Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study.

Background and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival. Methods: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ±â€…terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated. Results: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations. Conclusion: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.

A meta-analysis on small intestinal bacterial overgrowth in patients with different subtypes of irritable bowel syndrome.

BACKGROUND: Enteric microbiota is increasingly being recognized as an important factor in the pathogenesis of irritable bowel syndrome (IBS). The reported prevalence of small intestinal bacterial overgrowth (SIBO) in subjects with IBS is highly variable, and there is no consensus on the role of SIBO in different subtypes of IBS, and indications and methods of testing. METHODS: A comprehensive literature search was performed for studies applying tests for SIBO in subjects with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of SIBO in subjects with IBS using different tests. The odds ratios of SIBO among subjects with IBS as compared with healthy controls using different tests were calculated. RESULTS: Of the available studies (22, 17, 5, and 3 using lactulose and glucose hydrogen breath tests [LHBT and GHBT], jejunal aspirate culture, and more than one tests, respectively) meeting the inclusion criteria, 36.7% (95% confidence interval [CI] 24.2-44.6) had a positive test for SIBO. Patients with IBS were 2.6 (95% CI 1.3-6.9) and 8.3 (95% CI 3.0-5.9) times more likely to have a positive test for SIBO as compared with healthy controls using GHBT and jejunal aspirate culture, respectively. Patients with diarrhea-predominant IBS were more likely to have positive GHBT as compared with the other subtypes. CONCLUSIONS: Patients with IBS were more likely to have SIBO as compared with healthy subjects using GHBT and jejunal aspirate culture but not using LHBT. Patients with diarrhea-predominant IBS more often have SIBO.

Effectiveness and safety of adalimumab biosimilar in inflammatory bowel disease: A multicenter study.

BACKGROUND: Adalimumab has emerged as a useful drug for treating patients with Crohn's disease (CD) and ulcerative colitis (UC), not responding to conventional therapy. There is limited data on effectiveness and safety of adalimumab biosimilar in patients with inflammatory bowel disease (IBD). METHODS: Patients with IBD who received at least one dose of adalimumab biosimilar from October 2015 to February 2018 were retrospectively included in this multicenter data analysis. Its effectiveness in inducing and maintaining clinical remission at 8, 26, and 52 weeks for CD and UC and safety profile of the drug was studied. RESULTS: Seventy patients (49 CD; 21 UC) with a median age of 39 (range 13-73) years, male predominance (64.3%), and median (IQR) disease duration of 72 (33-104) months were included. Adalimumab biosimilar was effective in inducing remission (at 8 weeks) in 46.9% and 52.4% patients with CD and UC, respectively, of whom  32.7% and 33.3% (three fourths of remitters) maintained remission over 1 year, respectively. Twenty (28.6%) patients experienced adverse events; seven (10%) were serious of whom  three had developed tuberculosis. CONCLUSIONS: Adalimumab biosimilar in usual clinical practice is safe and effective in inducing and maintaining remission in Indian patients with IBD. Steroid-free clinical remission was observed in one third of patients with UC and CD at 1 year of therapy. Graphical Abstract.