To determine the efficacy of tenofovir disoproxil fumarate (TDF) in adults with chronic hepatitis B virus (HBV) infection who had previously failed lamivudine (LAM) and had significant viral ...replication (HBV DNA >10⁵ copies/ml if HBeAg positive, > 10⁴ copies/ml if HBeAg negative) despite at least 24 weeks of treatment with adefovir dipivoxil (ADV).
A prospective open-label study of TDF 300 mg daily. Patients receiving combination ADV/LAM prior to baseline were switched to TDF/LAM.
Multiple tertiary referral centres.
Sixty patients were enrolled. The median age was 48.5 years (range 21e80), 46 (77%) were male and 40 (67%) were HBeAg positive. Thirty-eight patients (63%) were switched from ADV to TDF, the remainder from ADV/LAM to TDF/LAM. At baseline, substitutions conferring resistance to LAM or ADV were present in 20 patients (33%) and 17 patients (28%), respectively. The median baseline viral load was 5.33 log₁₀ IU/ml (range 2.81-8.04). Patients initially treated with TDF monotherapy with persistent viral replication at or after 24 weeks were switched to TDF/LAM. The main outcome measures were change in HBV viral load from baseline and percentage of patients achieving an undetectable viral load (<15 IU/ml).
Results are reported at 96 weeks of treatment. One patient discontinued TDF at 10 days due to rash. The time-weighted change in viral load from baseline to week 12 was -2.19 log10 IU/ml overall. The median change in HBV DNA from baseline to weeks 12, 24, 48 and 96 was -2.86, -3.23, -3.75 and -4.03 log₁₀ IU/ml, respectively. At 48 and 96 weeks, 27/59 (46%) and 38/59 (64%) patients achieved a HBV DNA <15 IU/ml. The response was independent of baseline LAM therapy or mutations conferring ADV resistance.
In heavily pretreated patients with a high rate of genotypic resistance, TDF retains significant activity against HBV although this appears diminished in comparison with studies of naïve patients.
Cold biopsy forceps polypectomy (CBP) is often used for the removal of diminutive polyps. The efficacy of the technique has not been thoroughly assessed. The aim of this study was to prospectively ...assess the efficacy of CBP for removing diminutive polyps.
This was a prospective study from St Vincent's Hospital, a tertiary referral hospital in Melbourne, Australia. A total of 143 patients were screened and 52 patients with ≥ 1 diminutive polyps were enrolled. CBP was used to resect diminutive polyps until no polyp tissue was visible. The polyp base was then resected using endoscopic mucosal resection (EMR) with a 1 - 2-mm margin. The CBP and EMR samples were compared to assess completeness of the resection.
Overall 39 % (21 / 54) of diminutive polyps were completely resected using CBP. After binary logistic regression analysis, polyp histology was found to be predictive of resection, with complete resection of 62 % (13 / 21) for adenomas and 24 % (8 / 33) for hyperplastic polyps (odds ratio 5.1; P = 0.008). The size and number of bites taken with the forceps were not predictive of complete response.
Within the limitations of a modest sample size, CBP appears to be inadequate treatment for the removal of diminutive polyps.
Summary
Background
Crohn's disease recurs in the majority of patients after intestinal resection.
Aim
To compare the relative efficacy of thiopurines and anti‐TNF therapy in patients at high risk of ...disease recurrence.
Methods
As part of a larger study comparing post‐operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine‐intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment.
Results
A total of 101 patients 50% male; median (IQR) age 36 (25–46) years were included. There were no differences in disease history between thiopurine‐ and adalimumab‐treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2–i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab‐treated patients intention‐to‐treat (ITT); P = 0.028 or 24 of 62 (39%) vs. 3 of 24 (13%) respectively per‐protocol analysis (PPA); P = 0.020. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab).
Conclusions
In Crohn's disease patients at high risk of post‐operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
Advances in endoscopic imaging techniques have enabled more accurate identification of subtle mucosal abnormalities. The aim of the study was to assess the accuracy of predicting high grade dysplasia ...(HGD) and intramucosal cancer (IMC) in mucosa predicted as being nondysplastic vs. dysplastic by high definition white light endoscopy (HD-WLE), narrow band imaging (NBI), and confocal laser endomicroscopy (CLE).
A cross-sectional study was performed in a tertiary referral setting between February 2010 and September 2011. A total of 50 consecutive patients who were referred to St Vincent's Hospital for management of dysplastic Barrett's esophagus were included. A prediction of likely histology was made for each mucosal point (four-quadrant every 1 cm and any visible mucosal abnormality), first with HD-WLE, followed by NBI, and finally CLE. Biopsies were taken at all of these points.
A total of 1190 individual biopsy points were assessed. At histology, 39 biopsy points were found to harbor HGD and 52 biopsy points harbored IMC. For the detection of HGD/IMC the sensitivity, specificity, and accuracy were: HD - WLE, 79.1 %, 83.1 %, and 82.8 %; NBI, 89.0 %, 80.1 %, and 81.4 %; and CLE, 75.7 %, 80.0 %, and 79.9 %, respectively. All mucosal points with IMC and all patients with HGD were detected by targeted biopsies guided by HD-WLE and NBI without the need for random Seattle protocol biopsies.
HD-WLE in combination with NBI is highly accurate in the detection of HGD/IMC. Performing targeted biopsies in the surveillance of Barrett's esophagus is possible in expert centers.
Summary
Background
Inflammatory bowel disease can impact on a patient's ability to maintain normal physical and mental function, and fulfil their social, family and work roles. Aspects of disability ...in IBD have received little attention.
Aim
To develop, validate and apply a questionnaire directed towards evaluating these disease aspects.
Methods
A literature review on disability in IBD was undertaken, and opinion about aspects of disability to measure was sought from six IBD‐specialised gastroenterologists. A questionnaire was developed, and IBD patients completed the new disability questionnaire, the SF‐36 and the short‐IBD (SIBDQ ‐ 10 point). A subgroup of patients completed the questionnaire again 4 weeks later. Healthy volunteers were studied as a control group.
Results
A total of 116 IBD out‐patients were approached, of whom 81 (52 Crohn's disease and 28 ulcerative colitis) participated. Nineteen patients were re‐evaluated at 4 weeks. Twenty‐five controls were studied. All subscales demonstrated good Cronbach's alpha reliability and reproducibility. There was a significant inverse correlation between the disability score and the SIBDQ and between the disability score and the SF36 and a positive correlation with the Crohn's Disease Activity Index (CDAI) (all P < 0.001). Disability differed between ulcerative colitis and controls, but not between active and inactive disease.
Conclusions
The new disability questionnaire is sensitive for detecting disability, is reliable and reproducible, and correlates with disease activity in Crohn's disease, but not ulcerative colitis. Further prospective testing is now needed in the longer term, larger patient populations and in different countries and ethnicities.
Summary
IL28B genotype has been shown to be the strongest pretreatment predictor of sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C infection (CHC) treated with ...pegylated interferon (peg‐IFN) and ribavirin (RBV). Patients carrying the good response genotype have a two‐ to threefold higher chance of SVR than those with a poor response genotype, manifest as dramatically improved early viral kinetics. However, the treatment paradigm for CHC is changing with the introduction of potent direct‐acting antivirals (DAAs). IL28B genotype remains relevant to both telaprevir and boceprevir treatment regimens, although the strength of association with virological response is attenuated. The association between IL28B genotype and outcomes of treatment regimens that involve peg‐IFN plus combination DAA therapy, or IFN‐free regimens, is currently being evaluated. IL28B genotype may remain relevant to individualizing the choice of treatment regimen in the future.
Summary
Background
Post‐prandial worsening of symptoms as well as adverse reactions to one or more foods are common in the patients with functional gastrointestinal diseases, such as irritable bowel ...syndrome (IBS) and functional dyspepsia (FD). However, the role played by true food allergy in the pathogenesis of these diseases is still controversial and there are no well‐established tests to identify food allergy in this condition.
Objective
To investigate serum food antigen‐specific IgG, IgE antibody and total IgE antibody titres in controls and patients with IBS and FD, and to correlate symptoms with the food antigen‐specific IgG titres in IBS and FD patients.
Methods
Thirty‐seven IBS patients, 28 FD patients and 20 healthy controls participated in this study. Serum IgG and IgE antibody titres to 14 common foods including beef, chicken, codfish, corn, crab, eggs, mushroom, milk, pork, rice, shrimp, soybean, tomatoes and wheat were analysed by ELISA. Serum total IgE titres were also measured. Last, symptomatology was assessed in the study.
Results
IBS patients had significantly higher titres of IgG antibody to crab (P=0.000), egg (P=0.000), shrimp (P=0.000), soybean (P=0.017) and wheat (P=0.004) than controls. FD patients had significantly higher titres of IgG antibody to egg (P=0.000) and soybean (P=0.017) than controls. The percentage of individuals with detectable positive food antigen‐specific IgE antibodies of the three groups did not show any significant differences (P=0.971). There were no significant differences between IBS patients, FD patients and controls in the serum total IgE antibody titres (P=0.978). Lastly, no significant correlation was seen between symptom severity and serum food antigen‐specific IgG antibody titres both in IBS and FD patients.
Conclusion
Serum IgG antibody titres to some common foods increased in IBS and FD patients compared to controls. But there is no significant correlation between symptom severity and elevated serum food antigen‐specific IgG antibodies in these patients.
In patients with chronic hepatitis C, alcohol consumption has been proposed as a risk factor for the progression of liver disease; however, evidence for this remains conflicting. Two hundred ...thirty‐four anti–hepatitis C virus (HCV)–positive patients who had a liver biopsy performed within the past 24 months were studied. Demographic data and information on risk factors were recorded. A detailed lifetime alcohol consumption history was obtained. Viral studies included HCV viral titer and HCV genotype. Mean age (± SEM) of the group was 40.8 ± 0.7 years. One hundred sixty‐six (71%) were male. A risk factor for HCV infection was found in 195 patients (86%). Genotype distribution was: 1b: 22%; 1a: 15%; 1(nonsubtypable): 15%; 3a: 34%; and 2: 7%. Fifty (21%) patients had cirrhosis. Patients with cirrhosis were older (51.6 ± 1.8 years) than those with chronic hepatitis (37.6 ± 0.6 years; P = .0001), were infected at an older age (25.9 ± 2.0 vs. 20.9 ± 0.6 years; P = .001), and had a longer duration of infection (20.5 ± 1.3 vs. 16.2 ± 0.5 years; P
= .0008). Patients with cirrhosis had a greater total lifetime alcohol consumption (288,765 ± 58,115 g) than those with chronic hepatitis (189,941 ± 15,453 g; P = .018). Cirrhotic patients also had greater total alcohol consumption during the period of infection with HCV (240,962 ± 63,756 g vs. 146,510 ± 12,862 g;
P = .02). On multivariate analysis, subject age and total alcohol consumption were independently associated with the presence of cirrhosis. Total lifetime alcohol consumption is a risk factor for the progression of liver disease caused by HCV.
Programmes specific to inflammatory bowel disease (IBD) that facilitate transition from paediatric to adult care are currently lacking.
We aimed to explore the perceived needs of adolescents with IBD ...among paediatric and adult gastroenterologists and to identify barriers to effective transition.
A web-based survey of paediatric and adult gastroenterologists in Australia and New Zealand employed both ranked items (Likert scale; from 1 not important to 5 very important) and forced choice items regarding the importance of various factors in facilitating effective transition of adolescents from paediatric to adult care.
Response rate among 178 clinicians was 41%. Only 23% of respondents felt that adolescents with IBD were adequately prepared for transition to adult care. Psychological maturity (Mean = 4.3, standard deviation (SD) = 0.70) and readiness as assessed by adult caregiver (Mean = 4, SD = 0.72) were prioritised as the most important factors in determining timing of transfer. Self-efficacy and readiness as assessed by adult caregiver were considered the two most important factors to determine timing of transition by both groups of gastroenterologists. Poor medical and surgical handover (Mean = 4.10, SD = 0.8) and patients' lack of responsibility for their own care (Mean= 4.10, SD = 0.82) were perceived as major barriers to successful transition by both paediatric and adult gastroenterologists.
Deficiencies exist in current transition care of adolescents with IBD in Australia and New Zealand. Standardising transition care practices with strategies aimed at optimising communication, patient education, self-efficacy and adherence may improve outcomes.
To establish breakpoint concentrations for the fluoroquinolones (moxifloxacin MFX and ofloxacin OFX) and injectable second-line drugs (amikacin AMK, kanamycin KM and capreomycin CPM) using the ...microscopic observation drug susceptibility (MODS) assay.
A multinational study conducted between February 2011 and August 2012 in Peru, India, Moldova and South Africa.
In the first phase, breakpoints for the fluoroquinolones and injectable second-line drugs (n = 58) were determined. In the second phase, MODS second-line drug susceptibility testing (DST) as an indirect test was compared to MGIT™ DST (n = 89). In the third (n = 30) and fourth (n = 156) phases, we determined the reproducibility and concordance of MODS second-line DST directly from sputum.
Breakpoints for MFX (0.5 μg/ml), OFX (1 μg/ml), AMK (2 μg/ml), KM (5 μg/ml) and CPM (2.5 μg/ml) were determined. In all phases, MODS results were highly concordant with MGIT DST. The few discrepancies suggest that the MODS breakpoint concentrations for some drugs may be too low.
MODS second-line DST yielded comparable results to MGIT second-line DST, and is thus a promising alternative. Further studies are needed to confirm the accuracy of the drug breakpoints and the reliability of MODS second-line DST as a direct test.
PDF
