Alida Andrealli

Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis

BACKGROUND & AIMS Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy. METHODS Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis. RESULTS Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14±3 vs. 8±1, respectively p<0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ⩾11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin. CONCLUSIONS Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment.

A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life.

A dietary interview performed by expert personnel is the best method to check whether patients with coeliac disease follow a strict gluten-free diet (GFD). We previously developed a score based on four fast and simple questions that can be administered even by non-expert personnel. The aim of the present study is to verify the reliability of our questionnaire in a new cohort of patients. The questionnaire has a five-level score. From March 2008 to January 2011, the questionnaire was administered to 141 coeliac patients on a GFD, who were undergoing re-evaluation. The score obtained was compared with persistence of both villous atrophy and endomysial antibodies (EMA). The rate of lower scores was higher among the patients with persistence of either villous atrophy (Fishers exact, P < 0·001; test for trend, P < 0·001) or positive EMA (Fishers exact, P = 0·001; test for trend, P = 0·018). Given that the coeliac patients have been well instructed on what a GFD means and on how to follow it, our questionnaire is a reliable and simple method to verify compliance to a GFD.

Prevention of paracentesis-induced circulatory dysfunction in cirrhosis: Standard vs half albumin doses. A prospective, randomized, unblinded pilot study

BACKGROUND Paracentesis-induced circulatory dysfunction is a well-known complication of large volume paracentesis. Albumin infusion (8g of albumin/L of ascites removed) is effective in preventing it, but high costs and scant availability limit its use. AIM To compare standard vs half albumin doses. METHODS Seventy cirrhotic patients treated with large volume paracentesis were randomized to receive intravenous albumin as prevention of paracentesis-induced circulatory dysfunction: group 1 (35 patients) received 4g/L of ascites removed, group 2 (35 patients) received 8g/L of ascites removed. RESULTS The incidence of paracentesis-induced circulatory dysfunction (14% vs 20% in group 1 and group 2, respectively; p=ns), hyponatremia (9% vs 6%, p=ns) and renal impairment (0% in both groups) on the 6th day from paracentesis was similar between the two groups. After 6 months of follow-up, rates of survival and of recurrence of ascites requiring large volume paracentesis were not different between the two groups. CONCLUSIONS This unblinded, randomized, pilot study suggests that treatment with half doses of albumin is effective in the prevention of paracentesis-induced circulatory dysfunction and its related clinical complications in cirrhotic patients with tense ascites treated by large volume paracentesis. If confirmed, these results could support a significant costs reduction in the management of ascites in cirrhotic patients.

Role of bowel ultrasound as a predictor of surgical recurrence of Crohn's disease

Abstract Background. In Crohns disease natural history, about 80% of the patients require surgery, which is not curative: unfortunately, the disease recurs in many patients. Objective. To investigate the role of intestinal ultrasound to predict the risk of post-operative surgical recurrence in Crohns disease. Material and methods. A total of 196 patients, with ileal or ileocolonic Crohns disease, undergoing intestinal resection, were retrospectively enrolled. All patients underwent bowel ultrasonography 6–15 months after resection. Wall thickness at the anastomosis level was measured, and thickening >3 mm was evaluated as risk factor of long-term need for reoperation. Results. Patients who have a bowel wall thickness >3 mm have an risk ratio (RR) of surgical recurrence = 2.1 [95% confidence interval (CI) = 1.12–3.74] higher than those with a thickness of ≤3 mm. The absolute incidence of new surgical intervention is 13% in patients with thickness of 3 mm, 28% in patients with thickness >3 mm, 29,1% with thickness >4 mm, 34% with thickness >5 mm, and 40% with thickness >6 mm. Conclusions. Bowel wall thickness >3 mm at ultrasound may be a non-invasive predictor of early surgical recurrence after ileo-colonic resection.

PROgnosticating COeliac patieNts SUrvivaL: the PROCONSUL score.

Introduction It has been shown that mortality rates of coeliac patients correlate with age at diagnosis of coeliac disease, diagnostic delay for coeliac disease, pattern of clinical presentation and HLA typing. Our aim was to create a tool that identifies coeliac patients at higher risk of developing complications. Methods To identify predictors of complications in patients with coeliac disease, we organised an observational multicenter case-control study based on a retrospective collection of clinical data. Clinical data from 116 cases (patients with complicated coeliac disease) and 181 controls (coeliac patients without any complications) were collected from seven European centres. For each case, one or two controls, matched to cases according to the year of assessment, gender and age, were selected. Diagnostic delay, pattern of clinical presentation, HLA typing and age at diagnosis were used as predictors. Results Differences between cases and controls were detected for diagnostic delay and classical presentation. Conditional logistic models based on these statistically different predictors allowed the development of a score system. Tertiles analysis showed a relationship between score and risk of developing complications. Discussion A score that shows the risk of a newly diagnosed coeliac patient developing complications was devised for the first time. This will make it possible to set up the follow-up of coeliac patients with great benefits not only for their health but also for management of economic resources. Conclusions We think that our results are very encouraging and represent the first attempt to build a prognostic score for coeliac patients.

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

BACKGROUND Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING Italian Medicine Agency.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses

BackgroundCoeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases.MethodsClinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres.Results87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases.ConclusionsComplicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

LINKED COLOR IMAGING REDUCES THE MISS RATE OF NEOPLASTIC LESIONS IN THE RIGHT COLON: A RANDOMIZED TANDEM COLONOSCOPY STUDY

BACKGROUND Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI). METHODS Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate. RESULTS Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively (P < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group (P = 0.01). CONCLUSIONS LCI could reduce the miss rate of neoplastic lesions in the right colon.

Adrenal function and microbial DNA in noninfected cirrhotic patients with ascites: Relationship and effect on survival.

BACKGROUND There are few data on clinical relevance of adrenal dysfunction and its relationship with occult microbial DNA in noninfected haemodynamically stable cirrhotic patients with ascites. AIMS The aim of this study was to evaluate prognostic role of adrenal dysfunction, microbial DNA, and their relationship. METHODS Adrenal function was assessed in 93 consecutive patients following a corticotropin stimulation test. Adrenal dysfunction was defined as: basal cortisol <10 μg/dl, delta cortisol <9 μg/dl, or peak cortisol <18 μg/dl. Microbial DNA was assessed in blood and ascites of 54 consecutive patients. Patients were followed up until liver transplantation or death. RESULTS Adrenal dysfunction was not significantly associated with mortality, while the risk of death rose significantly with an increase in basal cortisol values (HR 1.13 per 1-μl/dl increase; 95% CI 1.01-1.26). Microbial DNA was independently associated with reduced survival (HR 8.05, 95% CI 1.57-41.2). In microbial DNA-positive patients a significant correlation was found between Model for End-Stage Liver Disease (MELD) score and basal cortisol values (Pearsons r=0.5107; p=0.018). CONCLUSIONS Microbial DNA and MELD score, but not adrenal function, were the best independent predictors of mortality in noninfected cirrhotic patients with ascites. High serum cortisol levels may be a systemic reaction to microbial translocation, increasing in parallel with deterioration of liver function.

Educational strategies for colonoscopy bowel prep overcome barriers against split-dosing: A randomized controlled trial

Background A split-dose (SD) regimen is crucial for colonoscopy quality. Compliance with SD for early morning colonoscopy is generally poor. The present study evaluated whether pre-colonoscopy counselling, in addition to a dedicated leaflet, might increase SD uptake. Methods Consecutive 50–69-year-old patients undergoing screening colonoscopy before 10 a.m. were randomized to either receive written information only on bowel preparation (Written Group, WG) or written and oral instructions (Written and Oral Group, WaOG). The leaflet strongly encouraged SD adoption. The primary endpoint was the number of patients adopting SD in each group. The secondary endpoints were predictors of SD uptake, compliance with preparation schemes and cleansing adequacy. Results A total of 286 patients (143 WG, 143 WaOG) were enrolled (mean age 59.6 ± 6.1 years, men 49.3%). SD was adopted by 114 and 125 patients in the WG and WaOG, respectively (79.7% versus 87.4%, p = 0.079). No significant differences were observed for the proportion of patients with full compliance with preparation scheme (97.9% versus 97.2%, p = 0.99) and of procedures with adequate bowel cleansing (95.6% versus 95.1%, p = 0.77). At multivariate analysis, a > 1 h travel time to the endoscopy service was inversely correlated with SD uptake (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09–0.98). Conclusions Our leaflet guaranteed satisfactory uptake of SD and excellent adherence to the preparation scheme for early morning colonoscopy. Its use might marginalize the need for additional oral instructions, particularly in open-access settings.