The outcomes of lamivudine-resistant chronic hepatitis B patients treated with long-term adefovir dipivoxil have not been well described. This study aims to characterize the virological and biochemical response and to determine factors that may influence the development of resistance to adefovir.A retrospective review was conducted on all patients with lamivudine-resistant chronic hepatitis B treated with adefovir for a minimum of 6 months at two tertiary referral centers.Data on 161 patients were analyzed. Seventy-two percent achieved an initial virological response with eventual normalization of alanine aminotransferase in only 67% of patients. Seventeen patients developed adefovir resistance with cumulative resistance rates of 3.2%, 8.8%, and 18% at 12, 24, and 36 months, respectively. Twelve (71%) of these patients had a biochemical breakthrough, with one death from fulminant hepatic failure. The median duration of lamivudine crossover was 1 month in adefovir-resistant patients, compared with 12 months for the remainder of the cohort (P < 0.01). Longer crossover therapy reduced the adefovir resistance rate, but did not eliminate it. No adefovir resistance is reported in those who were continued on long-term combination lamivudine-adefovir without a period of adefovir monotherapy.Combination lamivudine-adefovir therapy protected against the emergence of adefovir resistance.
Objective Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. Design For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Results Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development. Conclusions These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.
Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.
Non-invasive biomarkers for diagnosing and prognosing hepatocellular carcinoma (HCC) are urgently needed. Cirrhosis is present in 80-90% of HCC patients. Cirrhosis is characterized by deposition and cross-linking of collagens that have crucial roles in HCC initiation and progression. We evaluated circulating cross-linked pro-peptides of type III collagen (PC3X) as a diagnostic and prognostic biomarker for HCC.PC3X was measured by ELISA in plasma from patients with HCC (n=79), cirrhosis (n=86), non-cirrhotic hepatitis-B infection (n=74) and from healthy controls (n=44). PC3X was compared to the liver fibrosis marker PRO-C3 and the HCC tumor-cell derived marker alpha-fetoprotein (AFP). Diagnostic and prognostic potential was evaluated by AUROC and by calculating hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS).PC3X, PRO-C3 and AFP were significantly elevated in patients with HCC compared to other liver diseases and healthy controls (p=0.0002, p<0.0001). In patients with normal AFP (<20 IU/mL), PC3X and PRO-C3 separated HCC from cirrhosis with an AUROC of 0.72 and 0.68, respectively. High PC3X and AFP predicted for poor PFS (HRPC3X=1.80, p=0.032; HRAFP=1.70, p=0.031) and OS (HRPC3X=2.12, p=0.024; HRAFP=2.55; p=0.003), whereas PRO-C3 did not (PFS: HR=1.19, p=0.059 and OS: HR=1.12, p=0.324). PC3X was independent of AFP (PFS: HR=1.74, p=0.045 and OS: HR=2.21, p=0.018) and combining the two improved prognostic value (PFS: HR=2.66, p=0.004 and OS: HR=5.86, p<0.0001).PC3X is associated with HCC independent of AFP and provides diagnostic and prognostic value for HCC patients. If validated, this suggests that PC3X has biomarker potential for HCC.
The immature stages of the 12 species of butterflies of the subfamily Danainae and their larval food plants in Sri Lanka are presented.The immature stages of six species and their larval food plants are documented for the first time.The immature stages of the remaining six species that have been previously described from Sri Lankan material are compared to findings of the current study and additional observations are presented.For these six species, new larval food plants are reported for the first time.For two of these species, larval food plants previously reported in Sri Lanka are confirmed.This study provides the basic information for further studies on the biology of these species.It also provides information for conservation management programs for butterflies in Sri Lanka.
Abstract Significant weight loss can modify the progression of Nonalcoholic fatty liver disease (NAFLD) with the most convincing evidence coming from bariatric surgery cohorts. Effective ways to non-invasively characterise NAFLD in these patients has been lacking, with high Fibroscan failure rates reported. We prospectively evaluated the utility of Fibroscan using XL-probe over a two-year period. 190 consecutive patients undergoing bariatric surgery were followed as part of their routine care. All patients had Fibroscan performed on the day of surgery and at follow-up a mean of 13 months (± 6.3) later. The majority of patients were female (82%) with mean age of 42. Fibroscan was successful in 167 (88%) at baseline and 100% at follow up. Patients with a failed Fibroscan had higher body mass index (BMI) and alanine transaminase (ALT), but no difference in FIB-4/NAFLD score. Mean baseline Liver stiffness measurement was 5.1 kPa, with 87% of patients classified as no fibrosis and 4% as advanced fibrosis. Mean baseline controlled attenuation parameter was 291, with 78% having significant steatosis, 56% of which was moderate-severe. Significant fibrosis was associated with higher BMI and HbA1c. Significant steatosis was associated with higher BMI, ALT, triglycerides and insulin resistance. Mean follow up time was 12 months with weight loss of 25.7% and BMI reduction of 10.4 kg/m 2 . Seventy patients had repeat fibroscan with reductions in steatosis seen in 90% and fibrosis in 67%. Sixty-four percent had complete resolution of steatosis. Fibroscan can be performed reliably in bariatric cohorts and is useful at baseline and follow-up. Significant steatosis, but not fibrosis was seen in this cohort with substantial improvements post-surgery.
Abstract Background and Aim: Significant hepatic fibrosis is prognostic of liver morbidity and mortality in non‐alcoholic fatty liver disease (NAFLD); however, it remains unclear whether non‐invasive fibrosis models can determine this end‐point. We therefore compared the accuracy of simple bedside versus complex fibrosis models across a range of fibrosis in a multi‐centre NAFLD cohort. Methods: Simple (APRI, BARD) and complex (Hepascore, Fibrotest, FIB4) fibrosis models were calculated in 242 NAFLD subjects undergoing liver biopsy. Significant (F2‐4) and advanced fibrosis (F3,4) were defined using Kleiner criteria. Models were compared using area under the receiver operator characteristic curves (AUC). Cut‐offs were determined by Youden Index or 90% predictive values. Results: For significant fibrosis, non‐invasive fibrosis models had modest accuracy (AUC 0.707–0.743) with BARD being least accurate (AUC 0.609, P < 0.05 vs others). Using single cut‐offs, sensitivities and predictive values were < 80%; using two cut‐offs, > 75% of subjects fell within indeterminate ranges. Simple models had significantly more subjects within indeterminate ranges than complex models (99.1–100% vs 82.1–84.4% respectively, P < 0.05 for all). For advanced fibrosis, complex models were more accurate than BARD (AUC 0.802–0.858 vs 0.701, P < 0.05). Using two cut‐offs, complex models had fewer individuals within indeterminate ranges than BARD (11.1–32.3% vs 70.7%, P < 0.01 for all). For cirrhosis, complex models had higher AUC values than simple models. Conclusions: In NAFLD subjects, non‐invasive models have modest accuracy for determining significant fibrosis and have predictive values less than 90% in the majority of subjects. Complex models are more accurate than simple bedside models across a range of fibrosis.
Background: Long term Capsule Endoscopy (CE) retention is an uncommon, but potentially serious complication of CE. It is most frequently due to Crohn’s related small bowel strictures or neoplastic lesions but can be caused by post-surgical stenosis and non-steroidal anti-inflammatory drug (NSAID) enteropathy. We present a case of retained CE in the distal ileum due to NSAID enteropathy with striking photographs of the small bowel stricture and the moment of laparoscopic device retrieval.
Case report: An 83-year-old female on amlodipine and esomeprazole presented with a month-long history of melaena and was found to have iron deficiency anaemia. She had been investigated two years prior for a similar episode with gastroscopy, colonoscopy and CE without finding an underlying cause. Gastroscopy and colonoscopy were repeated, revealing gastritis and diverticular disease but no bleeding source. CE showed an inflamed distal ileal stricture, which prevented capsule passage. The patient was asymptomatic and X-ray and computed tomography (CT) confirmed retention of the capsule with no bowel obstruction. On directed questioning she admitted to infrequent use of a COX-II inhibitor for arthritis over the previous 3 years. She underwent double balloon enteroscopy with dilatation, which identified the stricture and the retained capsule, but it could not be safely retrieved at that time or one week later. She developed abdominal pain and ultimately proceeded to laparoscopic removal of the capsule and resection of the stricture. Histology was consistent with an NSAID etiology.
Conclusion: CE retention is a serious complication and can be caused by strictures related to occult NSAID use. Directed history taking and use of patency capsules could reduce the incidence of this problem.