Issue 4, Volume 2 – 3 articles

Review

14 October 2024

Sex and Gender Differences in Liver Fibrosis: Pathomechanisms and Clinical Outcomes

The accumulation of extracellular matrix proteins is the hallmark of liver fibrosis associated with all chronic liver disease (CLD) types. Liver fibrosis results from repeated bouts of liver injury, which trigger the wound-healing response, ultimately disrupting the normal hepatic architecture. Over time, fibrosis can progress to cirrhosis, portal hypertension, liver failure, and hepatocellular carcinoma, worsening patient outcomes. Biological modifiers, such as sex and socio-cultural constructs like gender, influence the development of liver fibrosis through various genetic, hormonal, immunological, metabolic, and lifestyle-related factors, including alcohol consumption, diet, sedentary behavior, and hormonal therapy. Moreover, liver fibrosis is significantly modulated by age, reproductive status, and the etiology of CLD. This review aims to summarize the most well-characterized pathomechanisms underlying sex and gender differences in hepatic fibrogenesis as well as liver-related complications (cirrhosis, portal hypertension, hepatic encephalopathy, liver failure, and hepatocellular carcinoma) and extra-hepatic correlates of liver fibrosis (sarcopenia, cardiovascular disease, diabetes, chronic kidney disease, and dementia) across various types of CLD due to viral-related, autoimmune, drug-induced and metabolic etiologies. Understanding these disease modifiers and their mechanisms is crucial for developing innovative treatment strategies and precision medicine approaches in this field.

Review

23 October 2024

The Notch3 Pathway in Organ Fibrosis

Fibrosis occurs in many organs, including the lung, heart, skin, liver or kidney, and is characterized by progressive tissue scarring in response to repetitive or chronic non-resolving injury, ultimately leading to organ failure and death. It is, in fact, a major cause of morbidity and mortality worldwide, being estimated to account for 45% of deaths in the world. Despite this fact, little progress has been made therapeutically, and fibrosis remains a major clinical and therapeutic challenge. Although significant advances in our understanding of cellular and molecular mechanisms driving tissue fibrosis have been made, the lack of an efficient treatment reflects the limited insight into the pathophysiological mechanisms underlying the initiation and progression of the fibrotic process. Thus, there is an urgent need for better understanding of tissue fibrosis and repair mechanisms that later lead to the development of new therapeutic approaches to fight fibrosis. The Notch pathway is a highly conserved signaling pathway that has been linked to tissue fibrosis in many organs and promises to open new therapeutic opportunities. This manuscript reviews the relevance of Notch signaling in the development and progression of tissue fibrosis in several organs with a special focus on the Notch3 pathway due to the unique features of this receptor.

Review

28 October 2024

Acute Exacerbations of Interstitial Lung Disease: Evolving Perspectives on Diagnosis and Management

Interstitial lung diseases (ILDs) are a heterogeneous group of chronic lung diseases caused by several potential etiologies but for many, the cause of a given ILD remains unknown. Accurate epidemiologic data are hard to find because of varying definitions, overlapping characteristics once thought to be unique to specific diseases, and ongoing changes in how ILDs are diagnosed and managed. In addition, there are significant variations in prevalence among different geographic populations, likely reflecting a combination of genetic and environmental differences. Certain risk factors, including exposure to cigarette smoke or environmental toxicants (asbestos, silica, fracking, coal dust, and air pollution), genetic mutations, and single nucleotide polymorphisms, have all been associated with developing interstitial lung disease. Due to the availability of high-resolution computed tomography (CT) scans, earlier and broader recognition of subtle imaging changes, and an aging worldwide population, the incidence and prevalence of ILDs are increasing. While a given cause of particular interstitial lung disease may vary, patients often experience breathlessness and a non-productive cough due to impaired alveolar gas exchange. Patients with ILD are prone to the development of acute exacerbations, marked by acute or chronic respiratory failure because of an acute exacerbation of the underlying lung disease. In this review, we discuss the definition of an acute exacerbation and comment on what is known about the underlying pathophysiology in exacerbations of idiopathic pulmonary fibrosis and other ILDs. We also emphasize the similarities in the clinical presentation of the acute exacerbations regardless of the underlying ILD, highlight key prognostic features of the diagnosis, and underscore the importance of interdisciplinary management of acute interstitial lung disease exacerbations.

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