Reversing Advanced Hepatic Fibrosis in NASH: Clearly Possible, but Widely at Hand?

Caldwell, Stephen H.; Argo, Curtis K.

doi:10.1007/s10620-015-3540-0

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…A CTMC model can estimate both rates of progression as well as rates of regression at each stage in fibrosis. It is necessary to include the regression mechanism as the data in literature suggests fibrosis improves in patients advised on diet and exercise, as well as patients treated with pioglitazone ( 25 ). The disadvantage of this modeling approach is that it requires sufficient data to estimate each parameter and there is limited data for patients in the later stages of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH

Meyer

Musante

2023

Front. Med.

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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.

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Section: Discussionmentioning

confidence: 99%

A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH

Meyer

Musante

2023

Front. Med.

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“…8 In their recent review, Povsic et al found no reports of sustained weight loss and impact on outcomes in people with NASH. 9 Pharmacological intervention may also be needed, 10 although the success of such approaches depends on the extent of liver damage and expected treatment outcomes. There are currently no Food and Drug Administration/European Medicines Agency-approved NASH-specific pharmacological therapies, although substantial effort is ongoing to develop treatments, with many agents in clinical development.…”

Section: Introductionmentioning

confidence: 99%

Real-world management of non-alcoholic steatohepatitis differs from clinical practice guideline recommendations and across regions

et al. 2022

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…When the causative agent of liver damage disappears, fibrosis can be reversed, meaning that proteases degrade ECM [9]. However, under certain conditions, fibrosis only partially resolves in some patients without preventing the onset of severe complications, such as HCC [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Switching to Regular Diet Partially Resolves Liver Fibrosis Induced by High-Fat, High-Cholesterol Diet in Mice

et al. 2022

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The globally prevalent disease, non-alcoholic steatohepatitis (NASH), is characterized by a steatotic and inflammatory liver. In NASH patients, tissue repair mechanisms, activated by the presence of chronic liver damage, lead to the progressive onset of hepatic fibrosis. This scar symptom is a key prognostic risk factor for liver-related morbidity and mortality. Conflicting reports discuss the efficiency of dietary interventions on the reversibility of advanced fibrosis established during NASH. In the present study, the effect of dietary interventions was investigated in the outcome of the fibrosis settled in livers of C57BL/6J mice on a high-fat, high-cholesterol diet (HFHCD) for 5 or 12 consecutive weeks. Various clinico-pathological investigations, including a histological analysis of the liver, measurement of plasma transaminases, steatosis and fibrosis, were performed. To assess the effectiveness of the dietary intervention on established symptoms, diseased mice were returned to a standard diet (SD) for 4 or 12 weeks. This food management resulted in a drastic reduction in steatosis, liver injuries, inflammatory markers, hepatomegaly and oxidative stress and a gradual improvement in the fibrotic state of the liver tissue. In conclusion, our results demonstrated that dietary intervention can partially reverse liver fibrosis induced by HFHCD feeding.

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Reversing Advanced Hepatic Fibrosis in NASH: Clearly Possible, but Widely at Hand?

Cited by 6 publications

References 25 publications

A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH

A continuous-time Markov chain model of fibrosis progression in NAFLD and NASH

Real-world management of non-alcoholic steatohepatitis differs from clinical practice guideline recommendations and across regions

Switching to Regular Diet Partially Resolves Liver Fibrosis Induced by High-Fat, High-Cholesterol Diet in Mice

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