Background: Dysbiosis of the intestinal microbiome is common among patients with decompensated liver disease and has been associated with disease progression as well as life-threatening complications including infection and encephalopathy. However, the impact of pre- and post-liver transplant (LT) fecal microbial diversity on post-transplant clinical outcomes is not known. Methods: Consecutive adult LT candidates and recipients have been prospectively enrolled since 03/2014. Serial fecal samples were collected pre-LT, at weeks 1, 2, 3 and then monthly until 1 year post-LT. Patients with 1 year of post-LT follow up were included in this analysis. Bacterial 16S rRNA (V3-V4 region) sequencing was performed (Illumina MiSeq). Pre- and post-LT alpha- (Chao index) and beta-diversity were calculated using QIIME1 and R, and compared between patients who died by one year post-LT and those who survived. Results: 125 patients completed 1 year of follow up and are included in this analysis, with 495 samples sequenced (median 4 per patient). The mean age was 57.4, 62% were male, and the median (IQR) MELD at LT was high at 25 (18-31). Etiology of liver disease included most commonly HCV (44%), NALFD (16%) and alcohol (11%). Overall, 50 patients (40%) also had a concurrent diagnosis of HCC. Among pre-LT patients (n=53), alpha-diversity differed significantly based upon liver disease etiology (alcohol vs all other diagnoses, p<0.05), as well as severity of liver disease (CTP, p<0.0001). Overall, 10 patients (8%) died in the first year post-LT. Alpha-diversity post-transplant significantly increased over time in those who survived (p=0.003), yet not in those who died. This impact was especially seen in patients with HCV, whose microbiome alpha-diversity increased with time only in patients who survived one year post-LT (p=0.08). Conclusions: Liver disease etiology and severity affect the diversity of the intestinal microbiome in this ongoing cohort. This impact is not only pre- but also post-LT. Indication also affects the trajectory of alpha-diversity post-LT. Regardless of disease etiology, increased microbiome diversity over one year post-LT was seen in patients who survived during this timeframe, yet not in those who died. Dysbiosis of the intestinal microbiome may represent an important therapeutic target to prevent adverse post-LT outcomes.

CITATION INFORMATION: Verna E., Annavajhala M., Nenad M., Brown R., Sullivan S., Korakani G., Gidins M., Khan S., Gomez-Simmonds A., Uhlemann A-.C. Intestinal Microbiome Diversity is Associated with Liver Disease Etiology and Predicts Post-Liver Transplant Mortality Am J Transplant. 2017;17 (suppl 3).

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