Z Gastroenterol 2009; 47(9): 807-813
DOI: 10.1055/s-0028-1109058
Originalarbeit

© Georg Thieme Verlag KG Stuttgart · New York

Acute Liver Failure in a Metropolitan Area in Germany: a Retrospective Study (2002 – 2008)

Akutes Leberversagen in Deutschland (2002 – 2008)A. Canbay1 [*] , C. Jochum1 [*] , L. P. Bechmann1 , S. Festag1 , R. K. Gieseler1 , Z. Yüksel1 , P. Lütkes1 , F. H. Saner2 , A. Paul2 , G. Gerken1
  • 1Division of Gastroenterology and Hepatology, University Hospital Essen, Essen
  • 2Division of General and Transplantation Surgery, University Hospital Essen, Essen
Further Information

Publication History

manuscript received: 28.9.2008

manuscript accepted: 30.11.2008

Publication Date:
11 September 2009 (online)

Zusammenfassung

Ziele: Identifikation aktueller Ätiologien des akuten Leberversagens (ALV) in Deutschland sowie neuer prognostischer klinischer und / oder Laboratoriumsparameter des klinischen Verlaufs. Patienten: 134 erwachsene ALF-Patienten (63 % w / 37 % m) in einem Alter von 41 ± 16 Jahren (Median: 38 Jahre). Design und Setting: Retrospektive Studie (1 / 2002 – 4 / 2008) an ALF-Patienten des Ruhrgebiets, der größten urbanen Region Nordwestdeutschlands. Nach Studienaufnahme wurden klinische und Laboratoriumsparameter über 4 Wochen hinweg erhoben. Ergebnisse: ALF-Ätiologien waren Medikamententoxizität (39,6 %), Kombinationen viraler Hepatitiden (23,1 %) oder heterogen (16,4 %). In 20,9 % der Fälle konnte keine Ursache ermittelt werden. Das 4-Wochen-Überleben betrug 81,3 %. Unter Standardtherapie erholten sich 89 Patienten (66,4 %); 26 Patienten (19,4 %) mussten lebertransplantiert werden. Erhöhte Body-Mass-Indices (BMIs) korrelierten signifikant (p < 0,003) mit einem ungünstigen Verlauf, während hohe Spiegel cholestatischer Enzyme signifikant (p < 0,01) mit einem positiven Verlauf korrelierten. Schlussfolgerungen: Mit dieser Studie wurden nach langer Zeit erstmals aktuelle ALF-Ätiologien in Deutschland ermittelt. Demnach haben in der untersuchten Modellregion Deutschlands v. a. Acetaminophen-assoziierte, aber auch andere Fälle von Medikamententoxizität virale Hepatitiden als häufigste singuläre ALF-Ätiologie ersetzt. Gleichsinnige Befunde liegen aus den USA, Großbritannien und Skandinavien vor. Niedrige BMIs und erhöhte Cholestase-Parameter waren von statistisch signifikantem prognostischem Wert.

Abstract

Objectives: To determine current etiologies of acute liver failure (ALF) and clinical and laboratory parameters associated with the outcome upon ALF, so as to identify the frequency of present causes of ALF in Germany as well as potential new prognostic parameters. Patients: 134 adult patients (63 % females / 37 % males) aged 41 ± 16 years (median: 38 years) with established ALF criteria. Design and setting: A retrospective study (1 / 2002 – 4 / 2008) on ALF patients from the Ruhr Area, the largest urban region located in northwestern Germany. Clinical and laboratory data were collected for a period of four weeks after study admission. Results: Etiologies of ALF were identified as drug toxicity (39.6 % of the cases); combined viral hepatitides (23.1 %); or miscellaneous (16.4 %). In 20.9 % of the cases, the etiology remained indeterminate. Overall patient survival at four weeks was 81.3 %. While 89 patients (66.4 %) recovered under best supportive therapy, 26 patients (19.4 %) had to undergo liver transplantation. Increased body mass indices were significantly (p < 0.003) associated with a poor outcome. Intriguingly, high levels of cholestatic enzymes significantly (p < 0.01) correlated with a positive outcome. Conclusions: In providing first data on current ALF etiologies Germany, this study reveals that drug toxicity – in particular due to acetaminophen – has replaced viral hepatitis as the most single frequent cause of ALF in a densely populated urban area; this correlates with similar findings in the USA, the UK and Scandinavia. Lower body mass indices and elevated cholestatic enzyme levels had statistically significant prognostic power.

References

  • 1 O’Grady J G. Acute liver failure.  Postgrad Med J. 2005;  81 148-154
  • 2 Lee W M. Acute liver failure in the United States.  Semin Liver Dis. 2003;  23 217-226
  • 3 Ostapowicz G, Fontana R J, Schiodt F V. et al . Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.  Ann Intern Med. 2002;  137 947-954
  • 4 Bernal W, Wendon J. Liver transplantation in adults with acute liver failure.  J Hepatol. 2004;  40 192-197
  • 5 Wei G, Bergquist A, Broome U. et al . Acute liver failure in Sweden: etiology and outcome.  J Intern Med. 2007;  262 393-401
  • 6 Canbay A, Chen S Y, Gieseler R K. et al . Overweight patients are more susceptible for acute liver failure.  Hepatogastroenterology. 2005;  52 1516-1520
  • 7 Rutherford A, Davern T, Hay J E. et al . Influence of high body mass index on outcome in acute liver failure.  Clin Gastroenterol Hepatol. 2006;  4 1544-1549
  • 8 Choi W C, Arnaout W C, Villamil F G. et al . Comparison of the applicability of two prognostic scoring systems in patients with fulminant hepatic failure.  Korean J Intern Med. 2007;  22 93-100
  • 9 Yantorno S E, Kremers W K, Ruf A E. et al . MELD is superior to King’s College and Clichy’s criteria to assess prognosis in fulminant hepatic failure.  Liver Transpl. 2007;  13 822-828
  • 10 Taylor R M, Davern T, Munoz S. et al . Fulminant hepatitis A virus infection in the United States: Incidence, prognosis, and outcomes.  Hepatology. 2006;  44 1589-1597
  • 11 Pazzi P, Morsiani E, Vilei M T. et al . Serum bile acids in patients with liver failure supported with a bioartificial liver.  Aliment Pharmacol Ther. 2002;  16 1547-1554
  • 12 Demetris A J, Seaberg E C, Wennerberg A. et al . Ductular reaction after submassive necrosis in humans. Special emphasis on analysis of ductular hepatocytes.  Am J Pathol. 1996;  149 439-448
  • 13 Fausto N, Campbell J S, Riehle K J. Liver regeneration.  Hepatology. 2006;  43 S45-S53
  • 14 Huang W, Ma K, Zhang J. et al . Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration.  Science. 2006;  312 233-236
  • 15 Geier A, Trautwein C. Bile acids are “homeotrophic” sensors of the functional hepatic capacity and regulate adaptive growth during liver regeneration.  Hepatology. 2007;  45 251-253
  • 16 Geier A, Wagner M, Dietrich C G. et al . Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration.  Biochim Biophys Acta. 2007;  1773 283-308
  • 17 Hennes E M, Zeniya M, Czaja A J. et al . Simplified criteria for the diagnosis of autoimmune hepatitis.  Hepatology. 2008;  48 169-176
  • 18 Bower W A, Johns M, Margolis H S. et al . Population-based surveillance for acute liver failure.  Am J Gastroenterol. 2007;  102 2459-2463
  • 19 Bernal W, Ma Y, Smith H M. et al . The significance of autoantibodies and immunoglobulins in acute liver failure: a cohort study.  J Hepatol. 2007;  47 664-670
  • 20 Hadem J, Stiefel P, Bahr M J. et al . Prognostic implications of lactate, bilirubin, and etiology in German patients with acute liver failure.  Clin Gastroenterol Hepatol. 2008;  6 339-345
  • 21 Schiodt F V, Atillasoy E, Shakil A O. et al . Etiology and outcome for 295 patients with acute liver failure in the United States.  Liver Transpl Surg. 1999;  5 29-34
  • 22 Koskinas J, Deutsch M, Kountouras D. et al . Aetiology and outcome of acute hepatic failure in Greece: experience of two academic hospital centres.  Liver Int. 2008;  28 821-827
  • 23 Escorsell A, Mas A, Mata de la M. Acute liver failure in Spain: analysis of 267 cases.  Liver Transpl. 2007;  13 1389-1395
  • 24 Schimanski C C, Burg J, Mohler M. et al . Phenprocoumon-induced liver disease ranges from mild acute hepatitis to (sub-)acute liver failure.  J Hepatol. 2004;  41 67-74
  • 25 Larson A M, Polson J, Fontana R J. et al . Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study.  Hepatology. 2005;  42 1364-1372
  • 26 Gow P J, Jones R M, Dobson J L. et al . Etiology and outcome of fulminant hepatic failure managed at an Australian liver transplant unit.  J Gastroenterol Hepatol. 2004;  19 154-159
  • 27 Larsen F S, Kirkegaard P, Rasmussen A. et al . The Danish liver transplantation program and patients with serious acetaminophen intoxication.  Transplant Proc. 1995;  27 3519-3520
  • 28 Schmidt L E. Age and paracetamol self-poisoning.  Gut. 2005;  54 686-690
  • 29 Schmidt L E, Dalhoff K. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity.  Hepatology. 2002;  36 659-665
  • 30 Schmidt L E, Dalhoff K, Poulsen H E. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity.  Hepatology. 2002;  35 876-882
  • 31 Schmidt L E, Dalhoff K. Concomitant overdosing of other drugs in patients with paracetamol poisoning.  Br J Clin Pharmacol. 2002;  53 535-541
  • 32 Krahenbuhl S, Brauchli Y, Kummer O. et al . Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage.  Digestion. 2007;  75 232-237
  • 33 Bramlage P, Pittrow D, Wittchen H U. et al . Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled.  Am J Hypertens. 2004;  17 904-910
  • 34 Hach I, Ruhl U E, Klose M. et al . Obesity and the risk for mental disorders in a representative German adult sample.  Eur J Public Health. 2007;  17 297-305
  • 35 Angulo P. Nonalcoholic fatty liver disease.  N Engl J Med. 2002;  346 1221-1231
  • 36 Feldstein A, Canbay A, Guicciardi M E. et al . Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice.  J Hepatol. 2003;  39 978-983
  • 37 Court M H, Duan S X, Moltke L L. et al . Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms.  J Pharmacol Exp Ther. 2001;  299 998-1006
  • 38 Court M H. Acetaminophen UDP-glucuronosyltransferase in ferrets: species and gender differences, and sequence analysis of ferret UGT1A6.  J Vet Pharmacol Ther. 2001;  24 415-422
  • 39 Acuna von G, Foernzler D, Leong D. et al . Pharmacogenetic analysis of adverse drug effect reveals genetic variant for susceptibility to liver toxicity.  Pharmacogenomics J. 2002;  2 327-334
  • 40 Rust C, Gores G J. Apoptosis and liver disease.  Am J Med. 2000;  108 567-574
  • 41 Fausto N. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells.  Hepatology. 2004;  39 1477-1487

2 To be considered as co-first authors.

PD Dr. Ali Canbay

Gastroenterology and Hepatology, University Hospital Essen

Hufelandstr. 55

45122 Essen

Phone: ++ 49/2 01/7 23 36 12

Fax: ++ 49/2 01/7 23 57 19

Email: ali.canbay@uni-essen.de

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