Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure
Nucleic acid testing to confirm sustained virological response (SVR) after HCV therapy is technical, often expensive, and frequently unavailable where disease prevalence is highest. Alternative surrogate biomarkers merit evaluation. In a short-treatment trial in Vietnam (SEARCH-1; n = 52) we analyse...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Wolters Kluwer
2023
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| _version_ | 1811139450796769280 |
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| author | Flower, B Nguyen Thi Ngoc, P McCabe, L Le Ngoc, C Vo Thi, T Thi Kim, HV Dang Trong, T Rahman, M Thwaites, G Walker, AS Hung, LM Vinh Chau, NV Cooke, GS Day, JN |
| author2 | SEARCH and STOPHCV investigators |
| author_facet | SEARCH and STOPHCV investigators Flower, B Nguyen Thi Ngoc, P McCabe, L Le Ngoc, C Vo Thi, T Thi Kim, HV Dang Trong, T Rahman, M Thwaites, G Walker, AS Hung, LM Vinh Chau, NV Cooke, GS Day, JN |
| author_sort | Flower, B |
| collection | OXFORD |
| description | Nucleic acid testing to confirm sustained virological response (SVR) after HCV therapy is technical, often expensive, and frequently unavailable where disease prevalence is highest. Alternative surrogate biomarkers merit evaluation. In a short-treatment trial in Vietnam (SEARCH-1; n = 52) we analysed how changes in alanine transaminase (ΔALT) and aspartate transaminase (ΔAST), from end of treatment (EOT) to EOT + 12 weeks, related to SVR, defined as HCV RNA < lower limit of quantification 12 weeks after EOT. In a separate UK trial (STOPHCV1; n = 202), we then tested the hypothesis that any elevation in ALT or AST between EOT and EOT12 is a sensitive screen for treatment failure. In SEARCH-1, among 48 individuals with data, 13 failed to achieve SVR. Median ΔALT and ΔAST were negative in cured patients but elevated when treatment failed [median ΔALT (IQR): -2 IU/L (-6, +2)] versus +17 IU/L (+7.5, +38) (p< 0.001). Amongst treatment failures, 12/13 had increase in ALT and 13/13 had increase in AST after EOT, compared with 12/35 in those cured. In STOPHCV1, 196/202 patients had evaluable data, of which 57 did not achieve SVR. A rise in ALT after EOT was 100% sensitive (95% C.I. [93.7 - 100%]) and 51% specific (42.4 - 59.7%) for detecting treatment failure. ΔAST >0 IU/L was 98.1% (89.9 - 99.9%) sensitive and 35.8% (27.3 - 45.1%) specific. A rise in ALT or AST after HCV therapy is a highly sensitive screen for treatment failure in mild liver disease. This finding could reduce costs and complexity of managing HCV. |
| first_indexed | 2024-03-07T07:49:21Z |
| format | Journal article |
| id | oxford-uuid:03c68dda-d4d8-4248-bf13-5bd0bfb9022b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:06:17Z |
| publishDate | 2023 |
| publisher | Wolters Kluwer |
| record_format | dspace |
| spelling | oxford-uuid:03c68dda-d4d8-4248-bf13-5bd0bfb9022b2024-05-31T09:34:25ZRise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failureJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:03c68dda-d4d8-4248-bf13-5bd0bfb9022bEnglishSymplectic ElementsWolters Kluwer2023Flower, BNguyen Thi Ngoc, PMcCabe, LLe Ngoc, CVo Thi, TThi Kim, HVDang Trong, TRahman, MThwaites, GWalker, ASHung, LMVinh Chau, NVCooke, GSDay, JNSEARCH and STOPHCV investigatorsNucleic acid testing to confirm sustained virological response (SVR) after HCV therapy is technical, often expensive, and frequently unavailable where disease prevalence is highest. Alternative surrogate biomarkers merit evaluation. In a short-treatment trial in Vietnam (SEARCH-1; n = 52) we analysed how changes in alanine transaminase (ΔALT) and aspartate transaminase (ΔAST), from end of treatment (EOT) to EOT + 12 weeks, related to SVR, defined as HCV RNA < lower limit of quantification 12 weeks after EOT. In a separate UK trial (STOPHCV1; n = 202), we then tested the hypothesis that any elevation in ALT or AST between EOT and EOT12 is a sensitive screen for treatment failure. In SEARCH-1, among 48 individuals with data, 13 failed to achieve SVR. Median ΔALT and ΔAST were negative in cured patients but elevated when treatment failed [median ΔALT (IQR): -2 IU/L (-6, +2)] versus +17 IU/L (+7.5, +38) (p< 0.001). Amongst treatment failures, 12/13 had increase in ALT and 13/13 had increase in AST after EOT, compared with 12/35 in those cured. In STOPHCV1, 196/202 patients had evaluable data, of which 57 did not achieve SVR. A rise in ALT after EOT was 100% sensitive (95% C.I. [93.7 - 100%]) and 51% specific (42.4 - 59.7%) for detecting treatment failure. ΔAST >0 IU/L was 98.1% (89.9 - 99.9%) sensitive and 35.8% (27.3 - 45.1%) specific. A rise in ALT or AST after HCV therapy is a highly sensitive screen for treatment failure in mild liver disease. This finding could reduce costs and complexity of managing HCV. |
| spellingShingle | Flower, B Nguyen Thi Ngoc, P McCabe, L Le Ngoc, C Vo Thi, T Thi Kim, HV Dang Trong, T Rahman, M Thwaites, G Walker, AS Hung, LM Vinh Chau, NV Cooke, GS Day, JN Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure |
| title | Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure |
| title_full | Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure |
| title_fullStr | Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure |
| title_full_unstemmed | Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure |
| title_short | Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure |
| title_sort | rise in alanine aminotransferase after hcv treatment is a highly sensitive screen for treatment failure |
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