Background and Aim To synthesize data on circulating tumor necrosis factor (TNF)‐α levels between patients with histologically confirmed non‐alcoholic fatty liver disease (NAFLD) (simple steatosis or non‐alcoholic fatty liver [NAFL] and/or non‐alcoholic steatohepatitis [NASH]) and controls. Methods We performed a systematic search in PubMed, Scopus, and Cochrane Library. Fifty‐six studies, published between 2003 and 2019, were finally included, reporting data from 5848 individuals (1634 controls and 4214 NAFLD patients). Results Higher circulating TNF‐α levels were observed in NAFLD patients than controls (standardized mean difference [SMD] 0.84; 95% confidence interval [95% CI] 0.59–1.09), NAFL patients than controls (SMD 0.56; 95% CI 0.27–0.85), NASH patients than controls (SMD 0.93; 95% CI 0.64–1.22), and NASH than NAFL patients (SMD 0.31; 95% CI 0.16–0.46). There were only minimal changes in the comparisons between groups after excluding studies with morbidly obese populations (n = 11), or pediatric/adolescent populations (n = 6), or other than enzyme‐linked immunosorbent assay method of TNF‐α measurement (n = 8). There was high heterogeneity among studies in all comparisons, which was not essentially affected after sensitivity analyses. The meta‐regression analysis revealed that the male ratio was positively associated with TNF‐α SMD in the comparison between patients with NASH and NAFL (beta = 0.809; 95% CI 0.052–1.566) and accounted for 36% (P = 0.037) of the heterogeneity in this pair of comparison. TNF‐α SMD was not associated with age, body mass index, and alanine aminotransferase in any pair of comparisons. Conclusions Circulating TNF‐α levels were higher in patients with NAFLD compared with controls. Higher levels of circulating TNF‐α were also associated with the severity of NAFLD.

This case report represents the first suspected case of light chain deposition disease relapse associated with mRNA COVID-19 vaccination. The 75-year-old female patient of Greek ethnicity was admitted to the clinic for the investigation of worsening renal function detected on routine lab examinations, two weeks after she received the second dose of the Moderna COVID-19 vaccine (mRNA-1273). Rapidly progressive glomerulonephritis and anemia were the most notable findings. She had a history of LCDD, which had remained stable for four years. Serum protein immunofixation showed monoclonal kappa zones, and a bone marrow biopsy revealed 5% plasma cell infiltration. These, along with other investigations, established the diagnosis of LCDD recurrence. The patient was started on chemotherapy, which improved her immunological profile, but not her renal function. The patient has remained on hemodialysis since. The association between mRNA vaccinations and LCDD relapse may be grounds for investigations into the pathophysiology of MGRS, given the patient’s previous long-term remission. This case report is not intended to directly inform changes in clinical practice. We must stress the importance of following all standardized vaccination protocols, especially in immunocompromised patients.

Introduction This case report represents, to our knowledge, the first suspected case of Light Chain Deposition Disease (LCDD) relapse associated with mRNA COVID-19 vaccination. It must be made clear that timing is the only link between the vaccination and the relapse of LCDD, and since millions of individuals received these vaccines, an event like this may be due to chance. At the same time, this case report may be an entry point into further explorations of the pathogenesis of LCDD, given the mechanism of action of the vaccine and the pathophysiology of the disease, as it is currently understood. Case presentation The 75-year-old female patient of Greek ethnicity was admitted into our clinic for the investigation of worsening renal function that was detected on routine lab examinations two weeks after she received the second dose of the moderna COVID vaccine (mRNA-1273). Rapidly progressive glomerulonephritis and anemia were the most notable findings upon admission. She had a history of Light Chain Deposition Disease (LCDD) which had remained stable under management for four years. Serum protein electrophoresis was performed and showed monoclonal kappa zones, while bone marrow biopsy revealed 5% plasma cell infiltration. All the above, along with other investigations, established the diagnosis of LCDD recurrence. She was started on chemotherapy, which improved her immunological profile but not her renal function. The patient has remained on hemodialysis since. Conclusions The association between mRNA vaccinations and LCDD relapse may be ground for investigations into the pathophysiology of MGRS, given the patient’s previous long-term remission. In this context, we want to stress once again the importance of following standardized routine mandates on COVID vaccination, especially in immunocompromised patients. This case report is not intended to directly inform changes in clinical practice.