Insulin-Like Growth Factor-1 (IGF-1) Deficiency and Metabolic-Dysfunction-Associated Steatotic Liver Disease in a...

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in the Western world. MASLD-associated cirrhosis prevalence is on the rise along with the obesity and metabolic syndrome epidemic. Genetic factors are included in the multi-hit model of MASLD pathogenesis and insulin-like growth factor-1 (IGF-1) has an important role.  We report the case of a man who was referred to a hepatology clinic due to elevated liver enzymes as probable drug-induced liver injury (DILI). A 35-year-old man was diagnosed with compensated cirrhosis with an estimated Child-Pugh score of 5 points (Class A) and underwent further investigation of the causative factor. MASLD-cirrhosis was the preliminary diagnosis, but high serum and urine copper levels needed further investigation. Whole-genome sequencing revealed heterozygosity for a rare variant of the IGF-1 receptor, a metabolic factor whose role is crucial in the GH/IGF-1 axis to fatty liver and cirrhosis. MASLD diagnosis is really challenging, especially at the progressive stages of fibrosis. Clinical features, somatometric parameters, laboratory tests and liver biopsy guide us to establish the diagnosis. Despite all these findings, the heterogeneity of disease's pathogenesis through metabolic pathways underlines the need for deeper investigation, especially genetic factors such as IGF-1 and their penetration in disease progression and liver fibrosis.