Endocrine Abstracts

Background: Liver fibrosis is the result of the chronic hepatocyte damage due to different causes. Among them, Non-alcoholic Fatty Liver Disease (NAFLD) is estimated to account for nearly 30% of cases, representing a leading cause of chronic liver disease. NAFLD can evolve into non-alcoholic steatohepatitis, with or without fibrosis, whose diagnosis requires a liver biopsy, a costly and invasive procedure. Non-invasive tests have recently been proposed to screen patients at risk of fibrosis. For instance, fibrosis-4 index (FIB-4) is an effective screening tool for the selection of patients at risk of fibrosis who have indication to liver biopsy. Although there is no established treatment for NAFLD, studies suggested a favorable influence of specific anti-diabetes drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA) and peroxisome proliferator-activated receptor γ (PPARγ) agonists. It is still debated, however, whether these drugs are effective once liver fibrosis has occurred.

Clinical case: A 64-year-old woman referring to our outpatient clinic for dyslipidemia and type 2 diabetes was treated with Vildagliptin 50 mg/bid. and Simvastatin 20 mg/die. She complained of mild right upper quadrant abdominal pain thus, in consideration of her clinical history, FIB-4 was calculated (2.39, n.v. <1.45); Metavir score at liver elastography was F3 (severe fibrosis); liver biopsy confirmed mild fibrosis. Diabetes treatment was shifted to dulaglutide 1.5 mg/week and pioglitazone 30 mg/die. After 12 months, Metavir score at elastography was F1 (fibrosis absent or mild). FIB-4 decreased to 1.63, thus liver biopsy was not performed. 6 months later, weight gain and fluid retention occurred. Empagliflozin 25 mg/die was added to treatment, reducing the symptoms.

Discussion: Recent studies proved the efficacy of dulaglutide in reducing liver fat content and preventing the progression of fibrosis. Pioglitazone promotes the uptake of free fatty acids and lipogenesis, reducing the saturation of subcutaneous adipose tissue, a key factor in the deposition of visceral fat. The reduction of visceral fat and the anti-inflammatory effects of these drugs may explain why they could induce a partial regression of the fibrosis, particularly in early stages. Preclinic studies have demonstrated that, activating the PPARγ pathway, pioglitazone directly inhibits IGF-1-induced collagen deposition in hepatic stellate cells. This might enable hepatic progenitor cells to differentiate into functional hepatocytes and replace the damaged liver tissue. Nevertheless, pioglitazone is rarely used due to its unfavorable effects on weight gain. In our patient, the addition of a Sodium/Glucose Cotransporter 2 inhibitor partially counterbalanced these side effects.