Department of Pathology, Aristotle University Medical School, 54006, Thessaloniki, Greece.
Department of Pathology, New York University School of Medicine, 550 First Avenue, TH415, New York, NY, 10016, USA.
Virchows Arch. 2018 Jul;473(1):15-22. doi: 10.1007/s00428-018-2340-2. Epub 2018 Mar 27.
Cirrhosis has been traditionally viewed as an irreversible, end-stage condition. Eighteen years ago, Wanless, Nakashima, and Sherman published a study that was based on the concept that hepatic architecture is under constant remodeling in the course of chronic liver diseases, even during their most advanced stages; depending on the balance between injury and repair, the histologic changes might be progressing or regressing. These authors described in detail the morphologic features of regressing cirrhosis, identified a set of histologic features of regression that they called the "hepatic repair complex," and provided convincing morphologic evidence that incomplete septal cirrhosis represents regressed cirrhosis. In the years that followed publication of this pioneering article, a number of clinical studies with performance of pre- and post-treatment liver biopsies provided abundant evidence that cirrhosis can regress after successful therapy of chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis, and genetic hemochromatosis. Evidence for other chronic liver diseases may also be provided in the future, pending ongoing studies. Successful therapy allows resorption of fibrous septa, which can be followed by loss of nodularity and architectural improvement; however, many vascular lesions of cirrhotic livers are not thought to regress. Cases of cirrhosis that are considered more likely to improve than others include those of recent onset, with relatively thin fibrous septa and mild vascular changes. Histologic examination of liver biopsy specimens from patients with chronic liver diseases provides the opportunity to appreciate the features of the hepatic repair complex on a routine diagnostic basis; however, interpretation is often difficult, and can be aided by immunohistochemical stains. Clinicopathologic correlation is essential for a meaningful assessment of such cases. For many patients, cirrhosis is not an end-stage condition anymore; therefore, use of the term "cirrhosis" has been challenged, almost 200 years after its invention. However, regression of cirrhosis does not imply regression of molecular changes involved in hepatocarcinogenesis; therefore, surveillance for hepatocellular carcinoma should be continued in these patients.
肝硬化一直被视为一种不可逆转的终末期疾病。18 年前，Wanless、Nakashima 和 Sherman 发表了一项研究，该研究基于这样一种概念，即在慢性肝病的过程中，即使在其最晚期阶段，肝组织结构也在不断重塑；根据损伤和修复之间的平衡，组织学变化可能在进展或消退。这些作者详细描述了消退性肝硬化的形态特征，确定了一组他们称之为“肝修复复合体”的消退性肝硬化的组织学特征，并提供了令人信服的形态学证据，表明不完全间隔性肝硬化代表消退性肝硬化。在这篇开创性文章发表后的几年里，许多临床研究对慢性乙型肝炎、慢性丙型肝炎、自身免疫性肝炎和遗传性血色素沉着症进行了治疗前后的肝活检，提供了大量证据表明肝硬化可以在成功治疗后消退。在未来，随着正在进行的研究的进行，可能还会有其他慢性肝病的证据。成功的治疗可以使纤维间隔吸收，随后结节消失，结构改善；然而，许多肝硬化肝脏的血管病变被认为不会消退。与其他情况相比，那些更有可能改善的肝硬化病例包括发病时间较短、纤维间隔较薄、血管变化较轻的病例。对慢性肝病患者的肝活检标本进行组织学检查，为在常规诊断基础上了解肝修复复合体的特征提供了机会；然而，解释往往很困难，可以通过免疫组织化学染色来辅助。临床病理相关性对于对这些病例进行有意义的评估至关重要。对许多患者来说，肝硬化不再是一种终末期疾病；因此，在发明这个术语近 200 年后，对“肝硬化”一词的使用提出了质疑。然而，肝硬化的消退并不意味着参与肝癌发生的分子变化的消退；因此，这些患者仍应继续监测肝细胞癌。
