Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches

Ahmad, Aqil; Ahmad, Riaz

doi:10.4103/1319-3767.96445

Cited by 88 publications

(67 citation statements)

References 85 publications

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“…Excessive synthesis of ECM components leads to increased expression of α-SMA as well as changes in the expression of L-type voltage-operated Ca 2+ channels, which are known to mediate Ca 2+ influx and regulate cellular contraction (Gasull et al, 2001;Ahmad and Ahmad, 2012). In our study, HSCs co-cultured with HBx-expressing liver cells showed increased mRNA and protein expression of α-SMA compared to those cells co-cultured with live cells without expressing HBx.…”

Section: Effects Of Hbx On Hscsmentioning

confidence: 46%

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Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1

Chen

Huang

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We investigated the effects of the hepatitis B virus X gene (HBV X) on the activation of human hepatic stellate cells (HSCs) and the possible mechanisms underlying the pathway. Recombinant plasmid pHBV-X-IRES2-EGFP was constructed and transfected into HL-7702 cells using a lipid-mediated method. Transfected cells were screened by G418, which detected stable expression of the X gene by reverse transcription (RT)-PCR and Western blot analysis, and named L02/x. Cells not subjected to G418-selection were analyzed to confirm the transient expression of the X gene and named L02/48x. Subsequently, L02/x and L02/48x, together with non-HBx-expressing cells, were cocultured with HSCs in a non-contact transwell system. After 36 h of co-culture, the proliferation and migration of HSCs was detected using different cell counting methods. Finally, the mRNA and protein levels of α-SMA, Col I, and TGFβ1 in HSCs were detected by real-time PCR and western blot analysis. RT-PCR and Western blot analysis showed that L02/x and L02/48x cells can express HBV X gene mRNA and protein. Additionally, HSCs co-cultured with L02/x or L02/48x cells showed significantly higher proliferation and migration levels than

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Section: Effects Of Hbx On Hscsmentioning

confidence: 46%

“…When HSCs are activated, excessive ECM products, particularly Col I, are produced and secreted (Pinzani and Marra, 2001;Ahmad and Ahmad, 2012). Thus, increased expression of Col I is an indicator of HSC activation.…”

Section: Effects Of Hbx On Hscsmentioning

confidence: 99%

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1

Chen

Huang

et al. 2014

Genet. Mol. Res.

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“…58,59,226 These site-specific interventions have had their anti-fibrotic effects demonstrated in cell cultures, animal models, or preliminary human experiences and none has been integrated into a management algorithm. 60 Autoimmune hepatitis already has an effective therapy with drugs that have primary immunosuppressive and anti-inflammatory actions and secondary anti-fibrotic effects.…”

Section: Feasible Anti-fibrotic Interventions In Autoimmune Hepatitismentioning

confidence: 99%

“…157,166,193,263 Individualised modifications in conventional treatment may be beneficial, 16 and promising anti-fibrotic therapies that can supplement treatment must be evaluated and incorporated if validated. 58,59,226 Patients who are able to resolve all laboratory and histological manifestations of their disease within 6-12 months of conventional therapy have a low frequency of progressive hepatic fibrosis.…”

Section: Management Perspectivesmentioning

confidence: 99%

“…256 Other limited experiences have been less supportive of the anti-fibrotic effect of angiotensin inhibition in patients with chronic hepatitis C. 257,258 Treatment efficacies can vary between different types of liver disease, and they can also be affected by the nature of the principal treatment strategy. 59,226 The experiences with the angiotensin inhibitors in patients with chronic hepatitis C provide a basis for their evaluation in autoimmune hepatitis.…”

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confidence: 99%

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Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis

Czaja

2014

Aliment Pharmacol Ther

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SummaryBackgroundImmunosuppressive treatment of autoimmune hepatitis can prevent or reverse hepatic fibrosis, but these anti‐fibrotic effects are inconsistent secondary gains.AimTo describe the anti‐fibrotic effects of current therapies for autoimmune hepatitis, discuss the pathogenic mechanisms of hepatic fibrosis that might be targeted by anti‐fibrotic interventions, indicate the non‐invasive diagnostic tests of hepatic fibrosis that must be validated in autoimmune hepatitis and to suggest promising treatment opportunities.MethodsStudies cited in PubMed from 1972 to 2013 for autoimmune hepatitis, hepatic fibrosis, cirrhosis, anti‐fibrotic therapy and non‐invasive tests of hepatic fibrosis were selected.ResultsHepatic fibrosis improves in 53–57% of corticosteroid‐treated patients with autoimmune hepatitis; progressive fibrosis slows or is prevented in 79%; and cirrhosis may be reversed. Progressive hepatic fibrosis is associated with liver inflammation, and the inability to fully suppress inflammatory activity within 12 months is associated with progression to cirrhosis (54%) and death or need for liver transplantation (15%). Liver tissue examination remains the gold standard for assessing hepatic fibrosis, but laboratory and radiological tests may be useful non‐invasive methods to measure the fibrotic response. Severe liver inflammation can confound radiological assessments, and the preferred non‐invasive test in autoimmune hepatitis is uncertain. Individualised treatment adjustments and adjunctive anti‐fibrotic therapies are poised for study in this disease.ConclusionsThe prevention and reversal of hepatic fibrosis are achievable objectives in autoimmune hepatitis. Strategies that evaluate individualised therapies adjusted to the rapidity and completeness of the inflammatory response, and the use of adjunctive anti‐fibrotic interventions, must be evaluated.

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The protective effects of Acanthus ilicifolius alkaloid A and its derivatives on pro‐ and anti‐inflammatory cytokines in rats with hepatic fibrosis

Wai

Liang

Zhou

et al. 2014

Biotech and App Biochem

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This study was designed to investigate the protective effects of Acanthus ilicifolius alkaloid A [4-hydroxy-2-benzoxazolone (HBOA)] and its acetylated derivatives including 4-acetoxy-2-benzoxazolone (TC-2) and 3-acetyl-4-acetoxy-2-benzoxazolone (TC-3) on carbon tetrachloride (CCl4 )-induced liver fibrosis in rats. Sprague-Dawley rats were given CCl4 twice per week for 8 weeks to induce liver fibrosis. Then, they were treated with HBOA, TC-2, and TC-3 daily for 4 weeks, respectively. The serum indicators including total protein (TP), albumin (Alb), globulin, hyaluronic acid (HA), and laminin (LN) were measured by commercial kits. The messenger ribonucleic acid expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPAR-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1 ) and Toll-like receptor 4 (TLR4 ) was determined by reverse-transcriptase -PCR. The proteins of adiponectin, TGF-β1 , α-smooth muscle actin (α-SMA), and TLR4 were also detected by the immunohistochemical assay. The results showed that HBOA, TC-2, and TC-3 significantly attenuated the fibrotic degree induced by CCl4 as evidenced by higher levels of TP, Alb, adiponectin, and PPAR-γ, which in turn decreased the proliferation of hepatic stellate cells. Moreover, those drugs markedly decreased the levels of HA, LN, TNF-α, IL-6, TGF-β1 , α-SMA, and TLR4 . Our study indicates that HBOA, TC-2, and TC-3 have beneficial effects against liver fibrosis, and the mechanisms may be related to the inhibition of inflammatory response.

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Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches

Cited by 88 publications

References 85 publications

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1

Hepatitis B virus X protein activates human hepatic stellate cells through upregulating TGFβ1

Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis

The protective effects of Acanthus ilicifolius alkaloid A and its derivatives on pro‐ and anti‐inflammatory cytokines in rats with hepatic fibrosis

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