SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common comorbidity with type 2 diabetes.The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD.Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis.The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIM To assess the effect of sodium glucose cotransporter-2(SGLT-2)inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODS We searched PubMed/MEDLINE,Cochrane library,Google scholar,and Clinicaltrials.gov for the relevant articles to be included in this systematic review.Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included.Data from eight studies(four randomised controlled trials and four observational studies)were extracted and a narrative synthesis was done.A total of 214 patients were treated with SGLT-2 inhibitors in these studies(94 in randomised controlled trials and 120 in observational studies).RESULTS The primary outcome measure was change in serum alanine aminotransferase level.Out of eight studies,seven studies showed a significant decrease in serum alanine aminotransferase level.Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase.Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors.Likewise,among the three studies that evaluated a change in indices of hepatic fibrosis,two studies revealed a significant improvement in liver fibrosis.Moreover,there was an improvement in obesity,insulin resistance,glycaemia,and lipid parameters in those subjects taking SGLT-2 inhibitors.The studies disclosed that about 17%(30/176)of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40%(10/23)of them had genitourinary tract infections.CONCLUSION Based on low to moderate quality of evidence,SGLT-2 inhibitors improve the serum level of liver enzymes,decrease liver fat,and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.

Assessment of Arterial Stiffness Index in Hypertensive Patients in Relation to Their Treatment Status Attending a Tertiary Care Center in South India

Objectives: To assess the arterial stiffness index (ASI) and pulse wave velocity (PWV) in patients with hypertension and to compare with age matched healthy controls;to assess and compare the ASI and PWV in relation to the treatment status. Methods: The study was observational-cross sectional. Group one included chronic hypertensive patients on regular treatment for more than 2 months;group two included newly diagnosed hypertensive patients and group three had age matched healthy controls with normal blood pressure. The hypertensives subjects with other comormid conditions such as renal disease, diabetes were excluded from the study. The study was approved by the Institute Ethics Committee. The subjects were interviewed and explained the purpose of the study. All subjects gave written informed consent. The noninvasive periscope device was used to measure PWV, ASI and pulse pressure. Results: PWV, ASI and pulse pressure were statistically higher in hypertensive patients when compared to controls. Further, carotid-femoral PWV was correlated with mean arterial pressure in hypertensive subjects and was found to be statistically significant. Conclusion: PWV, ASI and pulse pressure are significantly higher in chronic and newly diagnosed non-diabetic hypertensives as compared to controls irrespective of their treatment status.

Hepatitis B Vaccine and Immunoglobulin: Key Concepts

Hepatitis B virus(HBV)immunization is safe and has been accepted worldwide as a routine practice.The target of such vaccination is to induce the immune response in the host,resulting in the prevention of replication of HBV.There are several immunological and clinical factors which determine the clinical efficacy and safety of the HBV vaccine.In this article we have highlighted the response of the host immune system to HBV vaccination(immunogenicity),efficacy,and safety of the vaccine,issues with booster dosing,paths of development(preclinical and clinical)of the HBV vaccine,novel and upcoming strategies for improvement of HBV vaccination,and the concept of therapeutic HBV vaccination.The different aspects and regulatory recommendations pertaining to HBV vaccine development are also discussed.The new strategies for improvement of HBV vaccination include pre-S1 and pre-S2 portions of the HBV surface antigen,increasing the antigen dose,accelerated vaccination schedules,alternative vaccination route,use of adjuvants like immunostimulatory DNA sequences,etc.Therapeutic vaccination is being explored for initiation of a multifunctional and multispecific T cell response against the major HBV antigens and also effective activation of humoral immunity for viral control.