Use of putative hepatoprotective agents as an adjunct to anti-TB treatment in Europe

O Kirakosyan¹, M Reimann^{1

2

3}, A B Andersen⁴, A Bjarnason⁵, Á Bakos⁶, A M Dyrhol-Riise^{7

8}, A M McLaughlin⁹, C Nita¹⁰, D Pieridou¹¹, D Chesov^{1

12}, E V Davidavičienė¹³, G Günther^{14

15}, H Atshemyan¹⁶, I Muylle¹⁷, I Solovic¹⁸, J Bruchfeld^{19

20}, K Manika²¹, L Kuksa²², L R Codecasa²³, M Stosic^{24

25}, M Skowroński²⁶, M J Makek^{27

28}, M Fréchet Jachym²⁹, M Knappik³⁰, M Santin^{31

32

33}, N Yatskevich³⁴, O Konstantynovska^{35

36}, O Akkerman^{37

38}, P Svetina³⁹, P Viiklepp⁴⁰, R Duarte^{41

42

43

44}, S Zeynel⁴⁵, T Togonidze⁴⁶, T Vasankari^{47

48}, V Parris⁴⁹, Ş Özkara^{50

51}, C Lange^{1

2

3

52

53}, T T Brehm^{1

2

54}

Affiliations

¹ Department of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
² German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.
³ Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany.
⁴ Odense University Hospital, Department of Infectious Diseases, Copenhagen, Denmark.
⁵ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁶ Koranyi National Institute for Pulmonology, Budapest, Hungary.
⁷ Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
⁸ University of Oslo, Oslo, Norway.
⁹ National TB Centre, St James's Hospital, Dublin, Ireland.
¹⁰ Marius Nasta National Center of Pneumology, Bucharest, Romania.
¹¹ National Reference Laboratory for Mycobacteria, Nicosia General Hospital, Nicosia, Cyprus.
¹² Department of Pulmonology and Allergology, State University of Medicine and Pharmaceutics "Nicolae Testemiţanu", Chisinau, Moldova.
¹³ Vilnius University Hospital Santaros Klinikos, Department of Tuberculosis State Information System, Vilnius, Lithuania.
¹⁴ Department of Pulmonary Medicine and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁵ Department of Medical Sciences, School of Medicine, University of Namibia, Windhoek, Namibia.
¹⁶ National Center of Pulmonology, Yerevan, Armenia.
¹⁷ Division of Pneumology, Onze-Lieve-Vrouw Ziekenhuis (OLV) Aalst, Aalst, Belgium.
¹⁸ National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Slovakia.
¹⁹ Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
²⁰ Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
²¹ Respiratory Diseases and Tuberculosis Pulmonary Department, Aristotle University of Thessaloniki, "G. Papanikolaou" Hospital, Thessaloniki, Greece.
²² Riga East University Hospital, Tuberculosis and Lung Disease Clinic, WHO CC, Riga, Latvia.
²³ Regional TB Reference Centre, Villa Marelli Institute-Niguarda Hospital, Milan, Italy.
²⁴ Institute of Public Health of Serbia "Dr Milan Jovanovic Batut", Belgrade, Serbia.
²⁵ University of Health and Business Studies Valjevo, Valjevo, Serbia.
²⁶ Tuberculosis Department, Wielkopolskie Center of Pulmonology and Thoracic Surgery, Poznań, Poland.
²⁷ University of Zagreb, School of Medicine, Zagreb, Croatia.
²⁸ University Hospital Centre Zagreb, Department for Pulmonary Diseases, Zagreb, Croatia.
²⁹ Centre Hospitalier de Bligny, Briis-sous-Forges, France.
³⁰ Klinik Penzing, Vienna, Austria.
³¹ Tuberculosis Unit, Department of Infectious Diseases, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
³² Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
³³ Centre for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
³⁴ The Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus.
³⁵ V. N. Karazin Kharkiv National University, Department of Infectious Diseases and Clinical Immunology, Kharkiv, Ukraine.
³⁶ Regional Phtisiopulmonological Center of the Kharkiv Regional Council, Kharkiv, Ukraine.
³⁷ University of Groningen, University Medical Centrum Groningen, Dept of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.
³⁸ University of Groningen, University Medical Centrum Groningen, TB Center Beatrixoord, Groningen, The Netherlands.
³⁹ National TB Program and Tuberculosis Registry of Republic of Slovenia, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
⁴⁰ National Institute for Health Development, Tallinn, Estonia.
⁴¹ Unidade de Investigação em Epidemiologia (EPI Unit), Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal.
⁴² Departamento de Saúde Comunitaria, Estudos de Populações, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
⁴³ Serviço de Pneumologia, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
⁴⁴ Unidade de Investigação Clínica, Administração Regional de Saúde do Norte, Porto, Portugal.
⁴⁵ Institute for Lung Diseases and Tuberculosis, Skopje, North Macedonia.
⁴⁶ National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
⁴⁷ Finnish Lung Health Association (Filha), Helsinki, Finland.
⁴⁸ University of Turku, Turku, Finland.
⁴⁹ London North West University Healthcare NHS Trust, London, UK.
⁵⁰ Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, 8th Clinic, Sanatoryum Caddesi, Ankara, Turkey.
⁵¹ Nergis Sokak 15/4, Ankara, Turkey.
⁵² Baylor College of Medicine and Texas Children's Hospital, Global Tuberculosis Program, Houston, Texas, USA.
⁵³ Institute for Infection Research and Vaccine Development (IIRVD), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵⁴ Division of Infectious Diseases, I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PMID: 39959402
PMCID: PMC11827669
DOI: 10.5588/ijtldopen.24.0498

Use of putative hepatoprotective agents as an adjunct to anti-TB treatment in Europe

O Kirakosyan et al. IJTLD Open. 2025.

. 2025 Feb 1;2(2):101-106.

doi: 10.5588/ijtldopen.24.0498. eCollection 2025 Feb.

Authors

Affiliations

¹ Department of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
² German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.
³ Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany.
⁴ Odense University Hospital, Department of Infectious Diseases, Copenhagen, Denmark.
⁵ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁶ Koranyi National Institute for Pulmonology, Budapest, Hungary.
⁷ Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
⁸ University of Oslo, Oslo, Norway.
⁹ National TB Centre, St James's Hospital, Dublin, Ireland.
¹⁰ Marius Nasta National Center of Pneumology, Bucharest, Romania.
¹¹ National Reference Laboratory for Mycobacteria, Nicosia General Hospital, Nicosia, Cyprus.
¹² Department of Pulmonology and Allergology, State University of Medicine and Pharmaceutics "Nicolae Testemiţanu", Chisinau, Moldova.
¹³ Vilnius University Hospital Santaros Klinikos, Department of Tuberculosis State Information System, Vilnius, Lithuania.
¹⁴ Department of Pulmonary Medicine and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁵ Department of Medical Sciences, School of Medicine, University of Namibia, Windhoek, Namibia.
¹⁶ National Center of Pulmonology, Yerevan, Armenia.
¹⁷ Division of Pneumology, Onze-Lieve-Vrouw Ziekenhuis (OLV) Aalst, Aalst, Belgium.
¹⁸ National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Slovakia.
¹⁹ Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
²⁰ Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
²¹ Respiratory Diseases and Tuberculosis Pulmonary Department, Aristotle University of Thessaloniki, "G. Papanikolaou" Hospital, Thessaloniki, Greece.
²² Riga East University Hospital, Tuberculosis and Lung Disease Clinic, WHO CC, Riga, Latvia.
²³ Regional TB Reference Centre, Villa Marelli Institute-Niguarda Hospital, Milan, Italy.
²⁴ Institute of Public Health of Serbia "Dr Milan Jovanovic Batut", Belgrade, Serbia.
²⁵ University of Health and Business Studies Valjevo, Valjevo, Serbia.
²⁶ Tuberculosis Department, Wielkopolskie Center of Pulmonology and Thoracic Surgery, Poznań, Poland.
²⁷ University of Zagreb, School of Medicine, Zagreb, Croatia.
²⁸ University Hospital Centre Zagreb, Department for Pulmonary Diseases, Zagreb, Croatia.
²⁹ Centre Hospitalier de Bligny, Briis-sous-Forges, France.
³⁰ Klinik Penzing, Vienna, Austria.
³¹ Tuberculosis Unit, Department of Infectious Diseases, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
³² Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
³³ Centre for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
³⁴ The Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus.
³⁵ V. N. Karazin Kharkiv National University, Department of Infectious Diseases and Clinical Immunology, Kharkiv, Ukraine.
³⁶ Regional Phtisiopulmonological Center of the Kharkiv Regional Council, Kharkiv, Ukraine.
³⁷ University of Groningen, University Medical Centrum Groningen, Dept of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.
³⁸ University of Groningen, University Medical Centrum Groningen, TB Center Beatrixoord, Groningen, The Netherlands.
³⁹ National TB Program and Tuberculosis Registry of Republic of Slovenia, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
⁴⁰ National Institute for Health Development, Tallinn, Estonia.
⁴¹ Unidade de Investigação em Epidemiologia (EPI Unit), Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal.
⁴² Departamento de Saúde Comunitaria, Estudos de Populações, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
⁴³ Serviço de Pneumologia, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
⁴⁴ Unidade de Investigação Clínica, Administração Regional de Saúde do Norte, Porto, Portugal.
⁴⁵ Institute for Lung Diseases and Tuberculosis, Skopje, North Macedonia.
⁴⁶ National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
⁴⁷ Finnish Lung Health Association (Filha), Helsinki, Finland.
⁴⁸ University of Turku, Turku, Finland.
⁴⁹ London North West University Healthcare NHS Trust, London, UK.
⁵⁰ Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, 8th Clinic, Sanatoryum Caddesi, Ankara, Turkey.
⁵¹ Nergis Sokak 15/4, Ankara, Turkey.
⁵² Baylor College of Medicine and Texas Children's Hospital, Global Tuberculosis Program, Houston, Texas, USA.
⁵³ Institute for Infection Research and Vaccine Development (IIRVD), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵⁴ Division of Infectious Diseases, I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PMID: 39959402
PMCID: PMC11827669
DOI: 10.5588/ijtldopen.24.0498

Abstract

Background: Anecdotal information suggests that clinical practice regarding the use of putative hepatoprotective agents in TB treatment varies across countries in the WHO European Region.

Methods: Between November 2023 and May 2024, we conducted a standardised questionnaire survey on the use of putative hepatoprotective agents in patients receiving TB treatment among Tuberculosis Network European Trials Group (TBnet) representatives in countries in the WHO European Region.

Results: We received valid responses from 37 of 53 countries (69.8%), with 16 (43.2%) reporting regular use of putative hepatoprotective agents during anti-TB treatment. Half of these countries (n = 8) are part of the former Soviet Union. In five countries, these agents are recommended by national guidelines. The most commonly used hepatoprotective agents were silibin/silymarin (n = 9, 56.3%), ursodeoxycholic acid (n = 5, 31.3%), and soy phospholipids (n = 4, 25.0%). Treatment duration varied, with 56.3% (n = 9) using them for less than 1 month, 18.8% (n = 3) for 1-3 months, and 18.8% (n = 3) for 4-6 months.

Conclusions: Putative hepatoprotective agents are widely used as an adjunct to TB treatment in the WHO European Region, particularly in the countries of the former Soviet Union, some of which have included them in their national guidelines.

Keywords: drug-induced liver injury; hepatitis; hepatotoxicity; silibinin; ursodeoxycholic acid.

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Figures

**Figure 1.**
Flow diagram of participating countries

**Figure 2.**
National practices on the use of putative hepatoprotective agents in TB treatment. Twelve countries were excluded because of their small population or lack of contacts through the TBnet network. A further four countries did not respond to the questionnaire.

**Figure 3.**
Putative hepatoprotective agents used as an adjunct to anti-TB treatment in European countries regularly or as part of guideline recommendations. *Includes ornithine, vitamin B, aspartate, Antral^® (Farmak JSC, Kyiv, Ukraine), arginine glutamate and Remaxol^® (POLYSAN Ltd, St Petersburg, Russia) (n = 1 country each).

See this image and copyright information in PMC

References

1. European Centre for Disease Prevention and Control & World Health Organization, Regional Office for Europe . Tuberculosis surveillance and monitoring in Europe 2024: 2022 data. Solna, Sweden: ECDC, 2024.
1. World Health Organization . WHO consolidated guidelines on tuberculosis. Module 4: Treatment – Drug-susceptible tuberculosis treatment. Geneva, Switzerland: WHO, 2022. - PubMed
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1. Huang YS, et al. . Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology. 2003;37(4):924–930. - PubMed
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Use of putative hepatoprotective agents as an adjunct to anti-TB treatment in Europe

Affiliations

Use of putative hepatoprotective agents as an adjunct to anti-TB treatment in Europe

Authors

Affiliations

Abstract

Figures

References

LinkOut - more resources

Full Text Sources