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75 active trials for Cirrhosis

Probiotics in the Prevention of Hepatocellular Carcinoma in Cirrhosis

Background. The main risk factor for the development of hepatocellular carcinoma (HCC) is cirrhosis of any etiology, with an annual risk between 1 and 6%, being currently the leading cause of death in patients with cirrhosis and the third cause of death for cancer in the world. In our country there is little information about the incidence of HCC in this population. It has been shown that there is a change in the gut microbiome (set of genetic material of microorganisms that make up the intestinal bacterial flora) as the severity of the cirrhosis progresses. This change in the microbiome has been associated with clinical decompensation events of cirrhosis. However, there are no previous studies in the world that demonstrate an impact of the change of the microbiome in cirrhosis as a precursor to the development of HCC. Our team has compared the profile of the microbiome in patients with cirrhosis with and without HCC. We observed that patients with HCC present changes in the phylum Firmicutes, genus Fusobacterium and change in the bacteroides / prevotella ratio. This pattern was associated with a pro-inflammatory profile. In murine models, it has been postulated that modulation of the gut microbiome through the use of probiotics could have a clinical role in the prevention of HCC development. This research project aims to answer the following question: in patients with cirrhosis, does the nutritional supplement with probiotics prevent HCC development? Objective: To compare the incidence of HCC through intervention with probiotics in cirrhosis. Methods: A randomized, double-blind, placebo controlled trial of probiotics in patients with Child Pugh A-B cirrhosis at 3-year follow-up. Likewise, the type of microbiome found as a predictor of the risk of HCC development will be evaluated. It will include 280 patients, 140 in each branch. Basal blood and stool samples will be obtained and every 6 months. The typing and quantification of the microbiome in samples of fecal matter will be carried out by amplifying a specific region (V3-V4) of the bacterial 16s rRNA gene. Likewise, the presence of endotoxins (LPS) and cytokines (IL6, TNF alpha) in plasma will be determined to analyze the immune environment and the expression of the TLR4 receptor in mononuclear cells.

Start: May 2019
A Prospective Study to Monitor Liver Diseases Dynamically by Ultrasound Viscoelasticity

The accuracy of ultrasound elastography for assessing liver fibrosis by measuring liver stiffness (elastic modulus) is better than traditional method. Elastography has certain advantage such as non-invasive, simple, real-time and it has been recommended by clinical guidelines. However, some chanllenging scientific problems showed up with further research and clinical practice. Firstly, present elastography machines can only calculate liver stiffness from shear wave speed or elastic modulus but ignore other physical characteristics such as tissue viscosity. So far, present technique simply assume liver as an idealized model with isotropic elasticity to assess liver fibrosis while liver is actually anisotropic and viscoelastic. What's more, theoretically, there are not only different solid state structures such as cell organization and vessel but also flowing liquid such as blood and bile. Thus, ignoring viscosity and evaluating elasticity only is unreasonable. In the other hand, a number of confounding factors have been found to influence liver stiffness measurement by elastography. Different pathological chang of liver including inflammation, necrosis, cholestasis and inhomogeneity among the individuals such as obesity, ascites, et,al. will decrease the accuracy of liver stiffness measurement and liver fibrosis staging by elastography. In fact, liver fibrosis is a dynamic process. Liver fibrosis is a reaction of compensation and repair for inflammation and necrosis as well as a contributing factor for liver damage. This dynamic process constitutes the common characteristic of chronic liver disease and result in the complicated biological mechanical characteristics of liver. In consequence, how to measure liver viscosity and elasticity respectively, and to evaluate liver fibrosis stage and Inflammation degree accurately during the complicated and dynamic pathological process is the key scientific problem demanding solution, which is also the urgent requirement of related fundamental research and clinical practice. Therefore, this project plan to apply LOGIQ E viscoelastography machine as research tool, rat liver fibrosis model and rat liver failure model as research object to investigate the correlation between liver viscoelastography measurement and liver fibrosis stage and Inflammation degree. The investigators also aim to assess the feasibility of using ulstrasound viscoelastography to evaluate liver fibrosis stage and Inflammation degree dynamically.

Start: January 2019