Gluten’s silent strike: Unmasking its impact on liver health

Abstract

Once considered a concern solely for the gut, gluten is now recognized as an important factor in the pathogenesis of metabolic dysfunction-associated steatotic liver disease. Studies estimate that 18%-40% of individuals with gluten-related diseases have elevated liver enzyme levels, with 9% of patients with unexplained hypertransaminasemia ultimately diagnosed with gluten sensitivity. Hepatic manifestations of gluten sensitivity range from mild transaminase elevations to autoimmune liver diseases, metabolic dysfunction-associated steatotic liver disease, and even cirrhosis. Up to 50% of untreated cases of gluten-induced liver dysfunction show significant hepatic injury, which can lead to liver failure in severe cases. The pathophysiology is multifaceted and involves increased intestinal permeability, immune dysregulation, and shared genetic risk factors. A gluten-free diet leads to normalized liver enzymes in 75%-90% of cases within 1 year. Long-term gluten-free diet adherence has been paradoxically linked to higher body mass index, insulin resistance and increased hepatic steatosis risk, which raise concerns about its metabolic impact. Our review dissects the gluten-liver axis, emphasizing a need for early recognition, targeted screening, and personalized dietary interventions. Ultimately, given the increasing global burden of metabolic and autoimmune liver diseases, understanding gluten’s role is essential for optimizing liver health and preventing progressive hepatic injury.

Keywords: Gluten; Liver dysfunction; Gut-liver axis; Gluten-free diet; Metabolic liver disease; Autoimmune hepatitis; Transaminase elevation; Hepatic steatosis; Celiac hepatitis; Non-celiac gluten sensitivity

Core Tip: Gluten, once viewed solely as a gastrointestinal concern, is now implicated in a wide spectrum of hepatic disorders ranging from mild hypertransaminasemia to cirrhosis. Up to 40% of patients with celiac disease and 9% of those with unexplained elevated liver enzymes may have underlying gluten sensitivity. A gluten-free diet normalizes transaminase levels in most cases, yet long-term adherence may paradoxically exacerbate metabolic liver disease. This article elucidates the complex interplay between gluten, gut permeability, immune activation, and liver pathology. Recognizing gluten’s hepatic implications is crucial for early screening, tailored dietary management, and prevention of progressive liver injury in at-risk individuals.