Inova Fairfax Hospital, Falls Church, VA, USA.
Inova Fairfax Hospital, Falls Church, VA, USA.
J Hepatol. 2018 Dec;69(6):1365-1370. doi: 10.1016/j.jhep.2018.08.013. Epub 2018 Aug 23.
BACKGROUND & AIMS: Although patients with cryptogenic cirrhosis have historically been considered as having "burnt-out" non-alcoholic steatohepatitis (NASH), some controversy remains. The aim of this study was to compare outcomes of patients with cryptogenic cirrhosis and NASH-related cirrhosis from a cohort with longitudinal follow-up data.
Patients with cryptogenic cirrhosis or NASH cirrhosis were screened for a clinical trial. Patients with <5% hepatic steatosis regardless of other histologic features were considered to have cryptogenic cirrhosis. Clinico-laboratory data and adjudicated liver-related events (e.g. decompensation, qualification for transplantation, death) were available.
A total of 247 patients with cirrhosis (55.3 ± 7.4 years, 37% male) were included; 144 had NASH cirrhosis and 103 had cryptogenic cirrhosis. During a median follow-up of 29 (IQR 21-33) months (max 45 months), 20.6% of patients had liver-related clinical events. Patients with NASH cirrhosis and cryptogenic cirrhosis were of a similar age and gender, as well as having a similar body mass index, PNPLA3 rs738409 genotype, and prevalence of diabetes (p >0.05). However, patients with cryptogenic cirrhosis had higher serum fibrosis markers and greater collagen content and α-smooth muscle actin expression on liver biopsy. Compared to cirrhotic patients with NASH, patients with cryptogenic cirrhosis experienced significantly shorter mean time to liver-related clinical events (12.0 vs. 19.4 months; p = 0.001) with a hazard ratio of 1.76 (95% CI 1.02-3.06).
Populations with NASH and cryptogenic cirrhosis have similar demographics, but patients with cryptogenic cirrhosis have evidence of more active fibrosis and a higher risk of liver-related clinical events. Thus, we believe these patients belong to the same spectrum of disease, with cryptogenic cirrhosis representing a more advanced stage of fibrosis.
Significant liver damage and cirrhosis of the liver may develop without a known cause - a liver disease referred to as cryptogenic cirrhosis. In this work we found that, in the presence of metabolic abnormalities, cryptogenic cirrhosis may actually be a part of the non-alcoholic fatty liver disease spectrum. Yet, it appears to be more progressive than typical non-alcoholic fatty liver disease, leading to advanced liver disease at a faster rate.
虽然以往认为隐源性肝硬化患者的非酒精性脂肪性肝炎（NASH）已经“耗尽”，但仍存在一些争议。本研究的目的是比较具有长期随访数据队列中隐源性肝硬化和 NASH 相关肝硬化患者的结局。
筛选参加临床试验的隐源性肝硬化或 NASH 相关肝硬化患者。无论其他组织学特征如何，肝脂肪变性<5%的患者被认为患有隐源性肝硬化。临床-实验室数据和裁定的肝脏相关事件（例如失代偿、符合移植条件、死亡）可用。
共纳入 247 例肝硬化患者（55.3±7.4 岁，37%为男性）；144 例为 NASH 肝硬化，103 例为隐源性肝硬化。中位随访时间为 29（IQR 21-33）个月（最长 45 个月），20.6%的患者发生肝脏相关临床事件。NASH 肝硬化和隐源性肝硬化患者的年龄和性别相似，体重指数、PNPLA3 rs738409 基因型和糖尿病患病率也相似（p>0.05）。然而，与 NASH 肝硬化患者相比，隐源性肝硬化患者的血清纤维化标志物更高，肝活检胶原含量和α-平滑肌肌动蛋白表达更高。与 NASH 相关的肝硬化患者相比，隐源性肝硬化患者发生肝脏相关临床事件的平均时间明显更短（12.0 个月 vs. 19.4 个月；p=0.001），风险比为 1.76（95%CI 1.02-3.06）。
NASH 和隐源性肝硬化患者的人群特征相似，但隐源性肝硬化患者有更活跃的纤维化证据，发生肝脏相关临床事件的风险更高。因此，我们认为这些患者属于同一疾病谱，隐源性肝硬化代表更晚期的纤维化阶段。
一种称为隐源性肝硬化的肝脏疾病，可能在没有明确病因的情况下发生严重的肝损伤和肝硬化。在这项工作中，我们发现，在存在代谢异常的情况下，隐源性肝硬化实际上可能是非酒精性脂肪性肝病谱的一部分。然而，它似乎比典型的非酒精性脂肪性肝病更具进展性，导致肝脏疾病的进展速度更快。
