Skip to main content
Erschienen in: Digestive Diseases and Sciences 5/2013

01.05.2013 | Original Article

Improvements in Hepatic Serological Biomarkers Are Associated with Clinical Benefit of Intravenous N-Acetylcysteine in Early Stage Non-Acetaminophen Acute Liver Failure

verfasst von: Sundeep Singh, Linda S. Hynan, William M. Lee, The Acute Liver Failure Study Group

Erschienen in: Digestive Diseases and Sciences | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

N-acetylcysteine (NAC) improves transplant-free survival in early coma grade (I–II) patients with non-acetaminophen induced acute liver failure (ALF). We determined whether the clinical benefit was associated with improvements in hepatic function.

Methods

In a prospective, double blind trial, 173 ALF patients without evidence of acetaminophen overdose were stratified by coma grade (I–II vs. III–IV) and randomly assigned to receive either intravenous NAC or dextrose (placebo) for 72 h, resulting in four patient groups. INR, ALT, bilirubin, creatinine, and AST obtained on admission (day 1) and subsequent days (days 2–4) were used for secondary analysis performed by fitting longitudinal logistic regression models to predict death or transplantation or transplantation alone.

Results

Treatment group and day of study in models including bilirubin or ALT were predictors of transplantation or death (maximum p < 0.03). Those patients with early coma grade who were treated with NAC showed significant improvement in bilirubin and ALT levels when compared to the other three groups (maximum p < 0.02 for NAC 1–2 vs. the 3 other treatments) when predicting death or transplantation. Treatment group, day of study, and bilirubin were predictors of transplantation (maximum p < 0.03) in ALF patients.

Conclusion

The decreased risk of transplantation or death or of transplantation alone with intravenous NAC in early coma grade patients with non-acetaminophen induced ALF was reflected in improvement in parameters related to hepatocyte necrosis and bile excretion including ALT and bilirubin, but not in INR, creatinine, or AST. Hepatic recovery appears hastened by NAC as measured by several important lab values.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Trey C, Davidson CS. The management of fulminant hepatic failure. In: Popper H, Schaffner F, eds. Progress in Liver Diseases. New York: Grune & Stratton; 1970:282–298. Trey C, Davidson CS. The management of fulminant hepatic failure. In: Popper H, Schaffner F, eds. Progress in Liver Diseases. New York: Grune & Stratton; 1970:282–298.
2.
Zurück zum Zitat Hoofnagle JH, Carithers RL, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology. 1995;21:240–252.PubMed Hoofnagle JH, Carithers RL, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology. 1995;21:240–252.PubMed
3.
Zurück zum Zitat Ostapowicz G, Fontanta RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947–955.PubMedCrossRef Ostapowicz G, Fontanta RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947–955.PubMedCrossRef
4.
Zurück zum Zitat Prescott LF, Critchley JA. The treatment of acetaminophen poisoning. Ann Rev Pharmacol Toxicol. 1983;23:87–101.CrossRef Prescott LF, Critchley JA. The treatment of acetaminophen poisoning. Ann Rev Pharmacol Toxicol. 1983;23:87–101.CrossRef
5.
Zurück zum Zitat Hamlyn AN, Douglas AP, James O. The spectrum of paracetamol (acetaminophen) overdose: clinical and epidemiological studies. Postgrad Med J. 1978;54:400–404.PubMedCrossRef Hamlyn AN, Douglas AP, James O. The spectrum of paracetamol (acetaminophen) overdose: clinical and epidemiological studies. Postgrad Med J. 1978;54:400–404.PubMedCrossRef
6.
Zurück zum Zitat Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137:856–864.PubMedCrossRef Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137:856–864.PubMedCrossRef
7.
Zurück zum Zitat Harrison PM, Wendon JA, Gimson AE, et al. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991;324:1852–1857.PubMedCrossRef Harrison PM, Wendon JA, Gimson AE, et al. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991;324:1852–1857.PubMedCrossRef
8.
Zurück zum Zitat Walsh TS, Hopton P, Philips BJ, et al. The effect of N-acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure. Hepatology. 1998;27:1332–1340.PubMedCrossRef Walsh TS, Hopton P, Philips BJ, et al. The effect of N-acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure. Hepatology. 1998;27:1332–1340.PubMedCrossRef
9.
Zurück zum Zitat Rank N, Michel C, Haertel C, et al. N-acetylcysteine increases blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. Crit Care Med. 2000;28:3799–3807.PubMedCrossRef Rank N, Michel C, Haertel C, et al. N-acetylcysteine increases blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. Crit Care Med. 2000;28:3799–3807.PubMedCrossRef
10.
Zurück zum Zitat Chen Y, Johansson E, Yang Y, et al. Oral N-acetylcysteine rescues lethality of hepatocyte-specific GcIc-knockout mice, providing a model for hepatic cirrhosis. J Hepatol. 2010;53:1085–1094.PubMedCrossRef Chen Y, Johansson E, Yang Y, et al. Oral N-acetylcysteine rescues lethality of hepatocyte-specific GcIc-knockout mice, providing a model for hepatic cirrhosis. J Hepatol. 2010;53:1085–1094.PubMedCrossRef
11.
Zurück zum Zitat González R, Ferrín G, Hidalgo AB, et al. N-acetylcysteine, coenzyme Q10 and superoxide dismutase mimetic prevent mitochondrial cell dysfunction and cell death induced by d-galactosamine in primary culture of human hepatocytes. Chem Biol Interact. 2009;181:95–106.PubMedCrossRef González R, Ferrín G, Hidalgo AB, et al. N-acetylcysteine, coenzyme Q10 and superoxide dismutase mimetic prevent mitochondrial cell dysfunction and cell death induced by d-galactosamine in primary culture of human hepatocytes. Chem Biol Interact. 2009;181:95–106.PubMedCrossRef
12.
Zurück zum Zitat Jin X, Wang L, Wu HS, et al. N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice. Hepatobiliary Pancreat Dis Int. 2007;6:284–289.PubMed Jin X, Wang L, Wu HS, et al. N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice. Hepatobiliary Pancreat Dis Int. 2007;6:284–289.PubMed
Metadaten
Titel
Improvements in Hepatic Serological Biomarkers Are Associated with Clinical Benefit of Intravenous N-Acetylcysteine in Early Stage Non-Acetaminophen Acute Liver Failure
verfasst von
Sundeep Singh
Linda S. Hynan
William M. Lee
The Acute Liver Failure Study Group
Publikationsdatum
01.05.2013
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 5/2013
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-012-2512-x

Weitere Artikel der Ausgabe 5/2013

Digestive Diseases and Sciences 5/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.