Fibrosis in Chronic Liver Disease: An Update on Diagnostic and Treatment Modalities

Manka, Paul; Zeller, Amos; Syn, Wing Kin

doi:10.1007/s40265-019-01126-9

Cited by 54 publications

(35 citation statements)

References 214 publications

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“…1 The negative functional consequences of these ECM changes are readily apparent in advanced organ diseases of the lung, liver, and kidney, where regulatory mechanisms and therapeutics have been extensively studied, but fibrosis also has dramatic effects on musculoskeletal tissues which can significantly affect physical function. [2][3][4] Notably, fibrosis is believed to drive post-traumatic joint contracture which affects approximately 50% of patients after injury and permanently limits joint function. [5][6][7][8] Currently, there are no treatment strategies which have consistently prevented joint contracture.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4]16 While these treatments have been shown to slow the progression of fibrosis, they lack the ability to prevent organ dysfunction. 4 Similarly, pharmacological strategies to minimize fibrosis in orthopedic tissues have exhibited decreased fibroblast proliferation and collagen deposition, but these changes have often not led to a corresponding improvement in function. [17][18][19][20] Safety concerns also arise because these drugs have pleiotropic effects, which could also alter angiogenesis, immunomodulation, and cell proliferation in non-fibrotic tissues.…”

Section: Introductionmentioning

confidence: 99%

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Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

et al. 2020

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Fibrosis is driven by a misdirected cell response causing the overproduction of extracellular matrix and tissue dysfunction. Numerous pharmacological strategies have attempted to prevent fibrosis but have attained limited efficacy with some detrimental side effects. While stem cell treatments have provided more encouraging results, they have exhibited high variability and have not always improved tissue function. To enhance stem cell efficacy, we evaluated whether mechanical memory could direct cell response. We hypothesized that mechanically pre‐conditioning on a soft matrix (soft priming) will delay adipose‐derived stem cell (ASC) transition to a pro‐fibrotic phenotype, expanding their regenerative potential, and improving healing in a complex tissue environment. Primary ASCs isolated from rat and human subcutaneous fat exhibited mechanical memory, demonstrated by a delayed cell response to stiffness following two weeks of soft priming including decreased cell area, actin coherency, and extracellular matrix production compared to cells on stiff substrates. Soft primed ASCs injected into our rat model of post‐traumatic elbow contracture decreased histological evidence of anterior capsule fibrosis and increased elbow range‐of‐motion when evaluated by joint mechanics. These findings suggest that exploiting mechanical memory by strategically controlling the culture environment during cell expansion may improve the efficacy of stem cell‐based therapies targeting fibrosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

et al. 2020

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“…Up to date, there are no antifibrotic agents available in the market. The approach used to treat LF is by managing the underlying disease [1], [3], [5].…”

Section: Introductionmentioning

confidence: 99%

Antifibrotic Activity of Phaleria macrocarpa Extract in Rat Liver-fibrosis Model: Focus on Oxidative Stress Markers, TGF-β1 and MMP-13

Wardhani

Sundari

Tjandrawinata³

et al. 2020

Open Access Maced J Med Sci

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AIM: This study was aimed to determine the antifibrotic activity of Phaleria macrocarpa (PM) extract in liver fibrosis (LF) and its possible mechanism in the rat model. METHODS: Sprague Dawley male rats were injected with 2 mL/kg BW of carbon tetrachloride intraperitoneally twice a week for 2 weeks, followed by 1 mL/kg BW for 6 weeks. Afterward, the treatments began from the 3rd week: Silymarin 100 mg/kg BW/day, standardized PM extract (Proliverenol) 75 or 150 mg/kg BW/day orally. Rats were sacrificed in the 8th week. Blood and liver were collected to analyze liver function, liver damage and fibrosis marker, oxidative stress markers, pro-fibrogenic cytokine, and antifibrotic marker. RESULTS: Our study showed that the treatment of silymarin and PM resulted in the normalized activity of liver function, followed by the amelioration of oxidative stress, demonstrated by the decreased malondialdehyde levels and an increased ratio of glutathione and glutathione disulfide. All markers examined showed that PM extract has antioxidant activity due to decreased hepatic stellate cell activation. We also found a decrease in tumor growth factors-β1 and protein expressions of matrix metalloproteinases-13 in all treatment groups compared to the carbon tetrachloride group. There were tendencies of the decreased fibrotic area following improvements of biochemical parameters. CONCLUSION: PM extracts ameliorate carbon tetrachloride-induced LF. The proposed mechanism is by overcoming oxidative stress and regulating pro-fibrogenic cytokine and antifibrotic markers.

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“…However, antifibrotic drugs are still in the animal experimental stage, and no effective antifibrotic drug is available in Western medicine [ 5 ]. Most CHB patients with hepatic fibrosis are treated with antiviral drugs, which have the potential for promoting regression of fibrosis; however, fibrosis progresses in many CHB-fibrosis patients treated with these medications.…”

Section: Introductionmentioning

confidence: 99%

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes

Shi

Xiao

Xie

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.

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Fibrosis in Chronic Liver Disease: An Update on Diagnostic and Treatment Modalities

Cited by 54 publications

References 214 publications

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

Antifibrotic Activity of Phaleria macrocarpa Extract in Rat Liver-fibrosis Model: Focus on Oxidative Stress Markers, TGF-β1 and MMP-13

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes

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