Fatty liver disease (FLD), including its more severe pathologies, namely steatohepatitis, hepatocarcinoma, and cirrhosis, is the most common cause of chronic liver disease worldwide and is projected to become the leading cause of hepatocellular carcinoma and end-stage liver disease. FLD is heterogeneous with multiple etiologies and diverse histological phenotypes, so therapies will ultimately need to be individualized for relevant targets. Inherited factors contribute to FLD, and most of the genetic variation influencing liver disease development and progression is derived from genes involved in lipid biology, including PNPLA3, TM6SF2, GCKR, MBOAT7, and HSD17B13. From this point of view, we focus in this perspective on how human molecular genetics of FLD have highlighted defects in hepatic lipid handling as a major common mechanism of its pathology and how this insight could be leveraged to treat and prevent its more serious complications.

中文翻译：

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利用人类遗传学确定脂肪肝疾病的潜在新疗法。

脂肪肝疾病（FLD）包括更严重的病理，即脂肪性肝炎，肝癌和肝硬化，是全世界慢性肝病的最常见原因，并且预计将成为肝细胞癌和终末期肝病的主要原因。FLD具有多种病因和不同的组织学表型，因此最终需要针对相关靶点进行个体化治疗。遗传因素促成FLD，影响肝病发展和进程的大多数遗传变异均来自脂质生物学相关基因，包括PNPLA3，TM6SF2，GCKR，MBOAT7和HSD17B13。从这个角度来看，