Microplastics, Cirrhosis and Portal Hypertension

Overview

Cirrhosis and portal hypertension are associated with an hyperdynamic circulation and hepatic inflammation, leading to complications like ascites, variceal bleeding, acute kidney injury, and higher infection risk. Microplastics (MPs) are a global plastic pollution issue, and studies have found plastic MPs or nanoparticles (NPs) contaminating human, animal and environmental ecosystems.It has been noted that the accumulation of MPs increases with a reduction in size of the plastic particle. MPs are categorized into primary particles such as manufactured plastics including pellets and cosmetic microbeads and secondary particles which originate from mechanical and ultraviolet disruption of large plastic particles. MPs can be ingested via food or beverages, especially plastic packaged comestibles or inhaled as environmental pollutants. Contamination of medications such as antibiotics, intravenous fluids, albumin and medical devices is another source of exposure to microplastics in patients with chronic liver disease (CLD)In particular exposure to endoscopic interventions, liver biopsy, and invasive procedures such as paracentesis and interventional radiology procedures can lead to plastic exposure and deposition of MPs in the liver and other tissues in patients with cirrhosis. It may be hypothesized that these may contribute to hepatic inflammation and progression of cirrhosis and portal hypertension. Globally, there is new research on the influence of MPs on the environment, plant and animal ecosystems and human health. Polystyrene (PS) microspheres that concentrate in the liver, intestine and the kidneys of mammals disrupt lipid and energy metabolism, impair mucus secretion, and alter the microbiome. Therefore, studies are required to assess how and to what extent, MPs impact human health, and affect chronic diseases like cirrhosis and reduce longevity. In the proposed study we will assess the presence of MPs in the liver, kidneys and intestine of patients with liver cirrhosis and compare it with those without underlying liver disease and determine the impact on portal hypertension and fibrosis, and cardiovascular and metabolic function.

First, because the methodology requires chemical digestion, it is unclear where in the liver MPs are deposited. For instance, it is indeterminate if MPs are deposited intracellularly, in Kupffer cells, endothelium or hepatocytes/cholangiocytes. In the present study we intend to perform histopathological assessments of the liver tissue to determine the presence of the MPs. * Furthermore, our study will assess various polymer types of MP in cirrhotic liver tissue including commonly observed plastic polymers PS (polystyrene), PE (polyethylene), PP (polypropylene), PVC (polyvinyl chloride), PET (polyethylene terephthalate), PC (polycarbonate), and PMMA (polymethyl methacrylate). * Therefore, we need to assess potential cellular sites of deposition in the liver. If the MPs were in the systemic circulation, without any liver parenchymal residues, such particles should also be identified in spleen and kidney samples. * In the present study we intend to overcome these limitations by histopathology and electron microscopy of the liver tissue which should clarify the specific accumulation sites.