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High risk of complications and acute-on-chronic liver failure in cirrhosis patients with acute pancreatitis

      Highlights

      • liver cirrhosis (LC) predisposes to adverse outcomes of acute pancreatitis (AP), with high rates of acute-on-chronic liver failure (ACLF) and significant mortality.
      • cirrhosis patients require significantly more radiological and endoscopic interventions over the course of AP, with higher complication rates compared to non-cirrhotic AP patients.
      • adverse outcomes of LC-AP are not adequately predicted by established AP scores, but by SOFA, ACLFs and particularly MELD scores.
      • clinical evidence of overt portal hypertension identifies LC patients at highest risk of AP-related complications, further decompensation and death.

      Abstract

      Background & aims

      Acute pancreatitis (AP) is a frequent indication for hospitalization and may present with varying degrees of severity. AP often coincides with hepatic disease, yet the impact of liver cirrhosis (LC) on the course of AP is uncertain, and early identification of patients at risk for complications remains challenging. We aimed to assess the impact of LC on the development of pancreatic and extra-pancreatic complications of AP, and to identify predictors of adverse outcomes in cirrhotic patients.

      Methods

      All adult patients with LC and AP (LC-AP, n = 52) admitted to our institution between 01/2011–03/2020 were subjected to a 1:2 matched-pair analysis with patients with AP but without LC (NLC-AP, n = 104).

      Results

      At hospital admission, Glasgow-Imrie and Ranson scores as well as markers of systemic inflammation were comparable in LC-AP and NLC-AP patients, and both groups had similar rates of necrotizing AP. Infectious complications were more prevalent, and medical interventions were performed more often and with higher complication rates in LC-AP patients. While only 12.5% of NLC-AP patients developed organ failures, 48% of LC-AP patients developed single (7.7%) or multiple organ failure (40.4%), resulting in 44% of LC-AP patients with acute-on-chronic liver failure (ACLF). Patients with overt portal hypertension were particularly prone for decompensation. Mortality was higher among LC-AP compared to NLC-AP patients (6-month mortality 25% vs. 1.9%, p < 0.001), and SOFA and MELD scores at admission most accurately predicted outcomes in LC-AP.

      Conclusion

      Among AP patients, concomitant cirrhosis substantially increases the risk for infections, periprocedural complications, multiorgan failure and death.

      Keywords

      Abbreviations:

      ACLF (acute-on-chronic liver failure), AP (acute pancreatitis), CCI (Charlson comorbidity index), LC (liver cirrhosis), MELD (model for end-stage liver disease)
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      References

        • Lankisch P.G.
        • Apte M.
        • Banks P.A.
        Acute pancreatitis.
        Lancet. 2015; 386 (Jul 4PubMed PMID: 25616312. Epub 2015/01/27): 85-96
        • Lee P.J.
        • Papachristou G.I.
        New insights into acute pancreatitis.
        Nat Rev Gastroenterol Hepatol. 2019; 16 (AugPubMed PMID: 31138897. Epub 2019/05/30): 479-496
        • Tenner S.
        • Baillie J.
        • DeWitt J.
        • Vege S.S.
        • American College of Gastroenterology
        American college of gastroenterology guideline: management of acute pancreatitis.
        Am J Gastroenterol. 2013; 108 (Sep, Epub 2013 Jul 30): 1400-1415https://doi.org/10.1038/ajg.2013.218
        • Banks P.A.
        • Bollen T.L.
        • Dervenis C.
        • Gooszen H.G.
        • Johnson C.D.
        • Sarr M.G.
        • et al.
        Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus.
        Gut. 2013; 62 (JanPubMed PMID: 23100216. Epub 2012/10/27): 102-111
        • Tenner S.
        Initial management of acute pancreatitis: critical issues during the first 72h.
        Am J Gastroenterol. 2004; 99 (DecPubMed PMID: 15571599. Epub 2004/12/02): 2489-2494
        • Moon A.M.
        • Singal A.G.
        • Tapper E.B.
        Contemporary epidemiology of chronic liver disease and cirrhosis.
        Clin Gastroenterol Hepatol. 2020; 18 (Epub 2019 Aug 8): 2650-2666https://doi.org/10.1016/j.cgh.2019.07.060
        • Collaboration N.C.D.R.F
        Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults.
        Lancet. 2017; 390 (Dec 16PubMed PMID: 29029897. Pubmed Central PMCID: PMC5735219. Epub 2017/10/17): 2627-2642
        • Khatua B.
        • El-Kurdi B.
        • Singh V.P.
        Obesity and pancreatitis.
        Curr Opin Gastroenterol. 2017; 33 (SepPubMed PMID: 28719397. Pubmed Central PMCID: PMC6640854. Epub 2017/07/19): 374-382
        • Camilleri M.
        • Malhi H.
        • Acosta A.
        Gastrointestinal complications of obesity.
        Gastroenterology. 2017; 152 (MayPubMed PMID: 28192107. Pubmed Central PMCID: PMC5609829. Epub 2017/02/14): 1656-1670
        • Clemens D.L.
        • Mahan K.J.
        Alcoholic pancreatitis: lessons from the liver.
        World J Gastroenterol. 2010; 16 (Mar 21PubMed PMID: 20238397. Pubmed Central PMCID: PMC2842522. Epub 2010/03/20): 1314-1320
        • Pace A.
        • de Weerth A.
        • Berna M.
        • Hillbricht K.
        • Tsokos M.
        • Blaker M.
        • et al.
        Pancreas and liver injury are associated in individuals with increased alcohol consumption.
        Clin Gastroenterol Hepatol. 2009; 7 (NovPubMed PMID: 19560556. Epub 2009/06/30): 1241-1246
        • Simons-Linares C.R.
        • Abushamma S.
        • Romero-Marrero C.
        • Bhatt A.
        • Lopez R.
        • Jang S.
        • et al.
        Clinical outcomes of acute pancreatitis in patients with cirrhosis according to liver disease severity scores.
        Dig Dis Sci. 2021; 66 (AugPubMed PMID: 32892261. Epub 2020/09/07): 2795-2804
        • Baron T.H.
        • Morgan D.E.
        Acute necrotizing pancreatitis.
        N Engl J Med. 1999; 340 (May 6PubMed PMID: 10228193. Epub 1999/05/06): 1412-1417
        • Banks P.A.
        • Freeman M.L.
        • Practice Parameters Committee of the American College of Gastroenterology
        Practice guidelines in acute pancreatitis.
        Am J Gastroenterol. 2006; 101 (OctPubMed PMID: 17032204. Epub 2006/10/13): 2379-2400https://doi.org/10.1111/j.1572-0241.2006.00856.x
        • Vincent J.L.
        • Moreno R.
        • Takala J.
        • Willatts S.
        • De Mendonca A.
        • Bruining H.
        • et al.
        The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the european society of intensive care medicine.
        Intensive Care Med. 1996; 22 (JulPubMed PMID: 8844239. Epub 1996/07/01): 707-710
        • Triester S.L.
        • Kowdley K.V.
        Prognostic factors in acute pancreatitis.
        J Clin Gastroenterol. 2002; 34 (FebPubMed PMID: 11782614. Epub 2002/01/10): 167-176
        • Moreau R.
        • Jalan R.
        • Gines P.
        • Pavesi M.
        • Angeli P.
        • Cordoba J.
        • et al.
        Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.
        Gastroenterology. 2013; 144 (Jun1437 e1421-1429. PubMed PMID: 23474284. Epub 2013/03/12): 1426-1437
        • Jalan R.
        • Saliba F.
        • Pavesi M.
        • Amoros A.
        • Moreau R.
        • Gines P.
        • et al.
        Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure.
        J Hepatol. 2014; 61 (NovPubMed PMID: 24950482. Epub 2014/06/21): 1038-1047
        • Dindo D.
        • Demartines N.
        • Clavien P.A.
        Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.
        Ann Surg. 2004; 240 (AugPubMed PMID: 15273542. Pubmed Central PMCID: PMC1360123. Epub 2004/07/27): 205-213
        • Wiesner R.
        • Edwards E.
        • Freeman R.
        • Harper A.
        • Kim R.
        • Kamath P.
        • et al.
        Model for end-stage liver disease (MELD) and allocation of donor livers.
        Gastroenterology. 2003; 124 (Jan PubMed PMID: 12512033. Epub 2003/01/04): 91-96
        • Ouyang G.
        • Pan G.
        • Liu Q.
        • Wu Y.
        • Liu Z.
        • Lu W.
        • et al.
        The global, regional, and national burden of pancreatitis in 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017.
        BMC Med. 2020; 18 (Dec 10PubMed PMID: 33298026. Pubmed Central PMCID: PMC7726906. Epub 2020/12/11): 388
        • Diseases G.B.D.
        • Injuries C.
        Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease Study 2019.
        Lancet. 2020; 396 (Oct 17PubMed PMID: 33069326. Pubmed Central PMCID: PMC7567026. Epub 2020/10/19): 1204-1222
        • Manthey J.
        • Shield K.D.
        • Rylett M.
        • Hasan O.S.M.
        • Probst C.
        • Rehm J.
        Global alcohol exposure between 1990 and 2017 and forecasts until 2030: a modelling study.
        Lancet. 2019; 393 (Jun 22PubMed PMID: 31076174. Epub 2019/05/12): 2493-2502
        • Fuster D.
        • Samet J.H.
        Alcohol use in patients with chronic liver disease.
        N Engl J Med. 2018; 379 (Sep 27PubMed PMID: 30257164. Epub 2018/09/27): 1251-1261
        • Fujioka K.
        Safety and tolerability of medications approved for chronic weight management.
        Obesity (Silver Spring). 2015; 23 (AprPubMed PMID: 25900872. Epub 2015/04/23): S7-11
        • Alsubaie S.
        • Almalki M.H.
        Metformin induced acute pancreatitis.
        Dermatoendocrinol. 2013; 5 (Apr 1PubMed PMID: 24194972. Pubmed Central PMCID: PMC3772920. Epub 2013/11/07): 317-318
        • Simons-Linares C.R.
        • Elkhouly M.A.
        • Salazar M.J.
        Drug-induced acute pancreatitis in adults: an update.
        Pancreas. 2019; 48 (Nov/DecPubMed PMID: 31688589. Epub 2019/11/07): 1263-1273
        • Klein L.M.
        • Chang J.
        • Gu W.
        • Manekeller S.
        • Jansen C.
        • Lingohr P.
        • et al.
        The development and outcome of acute-on-chronic liver failure after surgical interventions.
        Liver Transpl. 2020; 26 (FebPubMed PMID: 31693788. Epub 2019/11/07): 227-237
        • Trebicka J.
        • Gu W.
        • Ibanez-Samaniego L.
        • Hernandez-Gea V.
        • Pitarch C.
        • Garcia E.
        • et al.
        Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.
        J Hepatol. 2020; 73 (NovPubMed PMID: 32339602. Epub 2020/04/28): 1082-1091
        • Fernandez J.
        • Acevedo J.
        • Wiest R.
        • Gustot T.
        • Amoros A.
        • Deulofeu C.
        • et al.
        Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis.
        Gut. 2018; 67 (OctPubMed PMID: 28847867. Epub 2017/08/30): 1870-1880
        • Simons-Linares C.R.
        • Romero-Marrero C.
        • Jang S.
        • Bhatt A.
        • Lopez R.
        • Vargo J.
        • et al.
        Clinical outcomes of acute pancreatitis in patients with cirrhosis.
        Pancreatology. 2020; 20 (JanPubMed PMID: 31734110. Epub 2019/11/18): 44-50
        • Jang D.K.
        • Ahn D.W.
        • Lee K.L.
        • Kim B.G.
        • Kim J.W.
        • Kim S.H.
        • et al.
        Impacts of body composition parameters and liver cirrhosis on the severity of alcoholic acute pancreatitis.
        PLoS One. 2021; 16 (PubMed PMID: 34807958. Pubmed Central PMCID: PMC8608310. Epub 2021/11/23)e0260309
        • Martinez J.
        • Sanchez-Paya J.
        • Palazon J.M.
        • Suazo-Barahona J.
        • Robles-Diaz G.
        • Perez-Mateo M.
        Is obesity a risk factor in acute pancreatitis? A meta-analysis.
        Pancreatology. 2004; 4 (PubMed PMID: 14988657. Epub 2004/02/28): 42-48
        • Katuchova J.
        • Bober J.
        • Harbulak P.
        • Hudak A.
        • Gajdzik T.
        • Kalanin R.
        • et al.
        Obesity as a risk factor for severe acute pancreatitis patients.
        Wien Klin Wochenschr. 2014; 126 (AprPubMed PMID: 24522641. Epub 2014/02/14): 223-227
        • Winters B.D.
        • Eberlein M.
        • Leung J.
        • Needham D.M.
        • Pronovost P.J.
        • Sevransky J.E.
        Long-term mortality and quality of life in sepsis: a systematic review.
        Crit Care Med. 2010; 38 (MayPubMed PMID: 20308885. Epub 2010/03/24): 1276-1283
        • Crockett S.D.
        • Wani S.
        • Gardner T.B.
        • Falck-Ytter Y.
        • Barkun A.N.
        • American Gastroenterological Association Institute Clinical Guidelines Committee
        American gastroenterological association institute guideline on initial management of acute pancreatitis.
        Gastroenterology. 2018; 154 (MarPubMed PMID: 29409760. Epub 2018 Feb 3): 1096-1101https://doi.org/10.1053/j.gastro.2018.01.032
        • Trikudanathan G.
        • Wolbrink D.R.J.
        • van Santvoort H.C.
        • Mallery S.
        • Freeman M.
        • Besselink M.G.
        Current concepts in severe acute and necrotizing pancreatitis: an evidence-based approach.
        Gastroenterology. 2019; 156 (Maye1993PubMed PMID: 30776347. Epub 2019/02/19): 1994-2007
        • Boxhoorn L.
        • van Dijk S.M.
        • van Grinsven J.
        • Verdonk R.C.
        • Boermeester M.A.
        • Bollen T.L.
        • et al.
        Immediate versus postponed intervention for infected necrotizing pancreatitis.
        N Engl J Med. 2021; 385 (Oct 7PubMed PMID: 34614330. Epub 2021/10/07): 1372-1381
        • Yan L.
        • Qian C.
        • Duan X.
        • Ding J.
        • Zhang W.
        Poor prognosis of liver transplantation for acute liver failure with acute pancreatitis: two case reports.
        Medicine (Baltimore). 2020; 99 (Oct 23PubMed PMID: 33120850. Pubmed Central PMCID: PMC7581164. Epub 2020/10/31): e22934
        • Kirino I.
        • Fujimoto Y.
        • Hata K.
        • et al.
        Liver transplantation for acute liver failure accompanied by severe acute pancreatitis.
        BMJ Case Rep. 2016; (2016:bcr2016215959)
        • Russell T.A.
        • Park S.
        • Agopian V.G.
        • Zarrinpar A.
        • Farmer D.G.
        • O'Neill S.
        • et al.
        Peritransplant pancreatitis: a marker of high mortality and graft failure in liver transplant patients.
        Liver Transpl. 2017; 23 (JulPubMed PMID: 28294516. Epub 2017/03/16): 925-932
        • Gustot T.
        • Fernandez J.
        • Garcia E.
        • Morando F.
        • Caraceni P.
        • Alessandria C.
        • et al.
        Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis.
        Hepatology. 2015; 62 (JulPubMed PMID: 25877702. Epub 2015/04/17): 243-252
        • Engelmann C.
        • Claria J.
        • Szabo G.
        • Bosch J.
        • Bernardi M.
        Pathophysiology of decompensated cirrhosis: portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction.
        J Hepatol. 2021; 75 (JulPubMed PMID: 34039492. Epub 2021/05/28): S49-S66
        • Quero G.
        • Covino M.
        • Ojetti V.
        • Fiorillo C.
        • Rosa F.
        • Menghi R.
        • et al.
        Acute pancreatitis in oldest old: a 10-year retrospective analysis of patients referred to the emergency department of a large tertiary hospital.
        Eur J Gastroenterol Hepatol. 2020; 32 (FebPubMed PMID: 31651648. Epub 2019/10/28): 159-165
        • Jamal S.
        • Khan M.Z.
        • Kichloo A.
        • Edigin E.
        • Bailey B.
        • Aljadah M.
        • et al.
        The effect of atrial fibrillation on inpatient outcomes of patients with acute pancreatitis: a two-year national inpatient sample database study.
        J Innov Card Rhythm Manag. 2020; 11 (DecPubMed PMID: 33408954. Pubmed Central PMCID: PMC7769503. Epub 2021/01/08): 4338-4344
        • Mehta H.
        • Shah I.
        • Pahuja M.
        • Amin S.
        • Bhurwal A.
        • Moni S.
        • et al.
        Outcomes of acute pancreatitis in patients with heart failure: insights from the nationwide inpatient sample.
        J. Card. Fail. 2019; 25 (2019/08/01/): S57-S58