Altered profiles of circulating cytokines in chronic liver diseases (NAFLD/HCC): Impact of the PNPLA3 I148M risk allele

Abstract

Background: Individuals carrying the risk variant p.I148M of patatin-like phospholipase domain-containing protein 3 (PNPLA3) have a higher susceptibility to fatty liver diseases and associated complications, including HCC, a cancer closely linked to chronic inflammation. Here, we assessed circulating cytokine profiles for patients with chronic liver diseases genotyped for PNPLA3. Methods: Serum concentrations of 22 cytokines were measured by multiplex sandwich-ELISA. The cohort comprised 123 individuals: 67 patients with NAFLD without cirrhosis (57 steatosis, 10 NASH), 24 patients with NAFLD with cirrhosis, 21 patients with HCC (15 cirrhosis), and 11 healthy controls. Receiver operator characteristic analyses were performed to assess the suitability of the cytokine profiles for the prediction of steatosis, cirrhosis, and HCC. Results: HGF, IL-6, and IL-8 levels were increased in patients, with ∼2-fold higher levels in patients with cirrhosis versus healthy, while platelet derived growth factor-BB (PDGF-BB) and regulated on activation, normal T cell expressed and secreted (RANTES) showed lower concentrations compared to controls. Migration inhibitory factor and monocyte chemoattractant protein-1 (MCP-1) were found at higher levels in NAFLD samples (maximum: NAFLD-cirrhosis) versus healthy controls and HCC samples. In receiver operator characteristic analyses, migration inhibitory factor, IL-8, IL-6, and monocyte chemoattractant protein-1 yielded high sensitivity scores for predicting noncirrhotic NAFLD (vs. healthy). The top combination to predict cirrhosis was HGF plus PDGF-BB. Migration inhibitory factor performed best to discriminate HCC from NAFLD; the addition of monokine induced gamma (MIG), RANTES, IL-4, macrophage colony-stimulating factor (M-CSF), or IL-17A as second parameters further increased the AUC values (> 0.9). No significant impact of the PNPLA3 I148M allele on cytokine levels was observed in this cohort. Conclusions: Cytokines have biomarker potential in patients with fatty liver, possibly suited for early HCC detection in patients with fatty liver. Patients carrying the PNPLA3 risk allele did not present significantly different levels of circulating cytokines.

Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology

“…The similarities in cytokine levels in NALFD and cryptogenic HCC may therefore point towards a similar origin of their HCC, such as NAFLD. A recent European study identified MIG and MIF 34 as biomarkers for distinguishing non-cirrhotic NAFLD-associated HCC from NAFLD controls. Consistent with our previous findings in a larger cohort, these markers held no value in the detection of NAFLD-related complications.…”

Antinuclear antibodies in children with Wilson’s disease

“…Процесс фиброзирования печени сопровождается изменениями в профиле циркулирующих цитокинов при хронических заболеваниях печени, по концентрации которых можно проводить дифференциальную диагностику между стадиями фиброза [12,13].…”

“…Помимо этого была отмечена тенденция к более высокому содержанию IL4 и IL9 у детей с наличием АНА. Стоит отметить большой разброс показателей уровней циркулирующих цитокинов, что также может быть связано с тем, что у детей с БВ в данной выборке были разные стадии фиброза печени, а изменение цитокино-вого профиля пациентов связано со стадией фиброза печени [12,13].…”