Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH

• DOI: 10.1016/j.jhep.2020.02.028
• Publication Date: 2020-03-06T02:43:12Z
• Authors: Javier Ampuero; Rocío Aller; Rocío Gallego-Durán; Javier Crespo; José Luis Calleja; Carmelo García-Mo...; Judith Gómez-Cama...; Joan Caballería; Oreste Lo Iacono; Luis Ibañez; Javier García-Sam...; Agustín Albillos; Rubén Francés; Conrado Fernández...; Moisés Diago; Germán Soriano; Raúl J. Andrade; Raquel Latorre; Francisco Jorquera; Rosa María Morillas; Desamparados Escu...; Pamela Estévez; Manuel Hernández ...; Salvador Augustín; Jesús M. Banales; Patricia Aspichueta; Salvador Benlloch; José Miguel Rosales; Javier Salmerón; Juan Turnes; Manuel Romero Gómez
• Keywords: Arterial hypertension; Adult; Liver Cirrhosis; Male; 0301 basic medicine; Biopsy; Risk Assessment; Severity of Illness Index; 03 medical and health sciences; Diabetes mellitus; Non-alcoholic Fatty Liver Disease; Risk Factors; NAFLD; Humans; Longitudinal Studies; Dyslipidemias; 2. Zero hunger; Incidence; Middle Aged; Hepamet score; Prognosis; Fibrosis; 3. Good health; Diabetes Mellitus, Type 2; Liver; Spain; Hypertension; Disease Progression; Female

Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients.We included 178 metabolically healthy-defined by the absence of baseline T2DM, AHT, dyslipidemia-patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia.During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19-7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14-5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS <0.12 4.5% [4/88]; logRank 6.658, p = 0.010).Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM.Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.