Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD.

BACKGROUND AND AIMS: Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis. METHODS: EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks. The hepatic origin of MVs was addressed using AlbCrexmT/mG mice fed a Western (WD) or Dual diet for 23 weeks. Besides, we assessed plasma MVs in 130 biopsy-proven NAFLD patients. RESULTS: Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy-proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4 ± 61.9 vs 758.4 ± 82.3; p < 0.001). Patients with ballooning 367 ± 40.6 vs 532.0 ± 45.1; p = 0.01 and lobular inflammation (321.1 ± 74.1 vs 721.4 ± 80.1; p = 0.001), showed higher levels of these EVs. These findings were replicated in an independent cohort. CONCLUSIONS: Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non-invasive biomarker for the evaluation and management of these patients.

Navigating the Link Between Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis and Cardiometabolic Syndrome.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is nearly 25% and is increasing rapidly. The spectrum of liver damage in NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis, characterised by the presence of lobular inflammation and hepatocyte ballooning degeneration, with or without fibrosis, which can further develop into cirrhosis and hepatocellular carcinoma. Not only is NAFLD a progressive liver disease, but numerous pieces of evidence also point to extrahepatic consequences. Accumulating evidence suggests that patients with NAFLD are also at increased risk of cardiovascular disease (CVD); in fact, CVDs are the most common cause of mortality in patients with NAFLD. Obesity, type 2 diabetes and higher levels of LDL are common risk factors in both NAFLD and CVD; however, how NAFLD affects the development and progression of CVD remains elusive. In this review, we comprehensively summarise current data on the key extrahepatic manifestations of NAFLD, emphasising the possible link between NAFLD and CVD, including the role of proprotein convertase substilisin/kenin type 9, extracellular vesicles, microbiota, and genetic factors.

Trends in Mortality from Ischemic Heart Disease in Peru, 2005 to 2017.

The highest proportion of deaths among patients with cardiovascular diseases is due to ischemic heart disease (IHD), which is the second most common cause of death in Peru. This study aims to measure and identify changes in the temporal trend in mortality from ischemic heart disease in the Peruvian population. An ecological study was carried out with data from individual death records from the Ministry of Health between 2005 and 2017. A death was considered attributable to IHD if it was registered with the codes I20 to I25 of the ICD-10. Crude and adjusted mortality rates for IHD were calculated for the general population by age and according to sex. A joinpoint regression analysis was performed to assess trends in IHD mortality. There were 61,524 deaths due to IHD (55.69% men) from 2005 to 2017. According to the ICD-10, acute myocardial infarction (I21) accounted for the highest proportion of deaths (88.16%), followed by chronic IHD (I25), with 6.53%. In general, a decrease in adjusted IHD mortality rates was found in the general population over time (45.34 in 2005; 22.18 in 2017). By sex, men possessed a 1.5-fold higher rate than women. The highest mortality rates from IHD were found in the natural coastal region (68.55%) and in urban areas (86.43%). A joinpoint regression analysis showed a reduction in the mortality trend over time due to IHD for both the general population and the population when grouped by sex. In conclusion, there was a continuous decrease in mortality rates due to IHD in the Peruvian population between 2005 and 2017. Strategies focused on mitigating the impact of this disease are required and should emphasize the subgroups most likely to die from this cause.