Skip to main content

Advertisement

SpringerLink
Log in

Role of liver biopsy in the era of clinical prediction scores for “drug-induced liver injury” (DILI): experience of a tertiary referral hospital

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The clinical implications of the biopsy findings in cases of drug-induced liver injury (DILI) are not fully elucidated. The aim of this study was to evaluate the histopathological findings of cases diagnosed as DILI and to correlate them with clinical and biochemical findings (such as causality assessment algorithms). We searched our department database for all cases of liver biopsy with findings consistent with toxic liver disease and selected those with a clinical diagnosis of DILI. The causative relationships were established according to Roussel Uclaf Causality Assessment Method (RUCAM). A total of 53 cases of DILI were reviewed, most of them diagnosed in hospitalized patients (83%). The analytical toxicity profile was hepatocellular (R > 5) in 60% of the cases and cholestatic (R < 2) in 26.4% of cases. The group of drugs most implicated was the anti-microbials (18, 34%). The predominant histological patterns were “necroinflammation” (67.9%) and “cholestasis” (28.3%). The hepatocellular biochemical pattern was not associated with the presence of predominantly necroinflammatory findings in the biopsy (p = 0.44), and the biochemical cholestatic pattern was not associated with the presence of predominantly cholestatic findings in the biopsy (p = 0.51). This study supports that a better insight into the pathologic mechanisms associated with DILI should be based on liver biopsy due to the lack of a uniform correlation between clinical and biochemical patterns. Also, a liver biopsy may be used in those cases where clinical suspicion of DILI persists despite a low score on current causality assessment algorithms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Fontana RJ, Seeff LB, Andrade RJ, Bjornsson E, Day CP, Serrano J, Hoofnagle JH (2010) Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. Hepatology 52(2):730–742. https://doi.org/10.1002/hep.23696

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L, Crippin JS, Blei AT, Samuel G, Reisch J, Lee WM (2002) Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 137(12):947–954. https://doi.org/10.7326/0003-4819-137-12-200212170-00007

    Article  PubMed  Google Scholar 

  3. Temple RJ, Himmel MH (2002) Safety of newly approved drugs: implications for prescribing. Jama 287(17):2273–2275. https://doi.org/10.1001/jama.287.17.2273

    Article  PubMed  Google Scholar 

  4. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH (2002) Timing of new black box warnings and withdrawals for prescription medications. Jama 287(17):2215–2220. https://doi.org/10.1001/jama.287.17.2215

    Article  PubMed  Google Scholar 

  5. Chalasani N, Bjornsson E (2010) Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology 138(7):2246–2259. https://doi.org/10.1053/j.gastro.2010.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Goodman ZD (2017) Phenotypes and pathology of drug-induced liver disease. Clin Liver Dis 21(1):89–101. https://doi.org/10.1016/j.cld.2016.08.006

    Article  PubMed  Google Scholar 

  7. Watkins PB, Seeff LB (2006) Drug-induced liver injury: summary of a single topic clinical research conference. Hepatology 43(3):618–631. https://doi.org/10.1002/hep.21095

    Article  PubMed  Google Scholar 

  8. Teschke R, Schwarzenboeck A, Hennermann KH (2008) Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol 20(12):1182–1193. https://doi.org/10.1097/MEG.0b013e3283036768

    Article  PubMed  Google Scholar 

  9. Kleiner DE, Chalasani NP, Lee WM, Fontana RJ, Bonkovsky HL, Watkins PB, Hayashi PH, Davern TJ, Navarro V, Reddy R, Talwalkar JA, Stolz A, Gu J, Barnhart H, Hoofnagle JH (2014) Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology 59(2):661–670. https://doi.org/10.1002/hep.26709

    Article  PubMed  Google Scholar 

  10. Kleiner DE (2014) Liver histology in the diagnosis and prognosis of drug-induced liver injury. Clin Liver Dis 4(1):12–16. https://doi.org/10.1002/cld.371

    Article  Google Scholar 

  11. Katoonizadeh A, Nevens F, Verslype C, Pirenne J, Roskams T (2006) Liver regeneration in acute severe liver impairment: a clinicopathological correlation study. Liver Int 26(10):1225–1233. https://doi.org/10.1111/j.1478-3231.2006.01377.x

    Article  PubMed  Google Scholar 

  12. Bjornsson E, Kalaitzakis E, Olsson R (2007) The impact of eosinophilia and hepatic necrosis on prognosis in patients with drug-induced liver injury. Aliment Pharmacol Ther 25(12):1411–1421. https://doi.org/10.1111/j.1365-2036.2007.03330.x

    Article  CAS  PubMed  Google Scholar 

  13. Kleiner DE (2011) Liver injury due to drugs and herbal agents. In: Saxena R (ed) Practical hepatic pathology. 1st edition edn. Sanders, Philadelphia, pp 311–352

    Google Scholar 

  14. Batts KP, Ludwig J (1995) Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 19(12):1409–1417

    Article  CAS  Google Scholar 

  15. EASL Clinical Practice Guidelines: Autoimmune hepatitis (2015). J Hepatol 63 (4):971–1004. doi:https://doi.org/10.1016/j.jhep.2015.06.030

  16. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis (2017). J Hepatol 67 (1):145–172. doi:https://doi.org/10.1016/j.jhep.2017.03.022

  17. Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, Wilke RA, Avigan M, Kaplowitz N, Bjornsson E, Daly AK (2011) Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 89(6):806–815. https://doi.org/10.1038/clpt.2011.58

    Article  CAS  PubMed  Google Scholar 

  18. Benichou C (1990) Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol 11(2):272–276

    Article  CAS  Google Scholar 

  19. Bjornsson E (2006) Drug-induced liver injury: Hy’s rule revisited. Clin Pharmacol Ther 79(6):521–528. https://doi.org/10.1016/j.clpt.2006.02.012

    Article  CAS  PubMed  Google Scholar 

  20. Reuben A (2004) Hy’s law. Hepatology 39(2):574–578. https://doi.org/10.1002/hep.20081

    Article  PubMed  Google Scholar 

  21. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WGE, Czaja AJ, Desmet VJ, Donaldson PT, Eddleston ALWF, Fainboim L, Heathcote J, Homberg JC, Hoofnagle JH, Kakumu S, Krawitt EL, Mackay IR, MacSween RNM, Maddrey WC, Manns MP, McFarlane IG, Meyer zum Büschenfelde KH, Mieli-Vergani G, Nakanuma Y, Nishioka M, Penner E, Porta G, Portmann BC, Reed WD, Rodes J, Schalm SW, Scheuer PJ, Schrumpf E, Seki T, Toda G, Tsuji T, Tygstrup N, Vergani D, Zeniya M (1999) International Autoimmune Hepatitis Group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 31(5):929–938. https://doi.org/10.1016/S0168-8278(99)80297-9

    Article  CAS  PubMed  Google Scholar 

  22. EASL Clinical Practice Guidelines: Drug-induced liver injury (2019). J Hepatol 70 (6):1222–1261. doi:https://doi.org/10.1016/j.jhep.2019.02.014

  23. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD (2009) Liver biopsy. Hepatology 49(3):1017–1044. https://doi.org/10.1002/hep.22742

    Article  PubMed  Google Scholar 

  24. Gasmi B, Kleiner DE (2020) Liver histology: diagnostic and prognostic features. Clin Liver Dis 24(1):61–74. https://doi.org/10.1016/j.cld.2019.09.004

    Article  PubMed  Google Scholar 

  25. Becker MW, Lunardelli MJM, Tovo CV, Blatt CR (2019) Drug and herb-induced liver injury: a critical review of Brazilian cases with proposals for the improvement of causality assessment using RUCAM. Ann Hepatol 18(5):742–750. https://doi.org/10.1016/j.aohep.2019.03.010

    Article  PubMed  Google Scholar 

  26. Teschke R, Frenzel C (2013) Drug induced liver injury: do we still need a routine liver biopsy for diagnosis today? Ann Hepatol 13(1):121–126

    Article  Google Scholar 

  27. Hayashi PH (2009) Causality assessment in drug-induced liver injury. Semin Liver Dis 29(4):348–356. https://doi.org/10.1055/s-0029-1240003

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastroenterology Department, Centro Hospitalar e Universitário São João, Porto, Portugal

    Pedro Costa-Moreira, Rui Gaspar, Pedro Pereira, Susana Lopes & Guilherme Macedo

  2. Faculty of Medicine, University of Porto, Porto, Portugal

    Pedro Costa-Moreira, Rui Gaspar, Pedro Pereira, Susana Lopes, Fátima Carneiro & Guilherme Macedo

  3. Pathology Deparment, Centro Hospitalar e Universitário São João, Porto, Portugal

    Pedro Canão, Joanne Lopes & Fátima Carneiro

Authors
  1. Pedro Costa-Moreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui Gaspar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pedro Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susana Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pedro Canão
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joanne Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fátima Carneiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guilherme Macedo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Pedro Costa-Moreira was responsible for the study design, acquisition, and interpretation of data, drafting the manuscript, and statistical analysis. Rui Gaspar, Pedro Pereira, Susana Lopes, Pedro Canão, and Joanne Lopes were responsible for the acquisition and interpretation of data. Fátima Carneiro and Guilherme Macedo were responsible for critical revision of the manuscript for relevant intellectual content.

Corresponding author

Correspondence to Pedro Costa-Moreira.

Ethics declarations

This study was conducted according to the Declaration of Helsinki. The ethical approval for this study was obtained from the Ethics Committee of “Centro Hospitalar e Universitário São João”/Faculty of Medicine of the Porto University. Informed consent for research use of the histopathological data was obtained from each patient before the liver biopsy was performed.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Costa-Moreira, P., Gaspar, R., Pereira, P. et al. Role of liver biopsy in the era of clinical prediction scores for “drug-induced liver injury” (DILI): experience of a tertiary referral hospital. Virchows Arch 477, 517–525 (2020). https://doi.org/10.1007/s00428-020-02824-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-020-02824-6

Keywords

Search

Navigation