Impact of Sex and Gender on Clinical Management of Patients with Advanced Chronic Liver Disease and Type 2 Diabetes

Abstract

Gender differences in the epidemiology, pathophysiological mechanisms and clinical features in chronic liver diseases that may be associated with type 2 diabetes (T2D) have been increasingly reported in recent years. This sexual dimorphism is due to a complex interaction between sex- and gender-related factors, including biological, hormonal, psychological and socio-cultural variables. However, the impact of sex and gender on the management of T2D subjects with liver disease is still unclear. In this regard, sex-related differences deserve careful consideration in pharmacology, aimed at improving drug safety and optimising medical therapy, both in men and women with T2D; moreover, low adherence to and persistence of long-term drug treatment is more common among women. A better understanding of sex- and gender-related differences in this field would provide an opportunity for a tailored diagnostic and therapeutic approach to the management of T2D subjects with chronic liver disease. In this narrative review, we summarized available data on sex- and gender-related differences in chronic liver disease, including metabolic, autoimmune, alcoholic and virus-related forms and their potential evolution towards cirrhosis and/or hepatocarcinoma in T2D subjects, to support their appropriate and personalized clinical management.

High Prevalence of Severe Hepatic Fibrosis in Type 2 Diabetic Outpatients Screened for Non-Alcoholic Fatty Liver Disease

“…Besides the pathogenetic background, the finding of a higher risk of liver fibrosis in unaware T2D obese patients should prompt physicians to investigate liver damage in these patients, also in light of their correct management. Thus, although no medical treatment has been currently authorized for the management of NAFLD in patients with T2D, a growing body of evidence points to the beneficial effects of insulin-sensitivity drugs, such as pioglitazone, metformin, GLP-1RAs, and SGLT2i, irrespective of their beneficial effect on body weight [52][53][54]. In particular, a recent meta-analysis showed that treatment with GLP-1RAs was associated with significant reductions in the absolute percentage of liver fat content, serum liver enzyme levels, and a greater histological resolution of NASH without worsening liver fibrosis compared to placebo or reference therapies, indicating the great potential of this class of drugs for the treatment of T2D patients with NAFLD [55].…”