A phase 2, open-label, randomized, multiple-dose study evaluating Inarigivir in treatment-naïve patients with chronic hepatitis B.

BACKGROUND/AIMS: Novel agents acting against hepatitis B virus (HBV) are needed to improve HBsAg seroclearance or termed as 'functional cure'. Inarigivir (retinoic acid-inducible gene I agonist) has immunomodulatory and direct antiviral actions against HBV. We aimed to determine the safety and efficacy of Inarigivir for the treatment of HBV infection. PATIENTS/METHODS: 80 treatment-naïve patients were randomized in 4 ascending dose cohorts to receive 12 weeks of Inarigivir 25, 50, 100, 200 mg or placebo in a ratio of 4:1. All patients were then given tenofovir for another 12 weeks. RESULTS: Least squares (LS) mean reductions in HBV DNA from baseline increased with higher doses of Inarigivir (0.6116 in 25 mg and 1.5774 in 200 mg groups vs. 0.0352 in placebo group) (95% CI 0.9518-0.2011 and 1.921-1.1634 respectively). LS mean changes in HBV RNA and HBsAg from baseline ranged from -0.3856 to -0.5794 versus -0.1474 and -0.0956 to -0.1818 versus +0.0026 in Inarigivir-treated versus placebo groups respectively. During the tenofovir-treated period, LS mean reductions in HBsAg in the Inarigivir-treated groups ranged from 0.1709 to 0.3529 versus 0.1984 in the placebo group. Inarigivir-treated groups showed mean reductions in ALT from baseline between 23.3 and 33.8 versus 0.7 U/L in the placebo group. Treatment-emergent adverse events related to Inarigivir and placebo occurred in 4.7% and 6.3% patients respectively. CONCLUSIONS: Twelve-week Inarigivir up to 200 mg dose was associated with a reduction of HBV DNA, HBV RNA and antigen levels. A trend for greater HBsAg reduction was observed in Inarigivir pre-treated patients after switching to tenofovir.

Comparison of pancreatic volume and fat amount linked with glucose homeostasis between healthy Caucasians and Koreans.

AIM: To compare pancreatic volume and fat amount, and their associations with glucose homeostasis, in a Korean and a white population. MATERIALS AND METHODS: In 43 healthy Korean and 43 healthy white people, matched for age (±3 years) and body mass index (BMI; ±1 kg/m2 ), we measured pancreatic volume and fat amount in the pancreas and abdomen using computed tomography. Pancreatic ß-cell function and insulin resistance were estimated according to biochemical characteristics and a 75-g oral glucose tolerance test. Body composition and resting energy expenditure (REE) were examined using bioimpedance and indirect calorimetry, respectively. RESULTS: The mean ±SD age of the participants was 29.9 ± 5.9 years and 30.0 ± 5.2 years, and BMI was 24.0 ±3.7 and 24.1 ±3.2 kg/m2 in the white participants and the Korean participants, respectively. Pancreatic volume in the white participants was greater than that in Korean participants (77.8 ±11.6 vs 68.2 ±12.1 cm3 ; P < .001). Pancreatic fat content in Korean participants was 22.8% higher than in white participants (P = .051). Insulinogenic index, disposition index, muscle mass and REE were significantly lower in Korean participants. Pancreatic volume was positively associated with indices linked to ß-cell function; fat content in the pancreas was negatively associated with such indices, and positively with insulin resistance after adjusting for relevant variables including REE. CONCLUSIONS: A smaller pancreas and higher fat deposition might be crucial determinants of vulnerability to diabetes in Korean people compared with white people with similar BMI and body fat levels.

Incidence and quantitative analysis of dissociated optic nerve fiber layer appearance: real loss of retinal nerve fiber layer?

PURPOSE: To assess the association between appearance of dissociated optic nerve fiber layer (DONFL) after internal limiting membrane (ILM) peeling and changes in the macular nerve fiber layer (NFL) area by spectral-domain optical coherence tomography (SD-OCT). METHODS: This study included 132 consecutive patients who had successfully undergone vitrectomy with ILM peeling for idiopathic epiretinal membrane or macular holes and had been followed up for ≥6 months. Two examiners evaluated macular 5-line raster horizontal SD-OCT images and categorized the patients on the basis of presence (group I) or absence (group II) of DONFL. The average macular NFL areas in both groups were measured using ImageJ at baseline and 1, 3, and 6 months after surgery. RESULTS: Among the 132 eyes of 132 patients, DONFL was noted in 42 (31.8%), 104 (78.8%), 106 (80.3%), and 106 (80.3%) eyes at 1, 3, and 6 months and at the last visit (12.8 ± 6.5 months) after surgery. These layers appeared most commonly between 1 and 3 months after ILM peeling. There was no significant difference in average macular NFL area between groups I and II (3453.4 ± 125.3 and 3513.0 ± 100.2 pixels, respectively) at 6 months after surgery (p = 0.56). CONCLUSIONS: Appearance of DONFL increased between postoperative months 1 and 3. Moreover, there was no significant difference in average NFL in terms of DONFL. Thus, appearance of DONFL might represent macular NFL rearrangement and reorganization rather than true mechanical damage to the NFL after ILM peeling.

Molecular characterization of the Tobacco rattle virus RNA2 genome isolated from Gladiolus.

Tobacco rattle virus (TRV-K) was first identified in a symptomatic Gladiolus plant cultivated in Korea. We analyzed the TRV-K genome and compared its phylogeny with other TRV isolates. After constructing of a full-length genomic RNA2 strand clone, a complete sequence was generated from several overlapping clones. The cloned genome was 3261 bases in length, identical to TRV-K, and had three open reading frames. TRV-K had the highest sequence identity with the American isolate TRV-ORY. Sequence analysis of the RNA2 genome showed that TRV-K contains an intact 2a, 2b, and 2c coding sequence and an RNA1-related 3' terminus, which is typical of TRV RNA2. Phylogenetic analysis revealed that TRV-K is in the same cluster as the American isolates and another Korean isolate, TRV-SK; however, it was in a different cluster than the European isolates.

Characteristics of spontaneous idiopathic epiretinal membrane separation in spectral domain optical coherence tomography.

PURPOSE: To investigate the prevalence, characteristics, and visual acuity of spontaneous idiopathic epiretinal membrane (ERM) separations using spectral domain optical coherence tomography. METHODS: In a series of 1,248 consecutive eyes with idiopathic ERM, Group I with preexisting posterior vitreous detachment included 1,091 eyes (87.4%) and Group II without preexisting posterior vitreous detachment included 157 eyes (12.6%). Groups IA and IIA included self-resolution cases of ERM from Groups I and II, respectively. RESULTS: The ERM self-separation occurred in 37 eyes (3.0%) for 32.6 ± 11.7 months, with 16 eyes (1.5%) in Group IA and 21 eyes (13.4%) in Group IIA. The mean best-corrected visual acuity (logMAR) improved in Groups IA and IIA by 0.1 (P = 0.013) and 0.06 (P = 0.078), respectively. From tomographic analyses, dominant undulation and retinal nerve fiber layer defects were more frequent in Group IA than Group IIA (P < 0.001 and P = 0.024, respectively). However, the completeness of ERM separation, inner segment/outer segment junction defects, and ERM recurrence were more frequent in Group IIA than Group IA (P = 0.039, P = 0.023 and P = 0.041, respectively). Multivariate analysis for factors related to visual improvement revealed only inner segment/outer segment junction defects as significantly associated (P = 0.025). CONCLUSION: Different mechanisms underlying the self-resolution of idiopathic ERM lead to distinct tomographic characteristics and may affect the postseparation visual function.

Visceral adipose tissue area is an independent risk factor for hepatic steatosis.

BACKGROUND AND AIM: Recent data indicate that hepatic steatosis is associated with insulin resistance, dyslipidemia and obesity (especially central body fat distribution). There have been few studies on the correlation between biopsy-proven hepatic steatosis and the above factors in a disease-free population. The aim of the present study was to evaluate the relation between hepatic steatosis assessed by biopsy and clinical characteristics including regional fat distribution measured by computed tomography (CT) in living liver donors. METHODS: Laboratory data, liver/spleen Hounsfield ratio (L/S ratio), regional fat distribution by CT and liver status by biopsy were evaluated retrospectively in a total of 177 living liver donors without a history of alcohol intake. RESULTS: The unpaired t-test showed that age, triglycerides (TG), high density lipoprotein, total cholesterol, alanine aminotransferase, body mass index, L/S ratio, visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) were associated with hepatic steatosis. In the multiple logistic regression analysis, VAT (odds ratio 1.031, 95% CI 1.013-1.048, P < 0.01) and TG (odds ratio 1.012, 95% CI 1.004-1.020, P < 0.01) were independent risk factors of hepatic steatosis. Subgroup analysis also showed that VAT was an independent risk factor in men (odds ratio 1.022, 95% CI 1.003-1.041, P < 0.05) and women (odds ratio 1.086, 95% CI 1.010-1.168, P < 0.05). CONCLUSION: Our results suggest that visceral abdominal adiposity is correlated with hepatic steatosis in healthy living liver donors.

CD45RO enriches for activated, highly mutated human germinal center B cells.

To date, there is no consensus regarding the influence of different CD45 isoforms during peripheral B-cell development. Examining correlations between surface CD45RO expression and various physiologic processes ongoing during the germinal center (GC) reaction, we hypothesized that GC B cells, like T cells, that up-regulate surface RO should progressively acquire phenotypes commonly associated with activated, differentiating lymphocytes. GC B cells (IgD(-)CD38(+)) were subdivided into 3 surface CD45RO fractions: RO(-), RO(+/-), and RO(+). We show here that the average number of mutations per IgV(H) transcript increased in direct correlation with surface RO levels. Conjunctional use of RO and CD69 further delineated low/moderately and highly mutated fractions. Activation-induced cytidine deaminase (AID) mRNA was slightly reduced among RO(+) GC B cells, suggesting that higher mutation averages are unlikely due to elevated somatic mutation activity. Instead, RO(+) GC B cells were negative for Annexin V, comprised mostly (93%) of CD77(-) centrocytes, and were enriched for CD69(+) cells. Collectively, RO(+) GC B cells occupy what seems to be a specialized niche comprised mostly of centrocytes that may be in transition between activation states. These findings are among the first to sort GC B cells into populations enriched for live mutated cells solely using a single extracellular marker.