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Cited by 0Drug-Induced Hepatotoxicity and ProtectionPharmacovigilance and Adverse Drug ReactionsDrug-Induced Adverse Reactions

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index; 5 of the 51 sources its claims cite were checked for support.

DILI Differences and Similarities between the US and Europe

Open access
Toro-Ortiz, Juan Pedro, Andrade, Raúl J., Pinazo-Bandera, José·2026·Current Hepatology Reports
DOI 10.1007/s11901-026-00733-x
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Abstract

Purpose of review: To evaluate the critical role of international registries in understanding idiosyncratic drug-induced liver injury (DILI) by comparing clinical and epidemiological data from the Spanish DILI Registry, the Pro-Euro DILI registry, and the US DILIN. Recent findings: Although amoxicillin-clavulanic acid remains the leading global DILI trigger, DILI cases in the US show higher severity and more herbal supplement involvement. Immune checkpoint inhibitors present new toxicity phenotypes. Registry collaborations have yielded advanced prognostic tools like the nR criteria for predicting liver failure, and RECAM, a novel electronic causality assessment scale offering greater diagnostic precision than RUCAM. Summary: Registries are crucial for identifying rare DILI events that are missed by clinical trials, as well as for highlighting regional differences in triggers and outcomes. These networks are essential for identifying diagnostic biomarkers, and their findings benefit not only clinicians, but also regulators. Future research should prioritize the global validation of RECAM and utilize multinational biobanks to identify genetic risk factors, ultimately improving drug safety.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review compares idiosyncratic drug-induced liver injury (DILI) across the Spanish DILI Registry, the Pro-Euro DILI Registry, and the US DILIN, highlighting regional differences in triggers, severity, and herbal supplement involvement. It also summarizes registry-derived tools such as the nR criteria and RECAM and calls for global validation and multinational biobanks.

Key findings

  • Amoxicillin-clavulanate was the leading DILI trigger in all three registries: 22.9% in the Spanish registry, 12% in Pro-Euro DILI, and 10.1% in US DILIN. Second-place agents differed: anti-tuberculosis drugs (4.5%) in Spain, flucloxacillin (11%) in Europe, and isoniazid (5.3%) in the US.
  • US DILIN showed higher severity: severe cases were 19% versus 8.1% in Pro-Euro and 6.2% in the Spanish registry; liver transplantation was 4.0% versus 2.5% and 1.5%, respectively. Herbal/dietary supplements and anabolic androgenic steroids accounted for 16.1% in the US versus 6.0% in both European registries.
  • Demographic differences included mean age 49 years in US DILIN versus 56 in Pro-Euro and 54 in the Spanish registry; female sex was 59%, 57%, and 48%, respectively. Pre-existing liver disease was 9.9% in the US versus 3.6% in Pro-Euro and 6.3% in Spain.
  • Registry collaborations produced the nR criteria for predicting liver failure and RECAM, a revised electronic causality scale reported to outperform RUCAM at diagnostic extremes; DILIN also reported that DILI led directly or indirectly to fatality in 7.6% of cases, with 40% of these having non-acute liver failure courses.

Methods

  • Narrative review comparing three prospective DILI registries: the Spanish DILI Registry (established 1994), the Pro-Euro DILI Registry (EASL-funded from 2014, coordinated by the University of Málaga and University of Nottingham), and the US DILIN (established 2003 by the US NIDDK, with eight clinical centres and a coordinating centre at Duke University).
  • Data were drawn from the latest published reports for each registry and summarized in Table 1; the paper states that no datasets were generated or analysed during the current study.
  • The main analysis is a descriptive comparison of demographic, clinical, and etiological features across registries; no formal meta-analysis or primary statistical testing is described.

Limitations

  • Stated in the paper: the three registry studies were published in different years, which may mean findings have changed, particularly with the arrival of immune checkpoint inhibitors; LiverTox tends to ignore agents not marketed in the United States; and caution is required before standardizing RECAM across other DILI cohorts worldwide.
  • Evident from the text: as a review, it does not generate primary data and does not describe a systematic search or meta-analysis; registry comparisons may also be affected by differing inclusion criteria and causality assessment methods (Spanish registry uses CIOMS/RUCAM, Pro-Euro uses RUCAM, and DILIN uses an expert opinion scale).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s11901-026-00733-x

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

5 of 51 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Findingcitation

    Regarding herbal products, the percentage is much higher in the American registry (145 cases, 16%) than in the Spanish and European registries (6% in both, including cases of anabolic steroids).

    “Regarding to herbal products, the percentage is much higher in the American registry (145 cases, 16%) than in the Spanish and European registries (6% in both, including cases of anabolic steroids) [3][4][5]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.
  • Findingcitation

    In the Spanish register there is a predominance of males, compared to the other two where females predominate (48% in Spanish, 57% in European and 59% in American).

    “Furthermore, in the Spanish register there is a predominance of males, compared to the other two where females predominate (48% in Spanish, 57% in European and 59% in American) [3][4][5].”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.
  • Findingcitation

    In its cohort of over 1,000 patients, DILIN demonstrated that the nR Hy's law better identifies risk for death compared to the original Hy's law.

    “and also demonstrated in its cohort of over 1,000 patients that the nR Hy's law better identifies risk for death compared to the original Hy's law [31].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Hayashi PH, Rockey DC, Fontana RJ, Tillmann HL, Kaplowitz N, Barnhart HX, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017;66(4):1275–85. source
  • Findingcitation

    RECAM is an evidence-based update that is at least as effective as RUCAM at diagnosing DILI as expert opinion.

    “However, in a high-impact collaborative study, both the Spanish Registry and DILIN defined a new electronic causality scale called RECAM, which is an evidence-based update that is at least as effective as RUCAM at diagnosing DILI as expert opinion, but outperforms RUCAM at the diagnostic extremes [34] (Table 2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Hayashi PH, Lucena MI, Fontana RJ, Bjornsson ES, Aithal GP, Barnhart H, et al. A revised electronic version of RUCAM for the diagnosis of DILI. Hepatology. 2022;76(1):18–31. source
  • Findingcitation

    Amoxicillin-clavulanic acid is the most common xenobiotic, accounting for 10.1%, 22.9% and 12% in American, Spanish and European registries, respectively.

    “Evaluating only the responsible agents separately, amoxicillin-clavulanic acid is the most common xenobiotic, accounting for 10.1%, 22.9% and 12% in American, Spanish and European registries, respectively [3][4][5].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.
  • It may state two separate claims as one. 13
  • Probably not a substantial claim. 7

  • It may state two separate claims as one.

    Findingcitation

    Second place is occupied by anti-tuberculosis drugs (4.5%) in the Spanish registry and isoniazid in the American registry (5.3%).

    “Second place is occupied by anti-tuberculosis drugs (4.5%) in the Spanish registry and isoniazid in the American registry (5.3%) [3,4].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source

      The Results section (‘DILI in underlying liver disease’; page unavailable) identifies isoniazid as an implicated drug in the American DILIN cohort. The passages on the most frequently implicated drugs do not establish that it ranked second or accounted for 5.3% of cases. The Spanish-registry figure appears to be attributed to the other citation in the sentence. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • It may state two separate claims as one.

    Findingcitation

    The percentage of underlying liver disease was higher in the American registry (around 10%) than in the Spanish registry (6.3%), although the proportion of patients with immunoallergic phenotype was the same in both registries (15%).

    “The percentage of underlying liver disease was higher in the American registry (around 10%) than in the Spanish registry (6.3%), although the proportion of patients with immunoallergic phenotype was the same in both registries (15%) [3,4].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source

      The Results section on underlying liver disease reports that 89 of 899 patients (10%) in the American DILIN cohort had pre-existing chronic liver disease. The Results section on clinical patterns reports immuno-allergic features by injury pattern (11%, 16%, and 18%), not an overall 15%. This paper does not supply the Spanish registry figures or establish that the proportions were the same in both registries; the sentence also cites another source. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Interpretationcitation

    DILI diagnosis will become more precise, reliable and consistent thanks to RECAM's enhanced objectivity and clarity.

    “In addition, DILI diagnosis will become more precise, reliable and consistent thanks to RECAM's enhanced objectivity and clarity [34].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [34] Hayashi PH, Lucena MI, Fontana RJ, Bjornsson ES, Aithal GP, Barnhart H, et al. A revised electronic version of RUCAM for the diagnosis of DILI. Hepatology. 2022;76(1):18–31. source

  • It may state two separate claims as one.

    Findingcitation

    In terms of severity of liver injury, percentages are fairly homogeneous between the Spanish and European registries, with a higher frequency of severe and fatal outcomes in the American registry, at 19% and 7% respectively.

    “In terms of severity of liver injury, percentages are fairly homogeneous between the Spanish and European registries, with a higher frequency of severe and fatal outcomes in the American registry, at 19% and 7% respectively.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.
    • Rests on an assumption: The US DILIN's higher severity and different etiologies are not due to differences in healthcare access, reporting, or inclusion criteria.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Findingcitation

    In 2017, the DILIN group reported that DILI leads directly or indirectly to fatality in 7.6% of cases, and 40% of these had non-acute liver failure courses.

    “In 2017, the DILIN group reported that DILI leads directly or indirectly to fatality in 7.6% of cases, and 40% of these had non-acute liver failure courses”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Hayashi PH, Rockey DC, Fontana RJ, Tillmann HL, Kaplowitz N, Barnhart HX, et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology. 2017;66(4):1275–85. source

  • It may state two separate claims as one.

    Findingcitation

    In all three registries, the predominant pattern was hepatocellular, with jaundice rates of between 60 and 70%.

    “In all three registries, the predominant pattern was hepatocellular, with jaundice rates of between 60 and 70% [3][4][5].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • It may state two separate claims as one.

    Findingcitation

    The average age was around 55 years in both the European and Spanish hepatotoxicity registries, being slightly lower (49 years on average) in the North American registry.

    “Regarding to demographic data, it should be noted that the average age was around 55 years in both the European and Spanish hepatotoxicity registries, being slightly lower (49 years on average) in the North American registry.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • It may state two separate claims as one.

    Findingcitation

    In the more recent European registry, there is a notable increase in the presence of flucoxacillin (11%), atorvastatin (8%), and nivolumab-ipilimumab, a combination with 16 cases (8%).

    “In contrast, in the more recent European registry, there is a notable increase in the presence of flucoxacillin (11%), atorvastatin (8%), and nivolumab-ipilimumab, a combination with 16 cases (8%) [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • It may state two separate claims as one.

    Interpretationreasoning

    Registries play an important role in monitoring the safety of medicines, particularly after they have been placed on the market, as they can detect and characterise 'signals of hepatotoxicity' and are potentially valuable sources of data to support decision-making by regulatory agencies.

    “These registries play an important role in monitoring the safety of medicines, particularly after they have been placed on the market, as they can detect and characterise 'signals of hepatotoxicity' and are potentially valuable sources of data to support decisionmaking by regulatory agencies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Traditionally, the most widely accepted causality scale for idiosyncratic DILI has been the CIOMS-RUCAM scale.

    “Traditionally, the most widely accepted causality scale for idiosyncratic DILI has been the CIOMS-RUCAM scale [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990;11(2):272–6. source

  • Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.

    Interpretationnone given

    These networks are essential for identifying diagnostic biomarkers.

    “These networks are essential for identifying diagnostic biomarkers, and their findings benefit not only clinicians, but also regulators.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • It may state two separate claims as one.

    Premisecitation

    The pharmacological groups most frequently involved in DILI are antimicrobials, cardiovascular system drugs, and musculoskeletal system drugs, although this varies according to country and areas of the world.

    “The pharmacological groups most frequently involved in DILI are antimicrobials, cardiovascular system drugs, and musculoskeletal system drugs, although this varies according to country and areas of the world [3][4][5][6].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [3] Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–52. e7. source
    • cites [4] Stephens C, Robles-Diaz M, Medina-Caliz I, Garcia-Cortes M, Ortega-Alonso A, Sanabria-Cabrera J, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86–97. source
    • cites [5] Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43(1):115–26. source
    • cites [6] Bessone F, Hernandez N, Medina-Caliz I, Garcia-Cortes M, Schinoni MI, Mendizabal M, et al. Drug-induced Liver Injury in Latin America: 10-year Experience of the Latin American DILI (LATINDILI) Network. Clin Gastroenterol Hepatol. 2025;23(1):89–102. source

  • Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.

    Interpretationcitation

    Innovations like the nR criteria for predicting liver failure and the RECAM causality scale represent major leaps toward standardized, objective DILI management and helping regulators to better identify serious DILI signals.

    “Innovations like the nR criteria for predicting liver failure and the RECAM causality scale represent major leaps toward standardized, objective DILI management and helping regulators to better identify serious DILI signals.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.

    Interpretationreasoning

    Registries have fundamentally transformed our approach to idiosyncratic drug-induced liver injury (DILI), bridging the critical gap left by underpowered clinical trials.

    “Registries have fundamentally transformed our approach to idiosyncratic drug-induced liver injury (DILI), bridging the critical gap left by underpowered clinical trials.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • It may state two separate claims as one.

    Premisecitation

    The vast majority of DILI cases occur at therapeutic doses in a small proportion of individuals exposed to the drug, representing an idiosyncratic reaction, and are unpredictable based on the drug's mechanism of action and related to the uniqueness of the individual.

    “The vast majority of cases of DILI occur at therapeutic doses in a small proportion of individuals exposed to the drug, representing an idiosyncratic reaction, and therefore unpredictable based on the drug's mechanism of action and related to the uniqueness of the individual [1,2].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Andrade RJ, Chalasani N, Bjornsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, et al. Drug-induced liver injury. Nat Rev Dis Primers. 2019;5(1):58. source
    • cites [2] European Association for the Study of the Liver. Electronic address eee, Clinical Practice Guideline Panel C, Panel m, representative EGB. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019;70(6):1222–61. source

  • It may state two separate claims as one.

    Interpretationreasoning

    By systematically collecting prospective data, the Spanish DILI Registry, the Pro-Euro DILI registry, and the US DILIN have not only mapped the shifting epidemiology of DILI, but also delivered tangible clinical tools.

    “By systematically collecting prospective data, the Spanish DILI Registry, the Pro-Euro DILI registry, and the US DILIN have not only mapped the shifting epidemiology of DILI, but also delivered tangible clinical tools.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Drug-induced liver injury (DILI) is an uncommon adverse reaction to drugs and other chemicals, including herbal and dietary supplements (HDS).

    “Drug-induced liver injury (DILI) is an uncommon adverse reaction to drugs, and other chemicals, including herbal and dietary supplements (HDS).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Andrade RJ, Chalasani N, Bjornsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, et al. Drug-induced liver injury. Nat Rev Dis Primers. 2019;5(1):58. source
    • cites [2] European Association for the Study of the Liver. Electronic address eee, Clinical Practice Guideline Panel C, Panel m, representative EGB. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019;70(6):1222–61. source
17 of 17

  • The paper relies on this without support.

    The three registries' case definitions, data collection methods, and reporting periods are sufficiently similar to allow valid comparison of etiologies and outcomes.

    “The demographic, clinical, and etiological characteristics of the three cohorts are summarized in Table 1.”
    “These differences in severity in the registries forced us to examine in detail the main agents responsible for drug-induced liver injury, as the characteristics of population are quite similar.”

  • The paper relies on this without support.

    The US DILIN's higher severity and different etiologies are not due to differences in healthcare access, reporting, or inclusion criteria.

    “In terms of severity of liver injury, percentages are fairly homogeneous between the Spanish and European registries, with a higher frequency of severe and fatal outcomes in the American registry, at 19% and 7% respectively.”
2 of 2

Citations

Cites

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Research works printed but not linked: 1

  1. LiverTox. LiverTox [cited 2026 9th March]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK571102

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Related

Metadata

Authors
Toro-Ortiz, J. P., Andrade, R. J., & Pinazo-Bandera, J.
Affiliations
  • Instituto de Investigación Biomédica de Málaga (ES)
  • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
Corresponding author
Andrade, Raúl J.
ORCID
Venue
Current Hepatology Reports
Publisher
Springer Science and Business Media LLC
Published
2026-05-11
Volume
25
Issue
1
ISSN
  • 1540-3416 (ISSN-L)
  • 2195-9595
DOI
10.1007/s11901-026-00733-x
OpenAlex
W7160843407
Cited by
0
References
33
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
Current Hepatology Reports (publishedVersion, cc-by)
Funders
Universidad de Málaga
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Pharmacology (medical) › Drug-Induced Adverse Reactions
Keywords
idiosyncratic drug-induced liver injury, amoxicillin-clavulanic acid, herbal supplements, immune checkpoint inhibitors, RUCAM, drug safety, genetic risk factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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