EDITORIALS 8. Aubert J, Begriche K, Knockaert L, et al. Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol 2011;35:630–637. 9. Alla V, Bonkovsky HL. Iron in non-hemochromatotic liver disorders. Semin Liver Dis 2005;25:461–472. 10. Caballes FR, Sendi H, Bonkovsky HL. Hepatitis C, porphyria cutanea tarda, and liver iron: an update. Liver Intl 2012;32:880–893. 11. Russ TC, Kivimäki M, Morling JR, et al. Association between psychological distress and liver disease mortality: a meta-analysis of individual study participants. Gastroenterology 2015;148:958–966. 12. Russ TC, Stamatakis E, Hamer M, et al. Association between psychological distress and mortality: individual participant pooled analysis of 10 prospective cohort studies. BMJ 2012;345:e4933. 13. Russ TC, Hamer M, Stamatakis E, et al. Psychological distress as a risk factor for dementia death. Arch Intern Med 2011;171:1858–1859. 14. Batty GD, Russ TC, Stamatakis E, et al. Psychological distress and risk of peripheral vascular disease, abdominal aortic aneurysm and hear failure: Pooling of sixteen cohort studies. Atherosclerosis 2014;236: 385–388. 15. Aalto AM, Elovainio M, Kivimaki M, et al. The Beck Depression Inventory and General Health Questionnaire as measures of depression in the general population: a validation study using the Composite International
16.
17.
18.
19.
Diagnostic Interview as the gold standard. Psychiatry Res 2012;197:163–171. Facchini FS, Hua NW, Stoohs RA. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of non-alcoholic fatty liver disease. Gastroenterology 2002;122:931–939. Fernandez-Real JM, Mano M. Effects of iron overload on chronic metabolic diseases. Lancet—Diabetes-Endocrinology 2013;30:S2213–S8587. Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015;61:506–514. Gandhi CR, Cahillet JR, Nalesnick MA, et al. Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice. Gastroenterology 2015;148:379–391.
Reprint requests Address requests for reprints to: Herbert L. Bonkovsky, MD, Professor of Medicine, Chief of Hepatology, Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine, Nutrition Building, Room E-112, 1 Medical Center Blvd, Winston-Salem, North Carolina 27157. e-mail: [email protected].
Conflicts of interest The authors disclose no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2015.03.024
Decreasing Mortality in Patients Hospitalized With Cirrhosis See “Decreasing mortality among patients hospitalized with cirrhosis in the United States from 2002 through 2010,” by Schmidt ML, Barritt AS, Orman ES, et al on page 967.
C
irrhosis of the liver is a common condition. Approximately 700,000 Americans have been diagnosed with cirrhosis.1 Hospital discharges for cirrhosis in the United States increased by 30% from 2006 to 2011.2 Cirrhosis is the second most common cause of digestive disease–related mortality, and contributes the greatest number of years of potential life lost.3,4 Within this context, cirrhosis constitutes a significant health problem in the United States, yet its epidemiology is poorly understood. In this issue of Gastroenterology, Schmidt et al5 present the temporal trends in the risk of in-hospital mortality among patients with cirrhosis. For this study, the authors used the Healthcare Cost and Utilization Project’s National Inpatient Sample (HCUP NIS) and analyzed >780,000 hospitalizations of patients with cirrhosis from 2002 to 2010. To provide an internal anchor, the authors compared the trends in in-hospital mortality among patients with cirrhosis with corresponding time trends in 2 concurrent groups of
patients hospitalized during the same timeframe: patients who did not have cirrhosis (negative controls) and those with congestive heart failure (positive controls). The findings were remarkable (albeit not completely unexpected). Despite a steady increase in the number of cirrhosis hospitalizations, in-hospital mortality in patients with cirrhosis decreased from 9.1% in 2002 to 5.4% in 2010, representing a 40% decline over time. Importantly, this decline occurred despite increasing age and comorbidities in patients with cirrhosis and was consistent across all age groups. Similarly, mortality fell for all cirrhosis patients regardless of the nature of cirrhosis complications. The only exception was sepsis; the risk of death actually increased over time among cirrhosis patients who had sepsis during the in-patient stay (22% higher in 2010 compared with 2002). Overall, the relative decrease in mortality was significantly greater for patients with cirrhosis compared with patients who did not have cirrhosis. However, mortality decreased to the same extent in patients with cirrhosis and those with heart failure.5 This study provides one of the first data on the trends in overall in-hospital mortality among a large group of cirrhosis patients who were treated in U.S. hospitals. The substantial improvement in survival is encouraging for patients and their clinicians. Several other reports found similar trends in
897
EDITORIALS patient outcomes,6–11 providing convergent validity to the findings reported by Schmidt et al.5 However, most of the previous studies were limited to patients with specific cirrhosis complications, reported data from single centers, or did not include patients cared for in the U.S. hospitals. In these regards, the study by Schmidt et al fills in a significant gap in our understanding of the current burden of cirrhosis in the United States. The main conclusion of this study is unequivocal: inpatient mortality in cirrhosis patients has declined in the last decade. However, the explanations underlying the observed trend are less clear, and are likely multifactorial. For example, as discussed by the authors, treatment effectiveness might have played a role. There have been many advances in the medical management of patients with cirrhosis, particularly for cirrhosis complications that require in-patient admission.12,13 The resulting clinical practice changes could have resulted in the improved survival. However, it is not possible to establish conclusively a causal relationship between improving cirrhosis-specific care and decreasing in-hospital mortality from this study. For example, with the exception of timely paracentesis, the study did not find any associations between receipt of cirrhosis-specific interventions and declining mortality.5 It is plausible (and perhaps more likely) that the decrease in cirrhosis in-hospital mortality actually represents an improvement in the overall diagnostic and therapeutic care in general and intensive/critical care in particular. Several studies have reported a steady improvement in the survival of patients (with and without cirrhosis) requiring treatment in intensive care setting.14,15 The parallel decrease in mortality among patients admitted for heart failure in this study provides support for this notion. Others have reported similar temporal decreases in in-hospital mortality in patients admitted for chronic obstructive pulmonary disease, stroke, and upper gastrointestinal bleeding,16–19 suggesting that the care of all in-patients, particularly those with serious medical conditions (including those with cirrhosis), might have improved over time. It is also difficult to construe the current data as evidence that overall survival in patients with cirrhosis has improved. The study was based on information from hospital discharge records and could not capture fully the burden of overall (such as 30-day, 90-day, or 1-year) mortality in patients with cirrhosis. The increasing emphasis on reducing duration of hospital stay might have confounded trends in outcomes. For example, it is possible that, although in-hospital mortality decreased over time, more and more patients were discharged earlier (and this is suggested by the decline in the duration of stay in the current study); some might have died outside the hospital, artificially reducing the in-hospital mortality statistic. Coding practices may also have changed over time. Similarly, the wide availability of noninvasive tests for liver fibrosis could have resulted in more patients being identified earlier in their disease course, resulting in case mix differences. Unfortunately, the HCUP NIS does not capture accurately liver disease severity and the authors could not 898
test for the effect of changing liver disease severity on improving survival. Notwithstanding these caveats, the study by Schmidt et al has significant implications.5 Because most cirrhosis patients require hospitalization within 5 years of diagnosis,9 reliable estimates are needed to better understand and track the risk and outcomes of cirrhosis admissions. Schmidt et al provide these estimates. More important, their findings identify a large disparity in the absolute rates of cirrhosis and heart failure mortality. Specifically, the absolute risk of death was much higher in patients with cirrhosis than in patients with heart failure throughout the study years. For example, in 2010, the in-hospital mortality was 5.4% in patients with cirrhosis compared with 1.5% for patients with heart failure. This difference may represent a higher disease burden in patients with cirrhosis, but may also stem from the wide chasm in the established (and evidence-based) processes, protocols, and care pathways targeting patients with heart failure versus for those with cirrhosis.20,21 Within this context, data from the current study may serve as a much-needed impetus for clinicians, researchers, and policymakers to work toward defining an effective (and sustainable) management strategy that can improve outcomes for (both in-hospital and ambulatory) patients with cirrhosis. Better management of bacterial infections may represent a high-yield and potentially modifiable target for these initiatives. Not surprisingly, concurrent sepsis increased mortality significantly in patients with cirrhosis in this study. Indeed, the highest independent risk for death was seen with sepsis (relative risk, 4.70; 95% CI, 4.61-4.79), and this risk increased over time.5 Infections are the leading cause of death in patients with cirrhosis,22,23 and this remains the case despite advances in critical care as well as the use of prophylactic antibiotics for cirrhosis patients at risk for infections. Recent data also suggest an evolution in the epidemiology of infections in patients with cirrhosis. Results from a prospective, multicenter cohort study of hospitalized patients with cirrhosis show that most infections in patients with cirrhosis were health care associated (71%), followed by nosocomial (15%) and community-acquired (14%) infections.24 In this study, infections were classified as community acquired if they were diagnosed within 48 hours of admission without hospitalizations in the previous 6 months; health care associated if they were diagnosed within 48 hours of admission in patients with hospitalization for 2 days in the previous 6 months; and nosocomial if the infection was diagnosed beyond 48 hours of admission. Second infections, seen in approximately 25% of these patients, significantly increased the risk of deaths, and were largely preventable.24 Although the best approach to reducing sepsis-related mortality in cirrhosis patients remains undefined, early prevention of second infections may be 1 way to reduce this risk. Existing and future efforts should focus on stemming this rising tide of sepsis-related morbidity and mortality in in-patients with cirrhosis.24,25 In conclusion, the finding that patients with cirrhosis are far more likely to leave the hospital alive now than 10
EDITORIALS years ago is welcome news. Yet, there remains much room for improvement. Patients with cirrhosis are 3-4 times more likely to die as in-patients than those with heart failure. The study highlights the need for systematic efforts targeted at reducing cirrhosis related in-hospital mortality while reaffirming the subgroup (with sepsis) that needs them the most because of their high risk of short-term complications. FASIHA KANWAL Division of Gastroenterology and Hepatology Baylor College of Medicine Houston, Texas
References 1. Scaglione S, Kliethermes S, Cao G, et al. The epidemiology of cirrhosis in the United States: a populationbased study. J Clin Gastroenterol 2014 Oct 8 [Epub ahead of print]. 2. Kanwal F, Volk M, Singal A, et al. Improving quality of health care for patients with cirrhosis. Gastroenterology 2014;147:1204–1207. 3. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States part I: overall and upper gastrointestinal diseases. Gastroenterology 2009;136:376–386. 4. Everhart JE, ed. The burden of digestive diseases in the United States. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2008. NIH Publication No. 09–6443. Available at: http://www.niddk.nih.gov/about-niddk/ strategic-plans-reports/Pages/burden-digestive-diseasesin-united-states-report.aspx#CHAPTER25. Accessed March 2015. 5. Schmidt M, Barritt AS, Orman ES, et al. Decreasing mortality among patients hospitalized with cirrhosis in the United States from 2002 through 2010. Gastroenterology 2015;148:967–977. 6. Stepanova M, Mishra A, Venkatesan C, et al. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clin Gastroenterol Hepatol 2012;10:1034–1041. 7. Singal AK, Salameh H, Kamath PS. Prevalence and inhospital mortality trends of infections among patients with cirrhosis: a nationwide study of hospitalized patients in the United States. Aliment Pharmacol Ther 2014; 40:105–112. 8. Mishra A, Otgonsuren M, Venkatesan C, et al. The inpatient economic and mortality impact of hepatocellular carcinoma from 2005 to 2009: analysis of the US nationwide inpatient sample. Liver Int 2013;33:1281–1286. 9. Ratib S, Fleming KM, Crooks CJ, et al. 1 and 5 year survival estimates for people with cirrhosis of the liver in England, 1998-2009: a large population study. J Hepatol 2014 Feb;60:282–289. 10. Cheung AC, Rabie RN, Marquez M, et al. The clinical presentation of decompensated cirrhosis: a comparison of two time periods. Hepatology 2013;58:1197A.
11. Vergara M, Cleries M, Vela E, et al. Hospital mortality over time in patients with specific complications of cirrhosis. Liver Int 2013;33:828–833. 12. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46:922–938. 13. Runyon BA, American Association for the Study of Liver Diseases. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology 2013;57: 1651–1653. 14. Galbois A, Aegerter P, Martel-Samb P, et al. Collège des Utilisateurs des Bases des données en Réanimation (CUB-Réa) Group. Improved prognosis of septic shock in patients with cirrhosis: a multicenter study*. Crit Care Med 2014;42:1666–1675. 15. Zimmerman JE, Kramer AA, Knaus WA. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care 2013;17:R81. 16. Chen J, Dharmarajan K, Wang Y, Krumholz HM. National trends in heart failure hospital stay rates, 2001 to 2009. J Am Coll Cardiol 2013;61:1078–1088. 17. Ovbiagele B, Markovic D, Towfighi A. Recent age- and gender-specific trends in mortality during stroke hospitalization in the United States. Int J Stroke 2011; 6:379–387. 18. Taefi A, Cho WK, Nouraie M. Decreasing trend of upper gastrointestinal bleeding mortality risk over three decades. Dig Dis Sci 2013;58:2940–2948. 19. Supkal R, Jinjuvadia C, Liangpunsakul S, et al. Trends in outcomes, hospitalization costs, financial burden, and mortality for chronic obstructive pulmonary disease. Comparative effectiveness: treatments, research, and practice [May 1, 2014], A3721–A3721. Available at: http:// www.atsjournals.org/doi/abs/10.1164/ajrccm-conference. 2014.189.1_MeetingAbstracts.A3721. Accessed March 2015. 20. Heidenreich PA, Lewis WR, LaBresh KA, et al. Hospital performance recognition with the Get With The Guidelines Program and mortality for acute myocardial infarction and heart failure. Am Heart J 2009;158: 546–553. 21. Peterson PN, Rumsfeld JS, Liang L, et al. American Heart Association Get With The Guidelines-Heart Failure Program. Treatment and risk in heart failure: gaps in evidence or quality? Circ Cardiovasc Qual Outcomes 2010; 3:309–315. 22. Sargenti K, Prytz H, Nilsson E, et al. Predictors of mortality among patients with compensated and decompensated liver cirrhosis: the role of bacterial infections and infection-related acute-on-chronic liver failure. Scand J Gastroenterol 2015;19:1–9. 23. Tandon P, Delisle A, Topal JE, et al. High prevalence of antibiotic-resistant bacterial infections among patients with cirrhosis at a US liver center. Clin Gastroenterol Hepatol 2012;10:1291–1298. 24. Bajaj JS, O’Leary JG, Reddy KR, et al. North American Consortium for the Study of End-Stage Liver Disease
899
EDITORIALS (NACSELD). Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American consortium for the study of end-stage liver disease (NACSELD) experience. Hepatology 2012; 56:2328–2335. 25. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 2014;60: 1310–1324.
900
Reprint requests Address requests for reprints to: Fasiha Kanwal, Division of Gastroenterology and Hepatology, Baylor College of Medicine, 2002 Holcombe Boulevard (152), Houston, Texas 77030. e-mail: [email protected].
Conflicts of interest The author discloses no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2015.03.023
16.
17.
18.
19.
Diagnostic Interview as the gold standard. Psychiatry Res 2012;197:163–171. Facchini FS, Hua NW, Stoohs RA. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of non-alcoholic fatty liver disease. Gastroenterology 2002;122:931–939. Fernandez-Real JM, Mano M. Effects of iron overload on chronic metabolic diseases. Lancet—Diabetes-Endocrinology 2013;30:S2213–S8587. Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015;61:506–514. Gandhi CR, Cahillet JR, Nalesnick MA, et al. Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice. Gastroenterology 2015;148:379–391.
Reprint requests Address requests for reprints to: Herbert L. Bonkovsky, MD, Professor of Medicine, Chief of Hepatology, Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine, Nutrition Building, Room E-112, 1 Medical Center Blvd, Winston-Salem, North Carolina 27157. e-mail: [email protected].
Conflicts of interest The authors disclose no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2015.03.024
Decreasing Mortality in Patients Hospitalized With Cirrhosis See “Decreasing mortality among patients hospitalized with cirrhosis in the United States from 2002 through 2010,” by Schmidt ML, Barritt AS, Orman ES, et al on page 967.
C
irrhosis of the liver is a common condition. Approximately 700,000 Americans have been diagnosed with cirrhosis.1 Hospital discharges for cirrhosis in the United States increased by 30% from 2006 to 2011.2 Cirrhosis is the second most common cause of digestive disease–related mortality, and contributes the greatest number of years of potential life lost.3,4 Within this context, cirrhosis constitutes a significant health problem in the United States, yet its epidemiology is poorly understood. In this issue of Gastroenterology, Schmidt et al5 present the temporal trends in the risk of in-hospital mortality among patients with cirrhosis. For this study, the authors used the Healthcare Cost and Utilization Project’s National Inpatient Sample (HCUP NIS) and analyzed >780,000 hospitalizations of patients with cirrhosis from 2002 to 2010. To provide an internal anchor, the authors compared the trends in in-hospital mortality among patients with cirrhosis with corresponding time trends in 2 concurrent groups of
patients hospitalized during the same timeframe: patients who did not have cirrhosis (negative controls) and those with congestive heart failure (positive controls). The findings were remarkable (albeit not completely unexpected). Despite a steady increase in the number of cirrhosis hospitalizations, in-hospital mortality in patients with cirrhosis decreased from 9.1% in 2002 to 5.4% in 2010, representing a 40% decline over time. Importantly, this decline occurred despite increasing age and comorbidities in patients with cirrhosis and was consistent across all age groups. Similarly, mortality fell for all cirrhosis patients regardless of the nature of cirrhosis complications. The only exception was sepsis; the risk of death actually increased over time among cirrhosis patients who had sepsis during the in-patient stay (22% higher in 2010 compared with 2002). Overall, the relative decrease in mortality was significantly greater for patients with cirrhosis compared with patients who did not have cirrhosis. However, mortality decreased to the same extent in patients with cirrhosis and those with heart failure.5 This study provides one of the first data on the trends in overall in-hospital mortality among a large group of cirrhosis patients who were treated in U.S. hospitals. The substantial improvement in survival is encouraging for patients and their clinicians. Several other reports found similar trends in
897
EDITORIALS patient outcomes,6–11 providing convergent validity to the findings reported by Schmidt et al.5 However, most of the previous studies were limited to patients with specific cirrhosis complications, reported data from single centers, or did not include patients cared for in the U.S. hospitals. In these regards, the study by Schmidt et al fills in a significant gap in our understanding of the current burden of cirrhosis in the United States. The main conclusion of this study is unequivocal: inpatient mortality in cirrhosis patients has declined in the last decade. However, the explanations underlying the observed trend are less clear, and are likely multifactorial. For example, as discussed by the authors, treatment effectiveness might have played a role. There have been many advances in the medical management of patients with cirrhosis, particularly for cirrhosis complications that require in-patient admission.12,13 The resulting clinical practice changes could have resulted in the improved survival. However, it is not possible to establish conclusively a causal relationship between improving cirrhosis-specific care and decreasing in-hospital mortality from this study. For example, with the exception of timely paracentesis, the study did not find any associations between receipt of cirrhosis-specific interventions and declining mortality.5 It is plausible (and perhaps more likely) that the decrease in cirrhosis in-hospital mortality actually represents an improvement in the overall diagnostic and therapeutic care in general and intensive/critical care in particular. Several studies have reported a steady improvement in the survival of patients (with and without cirrhosis) requiring treatment in intensive care setting.14,15 The parallel decrease in mortality among patients admitted for heart failure in this study provides support for this notion. Others have reported similar temporal decreases in in-hospital mortality in patients admitted for chronic obstructive pulmonary disease, stroke, and upper gastrointestinal bleeding,16–19 suggesting that the care of all in-patients, particularly those with serious medical conditions (including those with cirrhosis), might have improved over time. It is also difficult to construe the current data as evidence that overall survival in patients with cirrhosis has improved. The study was based on information from hospital discharge records and could not capture fully the burden of overall (such as 30-day, 90-day, or 1-year) mortality in patients with cirrhosis. The increasing emphasis on reducing duration of hospital stay might have confounded trends in outcomes. For example, it is possible that, although in-hospital mortality decreased over time, more and more patients were discharged earlier (and this is suggested by the decline in the duration of stay in the current study); some might have died outside the hospital, artificially reducing the in-hospital mortality statistic. Coding practices may also have changed over time. Similarly, the wide availability of noninvasive tests for liver fibrosis could have resulted in more patients being identified earlier in their disease course, resulting in case mix differences. Unfortunately, the HCUP NIS does not capture accurately liver disease severity and the authors could not 898
test for the effect of changing liver disease severity on improving survival. Notwithstanding these caveats, the study by Schmidt et al has significant implications.5 Because most cirrhosis patients require hospitalization within 5 years of diagnosis,9 reliable estimates are needed to better understand and track the risk and outcomes of cirrhosis admissions. Schmidt et al provide these estimates. More important, their findings identify a large disparity in the absolute rates of cirrhosis and heart failure mortality. Specifically, the absolute risk of death was much higher in patients with cirrhosis than in patients with heart failure throughout the study years. For example, in 2010, the in-hospital mortality was 5.4% in patients with cirrhosis compared with 1.5% for patients with heart failure. This difference may represent a higher disease burden in patients with cirrhosis, but may also stem from the wide chasm in the established (and evidence-based) processes, protocols, and care pathways targeting patients with heart failure versus for those with cirrhosis.20,21 Within this context, data from the current study may serve as a much-needed impetus for clinicians, researchers, and policymakers to work toward defining an effective (and sustainable) management strategy that can improve outcomes for (both in-hospital and ambulatory) patients with cirrhosis. Better management of bacterial infections may represent a high-yield and potentially modifiable target for these initiatives. Not surprisingly, concurrent sepsis increased mortality significantly in patients with cirrhosis in this study. Indeed, the highest independent risk for death was seen with sepsis (relative risk, 4.70; 95% CI, 4.61-4.79), and this risk increased over time.5 Infections are the leading cause of death in patients with cirrhosis,22,23 and this remains the case despite advances in critical care as well as the use of prophylactic antibiotics for cirrhosis patients at risk for infections. Recent data also suggest an evolution in the epidemiology of infections in patients with cirrhosis. Results from a prospective, multicenter cohort study of hospitalized patients with cirrhosis show that most infections in patients with cirrhosis were health care associated (71%), followed by nosocomial (15%) and community-acquired (14%) infections.24 In this study, infections were classified as community acquired if they were diagnosed within 48 hours of admission without hospitalizations in the previous 6 months; health care associated if they were diagnosed within 48 hours of admission in patients with hospitalization for 2 days in the previous 6 months; and nosocomial if the infection was diagnosed beyond 48 hours of admission. Second infections, seen in approximately 25% of these patients, significantly increased the risk of deaths, and were largely preventable.24 Although the best approach to reducing sepsis-related mortality in cirrhosis patients remains undefined, early prevention of second infections may be 1 way to reduce this risk. Existing and future efforts should focus on stemming this rising tide of sepsis-related morbidity and mortality in in-patients with cirrhosis.24,25 In conclusion, the finding that patients with cirrhosis are far more likely to leave the hospital alive now than 10
EDITORIALS years ago is welcome news. Yet, there remains much room for improvement. Patients with cirrhosis are 3-4 times more likely to die as in-patients than those with heart failure. The study highlights the need for systematic efforts targeted at reducing cirrhosis related in-hospital mortality while reaffirming the subgroup (with sepsis) that needs them the most because of their high risk of short-term complications. FASIHA KANWAL Division of Gastroenterology and Hepatology Baylor College of Medicine Houston, Texas
References 1. Scaglione S, Kliethermes S, Cao G, et al. The epidemiology of cirrhosis in the United States: a populationbased study. J Clin Gastroenterol 2014 Oct 8 [Epub ahead of print]. 2. Kanwal F, Volk M, Singal A, et al. Improving quality of health care for patients with cirrhosis. Gastroenterology 2014;147:1204–1207. 3. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States part I: overall and upper gastrointestinal diseases. Gastroenterology 2009;136:376–386. 4. Everhart JE, ed. The burden of digestive diseases in the United States. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2008. NIH Publication No. 09–6443. Available at: http://www.niddk.nih.gov/about-niddk/ strategic-plans-reports/Pages/burden-digestive-diseasesin-united-states-report.aspx#CHAPTER25. Accessed March 2015. 5. Schmidt M, Barritt AS, Orman ES, et al. Decreasing mortality among patients hospitalized with cirrhosis in the United States from 2002 through 2010. Gastroenterology 2015;148:967–977. 6. Stepanova M, Mishra A, Venkatesan C, et al. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clin Gastroenterol Hepatol 2012;10:1034–1041. 7. Singal AK, Salameh H, Kamath PS. Prevalence and inhospital mortality trends of infections among patients with cirrhosis: a nationwide study of hospitalized patients in the United States. Aliment Pharmacol Ther 2014; 40:105–112. 8. Mishra A, Otgonsuren M, Venkatesan C, et al. The inpatient economic and mortality impact of hepatocellular carcinoma from 2005 to 2009: analysis of the US nationwide inpatient sample. Liver Int 2013;33:1281–1286. 9. Ratib S, Fleming KM, Crooks CJ, et al. 1 and 5 year survival estimates for people with cirrhosis of the liver in England, 1998-2009: a large population study. J Hepatol 2014 Feb;60:282–289. 10. Cheung AC, Rabie RN, Marquez M, et al. The clinical presentation of decompensated cirrhosis: a comparison of two time periods. Hepatology 2013;58:1197A.
11. Vergara M, Cleries M, Vela E, et al. Hospital mortality over time in patients with specific complications of cirrhosis. Liver Int 2013;33:828–833. 12. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46:922–938. 13. Runyon BA, American Association for the Study of Liver Diseases. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology 2013;57: 1651–1653. 14. Galbois A, Aegerter P, Martel-Samb P, et al. Collège des Utilisateurs des Bases des données en Réanimation (CUB-Réa) Group. Improved prognosis of septic shock in patients with cirrhosis: a multicenter study*. Crit Care Med 2014;42:1666–1675. 15. Zimmerman JE, Kramer AA, Knaus WA. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care 2013;17:R81. 16. Chen J, Dharmarajan K, Wang Y, Krumholz HM. National trends in heart failure hospital stay rates, 2001 to 2009. J Am Coll Cardiol 2013;61:1078–1088. 17. Ovbiagele B, Markovic D, Towfighi A. Recent age- and gender-specific trends in mortality during stroke hospitalization in the United States. Int J Stroke 2011; 6:379–387. 18. Taefi A, Cho WK, Nouraie M. Decreasing trend of upper gastrointestinal bleeding mortality risk over three decades. Dig Dis Sci 2013;58:2940–2948. 19. Supkal R, Jinjuvadia C, Liangpunsakul S, et al. Trends in outcomes, hospitalization costs, financial burden, and mortality for chronic obstructive pulmonary disease. Comparative effectiveness: treatments, research, and practice [May 1, 2014], A3721–A3721. Available at: http:// www.atsjournals.org/doi/abs/10.1164/ajrccm-conference. 2014.189.1_MeetingAbstracts.A3721. Accessed March 2015. 20. Heidenreich PA, Lewis WR, LaBresh KA, et al. Hospital performance recognition with the Get With The Guidelines Program and mortality for acute myocardial infarction and heart failure. Am Heart J 2009;158: 546–553. 21. Peterson PN, Rumsfeld JS, Liang L, et al. American Heart Association Get With The Guidelines-Heart Failure Program. Treatment and risk in heart failure: gaps in evidence or quality? Circ Cardiovasc Qual Outcomes 2010; 3:309–315. 22. Sargenti K, Prytz H, Nilsson E, et al. Predictors of mortality among patients with compensated and decompensated liver cirrhosis: the role of bacterial infections and infection-related acute-on-chronic liver failure. Scand J Gastroenterol 2015;19:1–9. 23. Tandon P, Delisle A, Topal JE, et al. High prevalence of antibiotic-resistant bacterial infections among patients with cirrhosis at a US liver center. Clin Gastroenterol Hepatol 2012;10:1291–1298. 24. Bajaj JS, O’Leary JG, Reddy KR, et al. North American Consortium for the Study of End-Stage Liver Disease
899
EDITORIALS (NACSELD). Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American consortium for the study of end-stage liver disease (NACSELD) experience. Hepatology 2012; 56:2328–2335. 25. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 2014;60: 1310–1324.
900
Reprint requests Address requests for reprints to: Fasiha Kanwal, Division of Gastroenterology and Hepatology, Baylor College of Medicine, 2002 Holcombe Boulevard (152), Houston, Texas 77030. e-mail: [email protected].
Conflicts of interest The author discloses no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2015.03.023
