Research & Advocacy

Participate in research.

Patients and families can play a direct role in advancing ARPKD/CHF research. Below are clinical studies actively recruiting participants.

Actively Recruiting

Natural History of Noncirrhotic Portal Hypertension

A study following the course of noncirrhotic portal hypertension, which can occur with Congenital Hepatic Fibrosis.

View on ClinicalTrials.gov (NCT02417740)

While almost all individuals with Autosomal Recessive Polycystic Kidney Disease (ARPKD) have underlying liver involvement (congenital hepatic fibrosis), noncirrhotic portal hypertension does not always develop, nor does it always present to a severe degree.

Liver involvement begins at birth on a microscopic level, but the progression toward clinically significant portal hypertension varies greatly from person to person.

Source (NCBI, PMC2918426)

Learn more about progression

The liver connection: ductal plate malformation: ARPKD is caused by mutations in the PKHD1 gene, which affect both the kidneys and the liver. In the liver, this leads to congenital hepatic fibrosis (CHF) — a condition where immature embryonic bile ducts persist and stimulate scar tissue in the portal areas. This scarring changes the architecture of the liver, creating resistance to blood flow and potentially leading to noncirrhotic portal hypertension.
Variability in portal hypertension: While the microscopic liver changes are universally present, clinical symptoms of portal hypertension — an enlarged spleen (splenomegaly), low platelets (hypersplenism), and esophageal varices — occur in only 36% to 70% of patients. For many, the scarring is mild enough that they never develop noticeable portal hypertension; for others, it appears later in childhood, adolescence, or even adulthood.
Key differences from cirrhosis: ARPKD-related portal hypertension is noncirrhotic: despite extensive scarring, the liver's functional tissue remains largely healthy. Because the liver's synthetic functions (filtering toxins, producing proteins) are preserved, patients typically do not experience liver failure as they would with traditional cirrhosis.
Why does severity vary?: Why some patients remain asymptomatic while others experience complications like gastrointestinal bleeding is not fully understood. Notably, there is no direct correlation between the severity of the kidney disease and the severity of the liver disease — some patients with relatively mild kidney function have more prominent liver and portal-hypertension phenotypes.
Management: Because the liver disease is noncirrhotic, management focuses on monitoring pressure indirectly (e.g., spleen size and platelet counts) rather than treating liver failure. When portal hypertension becomes symptomatic, it can be managed with medications, endoscopic procedures (such as banding varices), or occasionally shunts; liver transplants are rarely required.

Key references

A Study to See If Tolvaptan Is Safe in Infants and Children with ARPKD

Evaluating the safety of tolvaptan in patients from 28 days to under 18 years old with Autosomal Recessive Polycystic Kidney Disease.

View on ClinicalTrials.gov (NCT04782258)

Imaging Assessments of ARPKD Kidney Disease Progression (IMAGE-ARPKD)

Using imaging to track how ARPKD kidney disease progresses over time.

View on ClinicalTrials.gov (NCT07201025)

Please note: The NIH Natural History Study — Clinical Investigations into Autosomal-Recessive Polycystic Kidney Disease and Congenital Hepatic Fibrosis — has finished and is now closed to new participants. Learn about its findings on our Landmark NIH Study page.

Looking for more?

To see additional research trials — including studies outside the United States — search ClinicalTrials.gov. For published medical literature, search PubMed.