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Pathophysiology and Treatment Options for Hepatic Fibrosis: Can It Be Completely Cured?

ABSTRACT: Hepatic fibrosis is a dynamic process that occurs as a wound healing response against liver injury. During fibrosis, crosstalk between parenchymal and non-parenchymal cells, activation of different immune cells and signaling pathways, as well as a release of several inflammatory mediators take place, resulting in inflammation. Excessive inflammation drives hepatic stellate cell (HSC) activation, which then encounters various morphological and functional changes before transforming into proliferative and extracellular matrix (ECM)-producing myofibroblasts. Finally, enormous ECM accumulation interferes with hepatic function and leads to liver failure. To overcome this condition, several therapeutic approaches have been developed to inhibit inflammatory responses, HSC proliferation and activation. Preclinical studies also suggest several targets for the development of anti-fibrotic therapies; however, very few advanced to clinical trials. The pathophysiology of hepatic fibrosis is extremely complex and requires comprehensive understanding to identify effective therapeutic targets; therefore, in this review, we focus on the various cellular and molecular mechanisms associated with the pathophysiology of hepatic fibrosis and discuss potential strategies to control or reverse the fibrosis.

SUBMITTER: Khanam A

PROVIDER: S-EPMC8147843 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFunctional tricuspid regurgitation (TR) appears frequently in the presence of left-sided heart valve diseases, combined with symptoms of heart failure, worsens if left untreated, and is associated with poor patient survival. Correct indications for surgery and the choice of suitable technique, which should be based on pathophysiology of disease are of utmost importance to ensure longevity and durability of repair; particularly given the risky nature of reoperations due to residual/recurrent TR.MethodsA systematic review was performed using Embase, Ovid Medline, Cochrane, Web of Science, and Google to deepen knowledge of major and controversial aspects of the subject.ResultsA total of 1,579 studies were reviewed, and 32 of these were enclosed in the final review: 13 studies were primarily focused on pathophysiology and preoperative assessment of functional TR; 19 studies on surgical treatment of functional TR. A total of 15,509 patients were included.ConclusionsIndications for treatment of TR are based on the severity of regurgitation (grading), as well as on the presence of signs and symtoms of right-sided heart failure and on the extent of tricuspid annular dilation, leaflet tethering, and pulmonary hypertension (staging of disease). Despite improved knowledge of the underlying pathophysiology of TR, issues regarding indications for treatment and options of repair remain present. There is no consensus within the scientific community, for the preferred method to quantify the severity of TR; the recently introduced 5-grade TR classification based on objective quantitative parameters has not yet become common practice. The assessment of TR during stress exercise is rarely performed, though it takes into account the changes in severity of regurgitation that occur under different physiological conditions. Magnetic resonance imaging, which is the gold standard for the right heart evaluation is occasionally carried out before surgery. The threshold beyond which the tricuspid annular dilation should be repaired is unclear and recent studies put forward the idea that it may be lower than current recommendations. Tricuspid valve annuloplasty is the most adopted surgical option today. However, the ideal annuloplasty device remains elusive. In addition, as severe leaflet tethering cannot be addressed by annuloplasty alone, the addition of new techniques further increasing leaflet coaptation might optimize long-term valve continence. Further investigations are needed to address all these issues, alongside the potential of percutaneous options.

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Pathophysiology and Treatment Options for Hepatic Fibrosis: Can It Be Completely Cured?

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