Mesenchymal Stem Cell-Derived Exosomes Mitigate Acute Murine Liver Injury via Ets-1 and Heme Oxygenase-1 Up-regulation.

BACKGROUND: Mesenchymal stem cells (MSCs)-derived exosomes have been previously demonstrated to promote tissue regeneration in various animal disease models. This study investigated the protective effect of exosome treatment in carbon tetrachloride (CCl4)-induced acute liver injury and delineated possible underlying mechanism. METHODS: Exosomes collected from conditioned media of previously characterized human umbilical cord-derived MSCs were intraperitoneally administered into male CD-1 mice with CCl4-induced acute liver injury. Biochemical, histological and molecular parameters were used to evaluate the severity of liver injury. A rat hepatocyte cell line, Clone-9, was used to validate the molecular changes by exosome treatment. RESULTS: Exosome treatment significantly suppressed plasma levels of AST, ALT, and pro-inflammatory cytokines, including IL-6 and TNF-, in the mice with CCl4-induced acute liver injury. Histological morphometry revealed a significant reduction in the necropoptic area in the injured livers following exosome therapy. Consistently, western blot analysis indicated marked elevations in hepatic expression of PCNA, c-Met, Ets-1, and HO-1 proteins after exosome treatment. Besides, the phosphorylation level of signaling mediator JNK was significantly increased, and that of p38 was restored by exosome therapy. Immunohistochemistry double staining confirmed nuclear Ets-1 expression and cytoplasmic localization of c-Met and HO-1 proteins. In vitro studies demonstrated that exosome treatment increased the proliferation of Clone-9 hepatocytes and protected them from CCl4-induced cytotoxicity. Kinase inhibition experiment indicated that the exosome-driven hepatoprotection might be mediated through the JNK pathway. CONCLUSION: Exosome therapy activates the JNK signaling activation pathway as well as up-regulates Ets-1 and HO-1 expression, thereby protecting hepatocytes against hepatotoxin-induced cell death.

Improvement in Skin Penetration Capacity of Linalool by Using Microemulsion as a Delivery Carrier: Formulation Optimization and In Vitro Evaluation.

Linalool is an aromatic oil with analgesic, anti-inflammatory and anti-UVB-induced skin damage effects. The aim of this study was to develop a linalool-loaded microemulsion formulation for topical application. In order to quickly obtain an optimal drug-loaded formulation, statistical tools of the response surface methodology and a mixed experimental design with four independent variables of oil (X1), mixed surfactant (X2), cosurfactant (X3) and water (X4) were used to design a series of model formulations in order to analyze the effect of the composition on the characteristics and permeation capacity of linalool-loaded microemulsion formulations and to obtain an appropriate drug-loaded formulation. The results showed that the droplet size, viscosity and penetration capacity of linalool-loaded formulations were significantly affected by formulation component proportions. The skin deposition amount of the drug and flux of such formulations expressively increased about 6.1-fold and 6.5-fold, respectively, when compared to the control group (5% linalool dissolved in ethanol). After 3 months of storage, the physicochemical characteristics and drug level did not show a significant change. The linalool formulation-treated rat skin showed non-significant irritation compared to skin treatments in the distilled-water-treated group. The results showed that specific microemulsion applications might be considered as potential drug delivery carriers for essential oil topical application.

Effect of Bacillus species-fermented products and essential oils on growth performance, gut morphology, cecal short-chain fatty acid levels, and microbiota community in broilers.

In this study, the effects of Bacillus species-fermented products (synbiotics [SYNs]) and essential oils (EOs) on the growth performance, gut morphology, cecal short-chain fatty acid (SCFA) levels, and microbiota of broilers were investigated. A total of 180 one-day-old unsexed broiler chicks (Ross 308) were randomly assigned to 5 dietary treatments as follows: basal diet (control group), basal diet plus enramycin (10 mg/kg; A group), basal diet plus SYNs (3 × 1011 CFU spore/kg of feed; SYN group), basal diet plus EOs (100 mg/kg; EO group), and basal diet plus SYNs and EOs (SYN + EO group), with 6 replicate cages per treatment group and 6 birds per cage. The SYN+EO treatment resulted in a higher (P = 0.003) average daily gain at 1 to 14 d of age than did the control and EO treatments. SYNs had a significant effect on the average daily gain at 1 to 14 d (P < 0.001) and 1 to 35 d (P = 0.045) of age. EOs had a significant effect on the villus height of the duodenum (P = 0.015) and jejunum (P = 0.027). Superoxide dismutase (SOD) and mucin 2 (MUC2) mRNA expression in the duodenum, jejunum, and ileum in the SYN + EO group was higher (P < 0.001) than that in any of the other groups. The SYN+EO treatment resulted in higher (P < 0.001) 2-methylbutyric acid and 3-methylbutyric acid levels in the cecal digesta of the broilers than did the control treatment. Cecal species evenness in the SYN + EO group was higher (P < 0.001) than that in the control group. The abundance of the phylum Firmicutes in the cecal digesta of the broilers was higher (P < 0.001) in the SYN+EO group than in the control group. SYNs had a significant effect (P < 0.001) on the abundance of the genus Lactobacillus in the cecal digesta of the broilers. The abundance of the genus Lactobacillus was positively associated with 2-methylbutyric acid and 3-methylbutyric acid levels. The 2-methylbutyric acid and 3-methylbutyric acid levels were positively correlated with the villus height of the duodenum and ileum. These results suggest that simultaneous supplementation with SYNs and EOs can increase the average daily gain, improve gut health-associated gene expression, increase SCFA levels, and modulate the gut microbiota composition of broilers.

Low disease awareness as a contributing factor to the high prevalence of hepatitis C infection in Tzukuan, a hyperendemic area of southern Taiwan.

Understanding the barriers and tackling the hurdles of hepatitis C virus (HCV) care cascades is key to HCV elimination. The current study aimed to investigate the rates of disease awareness, link-to-care, and treatment uptake of HCV in a hyperendemic area in Taiwan. Tzukuan residents from 2000 to 2018 were invited to participate in the questionnaire-based interviews for HCV. The rates of disease awareness, accessibility, and anti-HCV therapy were evaluated in anti-HCV-seropositive participants. Among 10,348 residents, 1789 (17.3%) were anti-HCV seropositive. Of these 1789 anti-HCV-seropositive participants, data of 594 participants from questionnaire-based interviews in 2005-2018 were analyzed for HCV care cascades. Overall, 24.9% of anti-HCV-seropositive HCV participants had disease awareness, 53.9% of aware participants had accessibility, and 79.8% of assessed participants had received HCV treatment, with a community effectiveness of 10.7%. HCV prevalence decreased over time, from 21.2% in the early cohort to 9.3% in the recent cohort. Disease awareness increased over time, from 15.6% to 41.7%, with the community effectiveness increasing from 1.3% to 28.8%. Lower education levels and normal liver biochemistry were associated with a lower rate of disease awareness. Notably, 68% of participants with abnormal liver biochemistry and 69% of those with advanced fibrosis (FIB-4 > 3.25) were unaware of their HCV disease. We demonstrated huge gaps in disease awareness, link-to-care, and treatment uptake in the HCV care cascade in an HCV-hyperendemic area, even in the initial era of direct-acting antiviral agents. There is an urgent need to overcome these hurdles to achieve HCV elimination.

Measurement of Body Surface Area for Psoriasis Using U-net Models.

During the evaluation of body surface area (BSA), precise measurement of psoriasis is crucial for assessing disease severity and modulating treatment strategies. Physicians usually evaluate patients subjectively through direct visual evaluation. However, judgment based on the naked eye is not reliable. This study is aimed at evaluating the use of machine learning methods, specifically U-net models, and developing an artificial neural network prediction model for automated psoriasis lesion segmentation and BSA measurement. The segmentation of psoriasis lesions using deep learning is adopted to measure the BSA of psoriasis so that the severity can be evaluated automatically in patients. An automated psoriasis lesion segmentation method based on the U-net architecture was used with a focus on high-resolution images and estimation of the BSA. The proposed method trained the model with the same patch size of 512 × 512 and predicted testing images with different patch sizes. We collected 255 high-resolution psoriasis images representing large anatomical sites, such as the trunk and extremities. The average residual of the ground truth image and the predicted image was approximately 0.033. The interclass correlation coefficient between the U-net and dermatologist's segmentations measured in the ratio of affected psoriasis over the body area in the test dataset was 0.966 (95% CI: 0.981-0.937), indicating strong agreement. Herein, the proposed U-net model achieved dermatologist-level performance in estimating the involved BSA for psoriasis.

Capsaicin attenuates imiquimod-induced epidermal hyperplasia and cutaneous inflammation in a murine model of psoriasis.

Psoriasis is one of the most common chronic inflammatory diseases that is characterized by well-defined erythematous plaques, with typical histopathological findings of lymphocytic infiltration and epidermal hyperplasia. Topical treatments of psoriasis are either associated with limited response or with side effects. Up to date, topicals targeting neuroimmune axis in psoriasis or psoriasiform dermatitis have not been explored. Here, we investigated whether percutaneous delivery of capsaicin could attenuate the pathological change of psoriasiform inflammation. Imiquimod-induced psoriasis-like murine model was used to evaluate therapeutic effects from topical application of capsaicin. An additional model of psoriasiform dermatitis induced by direct IL-23 injection was used to identify the level of action from capsaicin in this neuroimmune axis. Cutaneous inflammation was assessed by erythema level and ear thickness change. Key cytokines, infiltrating cells in the skin, and draining lymph node cells were investigated. The results showed that capsaicin administration obstructed the activation of IL-23/IL-17 pathway induced by imiquimod, presenting with significantly reduced psoriasiform dermatitis both in gross appearance and microscopic features. Tissue gene expression of psoriatic core cytokines induced by imiquimod (including IL-23, IL-17A, IL-22, TNF-α, and IL-6) were greatly decreased by capsaicin application. This protective effect from capsaicin could be hampered by direct intradermal injection of IL-23. CONCLUSION: Epicutaneous delivery of capsaicin on imiquimod-treated murine skin could significantly decrease expression of multiple inflammatory cytokines and the severity of prototypic change of psoriasiform inflammation. The beneficial effect imposed by capsaicin reinforces the neuroimmune contribution towards psoriasiform inflammation and provides a potential non-steroidal therapeutic alternative for topical treatment of psoriasiform dermatitis.

Changing epidemiology and viral interplay of hepatitis B, C and D among injecting drug user-dominant prisoners in Taiwan.

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10-0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13-0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04-40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

Significant amelioration of hepatitis C virus infection in a hyperendemic area: longitudinal evidence from the COMPACT Study in Taiwan.

OBJECTIVES: Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. Tzukuan, located in the southwestern area of Taiwan, is an HCV hyperendemic area (>30%). This study aimed to assess the changing epidemiological characteristics of HCV infection and to evaluate the long-term outcomes after the implementation of public health strategies for two decades. DESIGN: A population-based retrospective cohort study. SETTING: A comprehensive care programme was implemented, namely COMPACT Study, in Tzukuan since 1997. PARTICIPANTS: A total of 10 714 residents participated the screening. OUTCOME MEASURES: The HCV status, demographic and clinical profiles of the participants were recorded and validated annually from 2000 through 2019. RESULTS: The HCV infection prevalence rates were 21.1% (1076/5099) in 2000-2004, 18.8% (239/1269) in 2005-2009, 14.1% (292/2071) in 2010-2014 and 10.3% (234/2275) in 2015-2019 (p for trend test <0.0001). Among them, 1614 underwent repeated tests during the follow-up period. The annual incidence rates were 0.54% in 2005-2009, 0.4% in 2010-2014 and 0.22% in 2015-2019, respectively (p=0.01). In addition to old age, lower education level was a major risk factor for HCV infection across different periods. HCV infection prevalence rate among those illiterates reached 40.9%, followed by 28.5% in those with elementary school level, and <10% in those with high school or higher levels. The major risk factor has shifted from iatrogenic exposure in 2000-2009 to household transmission after 2010. CONCLUSIONS: HCV infection has been decreasing and the epidemiological features are changing in the hyperendemic area by continuing education, prevention and treatment strategies.

Risk stratification of non-alcoholic fatty liver disease across body mass index in a community basis.

BACKGROUND: The features and risk analysis of non-alcoholic fatty liver disease (NAFLD) in a community-based setting remain elusive. The predictors between obese and lean subjects need further clarification. We aimed to assess the characteristics of NAFLD during a community screening. The associated metabolic abnormalities and cardiovascular risk assessment were also analyzed. METHODS: A total of 2483 subjects receiving multi-purpose health screening at 10 primary care centers were recruited. They received clinical assessment, including demographic data, laboratory examination, and abdominal sonography. RESULTS: The prevalence of NAFLD and metabolic syndrome were 44.5%, and 15.8%, respectively. Among those NAFLD subjects, 1212 (48.8%) subjects were obese (BMI≥ 24 kg/m2). There was an increasing trend of NAFLD according to age, ranging from 25.8% of those aged <30 years to 54.4% of those aged 50-70 years (P for trend< 0.0001). High insulin resistance (IR) was the significant predictive factor for NAFLD in both obese (odds ratio [OR] = 3.85, 95% confidence interval [CI] = 1.87-8.36, P = 0.0002) and lean subjects (OR = 2.52, 95% CI = 1.13-5.54, p = 0.02). The prevalence of high Framingham Risk Score (≥7.5%) was 56.7% (211/372) among the male subjects, which was significantly higher than that (26%, 191/734) of the females (P < 0.001). There was a significant increase of high Framingham Risk Score according to BMI, ranging from 23.1% of BMI<24 kg/m2 to 45% of BMI>27 kg/m2 (P for trend< 0.0001). CONCLUSION: IR is predictive of NAFLD irrespective of BMI. The cardiovascular risk may exist in lean NAFLD subjects.

Using Microemulsion as Carrier for Drug Transdermal Delivery: The Effect of Surfactants and Cosurfactants.

BACKGROUND: The purpose of this study was to evaluate the effect of types of surfactants and cosurfactants on physicochemical properties and permeability of sumatriptan-loaded microemulsions through rat skin. METHODS: Different types of surfactants and cosurfactants were used to prepare drug-loaded microemulsions. The physicochemical characters and permeability parameters of these formulations were measured. RESULTS: The experimental microemulsions with varying components had small droplet size ranging from 24.6 nm to 2568.8 nm, low viscosity ranging from 7.49 to 43.34 cps and significant permeation enhancement ratio ranging from 23.0 to 98.6 when compared to the control group. CONCLUSION: The composition and proportion of surfactants and cosurfactants were key factors for the physiochemical properties of drug-loaded microemulsions. The cumulative transdermal amount of the microemulsion containing mixture surfactant of Laureth-3/Laureth-23 was higher than that of the microemulsion with a mixture of Tween 80/Span 20. In the selected cosurfactant, diethylene glycol monoethyl ether (DEGMEE) showed highest permeation enhancement. Thermodynamic stability tests revealed that the experimental microemulsion was a stable enough formulation to be considered as a suitable carrier for sumatriptan.

Super-SILAC mix coupled with SIM/AIMS assays for targeted verification of phosphopeptides discovered in a large-scale phosphoproteome analysis of hepatocellular carcinoma.

Plentiful studies have established a close association between aberrant phosphorylation and hepatocellular carcinoma (HCC). Here, we applied a quantitative phosphoproteomics platform combining dimethylation labeling and online 3D strong cation exchange chromatography (SCX)-titanium oxide (TiO2)/RP-LTQ-Orbitrap to compare phosphoproteomes between three pairs of HCC tissues and non-tumor counterparts. This analysis yielded 7868 quantifiable phosphopeptides and numerous up- or down-regulated candidates. Increased phosphorylation of LMNA and NIPA was confirmed using specific antibodies. To expand our verification capability, we evaluated the use of LTQ-Orbitrap run in SIM/Accurate inclusion mass screening (AIMS) mode with a super-SILAC mixture as an internal standard to quantify a subset of phosphopeptide candidates in HCC tissue samples. In sample I used for discovery experiment, we successfully quantified 32 (in SIM mode) and 30 (in AIMS mode) phosphopeptides with median coefficients of variation (CVs) of 7.5% and 8.3%, respectively. When the assay was applied to other three pairs of HCC specimens for verification experiment, 40 target phosphopeptides were quantified reliably (~7.5% CV), and more than half of them were differentially expressed between tumor and adjacent non-tumor tissues. Collectively, these results indicate the feasibility of using super-SILAC mix-SIM/AIMS assays for targeted verification of phosphopeptides discovered by large-scale phosphoproteome analyses of HCC specimens. SIGNIFICANCE: In this study, we developed a strategy for conducting both discovery and targeted verification of deregulated phosphoproteins in HCC tissue specimens on LTQ-Orbitrap. This strategy allowed us to generate a quantitative HCC tissue phosphoproteome dataset containing significantly deregulated phosphoproteins that represents a valuable resource for the identification of potential HCC biomarkers and/or therapeutic targets. Furthermore, our proof-of-concept experiments demonstrated the feasibility of applying LTQ-Orbitrap, operated in SIM/AIMS mode, to multiplex and targeted verification of phosphopeptides in individual tissue specimens using a super-SILAC mix as an internal phosphopeptide standard. This method could be readily applied to verify dozens of phosphopeptide candidates in a larger HCC sample set.

The feasibility of using manual segmentation in a multifeature computer-aided diagnosis system for classification of skin lesions: a retrospective comparative study.

OBJECTIVES: To investigate the feasibility of manual segmentation by users of different backgrounds in a previously developed multifeature computer-aided diagnosis (CADx) system to classify melanocytic and non-melanocytic skin lesions based on conventional digital photographic images. METHODS: In total, 347 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed, and manually segmented by two groups of physicians, dermatologists and general practitioners, as well as by an automated segmentation software program, JSEG. The performance of CADx based on inputs from these two groups of physicians and that of the JSEG program was compared using feature agreement analysis. RESULTS: The estimated area under the receiver operating characteristic curve for classification of benign or malignant skin lesions based were comparable on individual segmentation by the gold standard (0.893, 95% CI 0.856 to 0.930), dermatologists (0.886, 95% CI 0.863 to 0.908), general practitioners (0.883, 95% CI 0.864 to 0.903) and JSEG (0.856, 95% CI 0.812 to 0.899). The agreement in the malignancy probability scores among the physicians was excellent (intraclass correlation coefficient: 0.91). By selecting an optimal cut-off value of malignancy probability score, the sensitivity and specificity were 80.07% and 81.47% for dermatologists and 79.90% and 80.20% for general practitioners. CONCLUSIONS: This study suggests that manual segmentation by general practitioners is feasible in the described CADx system for classifying benign and malignant skin lesions.

Huge gap between clinical efficacy and community effectiveness in the treatment of chronic hepatitis C: a nationwide survey in Taiwan.

Peginterferon/ribavirin provides a substantially high treatment efficacy for chronic hepatitis C virus (HCV) infections in Asians. Whether the clinical efficacy can be translated to community effectiveness remains unclear. The disease awareness, treatment accessibility, recommendations, acceptance, and barriers to anti-HCV treatment were explored to clarify the issue with a 3-step nationwide investigation in Taiwan. A crude HCV-infected population was estimated using databases from 3 large-scale surveillance studies and age-/geographic-specific population database. HCV awareness and accessibility were investigated at the patient level in 58,129 residents. The recommendations/acceptances and barriers to treatment at the provider level were evaluated using a prospective, nationwide approach to 89 gastroenterologists/hepatologists. The estimated 10-year interval age-adjusted anti-HCV-seropositive population is 745,109 (3.28%), with an anticipated HCV-viremic population of 554,361. Of anti-HCV-seropositive subjects, 36.2% had disease awareness. Among those with awareness, 39.6% had accessibility. The recommendation/acceptance rate of antiviral therapy was 70.6%. The treatment rate was 10.1% and 13.7% for the anti-HCV-seropositive and HCV-viremic population, respectively. With an anticipated treatment success rate of 80% in Taiwan, 8.1% of the anti-HCV-seropositive and 10.9% of the HCV-viremic population achieved successful treatment. The major treatment barriers were fear of adverse effects (37%), major disorders (17.6%), ineligibility for insurance reimbursement (17.6%), and lack of therapy awareness (11.3%). Despite the high rates of treatment response and nationwide coverage of insurance reimbursement, there remains a large gap between clinical efficacy and community effectiveness in anti-HCV treatment in Taiwan. Increasing disease awareness/treatment accessibility and introducing new therapeutic strategies with high tolerability are warranted.

Computer-aided diagnosis of skin lesions using conventional digital photography: a reliability and feasibility study.

BACKGROUND: Computer-aided diagnosis (CADx) software that provides a second opinion has been widely used to assist physicians with various tasks. In dermatology, however, CADx has been mostly limited to melanoma or melanocytic skin cancer diagnosis. The frequency of non-melanocytic skin cancers and the accessibility of regular digital macrographs have raised interest in developing CADx for broader applications. OBJECTIVES: To investigate the feasibility of using CADx to diagnose both melanocytic and non-melanocytic skin lesions based on conventional digital photographic images. METHODS: This study was approved by an institutional review board, and the requirement to obtain informed consent was waived. In total, 769 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed and used to develop a CADx system. Conventional and new color-related image features were developed to classify the lesions as benign or malignant using support vector machines (SVMs). The performance of CADx was compared with that of dermatologists. RESULTS: The clinicians' overall sensitivity, specificity, and accuracy were 83.33%, 85.88%, and 85.31%, respectively. New color correlation and principal component analysis (PCA) features improved the classification ability of the baseline CADx (p = 0.001). The estimated area under the receiver operating characteristic (ROC) curve (Az) of the proposed CADx system was 0.949, with a sensitivity and specificity of 85.63% and 87.65%, respectively, and a maximum accuracy of 90.64%. CONCLUSIONS: We have developed an effective CADx system to classify both melanocytic and non-melanocytic skin lesions using conventional digital macrographs. The system's performance was similar to that of dermatologists at our institute. Through improved feature extraction and SVM analysis, we found that conventional digital macrographs were feasible for providing useful information for CADx applications. The new color-related features significantly improved CADx applications for skin cancer.

A robust hair segmentation and removal approach for clinical images of skin lesions.

Artifacts such as hair are major obstacles to automatic segmentation of pigmented skin lesion images for computer-aided diagnosis systems. It is even more challenging to process clinical images taken by a regular digital camera, where the shadows of the skin texture may mimic hair-like curvilinear structures. In this study, we examined the popular DullRazor software with a dataset of 20 clinical images. The software, specifically designed for dermoscopic images, was unable to remove fine hairs or hairs in the shade. Alternatively, we proposed using conventional matched filters to enhance curvilinear structures. The more complicate hair intersection patterns, which were known to generate low matched filtering responses, were recovered by using region growing algorithms from nearby detected hair segments with linear discriminant analysis (LDA) based on a color similarity criterion. The preliminary results indicated the proposed method was able to remove more fine hairs and hairs in the shade, and lower false hair detection rate by 58% (from 0.438 to 0.183) as compared to the DullRazor's approach.

Association between gallbladder stones and chronic hepatitis C: ultrasonographic survey in a hepatitis C and B hyperendemic township in Taiwan.

Gallbladder (GB) stones have been associated with several metabolic factors and liver diseases. This community-based study aimed at investigating the prevalence rate of GB stones and its associated factors in a hepatitis B virus (HBV)/hepatitis C virus (HCV)-endemic township in southern Taiwan. A total of 1701 residents (689 males and 1012 females; mean age: 51.2 ± 16.0 years) were enrolled in this prospectively designed screening project. Serum biochemistry tests, including testing for levels of serum aspartate aminotransferase, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and antibody to HCV (anti-HCV) were conducted. In addition, a hepatobiliary ultrasonographic (US) examination was also conducted. Of the 1701 residents, 243 (14.3%) and 475 (27.9%) were found to be positive for HBsAg and anti-HCV, respectively. Results of the US examination revealed the prevalence rate of GB stone and fatty liver to be 6.8% and 55.6%, respectively. Using univariate analyses we found that significantly higher proportions of the participants with GB stone were male, over 50 years of age, positive for anti-HCV (p = 0.001, p < 0.001, and p = 0.001, respectively), with significantly higher mean age and ALT level (p ≤ 0.001 and p = 0.048, respectively) than did those without GB stone. By applying multivariate analyses, male gender, positive anti-HCV, and older age (>50 year) were identified as independent factors associated with the formation of GB stones. Anti-HCV was associated with GB stones in males but not in females in both univariate and multivariate analyses. GB stones were found to have a prevalence rate of 6.8% in this HCV/HBV hyperendemic township and are associated with higher mean age. A correlation between chronic hepatitis C and GB stones is observed only among males.

Antinuclear antibody titer and treatment response to peginterferon plus ribavirin for chronic hepatitis C patients.

Positive serum antinuclear antibody (ANA) is not infrequent in chronic hepatitis C virus (HCV)-infected patients. This prospective study evaluated the impact of ANA on the response to and safety of peginterferon/ribavirin combination therapy for chronic hepatitis C patients in clinical practice. We enrolled 243 consecutive patients who were treated with a 24-week regimen of peginterferon-α plus ribavirin, with a 24-week follow-up period. ANA titer was determined before antiviral treatment. The primary end-point was sustained virological response (SVR), defined as HCV RNA <50 IU/mL throughout the follow-up period. Overall, 187 (77.0%) patients experienced a SVR. In the 105-patient HCV genotype non-1 group, patients with ANA titer ≥1:80 had a significantly lower SVR rate than those with ANA titer <1:80 (67.7% vs. 95.8%, respectively, p = 0.013). In contrast, in the 138-patient HCV genotype 1 group, the SVR rate did not differ between patients with and without ANA titer ≥1:80. Multivariate regressive analyses showed that ANA ≥1:80, age and HCV RNA levels were independent factors associated with SVR in HCV genotype non-1 patients; whereas HCV RNA levels and hepatic fibrosis were prognostic predictors of SVR in HCV genotype 1 patients. The frequencies of adverse events were similar between patients with and without ANA seropositivity. Peginterferon/ribavirin combination therapy is effective and safe in ANA-positive chronic hepatitis C patients. A high ANA titer was a negative prognostic factor for treatment response in HCV genotype non-1 patients.

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients.

UNLABELLED: Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r2 = 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P = 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) = 4.27, 95% confidence interval (CI) = 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR = 0.28, 95% CI = 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR = 3.10, 95% CI = 1.34-7.21, P = 0.008), and the pretreatment level of aspartate aminotransferase (OR = 0.996, 95% CI = 0.99-1.00, P = 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI = 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. CONCLUSION: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients.