Dataset Information

Gut metagenome-derived signature predicts hepatic decompensation and mortality in NAFLD-related cirrhosis.

ABSTRACT:

Background

There are limited data on the diagnostic accuracy of gut microbial signatures for predicting hepatic decompensation in patients with cirrhosis.

Aims

To determine whether a stool metagenome-derived signature accurately detects hepatic decompensation and mortality risk in cirrhosis secondary to non-alcoholic fatty liver disease (NAFLD) METHODS: Shotgun metagenomic sequencing was performed on faecal samples collected at study entry from a prospective cohort of adults with NAFLD-related cirrhosis. A Random Forest machine learning algorithm was utilised to identify a metagenomic signature of decompensated cirrhosis (defined by ascites, hepatic encephalopathy or variceal haemorrhage) and subsequently validated in an external cohort. A Cox proportional hazards regression model was used to examine predictors of all-cause mortality.

Results

In all, 25 adults with NAFLD-related cirrhosis (training cohort) were included. Among the 16 participants with decompensated cirrhosis, 33% had ascites, 56% had hepatic encephalopathy and 22% had experienced a variceal haemorrhage (not mutually exclusive). We identified a stool metagenomic signature comprising 13 discriminatory species that reliably distinguished decompensated NAFLD-related cirrhosis (diagnostic accuracy, 0.97, 95% confidence interval [CI] 0.96-0.99). Diagnostic accuracy of the 13-species signature remained high after adjustment for lactulose (area under the curve [AUC] 0.99) and rifaximin use (AUC 0.93). The discriminative ability of 13-species metagenomic signature was robust in an independent test cohort (AUC 0.95, 95% CI 0.81-1.00). The 13-species metagenomic signature (hazard ratio [HR] 1.54, 95% CI 1.10-2.15, p = 0.01) was a stronger predictor of mortality than the Model for End-Stage Liver Disease score (HR 1.25, 95% CI 1.03-1.53, p = 0.03).

Conclusions

This study provides evidence for a gut metagenome-derived signature with high diagnostic accuracy for hepatic decompensation that predicts risk of mortality in NAFLD-related cirrhosis.

SUBMITTER: Sharpton SR

PROVIDER: S-EPMC9746351 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Gut metagenome-derived signature predicts hepatic decompensation and mortality in NAFLD-related cirrhosis.

Sharpton Suzanne R SR Oh Tae Gyu TG Madamba Egbert E Wang Chenjingyi C Yu Ruth T RT Atkins Annette R AR Huan Tao T Downes Michael M Evans Ronald M RM Loomba Rohit R

Alimentary pharmacology & therapeutics 20220926 10

<h4>Background</h4>There are limited data on the diagnostic accuracy of gut microbial signatures for predicting hepatic decompensation in patients with cirrhosis.<h4>Aims</h4>To determine whether a stool metagenome-derived signature accurately detects hepatic decompensation and mortality risk in cirrhosis secondary to non-alcoholic fatty liver disease (NAFLD) METHODS: Shotgun metagenomic sequencing was performed on faecal samples collected at study entry from a prospective cohort of adults with ...[more]

PMID: 36164267

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Project description:Background & aimsBody composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients.MethodsA total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort.ResultsOur cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p <0.001) as well as visceral and subcutaneous fat density (HR 1.013 and 1.014, respectively, p <0.001). Models utilizing these features outperformed MELD alone for mortality discrimination in both the derivation and validation cohort, particularly for those with compensated cirrhosis (C-statistics of 0.74 vs. 0.58). Using competing risk analysis, we found that subcutaneous fat density was most predictive of decompensation (subdistribution HR 1.018, p = 0.0001).ConclusionThe addition of body composition features to predictive models improves the prospective determination of prognosis in patients with cirrhosis, particularly those with compensated disease. Fat density, a novel feature, is associated with the risk of decompensation.Lay summaryAm I at high risk of getting sicker and dying? This is the key question on the mind of patients with cirrhosis. The problem is that we have very few tools to help guide our patients, particularly if they have early cirrhosis (without symptoms like confusion or fluid in the belly). We found that how much muscle and fat the patient has and what that muscle or fat looks like on a CT scan provide helpful information. This is important because many patients have CT scans and this information is hiding in plain sight.

Dataset Information

Gut metagenome-derived signature predicts hepatic decompensation and mortality in NAFLD-related cirrhosis.

Background

Aims

Results

Conclusions

Publications

Gut metagenome-derived signature predicts hepatic decompensation and mortality in NAFLD-related cirrhosis.

Similar Datasets

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