Alimentary Pharmacology and Therapeutics Invited Editorials
Editorial: chronic liver disease and deaths from peptic ulcer bleeding D. E. Sigounas & I. D. Penman Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, UK. E-mail: [email protected] doi:10.1111/apt.13119
The impact of cirrhosis on mortality from peptic ulcer (PU) bleeding has been highlighted recently. Most, if not all studies,1 including a meta-analysis,2, 3 have shown significantly greater mortality in patients with chronic liver disease (CLD). Holland-Bill et al. provide further evidence supporting this observation.4 Using the Danish National Registries for patients and prescriptions, they included over 20 000 patients with an index episode of PU bleeding and compared 90-day mortality in those with or without cirrhosis or noncirrhotic CLD. Adjusting for other factors, cirrhosis was associated with a more than doubling of the risk of dying from PU bleeding, up to 25.3%. Noncirrhotic CLD had a similar but less prominent effect. The authors should be congratulated for their rigour in analysing data from their national registries: large numbers, complete data with only two patients lost to follow-up, assessment for confounding factors, good sensitivity analysis and importantly, checking of the proportional hazards assumption all contributed to strengthening the validity of the findings. However, failure to consider all potential confounding factors remains
Editorial: chronic liver disease and deaths from peptic ulcer bleeding – authors’ reply L. Holland-Bill*, C. F. Christiansen*, H. Gammelager*,† & H. T. Sørensen* *Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. † Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark. E-mail: [email protected] doi:10.1111/apt.13134
We thank Drs Sigounas and Penman for their interest in our paper on the impact of chronic liver disease on mortality from peptic ulcer bleeding.1, 2 Aliment Pharmacol Ther 2015; 41: 785–788 ª 2015 John Wiley & Sons Ltd
possible. For example, almost 20% of patients with a diagnosis of PU bleeding were so labelled without undergoing endoscopy for confirmation or treatment. Furthermore, treatment allocation between groups of patients might be influenced by factors that are poorly documented and difficult to discern in this type of study. That patients with cirrhosis are at higher risk of dying from PU bleeding seems in little doubt, but improving outcomes for these patients demand an understanding of underlying mechanisms. The authors suggest it is liverspecific rather than a reflection of overall comorbidity, but whether it is the severity of the bleeding, sepsis, multiorgan failure or even possibly differential use of transfusion of blood products in this group needs further study.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Rudler M, Rousseau G, Benosman H, et al. Peptic ulcer bleeding in patients with or without cirrhosis: different diseases but the same prognosis? Aliment Pharmacol Ther 2012; 36: 166–72. 2. Leontiadis GI, Molloy-Bland M, Moayyedi P, Howden CW. Effect of comorbidity on mortality in patients with peptic ulcer bleeding: systematic review and meta-analysis. Am J Gastroenterol 2013; 108: 331–45. 3. Venkatesh PG, Parasa S, Njei B, Sanaka MR, Navaneethan U. Increased mortality with peptic ulcer bleeding in patients with both compensated and decompensated cirrhosis. Gastrointest Endosc 2014; 79: 605–14. 4. Holland-Bill L, Christiansen CF, Gammelager H, et al. Chronic liver disease and 90-day mortality in 21 359 patients following peptic ulcer bleeding – a Nationwide Cohort Study. Aliment Pharmacol Ther 2015; 41: 564–72.
Referring to the 20% of patients without endoscopic or surgical confirmation or treatment, Drs Sigounas and Penman raise an important question concerning the influence of potential misclassification of peptic ulcer bleeding on our results. We agree that such misclassification may attenuate our risk estimates. To evaluate the magnitude of such potential bias, we performed a sensitivity analysis where we restricted to patients with a concurrent surgical or gastroscopy procedure code during the peptic ulcer bleeding-associated hospitalisation. We found that such misclassification could not explain the higher mortality rate observed among patients with chronic liver disease. As expected, we may have slightly underestimated the true effect of chronic liver disease, as the restriction resulted in increase in adjusted mortality 787
Editorial: chronic liver disease and deaths from peptic ulcer bleeding D. E. Sigounas & I. D. Penman Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, UK. E-mail: [email protected] doi:10.1111/apt.13119
The impact of cirrhosis on mortality from peptic ulcer (PU) bleeding has been highlighted recently. Most, if not all studies,1 including a meta-analysis,2, 3 have shown significantly greater mortality in patients with chronic liver disease (CLD). Holland-Bill et al. provide further evidence supporting this observation.4 Using the Danish National Registries for patients and prescriptions, they included over 20 000 patients with an index episode of PU bleeding and compared 90-day mortality in those with or without cirrhosis or noncirrhotic CLD. Adjusting for other factors, cirrhosis was associated with a more than doubling of the risk of dying from PU bleeding, up to 25.3%. Noncirrhotic CLD had a similar but less prominent effect. The authors should be congratulated for their rigour in analysing data from their national registries: large numbers, complete data with only two patients lost to follow-up, assessment for confounding factors, good sensitivity analysis and importantly, checking of the proportional hazards assumption all contributed to strengthening the validity of the findings. However, failure to consider all potential confounding factors remains
Editorial: chronic liver disease and deaths from peptic ulcer bleeding – authors’ reply L. Holland-Bill*, C. F. Christiansen*, H. Gammelager*,† & H. T. Sørensen* *Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. † Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark. E-mail: [email protected] doi:10.1111/apt.13134
We thank Drs Sigounas and Penman for their interest in our paper on the impact of chronic liver disease on mortality from peptic ulcer bleeding.1, 2 Aliment Pharmacol Ther 2015; 41: 785–788 ª 2015 John Wiley & Sons Ltd
possible. For example, almost 20% of patients with a diagnosis of PU bleeding were so labelled without undergoing endoscopy for confirmation or treatment. Furthermore, treatment allocation between groups of patients might be influenced by factors that are poorly documented and difficult to discern in this type of study. That patients with cirrhosis are at higher risk of dying from PU bleeding seems in little doubt, but improving outcomes for these patients demand an understanding of underlying mechanisms. The authors suggest it is liverspecific rather than a reflection of overall comorbidity, but whether it is the severity of the bleeding, sepsis, multiorgan failure or even possibly differential use of transfusion of blood products in this group needs further study.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Rudler M, Rousseau G, Benosman H, et al. Peptic ulcer bleeding in patients with or without cirrhosis: different diseases but the same prognosis? Aliment Pharmacol Ther 2012; 36: 166–72. 2. Leontiadis GI, Molloy-Bland M, Moayyedi P, Howden CW. Effect of comorbidity on mortality in patients with peptic ulcer bleeding: systematic review and meta-analysis. Am J Gastroenterol 2013; 108: 331–45. 3. Venkatesh PG, Parasa S, Njei B, Sanaka MR, Navaneethan U. Increased mortality with peptic ulcer bleeding in patients with both compensated and decompensated cirrhosis. Gastrointest Endosc 2014; 79: 605–14. 4. Holland-Bill L, Christiansen CF, Gammelager H, et al. Chronic liver disease and 90-day mortality in 21 359 patients following peptic ulcer bleeding – a Nationwide Cohort Study. Aliment Pharmacol Ther 2015; 41: 564–72.
Referring to the 20% of patients without endoscopic or surgical confirmation or treatment, Drs Sigounas and Penman raise an important question concerning the influence of potential misclassification of peptic ulcer bleeding on our results. We agree that such misclassification may attenuate our risk estimates. To evaluate the magnitude of such potential bias, we performed a sensitivity analysis where we restricted to patients with a concurrent surgical or gastroscopy procedure code during the peptic ulcer bleeding-associated hospitalisation. We found that such misclassification could not explain the higher mortality rate observed among patients with chronic liver disease. As expected, we may have slightly underestimated the true effect of chronic liver disease, as the restriction resulted in increase in adjusted mortality 787
