Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis

Sukriti, S.; Maras, Jaswinder Singh; Bihari, Chhagan; Das, Subodh K.; Vyas, Ashish Kumar; Sharma, Shvetank; Hussain, Shabbir; Shasthry, Saggere Muralikrishna; Choudhary, Ashok; Premkumar, Madhumita; Kumar, Divyesh; Kumar, Guresh; Mukhopadhyay, Chinmay K.; Kumar, Anupam; Trehanpati, Nirupama; Rautou, Pierre‐Emmanuel; Moreau, Richard; Sarin, Shiv Kumar

doi:10.1111/apt.14564

Cited by 28 publications

(24 citation statements)

References 27 publications

(53 reference statements)

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“…Alternatively, high circulating levels of bacterial DNA may predict the development of infection within the first 7 days of corticosteroid therapy and identify non‐responders . A further study found that circulating microvesicles, reflective of oxidative stress, are more numerous and larger in patients with a Lille non‐response as are higher levels of urinary albumin . Higher levels of lipopolysaccharide, procalcitonin and the presence of the systemic inflammatory response syndrome (SIRS) have also been shown to indicate a worse outcome at 90 days in corticosteroid treated patients .…”

Section: Discussionmentioning

confidence: 97%

Baseline neutrophil‐to‐lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

Forrest

Storey

Sinha³

et al. 2019

Aliment Pharmacol Ther

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Summary Background Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7 days to assess “response”. Aim To assess the prognostic and therapeutic implications of baseline neutrophil‐to‐lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis. Methods Patients recruited to the STOPAH trial and an independent validation group were analysed retrospectively. Area under the receiver operating curve (AUC) analysis was performed. Kaplan‐Meier analysis was used to assess survival. Log‐rank test and odds ratio (OR) were used for comparative analysis. Results Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90‐day outcome (0.660), but was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety‐day survival was not affected by prednisolone treatment if NLR < 5 or > 8 but mortality was reduced with prednisolone treatment when the NLR was 5‐8 (21.0% cf. 34.5%; P = 0.012). Prednisolone treatment increased the chance of Lille response if the NLR was ≥ 5 (56.5% cf. 41.1%: P = 0.01; OR 1.86) but increased the risk of day 7 infection (17.3% cf. 7.4%: P = 0.006; OR 2.60) and AKI (20.8% cf. 7.0%: P = 0.008; OR 3.46) if the NLR was > 8. Incorporation of NLR into a modified Glasgow alcoholic hepatitis score (mGAHS) improved the AUC to 0.783 and 0.739 for 28‐day and 90‐day outcome, respectively. Conclusion The NLR is associated with AKI and infection in severe alcoholic hepatitis. The NLR identifies those most likely to benefit from corticosteroids at baseline (NLR 5‐8). The mGAHS has a good predictive value for 28‐ and 90‐day outcomes.

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Section: Discussionmentioning

confidence: 97%

Baseline neutrophil‐to‐lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

Forrest

Storey

Sinha³

et al. 2019

Aliment Pharmacol Ther

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“…Test performances were higher when total fragments were assessed and when using a diagnostic algorithm, diagnostic accuracy reached 81%. Sukriti et al analysed EV population in peripheral and hepatic vein blood obtained from patients with severe alcoholic hepatitis treated with corticosteroid . At admission, blood counts of CD3+/CD4+ (T‐cell origin), CD68+/CD11b+ (macrophage origin), CD34+ (hematopoietic stem cells) and ASGPR+ (hepatocytes) EV were higher in non‐responders compared to patient who did respond to steroid therapy, whereas neutrophil‐ and natural killer cell EV counts remained unchanged.…”

Section: Extracellular Vesicles In Chronic Liver Diseasesmentioning

confidence: 89%

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Balaphas

Meyer

Sadoul

et al. 2019

Liver International

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Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non‐parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.

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“…The collected EVs were confirmed and characterized using different size latex beads using flow cytometer. Detailed protocol described previously and in Data . However, the presence of other types of vesicles cannot be excluded, and we have therefore referred to the isolated vesicles as extracellular vesicles.…”

Section: Methodsmentioning

confidence: 99%

Extracellular vesicles from hepatitis B patients serve as reservoir of hepatitis B virus DNA

Sukriti

Choudhary

Maras

et al. 2018

Journal of Viral Hepatitis

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Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis

Abstract: SummaryBackground: Severe alcoholic hepatitis patients have high mortality and limited

Cited by 28 publications

References 27 publications

Baseline neutrophil‐to‐lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

Baseline neutrophil‐to‐lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Extracellular vesicles from hepatitis B patients serve as reservoir of hepatitis B virus DNA

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