Nonalcoholic fatty liver disease in inflammatory arthritis: Relationship with cardiovascular risk

Abstract

Liver disease is one of the most important causes of morbidity and mortality worldwide whose prevalence is dramatically increasing. The first sign of hepatic damage is inflammation which could be accompanied by the accumulation of fat called non-alcoholic fatty liver disease (NAFLD), causing damage in the hepatocytes. This stage can progress to fibrosis where the accumulation of fibrotic tissue replaces healthy tissue reducing liver function. The next stage is cirrhosis, a late phase of fibrosis where a high percentage of liver tissue has been replaced by fibrotic tissue and liver functionality is substantially impaired. There is a close interplay of cardiovascular disease (CVD) and hepatic alterations, where different mechanisms mediating this relation between the liver and systemic vasculature have been described. In chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which the CVD risk is high, hepatic alterations seem to be more prevalent compared to the general population and other rheumatic disorders. The pathogenic mechanisms involved in the development of this comorbidity are still unraveled, although chronic inflammation, autoimmunity, treatments, and metabolic deregulation seem to have an important role. In this review, we will discuss the involvement of liver disease in the cardiovascular risk associated with inflammatory arthritis, the pathogenic mechanisms, and the recognized factors involved. Likewise, monitoring of the liver disease risk in routine clinical practice through both, classical and novel techniques and indexes will be exposed. Finally, we will examine the latest controversies that have been raised about the effects of the current therapies used to control the inflammation in RA and PsA, in the liver damage of those patients, such as methotrexate, leflunomide or biologics.

Antirheumatic drugs and the risk of nonalcoholic fatty liver disease in patients with rheumatoid arthritis: A nationwide, population‐based cohort study

“…33 Previous study noticed that the use of leflunomide at higher doses of 20 mg/day might elevate the incidence of liver damage. 34 decreased risk of NAFLD, but did not achieve the statistical significance (Table 4). Nevertheless, we can still look forward to the benefits brought by the use of bDMARDs, according to previous studies.…”

“…Leflunomide may induce potential deleterious effects on the liver through different molecular mechanisms, such as the induction of mitochondrial and endoplasmic reticulum stress, or alterations in metabolic and inflammatory pathways promoting hepatic fibrosis 33 . Previous study noticed that the use of leflunomide at higher doses of 20 mg/day might elevate the incidence of liver damage 34 . Our study found significantly increased risk of NAFLD with Leflunomide users, but only in patients without obesity‐related comorbidities (aHR of 1.52; 95% CI: 1.02–2.26) (Table S7).…”

Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker

“…Whether these genetic variants modulate TNFSF14 production by synovial cells needs further investigations. LIGHT level is elevated in SF of other inflammatory joints such as rheumatoid arthritis and psoriatic arthritis 30 31. This local production may contribute to the amplification of gout flare via the production of other inflammatory mediators and its vascular effects 32 33.…”

Dyslipidemia and Nonalcoholic Fatty Liver Disease in Rheumatoid Arthritis Patients

“…In addition, the liver injury might be considered as an extra-articular manifestation of these inflammatory arthritis, especially the development of NAFLD [7]. However, there is some controversy between the occurrence of liver pathology as an extra-articular manifestation or as a result of hepatotoxicity of anti-inflammatory and disease-modifying treatment [4].…”