Circulating miR-122 and miR-200a as biomarkers for fatal liver disease in ART-treated, HIV-1-infected individuals

Murray, Daniel D.; Suzuki, Kazuo; Law, Matthew; Trebicka, Jonel; Nordwall, Jacquie Neuhaus; Johnson, Margaret; Vjecha, Michael J.; Kelleher, Anthony D.; Emery, Sean

doi:10.1038/s41598-017-11405-8

Cited by 28 publications

(24 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An unsuppressed HIV infection itself could impair stiffness regression as profibrotic effects have been proposed to occur. In addition, ART may influence the evolution of hepatic fibrosis or inflammation in both directions [12][13][14][15][16][30][31][32]. However, our own data do not suggest an influence of ART on stiffness regression.…”

Section: Discussionmentioning

confidence: 83%

“…This may be caused by impaired CD4 T-cell activity [8][9][10][11]. Another possible explanation is a profibrotic effect of antiretroviral therapy (ART) or HIV itself [12][13][14][15][16]. Transient elastography (TE), a noninvasive ultrasound-based technique, has now been validated and is widely accepted for the assessment of liver fibrosis [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Liver stiffness regression after successful Hepatitis C treatment is independent of HIV coinfection

et al. 2019

View full text Add to dashboard Cite

Objectives The aim of the study was to assess the regression of liver stiffness after successful direct‐acting antiviral (DAA) treatment in patients with hepatitis C virus (HCV) monoinfection and HCV/‐HIV coinfection. In addition, we aimed to identify factors associated with liver stiffness regression. Methods We studied patients treated with interferon‐free DAA regimens with a sustained virological response at week 12 (SVR12) or 24 (SVR24) post‐treatment. Liver stiffness was assessed by transient elastography (TE) before the initiation and after the end of treatment (median 12 weeks). Results Of 214 enrolled patients, 85 (40%) were HCV monoinfected and 129 (60%) HCV/HIV coinfected. Baseline median TE values were 7.8 kPa [interquartile range (IQR) 5.9–12.0 kPa] in mono‐infected patients and 10.7 kPa (IQR 7.8–17.0 kPa) in coinfected patients. Overall, the median TE value decreased from 10.1 to 6.8 kPa (n = 214; P < 0.0001). There was no difference between mono‐ and coinfected patients (−2.2 versus −3.3 kPa, respectively; P = 0.88), which was verified by an analysis of covariance (ANCOVA) adjusting for baseline TE values. Significant (≥ 30%) regression of liver stiffness was achieved by 45% of patients (54% with baseline TE ≥ 7.1 kPa). In multivariate analysis, a prior HCV treatment was a negative predictor of liver stiffness regression [odds ratio (OR) 0.31; P = 0.001]. A higher baseline TE value was positively associated with achieving a significant regression (OR 1.06; P = 0.02). HIV coinfection status, HCV genotype, age, sex, treatment duration, controlled attenuation parameter value, bilirubin concentration, platelet count and aspartate aminotransferase concentration were not associated with liver stiffness regression. Conclusions Regression of liver stiffness after successful DAA treatment did not differ in patients with HCV monoinfection and those with HCV/HIV coinfection. Half of all patients achieved a significant (≥ 30%) regression. Prior treatment for HCV was a negative predictor for this endpoint, while a higher baseline TE value was positively associated with regression.

show abstract

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Liver stiffness regression after successful Hepatitis C treatment is independent of HIV coinfection

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In a very recent report based on 13 liver disease-associated fatal cases in a cohort of HIV infected, ART treated individuals, miR-122 was identified as a probable biomarker for liver disease in this population [36]. It would be worthwhile to assess miR-122 as biomarkers for fulminant hepatitis E. A previous study documented 100 fold rise in circulating miR-122 levels in patients with acute liver failure caused by different etiologies [37].…”

Section: Discussionmentioning

confidence: 93%

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

Haldipur

Arankalle

2019

ExRNA

View full text Add to dashboard Cite

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.

show abstract

“…Most of the studies considering circulating miRNAs as biomarkers focused on using blood as the miRNA source. However, human blood contains a variety of cell types, hence making it challenging to identify the cell origin of the particular miRNA focused on in a study (Endzeliņš et al, 2017;Murray et al, 2017).…”

Section: Limitations In Mirna Biomarker Studiesmentioning

confidence: 99%

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

2020

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19-25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nervous system disorders, cardiovascular disorders, and diabetes. We summarize other research findings regarding the use of miRNA from these two sources as biomarkers in diagnostics and clinical use. The challenges in using miRNA from these two sources in cancer and disease diagnostics are evaluated and discussed. Validation of specific miRNA signatures as biomarkers is a critical milestone in diagnostics.

show abstract

Circulating miR-122 and miR-200a as biomarkers for fatal liver disease in ART-treated, HIV-1-infected individuals

Cited by 28 publications

References 50 publications

Liver stiffness regression after successful Hepatitis C treatment is independent of HIV coinfection

Liver stiffness regression after successful Hepatitis C treatment is independent of HIV coinfection

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

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

Contact Info

Product

Resources

About