Boeckmans Joost, Gatzios Alexandra, Schattenberg Jörn M, Koek Ger H, Rodrigues Robim M, Vanhaecke Tamara
Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Metabolic Liver Research Center, Department of Medicine, University Medical Center Mainz, Mainz, Germany.
Liver Int. 2023 May;43(5):975-988. doi: 10.1111/liv.15533. Epub 2023 Feb 16.
It is unclear whether the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C-to-G single nucleotide polymorphism, resulting in the substitution of isoleucine to methionine at position 148 (I148M), impedes regression of hepatic steatosis when treating non-alcoholic fatty liver disease (NAFLD).
Investigate if carriage of the PNPLA3 148M allele affects the anti-steatotic efficacy of all possible anti-NAFLD interventions, identify gaps in current knowledge and provide guidance for individual treatment.
Research available in public databases was searched up to 13 November 2022. Studies were included if a treatment in NAFLD patients decreased hepatic steatosis in the pooled patient group or a PNPLA3 I148M polymorphism subgroup (II/IM/MM). The risk of bias was assessed using the Cochrane Risk-Of-Bias 2 Tool and the Newcastle-Ottawa Scale.
Moderate evidence indicates that NAFLD patients homozygous for the PNPLA3 148M allele benefit less or not at all from omega-3 carboxylic acids to decrease liver fat, while the PNPLA3 148I allele shows moderate benefit. Low evidence suggests that interventions employing lifestyle changes are more effective to reduce liver fat in NAFLD patients homozygous for the PNPLA3 148M allele compared to patients with wild-type PNPLA3.
NAFLD patients homozygous for the PNPLA3 148M allele might not benefit from omega-3 carboxylic acids to reduce hepatic steatosis in contrast to patients with wild-type PNPLA3. Instead, patients with two PNPLA3 148M alleles should be especially advised to adopt lifestyle changes. Genotyping for PNPLA3 I148M should be encouraged in therapeutic studies for NAFLD.
REGISTRATION NUMBER (PROSPERO): CRD42022375028.
含patatin样磷脂酶结构域蛋白3（PNPLA3）的rs738409 C到G单核苷酸多态性导致148位异亮氨酸被甲硫氨酸取代（I148M），在治疗非酒精性脂肪性肝病（NAFLD）时是否会阻碍肝脂肪变性的消退尚不清楚。
研究携带PNPLA3 148M等位基因是否会影响所有可能的抗NAFLD干预措施的抗脂肪变性疗效，找出当前知识的空白并为个体化治疗提供指导。
检索截至2022年11月13日公共数据库中的研究。纳入的研究需满足NAFLD患者的某种治疗能使合并患者组或PNPLA3 I148M多态性亚组（II/IM/MM）的肝脂肪变性减轻。使用Cochrane偏倚风险2工具和纽卡斯尔-渥太华量表评估偏倚风险。
中等证据表明，PNPLA3 148M等位基因纯合的NAFLD患者从ω-3羧酸降低肝脏脂肪中获益较少或根本无获益，而PNPLA3 148I等位基因显示出中等获益。低证据表明，与野生型PNPLA3患者相比，采用生活方式改变的干预措施对PNPLA3 148M等位基因纯合的NAFLD患者减少肝脏脂肪更有效。
与野生型PNPLA3患者相比，PNPLA3 148M等位基因纯合的NAFLD患者可能无法从ω-3羧酸中获益以减轻肝脂肪变性。相反，应特别建议携带两个PNPLA3 148M等位基因的患者改变生活方式。在NAFLD的治疗研究中应鼓励对PNPLA3 I148M进行基因分型。
注册号（PROSPERO）：CRD42022375028
