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.
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.
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).
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.
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.
Interferon-based therapy (IBT) has been the standard of care for hepatitis C virus (HCV) infection. However, conflicting results exist regarding the effects of IBT on risk of developing ...hepatocellular carcinoma (HCC) and cirrhosis-associated complications, and most included highly selected patients.
This 8-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 (>23.7 million). Patients with newly detected HCV infections (n=11,264) were classified based on treatment and clinical outcomes. IBTs were defined as regimens that included interferon- alfa, pegylated interferon- alfa -2a, or pegylated interferon- alfa -2b for at least 3 months. The Cox proportional hazards models were used to estimate the hazard ratio (HR) and associated confidence interval (CI) of HCC and cirrhosis-associated complications for IBT.
The 8-year incidence rate for HCC was 3.9% among patients who received IBT and 5.6% among those who did not. The HCC-free survival rate was significantly higher among patients receiving IBT during the 8-year period than their counterpart (adjusted HR, 0.50; 95% CI, 0.31-0.81; P= .004). Similarly, the event-free survival rates for esophageal variceal bleeding (adjusted HR, 0.45; 95% CI, 0.22-0.91; P= .026), hepatic encephalopathy (adjusted HR, 0.38; 95% CI, 0.21-0.69; P= .001), ascites (adjusted HR, 0.28; 95% CI, 0.14-0.57; P<.001), and cirrhosis (adjusted HR, 0.63; 95% CI, 0.44-0.91; P= .013) were significantly higher among patients who received IBT than those who did not, after adjustment for associated factors.
Treatment with interferon may reduce the 8-year risk of HCC and cirrhosis-associated complications in patients with chronic HCV infection.
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.
Abstract 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.
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.
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.
Background/Aims In this revaccination study, we explored the determinants of response to booster hepatitis B (HB) vaccination in anti-HBs-seronegative adolescents who had received primary HB ...vaccination 15–18 years before. Results After controlling for prebooster anti-HBs levels, cigarette smoking, betel–quid chewing, alcohol drinking, and indigenous ethnicity were significantly associated with elevated risks of non-response to booster HB vaccination. The adjusted odds ratios (aORs) were 3.21 (CI: 1.33–7.84), 8.78 (CI: 2.03–37.94), 2.64 (CI: 1.15–6.02), and 2.46 (CI: 1.28–4.72), respectively. Among adolescents with undetectable prebooster anti-HBs titers, only indigenous ethnicity significantly associated with elevated risk, with an adjusted OR of 2.57 (CI: 1.20–5.54), of non-response to booster HB vaccination. On the contrary, the influences of cigarette smoking, betel–quid chewing, and alcohol drinking were restricted to adolescents with prebooster anti-HBs titers of 0.1–9.9 mIU/mL. The corresponding multivariate-adjusted ORs were 5.70, 17.41, and 3.72, respectively. Adolescents who smoked cigarettes and chewed betel–quid were at highest risk of non-response (aOR, 25.3; CI: 2.97–215.7). Conclusions A booster dose of HB vaccine may be insufficient to induce immunological response in healthy adolescents who had undetectable prebooster anti-HBs titers or who were of Malay-Polynesian ethnicity. Responses to booster vaccination are probably modified by recent cigarette smoking and/or betel–quid chewing.
Aim
The efficacy of entecavir (ETV) in treatment‐experienced chronic hepatitis B (CHB) patients remains unclear. We evaluated the therapeutic responses and virological breakthrough following ETV ...treatment in hepatitis B e‐antigen (HBeAg) positive CHB patients with prior exposure to interferon or nucleoside/nucleotide analog and treatment‐naive patients.
Methods
This was a retrospective, multicenter study of treatment (>1 year) with 0.5 mg ETV in 248 treatment‐naive and 48 treatment‐experienced HBeAg positive CHB patients (70.5% male; mean age, 40.5 years). The rates of undetectable hepatitis B virus (HBV) DNA, HBeAg loss and virological breakthrough were analyzed.
Results
The median duration of ETV treatment was 27.3 months (range, 18.4–34.5). The rate of HBeAg loss was 41.9% (104/248) in treatment‐naive and 45.8% (22/48) in treatment‐experienced patients. The baseline serum HBV DNA and alanine aminotransferase levels were significant predictors for HBeAg loss (P = 0.01 and P = 0.04, respectively). There was no statistical difference between the groups in the rates of undetectable HBV DNA and HBeAg loss at any time point. Virological breakthrough occurred in 1.6% (4/248) of treatment‐naive and 8.3% (4/48) of treatment‐experienced patients. The four treatment‐experienced patients with virological breakthrough had received prior lamivudine treatment. After excluding those treated with interferon, lamivudine‐experienced patients had significantly greater virological breakthrough compared with treatment‐naive patients (log–rank test, P = 0.034; univariate Cox regression, P = 0.047).
Conclusion
ETV treatment efficacy, including virological response and HBeAg loss, was comparable between treatment‐naive and treatment‐experienced HBeAg positive CHB patients. Lamivudine‐experienced patients had a higher risk of virological breakthrough than treatment‐naive patients.
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