Advances in genomic analyses using high throughput technologies has resulted in a comprehensive understanding of the underlying pathobiological process associated with liver disease. Using sophisticated next-generation sequencing (NGS) technologies we have analysed involvement of micro RNA and gene expression in pregnant females with hepatitis E infection.
Hepatitis E is known to be more serious with fatal acute liver failure (FALF) and death in 15-20% of infected pregnant females. Integration of Small RNA deep sequencing and microarray analysis was helpful in identifying putative miRNA signatures indicative of fatal acute liver failure and Survival in HEV infection in pregnancy. Furthermore, we were able to select a panel of micro RNAs specific to HEV infection and Liver Failure
- The Multi-omics in Liver Disease (PIs : Dr Shvetank Sharma, Dr. Jaswinder Maras, Prof. Shiv K Sarin)
The multi-omics facility at ILBS involves a well integrated group employing genomics, metagenomics, proteomics and metabolomics, to understand the underlying processes in disease development and progression.
- Genomics The genomics lab at ILBS is directed towards understanding the basic layout of the liver genome and how it correlates with disease. The genomics unit has recently determined a possible cause of lack of steroid response in severe alcoholic hepatitis patients utilizing next generation sequencing technologies . The genomics group is now engaged in determination and characterization of gene communities that function in coherence and yield the effect at a system level.
- Metagenomics : The study of microbial communities, and genes thereof, colonizing the human body has emerged as a powerful tool in understanding disease establishment and progression. Currently the lab is working on the alcohol induced metagenomic alterations in the gut and corresponding variations in functions of the hepatocytes. As a significant progress in liver disease treatment, ILBS has for the first time in the world run a pilot study on fecal microbiota transplantation (FMT) from a healthy stool donor in server alcoholic hepatitis patients, who could not be given steroids. The outcome of the study have been very promising.
- Proteomics and Metabolomics : The urine meatbolome in severe alcoholic hepatitis (SAH) has resulted in a new discovery at ILBS. Metabolmic profiling was done to identify the baseline metabolic phenotype that could help stratify patients not likely to respond to steroid therapy and to have an unfavorable outcome. For the same baseline urine metabolome was studied in patients with SAH using ultrahigh performance liquid chromatography and high-resolution mass spectrometry. A total of nine urinary metabolites linked to mitochondrial functions significantly discriminated nonresponders of which the most important one was acetyl-L-carnitine. Infact Acetyl-L-carnitine at a level of >2,500 ng/mL reliably segregated survivors from nonsurvivors (P<0.01, log-rank test) in our study cohort. We were able to conclude that urinary metabolome signatures related to mitochondrial functions can predict pretherapy steroid response and disease outcome in patients with SAH.
MicroRNAs in liver disease (Dr. Avishek, Dr. Vijay Kumar and Dr. S.K.Sarin) : Using high throughput microarray based applications the group has identified miRNA networks and their target genes in the liver of hepatitis B patients involved in HBV replication, liver injury and liver fibrosis. The work revealed that immune tolerant group showed elevated miR-199a-5p, miR-221-3p and Let-7a-3p levels which could target genes involved in innate immune response and viral replication. In acute viral hepatitis miR-125b- by effecting STAT3 pathway which emerged as a key player. In HBV early fibrosis and cirrhotic groups, micro RNAs identified had a role on chronic inflammation ( Singh AK, et al, Hepatology, 2018)