Prospective evaluation of transoral outlet reduction (TORe) after Roux-en-Y gastric bypass (RYGB) failure.

BACKGROUND AND AIMS: Weight regain after RYGB is multifactorial including dilatation of the gastro-jejunal anastomosis. Transoral outlet reduction (TORe) procedure is a minimally invasive alternative to surgical anastomotic revision. METHODS: We conducted a prospective, multicenter, simple blind, randomized study in patients with weight regain following RYGB, comparing the efficacy of conventional nutritional and behavioral management associated with a TORe procedure (TORe group) with conventional management alone and a Sham procedure (Sham group). The main objective of this study was to evaluate the percentage of excess weight loss (%EWL) at 12 months after endoscopy. RESULTS: From January 2015 to January 2019, 73 subjects were randomized in four French Bariatric centers. The final analysis involved 50 subjects, 25 in each group, 44 women, 6 men, with an average BMI of 40.6 kg/m2. At 12 months, the average %EWL was significantly higher in the TORe group than in the Sham group (13.5 ± 14.1 vs. - 0.77 ± 17.1; p = 0.002). Cohen's d was 0.91, indicating a large effect size of the procedure on the %EWL. There was no significant difference between groups concerning the improvement of obesity-related comorbidities (diabetes and dyslipidemia) and quality of life at 12 months. We report frequent adverse events in the TORe group (20% had adverse events related to the procedure). Three adverse events were serious, including two perforations of the gastro-jejunal anastomosis after TORe group that led to the premature termination of the study. CONCLUSIONS: After RYGBP failure linked to the dilatation of the gastro-jejunal anastomosis, TORe procedure with nutritional management results in significantly higher %EWL at 12 months compared to patients with nutritional management alone. As surgery, this minimally invasive endoscopic procedure can be associated with severe adverse events.

Management of the Zenker diverticulum: multicenter retrospective comparative study of open surgery and rigid endoscopy versus flexible endoscopy.

BACKGROUND AND STUDY AIM: Zenker's diverticulum is a rare disease that affects quality of life due to dysphagia and regurgitation. This condition can be treated by various surgical or endoscopic methods. PATIENTS AND METHOD: Patients treated for Zenker's diverticulum in three centers in the south of France between 2014 and 2019 were included. The primary objective was clinical efficacy. Secondary objectives were technical success, morbidities, recurrences, and need for a new procedure. RESULTS: One hundred forty-four patients with a total of one hundred sixty-five procedures performed were included. A significant difference was found between the different groups in terms of clinical success (97% for open surgery versus 79% for rigid endoscopy versus 90% for flexible endoscopy, p = 0.009). Technical failure occurred more frequently in the rigid endoscopy group than in the flexible endoscopy and surgical groups (p = 0.014). Median procedure duration, median time to resumption of feeding, and hospital discharge were statistically shorter for endoscopies than for open surgery. On the other hand, more recurrences occurred in patients treated by endoscopy than those treated by surgery, and more reinterventions were required. CONCLUSION: Flexible endoscopy appears to be as effective and safe as open surgery in the treatment of Zenker's diverticulum. Endoscopy allows a shorter hospital stay at the expense of a higher risk of recurrence of symptoms. It could be used as an alternative to open surgery for the treatment of Zenker's diverticulum, especially in frail patients.

Upfront Laparoscopic Management of Common Bile Duct Stones: What Are the Risk Factors of Failure?

BACKGROUND: Treatment of common bile duct stones (CBDS) includes laparoscopic cholecystectomy (LC) with either laparoscopic common bile duct exploration (LCBDE) or perioperative endoscopic retrograde cholangiopancreatography (ERCP). The main objective of this study was to identify predictive factors for the failure of upfront and exclusive surgical treatment by LCBDE. METHODS: This is a single-center, retrospective study on patients with CBDS and operated for LC between 2007 and 2019. The use of intra- or postoperative endoscopy for CBD clearance within 6 months after surgery was considered as failure of LCBDE. Predictors for the failure of LCBDE were investigated and outcomes were compared. RESULTS: Among 222 operated patients, LCBDE was successfully performed in 173 patients (78%) and 49 (22%) required ERCP with sphincterotomy (intraoperative (n=29) or postoperative (n=20)). Independent risk factors for surgical failure were male sex (OR: 2.525 (1.111-5.738); p=0.027), anesthesia induction time ≥ 4 p.m. (OR: 4.858 (1.731-13.631); p=0.003), pediculitis (OR: 4.147 (1.177-14.606); p=0.027), and thin CDB < 4mm (OR: 11.951 (3.562-40.097), p< 0.0001). Age, ASA score, cystic anatomy, presence of cholecystitis, and the surgeon's experience were not identified as predictors for surgical failure. A general anesthesia number >1 (6% vs. 33%; p < 0.0001), length of initial stay (6 [1-42] vs. 8 [2-27], p=0.012), total length of hospitalization (6 [1-45] vs. 9 [2-27]; p=0.010), and the rate of emergency readmissions (3.5% vs. 12.2%; p=0.027) were significantly higher in the LCBDE failure group. CONCLUSIONS: Upfront LCBDE for CBDS was associated with improved outcomes compared to intra-/postoperative ERCP recourse. Male sex, pediculitis, thin CBD, and surgery later than 4 p.m were associated with LCBDE failure and the need for endoscopic treatment. REGISTRATION NUMBER AND AGENCY: The present retrospective study was approved by our local ethics committee and was declared on ClinicalTrials.gov (ID: NCT04467710).

Multicenter randomized trial comparing diagnostic sensitivity and cellular abundance with aggressive versus standard biliary brushing for bile duct stenosis without mass syndrome.

BACKGROUND : The diagnosis of cholangiocarcinoma in patients with a biliary stricture without mass syndrome can be obtained by biliary brushing with a sensitivity of ~50 %. We performed a multicenter randomized crossover trial comparing the aggressive Infinity brush with the standard RX Cytology Brush. The aims were to compare sensitivity for cholangiocarcinoma diagnosis and cellularity obtained. METHODS : Biliary brushing was performed consecutively with each brush, in a randomized order. Cytological material was studied with blinding to the brush type used and order. The primary end point was sensitivity for cholangiocarcinoma diagnosis; the secondary end point was the abundance of cellularity obtained with each brush, with cellularity quantified in order to determine if one brush strongly outperformed the other. RESULTS : 51 patients were included. Final diagnoses were cholangiocarcinoma (n = 43; 84 %), benign (n = 7; 14 %), and indeterminate (n = 1; 2 %). Sensitivity for cholangiocarcinoma was 79 % (34 /43) for the Infinity brush versus 67 % (29/43) for the RX Cytology Brush (P = 0.10). Cellularity was rich in 31/51 cases (61 %) with the Infinity brush and in 10/51 cases (20 %) with the RX Cytology Brush (P < 0.001). In terms of quantification of cellularity, the Infinity brush strongly outperformed the RX Cytology Brush in 28/51 cases (55 %), while the RX Cytology Brush strongly outperformed the Infinity brush in 4/51 cases (8 %; P < 0.001). CONCLUSIONS : This randomized crossover trial showed that the Infinity brush is not significantly more effective than the RX Cytology Brush for biliary stenosis without mass syndrome in terms of sensitivity for cholangiocarcinoma diagnosis, but does offer a significantly higher abundance of cellularity.

Oral mannitol for bowel preparation: a dose-finding phase II study.

BACKGROUND: Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety. AIMS: The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study. METHODS: The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH4, H2, O2), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study. RESULTS: The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations. CONCLUSIONS: The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study.

EUS-guided drainage of the pancreatic duct for the treatment of postoperative stenosis of pancreatico-digestive anastomosis or pancreatic duct stenosis complicating chronic pancreatitis: Experience at a tertiary care center.

Background and Objectives: For the treatment of pancreatic duct stenosis due to chronic pancreatitis (CP) or postoperative (PO) stenosis, endoscopic procedures are usually the first choice. In cases of failure of the recommended treatment by ERCP, anastomosis between the Wirsung duct and the stomach or duodenum can be performed under EUS guidance. The objective of this retrospective study was to compare the outcomes of pancreatico-gastric or pancreaticoduodenal anastomosis under EUS for PO stenosis versus CP stenosis. Subjects and Methods: This was a retrospective, single-center, consecutive case study of patients who underwent EUS-guided Wirsungo-gastric/bulbar anastomosis. Results: Forty-three patients were included. Twenty-one patients underwent treatment for PO stenosis, and 22 patients underwent treatment for CP stenosis. The technical success rate was 95.3% (41/43), with 100% in cases of PO stenosis and 90.9% in cases of CP stenosis. The clinical success rate was 72.5% (29/40): 75% (15/20) in cases of PO stenosis and 70% (14/20) in cases of CP stenosis. The overall morbidity rate was 34.9% (15/43). The main complication was postprocedural pain, occurring in 20.9% (9/443) of patients. The rate of stent migration or obstruction was 27.9% (12/43). There was no difference in patient outcomes or morbidity according to the etiology of the stenosis. The median follow-up duration in this study was 14 months. Conclusions: EUS-guided Wirsungo-gastric/duodenal anastomosis is a feasible, minimally invasive, safe, and relatively effective procedure. The rates of technical success, clinical success, and complications were not different between patients with PO and CP stenosis. However, the follow-up period was too short to assess recurrent symptoms in these patients.

Detection of soluble biomarkers of pancreatic cancer in endoscopic ultrasound-guided fine-needle aspiration samples.

BACKGROUND: Biomarkers are urgently needed for pancreatic ductal adenocarcinoma (PDAC). Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the cornerstone for diagnosing PDAC. We developed a method for discovery of PDAC biomarkers using the discarded EUS-FNA liquid. METHODS: This retrospective study included 58 patients with suspected pancreatic lesions who underwent EUS-FNA. Protein extracts from EUS-FNA liquid were analyzed by mass spectrometry. Proteomic and clinical data were modeled by supervised statistical learning to identify protein markers and clinical variables that distinguish PDAC. RESULTS: Statistical modeling revealed a protein signature for PDAC screening that achieved high sensitivity and specificity (0.92, 95 % confidence interval [CI] 0.79-0.98, and 0.85, 95 %CI 0.67-0.93, respectively). We also developed a protein signature score (PSS) to guide PDAC diagnosis. In combination with patient age, the PSS achieved 100 % certainty in correctly identifying PDAC patients > 54 years. In addition, 3 /4 inconclusive EUS-FNA biopsies were correctly identified using PSS. CONCLUSIONS: EUS-FNA-derived fluid is a rich source of PDAC proteins with biomarker potential. The PSS requires further validation and verification of the feasibility of measuring these proteins in patient sera.

Safety of endoscopic retrograde cholangiopancreatography in the pediatric population: a multicenter study.

INTRODUCTION: The aims of this retrospective multicenter study were to assess the technical success and adverse events of endoscopic retrograde cholangiopancreatography (ERCP) procedures in children in French and Belgian centers. METHODS: All children aged 1 day to 17 years who underwent ERCP between January 2008 and March 2019 in 15 tertiary care hospitals were retrospectively included. RESULTS: 271 children underwent 470 ERCP procedures. Clinical long-term follow-up was available for 72 % of our patients (340/470 procedures). The median age at intervention was 10.9 years. ERCP was therapeutic in 90 % (423/470) and diagnostic in cases of neonatal cholestasis in 10 % of the patients. The most common biliary indication was choledocholithiasis; the most common pancreatic indication was chronic pancreatitis. Biliary cannulation was successful in 92 % of cases (270/294); pancreatic cannulation in 96 % of cases (169/176); and planned therapeutic procedures in 92 % of cases (388/423). The overall complication rate was 19 % (65/340). The most common complication was post-ERCP pancreatitis (PEP) in 12 % of cases (40/340) and sepsis in 5 % (18/340). On univariate analyses, pancreatic stent removal was protective against PEP (odds ratio [OR] 0.1, 95 % confidence interval [CI] 0.01 - 0.75; P = 0.03), and sepsis was associated with history of liver transplantation (OR 7.27, 95 %CI 1.7 - 31.05; P = 0.01). Five patients had post-ERCP hemorrhage and two had intestinal perforation. All complications were managed with supportive medical care. There was no procedure-related mortality. CONCLUSION: Our cohort demonstrates that ERCP can be performed safely with high success rates in many pancreaticobiliary diseases of children. The rate of adverse events was similar to that in previous reports.

EUS-guided choledochoduodenostomy by use of electrocautery-enhanced lumen-apposing metal stents: a French multicenter study after implementation of the technique (with video).

BACKGROUND AND AIMS: EUS-guided biliary drainage is indicated in cases of impossibility or failure of classic biliary drainage by ERCP. Recently we reported good efficiency of EUS-guided choledochoduodenostomy (EUS-CDS) using the electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) in a retrospective multicenter study. Use of the recommended technique (direct puncture with the ECE-LAMS with use of a pure cut current and a 6-mm stent) was the only predictive factor of clinical success. We re-evaluated this procedure after 1 year in the same centers. METHODS: This was a French retrospective multicenter study of a prospective database including all cases of EUS-guided CDS with ECE-LAMS in the 7 centers that participated in the first study. RESULTS: Seventy consecutive patients were included in this study between September 1, 2017, and September 22, 2018. Failure of primary ERCP was due to duodenal stenosis in 44% of cases and to tumoral infiltration of the papilla in 22% of cases. The mean duration of the procedure was 5 ± 3 minutes. The recommended technique was used in 98.5% of cases. The technical and clinical success rates were both 97.1% (69/70). Short-term adverse events (periprocedural and intrahospital) occurred in 1.6%. CONCLUSIONS: EUS-CDS with the ECE-LAMS is efficacious and safe in distal malignant obstruction of the common bile duct in cases of ERCP failure with impressive results once expertise is acquired and the recommended technique (direct fistulotomy, pure cut current, and 6-mm stent) is followed.

Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Pancreatic Solid Pseudopapillary Neoplasm Before Surgical Resection: A European Multicenter Registry-Based Study on 149 Patients.

OBJECTIVES: The results of only a few endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic solid pseudopapillary neoplasm (SPN) have been published, and the safety of the procedure has never been investigated. Our study compared the recurrence rate in patients with and without preoperative EUS-FNA. METHODS: This European multicenter registry-based study was conducted in 22 digestive units, and retrospectively included all patients who underwent complete resection of a pancreatic SPN from 2000 to 2018. Patients with and without initial EUS-FNA were compared, and postsurgery recurrence and the associated risk factors were evaluated. RESULTS: A complete resection of a pancreatic SPN was performed in 149 patients (133 women, 89%), with a mean age of 34 (standard deviation, 14) years. There were no significant differences between the with (78 patients) and without (71 patients) EUS-FNA groups, except for age and tumor size and location.Preoperative EUS-FNA allowed pancreatic SPN diagnosis in 63/78 cases (81%). After a mean follow-up of 43 (standard deviation, 36) months, recurrence was noted in 4 patients (2.7%). Preoperative EUS-FNA was not correlated with recurrence, but an older age (P = 0.005) was significant. CONCLUSIONS: Preoperative EUS-FNA does not affect pancreatic SPN recurrence. In this series, old age was significantly correlated with recurrence.

Endoscopic ultrasound-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing stents: a retrospective analysis.

BACKGROUND: Endoscopic ultrasound-guided biliary drainage is an alternative to percutaneous biliary drainage in cases of malignant biliary obstruction and failure of classic endoscopic drainage by endoscopic retrograde cholangiopancreatography (ERCP). Recently, a new electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) that allows for endoscopic anastomosis (apposition stent) has become available for use in EUS-choledochoduodenostomy (EUS-CDS) and facilitates the procedure. METHODS: This was a retrospective study of all EUS-CDS procedures performed in France between April 2016 and August 2017. The primary end point was the technical and clinical success rates of EUS-CDS using an ECE-LAMS. RESULTS: 52 consecutive patients were included in the study. The etiology of distal bile duct obstruction was distal pancreatic adenocarcinoma in 43 patients (82.7 %). The technical success rate was 88.5 % (46 /52 patients), and the clinical success rate was 100 % (46/46 patients). The mean duration of the procedure was 10.2 minutes (range 1 - 90). Two patients (3.8 %) presented with short-term complications after EUS-CDS and before discharge from hospital. In univariate analyses, a small diameter of the common bile duct and not following the recommended procedure technique were significant risk factors for technical failure. Over a mean follow-up of 157 days, the median survival time without biliary complications was 135 days. CONCLUSION: EUS-CDS with an ECE-LAMS is efficacious and safe in distal malignant obstruction of the common bile duct and could be proposed as the first option in cases of ERCP failure.

The treatment of refractory ulcerative colitis.

Ulcerative proctitis is defined as a mucosal inflammation limited to the rectum. Ulcerative proctitis is responsible for distressing symptoms and alteration of patient quality of life. Effective treatment is important to prevent or delay proximal extension of the disease and to improve quality of life. Refractory ulcerative proctitis is defined as the failure of topical and oral 5-aminosalicylic acid and corticosteroids. Medical management of refractory ulcerative proctitis may be challenging as there is little evidence regarding drug efficacy in this clinical situation. Data are currently available for azathioprine, topical tacrolimus and anti-TNF monoclonal antibodies as rescue treatment for refractory ulcerative proctitis. Other biologics may be of benefit despite a lack of dedicated clinical trials. Ultimately, experimental therapies such as epidermal growth factor enemas, appendectomy or fecal transplantation may be tried before restorative proctocolectomy with J pouch anastomosis, which has demonstrated good results with regards to clinical remission and quality of life.

Oral vancomycin induces sustained deep remission in adult patients with ulcerative colitis and primary sclerosing cholangitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. The treatment of UC is challenging, especially when it is associated with primary sclerosing cholangitis (PSC), a chronic inflammatory disease of the bile ducts that affects around 5% of patients with UC, and leads to an increased risk of cholangiocarcinoma and colorectal cancer. Microbiota is considered to play an important role in the pathogenesis of UC, although the efficacy of antibiotics in this context is only limited and transient. Several studies have investigated the use of antibiotics for the treatment of PSC in adult and pediatric populations, with conflicting results. In this brief report, we describe the effect of oral vancomycin treatment in three patients with UC and PSC refractory to conventional and biologic therapies. All three patients achieved clinical remission and mucosal healing with vancomycin 500 mg twice a day administered orally. Maintenance treatment with oral vancomycin was well tolerated and led to sustained clinical and endoscopic remission in all three patients. Oral vancomycin also improved liver function tests in two patients who did not have pre-existing cirrhosis.

Diagnosis, Natural History and Treatment of Eosinophilic Enteritis: a Review.

PURPOSE OF REVIEW: To review recent findings regarding eosinophilic enteritis, including epidemiology, pathogenesis, natural history, and treatment. RECENT FINDINGS: A 2017 population-based study using a US healthcare system database identified 1820 patients with a diagnosis of eosinophilic enteritis among 35,826,830 individuals. The majority of patients with eosinophilic enteritis in this study were women (57.7%), Caucasian (77.5%), and adults (> 18 years of age) (83.5%). The overall prevalence of eosinophilic enteritis was estimated at 5.1/100,000 persons. Eosinophilic enteritis, also known as eosinophilic gastroenteritis, is a rare primary eosinophilic gastrointestinal disorder (EGID) of unknown etiology characterized by the presence of an intense eosinophilic infiltrate on histopathological examination of the intestinal mucosa. The etiology of eosinophilic enteritis remains unknown. However, there is evidence to support the role of allergens in the pathogenesis of this disorder, as children and adults with EGIDs often have positive skin testing to food allergens and a family history of allergic diseases. Recent studies unraveling the role of IgE-mediated but also delayed Th2-type responses have provided insight into the pathogenesis of this disease. Eosinophilic enteritis causes a wide array of gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, bloating, or ascites, and its diagnosis requires a high degree of clinical likelihood, given the nonspecific clinical presentation and physical examination findings. Oral corticosteroids are considered to be the mainstay of treatment and are generally used for a short period with good response rates. Antihistamine drugs and sodium cromoglycate have also been used to treat patients with eosinophilic enteritis. Preliminary studies have demonstrated the potential benefit of biological therapies targeting the eosinophilic pathway such as mepolizumab, an anti-IL5 antibody, or omalizumab, an anti-IgE monoclonal antibody. Eosinophilic enteritis is generally considered to be a benign disease without relapse, but up to 50% of patients may present a more complex natural history characterized by unpredictable relapses and a chronic course.

Stricturing Crohn's disease-like colitis in a patient treated with belatacept.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been involved in the development of intestinal inflammation, especially therapeutic monoclonal antibodies directed against CTLA-4. Here we report the appearance of a severe stricturing Crohn's disease-like colitis in a patient with a kidney allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion protein.

Endoscopic treatment of fistula after sleeve gastrectomy: results of a multicenter retrospective study.

BACKGROUND AND STUDY AIMS: Fistula is the main complication of laparoscopic sleeve gastrectomy (LSG), for which healing is difficult to achieve. The aims of the study were to evaluate the efficacy of interventional endoscopy for post-LSG fistula treatment, to evaluate various endoscopic techniques used and identify their complications, and to identify predictive factors of healing following endoscopic treatment. PATIENTS AND METHODS: This retrospective multicenter study included patients with post-LSG fistula. Therapeutic procedures were evaluated, taking into account complications and healing times. Endoscopic procedures were considered to have promoted healing if no other surgical procedure was performed. Predictive factors of healing were identified by univariate and multivariate analysis. RESULTS: A total of 110 patients were included, of whom 6 (5.5 %) healed spontaneously, 81 (73.6 %) healed following endoscopic treatment, and 19 (17.3 %) healed following surgery. Healing rates following endoscopic treatment were 84.4 % in the first 6 months of treatment (65/77), 52.4 % for treatment lasting 6 - 12 months (11/21), and 41.7 % after 12 months of treatment (5/12). A drainage procedure (surgical, endoscopic, or percutaneous) was performed in 92 patients (83.6 %). A total of 177 esogastric stents were placed in 88 patients (80.0 %). Surgical debridement, clip placement, glue sealing, and plug placement were also performed. Multivariate analysis identified four predictive factors of healing following endoscopic treatment: interval < 21 days between fistula diagnosis and first endoscopy (P = 0.003), small fistula (P = 0.01), interval between LSG and fistula ≤ 3 days (P = 0.01), no history of gastric banding (P = 0.04). CONCLUSION: Endoscopic treatment facilitated healing of post-LSG fistula in 74 % of patients. Early endoscopic treatment increased the likelihood of success, and was most effective during the first 6 months of management. After this point, surgical treatment should be considered.

Pegylated interferon-α2a and ribavirin versus pegylated interferon-α2b and ribavirin in chronic hepatitis C : a meta-analysis.

INTRODUCTION: Results of trials and meta-analyses comparing pegylated interferon (PEG-IFN)-α2a and PEG-IFN-α2b for the treatment of chronic hepatitis C are conflicting. OBJECTIVE: Our objective was to determine which PEG-IFN (α2a or α2b), in association with ribavirin, is the most effective for the treatment of chronic hepatitis C by performing an updated meta-analysis. METHOD: MEDLINE (1950-2012) and EMBASE (1974-2012) databases, as well as the Cochrane Central Register of controlled trials and the Cochrane Database of Systematic Reviews, were searched. Reference lists of retrieved articles were scanned, and proceedings of major international conferences were manually searched for abstracts. Randomized clinical trials and non-randomized clinical studies comparing PEG-IFN-α2a with PEG-IFN-α2b in association with ribavirin in adult patients with chronic hepatitis C were included. Studies including HIV-positive patients or liver transplant recipients were excluded. The data extraction from each study was conducted independently by two authors, with disagreements resolved by consensus or by a third reviewer. The trial quality of randomized clinical trials was assessed by taking into account generation of allocation sequence, allocation concealment, efficacy of randomization, investigator blindness, description of withdrawals and dropouts and adherence to the intention-to-treat principle. Two meta-analyses were performed, the first including randomized clinical trials only, and the second including both randomized and non-randomized clinical studies. The primary outcome measure was frequency of sustained virological response (SVR). Heterogeneity and publication bias were systematically taken into account. RESULTS: This meta-analysis included 26 studies, 11 randomized and 15 non-randomized, with a total of 18,260 patients: 8,125 treated with PEG-IFN-α2a and 10,135 treated with PEG-IFN-α2b. In the meta-analysis that included randomized trials only, the SVR was significantly higher for patients treated with PEG-IFN-α2a than for those treated with PEG-IFN-α2b for genotypes 1 and 4 [odds ratio (OR) 1.45; 95 % CI 1.09-2.06; p = 0.013] and for all genotypes (OR 1.34; 95 % CI 1.05-1.72; p = 0.02). In the meta-analysis including both randomized and non-randomized studies, the SVR was significantly higher for PEG-IFN-α2a than for PEG-IFN-α2b for all genotypes (OR 1.24; 95 % CI 1.10-1.40; p < 0.001) and for genotypes 1 and 4 (OR 1.25; 95 % CI 1.14-1.36; p < 0.001); for genotypes 2 and 3, the SVR was greater for treatment with PEG-IFN-α2a than with PEG-IFN-α2b, with the difference tending towards significance (OR 1.15; 95 % CI 0.98-1.35; p = 0.08). A certain degree of heterogeneity was present amongst the various studies included in this meta-analysis. Publication bias was detected (particularly for analyses including only randomized controlled trials) and taken into account using appropriate statistical methods. CONCLUSION: Current evidence suggests that PEG-IFN-α2a and ribavirin is associated with a higher SVR than PEG-IFN-α2b and ribavirin in patients mono-infected with hepatitis C, particularly for genotypes 1 and 4.