Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality
Background We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug-induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART). Methods Cases were drawn from a prospect...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Department of Medicine
2023
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613232622993408 |
|---|---|
| access_status_str | Open Access |
| author | Gunter, Hannah May |
| author2 | Cohen, Karen |
| author_browse | Cohen, Karen Gunter, Hannah May |
| author_facet | Cohen, Karen Gunter, Hannah May |
| author_sort | Gunter, Hannah May |
| collection | Thesis |
| description | Background We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug-induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART). Methods Cases were drawn from a prospective registry of hospitalised adults with suspected DILI due to ATT and/or ART in Cape Town, South Africa. Participants had to fulfil American Thoracic Society criteria for ATT interruption (alanine transaminase [ALT]≥5 times upper limit of normal [ULN]/ALT≥3 times [ULN] and symptomatic). Causality assessment by expert panel review served as reference standard. The panel ranked potentially implicated drugs as certain, probable, possible, or unlikely causes guided by World Health Organization Uppsala Monitoring Centre criteria. The RUCAM was performed for each potentially implicated drug. We calculated sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause for liver injury. Results We included 48 participants. All were HIV-positive. Twenty-seven were on concomitant ART and ATT, with a median of 6 potentially hepatotoxic drugs per case. Sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause of liver injury compared with expert panel review was 11% and 85% respectively. Implicated drugs (times ranked probable/certain by panel) were isoniazid (18/0), pyrazinamide (17/0), rifampicin (15/1), efavirenz (6/4), lopinavir/ritonavir (1/0). Conclusions HIV-positive patients with liver injury received multiple potentially implicated drugs, which may increase liver injury risk and complicates causality assessment. Compared with expert panel review, the RUCAM had low sensitivity in detecting probable or certain drug causes of liver injury. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/36963 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:52.713Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Department of Medicine |
| publisherStr | Department of Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/36963 Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality Gunter, Hannah May Cohen, Karen Clinical Pharmacology Background We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug-induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART). Methods Cases were drawn from a prospective registry of hospitalised adults with suspected DILI due to ATT and/or ART in Cape Town, South Africa. Participants had to fulfil American Thoracic Society criteria for ATT interruption (alanine transaminase [ALT]≥5 times upper limit of normal [ULN]/ALT≥3 times [ULN] and symptomatic). Causality assessment by expert panel review served as reference standard. The panel ranked potentially implicated drugs as certain, probable, possible, or unlikely causes guided by World Health Organization Uppsala Monitoring Centre criteria. The RUCAM was performed for each potentially implicated drug. We calculated sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause for liver injury. Results We included 48 participants. All were HIV-positive. Twenty-seven were on concomitant ART and ATT, with a median of 6 potentially hepatotoxic drugs per case. Sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause of liver injury compared with expert panel review was 11% and 85% respectively. Implicated drugs (times ranked probable/certain by panel) were isoniazid (18/0), pyrazinamide (17/0), rifampicin (15/1), efavirenz (6/4), lopinavir/ritonavir (1/0). Conclusions HIV-positive patients with liver injury received multiple potentially implicated drugs, which may increase liver injury risk and complicates causality assessment. Compared with expert panel review, the RUCAM had low sensitivity in detecting probable or certain drug causes of liver injury. 2023-02-22T08:25:36Z 2023-02-22T08:25:36Z 2022 2023-02-20T12:50:24Z Master Thesis Masters MMed http://hdl.handle.net/11427/36963 eng application/pdf Department of Medicine Faculty of Health Sciences |
| spellingShingle | Clinical Pharmacology Gunter, Hannah May Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality |
| thesis_degree_str | Master's |
| title | Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality |
| title_full | Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality |
| title_fullStr | Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality |
| title_full_unstemmed | Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality |
| title_short | Liver Injury in HIV-positive Patients on Antituberculosis and/or Antiretroviral Therapy – Assessing Causality |
| title_sort | liver injury in hiv positive patients on antituberculosis and or antiretroviral therapy assessing causality |
| topic | Clinical Pharmacology |
| url | http://hdl.handle.net/11427/36963 |
| work_keys_str_mv | AT gunterhannahmay liverinjuryinhivpositivepatientsonantituberculosisandorantiretroviraltherapyassessingcausality |