONS: AEE is not a rare condition, and constitutes 14.5% of the asymptomatic population. Male sex, hiatus hernia, and H. pylori infection are factors associated with AEE. These findings are not only helpful in identifying such asymptomatic patients, but also provide information to improve understanding of the relationship between H. pylori infection, reflux symptoms, and erosive esophagitis.

Elevation of serum aminotransferase activity increases risk of carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of atherosclerosis and alanine aminotransferase (ALT) is associated with insulin resistance independently of metabolic factors. The aim of the present study was to investigate whether NAFLD patients with ALT elevation had a higher risk of carotid atherosclerosis. METHODS: A total of 190 individuals were enrolled from the health management center. Among them, 20 subjects were excluded due to the presence of hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and cardiovascular disease. NAFLD was diagnosed by ultrasound examination. Carotid ultrasonography was used to measure maximal intima-media thickness (IMT) of the common carotid artery (CCA) and IMT (mean) > 1.0 mm was defined as the presence of carotid atherosclerosis. RESULTS: NAFLD patients with ALT elevation had increased risk of carotid atherosclerosis than those with normal ALT by Fisher's exact test (P < 0.05). Multivariate analyses showed that serum ALT levels were positively associated with carotid atherosclerosis after adjustment for age, sex, number of metabolic syndrome components or status of metabolic syndrome (OR, 1.44; 95% CI 1.09-1.89; OR, 1.45; 95% CI 1.11-1.91). In addition, the higher the serum ALT levels with every 10 IU/L increment, the greater the risk of carotid atherosclerosis. CONCLUSIONS: Serum ALT levels are positively associated with the risk of carotid atherosclerosis in patients with NAFLD, suggesting that serum ALT levels could serve as a surrogate marker of cardiovascular risk in this special clinical setting.

Response to hepatitis B vaccination is co-determined by HLA-DPA1 and -DPB1.

BACKGROUND AND AIMS: No report explored the combined effects of HLA-DPA1 and -DPB1 with long-term response to hepatitis B (HB) vaccination (HBVac). The specific aims of the study were to assess the combined effects and relative contributions of DPA1 and DPB1 genes. METHODS: The cases were 152 adolescents who had undetectable (<1.0 mIU/mL) post-booster anti-HBs titers and the controls were adolescents who had residual anti-HBs ≥ 10 mIU/mL at aged 16 years (n = 207) or had detectable (≥1.0 mIU/mL) anti-HBs titers after booster HBVac (n = 481). HLA-DPA1 and -DPB1 genotypes were determined by sequence-based typing. RESULTS: HLA-DPA1*01:03:01 was correlated with lower ORs of undetectable anti-HBs titers, while -DPA1*02:02:02 and -DPB1*05:01:01 were correlated with higher ORs. The ORs for HLA-DPA1*01:03:01-DPB1*05:01:01 and DPA1*02:02:02-DPB1*protective combinatory types were significantly less than 1.0. As compared with subjects who had no protective allele, the adjusted ORs (95% CI) were 0.545 (0.328-0.906), 0.350 (0.174-0.702), and 0.122 (0.058-0.257), for subjects who had protective alleles on DPA1only, DPB1 only, and both genes, respectively. Analyses of amino acid polymorphisms showed that subjects who carried Arg81-Pro158-Val191-Pro259α + Met234ß and Gln62-Arg82α + Met234ß combinations had 4.3-to-4.6 folds of risks. CONCLUSION: Both DPA1 and DPB1 genes contribute to the persistence of immunological response to primary infantile HBVac. The effects of HLA-DP risk alleles were dominated by the protective alleles and there were significant gene-gene interactions. Our findings provide evidences for the design of more potent HB vaccine.

Decreased neonatal hepatitis B virus (HBV) viremia by maternal tenofovir treatment predicts reduced chronic HBV infection in children born to highly viremic mothers.

BACKGROUND: Maternal anti-viral treatment prevents mother-to-infant transmission of hepatitis B virus (HBV), but the role of neonatal viremia on subsequent HBV infection is not clear. AIMS: To investigate the effect of maternal anti-viral treatment on neonatal serum HBV DNA and hepatitis B surface antigen (HBsAg) in infants born to highly viremic mothers and the roles of neonatal markers in predicting chronic HBV infection in children. METHODS: Serum HBV DNA and HBsAg were tested in children. Of the 201 pregnant mothers, 110 received tenofovir during the third trimester. Chronic infection in children was defined by HBsAg seropositivity at 6 or 12 months lasting more than 6 months. RESULTS: The maternal HBV viral loads from baseline to delivery were 8.25 ± 0.48 to 4.29 ± 0.98 log10  IU/mL; and 8.29 ± 0.49 to 8.12 ± 0.68 log10  IU/mL in the tenofovir and control group respectively. Of the 208 children, those in the tenofovir group had a lower rate of neonatal HBV DNA seropositivity at birth (5.22% vs 30.11%, P < 0.0001) and HBsAg seropositivity at 6 months (1.74% vs 11.83%, P = 0.003) and 12 months (1.74% vs 10.75%, P = 0.007). In a first multivariate analysis, maternal HBV DNA level at delivery (odds ratio = 1.70, P = 0.0172) and neonatal HBsAg positivity (odds ratio = 19.37, P < 0.0001) were significantly associated with children's chronic HBV infection. In a second model, neonatal HBV DNA positivity was a strong independent influence variable (odds ratio = 61.89, P = 0.0002). CONCLUSIONS: Maternal tenofovir therapy decreased maternal viral load and neonatal viremia. Positive neonatal HBV DNA was highly correlated with chronic HBV infection in children. Clinical Trial Identifier: NCT01312012.

SEN virus infection in patients on peritoneal dialysis.

BACKGROUND: Many reports have demonstrated SEN virus (SEN-V) infection rates in hemodialysis patients, but the SEN-V infection rate in peritoneal dialysis (PD) patients has never been reported. In this study, we determined the prevalence rate of SEN-V viremia in a PD population. METHODS: Serum samples from 47 PD patients and a control group of 43 subjects from the general population at their health examination were assayed for SEN-V-D and -H viremia using polymerase chain reaction. RESULTS: The proportions of female gender (p = 0.001), previous transfusion (p < 0.0001), and higher mean serum AST level (p = 0.012) were significantly higher in PD patients. The prevalence rates of SEN-V-D and/or -H viremia were not significantly different between PD patients and controls (27.7% vs 32.6%). SEN-V-D(+) patients had lower mean duration of PD than SEN-V(-) patients. Mean ALT level was significantly lower in SEN-V-H(+) than in SEN-V(-) patients (12.8 +/- 5.8 vs 19.6 +/- 12.1 (IU/L), p = 0.025). None of the SEN-V-infected PD patients had overt clinical or biochemical signs of liver disease. There were no statistically significant differences in prevalence of SEN-V-D and/or -H viremia between automated PD (APD) patients and continuous ambulatory PD (CAPD) patients. CONCLUSIONS: These results indicate that the SEN-V infection rate is not different between healthy individuals and PD patients. Infection with SEN-V is not associated with evident liver disease in PD patients and SEN-V infection rate is not different between APD patients and CAPD patients.