Risk of infections in patients with NAFLD and Type 2 Diabetes under treatment with SGLT2 inhibitors and relationship with liver outcomes: A retrospective case-control study.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries, with its incidence growing parallel to the epidemics of obesity and type 2 diabetes mellitus (T2DM). Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are becoming a cornerstone in the management of cardiovascular health and some studies suggest the potential role in NAFLD. However, patients under treatment with SGLT2i are at risk of developing genitourinary fungal infections (GFIs). Moreover, both NAFLD and SGLT2i have a strong influence on the immune system, and therefore the risk of infections other than GFIs could be increased in NAFLD patients treated with SGLT2i. We aimed to examine the possible association of SGLT2i with infections and hepatic outcomes in NAFLD patients. Methods: We conducted a case-control study including NAFLD patients with T2DM visited at the Liver Unit outpatient clinic from 2016 to 2021 with a minimum follow-up of 6 months by selecting 65 patients receiving SGLT2i and 130 matched patients with other types of antidiabetic treatment. Results: During follow-up, GFIs were significantly higher in the SGLT2i group (15.4% vs. 3.8%; p=0.008), whereas there were no differences in the occurrence of overall infections (41.5% vs. 30%; p=0.1) nor in other types of specific infections. In the multivariable analysis, treatment with SGLT2i was not independently associated with higher odds of overall infection. On the other hand, SGLT2i patients showed a significantly lower incidence of hepatic events (1.5% vs. 10.7%; p=0.02). There were no significant different in all-cause mortality between cases and controls. Conclusions: NAFLD patients with T2DM receiving SGLT2i more frequently presented GFIs, whereas the incidence of other types of infections was not found to be higher than in other patients with NAFLD and T2DM treated with other drugs. Moreover, SGLT2i-treated patients had a lower occurrence of hepatic events. Further studies are warranted to validate our data.

The role of liver steatosis as measured with transient elastography and transaminases on hard clinical outcomes in patients with COVID-19.

Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography [with Controlled Attenuation Parameter (CAP) measurements] was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p < 0.001). In conclusion, mild liver damage is prevalent in COVID-19 patients, but neither ALT elevation nor liver steatosis influenced hard clinical outcomes. Elevated baseline AST is a strong predictor of hard outcomes, especially in patients ⩾65 years.