Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Clin Gastroenterol Hepatol. 2011 Oct;9(10):902-909.e1. doi: 10.1016/j.cgh.2011.07.006. Epub 2011 Jul 23.
BACKGROUND & AIMS: Mallory-Denk bodies (MDBs) are inclusions found in hepatocytes of patients with chronic liver diseases. Their clinical significance and prognostic value are not understood.
We performed cross-sectional and longitudinal analyses of patients with chronic hepatitis C (CHC) enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial to identify clinical features associated with MDBs and changes in MDBs over time. Biopsy specimens were obtained at baseline and 1.5 and 3.5 years after patients were assigned to groups for the HALT-C trial; and patients were followed up to assess clinical and histologic outcomes.
Of biopsy samples collected from 1050 patients, MDBs were present in 15%. They were associated with insulin resistance and laboratory and histologic markers of advanced liver disease (higher levels of periportal fibrosis, pericellular fibrosis, steatosis, and inflammation). After adjusting for disease severity (the ratio of aspartate aminotransferase to alanine aminotransferase, albumin, platelets, fibrosis, steatosis), the presence of MDBs was associated with histologic progression (odds ratio, 1.97; P = .04). Of the 844 patients from whom serial biopsy samples were collected, 61 (7.2%) developed MDBs (MDB gain) and 101 (12.0%) lost MDBs (MDB loss). The presence or absence of diabetes mellitus was associated with MDB gain (P = .006) or loss (P = .024), respectively. Development of MDBs was associated with decompensation (adjusted hazard ratio, 2.81; P < .001) and histologic signs of progression (adjusted odds ratio, 4.02; P = .004).
The presence of MDBs in liver biopsy samples from patients with CHC is associated independently with fibrosis progression. Gain of MDBs over time is associated with decompensation and progression to cirrhosis; and occurs most frequently among diabetic patients. MDBs might be used as prognostic factors for patients with CHC.
Mallory-Denk 小体（MDB）是存在于慢性肝病患者肝细胞内的包涵体。其临床意义和预后价值尚不清楚。
我们对慢性丙型肝炎（CHC）患者进行了横断面和纵向分析，这些患者参与了丙型肝炎抗病毒长期治疗预防肝硬化（HALT-C）试验，以确定与 MDB 相关的临床特征，以及 MDB 随时间的变化。在患者被分配到 HALT-C 试验组的 1.5 年和 3.5 年后，从 1050 名患者的活检标本中获得基线和活检标本；并对患者进行随访以评估临床和组织学结果。
在 1050 名患者的活检样本中，有 15%存在 MDB。它们与胰岛素抵抗和肝纤维化（门脉周围纤维化、细胞周围纤维化、脂肪变性和炎症的更高水平）的实验室和组织学标志物相关。在调整疾病严重程度（天冬氨酸转氨酶与丙氨酸转氨酶、白蛋白、血小板、纤维化、脂肪变性的比值）后，MDB 的存在与组织学进展相关（比值比，1.97；P =.04）。在从 844 名患者中收集的连续活检样本中，有 61 名（7.2%）出现 MDB（MDB 增加），101 名（12.0%）丢失 MDB（MDB 丢失）。糖尿病的存在与否与 MDB 增加（P =.006）或丢失（P =.024）相关。MDB 的发展与失代偿（调整后的危险比，2.81；P <.001）和组织学进展迹象（调整后的优势比，4.02；P =.004）相关。
CHC 患者肝活检样本中 MDB 的存在与纤维化进展独立相关。随着时间的推移，MDB 的增加与失代偿和进展为肝硬化有关；并且最常发生在糖尿病患者中。MDB 可能被用作 CHC 患者的预后因素。
