Circulating miR-122 levels in self-recovering hepatitis E patients

Abstract

Background: 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. Lack of data in HE led to investigations in non-pregnant (NPR) and pregnant (PR) patients. Results: Self-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. Conclusion: HEV 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.

Specific Plasma MicroRNA Signatures Underlying the Clinical Outcomes of Hepatitis E Virus Infection

“…These results are consistent with previous studies that described a direct relationship between miR-122 levels and the clinical manifestations of viral hepatitis. For instance, circulating miR-122 levels were associated with hepatitis E severity during pregnancy ( 38 ) and correlated with ALT levels during HCV, HBV, and chronic HEV infections ( 20 , 24 , 26 ). Remarkably, miR-122 was proven essential for HCV replication because it stabilizes the viral genome, thereby increasing virus replication ( 39 , 40 ).…”

Micro RNAs—The Small Big Players in Hepatitis E Virus Infection: A Comprehensive Review

“…The direct interplay between miR-122 and the HEV genome was confirmed by immunoprecipitation and molecular approaches [ 19 ]. This direct interaction resulted in decreased serum levels of circulated miR-122 from patients with acute HEV infection in comparison with non-infected controls [ 58 ], or in acute viremic patients vs. chronic viremic and non-viremic ones [ 59 ]. Thereby, comparative analysis of circulating miRNA levels among HEV acute patients and healthy controls can be used as a predictive pattern for active HEV replication.…”

“…In recent years, the pivotal role of miR-122 in regulation of hepatocyte innate immunity was established, and was achieved by the repression of negative IFN regulation [ 60 ]. Thus, it can be hypothesized that by modulating miRNA-122 levels, as a direct complimentary binding, HEV affects the host inflammatory response and induces liver inflammation during infection [ 58 ]. The same correlation was detected for chronic hepatitis B patients, where the decrease in miR-122 levels led to enhanced inflammatory cytokine (C-C motif chemokine ligand and interleukin-6) expression [ 61 ].…”