We thank Drs. Sebode et al. for highlighting the hepatotoxic potential of metamizole. The publications they mention are the only two publications on metamizole and drug-induced liver injury (DILI) or acute liver failure (ALF), probably due to the fact that metamizole is no longer licensed in many countries because of the risk of agranulocytosis (1). In our study we did not explicitly search for (thus far unknown) drugs with the risk of DILI or ALF, but evaluated drugs known to be associated with acute liver failure from different publications (2, 3). For this reason we did not mention metamizole. It also should be considered that our method was not able to reflect over-the-counter medication. Therefore, a connection between prescriptions and ALF cannot be established on the basis of health insurance data. Identifying the cause of ALF is often difficult. On the basis of the data of Sebode and colleagues, metamizole should in future be considered as a cause of DILI or ALF.
Population-based studies investigate a specific question in a defined group, and the results should be transferable to a general population (4). Therefore, the difficulty lies in selecting a sample that is representative of the total (5). Several variations of study designs are possible—for example, a case-control study or cross sectional study—and the data collection may be prospective or retrospective. The study we presented is a retrospective population-based incidence study. Evaluating the association between disease and source was only the secondary study aim. Concerning Swart and Schmitt’s Standardized Reporting Of Secondary data Analyses“(STROSA) criteria, as cited by Strausberg, the publication contains the suggested components. In particular, the limitations of the study regarding the AOK members as adequate sample of the general population were discussed in detail. However, since ALF is not notifiable, a representative and prospective data collection is intricate. Data collected prospectively by specialized liver centers are biased by selection and may not represent the general population.
Footnotes
Conflict of interest statement
Dr. Weiler has received consultancy payments and lecture fees from Astellas and Novartis, and reimbursement of delegate fees and travel expenses from Biotest.
References
- 1.Levy M. (Chairmann) for the International Agranulocytosis and Aplastic Anemia Study: Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA. 1986;256:1749–1757. [PubMed] [Google Scholar]
- 2.Weiler N, Schlotmann A, Schnitzbauer AA, Zeuzem S, Welker MW. The epidemiology of acute liver failure—results of a population-based study including 25 million state-insured individuals. Dtsch Arztebl Int. 2020;117:43–50. doi: 10.3238/arztebl.2020.0043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Reuben A, Koch DG, Lee WM. Drug-induced acute liver failure: results of a US. multicenter, prospective study. Hepatology. 2010;52:2065–2076. doi: 10.1002/hep.23937. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 3rd ed: Lippincott Williams & Wilkins (LWW); 2008 [Google Scholar]
- 5.Szklo M. Population-based cohort studies. Epidemiol Rev. 1998;20:81–90. doi: 10.1093/oxfordjournals.epirev.a017974. [DOI] [PubMed] [Google Scholar]