C. Elia

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.

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.

Extrahepatic aneurysm of the portal venous system and portal hypertension

Portal venous aneurysm (PVA) is a rare condition characterized by dilatation of the portal venous system. PVA manifestation of symptoms is varied and depends on the aneurysm size, location and related-complications, such as thrombosis. While the majority of reported cases of PVA are attributed to portal hypertension, very little is known about the conditions pathophysiology and clinical management remains a challenge. Here, we describe a 67-year-old woman who presented with complaint of dyspepsia and without a significant medical history, for whom PVA was incidentally diagnosed. The initial upper abdominal ultrasound revealed marked dilatation of the main portal vein, and subsequent contrast-enhanced computed tomography with angiography revealed a large aneurysm arising from the extrahepatic troncus portion of the portal vein, as well as gastroesophageal varices. A conservative approach using beta-blocker therapy was chosen. The patient was followed-up for 60 mo, during which time the asymptomatic status was unaltered and the PVA remained stable.

Transcatheter arterial chemoembolization for hepatocellular carcinoma in cirrhosis: influence on portal hypertension.

Background Transcatheter arterial chemoembolization (TACE) is a routine treatment for hepatocellular carcinoma in cirrhotic patients. Whether TACE influences the degree of portal hypertension remains uncertain. Aim and Patients We retrospectively analyzed the clinical course of 283 TACE to investigate the incidence of variceal bleeding and ascites after the procedure. We also prospectively evaluated portal pressure by hepatic venous portal gradient (HVPG) before and within 3 days by TACE in a group of 15 patients. Results Before TACE, esophageal varices were present in 125 patients. Variceal bleeding occurred in three (1.5%) and ascites in two (1%) patients during the follow-up post-TACE. Patients with variceal bleeding were significantly older (P=0.019). In 15 patients who underwent portal pressure measurement before and within 3 days by TACE, HVPG was unchanged (mean 13.1 vs. 12.8 mmHg, P>0.05). Conclusion In our series portal hypertension-related complications after TACE were rare and did not result in higher mortality. As TACE did not influence HVPG, the preventive ligation of esophageal varices before TACE does not seem justified.

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.

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.

Prospective randomized trial: endoscopic follow up 3 vs 6 months after esophageal variceal eradication by band ligation in cirrhosis.

BACKGROUND AND OBJECTIVES Endoscopic variceal ligation (EVL) is recommended to treat esophageal varices (EV) in cirrhosis and portal hypertension. A program of endoscopic surveillance is not clearly established. The aim of this prospective randomized trial was to assess the most effective timing of endoscopic monitoring after variceal eradication and its impact on the patients outcome and on the costs. METHODS A hundred and two cirrhotic patients with esophageal varices treated by EVL were evaluated. After variceal eradication patients were randomized to receive first endoscopic control at 3 (Group 1) and 6 (Group 2) months respectively. RESULTS Variceal obliteration was achieved in all patients. Variceal recurrence was observed in 28 cases at the first control (29.1%) without difference between the two groups (32% vs 29% in group 1 and 2 respectively, p=0.75). The incidence of large varices is similar in the two groups (33% vs 38% respectively). Using a multivariate analysis, medical therapy with B blockers was the only independent predictor of lowest risk of variceal recurrence [OR 2.30, 95% CI (1.68-3.26)]. Bleeding related to recurrent varices occurred in 3.1% of cases and was associated with portal thrombosis. Child Pugh score ≥8 was the only predictor of mortality (p=0.0002). CONCLUSIONS Recurrence of varices after banding ligation is not rare but it is associated with a low risk of variceal progression and bleeding. Accordingly, a first endoscopic control at 6 months after variceal eradication associated with a good risk stratification might be a cost-effective strategy of monitoring.