Poly(3,3-dibenzyl-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine)/Platinum Composite Films as Potential Counter Electrodes for Dye-Sensitized Solar Cells.

In this study, poly(3,3-dibenzyl-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine)/platinum composite films (PProDOT-Bz2/Pt) were used as counter electrodes (CEs) in dye-sensitized solar cells (DSSCs). The composite films were prepared on fluorine-doped tin oxide (FTO) glass by radio frequency (RF) sputtering to deposit platinum (Pt) for 30 s. Afterwards, PProDOT-Bz2 was deposited on the Pt⁻FTO glass via electrochemical polymerization. The electron transfer process of DSSCs was investigated using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The DSSCs with 0.05 C/cm² PProDOT-Bz2-Pt composite films showed an open circuit voltage (Voc) of 0.70 V, a short-circuit current density (Jsc) of 7.27 mA/cm², and a fill factor (F.F.) of 68.74%. This corresponded to a photovoltaic conversion efficiency (η) of 3.50% under a light intensity of 100 mW/cm².

A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese.

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10(-14)), rs9276370 (HLA-DQA2, P = 1.9×10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10(-11) and P = 6.66×10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P = 1.48×10(-12); OR = 1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.

Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients.

UNLABELLED: The optimal duration of nucelos(t)ide analog (Nuc) treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B virus (HBV) infection is unknown. The Asian Pacific Association for the Study of the Liver (APASL) guidelines recommend that treatment can be discontinued if undetectable HBV-DNA has been documented on three occasions ≥ 6 months apart. This study aimed to test this stopping rule in HBeAg-negative chronic hepatitis B (CHB) patients treated with entecavir (ETV). Ninety-five patients (39 cirrhosis) were treated with ETV for a median of 721 (395-1,762) days before stopping therapy and were then monitored with serum HBV DNA and alanine aminotransferase (ALT) at least every 3 months. Within 1 year after stopping ETV therapy, "clinical relapse" (an episode of ALT elevation >2 × upper limit of normal plus HBV-DNA >2,000 IU/mL) occurred in 43 (45.3%) of the 95 patients. Of the 39 cirrhosis patients, 17 (43.6%) relapsed and one (2.6%) developed decompensation. The median duration until relapse was 230 days (74.4% >6 months). Logistic regression analysis showed that baseline HBV-DNA ≤ 2 × 10(5) IU/mL was the only significant independent factor for sustained response. The 1-year relapse rate was 29% in patients with a baseline HBV DNA ≤ 2 × 10(5) IU/mL versus 53% in those with HBV DNA >2 × 10(5) IU/mL (P = 0.027). For the latter, consolidation therapy >64 weeks reduced the relapse rate to 33.3% in patients without cirrhosis. CONCLUSION: With an overall 1-year relapse rate of 45% and 29% in those with a baseline serum HBV DNA ≤ 2 × 10(5) IU/mL, the APASL stopping rule for HBeAg-negative CHB patients with proper off-therapy monitoring is adequate even in patients with cirrhosis. Consolidation therapy >64 weeks seems more appropriate for those with higher baseline HBV DNA.

Clinical and virological characteristics post HBsAg seroclearance in hepatitis B virus carriers with hepatic steatosis versus those without.

BACKGROUND: It has been suggested hepatic steatosis contributes to seroclearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B virus (HBV) infection. Although HBsAg seroclearance generally confers favorable outcome, hepatic steatosis may account for progressive liver fibrosis and cirrhosis. Further studies are needed to compare clinical and virological characteristics post HBsAg seroclearance between subjects with hepatic steatosis and those without. METHODS: One-hundred and fifty-five HBsAg carriers with HBsAg seroclearance were enrolled. Subjects with moderate-severe hepatic steatosis as diagnosed by ultrasonography were designated as having hepatic steatosis. RESULTS: There were 69 subjects with hepatic steatosis and 86 without. Subjects with hepatic steatosis had significantly higher body mass index (BMI; 27.8 ± 3.5 vs. 23.0 ± 3.1, P < 0.001), were more likely to be male (78.3 vs. 63.9%, P = 0.05), and were significantly younger at HBsAg seroclearance (48.7 ± 8.9 years vs. 53.4 ± 8.9 years, P = 0.001), than those without. The frequency of anti-HBsAg seroconversion (56.5 vs. 59.3%, P = 0.72) and HBV viremia (20.3 vs. 15.1%, P = 0.40) was not significantly different between subjects with and without hepatic steatosis, but the incidence of abnormal AST and ALT was significantly higher in the former (23.2 vs. 0%, P < 0.0001; and 30.4 vs. 0%, P < 0.0001, respectively), and progression to liver cirrhosis tended to be more likely in the former than in the latter (10.1 vs. 3.5%, P = 0.09). CONCLUSIONS: In HBsAg carriers with increased body mass index, hepatic steatosis can accelerate HBsAg seroclearance by approximately 5 years. However, the beneficial effects of HBsAg seroclearance should be balanced against the harmful effects of hepatic steatosis.

Decreasing levels of HBsAg predict HBsAg seroclearance in patients with inactive chronic hepatitis B virus infection.

BACKGROUND & AIMS: Serum levels of hepatitis B surface antigen (HBsAg) decrease gradually during chronic hepatitis B virus infection. We investigated the association between levels of HBsAg and HBsAg seroclearance. METHODS: We studied data from 46 patients who underwent spontaneous seroclearance of HBsAg (median age at seroclearance, 48 y; 87% male; 76% infected with genotype B). There were 46 controls matched for age, sex, and hepatitis B virus genotype, and e antigen status with persistently normal levels of alanine aminotransferase and seropositive for HBsAg. Levels of HBsAg were assessed in serum specimens collected 5 years 3 years, and 1 year before HBsAg seroclearance (or before the last examination, for controls). RESULTS: The decrease in HBsAg level was significant and accelerated within the 3 years before HBsAg seroclearance; there was no significant decrease in serum level of HBsAg among controls (P < .0001). The positive predictive value (PPV) for HBsAg seroclearance within 1 year was 36% among patients with HBsAg levels of 200 IU/mL, increasing to 44%, 54%, and 67% among patients with HBsAg levels of 100 IU/mL, 50 IU/mL, or 10 IU/mL, respectively; the negative predictive value (NPV) for these levels was 96% or greater. The combination of HBsAg level less than 200 IU/mL and a decrease of 1 or more log(10) IU/mL in a preceding 2-year period had PPVs of 97% and 100% for HBsAg seroclearance at 1 and 3 years, respectively; the NPVs were 100% and 92%, respectively. CONCLUSIONS: The decrease in the level of HBsAg accelerates during the 3 years before HBsAg seroclearance. Levels of HBsAg of 200 IU/mL or less have high NPVs for HBsAg seroclearance; PPVs increase to 97% to 100% when combined with a 1 log IU/mL or more decrease in level of HBsAg over a 2-year period.

Viral load, genotypes, and mutants in hepatitis B virus-related hepatocellular carcinoma: special emphasis on patients with early hepatocellular carcinoma.

BACKGROUND/AIMS: The role of viral factors in the pathogenesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is still inconclusive. Whether virological features such as viral load or mutants might change with the progression of HCC remains unknown. A case-control study including patients with early HCC and HBsAg carriers who are presumed to be at the minimal potential of HCC as controls might better identify factors significantly associated with HCC development. METHODS: Virological features were compared between 59 patients with early HCC (a solitary tumor of size ≤ 3 cm) and 101 patients with non-early HCC. A case-control study was performed by comparing 59 patients with early HCC and 1:2 age-matched inactive carriers with persistent normal alanine aminotransferase (ALT) levels. RESULTS: HBV DNA levels, HBV genotypes, and the frequency of precore A1896 and basal core promoter T1762/A1764 mutations showed no significant difference between patients with early HCC and those with non-early HCC. In the case-control study, patients with early HCC had significantly higher HBV DNA levels, and higher frequencies of genotype C HBV and basal core promoter T1762/A1764 mutation, but a similar frequency of precore A1896 mutation. Multiple logistic regression analysis identified HBV DNA levels ≥ 2,000 IU/mL and basal core promoter T1762/A1764 mutation as being independent factors for HCC development. Additionally, there was a synergistic effect between high viral load and basal core promoter T1762/A1764 mutation on HCC development. CONCLUSIONS: Virological features did not change significantly with the progression of HCC. HBV DNA levels ≥ 2,000 IU/mL and basal core promoter T1762/A1764 mutation were two independent viral factors for HCC.

Prevalence of and risk factors for hepatitis B viremia after spontaneous hepatitis B surface antigen seroclearance in hepatitis B carriers.

In 118 previous hepatitis B surface antigen (HBsAg) carriers, low-level hepatitis B (HBV) viremia persisted at a rate of 15%-20% for >10 years after HBsAg seroclearance. The frequency of HBV viremia was significantly (P = .002) lower in patients with anti-HBsAg seroconversion (6 of 69 [8.7%]) than in those without seroconversion (15 of 49 [30.6%]).

Hepatitis B surface antigen seroclearance during chronic HBV infection.

Hepatitis B surface antigen (HBsAg) seroclearance in chronic HBV infection occurs at an annual incidence of 1-2%. The long-term outcome after HBsAg seroclearance is excellent if there is no pre-existing cirrhosis or viral superinfection. For this reason, HBsAg seroclearance has attracted recent interest in both long-term studies of the natural history of HBV infection and in patients receiving antiviral therapy. Here, we review a diverse range of studies investigating spontaneous HBsAg seroclearance in varied groups of patients and consider the many predictive factors - of both viral and host origin - for seroclearance. Studies to assess the effects of antiviral therapy, and in particular interferon treatment, are also discussed together with virological, biochemical and histological profiles following HBsAg seroclearance and the long-term outcomes.

Level of hepatitis B virus DNA in inactive carriers with persistently normal levels of alanine aminotransferase.

BACKGROUND & AIMS: Little is known about the level of hepatitis B virus (HBV) DNA in individuals with chronic, inactive HBV infections. Patients who test positive for the antibody to hepatitis B e antigen (anti-HBe) and have normal levels of alanine aminotransferase for more than 10 years have a low risk of HBV reactivation and are considered to be inactive carriers. We investigated HBV DNA levels in inactive carriers and identified factors that correlated with this state among anti-HBe-positive carriers with HBV DNA levels of 10(4) copies/mL or greater (5.26 copies/mL = 1 IU/mL). METHODS: HBV DNA levels were assayed in 250 inactive carriers with persistently normal alanine aminotransferase levels for more than 10 years. Clinical and virologic features were compared between inactive carriers (with HBV DNA levels > or =10(4) copies/mL) and age-matched patients with HBe antigen-negative chronic hepatitis (controls, n = 90). RESULTS: The median level of HBV DNA among inactive carriers was 3.70 log(10) copies/mL (range, undetectable to 5.98 log(10) copies/mL). Ninety (36%) had levels of 10(4) copies/mL or greater. Compared with control patients, significant differences of inactive carriers included sex (more female patients), lower HBV DNA levels, and lower prevalence of genotype C virus and the basal core promoter mutation T1762/A1764. The prevalence of the precore mutation A1896 was similar between groups. Multiple logistic regression analyses identified male sex, HBV DNA levels greater than 10(5) copies/mL, and the basal core promoter mutation as independent factors that correlated with active disease. CONCLUSIONS: Nearly 40% of inactive carriers had HBV DNA levels of 10(4) copies/mL or greater. Female sex, HBV DNA levels of 10(4) to 10(5) copies/mL, and wild-type basal core promoter correlated with inactive carrier state.

Relative roles of HBsAg seroclearance and mortality in the decline of HBsAg prevalence with increasing age.

OBJECTIVES: Mortality and hepatitis B surface antigen (HBsAg) seroclearance are the two extremes of prognostic destination of chronic hepatitis B virus (HBV) infection. Their relative roles in the decline of HBsAg prevalence with increasing age are unknown. METHODS: HBsAg-seropositive subjects with near normal alanine aminotransferase (ALT) were followed up every 3 to 12 months for >1 year. Serum HBsAg was assayed at entry and re-assayed at 3- to 5-year intervals. The morbidity and mortality data were obtained from hospital records, cancer registration, and the national mortality database. The mortality and HBsAg-seroclearance rates were examined by survival analysis. RESULTS: At entry, 1,386 subjects (20.9%) were hepatitis B e antigen (HBeAg) seropositive and 5,235 were HBeAg seronegative. The mean follow-up period was 13.6+/-5.4 years (median 13.2; range 1-29.1). HBsAg seroclearance occurred more frequently (555 cases, 8.4%) than mortality (97 cases, 1.5%; P<0.001; overall HBsAg seroclearance/mortality ratio: 5.6), of which only 40% were liver-related cases. Cox regression analysis revealed that male sex, HBeAg negativity, older age, low maximal ALT level, and hepatic steatosis were factors associated with HBsAg seroclearance. The estimated annual HBsAg seroclearance rate was around 1.05-1.61% after the age of 50 years, whereas the estimated mortality rate was quite low before the age of 60 and increased from 0.41% per year at ages 60-64 to 1.19% per year at ages 70-74 years. CONCLUSIONS: The HBsAg seroclearance over mortality rate was 5.6 in this cohort. This suggests that HBsAg seroclearance is the main reason for decreasing HBsAg prevalence with increasing age in the population.

Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B.

UNLABELLED: Hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B virus infection confers a favorable prognosis, but untoward outcomes may develop in some patients. The impact of the age of HBeAg seroconversion on prognosis is not clearly known. HBeAg-positive patients with biopsy-proven chronic hepatitis B were followed up long-term. Follow-up studies included liver biochemistry, alpha-fetoprotein, and ultrasonography every 3 to 6 months or more frequently if clinically indicated. Of the patients who underwent spontaneous HBeAg seroconversion, the incidences of HBeAg-negative hepatitis, cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen seroclearance were compared between patient groups with different ages at the time of HBeAg seroconversion using Kaplan-Meier survival analysis and Poisson regression model. Spontaneous HBeAg seroconversion was documented in 508 patients. Of the 483 patients who had no evidence of cirrhosis or HCC at the time of HBeAg seroconversion, HBeAg seroconversion occurred before age 30 in 218 patients (group A), between age 31 and 40 in 199 patients (group B), and after age 40 in 66 patients (group C). The 15-year cumulative incidences of HBeAg-negative hepatitis, cirrhosis, and HCC increased with increasing age of HBeAg seroconversion, the lowest being in group A (31.2%, 3.7%, and 2.1%, respectively) and highest being in group C (66.7% [P < 0.0001], 42.9% [P <0.0001], and 7.7% [P = 0.29], respectively). The hazard ratio of HBeAg-negative hepatitis, cirrhosis, and HCC was 2.95, 17.6, and 5.22, respectively, in group C compared with group A. CONCLUSION: Patients with HBeAg seroconversion before age 30 have excellent prognosis, whereas patients with delayed HBeAg seroconversion after age 40 have significantly higher incidences of HBeAg-negative hepatitis, cirrhosis, and HCC.

Immunopathology on hepatocyte expression of HBV surface, core, and x antigens in chronic hepatitis B: clinical and virological correlation.

PURPOSE: Hepatocyte expression of HBV surface, core, and x antigens (HBsAg, HBcAg and HBxAg), semi-quantitated by immunopathology, were correlated with clinical and virological data in 80 patients with chronic hepatitis B. RESULTS: Seventy patients were HBsAg positive in cytoplasm, 61 were HBcAg positive, including 45 in both nucleus and cytoplasm and 16 in cytoplasm only, and 47 were HBxAg positive in cytoplasm. The detection rates for HBcAg increased while those for HBsAg and HBxAg decreased with HBV DNA levels. Positive HBcAg staining usually suggested the presence of HBV DNA levels >10(6) copies/ml. HBcAg, HBsAg, and HBxAg expressions showed no significant differences between patients with genotype B and C. Serum HBeAg and HBV DNA levels correlated positively with nuclear or cytoplasmic HBcAg expression but inversely with HBsAg expression. By multiple regression analysis, HBV DNA levels correlated significantly only with nuclear HBcAg expression. ALT levels and inflammatory grades correlated with cytoplasmic HBcAg expression. There was an inverse quantitative relationship between HBcAg and HBsAg expression. Furthermore, HBxAg expression correlated significantly with HBsAg expression as well as male gender. CONCLUSIONS: With diminishing HBV DNA levels following HBeAg seroconversion, HBcAg expression decreased but HBsAg expression increased with a concomitant increase in HBxAg expression. Whether the finding that a significantly higher expression of HBxAg observed in males than females may account for the gender difference in long-term sequelae of chronic HBV infection needs further investigation.

Incidence and risk factors of progression to cirrhosis in inactive carriers of hepatitis B virus.

OBJECTIVES: Most hepatitis B virus (HBV) carriers are incidentally identified as inactive carriers (positive hepatitis B e antibody with normal alanine aminotransferase (ALT) levels), but their long-time outcome and risk of cirrhosis are incompletely understood. METHODS: A total of 1,965 inactive carriers (mean age: 35.6 years; males: 1,076) were studied. Cirrhosis was diagnosed using a high-resolution real-time ultrasound. RESULTS: During an 11.5-year mean follow-up, 314 carriers developed reactivation of hepatitis B (ALT was more than twice the upper limit of normal and positive HBV DNA was found using hybridization assays). The risk of reactivation of hepatitis B correlated significantly with advanced age at study entry (P<0.0001) and male sex (P<0.0001). A total of 57 patients developed cirrhosis, with the cumulative incidence being 15% after 25 years. The risk of cirrhosis correlated significantly with advanced age at entry (P=0.004) and reactivation of hepatitis B (P<0.0001). Of the 1,651 carriers without reactivation of hepatitis B, 10 developed cirrhosis, and advanced age at entry was the only significant factor (P=0.03). Of the 314 patients with reactivation of hepatitis B, cirrhosis developed in 47 of them, with the cumulative incidence being 8, 16, 27, and 46% at 5, 10, 15, and 20 years, respectively, after the onset of reactivation. Male sex (P=0.037) and advanced age at reactivation (P=0.006) were the two independent risk factors. CONCLUSIONS: The so-called inactive carrier state cannot be generally viewed as an innocent long-lasting condition of good prognosis; regular follow-up is necessary.

Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time.

UNLABELLED: The baseline alanine aminotransferase (ALT) level was reported to have prognostic value in chronic hepatitis B virus (HBV) infection, during which ALT may change over time. Instead of baseline ALT, this study aimed to study the prognostic value of the height of ALT during the course of chronic HBV infection. A total of 4376 asymptomatic hepatitis B e antigen (HBeAg) negative, surface antigen (HBsAg) carriers with baseline ALT less than 2 times the upper limit of normal (ULN) were monitored with ALT measurement and ultrasonography every 3 to 12 month for over 3 years. Maximal ALT levels during follow-up were correlated with long-term outcomes using morbidity and mortality data from hospital records, cancer registration, and national mortality database. Baseline ALT level was normal in 3673 subjects and increased to abnormal level in 1720 (46.8%) during a mean follow-up period of 13.4 +/- 5.2 (3.0-28.7) years. The incidence of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality increased with increasing maximal ALT level during follow-up, especially in those with maximal ALT of at least 2 times ULN, as compared with those who maintained normal ALT. Cox regression analysis indicated that age at entry, sex, and maximal ALT level during follow-up were significant independent factors associated with the development of cirrhosis, HCC, and mortality whereas cirrhosis was also an independent factor for HCC development and mortality. CONCLUSION: Persistently normal ALT was associated with excellent long-term prognosis, whereas increasing ALT levels of at least 2 times ULN during follow-up was associated with increasing morbidity and mortality. ALT of at least 2 times ULN is therefore an appropriate threshold for anti-HBV therapy, whereas those with ALT 1 to 2 times ULN require liver biopsy for decision.