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Hepatitis C virus (HCV) eradication through antivirals ameliorates metabolic profiles. The changes in 2‐h plasma glucose (2HPG) levels by oral glucose tolerance test (OGTT), in chronic hepatitis C (CHC) patients who receive directly acting antivirals (DAAs) was elusive. Five hundred and thirty‐three CHC patients who achieved sustained virological response (SVR, undetectable HCV RNA throughout 3 months after the end‐of‐treatment) by DAAs were consecutively enrolled. Pre‐ and posttreatment 2HPG levels and glucose status were compared. The proportion of patients with improved, worsened, and stable 2HPG was 14.4% (n = 77), 18.6% (n = 99), and 67.0% (n = 357), respectively. Compared with patients with worsening 2HPG, those with improved 2HPG had a higher proportion of cirrhosis (45.5% vs. 24.2%, p = 0.004) and higher pretreatment 2HPG levels (175.3 vs. 129.5 mg/dl, p < 0.001). High baseline 2HPG was independently associated with improved 2HPG in multivariate analysis (odds ratio [OR]/CI: 1.05/1.03–1.06, p < 0.001). When baseline 2HPG was not taken into account, cirrhosis was the only factor independently associated with improved 2HPG status (OR/CI: 2.58/1.29–5.15, p = 0.007). Linear regression analysis revealed that factors independently correlated to changes in 2HPG levels were female sex (β: 8.78; 95% CI:2.34, 15.22; p = 0.01), diabetes (β: −27.72; 95% CI: −50.16, −5.28; p = 0.02), liver cirrhosis (β: −8.91; 95% CI: −16.75, −2.20; p = 0.01), and genotype 1 of HCV (β: −0.12; 95% CI: −15.19, −2.43; p = 0.01). 2HPG improved after HCV eradication by DAAs, particularly in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) patients with low disease activity are at risk of liver fibrosis. The age‐adjusted fibrosis‐4 index (FIB4‐AA), developed in our previous publication, and was implemented to evaluate the tendency of liver fibrosis in these patients. We aimed to investigate the rate of liver fibrosis in CHB patients with low disease activity. Resuming our previous study, the FIB‐4 changes of 244 antiviral treatment‐naïve CHB patients, with a total of 1243.48 person‐years, were reviewed. Among the cohort, patients were categorized as FIB4‐AA positive or negative according to the results of their last FIB4‐AA minus their initial FIB‐4 during at least 18 months of observation time. The compound annual growth rate (CAGR) of FIB‐4 was calculated for the FIB4‐AA positive and negative groups. The assumed healthy controls had an FIB‐4 CAGR calculated to be 2.34% for both men and women, while the FIB‐4 CAGR of the whole study cohort was 2.84% ± 6.01%. FIB4‐AA positive effectively identifies CHB patients with higher mean FIB‐4 CAGR (7.11% ± 3.88% vs. −2.36% ± 3.52%, p < 0.0001). Overweight CHB patients had 10 times smaller mean FIB‐4 CAGR than lean ones (0.38% ± 10.35% vs. 3.83% ± 8.88%, p = 0.009). An increase in FIB4‐AA over at least 18 months in CHB patients with relatively low disease activity meant they were at greater risk of liver fibrosis, and these patients had a mean FIB‐4 CAGR of 7.11%. The FIB‐4 CAGR was compatible with the findings of previous studies on the collagen proportionate area in viral hepatitis patients. [ABSTRACT FROM AUTHOR]

Background and Aim: The serial serologic changes of hepatitis D virus (HDV) infection among chronic hepatitis B virus (HBV) infected patients who received oral nucleotide/nucleoside analogues are elusive. Methods: Serum anti‐HDV and HDV RNA among chronic hepatitis B (CHB) patients were tested at the time of initiating anti‐HBV therapy and subsequently during the follow‐up period. Results: The seropositive rate of anti‐HDV and HDV RNA among 2850 CHB patients, was 2.7% and 0.9%, respectively. Factors associated with anti‐HDV seropositivity were platelet counts (odds ratio [OR]/95% confidence intervals [CI]: 0.995/0.992–0.999; P = 0.006), HBV DNA levels (OR/CI: 0.81/0.70–0.94; P = 0.005), and hepatitis B e‐antigen (HBeAg) seropositivity (OR/CI: 0.22/0.05–0.95; P = 0.04). The only factor associated with HDV RNA positivity among anti‐HDV seropositive patients was age (OR/CI: 0.95/0.90–1.00; P = 0.03). The spontaneous clearance rate of serum anti‐HDV antibody was 3.0 per 100 person‐years with a median follow‐up period of 3.5 years (range 2–12 years), whereas the seroclearance rate of HDV RNA was 4.3 per 100 person‐years among anti‐HDV seropositive patients after a median follow‐up period of 6.0 years (range 2–11 years). A baseline anti‐HDV titer < 0.5 cut‐off index was the only factor predictive of anti‐HDV seroclearance (hazard ratio [HR]/CI: 30.11/3.73–242.85; P = 0.001). Conclusions: HDV infection was not common among patients treated for HBV in Taiwan. Seroclearance of anti‐HDV and HDV RNA did occur over time, albeit the chance is rare. [ABSTRACT FROM AUTHOR]

Background and Aim Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Methods Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. Results The overall SVR12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. Conclusions There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted. [ABSTRACT FROM AUTHOR]

Bioassay-guided fractionation of an AcOEt-soluble fraction of the liquid fermentation of an endophytic fungus Hypoxylon sp. BCRC 12F0687 associated with the root of Taiwanese Ilex formosana (Aquifoliaceae) resulted in the isolation of two new compounds, i.e., one benzenoid, hypoxyphenone ( 1), and one azaphilone derivative, hypoillexidiol ( 2), two metabolites isolated for the first time from natural source, (−)-(3 S)-3-hydroxy-3-methyloxindole ( 3) and (+)-vermelone ( 4), along with twelve previously identified compounds, 5- 16. Their structures were determined through in-depth spectroscopic and mass-spectrometric analyses. The effects of some isolates on the inhibition of NO and IL-6 production in lipopolysaccharide-activated RAW 264.7 murine macrophages were evaluated. Of the isolates, 2 and 3 exhibited potent anti-NO production activity, with IC50 values of 17.5±1.8 and 24.7±1.6 μ M, respectively, compared to that of quercetin, an iNOS inhibitor with an IC50 value of 35.9±1.7 μ M. Compounds 2, 4, 5, and 12 also showed moderate inhibition of IL-6 production, with IC50 values ranging from 27.2±1.8 to 35.3±5.8 μ M. This is the first report on an oxindole metabolite from the genus Hypoxylon. [ABSTRACT FROM AUTHOR]

Seven new metabolites, including three sesquiterpenoids, 10-hydroxythujopsene ( 1), akotriol ( 2), and xylaritriol ( 3), one diterpenoid, cubentriol ( 4), one aliphatic derivative, akoenic acid ( 5), one alkaloid, akodionine ( 6), and one isocoumarin, akolitserin ( 7), together with seven known compounds, 8- 14, were isolated from the AcOEt-soluble fraction of the fermentation broth of the endophytic fungus Xylaria cubensis, derived from the leaves of Litsea akoensis Hayata (Lauraceae). Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR experiments, and by HR-ESI-MS mass spectrometry. Among the isolates, (−)-( R)-7-hydroxymellein showed IL-6 inhibitory activity with an IC50 value of 9.41 μ M. [ABSTRACT FROM AUTHOR]

Summary AREA (NIT2) is a general transcription factor involved in derepression of numerous genes responsible for nitrogen utilization in Gibberella fujikuroi and many other fungi. We have previously shown that the deletion of areA-GF resulted in mutants with significantly reduced gibberellin (GA) production. Here we demonstrate that the expression level of six of the seven GA biosynthesis genes is drastically reduced in mutants lacking areA . Furthermore, we show that, despite the fact that GAs are nitrogen-free diterpenoid compounds, which are not obviously involved in nitrogen metabolism, AREA binds directly to the promoters of the six N-regulated genes. The binding of AREA was analysed in more detail using the promoter of one of the GA-biosynthesis genes encoding the ent -kaurene oxidase ( P450-4 ). Deletion/mutation analysis of the P450-4 promoter fused to the Escherichia coli uidA gene, which encodes β-glucuronidase, allowed the in vivo identification of functional GATA motifs. We have also analysed the nmr gene of G . fujikuroi ( nmr-GF ) which has high similarity to the Neurospora crassa nmr-1 and Aspergillus nidulans nmrA genes, both involved in nitrogen metabolite repression. In contrast to our expectation, deletion of nmr-GF did not result in significant derepression of the GA biosynthesis genes in the presence of ammonium, glutamine or glutamate. Overexpression of the nmr-GF gene fused to the strong promoter of the G. fujikuroi glutamine synthetase ( gs ) gene revealed only a very slight repression of the nitrate reductase ( niaD ) gene, resulting in weak resistance to chlorate. Surprisingly, this effect was only observed in the presence of high amounts of glutamate; cultivation on ammonium failed to induce any resistance to chlorate. Despite the limited effect of gene replacement and overexpression of nmr-GF on the nitrogen metabolism of G. fujikuroi itself, the gene fully restored nitrogen metabolite repression in A. nidulans and N. crassa nmr... [ABSTRACT FROM AUTHOR]