Natural History of Noncirrhotic Portal Hypertension

Background: \- Noncirrhotic Portal Hypertension (NCPH) is caused by liver diseases that increase pressure in the blood vessels of the liver. It seems to start slowly and not have many warning signs. Many people may not even know that they have a liver disease. There are no specific treatments for NCPH. Objectives: \- To learn more about how NCPH develops over time. Eligibility: \- People age 12 and older who have NCPH or are at risk for getting it. In the past year, they cannot have had other types of liver disease that typically result in cirrhosis, liver cancer, or active substance abuse. Design: * Participants will have 2 screening visits. * Visit 1: to see if they have or may develop NCPH. * Medical history * Physical exam * Urine and stool studies * Abdominal ultrasound * Fibroscan. Sound waves measure liver stiffness. \<TAB\>- Visit 2: * Blood tests * Abdominal MRI * Echocardiogram * Questionnaire * Liver blood vessel pressure (hepatic venous portal gradient (HVPG)) measurement. This is done with a small tube inserted in a neck vein. * They may have a liver biopsy. * All participants will visit the clinic every 6 months for a history, physical exam, and blood tests. They will also repeat some of the screening tests yearly. * Participants with NCPH will also have: * Upper endoscopy test. A tube inserted in the mouth goes through the esophagus and stomach. * At least every 2 years: Esophagogastroduodenoscopy. * At least every 4 years: testing including HVPG measurements and liver biopsy. * Participants without NCPH will also have: * Liver biopsy and HVPG measurements to see if they have NCPH. * Every 2 years: abdominal MRI and stool studies. * The study will last indefinitely.

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.