- Il presente studio ha mostrato che i pazienti con diagnosi di NAFLD (steatosi epatica non alcolica) o di elevato contenuto di grasso epatico sembrano avere un rischio aumentato di psoriasi.
- La randomizzazione mendeliana, però, utilizzando varianti genetiche, non ha mostrato un’evidenza di correlazione causale tra NAFLD e psoriasi; pertanto, l’associazione osservazionale sembra essere il risultato di fattori confondenti condivisi o di reverse causation.
Abstract
Background
Psoriasis is observationally associated with a higher risk of non-alcoholic fatty liver disease (NAFLD); however, the causal relationship between the two diseases remains unclear.
Objective
We hypothesized that individuals with NAFLD or elevated liver fat content have higher risk of psoriasis and that NAFLD is a causal risk factor for psoriasis. We tested this using a Mendelian randomization approach.
Methods
We included 108,835 individuals from the Danish general population, including 1,277 individuals with psoriasis and 802 individuals with NAFLD according to ICD codes. To estimate liver fat content, a subset of the participants (N = 7,416) also had a CT scan performed. First, we tested whether a diagnosis of NAFLD or elevated liver fat content was observationally associated with risk of psoriasis. Subsequently, we used the genetic variants PNPLA3 and TM6SF2, both strongly associated with NAFLD and high liver fat content, to test whether NAFLD was causally associated with increased risk of psoriasis.
Results
Observationally, individuals with vs. without a diagnosis of NAFLD had higher risk of psoriasis with an odds ratio of 2.03 (95% confidence interval 1.28-3.21). The risk of psoriasis increased in a stepwise manner with increasing liver fat content with an odds ratio of 5.00 (2.63-9.46) in individuals in the highest quartile of liver fat content compared to individuals in the lowest quartile. In genetic analyses, PNPLA3 and TM6SF2 were both associated with increased risk of NAFLD but not with increased risk of psoriasis.
Conclusions and perspectives
Observationally, a diagnosis of NAFLD or elevated liver fat content was associated with higher risk of psoriasis. However, using genetic variants as a proxy for NAFLD, we did not find evidence of a causal relationship between NAFLD and psoriasis. Thus, the observational association between NAFLD and psoriasis is presumably a result of shared confounding factors or reverse causation.