“I felt like trash.” Yvette Bosch is diabetic. The doctor diagnosed him with NASH. in 2002, and the first serious symptoms appeared 16 years later. Abdominal fluid flow (ascites), confusion, loss of sphincter control, inability to express her thoughts… she has to stop working. NASH, from “non-alcoholic steatohepatitis,” is a chronic liver disease that progresses very slowly. In some cases, it can degenerate into cirrhosis of the liver (and chronic inflammation leading to destruction of liver cells)even if people don’t drink alcohol. Ms. Bosch’s symptoms completely disappeared thanks to a liver transplant in 2020.
Unknown to the general public as well as general practitioners, NASH is the subject of an annual conference in Paris. “We need to raise awareness so that people at risk are systematically screened,” warns Professor Lawrence Serfaty. Head of the Department of Hepatology at the Hautpierre Hospital in Strasbourg and Chairman of the 7th NASH Paris Meeting. But what are the risk factors for fatty liver disease? Age over 50 years, overweight, cholesterol, diabetes… Their combination increases the risk of developing this stechatohepatitis by more than 90%.
1 in 2 diabetics have NASH
Today, about 4 million French people have diabetes, and 50% of them are said to suffer from “fatty liver”. For type 2 diabetics, this proportion rises to 8/10. However, many remain undiagnosed. “The liver is not diabetic radar. However, they are looking at the consequences for many other organs, such as the eyes or the kidneys,” explains the professor. Laurent Castera from the Hepatology Department of Beaujon Hospital. Thus, the challenge is primarily awareness raising and screening.
How it works ? Several examinations are possible: blood test, ultrasound or FibroScan (measurement of liver elasticity), which remains the best tool for detecting NASH, in addition to liver biopsy. Among other things, we are looking for deformations in the liver tissue (fibrosis). They may be associated with abundant proliferation of “myofibroblasts”, tissue repair cells. A study of 350 diabetic patients, called Quidnash, found 30% advanced fibrosis and 10% cirrhosis. “The disease is probably more severe in diabetics than in non-diabetics,” also points out teacher Laurent Caster.
In a cohort of 200,000 French people called “Constance”, 79% of obese people suffered from liver disease. The researchers also questioned the effect of birth weight on the incidence of NASH. “The curve is U-shaped. In people whose birth weight was more than 3.9 kg or less than 2.3 kg, the risk of developing this disease increases by 1.5 times. Lawrence Serfaty. Especially predisposed to this are people born prematurely.
Sometimes a simple resumption of a healthy lifestyle, exercise and a balanced diet can significantly reduce the effects of the disease. There is currently no drug treatment, but the five molecules show promising results. On average, 42% of people treated with one of these molecules show a clear improvement in liver cell function.
What do these new treatments do? Obeticholic acid aims to improve liver biopsy results by inhibiting the production of lipids called “lipogenesis”, much like the experimental drug aramchol., but the results are less significant. Lanifibranor, on the other hand, affects the receptors that allow cells to grow. Thus, it limits fibrosis, lipogenesis and, in particular, cholesterol levels.
Resmetir will also act on the activity of mitochondria (organelles present in our cells and essential for their proper functioning) damaged in NASH patients. The latter, semaglutide, has already been approved for the treatment of type 2 diabetes and obesity. In particular, it stimulates the production of insulin, a hormone that regulates blood sugar levels, which lowers blood sugar levels.
Liver transplantation remains particularly effective in the treatment of this disease, but it is not suitable for everyone. Therefore, researchers are studying new cell culture models of mini-organs that mimic architecture and function of the desired organ. The creation of the so-called “organoid” liver is made from harvested human cells. One of the prospects? Transplanting a person from their own cells will prevent rejection. In a few weeks, the clinical trial will go even further as a volunteer tries to grow a second liver in his body.