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Prevention of variceal rebleeding

2003; Elsevier BV; Volume: 361; Issue: 9376 Linguagem: Inglês

10.1016/s0140-6736(03)13750-6

1474-547X

Juan Carlos García–Pagán, Jaime Bosch,

Gastrointestinal Bleeding Diagnosis and Treatment

Authors' replySir—We thank Ulrich Thalheimer and colleagues for their correspondence. However, several of their points deserve comment.The different bleeding risk observed in prevention of first variceal bleeding versus rebleeding is well known, unquestionable, and out of the scope of our review, the aim of which was to assess whether pharmacological therapy is as effective as endoscopic treatments in prevention of rebleeding. In this context, we emphasised that drug therapy is especially effective when it results in a favourable haemodynamic response. We recognise that the studies by Escorsell and Bureau and their colleagues included patients in both primary and secondary prevention of variceal bleeding. However, in the first study, findings in primary and secondary prevention were almost identical (probably because of selection of patients with large varices) and, in the second, limiting data to prevention of rebleeding, rebleeding rates were 88% in non-responders versus 33% in responders. Therefore, our assertion that responders on HVPG criteria do better than non-responders is well supported.The data reported for Villanueva and colleagues' study were obtained via personal communication with Càndid Villanueva, and the reason for not quoting McCormick and co-workers' study was indeed that suggested by Thalheimer and colleagues. After publication of our review, another study analysed the prognostic value of HVPG response.1Abraldes JG Tarantino I Turnes J Garcia-Pagan J Rodes J Bosch J Hemodynamic response to pharmacologic treatment of portal hypertension and long-term prognosis of cirrhosis.Hepatology. 2003; 37: 902-908Crossref PubMed Scopus (396) Google Scholar The findings of that study suggest that target HVPG reductions are associated not only with reduced rebleeding, but also with improved survival and decreased risk of other complications of portal hypertension. Furthermore, available evidence indicates that haemodynamic response also correlates with clinical response in primary prophylaxis, as first shown by Groszmann and co-workers2Groszmann RJ Bosch J Grace ND et al.Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage.Gastroenterology. 1990; 99: 1401-1407Abstract PubMed Google Scholar and confirmed by Escorsell and colleagues.3Merkel C Bolognesi M Sacerdoti D et al.The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis.Hepatology. 2000; 32: 930-934Crossref PubMed Scopus (206) Google Scholar Overall, these studies include more than 400 patients; not a small number.Thalheimer and colleagues have read meticulously the data on haemodynamic response, but apparently not so thoroughly the rest of our review. They do not go beyond our discussion with their suggestion that further assessment of the clinical validity of HVPG measurements is essential, since we noted the same. Also, their comment on the need for early assessment of HVPG response seems redundant, since we clearly stated that the second HVPG measurement should preferably be done within 2 weeks of the first.The pathophysiological basis for these haemodynamic targets is simple: 12 mm Hg is the minimum threshold for clinical complications from portal hypertension; for the 20% reduction in HVPG, one should remember that variceal wall tension (the key variable in variceal rupture) is affected not only by portal pressure, but also by variceal radius and wall thickness. Hence, wall tension values at risk of variceal rupture can be reached at different absolute portal pressures. Accordingly, absolute falls in HVPG are associated with varying reductions in wall tension, whereas a 20% HVPG decrease is always associated with a similar fall in wall tension (actually, by a greater fall, because propranolol, for example, reduces more wall tension than variceal pressure, since it diminishes also variceal volume and radius).4Escorsell A Bordas JM Feu F Garcia-Pagán JC Gines A Bosch J Endoscopic assessment of variceal volume and wall tension in cirrhotic patients: effects of pharmacological therapy.Gastroenterology. 1997; 113: 1640-1646Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar Authors' reply Sir—We thank Ulrich Thalheimer and colleagues for their correspondence. However, several of their points deserve comment. The different bleeding risk observed in prevention of first variceal bleeding versus rebleeding is well known, unquestionable, and out of the scope of our review, the aim of which was to assess whether pharmacological therapy is as effective as endoscopic treatments in prevention of rebleeding. In this context, we emphasised that drug therapy is especially effective when it results in a favourable haemodynamic response. We recognise that the studies by Escorsell and Bureau and their colleagues included patients in both primary and secondary prevention of variceal bleeding. However, in the first study, findings in primary and secondary prevention were almost identical (probably because of selection of patients with large varices) and, in the second, limiting data to prevention of rebleeding, rebleeding rates were 88% in non-responders versus 33% in responders. Therefore, our assertion that responders on HVPG criteria do better than non-responders is well supported. The data reported for Villanueva and colleagues' study were obtained via personal communication with Càndid Villanueva, and the reason for not quoting McCormick and co-workers' study was indeed that suggested by Thalheimer and colleagues. After publication of our review, another study analysed the prognostic value of HVPG response.1Abraldes JG Tarantino I Turnes J Garcia-Pagan J Rodes J Bosch J Hemodynamic response to pharmacologic treatment of portal hypertension and long-term prognosis of cirrhosis.Hepatology. 2003; 37: 902-908Crossref PubMed Scopus (396) Google Scholar The findings of that study suggest that target HVPG reductions are associated not only with reduced rebleeding, but also with improved survival and decreased risk of other complications of portal hypertension. Furthermore, available evidence indicates that haemodynamic response also correlates with clinical response in primary prophylaxis, as first shown by Groszmann and co-workers2Groszmann RJ Bosch J Grace ND et al.Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage.Gastroenterology. 1990; 99: 1401-1407Abstract PubMed Google Scholar and confirmed by Escorsell and colleagues.3Merkel C Bolognesi M Sacerdoti D et al.The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis.Hepatology. 2000; 32: 930-934Crossref PubMed Scopus (206) Google Scholar Overall, these studies include more than 400 patients; not a small number. Thalheimer and colleagues have read meticulously the data on haemodynamic response, but apparently not so thoroughly the rest of our review. They do not go beyond our discussion with their suggestion that further assessment of the clinical validity of HVPG measurements is essential, since we noted the same. Also, their comment on the need for early assessment of HVPG response seems redundant, since we clearly stated that the second HVPG measurement should preferably be done within 2 weeks of the first. The pathophysiological basis for these haemodynamic targets is simple: 12 mm Hg is the minimum threshold for clinical complications from portal hypertension; for the 20% reduction in HVPG, one should remember that variceal wall tension (the key variable in variceal rupture) is affected not only by portal pressure, but also by variceal radius and wall thickness. Hence, wall tension values at risk of variceal rupture can be reached at different absolute portal pressures. Accordingly, absolute falls in HVPG are associated with varying reductions in wall tension, whereas a 20% HVPG decrease is always associated with a similar fall in wall tension (actually, by a greater fall, because propranolol, for example, reduces more wall tension than variceal pressure, since it diminishes also variceal volume and radius).4Escorsell A Bordas JM Feu F Garcia-Pagán JC Gines A Bosch J Endoscopic assessment of variceal volume and wall tension in cirrhotic patients: effects of pharmacological therapy.Gastroenterology. 1997; 113: 1640-1646Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar Prevention of variceal rebleedingThe topic of prevention of variceal rebleeding discussed by Jaime Bosch and Juan Carlos García-Pagán (March 15, p 952)1 is an important one. Full-Text PDF