Intestinal Fibrosis and Liver Fibrosis: Consequences of Chronic Inflammation or Independent Pathophysiology?

Overview

Journal Inflamm Intest Dis

Date 2018 Jun 21

PMID 29922656

Citations 11

Authors

Florian Rieder

Dominik Bettenworth

Jin Imai

Yutaka Inagaki

Affiliations

Soon will be listed here.

Abstract

Background: Intestinal fibrosis and liver fibrosis represent a significant burden for our patients and health-care systems. Despite the severe clinical problem and the observation that fibrosis is reversible, no specific antifibrotic therapies exist.

Summary: In this review, using an 'East-West' scientific collaboration, we summarize the current knowledge on principal mechanisms shared by intestinal fibrosis and liver fibrosis. We furthermore discuss inflammation as the cause of fibrogenesis in both entities, depict unique features of intestinal and hepatic fibrosis, and provide a future outlook on the development of antifibrotic therapies.

Key Messages: A collaborative effort in the field of fibrosis, covering multiple organ systems, will have the highest chance of leading to the development of a successful antifibrotic intervention.

Citing Articles

TWISTed fibroblasts: New drivers of intestinal fibrosis in Crohn's disease.

Lovisa S, Vetrano S Heliyon. 2024; 10(23):e40604.

PMID: 39654763 PMC: 11626011. DOI: 10.1016/j.heliyon.2024.e40604.

The Role of Genetic and Epigenetic Regulation in Intestinal Fibrosis in Inflammatory Bowel Disease: A Descending Process or a Programmed Consequence?.

Jarmakiewicz-Czaja S, Sokal A, Ferenc K, Motyka E, Helma K, Filip R Genes (Basel). 2023; 14(6).

PMID: 37372347 PMC: 10297896. DOI: 10.3390/genes14061167.

What Do NAFLD, Liver Fibrosis, and Inflammatory Bowel Disease Have in Common? Review of the Current Literature.

Jarmakiewicz-Czaja S, Gruszecka J, Filip R Metabolites. 2023; 13(3).

PMID: 36984818 PMC: 10051776. DOI: 10.3390/metabo13030378.

Therapeutic Potential of the Combination of Pentoxifylline and Vitamin-E in Inflammatory Bowel Disease: Inhibition of Intestinal Fibrosis.

Lee H J Clin Med. 2022; 11(16).

PMID: 36012952 PMC: 9410449. DOI: 10.3390/jcm11164713.

Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn's Disease Fibrosis.

Vieujean S, Hu S, Bequet E, Salee C, Massot C, Bletard N J Crohns Colitis. 2021; 15(10):1737-1750.

PMID: 33822017 PMC: 8861373. DOI: 10.1093/ecco-jcc/jjab061.

References

Afdhal N, Reddy K, Nelson D, Lawitz E, Gordon S, Schiff E . Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014; 370(16):1483-93. DOI: 10.1056/NEJMoa1316366. View

Hara M, Kono H, Furuya S, Hirayama K, Tsuchiya M, Fujii H . Interleukin-17A plays a pivotal role in cholestatic liver fibrosis in mice. J Surg Res. 2013; 183(2):574-82. DOI: 10.1016/j.jss.2013.03.025. View

Seki E, De Minicis S, Osterreicher C, Kluwe J, Osawa Y, Brenner D . TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 2007; 13(11):1324-32. DOI: 10.1038/nm1663. View

Friedman S, Sheppard D, Duffield J, Violette S . Therapy for fibrotic diseases: nearing the starting line. Sci Transl Med. 2013; 5(167):167sr1. DOI: 10.1126/scitranslmed.3004700. View

Trepo C, Chan H, Lok A . Hepatitis B virus infection. Lancet. 2014; 384(9959):2053-63. DOI: 10.1016/S0140-6736(14)60220-8. View

Bruns T, Peter J, Reuken P, Grabe D, Schuldes S, Brenmoehl J . NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis. Liver Int. 2011; 32(2):223-30. DOI: 10.1111/j.1478-3231.2011.02561.x. View

Uehara H, Nakagawa T, Katsuno T, Sato T, Isono A, Noguchi Y . Emergence of fibrocytes showing morphological changes in the inflamed colonic mucosa. Dig Dis Sci. 2009; 55(2):253-60. DOI: 10.1007/s10620-009-0730-7. View

Bettenworth D, Rieder F . Medical therapy of stricturing Crohn's disease: what the gut can learn from other organs - a systematic review. Fibrogenesis Tissue Repair. 2014; 7(1):5. PMC: 4230721. DOI: 10.1186/1755-1536-7-5. View

Uehara A, Takada H . Functional TLRs and NODs in human gingival fibroblasts. J Dent Res. 2007; 86(3):249-54. DOI: 10.1177/154405910708600310. View

10.

Kuhn A, Haust M, Ruland V, Weber R, Verde P, Felder G . Effect of bosentan on skin fibrosis in patients with systemic sclerosis: a prospective, open-label, non-comparative trial. Rheumatology (Oxford). 2010; 49(7):1336-45. DOI: 10.1093/rheumatology/keq077. View

11.

Babyatsky M, Rossiter G, Podolsky D . Expression of transforming growth factors alpha and beta in colonic mucosa in inflammatory bowel disease. Gastroenterology. 1996; 110(4):975-84. DOI: 10.1053/gast.1996.v110.pm8613031. View

12.

Hueber W, Sands B, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins P . Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012; 61(12):1693-700. PMC: 4902107. DOI: 10.1136/gutjnl-2011-301668. View

13.

Fallowfield J, Mizuno M, Kendall T, Constandinou C, Benyon R, Duffield J . Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. J Immunol. 2007; 178(8):5288-95. DOI: 10.4049/jimmunol.178.8.5288. View

14.

Burke J, Ferrante M, Dejaegher K, Watson R, Docherty N, De Hertogh G . Transcriptomic analysis of intestinal fibrosis-associated gene expression in response to medical therapy in Crohn's disease. Inflamm Bowel Dis. 2008; 14(9):1197-204. DOI: 10.1002/ibd.20482. View

15.

Cosnes J, Gower-Rousseau C, Seksik P, Cortot A . Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011; 140(6):1785-94. DOI: 10.1053/j.gastro.2011.01.055. View

16.

Kokot A, Sindrilaru A, Schiller M, Sunderkotter C, Kerkhoff C, Eckes B . alpha-melanocyte-stimulating hormone suppresses bleomycin-induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: melanocortin peptides as a novel treatment strategy for scleroderma?. Arthritis Rheum. 2009; 60(2):592-603. DOI: 10.1002/art.24228. View

17.

Higuchi Y, Kojima M, Ishii G, Aoyagi K, Sasaki H, Ochiai A . Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts. PLoS One. 2015; 10(6):e0129241. PMC: 4457624. DOI: 10.1371/journal.pone.0129241. View

18.

Rieder F, Fiocchi C . Intestinal fibrosis in IBD--a dynamic, multifactorial process. Nat Rev Gastroenterol Hepatol. 2009; 6(4):228-35. DOI: 10.1038/nrgastro.2009.31. View

19.

Schiff E, Lee S, Chao Y, Yoon S, Bessone F, Wu S . Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2010; 9(3):274-6. DOI: 10.1016/j.cgh.2010.11.040. View

20.

Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson I . Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2012; 381(9865):468-75. DOI: 10.1016/S0140-6736(12)61425-1. View