A. Krag

Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome.

Vasoconstrictor drugs may improve renal function in hepatorenal syndrome (HRS), but the effect on mortality has not been established. We therefore performed a systematic review of randomized trials on vasoconstrictor drugs for type 1 or type 2 HRS. Mortality was the primary outcome measure. Eligible trials were identified through electronic and manual searches. Intention‐to‐treat random effects meta‐analyses were performed. Ten randomized trials on terlipressin alone or with albumin, octreotide plus albumin, and noradrenalin plus albumin were included. The total number of patients was 376. Overall, vasoconstrictor drugs used alone or with albumin reduced mortality compared with no intervention or albumin (relative risk [RR], 0.82; 95% confidence interval [CI], 0.70–0.96). In subgroup analyses, the effect on mortality was seen at 15 days (RR, 0.60; 95% CI, 0.37–0.97) but not at 30 days (RR, 0.74; 95% CI, 0.40–1.39), 90 days (RR, 0.89; 95% CI, 0.66–1.22), or 180 days (RR, 0.83; 95% CI, 0.65–1.05). Subgroup analyses stratified by the treatments assessed showed that terlipressin plus albumin reduced mortality compared with albumin (RR, 0.81; 95% CI, 0.68–0.97). The effect was seen in subgroup analyses of type 1 but not type 2 HRS. The remaining trials were small and found no beneficial or harmful effects of the treatments assessed. Conclusion: Terlipressin plus albumin may prolong short‐term survival in type 1 HRS. The duration of the response should be considered when making treatment decisions and in the timing of potential liver transplantations. Considering the small number of patients included, the evidence does not allow for treatment recommendations regarding type 2 HRS or any of the remaining treatment comparisons assessed. (HEPATOLOGY 2009.)

Meta‐analysis: banding ligation and medical interventions for the prevention of rebleeding from oesophageal varices

In patients with oesophageal varices, the combination of endoscopic variceal ligation (EVL) and medical therapy is recommended as standard of care for prevention of rebleeding. The results of previous meta‐analyses on this topic are equivocal.

Meta-analysis: isosorbide-mononitrate alone or with either beta-blockers or endoscopic therapy for the management of oesophageal varices

Aliment Pharmacol Ther 2010; 32: 859–871

Systematic Review with Meta-Analyses of Randomized Trials on Isosorbide-Mononitrate Alone or With Beta-Blockers or Endoscopic Therapy for Esophageal Varices

Aliment Pharmacol Ther 2010; 32: 859–871

Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C: systematic review and meta-analysis of randomised controlled trials

Objectives To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C. Design Systematic review and meta-analyses of randomised controlled trials. Prospective cohort studies were included in sensitivity analyses. Data Sources Eligible trials were identified through electronic and manual searches. Study Selection Eight randomised controlled trials comparing antiviral therapy (interferon or pegylated interferon alone or with ribavirin) versus placebo or no intervention were included. Data extraction and synthesis Two independent reviewers assessed the methodological quality of studies and extracted data. Random effects meta-analyses were performed. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate sources of intertrial heterogeneity, the risk of bias and the robustness of the results after adjusting for multiple testing. Results Random effects meta-analysis showed that antiviral therapy reduced the risk of HCC (81/1156 vs 129/1174; risk ratio 0.53, 95% CI 0.34 to 0.81). In subgroup analyses, antiviral therapy was more beneficial (test for subgroup differences p=0.03) in virological responders (0.15, 0.05 to 0.45) than in non-responders (0.57; 0.37 to 0.85). No evidence of bias was seen in regression analyses. Sequential analysis confirmed the overall result. The sensitivity analyses showed that the cohort studies found that antiviral therapy reduced the risk of HCC. There was clear statistical evidence of bias in the cohort studies (p=0.02). Conclusions Antiviral therapy may reduce the risk of HCC in hepatitis C-related fibrosis and cirrhosis. The effect may be seen irrespective of the virological response, but is more pronounced among virological responders compared with non-responders.

Betablockers induce cardiac chronotropic incompetence

To the Editor:We read with great interest the paper by Serste et al. regardingeffects of non-selective beta-blockers (BB) and paracentesisinduced circulatory dysfunction (PICD) [1]. This is the first studyto explore the background for potential deleterious effects of BBin refractory ascites, as suggested in a previous study by theauthors [2]. The high risk of PICD after BB treatment seemsrelated to an inability to increase heart rate during a circulatorychallenge. BB bind to b

Fluoroquinolones in the Primary Prophylaxis of Spontaneous Bacterial Peritonitis

OBJECTIVES:Patients with Barretts high-grade dysplasia (HGD) or early esophageal adenocarcinoma (EAC) that is shown on biopsy alone continue to undergo esophagectomy without more definitive histological staging. Endoscopic resection (ER) may provide more accurate histological grading and local tumor (T) staging, definitive therapy, and complete Barretts excision (CBE); however, long-term outcome data are limited. Our objective was to demonstrate the effect on histological grade or local T stage, efficacy, safety and long-term outcome of ER for Barretts HGD/EAC and of CBE in suitable patients.METHODS:This prospective study at two Australian academic hospitals involved 75 consecutive patients over 7 years undergoing ER for biopsy-proven HGD or EAC, using multiband mucosectomy or cap technique. In addition, CBE by 2–3-stage radical mucosectomy was attempted for all Barretts segments ≤3 cm in length in patients aged <75 years with minimal comorbidities.RESULTS:Biopsy histology showed HGD in 89% of patients and EAC in 11%. However, ER histology resulted in altered grading or staging in 48% of patients (down 28%, up 20%), with HGD in 53%, low-grade dysplasia (LGD) in 19%, mucosal adenocarcinoma in 13%, submucosal adenocarcinoma in 9%, and no dysplasia in 4% of patients. The CBE success rate was 94%. Complications were one aspiration (hospitalization with full recovery) and six strictures successfully dilated endoscopically. During the mean follow-up of 31 months (range 3–89), there was no recurrence at ER sites, 11% developed metachronous lesions and five patients underwent esophagectomy for ER-demonstrated submucosal invasion. Esophagectomy specimens were T0N0M0 in three and T1N0M0 in two patients. There were no deaths due to adenocarcinoma.CONCLUSIONS:ER alters histological grade or local T stage in 48% of patients and dramatically reduces esophagectomy rates by providing safe and effective therapy. ER has a high success rate (94%) for CBE in short segment Barretts esophagus.

Safety and efficacy of Profermin® to induce remission in ulcerative colitis

AIM To test the efficacy and safety of Profermin(®) in inducing remission in patients with active ulcerative colitis (UC). METHODS The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index (SCCAI) > 4 and < 12 (median: 7.5), who were treated open-label with Profermin(®) twice daily for 24 wk. Daily SCCAI was reported observer blinded via the Internet. RESULTS In an intention to treat (ITT) analysis, the mean reduction in SCCAI score was 56.5%. Of the 39 patients, 24 (62%) reached the primary endpoint, which was proportion of patients with ≥ 50% reduction in SCCAI. Our secondary endpoint, the proportion of patients in remission defined as SCCAI ≤ 2.5, was in ITT analysis reached in 18 of the 39 patients (46%). In a repeated-measure regression analysis, the estimated mean reduction in score was 5.0 points (95% CI: 4.1-5.9, P < 0.001) and the estimated mean time taken to obtain half the reduction in score was 28 d (95% CI: 26-30). There were no serious adverse events (AEs) or withdrawals due to AEs. Profermin(®) was generally well tolerated. CONCLUSION Profermin(®) is safe and may be effective in inducing remission of active UC.

Safety of Terlipressin for Hepatorenal Syndrome

Terlipressin has affinity with vasopressin 1 and 2 receptors (V receptors), which reflects its pharmacological effects and safety profile. V1 receptor-related side effects occur when vasoconstriction

664 COMBINATION OF BANDING LIGATION AND MEDICAL INTERVENTION FOR SECONDARY PREVENTION IN ESOPHAGEAL VARICES: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Introduction: Elevation of Prothrombin time (PT) and/or INR following Hepatectomy is a well-known phenomenon and can lead to delays in initiation of thrombo-prophylaxis and epidural catheter removal with administration of prophylactic transfusions of Fresh Frozen Plasma (FFP). Recently, the role of PT-INR has been challenged as this test does not reflect the balance between proand anti-coagulants that is often preserved. Aims: We sought to compare these conventional tests with more global assays of hemostasis such as ROTEMTM, Thrombin Generation and Coagulant Factor activity. Design: We carried out a prospective observational study with full ethical approval in 48 patients undergoing major hepatectomy (>30% resection). Methods: Conventional tests, ROTEM analysis, endogenous thrombin potential (ETP) and proand anti-coagulant activity were measured at baseline, immediately after resection and postoperative days (POD) 1, 2, and 5. Results: Values are mean (±SD). Mean INR peaked at 1.8 (±0.42) on POD 1 and returned to baseline by POD 5. Platelets reached a nadir of 163 (±78) on POD 1 and exceeded baseline by POD 5. Clauss Fibrinogen stayed within normal range but peaked on POD5 at 4.4 g/dL (±1.4). ROTEM EXTEM and INTEM parameters as well as mean ETP values all remained within normal range for the entire study period. Mean levels of factor II, VII, IX and X all stayed above 30iu/dl for the entire study period. Factors VIII and von Willebrand factor (vWf) increased steadily from POD1 onwards. Mean levels of Protein C, Protein S and Anti-Thrombin all dropped to below 50iu/dl by POD1 but only protein S recovered by POD 5. Conclusions: Although PT/INR increased following major hepatic resection, ETP and viscoelastic parameters remained within normal limits and procoagulant factor levels were above the critical threshold of 30% required for normal haemostasis. Levels of endogenous anti-coagulants drop post-operatively and apart from protein S, remain suppressed at POD5. This combined with supranormal levels of factor VIII, vWf may create a hypercoaguable state. This has important healthcare implications if patients are not receiving thromboprophylaxis based on the INR, with inappropriate FFP transfusions and delays in invasive procedures.