Non-Alcoholic Fatty Liver Disease in Diabetic Patients as Risk Factor for Poor Prognosis of Covid-19: An Update of Potential Mechanisms and Treatment Considerations

Abstract

In the global context of COVID-19 outbreak, scientific efforts have been directed to investigate the risk factors associated with the development of severe illness. Emerging evidence linked the metabolic syndrome to more severe forms of the disease. The majority of the patients with these risk factors develop hepatic injury, particularly those previously diagnosed with nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common cause of chronic liver disease, affecting a quarter of the population worldwide. While type II diabetes mellitus is linked to a higher severity of COVID-19, it has not been established whether patients with metabolic-associated fatty liver disease are prone to worse outcomes. To have a closer look at the consequences of this association, we have systematically searched the latest updates and studies to assess the connection between NAFLD and the severity of COVID-19, as well as the treatment considerations. Rezumat În contextul pandemiei COVID-19, eforturile cercetătorilor au fost îndreptate spre a identifica factorii de risc asociați cu progresia severă a bolii. Studii recente scot în evidență legătura sindromului metabolic cu formele grave de COVID-19. O proporție mare din pacienții cu tulburări metabolice au dezvoltat afectare hepatică, în special cei diagnosticați anterior cu boala ficatului gras non-alcoolic (FGNA), patologie ce afectează peste un sfert din populația lumii. În timp ce diabetul zaharat tip II este cunoscut ca fiind factor de risc pentru evoluția severă a COVID-19, nu este încă stabilit dacă pacienții cu FGNA asociat cu sindromul metabolic au un prognostic nefast. Scopul acestei lucrări este de a analiza asocierea dintre FGNA și evoluția COVID-19, precum și posibilele implicații terapeutice, axându-se pe cele mai recente actualizări și cercetări din domeniu.

COVID-19 pandemic and alcohol consumption: Impacts and interconnections

“…There are no specific treatments for COVID-19 infection yet, although many candidate therapies are being evaluated in clinical trials [ [5] , [6] , [7] , [8] ] and several COVID-19 vaccines are approved or under evaluation for approval by authorities [ [9] , [10] , [11] ]. Initially, social distancing, along with increasing population testing, are the only effective measures to control the pandemic but with several consequences on long-term [ [12] , [13] , [14] ]. Public health measures include non-pharmacological interventions that can be used to reduce and delay community transmission [ 4 ].…”

Non-alcoholic fatty liver disease and clinical outcomes in patients with COVID-19: A comprehensive systematic review and meta-analysis

“…The SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) that are known to impair liver function through direct (translocation of the virus from gut to liver) or indirect mechanism (inflammation, ischemia, others) [ 35 ]. Co-morbid conditions such as obesity and dysmetabolism are shown to be associated with severe COVID-19 by exacerbating the infection, which eventually leads to the cytokine storm [ 36 ]. Studies have also found NAFLD in COVID-19 patients to be associated with elevated alanine aminotransferase (ALT) and aminotransferase (AST), which may lead to unfavorable clinical outcomes in this population [ 22 , 26 , 37 ].…”

The Impact of Increased Fib-4 Score in Patients with Type II Diabetes Mellitus on COVID-19 Disease Prognosis

“…Regarding COVID-19 severity, 36.3% (n = 50) patients were classified as non-severe and 63.7% (88) patients as severe. The median in-hospital stay was 16 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) LFT showed that 73.9% (n = 102) patients had at least one abnormal parameter upon hospital admission, and lactate dehydrogenase (LDH) was the most frequent (81.5%, n = 106). The injury pattern was mostly hepatocellular (64.6%, n = 84), while cholestatic liver enzymes were increased in the later stages of the disease.…”

“…In a recently published systematic review carried out by our team, we described the inter-relationship between MAFLD, T2DM and COVID-19. Patients with MAFLD presented severe forms of SARS-CoV-2 infection, had longer viral shredding time and a higher probability for developing abnormal liver function tests (LFT) from admission to discharge [ 11 ]. Numerous interconnected metabolic and inflammatory pathophysiologic consequences link T2DM and MAFLD to COVID-19 severity; MAFLD causes insulin resistance with dysfunctional fatty acid metabolism, generating a state of low-grade inflammation that seems to impair immune responses that contribute to a greater chance of COVID-19 “cytokine storm” [ 12 ].…”