Steatohepatitis, Nonalcoholic

The goal of this clinical trial is to learn if drug hydroxychloroquine works to treat steatohepatitis in adults. It will also learn about the safety of drug hydroxychloroquine. The main questions it aims to answer are: Does drug hydroxychloroquine improve steatohepatitis? What medical problems do participants have when taking drug hydroxychloroquine? Researchers will compare drug hydroxychloroquine to a placebo (a look-alike substance that contains no drug) to see if drug hydroxychloroquine works to treat steatohepatitis. Participants will: Take drug hydroxychloroquine 400mg or hydroxychloroquine 200mg or placebo every day for 12 months Visit the clinic once every 3 months for checkups and tests

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition, and when fatty liver is associated with inflammation and hepatocellular injury (steatohepatitis), it can lead to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. Liver biopsy is the gold standard for NAFLD assessment but has several drawbacks. Several drugs for NASH are now in phase 2-3 trials, and if medical treatments become available, non-invasive tools to identify patients who may benefit from a therapeutic intervention will be strongly needed. Some imaging methods have shown promising potential in fibrosis and NASH diagnosis. This study aims to evaluate the diagnostic accuracy of non-invasive imaging methods, including ultrasound (US) and Magnetic Resonance (MR) techniques, in diagnosing NASH and fibrosis in patients with or at high risk of NAFLD, using liver biopsy as the reference standard. Consecutive patients with a clinical indication for liver biopsy assessment of NAFLD are enrolled in this non-inferiority study. They undergo both a liver US and a multiparametric unenhanced liver MR examination. As reference standard, histological diagnosis of fibrosis and steatohepatitis made according to the fatty liver inhibition of progression (FLIP) algorithm is used. Sensitivity and specificity of imaging parameters alone or in different combinations will be calculated with the aim of finding one or more tests with at least 90% sensitivity/specificity compared to liver biopsy.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver condition worldwide; approximately 55% of the world population will have NAFLD by 2040. NAFLD is an unwanted side effect of common cancer therapies, such as chemotherapy. Ultrasound can detect NAFLD via measurement of the backscatter coefficient (BSC). It is an attractive technique because of its low cost and availability, potentially enabling earlier detection of NAFLD in a larger population through screening. This approach has shown promise in detecting NAFLD but is limited by variability in measurement due to several factors. Measurement of the BSC requires assumptions about the nature of the tissue being measured; if these assumptions are incorrect, they can lead to inaccurate BSC measurements. To improve accuracy, an algorithm (COSIE) was developed to quantify the suitability of tissue for BSC analysis. The investigators believe COSIE will enable more reliable BSC measurements by selecting the optimal regions of tissue to measure. By measuring the BSC in the livers of healthy volunteers and patients with evidence of fatty liver, the algorithm can be evaluated against liver fat percentage values obtained from MRI imaging. This study will assess whether applying the COSIE algorithm enhances the reliability of BSC measurements, bringing them closer in quality to MRI imaging.

The investigators hypothesize that very low ketogenic diet could represent a new therapeutic option in the management of patients with MASLD and cACLD. Therefore, the investigator propose a randomized controlled study that evaluates the impact of two dietary protocols -Mediterranean diet, and very low ketogenic diet- the MD and the VLCKD, in individuals with cACLD secondary to MASLD.

This clinical trial evaluated the safety, tolerability, pharmacokinetic properties, and immunogenicity of DNP007 when administered as a single dose. Since this is a phase 1 study for exploratory evaluation, to the extent that it meets the study objectives, In order to proceed with the minimum number of subjects, a total of 12 people, 3 for each dose group, was planned as the target number.