臨床前藥物安全性評價研究中常常發(fā)現(xiàn)藥物可誘導實驗動物的肝細胞肥大，可能并伴有肝臟質(zhì)量增加或血清生化中肝損傷指標的變化。近年來研究表明，眾多化合物可以通過激活核內(nèi)激素受體組成型雄甾烷受體（CAR）或過氧化物酶體激活受體α（PPARα）的機制誘導肝細胞肥大，并且該作用機制具有嚙齒類動物的種屬特異性，與人類缺乏相關性。然而，如何判定肝細胞肥大是不良反應還是非不良反應（適應性反應）是病理學家與毒理學家面臨的挑戰(zhàn)。該文從肝細胞肥大的定義、肝臟質(zhì)量、臨床病理學變化以及組織病理學變化等全面闡述了肝細胞肥大的特點，并依據(jù)證據(jù)權重分析方法探討評估肝細胞肥大的預測風險。

Preclinical drug safety evaluation studies have often found that drugs can induce hepatocyte hypertrophy in experimental animals, which may be accompanied by increased lver weight or changes of the indicators of liver injury in serum. Recent studies have shown that hepatocyte hypertrophy may be induced by many xenobiotics through a common mechanism of activation of the nuclear receptors CAR (constitutive androstane receptor) or PPARα (peroxisome activated receptor alpha), and the machanism is rodent-specific and is not related to humans. However, it is a common challenge for pathologists and toxicologists to clearly define what is considered adverse or non-adverse (adaptive response) in the context of hepatocellular hypertrophy. In this paper, the characteristics of hepatocellular hypertrophy were discussed from the definition, liver weights, clinical pathology and histopathology changes, and the predictive risk of hepatocellular hypertrophy was evaluated by weight of evidence analysis.

國家科技重大專項"生物大分子藥物特殊評價關鍵技術研究"（2015ZX09501007）；重大新藥創(chuàng)制"符合中藥特點的有毒中藥安全性評價關鍵技術研究"（2015ZX09501004-002）。