Hans Hsienhong Lin

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

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

Interferon-based therapy reduces risk of stroke in chronic hepatitis C patients: a population-based cohort study in Taiwan

Hepatitis C virus (HCV) infection has been linked to an increased risk of insulin resistance and carotid atherosclerosis.

Chronic hepatitis B infection in adolescents who received primary infantile vaccination

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. (HEPATOLOGY 2013)

Long‐term trends and geographic variations in the survival of patients with hepatocellular carcinoma: Analysis of 11 312 patients in Taiwan

Background/Aims:  The survival rates of patients with hepatocellular carcinoma (HCC) were investigated over the past 20 years to clarify the long‐term survival trend.

Do young hepatocellular carcinoma patients have worse prognosis? The paradox of age as a prognostic factor in the survival of hepatocellular carcinoma patients

Abstract: Background/Aims: Our previous study showed that male hepatocellular carcinoma (HCC) patients below 40 years of age had the worst survival in the initial several years, but had the best prognosis thereafter. Thus, it seems that age has a paradoxical influence on the prognosis. To further clarify the issue of age on HCC prognosis, we initiated this study.

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.

Increasing insulin resistance is associated with increased severity and prevalence of gastro‐oesophageal reflux disease

Aliment Pharmacol Ther 2011; 34: 994–1004

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

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.

HLA and response to booster hepatitis B vaccination in anti-HBs-seronegative adolescents who had received primary infantile vaccination

To explore contemporarily genetic and non-genetic determinants of long-term immunological memory to hepatitis B (HB) vaccination, we conducted a case-control study nested in an adolescent cohort of booster recipients who had received primary infantile HB vaccination but with residual anti-HBs titers <10 mIU/mL at 15-18 years of age. High-resolution phenotypes of human leukocyte antigen (HLA)-A, -B, and -DRB1 loci were determined by sequence-specific oligonucleotide probe hybridization. After controlling for pre-booster anti-HBs levels, the absences of HLA-A*02 and -DRB1*08, simply expressed as A*02(-) and -DRB1*08(-), and the presence of B*15 were significantly associated with elevated risks of non-response (post-booster anti-HBs titers<10 mIU/mL) to booster vaccination. The adjusted odds ratios (ORs) were 3.85 (CI, 1.82-8.33), 4.55 (CI, 1.23-16.67), 3.59 (CI, 1.40-9.17), respectively. There was multiplicative synergism between A*02 and B*15 on the risk of non-response to booster vaccination. The multivariate-adjusted ORs for A*02(-)/B*15, A*02(-)/B*15(-), A*02/B*15, and A*02/B*15(-) haplotypes were 20.39 (p=0.0003), 3.29 (p=0.007), 1.32 (p>0.05), and 1.0, respectively. Recent cigarette smoking and/or betel-quid chewing was associated with a 12-fold risk of non-response to booster vaccination. Further comparisons between responders and adolescents who had undetectable post-booster anti-HBs titers (<0.1 mIU/mL) demonstrated similar results. Our results indicated that response to booster HB vaccination as well as long-term immunological responses to HB vaccination are closely related with host genetic factors, and probably modified by recent substance use.

Systematic Review: Impact of Interferon-based Therapy on HCV-related Hepatocellular Carcinoma

Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC), and several antiviral agents are available for the treatment of chronic HCV infection. However, the impact of antiviral therapy on the long-term outcomes of HCV-related HCC patients remains inconclusive. We aimed to examine the impact of antiviral therapy on the long-term outcomes of HCV-related HCC patients. We conducted a systematic review using PRISMA guidelines to identify trials and English-language literature from PubMed, Ovid MEDLINE, Scopus and the Cochrane Library database till August 2014. Randomized trials of antiviral treatments examining the effects of antiviral therapy on CHC patients and HCV-related HCC patients were screened and selected. We identified 6 trials evaluated the effectiveness of interferon (IFN)-alfa treatment, 3 studies examined pegylated interferon-alfa treatment, and 2 studies examined IFN-beta treatment. IFN-based therapy may decrease HCC incidence in HCV cirrhotic patients after a >5-year follow-up, improve liver reserve, decrease HCC recurrence rate, and increase survival rate in HCV-related HCC patients after curative HCC therapy. In conclusion, IFN-based therapy is beneficial and may be recommended in the management of HCV-related HCC patients who are IFN eligible.