Role of the PNPLA3 polymorphism rs738409 on silymarin + vitamin E response in subjects with non-alcoholic fatty liver disease

Rev Esp Enferm Dig. 2018 Oct;110(10):634-640. doi: 10.17235/reed.2018.5602/2018.

Abstract

Background: non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. Lifestyle changes are the pillar of the treatment, although a pharmacological approach is sometimes required in the case of a failure to respond/adhere to the diet.

Objective: the aim of this study was to evaluate the effect of silymarin and the influence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant on the response to treatment in patients with NAFLD in a pilot study.

Methods: a total of 54 patients with a NAFLD proven biopsy were enrolled in an open prospective study and were treated with Eurosil 85® (silymarin + vitamin E) for six months. Biochemical parameters and cardiovascular risk factors (diabetes mellitus, dyslipidemia, hypertriglyceridemia, arterial hypertension and HOMA-IR > 2.5) were recorded before and after six months of treatment. Non-invasive indexes (fatty liver index, lipid accumulation product and NAFLD-fibrosis score) were also calculated. The rs738409 PNPLA3 gene polymorphism status was also determined.

Results: significant statistical changes from baseline values after six months of treatment were observed in transaminases levels but not in non-invasive index markers. Twenty patients (37.1%) were G allele carriers and had a higher percentage of lobular inflammation and ballooning on the basal liver biopsy. Patients with the G allele had a smaller decrease in transaminases levels after treatment with silymarin + vitamin E than non-G-allele carriers.

Conclusions: treatment with silymarin + vitamin E produced a decrease in transaminases after six months of treatment without an accompanying weight loss. PNPLA3 G-allele carriers responded poorly to the treatment.

MeSH terms

  • Antioxidants / administration & dosage*
  • Drug Combinations
  • Female
  • Humans
  • Lipase / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Pilot Projects
  • Polymorphism, Genetic*
  • Prospective Studies
  • Silymarin / administration & dosage*
  • Treatment Outcome
  • Vitamin E / administration & dosage*

Substances

  • Antioxidants
  • Drug Combinations
  • Membrane Proteins
  • Silymarin
  • Vitamin E
  • Lipase
  • adiponutrin, human