Impact of direct-acting antiviral agents on liver function in patients with chronic hepatitis C virus infection.

Whilst the benefit of direct-acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well-accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon-based therapy. Liver function was assessed by the albumin-bilirubin (ALBI) score or grade. Overall survival according to SVR status and baseline ALBI grade was examined. We also studied time to first decompensation according to ALBI grade, as well as longitudinal changes in ALBI score over time according to SVR. Among the patients receiving DAAs, 89% achieved SVR (Japan = 99%, UK = 78%). Amongst the decompensated patients in the UK cohort, three distinct risk groups according to ALBI grade at baseline were observed. The UK patients receiving DAAs, who had predominantly decompensated disease, showed clear evidence of improvement of liver function detectable within 2 years of the start of treatment, especially in those achieving SVR. These early changes in liver function were very similar to those observed in the first 2-3 years after interferon-based therapy. DAAs improve liver function especially in those with decompensated disease who achieve SVR. Experience with interferon-based therapy suggests that failure to achieve SVR is associated with long-term decline in liver function and, in contrast, patients who do achieve SVR can expect long-term disease improvement and subsequent stabilization of liver function. Our initial analysis suggests that those receiving DAAs are likely, in the long term, to follow a similar course.

The Hepatitis C Awareness Through to Treatment (HepCATT) study: improving the cascade of care for hepatitis C virus-infected people who inject drugs in England.

BACKGROUND AND AIMS: Previous studies have shown low rates of diagnosis and treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID). Our aims were to test the effect of a complex intervention [Hepatitis C Awareness Through to Treatment (HepCATT)] in drug and alcohol clinics-primarily, on engagement of HCV-positive PWID with therapy and, secondarily, on testing for HCV, referral to hepatology services and start of HCV treatment. DESIGN AND SETTING: A non-randomized pilot study in three specialist addiction clinics in England comparing an intervention year (starting between September 2015 and February 2016) with a baseline year (2014), together with three control clinics. PARTICIPANTS: Analysis included all attendees at the intervention and control specialist addiction clinics identified as PWID. INTERVENTION: The intervention comprised the placement of a half-time facilitator in each clinic for 12 months with the brief to increase diagnosis of HCV infection within clients at those services and the engagement of diagnosed individuals with an appropriate care pathway. The facilitator undertook various activities, which could include training of key workers, direct interaction with clients, streamlining and support for hepatology appointments and introduction of dried blood-spot testing. MEASUREMENTS: For each clinic and period, we obtained the total number of clients and, as relevant, their status as PWID, tested for HCV, known HCV-positive, engaged with HCV therapy or treated. FINDINGS: Compared with baseline, there was strong evidence that engagement with HCV therapy in the intervention year increased (P < 0.001) more in the HepCATT centres than controls, up + 31 percentage points [95% confidence interval (CI) = 19-43] versus -12 (CI = -31 to + 6) and odds ratio (OR) = 9.99 (CI = 4.42-22.6) versus 0.35 (CI = 0.08-1.56). HepCATT centres also had greater increases in HCV testing (OR = 3.06 versus 0.78, P < 0.001), referral to hepatology (OR = 9.60 versus 0.56, P < 0.001) and treatment initiation (OR = 9.5 versus 0.74, P < 0.001). CONCLUSIONS: Introducing a half-time facilitator into drug and alcohol clinics in England increased engagement of HCV-positive people who inject drugs with hepatitis C virus care pathways, with increased uptake also of testing, referral to hepatology and initiation of treatment.

WITHDRAWN: Interventions for dysphagia in oesophageal cancer.

BACKGROUND: The majority of oesophageal and gastro-oesophageal cancers are diagnosed at an advanced stage and palliative treatment is the realistic management option for most patients. The optimal intervention for the palliation of dysphagia in these patients has not been established. OBJECTIVES: To systematically analyse and summarise the efficacy of different interventions used in the palliation of dysphagia in primary oesophageal carcinoma. SEARCH STRATEGY: We undertook a search according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model using the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL and major conference proceedings up to August 2005. The literature search was re-run in August 2006 and March 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with inoperable or unresectable primary oesophageal cancer who underwent palliative treatment. We included rigid plastic intubation, self-expanding metallic stent (SEMS) insertion, brachytherapy, external beam radiotherapy, chemotherapy, oesophageal bypass surgery, chemical and thermal ablation therapy, either head-to-head or in combination. The primary outcome was dysphagia improvement. Secondary outcomes included recurrent dysphagia, technical success, procedure related mortality, 30-day mortality, adverse effects and quality of life. DATA COLLECTION AND ANALYSIS: One author assessed the eligibility criteria of each study and extracted data regarding outcomes and factors affecting risk of bias. MAIN RESULTS: We included 2542 patients from 40 studies. SEMS insertion is safer and more effective than plastic tube insertion. Thermal and chemical ablative therapy provide comparable dysphagia palliation but have an increased requirement for re-interventions and adverse effects. Anti-reflux stents provide comparable dysphagia palliation to conventional metal stents. Some anti-reflux stents might reduce gastro-oesophageal reflux compared to conventional metal stents. Brachytherapy might be a suitable alternative to SEMS in providing a survival advantage and possibly a better quality of life. AUTHORS' CONCLUSIONS: Self-expanding metal stent insertion is safe, effective and quicker in palliating dysphagia compared to other modalities. However, high-dose intraluminal brachytherapy is a suitable alternative and might provide additional survival benefit with a better quality of life. Self-expanding metal stent insertion and brachytherapy provide comparable palliation to endoscopic ablative therapy but are preferable due to the reduced requirement for re-interventions. Rigid plastic tube insertion, dilatation alone or in combination with other modalities, chemotherapy alone, combination chemoradiotherapy and bypass surgery are not recommended for palliation of dysphagia due to a high incidence of delayed complications and recurrent dysphagia.

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.

BACKGROUND: There is conflicting evidence regarding the clinical efficacy of proton pump inhibitors (PPI) initiated before endoscopy for upper gastrointestinal bleeding. OBJECTIVES: To systematically review evidence from randomised controlled trials (RCTs) of PPI treatment initiated before endoscopy for upper gastrointestinal bleeding. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE and CINAHL databases and major conference proceedings to September 2005, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model. Searches were re-run in February 2006 and October 2008. SELECTION CRITERIA: We selected randomised controlled trials (RCTs), of hospitalised participants with unselected upper gastrointestinal bleeding, undergoing active treatment with a proton pump inhibitor PPI (oral or intravenous) and control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment prior to endoscopy. Outcomes were assessed at 30 days and included mortality, rebleeding and surgery. Also assessed were stigmata of recent haemorrhage (SRH; active bleeding, non bleeding visible vessel or adherent clot) at index endoscopy, length of hospital stay, blood transfusion requirements and requirement for endoscopic therapy at index endoscopy. DATA COLLECTION AND ANALYSIS: At least two review authors assessed eligibility criteria and extracted data regarding outcomes and factors affecting methodological quality. MAIN RESULTS: Six RCTs comprising 2223 participants were included. There was no statistical heterogeneity among trials for dichotomous outcomes. There were no statistically significant differences in mortality, rebleeding or surgery between PPI and control treatment. Unweighted pooled mortality rates were 6.1% and 5.5% respectively (odds ratio (OR)1.12; 95% CI 0.72 to 1.73). Unweighted pooled rebleeding rates were 13.9% and 16.6% respectively (OR 0.81; 95%CI 0.61 to 1.09). Pooled rates for surgery were 9.9% and 10.2% respectively (OR 0.96 95% CI 0.68 to 1.35). PPI treatment compared to control significantly reduced the proportion of participants with SRH at index endoscopy; unweighted pooled rates were 37.2% and 46.5% respectively (OR 0.67; 95% CI 0.54 to 0.84). However, this result was not robust to sensitivity analysis. PPI treatment compared to control significantly reduced endoscopic therapy at index endoscopy; unweighted pooled rates were 8.6% and 11.7% respectively (OR 0.68; 95% CI 0.50 to 0.93). For continuous outcomes (length of hospital stay and blood transfusion requirements), quantitative analysis could not be performed. AUTHORS' CONCLUSIONS: PPI treatment initiated before endoscopy for upper gastrointestinal bleeding might reduce the proportion of participants with SRH at index endoscopy and significantly reduces requirement for endoscopic therapy during index endoscopy. However, there is no evidence that PPI treatment affects clinically important outcomes, namely mortality, rebleeding or need for surgery.

Interventions for dysphagia in oesophageal cancer.

BACKGROUND: The majority of oesophageal and gastro-oesophageal cancers are diagnosed at an advanced stage and palliative treatment is the realistic management option for most patients. The optimal intervention for the palliation of dysphagia in these patients has not been established. OBJECTIVES: To systematically analyse and summarise the efficacy of different interventions used in the palliation of dysphagia in primary oesophageal carcinoma. SEARCH STRATEGY: We undertook a search according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model using the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL and major conference proceedings up to August 2005. The literature search was re-run in August 2006 and March 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with inoperable or unresectable primary oesophageal cancer who underwent palliative treatment. We included rigid plastic intubation, self-expanding metallic stent (SEMS) insertion, brachytherapy, external beam radiotherapy, chemotherapy, oesophageal bypass surgery, chemical and thermal ablation therapy, either head-to-head or in combination. The primary outcome was dysphagia improvement. Secondary outcomes included recurrent dysphagia, technical success, procedure related mortality, 30-day mortality, adverse effects and quality of life. DATA COLLECTION AND ANALYSIS: One author assessed the eligibility criteria of each study and extracted data regarding outcomes and factors affecting risk of bias. MAIN RESULTS: We included 2542 patients from 40 studies. SEMS insertion is safer and more effective than plastic tube insertion. Thermal and chemical ablative therapy provide comparable dysphagia palliation but have an increased requirement for re-interventions and adverse effects. Anti-reflux stents provide comparable dysphagia palliation to conventional metal stents. Some anti-reflux stents might reduce gastro-oesophageal reflux compared to conventional metal stents. Brachytherapy might be a suitable alternative to SEMS in providing a survival advantage and possibly a better quality of life. AUTHORS' CONCLUSIONS: Self-expanding metal stent insertion is safe, effective and quicker in palliating dysphagia compared to other modalities. However, high-dose intraluminal brachytherapy is a suitable alternative and might provide additional survival benefit with a better quality of life. Self-expanding metal stent insertion and brachytherapy provide comparable palliation to endoscopic ablative therapy but are preferable due to the reduced requirement for re-interventions. Rigid plastic tube insertion, dilatation alone or in combination with other modalities, chemotherapy alone, combination chemoradiotherapy and bypass surgery are not recommended for palliation of dysphagia due to a high incidence of delayed complications and recurrent dysphagia.

Cost-effectiveness and long-term impact of Helicobacter pylori 'test and treat' service in reducing open access endoscopy referrals.

INTRODUCTION: We have shown that the introduction of a carbon urea breath test (13C-UBT) service for Helicobacter pylori screening and eradication is effective in reducing the rate of open access endoscopy referrals in patients aged < 40 years in the short term. This has been substantiated by several randomized controlled trials comparing a 'test and treat' strategy with early endoscopy in these patients. However, the long-term impact of such a strategy is not established. OBJECTIVE: To ascertain the influence of 13C-UBT services on open access endoscopy referral rates in dyspeptic patients under the age of 40 years over a period of 5 years. METHODS: Retrospective analysis of open access endoscopy referral rates between August 1990 and July 2000. Cost minimization analysis was performed with a Decision Analysis Model using Treeage Data 3.5. RESULTS: The total number of open access referrals for endoscopy during 1990-1995 was between 765 and 1325 per year. The proportion of endoscopies performed in patients < 40 years ranged between 33.4% and 34.6%. The total number of endoscopy referrals during 1995-2000 after the introduction of the 13C-UBT services was between 1178 and 1321 per year. However, there was a sustained reduction in the proportion of patients aged < 40 years, ranging between 23.2% and 26.2% (Chi2 = 153.9, degrees of freedom = 9, P < 0.0001) during this period. CONCLUSIONS: The H. pylori screening and treatment strategy using the 13C-UBT service results in a sustained reduction of the number of endoscopy referrals and is cost effective in dyspeptic patients under the age of 40 years, enabling better utilization of available resources.