Patatin-like phospholipase domain-containing protein-3 (PNPLA3), the transmembrane 6 superfamily member 2 protein (TM6SF2) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes are involved in non-alcoholic fatty liver disease (NAFLD) development and worsening. Following the actual scientific knowledge, some studies have identified the genetic background surrounding NAFLD, counting up to forty different genetic variants that seem to exert also a crucial role in the disease evolution, according to the natural history, until hepatocellular carcinoma onset. However, few data exist regarding their influence on the treatment response. The aim was to explore the effect of 303 mg of silybin-phospholipids complex, 10 mg of vitamin-D and 15 mg of vitamin-E twice a day for six months in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926 and MBOAT7-rs641738 genetic variants. The assessed mutations are independently associated with no response to a silybin/vitamin D-based therapy and could be useful therapeutic predictive markers in this context.
Name: Nutraceutical therapy
Description: The HOMA-IR was calculated using the following formula: fasting insulin (μU/mL) × plasma glucose (mmol/L)/22.5. The investigators considered the patients responder if at least one of the following criteria was addressed: normalization of the HOMA-IR (<2.5) at the end of treatment starting from baseline values greater than 2.5; reduction of the HOMA-IR ≥ 2 points at the end of treatment in comparison to baseline.
Measure: Number of participants in each study group which shown an improvement from baseline of insulin resistance assed by HOMA-IR Time: Six monthsDescription: The ALT levels were assessed using a colorimetric commercially available kits and expressed as IU/L. The investigators also considered the parameter improved from the baseline in case of normalization (<45 IU/L).
Measure: Mean change in ALT levels from baseline Time: Six monthsDescription: The insulin levels were measured enzymatically using commercially available kits and expressed as micro-IU/ml. The investigators also considered the parameter improved from the baseline in case of normalization (<24 micro-IU/ml).
Measure: Mean change in insulin levels from baseline Time: Six monthsDescription: The CRP levels were measured enzymatically using commercially available kits and expressed as mg/dl. The investigators also considered the parameter improved from the baseline in case of CRP normalization (<0.6 mg/dL) or reduction of at least 1 mg/dL.
Measure: Mean change in CRP levels from baseline Time: Six monthsDescription: TBARS assay was performed using 10 μl of serum. The cromogen TBARS was quantified using a spectrophotometer at a wavelength of 532nm with 1,1,3,3-tetramethoxyprophane as a standard. The amount of TBARS was expressed as nmol/μg of protein. The investigators also considered the parameter improved from the baseline in case of TBARS reduction of at least 10 nmol/μg
Measure: Mean change in TBARS levels from baseline Time: Six monthsAllocation: Randomized
Parallel Assignment
There is one SNP
One hundred two patients with histological diagnosis of NAFLD followed by the Hepatogastroenterology Division of the University of Campania "Luigi Vanvitelli, between January and October 2017 were screened, after signing an informed consent, for the PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 genetic variants and thirty-two met the inclusion criteria for the study and showed at least one among PNPLA3 I148I/M, I148M/M, TM6SF2 167E/K, 167K/K and MBOAT7 TMC4C/T or TMC4T/T genetic variants, were enrolled together with sixty patients without the mutations. --- I148M ---