Screening and surveillance of oesophageal varices in patients with HCV-positive liver cirrhosis successfully treated by direct-acting antiviral agents.

BACKGROUND & AIMS: limited evidence is available to guide hepatologists regarding endoscopic surveillance of oesophageal varices (EV) in Hepatitis C Virus (HCV)-positive cirrhotic patients achieving a sustained virologic response. To address these issues, we conducted a long-term prospective study on 427 HCV-positive cirrhotic patients successfully treated by Direct Antiviral Agents (DAAs). METHODS: Patients were divided into two groups according to their baseline Baveno VI status: Group 1 (92, 21.5%, favourable Baveno VI status) and Group 2 (335, 78.5%, unfavourable Baveno VI status). Each patient underwent baseline endoscopy and was endoscopically monitored for a median follow-up of 65.2 months according to Baveno VI recommendations. RESULTS: About 4.3% of Group 1 patients showed baseline EV compared with 30.1% of Group 2 patients (p < .0001). No patients belonging to Group 1 without baseline EV developed EV at follow-up endoscopy compared with 6.5% in Group 2 patients (p = .02); 69/107 (64.5%) patients with baseline EV showed small varices. During the endoscopic follow-up, EV disappeared/improved in 36 (33.6%), were stable in 39 (36.4%) and worsened in 32 (29.9%) patients, all belonging to Group 2 (p = .001). Improvement in Baveno VI status was observed in 118/335 (35.2%, p < .0001) of Group 2 patients and among those without pre-therapy EV, none developed EV throughout the follow-up. CONCLUSIONS: HCV-positive cirrhotic patients cured by DAAs showing baseline favourable Baveno VI status and no worsening during follow-up can safely avoid endoscopic screening and surveillance. Patients having unfavourable Baveno VI status without baseline EV who improve their status may suspend further endoscopic surveillance.

Long-term follow-up of diabetic and non-diabetic patients with chronic hepatitis C successfully treated with direct-acting antiviral agents.

BACKGROUND AND AIMS: Clearance of hepatitis C virus (HCV) is associated with improved glycometabolic control in patients with diabetes mellitus (DM) but whether this effect is maintained over the long term with a reduction in liver-related events (LRE) is still debated. To address these issues, we conducted a long-term prospective study on diabetic and non-diabetic patients with chronic hepatitis C cured by direct antiviral agents (DAAs). METHODS: Among 893 recruited patients, 15.7% were diabetic (Group 1) and 84.3% non-diabetic (Group 2); changes in fasting glucose (FG) and glycated haemoglobin (HbA1c) levels were assessed in Group 1 while the incidence of LRE was established in the whole cohort. Differences between groups were evaluated and independent predictors of unfavourable clinical outcome were established. RESULTS: After a mean follow up of 44.5 months, a significant reduction in FG and HbA1c values was found in Group 1. Death was reported in 5.7% of patients in Group 1 vs 1.6% in Group 2 (P = .003), hepatocellular carcinoma (HCC)-free survival was significantly lower in Group 2 (P = .015) as well as LRE-free survival in Group 1 cirrhotic patients (P = .0006). After adjustment for baseline variables, cirrhosis and albumin levels emerged as independent predictors of LRE; low albumin levels, DM and central obesity were associated with HCC risk in cirrhotic patients while insulin therapy emerged as unfavourable predictor among diabetics. CONCLUSIONS: SVR achieved by DAAs is associated with long-term improvement of glycometabolic control in diabetic patients, but among cirrhotics DM still exerts a detrimental effect on the liver.

Clinical outcomes in chronic hepatitis C long-term responders to pre-direct antiviral agents: a single-center retrospective study.

BACKGROUND: Obesity, type 2 diabetes (T2D), dyslipidemia, arterial hypertension as well as hepatic steatosis (HS) are common conditions that can affect clinical outcomes of patients with chronic hepatitis C (CHC) who achieved sustained virologic response (SVR). The aim of this study was to assess the impact of metabolic cofactors on the occurrence of clinical events during follow-up (FU) in a group of CHC long-term responders (LTRs) to interferon- (IFN) based therapy. METHODS: A total of 5172 medical records of CHC patients enrolled from 1990 to 2011 were examined; 1034 of 5172 (20%) patients were treated with IFN-based therapy and 382 of 1034 (37%) of them achieved SVR. A total of 188 (49%) LTRs underwent liver biopsy before antiviral treatment. Data on liver and cardiometabolic events such as cirrhosis and its complications, hepatocellular carcinoma, coronary artery disease, arterial hypertension, impaired fasting glucose (IFG)/type 2 diabetes (T2D) and dyslipidemia, were collected over time. RESULTS: The mean age of the whole cohort was 46±12 years and 114/188 (61%) patients were males. HS was found in 82 of 188 (43.6%) patients and most of them were infected by HCV genotype 3a. The prevalence of obesity, IFG/T2D, dyslipidemia and arterial hypertension was 4.3%, 6.9%, 37.2%, and 5.9%, and was similarly distributed among patients with and without HS. Cirrhosis was histologically diagnosed in 18 of 188 (9.6%) patients. After a median follow-up of 11 years (range 3-21 years), the cumulative incidence of cardiovascular events, IFG/T2D and dyslipidemia was higher in CHC-LTRs who had HS at baseline compared to those without HS (1.2%, 2.3%, and 3.0% vs. 0.4%, 0.8%, and 2.5%, respectively). At multivariable Cox regression analysis, HS was significantly associated to the development of cardiovascular events and IFG/T2D (HR=5.2, 95% CI: 1.3-20.7, P=0.019, and HR=2.6, 95% CI: 1.1-6.2, P=0.027, respectively). CONCLUSIONS: In CHC-LTRs, HS at baseline may predispose to the development of cardiovascular events and T2D during follow-up emphasizing the importance of an accurate counseling in order to prevent extra-hepatic complications.

Rifabutin-Based Rescue Therapy for Helicobacter pylori Eradication: A Long-Term Prospective Study in a Large Cohort of Difficult-to-Treat Patients.

The most commonly used regimens fail to eradicate Helicobacter pylori (H. pylori) infection in 5⁻10% of patients. Those not cured with treatments based on amoxicillin, clarithromycin, nitroimidazoles, fluoroquinolones, bismuth or tetracycline have no other conventional options thereafter. In this prospective long-term monocentric study, patients who failed to eradicate H. pylori following treatment with all conventional antibiotics were included. All subjects were treated with rifabutin 150 mg, amoxicillin 1 g and a standard dose of proton pump inhibitor, twice daily for 14 days. A negative 13C-urea breath test was used four weeks after treatment completion as an index of H. pylori eradication. Three hundred and two patients were included. Fifty-four percent (164/302) had peptic ulcer disease while 45.7% (138/302) had gastritis or functional dyspepsia. Per-protocol eradication and intention-to-treat eradication were achieved in 72.7% and 71.5%, respectively. A univariate analysis showed that gender, ethnic background, smoking habits and familial history of gastric diseases were not predictive factors of response, while with multiple logistic regression analysis, the ethnic background (Italian) predicted a poor response in the second period of the study (2010⁻2017). In conclusion, this study on a large cohort of very difficult-to-treat patients showed that rifabutin-based rescue therapy is an acceptable and safe strategy after multiple eradication failures with conventional antibiotics.

Evaluation of Clensia®, a new low-volume PEG bowel preparation in colonoscopy: Multicentre randomized controlled trial versus 4L PEG.

BACKGROUND: Success of colonoscopy is linked to the adequacy of bowel cleansing. Polyethylene glycol 4L (PEG 4L) solutions are widely used for colonic cleansing but with limitations concerning tolerability and acceptability. AIM: To demonstrate the equivalence of a new low-volume PEG containing citrates and simeticone (Clensia) versus a standard PEG 4L. METHODS: In this, multicentre, randomised, observer-blind trial, patients received either Clensia 2L or PEG 4L solution. Primary endpoint was the proportion of patients with colon cleansing evaluated as excellent or good. RESULTS: 422 patients received Clensia (n=213) or PEG 4L (n=209). Rate of excellent/good bowel cleansing was 73.6% and 72.3% in Clensia and PEG 4L group respectively. Clensia was demonstrated to be equivalent to PEG 4L. No SAEs were observed. Clensia showed better gastrointestinal tolerability (37.0% vs 25.4%). The acceptability was significantly better with Clensia in terms of proportion of subjects who felt no distress (Clensia 72.8% vs PEG 4L 63%, P=0.0314) and willingness-to-repeat (93.9% vs 82.2%, P=0.0002). The rate of optimal compliance was similar with both formulations (91.1% for Clensia vs 90.9% for PEG 4L, P=0.9388). CONCLUSIONS: The low-volume Clensia is equally effective and safe in bowel cleansing compared to the standard PEG 4L, with better gastrointestinal tolerability and acceptability.

Risk of microangiopathy in type 2 diabetes mellitus patients with or without chronic hepatitis C: Results of a retrospective long-term controlled cohort study.

BACKGROUND: Patients with chronic hepatitis C have an increased risk of diabetes mellitus but the type and risk of developing diabetes-related complications have not yet been evaluated. METHODS: In order to compare the incidence of diabetic microangiopathy in patients with new onset diabetes without microangiopathy we recruited 54 hepatitis C virus (HCV)-positive and 119 HCV-negative patients from January 2005 to December 2006. All patients were followed-up every 6 months for liver and diabetic complications and incidence of cardiovascular diseases up to December 2012 when data were retrospectively analyzed. RESULTS: The two cohorts were comparable at enrolment except for mean body mass index, obesity rate and family history of diabetes (p=0.007). After 7.2 years of follow-up, 13 HCV-positive (24.1%) and 37 HCV-negative patients (31%) showed at least one microangiopathic complication (p=0.34); 5 HCV-positive (9.3%) and 13 HCV-negative patients (10.8%) reported cardiovascular diseases (p=0.2); 14 HCV-positive (24.5%) compared to 0 HCV-negative patients developed liver-related complications (p=0.0003). One HCV-positive patient died due to liver cancer, 1 HCV-negative patient died from myocardial infarction (p=0.3). Increasing age (HR=1.04, 95% CI: 1.00-1.07, p=0.04) and smoking (HR=2.94, 95% CI: 1.06-8.17, p=0.04) were positively associated to diabetic complications. CONCLUSIONS: Incidence of microangiopathy is not significantly different in diabetics with or without chronic hepatitis C.

Narrow band imaging vs. high definition colonoscopy for detection of colorectal adenomas in patients with positive faecal occult blood test: a randomised trial.

BACKGROUND: The impact of narrow band imaging in improving the adenoma detection rate in a screening scenario is still unclear. AIM: To evaluate whether narrow band imaging compared with high definition white light colonoscopy can enhance the adenoma detection rate during screening colonoscopy. METHODS: Consecutive patients presenting for screening colonoscopy were included into this study and were randomly assigned to the narrow band imaging group (Group 1) or standard colonoscopy group (Group 2). Primary end point was the adenoma detection rate and secondary aim was the detection rate of advanced adenomas. RESULTS: Overall, 117 patients were allocated to Group 1 and 120 to Group 2. Both the adenoma detection rate and the detection rate of advanced adenomas were not significantly different between the two groups (respectively, 52.1% vs. 55%, RR=0.95, 95% CI 0.75-1.20; 32.5% vs. 44.2%, RR=0.74, 95% CI 0.53-1.02). No significant difference between the proportions of polypoid and flat adenomas was found. Male gender, no prior history of screening, and endoscopist's adenoma detection rate were independent predictive factors of higher advanced adenoma detection rate. CONCLUSIONS: In a screening scenario, narrow band imaging did not improve the adenoma nor advanced adenoma detection rates compared to high definition white light colonoscopy.

Durability of the response to peginterferon-α2b and ribavirin in patients with chronic hepatitis C: a cohort study in the routine clinical setting.

OBJECTIVES: To evaluate whether, in chronic hepatitis C-positive naive patients recruited in the routine clinical setting and treated with pegylated-interferon-α2b (Peg-IFN) and ribavirin (RBV), the sustained virologic response (SVR) is durable over the long term and whether it is associated with a decrease in liver complications and incidence of glucose abnormalities. PATIENTS AND METHODS: This was a prospective long-term follow-up study of 182 naive patients enrolled in 2001-2002 and treated with Peg-IFN and RBV and followed up to December 2010, with clinical, biochemical, and virological evaluations every 6-12 months. RESULTS: None of the 115 (63.2%) sustained responders showed late viremic relapse during the follow-up. SVR was better defined at 24 weeks (16/16 relapsers, 100%) than at 12 weeks after the end of therapy (14/16 relapsers, 87.5%). On multivariable analysis, viral genotype (odds ratio 0.16, 95% confidence interval 0.07-0.36, P=0.0001) and a greater than 20% RBV reduction (odds ratio 5.21, 95% confidence interval 1.54-17.67, P=0.008) predicted long-term response (LTR) independently. The incidence of cirrhosis was significantly higher among nonresponders (21.3%) compared with long-term responders (0.9%, P≤0.0001), but the risk of developing glucose abnormalities was not significantly reduced in long-term responders (hazard ratio 1.36, P=0.363). Hepatocellular carcinoma occurred only in three cases. CONCLUSION: SVR achieved in patients treated in the routine clinical setting with Peg-IFN and RBV is durable over the long term and LTR significantly reduces the risk of progression to cirrhosis; however, in a population with mild liver fibrosis, the clinical impact of LTR on the risk of glucose abnormalities seems negligible.

A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy.

BACKGROUND & AIMS: An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. METHODS: We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. RESULTS: Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. CONCLUSIONS: We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.

Safety of propofol in cirrhotic patients undergoing colonoscopy and endoscopic retrograde cholangiography: results of a prospective controlled study.

BACKGROUND AND AIMS: Safety of propofol sedation in patients with liver cirrhosis undergoing colonoscopy or endoscopic retrograde cholangiopancreatography (ERCP) remains to be studied. The aim of this study was to investigate whether the use of propofol is safe for endoscopic procedures more complex than gastroscopy in patients with liver cirrhosis in a prospective controlled study. METHODS: Two hundred and fourteen consecutive patients, with or without cirrhosis, who underwent colonoscopy or ERCP with propofol sedation were recruited between January and June 2009. Administration of sedation was performed by anesthesiologists and outcome measures were recorded. Main outcomes were complication rates and recovery times. RESULTS: Sixty-one (28.5%) cirrhotic patients and 153 (71.5%) noncirrhotic patients were included. The incidence of sedation-related complications did not significantly differ between the two populations (11.5 vs. 17.0%, respectively, P=0.31). The mean (±SD) dose of propofol administered (213±86 vs. 239±100 mg, P=0.07), the mean time to achieve adequate sedation (3.3±1.1 vs. 3.0±1.2 min, P=0.21), the mean total duration of the endoscopic procedure (24.5±10.6 vs. 27.4±11.8 min, P=0.08), the mean time to reach Observer's Assessment of Alertness and Sedation Scale 5 (17.2±4.4 vs. 18.4±5.6 min, P=0.15), the mean time from completion of the procedure to release (9.0±2.5 vs. 9.1±3.2 min, P=0.86), and the mean time to full recovery (42.2±7.3 vs. 42.3±7.8 min, P=0.88) were very similar between the two groups. The limitation of this study was lack of randomization, and a control group of cirrhotic patients using standard sedation with benzodiazepines and opioids. CONCLUSION: Propofol deep sedation administered by an anesthesiologist with appropriate monitorings seems to be a safe procedure during colonoscopy or ERCP in cirrhotic patients.

High-grade B-cell lymphoma arising in mucosa-associated lymphoid tissue of the duodenum.

Duodenal mucosa-associated lymphoid tissue lymphoma is a rare neoplasm. We report a case of a 70-year-old man with non-Hodgkin's lymphoma located in the descending duodenum that was not associated with Helicobacter pylori infection of the stomach. A surgical resection due to obstruction of the bowel lumen above the ligament of Treitz was performed. No invasion into the adjacent structure was confirmed at surgery. The pathological examination showed an infiltration of the duodenal mucosa and submucosa with B lymphocytes. Monoclonal proliferation of the lymphoid tissue was demonstrated by polymerase chain reaction. The histological appearance and the demonstration of monoclonality fulfilled the criteria for malignant high-grade B-cell lymphoma arising from mucosa-associated lymphoid tissue.