Impact of sodium glucose cotransporter-2 inhibitors on liver steatosis/fibrosis/inflammation and redox balance in non-alcoholic fatty liver disease

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT2-I)are the most recently approved drugs for type 2 diabetes(T2D).Recent clinical trials of these compounds reported beneficial cardiovascular(CV)and renal outcomes.A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress.Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress.AIM To investigate the effects of SGLT2-I on markers of oxidative stress,inflammation,liver steatosis,and fibrosis in patients of T2D with non-alcoholic fatty liver disease(NAFLD).METHODS We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre.We introduced the outpatients to an SGLT2-I(dapagliflozin,empagliflozin,or canagliflozin;n=26)or a different hypoglycemic drug[other glucose-lowering drugs(OTHER),n=26].We evaluated circulating interleukins and serum hydroxynonenal(HNE)-or malondialdehyde(MDA)-protein adducts,fatty liver index(FLI),NAFLD fibrosis score,aspartate aminotransferase(AST)/alanine aminotransferase(ALT)ratio,AST-to-platelet-ratio index(APRI),and fibrosis-4 on the day before(T0)and following treatment for six months(T1).We also performed transient elastography at T0 and T1.RESULTS Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups.Of note,following treatment for six months,a reduction of FLI and APRI,as well as of the FibroScan result,was reported in patients treated with SGLT2-I,but not in the OTHER group;furthermore,in the SGLT2-I group,we reported lower circulating levels of interleukin(IL)-1β,IL-6,tumor necrosis factor,vascular endothelial growth factor,and monocyte chemoattractant protein-1,and higher levels of IL-4 and IL-10.We did not observe any modification in circulating interleukins in the OTHER group.Finally,serum HNE-and MDA-protein adducts decreased significantly in SGLT2-I rather than OTHER patients and correlated with liver steatosis and fibrosis scores.CONCLUSION The present data indicate that treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status,more than optimizing glycemic control.

Liver injury in COVID-19:The hepatic aspect of the respiratory syndrome-what we know so far

The 2019 novel coronavirus disease(COVID-19)pandemic due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed a serious threat to global public health.Although primarily,the infection causes lung injury,liver enzyme abnormalities have also been reported to occur during the course of the disease.We conducted an extensive literature review using the PubMed database on articles covering a broad range of issues related to COVID-19 and hepatic injury.The present review summarizes available information on the spectrum of liver involvement,the possible mechanisms and risk factors of liver injury due to SARS-CoV-2 infection,and the prognostic significance of the presence of liver injury.Hopefully,this review will enable clinicians,especially the hepatologists,to understand and manage the liver derangements they may encounter in these patients better and provide guidance for further studies on the liver injury of COVID-19.

Non-alcoholic fatty liver disease in diabetes:When to refer to the hepatologist?

Non-alcoholic fatty liver disease(NAFLD)has become one of the most common chronic liver diseases worldwide.A strong relationship exists between NAFLD and diabetes mellitus.There is growing evidence of a mechanistically complex and strong association between the two diseases.Current data also shows that one disease actually leads to worsening of the other and vice versa.Understanding of the various pathophysiological mechanisms involved,natural history and spectrum of these two diseases is essential not only for early diagnosis and management but also for prevention of severe disease forms.Despite the tremendous progress made in recent times in acquiring knowledge about these highly prevalent diseases,the guidelines and recommendations for screening and management of diabetics with NAFLD remain ambiguous.An interdisciplinary approach is required to not only raise awareness of the prevalence of NAFLD in diabetics but also for better patient management.This can help attenuate the development of significant complications,such as cirrhosis,decompensation and hepatocellular carcinoma in these patients,thereby halting NAFLD in its tracks.This review focuses on the pivotal role of primary care physicians and endocrinologists in identification of NAFLD in diabetics in early stages and the role of proactive screening for prompt referral to hepatologist.

Association of non-alcoholic fatty liver disease and COVID-19: A literature review of current evidence

The coronavirus disease 2019(COVID-19)pandemic has swept through nations,crippled economies and caused millions of deaths worldwide.Many people diagnosed with COVID-19 infections are often found to develop liver injury,which,in a small portion of patients,progresses to severe liver disease.Liver injury in the form of elevated transaminases,hyperbilirubinemia and alterations in serum albumin has been observed to be higher in patients with severe forms of the disease.Those who already have insult to the liver from chronic disease,such as nonalcoholic fatty liver disease(NAFLD)may be at the greatest disadvantage.The severity of COVID-19 also seems to be driven by the presence of NAFLD and other co-morbidities.About 25%of the global population has NAFLD.With such a widespread prevalence of NAFLD,understanding the disease progression of COVID-19 and the occurrence of liver injury in this vulnerable population assumes great significance.In this review,we present an overview of COVID-19 infection in patients with NAFLD.