A given precipitating factor such as bacterial infection has very different outcome (e.g., no sepsis, sepsis, severe sepsis, and septic shock) for reasons that currently remain elusive. Similarly, it is unclear why among patients with alcohol-related hepatitis or gastrointestinal hemorrhage, some develop a very severe disease others don’t. Patient heterogeneity can also be related to differences in the treatment of choice, including non-selective beta-blockers, curative antibiotics, prophylactic antibiotics, corticosteroids, albumin infusion, albumin dialysis, vasopressors, renal replacement therapy, or mechanical ventilation.

Emerging high-throughput omics technologies allow to capture this patient heterogeneity with unprecedented precision. Leveraging these technologies in clinical decision making will help to bring about the long-heralded personalization of medicine.

The interest of using multi-omics approaches to acutely decompensated cirrhosis is illustrated by the example of acute decompensation precipitated by bacterial infections. 

Former studies looking at the presence of pre-specified single-nucleotide polymorphisms (SNPs) in genes such as NOD2, TLR2, and FXR have shown that some SNPs are associated with an increased risk of developing spontaneous bacterial peritonitis (SBP), as reviewed in Seminars in Liver Disease. These findings suggest that genetic variation in these genes could contribute to the risk of infection in cirrhosis. Moreover, previous work from the Grifols Chair for Translational Research showed that two SNPs in the interleukin (IL)-1 locus were associated with decreased intensity of systemic inflammation and lower risk of developing ACLF, suggetsing that SNPs can contribute to the severity of infection by modulating, for example, the intensity of the systemic inflammatory response to pathogens. 

Further investigations need to address alterations in the gut microbiome in patients with cirrhosis at risk of developing SBP. In addition, infections are associated with increased levels of systemic and/or local metabolites reflecting dramatic changes in gene expression (i.e., activation of metabolite-producing enzymes). Indeed, some metabolites (endogenous or produced by microbes) can impact gene expression in immune cells and, therefore, contribute to the overall response to infection. Based on these assumptions, metabolomics is likely to produce important information on metabolic changes associated with infection and, in this context, will eventually allow us to differentiate patients with traditional acute decompensation of cirrhosis from those with ACLF.