Häufigkeit und Risikofaktoren medikamentös-toxischer Leberschäden: eine umfragebasierte Studie in Apotheken

Zusammenfassung

Einleitung: Für die meisten Medikamente wird eine Häufigkeit schwerer Leberschäden von nur 0,001 – 0,01 % angegeben, eine höhere Inzidenz wird allerdings vermutet. Medikamentöse Leberschäden sind vielfältig und können bis hin zum akuten Leberversagen führen. Eine Vielzahl von Risikofaktoren wird diskutiert, das individuelle Risikoprofil ist bisher aber meist sehr schwer einzuschätzen. Ziel dieses Projekts war es, die Häufigkeit erhöhter Leberwerte nach Medikamenteneinnahme und potenzielle Risikofaktoren in einem Kollektiv von erwachsenen Personen, die Medikamente einnehmen, zu untersuchen.

Methoden: In den Jahren 2011 und 2012 wurden jeweils in 30 Apotheken in Deutschland über einem Zeitraum von 6 Wochen anonymisierte Fragebögen mit Fragen zu Demografie, Vorerkrankungen, Medikamenten und Leberwerten unselektiert an volljährige Kunden, die apotheken- oder verschreibungspflichtige Medikamente erhielten, verteilt.

Ergebnisse: Insgesamt konnten 1098 Fragebögen ausgewertet werden; die Rücklaufquote betrug 15,25 %. In unserem Patientenkollektiv (mittleres Alter 57,7 ± 17,1 Jahre; 62,6 % Frauen) gaben 141 Personen (12,8 %) an, dass bereits einmal erhöhte Leberwerte aufgrund der Einnahme von Medikamenten aufgetreten seien. In 65 Fällen (5,9 %) musste das Medikament daher abgesetzt werden, und bei 20 Patienten (1,8 %) war eine stationäre Behandlung notwendig. In der Gesamtgruppe der 141 Patienten mit erhöhten Leberwerten aufgrund von Medikamenten lagen folgende Faktoren in der multivariaten Analyse häufiger vor als bei Personen ohne Medikamentenreaktionen in der Anamnese (n = 957): chronische Leberkrankheit (14,4 vs. 2,4 %, Odds-Ratio [OR] 4,2, 95 %-Konfidenzintervall [KI] 2,0 – 9,0), chronische Niereninsuffizienz (20,0 vs. 6,8 %, OR 2,2, 95 %-KI 1,3 – 3,7), Diabetes mellitus (34 vs. 15,3 %, OR 2,0, 95 %-KI 1,3 – 3,2), Leberkrankheit in der Familie (19,9 vs. 7,7 %, OR 2,1, 95 %-KI 1,2 – 3,6) und Einnahme von Medikamenten über mindestens 5 Jahre (80,9 vs. 59,3 %, OR 2,1, 95 %-KI 1,3 – 3,5).

Schlussfolgerung: Diese Ergebnisse zeigen auf, dass in diesem erstmals untersuchten Kollektiv von Apothekenkunden Medikamente in unerwartet hoher Zahl zu erhöhten Leberwerten führen, und weisen auf Interaktionen mit multiplen Risikofaktoren hin.

Abstract

Aim: The reported incidence of drug-induced liver injury (DILI) ranges from 1 in 10 000 to 1 in 100 000 patients for most drugs, but the true incidence is expected to be much higher. Several risk factors for DILI susceptibility have been suggested, however there is insufficient data to define an individual risk profile. Therefore it was our aim to study the prevalence of DILI and potential risk factors within adult pharmacy customers in Germany.

Methods: We conducted two 6 week-survey studies in 30 pharmacies in 2011 and 2012, respectively, using a newly developed questionnaire comprising questions on demography, (liver) diseases, liver enzyme activities, and drug history. In each study, anonymized questionnaires were presented to non-selected adult customers taking (non-)prescription drugs.

Results: Combining the datasets from the 2011 and 2012 surveys, in total 1098 questionnaires were evaluated (mean age 57.7 ± 17.1 years; 62.6 % females, return rate 15.25 %). Overall, 141 individuals (12.8 %) reported elevated liver enzymes due to drugs, in 65 cases (5.9 %) the medication had to be stopped, and 20 customers (1.8 %) reported that they had been admitted to hospital due to DILI. Compared to individuals without adverse hepatic drug reactions (n = 957), the 141 persons with potential DILI presented more often the following risk factors in multivariate analysis: chronic liver disease (14.4 % vs. 2.4 %, odds ratio [OR] 4.2, 95 % confidence interval [CI] 2.0 – 9.0), chronic renal insufficiency (20.0 vs. 6.8 %, OR 2.2, 95 % CI 1.3 – 3.7), diabetes (34 vs. 15.3 %, OR 2.0, 95 % CI 1.3 – 3.2), family history of chronic liver disease (19.9 vs. 7.7 %, OR 2.1, 95 % CI 1.2 – 3.6), and continuous drug intake for more than 5 years (80.9 vs. 59.3 %, OR 2.1, 95 % CI 1.3 – 3.5).

Conclusion: These studies show an unexpected high prevalence of DILI in pharmacy customers and identify multiple potential risk factors.

Schlüsselwörter

Apothekenkunden - Fragebogen - medikamentöse Leberschädigung - Prävalenz - Risikofaktoren

Key words

pharmacy customers - questionnaire - drug induced liver injury - prevalence - risk factors

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