A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH
The specific pathways, timescales, and dynamics driving the progression of fibrosis in NAFLD and NASH are not yet fully understood. Hence, a mechanistic model of the pathogenesis and treatment of fibrosis in NASH will necessarily have significant uncertainties. The rate of fibrosis progression and t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1130890/full |
| _version_ | 1797816717251969024 |
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| author | Lyndsey F. Meyer Cynthia J. Musante Richard Allen |
| author_facet | Lyndsey F. Meyer Cynthia J. Musante Richard Allen |
| author_sort | Lyndsey F. Meyer |
| collection | DOAJ |
| description | The specific pathways, timescales, and dynamics driving the progression of fibrosis in NAFLD and NASH are not yet fully understood. Hence, a mechanistic model of the pathogenesis and treatment of fibrosis in NASH will necessarily have significant uncertainties. The rate of fibrosis progression and the heterogeneity of pathogenesis across patients are not thoroughly quantified. To address this problem, we have developed a continuous-time Markov chain model that is able to capture the heterogeneity of fibrosis progression observed in the clinic. We estimated the average time of disease progression through various stages of fibrosis using seven published clinical studies involving paired liver biopsies. Sensitivity analysis revealed therapeutic intervention at stage F1 or stage F2 results in greatest potential improvement in the average fibrosis scores for a typical patient cohort distribution. These results were in good agreement with a retrospective analysis of placebo-controlled pioglitazone clinical trials for the treatment of NAFLD and NASH. This model provides support for determining patient populations, duration, and potential successful endpoints for clinical trial design in the area of NAFLD and NASH. |
| first_indexed | 2024-03-13T08:42:53Z |
| format | Article |
| id | doaj.art-3051fb48e64a4ea79bba6d0b8696a938 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-13T08:42:53Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-3051fb48e64a4ea79bba6d0b8696a9382023-05-30T08:53:31ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-05-011010.3389/fmed.2023.11308901130890A continuous-time Markov chain model of fibrosis progression in NAFLD and NASHLyndsey F. MeyerCynthia J. MusanteRichard AllenThe specific pathways, timescales, and dynamics driving the progression of fibrosis in NAFLD and NASH are not yet fully understood. Hence, a mechanistic model of the pathogenesis and treatment of fibrosis in NASH will necessarily have significant uncertainties. The rate of fibrosis progression and the heterogeneity of pathogenesis across patients are not thoroughly quantified. To address this problem, we have developed a continuous-time Markov chain model that is able to capture the heterogeneity of fibrosis progression observed in the clinic. We estimated the average time of disease progression through various stages of fibrosis using seven published clinical studies involving paired liver biopsies. Sensitivity analysis revealed therapeutic intervention at stage F1 or stage F2 results in greatest potential improvement in the average fibrosis scores for a typical patient cohort distribution. These results were in good agreement with a retrospective analysis of placebo-controlled pioglitazone clinical trials for the treatment of NAFLD and NASH. This model provides support for determining patient populations, duration, and potential successful endpoints for clinical trial design in the area of NAFLD and NASH.https://www.frontiersin.org/articles/10.3389/fmed.2023.1130890/fullNAFLDNASHfibrosis progressionMarkov chain modelliver biopsyfibrosis score |
| spellingShingle | Lyndsey F. Meyer Cynthia J. Musante Richard Allen A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH Frontiers in Medicine NAFLD NASH fibrosis progression Markov chain model liver biopsy fibrosis score |
| title | A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH |
| title_full | A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH |
| title_fullStr | A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH |
| title_full_unstemmed | A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH |
| title_short | A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH |
| title_sort | continuous time markov chain model of fibrosis progression in nafld and nash |
| topic | NAFLD NASH fibrosis progression Markov chain model liver biopsy fibrosis score |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1130890/full |
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