The purpose of this study is to find out whether the study medications are better than placebo at reducing the occurrence of major liver-related complications. During the study, researchers will monitor participants for various liver problems including progression to cirrhosis (severe liver scarring), development of complications like varices (enlarged veins in the digestive tract), ascites (fluid buildup in the abdomen), hepatic encephalopathy (brain function problems caused by liver disease), and other serious liver conditions. The study will also track whether participants need liver transplantation or experience other serious outcomes.

Participants in this study will receive their assigned treatment over an extended period while being regularly monitored by the study team. The study requires participants to have evidence of liver fat confirmed by MRI (a type of imaging scan) and liver scarring confirmed through non-invasive tests, though a liver biopsy is not required to join the study. Throughout the study, participants will have regular check-ups and assessments to evaluate how well the treatment is working and to monitor their liver health and overall wellbeing.

During the study, participants will receive either the liquid form of Essentiale (1800 mg), Essentiale capsules, or a placebo. The medication or placebo will be taken daily for 87 days. The liquid medication comes in stick packs containing 1.8g of the substance, while the capsules contain 300 mg each. All participants will continue their regular liver disease treatment throughout the study.

The study will monitor changes in liver disease symptoms such as tiredness, depression, stomach discomfort, sleep problems, loss of appetite, and nausea. The medications and placebos are designed to look, taste, and smell the same so that participants cannot tell which form they are receiving. This helps ensure that the study results are reliable and unbiased.

The main purpose is to find out which treatment approach works best in reducing liver fat over an 18-month period. The amount of fat in the liver will be measured using Magnetic Resonance Imaging (MRI), which is a scanning technique that creates detailed pictures of the inside of the body without using radiation.

During the study, participants will receive different combinations of these medications along with lifestyle recommendations. The study will also look at how the body processes insulin, examine various substances in the blood, study gut bacteria, and look at how genetic differences might affect how well the treatments work. The total duration of treatment is 18 months, during which participants will take either Pioglitazone (15 mg daily) or Metformin (up to 1000 mg daily), or both medications together.

The purpose of the study is to determine how well Pegozafermin works in improving liver health and reducing the risk of further liver damage. Participants in the study will receive either Pegozafermin or a placebo through a pre-filled syringe, which is injected under the skin. The study will last for a period of up to 36 months, with key assessments taking place at 52 weeks and at the end of the study. During this time, the effects of the treatment on liver health will be closely monitored.

Throughout the study, participants will undergo various assessments, including imaging tests like Magnetic Resonance Imaging (MRI), to measure changes in liver fat and other liver-related health markers. The study aims to provide valuable insights into the potential benefits of Pegozafermin for individuals with MASH/NASH and fibrosis, ultimately contributing to better treatment options for this condition.

Participants in the study will receive either the new treatment, GSK4532990A, or a placebo, which is a substance with no active medication. The study is designed to be double-blind, meaning neither the participants nor the researchers will know who is receiving the actual treatment or the placebo. This helps ensure that the results are unbiased. The treatment will be administered through subcutaneous injection, which means it is injected under the skin. The study will last for a period of 48 weeks, during which participants will be monitored for any changes in their liver condition.

The main goal of the study is to see if GSK4532990A can lead to an improvement in liver fibrosis without worsening NASH, or if it can resolve NASH without worsening fibrosis. Participants will undergo various assessments to track their liver health throughout the study. This research aims to provide valuable insights into the potential benefits of GSK4532990A for individuals with NASH, potentially leading to new treatment options for this liver disease.

Participants in the study will receive the treatment and be monitored over a period of time to observe changes in their health. The study will look at how the body processes very low-density lipoproteins (VLDL) and triglycerides, which are types of fats in the blood, before, during, and after weight loss. Researchers will also examine other health indicators, such as insulin resistance, which is how well the body uses insulin, and various markers of inflammation, which is the body’s response to injury or infection.

The study will track changes in these health indicators over several months, comparing results from the beginning of the study to those after weight loss has stabilized. This will help researchers understand the relationship between weight loss and improvements in liver health and overall metabolism. The findings could provide valuable insights into managing obesity and NAFLD more effectively.

The purpose of this research is to determine if the combination of dasatinib and quercetin can improve liver scarring (also known as liver fibrosis) in people with NAFLD. The treatment will last for 21 weeks, during which participants will receive either the combination of these medications or placebo in the form of oral tablets.

During the study, doctors will monitor the condition of participants’ livers using various tests, including examining small samples of liver tissue. The treatment involves taking dasatinib up to 180 mg per day and quercetin up to 1000 mg per day. The study uses a double-blind design, which means neither the participants nor the doctors will know who receives which treatment until the study is complete.