The Alteration of Akkermansiaceae/Lachnospiraceae Ratio Is a Microbial Feature of Antibiotic-Induced Microbiota Remodeling.

Antibiotic treatment has been shown to cause gut microbiota dysbiosis. However, lacking critical features defining gut microbiota dysbiosis makes it challenging to prevent. By co-occurrence network analysis, we found that despite short antibiotic courses eliminating certain microbial taxa, the Akkermansia genus played the role of a high-centrality hub to maintain microbiota homeostasis. When the antibiotic courses continued, the elimination of Akkermansia induced a significant microbiota remodeling of the gut microbiota networks. Based on this finding, we found that under long-term antibiotic stress, the gut microbiota was rearranged into a stable network with a significantly lower Akkermansiaceae/Lachnospiraceae (A/L) ratio and no microbial hub. By functional prediction analysis, we confirmed that the gut microbiota with a low A/L ratio also had enhanced mobile elements and biofilm-formation functions that may be associated with antibiotic resistance. This study identified A/L ratio as an indicator of antibiotic-induced dysbiosis. This work reveals that besides the abundance of specific probiotics, the hierarchical structure also critically impacts the microbiome function. Co-occurrence analysis may help better monitor the microbiome dynamics than only comparing the differentially abundant bacteria between samples.

Insulin Resistance Associated Disorders Pivoting Long-Term Hepatitis B Surface Antigen Decline During Entecavir Therapy.

Insulin resistance associated disorders (IRAD), including prediabetes, type 2 diabetes mellitus (T2DM), and fatty liver are significant risk factors of liver-related death in chronic hepatitis B (CHB). However, their relationship remains unclear. We aimed to evaluate how IRAD influence the kinetics of serum hepatitis B surface antigen (HBsAg) in patients with CHB during long-term entecavir treatment. We enrolled 140 patients with CHB receiving at least 3 years of consecutive entecavir treatment in this retrospective study. A linear mixed effects model was adopted to examine the effects of variables and their interaction over time on the HBsAg trajectory. Furthermore, we acquired cytokine profiles and baseline fibrosis-4 index (FIB-4) scores for in-depth analysis. The median treatment time was 6.90 (4.47-9.01) years. Multivariate analysis revealed that older patients or those with prediabetes or T2DM had a significantly slower HBsAg decline over time (p = 0.0001 and p < 0.0001, respectively). Conversely, advanced fatty liver engendered a more rapid HBsAg decrease (p = 0.001). Patients with prediabetes or T2DM possessed higher IP-10 levels six years after entecavir therapy (p = 0.013). Compared to patients without prediabetes or T2DM, diabetic patients had more unfavorable features at the baseline, especially higher FIB-4 scores. Prediabetes or T2DM delays the clearance of HBsAg, but advanced hepatic fatty change counterbalances the effect. Additionally, IRAD could cause hepatic sequelae in CHB through immune-metabolic pathways.

Fecal microbiota transplantation for Clostridium difficile infection in Taiwan: Establishment and implementation.

Clostridium difficile infection (CDI) remains a major public health issue, and fecal microbiota transplantation (FMT) has become one of the standard therapies for recurrent or refractory CDI. When compared to medical therapies, such as metronidazole or vancomycin, FMT has a high rate of treatment response with acceptable safety and efficiency. Following promulgation of the amendments in September 2018 in Taiwan, FMT has been indicated for recurrent or refractory CDI. The Taiwan Microbiota Consortium contributed to the Taiwan FMT Expert Consensus, which established basic norms and stipulated essential principles, including the indications for transplantation, eligible locations and personnel, donor screening policies, fecal sample handling, and post-FMT follow-up. However, establishing an eligible FMT team in a qualified hospital remains a clinical challenge, and the requirement for facilities and well-screened donors impedes the implementation of FMT. In this review, we aim to provide domestic FMT teams with explicit instructions to facilitate realization and increase the practice of FMT. Based on the Taiwan FMT Expert Consensus and current regulations, we performed a literature review and integrated the experiences of Taiwanese multidisciplinary experts into this article. The content intends to offer clinicians up-to-date evidence and highlight the essential points of FMT.

Multifocal gastrointestinal varices: a rare manifestation of immunoglobulin G4-related disease.

Multifocal gastrointestinal varices are uncommon and often associated with liver cirrhosis. They consist of varices at the gastroesophageal region and the other sites (i.e. ectopic varices) simultaneously. The etiology includes venous system anomalies or thrombosis (congenital or acquired), vascular injury (iatrogenic or traumatic), or portal hypertension (either intrahepatic or extrahepatic). The clinical manifestations vary from asymptomatic lesions to life-threatening variceal hemorrhage. The identification of bleeding foci, as well as the etiology of varices, can be challenging. The treatment necessitates a multidisciplinary approach. Here, we report a case with multifocal gastrointestinal varices involving the stomach, duodenum, and transverse colon. The patient presented with intermittent melena and has no history of liver or heart disease. Serial endoscopic examinations confirmed the multiple sites of the gastrointestinal varices. Abdominal computed tomography demonstrated that the liver parenchyma is normal, and the hepatic veins, intrahepatic portal system, as well as vena cava, are all unobstructed. Nevertheless, it revealed typical features of autoimmune pancreatitis, retroperitoneal fibrosis, and compromised splenic and superior mesenteric veins. After the pancreatic tissue sampling, we eventually confirmed the etiology as immunoglobulin G4-related disease. In addition to steroid treatment for immunoglobulin G4-related disease, we successfully treated variceal bleeding with band ligation and prevented rebleeding with propranolol. He had been convalescing and has received periodic follow-up in our outpatient clinic for more than 12 months uneventfully.

Clinical utility of hepatitis B surface antigen kinetics in treatment-naïve chronic hepatitis B patients during long-term entecavir therapy.

AIM: To investigate the utility of hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment. METHODS: This retrospective study included treatment-naïve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen (HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, one-year and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies. RESULTS: A total of 211 patients were enrolled. The median treatment time was 5.24 (2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen (HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients (cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients (cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels. CONCLUSION: Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

Planar-shape prototype generation using a tree-based random greedy algorithm.

A prototype is representative of a set of similar objects. This paper proposes an approach that formulates the problem of prototype generation as finding the mean from a given set of objects, where the prototype solution must satisfy certain constraints. These constraints describe the important perceptual features of the sample shapes that the proposed prototype must retain. The contour prototype generated from a set of planar objects was used as an example of the approach, and the corners were used as the perceptual features to be preserved in the proposed prototype shape. However, finding a prototype solution for more than two contours is computationally intractable. A tree-based approach is therefore proposed in which an efficient greedy random algorithm is used to obtain a good approximation of the proposed prototype and analyze the expected complexity of the algorithm. The proposed prototype-generation process for hand-drawn patterns is described and discussed in this paper.