Response-guided therapy for patients with hepatitis C virus genotype 6 infection: a pilot study

Summary. The optimal duration of treatment with pegylated interferon (PEG‐IFN) plus ribavirin (RBV) in patients with hepatitis C virus (HCV) genotype 6 is unknown. This study was aimed at determining treatment response on the basis of rapid virological response (RVR) of HCV genotype 6 in comparison with genotypes 1 and 3. Sixty‐six treatment naïve patients were treated with PEG‐IFN‐α2a (180 μg/week) plus weight‐based RBV (1000–1200 mg/day). Patients with genotype 1 n = 16) and genotype 3 (n = 16) were treated for a fixed duration of 48 and 24 weeks, respectively. Patients with genotype 6 (n = 34) who achieved RVR were treated for 24 weeks (response‐guided therapy) and the remaining patients were treated for 48 weeks (standard therapy). The mean baseline HCV RNA levels were not statistically different between groups (6.4 ± 0.8, 6.0 ± 1.0 and 6.5 ± 0.8 Log₁₀ IU/mL for genotypes 1, 3 and 6, respectively). Patients with genotypes 1, 3 and 6 achieved RVR in 43.8%, 87.5% and 73.5% of cases, respectively. One patient with genotype 1 and 3 with genotype 6 were considered nonresponders and discontinued therapy. Sustained virological response (SVR) was achieved in 62.5%, 81.3% and 76.5% of patients with genotypes 1, 3 and 6, respectively. The SVR rate in patients with genotype 6 who underwent response‐guided therapy was 88%. This pilot study suggested that the SVR rate of HCV genotype 6 was at an intermediate level between those of genotypes 3 and 1. Treatment with PEG‐IFN plus RBV for 24 weeks may be sufficient for patients with genotype 6 who achieve RVR. Prospective randomized trials are required to evaluate this response‐guided strategy in a larger number of patients with genotype 6.     

Intrahepatic HBV DNA and covalently closed circular DNA (cccDNA) levels in patients positive for anti-HBc and negative for HBsAg

Covalently closed circular DNA (cccDNA) is a unique episomal replicative intermediate molecule of hepatitis B virus (HBV) which plays a key role in viral persistence. The aim of this study was to prove cccDNA persistence in the liver tissue of patients negative for hepatitis B surface antigen (HBsAg) and positive for antibody to hepatitis core antigen (anti-HBc). Intrahepatic HBV DNA and cccDNA were determined using real-time and semi-nested PCR assays on the liver tissues of 35 patients who were negative for HBsAg and positive for anti-HBc with or without anti-HBs. HBV DNA was detected in the liver tissue of 4 out of 35 patients who were positive for anti-HBc. None of the samples harbored cccDNA. In this study population, which is of Asian origin, very low levels of HBV DNA were detected in a small percentage of patients with anti-HBc. Even using the highly sensitive semi-nested PCR assay, HBV cccDNA was not detectable in any anti-HBc positive patients either with or without anti-HBs.     

Microcirculation of the healthy human gingiva

 The purpose of this study was to evaluate the microcirculation in healthy human gingiva. Forty-two adult volunteers with clinically healthy gingiva participated. The ages of this research sample ranged from 20 to 30 years. Periodontal conditions were evaluated and assessed by using the qualitative plaque index, gingival index, gingival bleeding index, tooth mobility, and laser Doppler flow-metry (LDF) on 12 maxillary and mandibular anterior teeth. The LDF data were recorded on the facial aspect of the free gingiva, interdental gingiva, attached gingiva, and alveolar mucosa of 12 maxillary and mandibular anterior teeth, utilizing an acrylic stent to stabilize the probe. This technique was then modified to circumvent contamination by saliva and gingival exudate. Blood flow in the maxillary anterior gingiva differed significantly from that in the mandibular anterior gingiva in interdental gingiva, attached gingiva, and alveolar mucosa, at P < 0.01. The maxillary anterior gingiva, at each point on the stent, showed significant differences in the mean LDF, at P < 0.01. For the mandibular anterior gingiva, the difference was significant only in the alveolar mucosa region. Received: November 10, 2000 / Accepted: January 23, 2002     

Dietary Intake of Total and Inorganic Arsenic by Adults in Arsenic-Contaminated Dan Chang District,Thailand, Using Duplicate Food Approach

Dan Chang district, approximately 100 km west of Bangkok, was a site of tin mines operated almost 40 years ago. Mining operations caused arsenic contamination in soil, surface water, and groundwater within the district. The specific aim of this study was to estimate the dietary intakes of total and inorganic arsenic in 60 adults (30 males and 30 females) residing in Dan Chang district, using a duplicate food approach. The daily intake rates of inorganic arsenic ranged from 0.496 to 1.817 μg/kg BW for males and 0.342 to 1.778 μg/kg BW for females.     

Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized,Double-Blinded,Placebo-Controlled Pilot Trial

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3–20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 10¹⁰ CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.     

Acute liver failure and death predictors in patients with dengue-induced severe hepatitis

BACKGROUND Liver injury in patients with dengue infection is common. Most patients have mild and transient hepatitis. Acute liver failure(ALF) in dengue infection is rare but results in an extremely poor prognosis.AIM To identify prognostic predictors of ALF and death in patients with dengueinduced severe hepatitis(DISH).METHODS We retrospectively reviewed 2311 serologically confirmed adolescent and adult dengue patients who were hospitalized during a 12-year study period(between 2007 and 2019) at the university hospital of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients with DISH [n = 134(5.80%)], defined as a baseline transaminase 10 times the normal reference cut-off level, and DISH with subsequent ALF as defined by the American Association for the Study of the Liver Diseases 2011 criteria [n = 17(0.74%)], were included. Predictors of ALF and in-hospital death were identified using logistic regression analysis.RESULTS Of the 151 dengue-infected patients with severe liver injury or ALF, 51% were female, with a mean age of 27.9 ± 14.5 years. Capillary leakage syndrome(CLS) occurred in 68.2%(n = 103) of DISH and 100% of ALF patients. The mortality rate was low in DISH patients(0.8%) but was remarkably high if ALF developed (58.8%). In univariate analysis, age, sex, hematocrit, white blood count, atypical lymphocyte count, platelet count, international normalized ratio(INR), bilirubin, serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, alkaline phosphatase, albumin, creatinine, Model for End-Stage Liver Disease(MELD) score, presence of liver comorbidity and presence of CLS were identified as potential prognostic parameters for ALF or death. In multivariate analysis, the MELD score remained the only predictor of ALF with an adjusted odds ratio(aOR) of 1.3 [95% confidence interval(CI): 1.1-1.5; P = 0.001]. An initial MELD score ≥ 15 was associated with ALF from DISH with an area under the receiver operating characteristic(AUROC) of 0.91, 88.2% sensitivity and 87.3% specificity. Regarding mortality prediction, the deterioration of liver function to ALF was the most significant factor related to death in DISH patients(aOR 108.5, 95%CI: 5.5-2145.4, P = 0.002). Other independent factors associated with death included baseline INR(aOR 10.4, 95%CI: 2.6-40.5, P = 0.001). An INR ≥ 1.5 predicted death from DISH with an AUROC of 0.83(81.8% sensitivity and 86.8% specificity).CONCLUSION The MELD score is the best predictor of ALF in DISH patients, a complication from dengue that is associated with high mortality. The presence of ALF and the baseline INR level are independent markers of death in DISH patients.     

Pretransplant prediction of prognosis after liver transplantation in primary sclerosing cholangitis using a Cox regression model

Liver transplantation remains the only treatment for patients with end-stage primary sclerosing cholangitis (PSC); however, selection criteria for the procedure and its timing remains uncertain. The aim of this study was to identify pretransplant variables associated with survival after transplantation and to devise a Cox regression model for prediction of post-transplant survival. We studied 118 patients transplanted for PSC at the Queen Elizabeth Hospital, Birmingham, UK, being followed for up to 91/4 years after the procedure. The association between pretransplant data and the post-transplant survival up to 1 year was studied using the logrank test (univariate analyses) and Cox multiple regression analysis. Univariate analyses showed the following variables to be associated with a decreased post-transplant survival: high serum creatinine, high serum bilirubin, biliary tree malignancy, previous upper abdominal surgery, hepatic encephalopathy, ascites, and Crohn's disease, whereas ulcerative colitis was associated with increased post-transplant survival (all P 相似文献