Geographic variation of genotype 6 hepatitis C virus infection in an endemic area of southern Taiwan.

Taiwan is a hepatitis C virus (HCV) endemic country with geographic variation of prevalence and main genotypes(GTs) are 1 b and 2a. We recently reported high GT6 prevalence in Tainan of southern Taiwan. To clarify this special genotype as a local endemic disease and its geographic variation, the prevalence rates of HCV GTs of 37 districts of Tainan were analyzed. A total of 3040 patients with HCV viremia were enrolled. The prevalence rates of HCV GT 1a, 1 b, 2, 3, 4, 6 and mixed types were 3.9%, 31.6%, 45.9%, 0.6%, 0.2%, 17.1% and 0.5% respectively. GT6 prevalence showed marked variation from 0 to 39.2%. Four districts with GT6 prevalence >30% are located between Jishui and Zengwen rivers. Preliminary subtyping data were 6 g/a/w. This geographic variation with spatial restriction by two rivers with 6 g/w is suggestive of local endemic infection of preexisting GT 6 HCV for centuries.

High prevalence of genotype 6 hepatitis C virus infection in Southern Taiwan using Abbott genotype assays.

BACKGROUND/PURPOSE: Abbott RealTime Genotype II assay can effectively identify hepatitis C virus (HCV) genotypes (GTs), but some GT 6 subtypes might not be differentiated from GT 1. Abbott RealTime Genotype II PLUS and sequencing might be needed to resolve these ambiguous results. Unlike the high prevalence of GT 6 in Southeast Asia, GT 6 had rarely been reported in Taiwan except in intravenous drug abusers (IDU). But the prevalence of GT 6 in Taiwan might be underestimated. We conducted this study to determine the GTs in a HCV endemic area in Southern Taiwan. METHODS: A total of 1147 patients with hepatitis C viremia for direct acting antivirals (DAA) treatment at the Chi Mei medical system in Tainan were enrolled. Genotype was determined using a working flow consisted of Abbott GT II, PLUS assays and 5' untranslated region (5' UTR)/core sequencing. RESULTS: Among the 1147 patients, 883 (77.0%) obtained GT results by GT II, 264 (23.0%) samples with ambiguous results by GT II assay received further tests, including 194 (73.5%) with PLUS assay and 70 (26.5%) with 5'UTR/core sequencing. Nearly three-quarters (73.5%) of ambiguous results by GT II assay were GT 6. Overall, 18.3% of samples were GT 6. Phylogenetic study of 11 samples of GT 6 subtypes showed 7 (63.6%) were 6 g. CONCLUSION: GT 6 is the major factor for high ambiguous rate by GT II. Unexpected high prevalence of GT 6 (18.3%) in Southern Taiwan, especially subtype 6 g, closely related to Indonesian strains, is first reported.

Correction: Accelerated weight gain, prematurity, and the risk of childhood obesity: A meta-analysis and systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0232238.].

Bile Duct Stone Size May Influence the Efficacy of Endoscopic Sphincterotomy With or Without Large-Balloon Dilation: A Meta-Analysis.

Purpose: Endoscopic sphincterotomy (EPT) combined with endoscopic papillary large balloon dilatation (EPBD) are used to remove large common bile duct (CBD) stones. This meta-analysis compared the efficacy and safety of EPT+EPBD versus EPT alone in the removal of stones based on stone size. Materials and Methods: Twenty-two studies (11 randomized control trials [RCTs] and 11 non-RCTs) were identified and reviewed based on searches of Embase, PubMed, and Web of Science. CBD stone's size was measured with reference to diameter of the duodenoscope (13 mm) and size of the large dilatation balloon (17 mm) seen on cholangiogram. The stone clearance rate, required mechanical lithotripsy (ML), procedure time, and pancreatitis were compared according to the mean stone size, and further divided into Groups A (small) 10-13 mm, B (medium) 13-17 mm, and C (large) >17 mm. Results: Subgroup analysis according to CBD stone size showed EPT + EPBD had a significantly better initial stone clearance rate than EPT in Groups B (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.20-4.77) and C (OR = 3.05, 95% CI: 1.86-5.03), but not for Group A (OR = 1.41, 95% CI: 0.90-2.21). EPT+EPBD also required significantly less ML than EPT in Groups B (OR = 0.34, 95% CI: 0.15-0.77) and C (OR = 0.31, 95% CI: 0.13-0.73). EPT+EPBD had significantly shorter procedure time than EPT in Group B (standardized mean difference = -1.20, 95% CI: -2.08 to 0.32). In meta-regression analysis, Group B had a better OR in initial stone clearance rate and less ML usage rate correlation with the size of CBD stone, but not for Group C with larger stones. Conclusions: EPT+EPBD had a significantly better initial stone clearance rate, and required less ML with shorter procedure time than EPT for removing medium-sized CBD stones, but the efficacy was limited to large CBD stones. The study protocol and trial registration had been registered in PROSPERO (Registration No. CRD42020171689).

Reversal of hypolipidemia in chronic hepatitis C patients after successful antiviral therapy.

BACKGROUND/PURPOSE: Chronic infection with the hepatitis C virus (HCV) is associated with impaired lipid metabolism. The aim of this study was to determine the impact of antiviral response on the serial change of serum lipids in chronic HCV patients. METHODS: A total of 165 consecutive patients with HCV infection were prospectively enrolled. Serum total cholesterol (TC) and triglyceride (TG) levels in these subjects were compared with age, sex and body mass index-matched healthy individuals and 55 patients with chronic infection with hepatitis B virus (HBV). Serum lipid levels were measured in 143 patients with chronic HCV infection receiving pegylated interferon plus ribavirin therapy at baseline, at the end of treatment, and at week 24 after the end of treatment. RESULTS: Patients with chronic HCV infection had significantly lower total TC and TG levels than normal controls (both p < 0.001). Serum TC levels were lower in HCV patients than in those infected with HBV (p < 0.001). Pretreatment serum lipid levels were not independent factors associated with sustained virological response (SVR). Among patients achieving a SVR, serum TC and TG levels significantly increased from 165 ± 30 mg/dL and 100 ± 47 mg/dL at baseline to 191 ± 36 mg/dL (p < 0.001) and 116 ± 77 mg/dL (p = 0.029) at week 24 posttreatment, whereas no evident change in lipid profile occurred in the non-SVR group. CONCLUSION: Our data suggest that chronic HCV infection is associated with hypocholesterolemia and hypotriglyceridemia, which can be reversed by successful eradication of HCV. The clinical significance of hypolipidemia reversal among SVR patients, such as the risk of coronary artery or cerebral vascular disease, should be further investigated.

What Would Be the Appropriate Number of Clinical ERCP Cases for Trainees to Acquire Basic Competence? A Systematic Review and Meta-Analysis.

Endoscopic retrograde cholangiopancreatography (ERCP) is technically demanding and carries significant risks. It is performed by gastrointestinal and surgical endoscopists. There is no consensus on the minimum number of ERCPs required during training. This study was conducted to analyze the minimum number of clinical ERCPs that a trainee needs to perform to achieve competency. PubMed, Ovid-Embase, and the Cochrane library were searched systematically for prospective and retrospective studies reporting on trainees' ERCP performance. Mete-analysis was conducted to analyze the success rate of cannulation, other basic techniques, and adverse event rate, using the random-effect model with Review Manager 5.3. Thirteen studies met the inclusion criteria, with 149 trainees performing a total of 18 794 ERCP procedures. The pooled cannulation success rate was 85.7% (95% CI: 78.1%-91.0%) at completion of training. The cannulation success rate was 76.5% (95% CI: 69.2%-82.5%) when the trainees had completed 180 ERCPs, which increased to 81.8% (95% CI: 69.8%-90.6%) after 200 ERCP procedures. Adverse events and post-ERCP pancreatitis rates were 4.7% (95% CI: 2.9%-9.1%) and 2.0% (0.9%-3.9%), respectively. Achieving a cannulation success rate of >90% was considered a quality indicator for ERCP training by most societal guidelines. However, our retrospective analysis indicated that trainees only attained a pooled cannulation success rate of only 81.8% after 200 procedures. Therefore, the minimum number of ERCPs required to achieve competency during training may need to be redefined to meet the basic requirement.

Hepatitis C Virus Subtypes Novel 6g-Related Subtype and 6w Could Be Indigenous in Southern Taiwan with Characteristic Geographic Distribution.

Hepatitis C virus (HCV) genotype (GT) 6 is the most genetically diverse GT and mainly distributed in Southeast Asia and south China but not Taiwan. Earlier studies showed the major HCV GTs in Taiwan were GT 1b and 2 with very rare GT 6 except in injection drug users (IDUs), and subtype 6a is the main GT 6 subtype among IDUs. Recently, we reported a much higher prevalence (18.3%) of GT 6 in Tainan City, southern Taiwan. This study was designed to clarify the subtypes of GT 6 in this endemic area. A total of 3022 (1343 men and 1679 women) HCV viremic patients were enrolled. Subtypes of GT 6 were determined by sequencing of core/E1 and nonstructural protein 5B in 322 of 518 GT 6 patients. The overall GT 6 prevalence rate was 17.1% (518/3022), with higher prevalence districts (>25%) located in northern Tainan. A novel 6g-related subtype is the most prevalent subtype (81.0%), followed by 6w (10.8%), 6a (7.5%), and 6n (0.7%). The high GT 6 prevalence in Tainan was mainly due to a novel 6g-related subtype and 6w. These two subtypes could be indigenous in Tainan with characteristic geographic distribution.

Accelerated weight gain, prematurity, and the risk of childhood obesity: A meta-analysis and systematic review.

The purpose of this systematic review and meta-analysis of the literature was to analyze and evaluate the impact of prematurity and accelerated weight gain on the risk of childhood and adolescent obesity. CINAHL, Embase, PubMed, and Web of Science databases were searched until December 2019 which yielded 19 studies with a total of 169,439 children enrolled were systematically reviewed. The results revealed that preterm infants had a greater likelihood of childhood obesity (defined as BMI ≥95th percentile for age-sex), than term infants (OR = 1.19, 95% CI [1.13, 1.26]). However, no difference of childhood obesity was found between "small for gestational age"(SGA) and "appropriate for gestational age"(AGA) among preterms. Accelerated weight gain (defined as weight gain velocity during first two years after birth) significantly increased the likelihood of subsequent childhood obesity among preterms (aOR = 1.87, 95% CI [1.57, 2.231]). In conclusion, accelerated weight gain at infancy among preterm children may be a critical contributor to obesity in later life. Establishing optimal growth trajectories and timely referral to health care providers may be of clinical importance.

Complete remission of nephrotic syndrome of hepatitis B virus-associated membranous glomerulopathy after lamivudine monotherapy.

We present the case of a 22-year-old male with chronic hepatitis B virus (HBV) infection, who developed nephrotic syndrome and had complete remission after lamivudine monotherapy. Renal biopsy showed membranous glomerulopathy, and the serum titer of HBV DNA increased to 1,130,000 copies/mL. As symptomatic therapy with angiotensin converting enzyme inhibitors did not improve the nephrotic syndrome, lamivudine 100 mg per day was started. His alanine aminotransferase level normalized 2 months after treatment, then hepatitis B e antigen seroconversion developed and serum HBV DNA became undetectable. His proteinuria improved subsequently and his leg edema disappeared completely 6 months after treatment. Neither hepatitis nor nephrotic syndrome had relapsed by month 13 when he came for follow-up. This suggests that lamivudine monotherapy may induce and maintain complete remission of membranous glomerulopathy associated with hepatitis B.

Current status of gastroesophageal reflux disease : diagnosis and treatment.

AIMS: The aim of this study was to explore the recent advances in diagnosis and treatment of gastroesophageal reflux disease (GERD). METHODS: Previous studies were searched using the terms "gastroesophageal reflux disease" and "diagnosis" or "treatment" in Medline and Pubmed. Articles that were not published in the English language, manuscripts without an abstract, reviews, meta-analysis, and opinion articles were excluded from the review. After a preliminary screening, all of the articles were reviewed and synthesized to provide an overview of the contemporary approaches to GERD. RESULTS: GERD has a variety of symptomatic manifestations, which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of other alarming symptoms, these symptoms allow one to make a presumptive diagnosis of GERD and initiate empiric therapy. GERD-associated complications include erosive esophagitis, peptic stricture, Barrett's esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modifications, medical and surgical therapy. Medical therapy involves acid suppression, which can be achieved with antacids, histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. CONCLUSION: The management of this disease requires a complex approach. Maintenance therapy of GERD after using anti-secretory drugs should be continuously monitored.

Increase in apoptosis by combination of metformin with silibinin in human colorectal cancer cells.

AIM: To investigate the effect of metformin on silibinin-induced apoptosis in human colorectal cancer (COLO 205) cells. METHODS: MTT assays were performed to quantify cell viability. Western blot assays were applied to identify the expression of signaling proteins. RESULTS: The combined treatment of COLO 205 cells with metformin and silibinin decreased cell survival at a dose insufficient to influence the non-malignant cells [Human colonic epithelial cells (HCoEpiC)]. Silibinin and metformin increased phosphatase and tensin homolog and 5'-adenosine monophosphate-activated protein kinase expression in COLO 205 cells and inhibited the phosphorylation of mammol/Lalian target of rapamycin. This combined treatment resulted in an increase in the expression of activated caspase 3 and apoptosis inducing factor, indicating apoptosis. CONCLUSION: The combined treatment of human colorectal cancer cells with silibinin and metformin may induce apoptosis at a dose that does not affect HCoEpiC. This finding reveals a potential therapeutic strategy for the treatment of colorectal cancer.