NAFLD and Infection, a Nuanced Relationship

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased significantly over the last few decades mirroring the increase in obesity and type II diabetes mellitus. NAFLD has become one of the most common indications for liver transplantation. The deleterious effects of NAFLD are not isolated to the liver only, for it has been recognized as a systemic disease affecting multiple organs through protracted low-grade inflammation mediated by the metabolic activity of excessive fat tissue. Extrahepatic manifestations of NAFLD such as cardiovascular disease, polycystic ovarian syndrome, chronic kidney disease, and hypothyroidism have been well described in the literature. In recent years, it has become evident that patients suffering from NAFLD might be at higher risk of developing various infections. The proposed mechanism for this association includes links through hyperglycemia, insulin resistance, alterations in innate immunity, obesity, and vitamin D deficiency. Additionally, a risk independent of these factors mediated by alterations in gut microbiota might contribute to a higher burden of infections in these individuals. In this narrative review, we synthetize current knowledge on several infections including urinary tract infection, pneumonia, Helicobacter pylori, coronavirus disease 2019, and Clostridioides difficile as they relate to NAFLD. Additionally, we explore NAFLD’s association with hidradenitis suppurativa.

Liver Injury and Elevated FIB-4 Define a High-Risk Group in Patients with COVID-19

“…Not least, there is purported evidence of a high susceptibility to numerous infections, which typically follow a more severe disease course when compared to non-MAFLD patients. The implications range from recurrent and more severe bacterial pneumonia, urinary tract infections and urolithiasis, Clostridoides difficile colitis, and even more frequent and severe complications of Helicobacter pylori infection [ 18 ]. Our study assessed the impact of imaging diagnosed MAFLD disease on hospital stay, risk of death, and severity of the disease (according to TSS score).…”

“…MAFLD is a common finding in patients with metabolic syndrome and/or diabetes mellitus, which are clear risk factors for a severe COVID-19 disease course and mortality. Classifying MAFLD patients as high-risk for a poor outcome can be grounded on the assumption that an intricate interrelation between obesity, vitamin D deficiency, and a chronic low-grade pro-inflammatory status leads to an ill-adapted immune response [ 18 ]. However, while MAFLD plus fibrosis (highly suggestive of NASH) appears to be associated with a worse outcome [ 13 , 19 ], there is conflicting data with regards to the role of quiescent MAFLD or incidental findings of steatosis in predicting definite endpoints [ 13 , 20 , 21 ].…”

Nonalcoholic Fatty Liver Disease—A Novel Risk Factor for Recurrent Clostridioides difficile Infection

“…Surprisingly, the investigation of the role of NAFLD in bacterial infections has only recently been initiated. Although patients with NAFLD might have a higher risk for infections due to the concomitant presence of obesity or diabetes mellitus, few studies that included NAFLD in the analysis consistently showed its outcome impact independently of the metabolic syndrome components [20]. So far, this was suggested for communityacquired pneumonia, bacteriaemia of gastrointestinal origin, sepsis and urinary tract infections [21][22][23][24][25].…”

Predictors of Development of Hepatorenal Syndrome in Hospitalized Cirrhotic Patients with Acute Kidney Injury

“…Interestingly, patients with cirrhosis are at increased risk of developing infections such as SBP, clostridium difficile and aspiration pneumonias possible due to increased intestinal bacterial translocation that results from portal hypertension and increased intestinal transient time [ 42 ], or due to a decreased innate pulmonary immunity [ 43 ]. One study suggested that changes in immunity and increased risk of infections might also be present in patients without advanced fibrosis or cirrhosis [ 44 ]. Infections in cirrhotic patients can precipitate a systemic inflammatory response which may be a precursor to the development of HRS-AKI.…”