Abstract
BackgroundHepatitis E (HE) is prevalent in developing countries in both epidemic and sporadic forms and is characterized by high mortality during pregnancy. miR-122, the major hepatic microRNA has been shown to be modulated during liver diseases. Lack of data in HE led to investigations in non-pregnant (NPR) and pregnant (PR) patients.ResultsSelf-recovering NPR patients and pregnant women presenting with clinical (PR-acute) or subclinical (PR-SC) HE and respective healthy controls were studied. Serum samples were tested for miR-122 levels using qRT-PCR. Acute-phase, NPR patients circulated lower miR-122 levels, reducing further during convalescence. In contrast to previous reports, circulating miR-122 levels did not correlate with serum aminotransferase (ALT). In PR-acute patients, miR-122 levels were significantly lower that reflected pregnancy status and not HEV effect. In PR-SC patients, miR-122 levels were lower than the pregnant controls and reduced further when examined one month apart. A pregnant, fulminant HE patient circulated very high miR-122 levels that increased further during convalescence. Correlation analysis of miR-122 and circulating cytokines showed moderate correlation with CCL2 (subclinical, pregnant) and IL-6 (NPR). This first report revealed downregulation of circulating miR-122 levels in self-recovering NPR-acute patients despite liver damage (raised serum ALT) suggestive of alternate mechanism of secretion in blood.ConclusionHEV infection during pregnancy led to differential modulation of serum miR-122 levels that correlated with clinical presentation. Utility of miR-122 as a prognostic marker for severe disease during pregnancy needs to be evaluated.
Highlights
Hepatitis E (HE) is prevalent in developing countries in both epidemic and sporadic forms and is characterized by high mortality during pregnancy. miR-122, the major hepatic microRNA has been shown to be modulated during liver diseases
MiR-122 levels decrease in Hepatitis E virus (HEV) infected NPR patients The NPR patients circulated significantly lower miR-122 levels than the healthy NPR controls (p < 0.0001, Fig. 2a)
Serum Alanine transaminase (ALT) levels returned to normal while miR-122 levels continued to be lower, though comparable with acute-phase levels (p = 0.98).There was no correlation of circulating miR-122 levels with serum ALT levels (Fig. 2c)
Summary
Hepatitis E (HE) is prevalent in developing countries in both epidemic and sporadic forms and is characterized by high mortality during pregnancy. miR-122, the major hepatic microRNA has been shown to be modulated during liver diseases. Hepatitis E (HE) is prevalent in developing countries in both epidemic and sporadic forms and is characterized by high mortality during pregnancy. Hepatitis E virus (HEV) is the predominant cause of waterborne, epidemic and sporadic acute viral hepatitis among adults from developing countries [1, 2]. Exposure of susceptible individuals to HEV can lead to: (1) subclinical infection (SC), (2) self-limiting clinical hepatitis (acute viral hepatitis (AVH-E)), and (3) Fulminant hepatic failure (FHF-E). Hepatitis E (HE) during pregnancy is characterized by high mortality (~ 15–30%), especially in the third trimester [3, 4]. HEV etiology has been extended to men and non-pregnant women with FHF [5]. Pregnant women from developed countries were shown to develop FHF-E [6]. HEV has been identified as an emerging cause of chronic hepatitis
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