Natural History of Noncirrhotic Portal Hypertension

Study Description: Up to 400 subjects with noncirrhotic portal hypertension or at risk for developing noncirrhotic portal hypertension by virtue of their underlying disease (as well as sporadic cases of noncirrhotic portal hypertension as referred to in this protocol) will be offered inclusion in the study. Objectives: Primary Objective: 1\. The goal of this natural history study is to generate understanding of the development and progression of NCPH. We will use our findings to generate novel biomarkers that will enable improved follow-up of patients, assist in preventing complications, and enhance transplant decision. Secondary Objectives: 1. Measurement of the bile acids and lipids to understand NCPH and porto-systemic shunting. 2. Identification of the genetic modifiers of NCPH. 3. Evaluation of hepatic transcriptome in absence and presence of NCPH. 4. Characterization of microbiome signatures in NCPH. Endpoints: Primary Endpoints: 1. Establish surveillance methods and guidelines for evaluation of NCPH. 2. Develop an understanding of the biological mechanisms of the progression of NCPH. 3. Identification of novel biomarkers correlating with NCPH progression. Secondary Endpoints: 1. Measurement of bile acids fractionated and total, as well as lipid panel to establish cut-off levels correlating with NCPH severity. 2. Establishment of positive or negative correlation between candidate susceptible genes and disease phenotype. 3. Identification of novel markers of fibrosis or the development of hepatic neoplasia from transcriptome analysis. 4. Characterization of microbiome signatures (taxonomic and functional), as well as identification of specific species.