Are liver cysts, such as those associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (ADPLD), congenital or acquired conditions?

Are Liver Cysts Congenital?

Yes, liver cysts associated with polycystic liver disease are congenital—you are born with the genetic mutations that cause them, though the cysts themselves typically develop and become visible later in life. 1, 2

Genetic Basis: Born with the Mutation, Not the Cysts

The key distinction is between having the genetic defect from birth versus when cysts actually appear:

• ADPKD and ADPLD are inherited genetic conditions caused by mutations in specific genes (PKD1, PKD2 for ADPKD; PRKCSH, SEC63, GANAB for ADPLD) that are present from conception 1, 3
• The genetic mutations are congenital, but cyst formation is progressive—cysts develop and accumulate throughout life rather than being present at birth 3, 4
• These conditions follow an autosomal dominant inheritance pattern, meaning you inherit one mutated gene copy from an affected parent (or rarely, it occurs as a de novo mutation) 1, 3

When Liver Cysts Actually Appear

Liver cysts manifest progressively with age, not at birth:

• In ADPKD patients, liver cysts are present in >80% by age 30 years, making them the most frequent extrarenal manifestation 2, 5
• Cyst number and liver volume increase with age, particularly in women 2
• The disease results from embryonic ductal plate malformation of the intrahepatic biliary tree, but actual cyst development requires accumulation of additional genetic "hits" (somatic mutations) in cyst epithelium over time 3, 4

The Two-Hit Mechanism

Why cysts develop later despite being born with the mutation:

• The rate-limiting step for cyst formation requires accumulation of somatic mutations in addition to the inherited germline mutation—this is the "two-hit" hypothesis 3, 4
• Loss of heterozygosity (losing the normal gene copy) in cyst epithelium contributes to hepatic cyst development 4
• This explains why cyst burden varies dramatically between individuals with the same genetic mutation and why cysts progressively accumulate with age 6

Clinical Implications for Diagnosis

The congenital nature affects screening strategies:

• Family history is critical—if a parent has ADPKD or ADPLD, children have a 50% chance of inheriting the mutation 1, 3
• Genetic testing confirms the diagnosis even before cysts are visible on imaging, particularly useful for young potential living kidney donors 1
• For patients ≥60 years with positive family history, ≥4 cysts in each kidney confirms ADPKD diagnosis 2

Important Caveat: Simple Cysts vs. Polycystic Disease

Not all liver cysts are congenital:

• Simple hepatic cysts occur in 2.5–18% of the general population and are acquired, not inherited—these are sporadic findings that increase with age 5
• These simple cysts are distinct from polycystic liver disease and do not indicate an inherited genetic condition 5, 3
• The presence of multiple cysts in both liver and kidneys strongly favors inherited ADPKD over simple acquired cysts 2