F. Politi

Prevention of First Bleeding in Cirrhosis: A Meta-Analysis of Randomized Trials of Nonsurgical Treatment

OBJECTIVE To assess the effectiveness of beta-blockers and endoscopic sclerotherapy in the prevention of first bleeding and reduction of mortality in patients with cirrhosis and esophagogastric varices. DATA SOURCES Pertinent studies were selected using MEDLINE (1980 to 1990), reference lists from published articles or reviews, and congress abstract lists. STUDY SELECTION Randomized trials comparing beta-blockers or sclerotherapy with a nonactive treatment. Nine randomized clinical trials of beta-blockers and 19 trials of sclerotherapy were reviewed. Seven trials of beta-blockers and 15 of sclerotherapy were published as full papers. DATA EXTRACTION Crude rates of bleeding and death in treated and control groups were extracted from each trial by three independent observers according to the intention-to-treat principle. The quality of published papers was systematically assessed and scored. DATA SYNTHESIS The Mantel-Haenszel-Peto method was used for statistical evaluation of heterogeneity and for pooling of the results. No substantial heterogeneity was found, and the incidence of bleeding in trials of beta-blockers was significantly reduced (pooled odds ratio, 0.54; 95% CI, 0.39 to 0.74), particularly in patients with large or medium-sized varices or in those with varices and a hepatic vein pressure gradient above 12 mm Hg; however, only a trend toward reduced mortality was obtained. Sclerotherapy trials were highly heterogeneous in the direction of the treatment effects on both bleeding (pooled odds ratio, 0.6; CI, 0.49 to 0.74) and mortality (pooled odds ratio, 0.76; CI, 0.61 to 0.94). The quality of the trials and the rate of bleeding in the untreated groups were the major sources of heterogeneity. The favorable results of sclerotherapy were obtained in trials with high bleeding rates among controls; several of these trials had a low quality score. CONCLUSIONS Beta-blockers may be recommended for prevention of first bleeding in cirrhotic patients with varices who have a high risk for bleeding. The effectiveness of sclerotherapy remains undetermined. Further trials in high-risk patients may prove useful if improved criteria to predict bleeding risk become available.

Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis : a randomized clinical trial

Between 1988 and 1990 an unblinded, randomized trial of terlipressin or vasopressin plus transdermal nitroglycerin, as part of a treatment strategy including emergency sclerotherapy for actively bleeding varices, was conducted during 165 admissions in 137 patients with cirrhosis and upper digestive bleeding. Eighty-four patient admissions were assigned to terlipressin (2 mg every 6 h) and 81 to vasopressin (0.4 to 0.8 unit per min) plus transdermal nitroglycerin (20 to 80 mg). The two groups were comparable for relevant clinical data, but there were slightly more patients with hepatocellular carcinoma or terminal conditions in the terlipressin group. After the 24-h study period, failure to control bleeding was 20/84 (25%) in the vasopressin and 14/81 (17%) in the terlipressin group (p = 0.19). Corresponding figures for patients bleeding from varices (emergency sclerotherapy in 43 and 45, respectively) were 13/55 (24%) and 5/56 (9%; p = 0.035), from other sources 5/16 (31%) and 2/15 (13%; p = 0.23), from undefined sources 2/10 (20%) and 7/13 (54%; p = 0.1). In a logistic multivariate regression model the odds ratio for terlipressin adjusted for prognostic factors was 0.45 (p = 0.07). There were seven major side effects requiring treatment discontinuation in the vasopressin and one in the terlipressin group. These results suggest that terlipressin alone is as effective as vasopressin plus transdermal nitroglycerin, with less severe side effects, in 24-h control of upper gastrointestinal bleeding in patients with cirrhosis.

Second study shows that octreotide may prevent early rebleeding in cirrhosis

EDITOR—Jenkins et al have reported a randomised trial showing that long term subcutaneous octreotide together with sclerotherapy significantly reduces the risk of recurrent bleeding from oesophageal varices in liver cirrhosis.1 In a double blind placebo controlled pragmatic trial we have found that a 15 day course of subcutaneous octreotide was effective in preventing early rebleeding in cirrhosis. After acute bleeding of the upper digestive tract had been controlled, 262 consecutive patients with cirrhosis were randomised to receive octreotide 100 μg subcutaneously three times a day for 15 days (n=131) or …

Portal Vein Thromboses in Cirrhosis: To Treat or Not to Treat?

2 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 Dear Editors: We believe that some further comment would be appropriate about the interesting systematic review and meta-analysis on the effects of anticoagulants in patients with cirrhosis and portal vein thrombosis (PVT), recently published in Gastroenterology. Overall, the study reports that anticoagulants increased recanalization and reduced progression of thrombosis, compared with patients who did not receive anticoagulants, with no excess of major and minor bleedings, and a lesser incidence of variceal bleeding. We agree with the authors about the need of planning interventional multicenter clinical trials with a larger sample size to evaluate the clinical usefulness of anticoagulants for PVT in cirrhosis, for a number of reasons. Although the possibility of spontaneous resolution and of improvement of PVT in cirrhosis has been previously shown, the present systematic review and meta-analysis on 353 patients, together with a previous one, are strong evidence of anticoagulant efficacy. However, data about safety about anticoagulant-related bleeding reported on only 257 patients seem less convincing if one considers that the benefit to risk ratio of anticoagulants has been studied in other clinical contexts, such as atrial fibrillation, in trials including thousands of patients. Furthermore, the results of the present study conflict with those of a recent similar systematic review and meta-analysis, which suggested that, owing to the heterogeneity of the studies and little sample size, further randomized, controlled trials would be warranted to confirm the risk-to-benefit of anticoagulants for PVT in cirrhosis, especially anticoagulantrelated bleeding. The rate of portal vein recanalization is only a surrogate endpoint; the real core issue of the topic is whether or not anticoagulants could ameliorate the outcome of underlying cirrhosis, because the prognostic value of PVT on cirrhosis outcome remains an unsolved issue. A recent meta-analysis reporting that PVT significantly affected both mortality and hepatic decompensation had the weakness of including studies with heterogeneous populations (partial and branch PVT excluded and in other partial and total PVT mixed);