肝损害之间的慢性HBV正常的，最低限度的高ALT更频繁

StephenW

Liver injury more frequent among chronic HBV with normal, minimally high ALT

Gong X, et al. PLoS One. 2015;doi:10.1371/journal.pone.0134532.
September 21, 2015


Researchers found that Chinese patients with chronic hepatitis B virus infection with persistent normal or minimally elevated alanine aminotransferase more frequently developed liver injury, such as fibrosis or necroinflammation, and may need increased surveillance.

“In this study, we present our analysis of liver histology in a large cohort of Chinese chronic hepatitis B patients with [persistent normal] ALT or minimally elevated ALT,” the researchers wrote. “Our analysis was focused on investigating mechanisms underlying normal or nearly normal alanine aminotransferase under conditions of liver injury and fibrosis.”

In a retrospective cross-sectional study, researchers evaluated 300 treatment-naive patients with chronic HBV admitted to the Hepatology Unit of Xiamen Hospital of Traditional Chinese Medicine, China, between January 2010 and October 2014. All patients had already undergone percutaneous liver biopsy, were positive for hepatitis B surface antigen (HBsAg) for at least 12 months, had HBV DNA levels greater than 500 IU/ml and persistent normal alanine aminotransferase (PNALT) or minimally elevated ALT.

Overall, 59% of patients were HBeAg-positive (n = 177). In the positive group, 28.2% of patients had PNALT levels (n = 50) and 71.8% of patients had minimally elevated ALT (n = 127). In the HBeAg-negative group, 51 patients were classified as having PNALT (41.5%) and 72 patients were categorized as having ALT slightly above the upper limit of normal (58.5%).

Approximately 42.9% of patients in the HBeAg-positive group showed changes in liver pathology compared with and 52.8% in the HBeAg-negative group. Fourteen-percent of the HBeAg-positive patients with PNALT (7/50) and 29.1% of patients with minimally elevated ALT showed significant necroinflammation. In the same group of HBeAg-positive patients, 24% with PNALT and 48% with minimally elevated ALT showed significant fibrosis. Fibrosis was detected more frequently compared with necroinflammation in the HBeAg-positive group of patients (P = .001).

Significant necroinflammation and fibrosis were found more frequently in patients with minimally elevated ALT compared with patients with normal ALT (P < .05).

The researchers concluded: “We detected significantly altered liver histology in almost 50% of chronic hepatitis B patients with persistent normal or minimally elevated ALT. We further elucidated the mechanisms of discordance between the appearance of normal or nearly normal ALT in the serum and the significant changes in liver pathology. We propose that small-scale liver injury, occurring intermittently is possibly responsible for such discordance.

“The fibrosis detected in the late HBeAg or in HBeAg-negative phase was possibly carried over from an early HBeAg phase, supporting therapeutic intervention in early HBeAg positive patients, as a priority. Lowering ALT [upper limit of normal] and increasing the frequency of ALT testing are recommended for management of patients with transiently elevated ALT.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.

StephenW

肝损害之间的慢性HBV正常的，最低限度的高ALT更频繁

龚X，等人。公共科学图书馆之一。 2015年，DOI：10.1371 / journal.pone.0134532。
2015年9月21日


研究人员发现，中国的慢性乙肝病毒感染的持续正常或轻度谷丙转氨酶升高更频繁地开发的肝损伤，如纤维化或坏死性炎症，并可能需要加强监督。

“在这项研究中，我们提出我们的肝脏组织学分析，在中国慢性乙型肝炎患者[持续正常] ALT或轻度ALT升高的大型队列，”研究人员写道。 “我们的分析，重点查处肝损伤和肝纤维化的条件下基本正常或接近正常丙氨酸氨基转移酶的机制。”

在一项回顾性横断面研究中，研究人员评估300初治慢性HBV考入中国传统医学，中国，厦门医院的肝病单位2010年1月和2014年10月之间的所有患者已接受经皮肝穿刺活检，分别为积极为乙肝表面抗原（HBsAg）至少12个月内，有HBV DNA水平大于500 IU / ml和持久的正常丙氨酸氨基转移酶（PNALT）或轻度ALT升高。

总体来说，患者59％为HBeAg阳性（N = 177）。在阳性组的患者28.2％的PNALT水平（50例）的患者71.8％有轻度升高ALT（N = 127）。在HBeAg阴性组，51例患者被列为有PNALT（41.5％）和72例患者归类为略高于正常值上限（58.5％），ALT。

大约有42.9％的患者在HBeAg阳性组与显示在HBeAg阴性组和52.8％相比变化肝脏病理。十四，百分之HBeAg阳性患者PNALT（7/50）的患者有轻度升高ALT 29.1％，表现出显著坏死性炎症。在同组的HBeAg阳性患者中，24％PNALT和48％，与轻度升高ALT显示显著纤维化。纤维化检测更频繁地与坏死性炎症的患者（P = 0.001）的HBeAg阳性组。

显著坏死性炎症和纤维化患者轻度升高ALT出现更为频繁的患者ALT正常（P <0.05）相比。

研究人员得出结论：“我们检测到的显著改变的肝组织学检查在慢性乙型肝炎患者持续正常或轻度升高ALT的近50％。我们进一步阐明偏差的机制的正常或接近正常ALT的血清中的出现和在肝脏病理显著变化之间。我们认为小规模的肝损伤，出现间歇性可能是负责这种不一致。

“在e抗原年底或HBeAg阴性阶段检测到的纤维化可能结转从大三阳早期阶段，早期HBeAg阳性患者辅助治疗干预作为优先事项。降低ALT [正常值上限]，增加ALT检测频率被推荐用于患者的瞬时升高ALT管理“ - 由梅林达·史蒂文斯

披露：研究人员报告没有相关财务披露。

StephenW

A Mechanistic Assessment of the Discordance between Normal Serum Alanine Aminotransferase Levels and Altered Liver Histology in Chronic Hepatitis B

    Xianqiong Gong,
    Jiaen Yang,
    Jinmo Tang,
    Chong Gu,
    Lijian Huang,
    Ying Zheng,
    Huiqing Liang,
    Min Wang,
    Chuncheng Wu,
    Yue Chen,
    Manying Zhang,
    Zhijian Yu,
    Qianguo Mao



    Published: July 31, 2015
    DOI: 10.1371/journal.pone.0134532

   

Abstract

To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort.

StephenW

正常血清谷丙转氨酶水平之间的不一致性的机理评估和改变肝脏组织学慢性乙型肝炎

    Xianqiong宫，
    家恩阳，
    今墨堂，
    崇古，
    利剑黄，
    嬴政，
    回青梁，
    王敏，
    吴春城，
    陈越，
    张满英，
    志坚宇，
    前郭茅



    发布时间：2015年7月31日，
    DOI：10.1371 / journal.pone.0134532

   

抽象的

要了解正常血清丙氨酸氨基转移酶（ALT）水平，并显著改变慢性乙型肝炎病毒（HBV）感染与持续ALT正常（PNALT）或轻度ALT升高肝脏组织学之间的不一致背后的机制。一共有300初治慢性HBV感染患者的PNALT（ALT≤正常上限[ULN，40单位/毫升]）或轻度升高ALT（1-2×ULN）进行回顾性入选。所有患者进行肝活检组织学变化，生化及乙肝标志物分析沿。其中300人参加，177为HBeAg阳性和123 HBeAg阴性。显著组织学发现异常42.9％（177分之76）和HBeAg阳性和HBeAg阴性患者的52.8％（一百二十三分之六十五），分别。显著纤维化，这是先有损伤的标志物，更经常检测到比显著坏死性炎症（暗示活性肝损伤）在两个HBeAg阳性和阴性组，表明间歇地发生在我们的队列肝损伤。无显著差异注意到患者HBeAg阳性和阴性相之间或年龄30和40 40之间，并通过严重纤维化百分比，这表明纤维化是从早期阶段可能结转。最后，降低ALT ULN（30 U / L，男性，19 U / L女）独显不足以增加ALT检测肝损伤的敏感性。然而，这项研究仅限于13 HBeAg阳性患者的小样本与ALT在修订后的正常范围内。我们发现显著肝脏病理在慢性HBV感染者的近50％，与PNALT（ALT≤40单位/毫升）或轻度ALT升高。我们推测，小规模的间歇性肝损伤，可能是负责对血清ALT正常，并在我们的队列显著肝脏变化之间的不一致。

StephenW

全文:
http://journals.plos.org/plosone ... ournal.pone.0134532