Fatty liver disease has become the most prevalent liver condition worldwide and a hot topic at the 58th Annual Meeting of the European Association for the Study of the Liver (EASL2023) and the EASL Congress 2023. The Hepatology Digest reporting team had the privilege of interviewing Doctor Raluca Pais from Pitié-Salpêtrière Hospital in Paris, an expert in the field of “Current therapeutic landscape in NAFLD and perspectives.” She discussed current treatment options for non-alcoholic fatty liver disease (NAFLD), particularly the benefits of weight loss therapy, prospects for new drug development, and the use of non-invasive assessments.
Hepatology Digest: Weight loss therapy has a very positive impact on improving non-alcoholic fatty liver disease (NAFLD). From current research, what overall benefits can weight loss therapy provide?
Doctor Raluca Pais: I consider that weight loss therapy is actually the cornerstone in the management of NAFLD, especially in the absence of approved therapeutic options and approved drugs for treating NAFLD. Weight loss has clear benefits for both cardiovascular metabolism and the histology and severity of liver damage. Furthermore, the impact on the severity of liver damage may vary depending on the amount of weight loss, and a dose-effect relationship has been observed in clinical studies. For example, a 5% to 7% weight loss can achieve some degree of NASH reversal. At least a 10% weight loss is required to obtain some benefit in fibrosis regression.
However, NAFLD patients often find it difficult to achieve weight loss, as most of them are elderly and suffer from morbid obesity and obesity-related comorbidities such as mechanical or metabolic diabetes and sleep apnea. Therefore, regular physical activity and weight loss can be challenging for these patients.
Hepatology Digest: What are the current methods for weight loss therapy?
Doctor Raluca Pais: Weight loss methods include physical activity, dietary adjustments, medication, and weight loss surgery.
Hepatology Digest: Currently, there is significant progress in research on new drugs for NASH. Could you please talk about the overall progress, which studies and new drugs show the most promise?
Doctor Raluca Pais: Considerable progress has been made in drug development for NASH patients. Some drugs currently undergoing preclinical trials may receive approval. Some of these drugs are already on the market but are indicated for conditions other than NAFLD. Others have been specifically developed for NASH patients. In the future, combination therapy may become a trend for treating these patients.
Hepatology Digest: Non-invasive assessments have widespread applications in NAFLD. Can non-invasive markers be used to evaluate treatment efficacy in NAFLD patients? Please discuss the progress and perspectives in this area.
Doctor Raluca Pais: I believe non-invasive markers may be used in everyday clinical practice because, if these drugs are approved, we cannot use liver biopsies to assess treatment response. Therefore, we must use non-invasive methods, some of which have been evaluated as secondary endpoints in NASH clinical trials.
Hepatology Digest: Finally, what challenges do you think we still face in NAFLD treatment, and what are your views on the future?
Doctor Raluca Pais: I believe the challenge lies in the heterogeneity of patients, ultimately leading to heterogeneity in treatment responses. The use of a single drug may not be sufficient to achieve treatment effects; we should employ combination therapy targeting multiple pathways to enhance treatment response. Another challenge is the lack of reliable non-invasive markers to assess treatment response.
