A 37-year-old man with autosomal polycystic kidney disease (ADPKD) was admitted to our hospital with a liver volume of 8,000 cm3. Hepatic arterial embolization was performed using a microcoil but was ineffective. Eight years later, the hepatomegaly progressed to liver failure and death. At autopsy, the liver weighed 21.5 kg, and the entire liver had been replaced by cysts; in the few remaining areas of liver parenchyma, microscopic, small cysts of various sizes and fibrosis were evident, with only a few normal hepatocytes observed. Hepatic arterial branches developed; however, the portal vein could not be observed.

α-1,2-mannosyltransferase (ALG9) germline variants are linked to autosomal dominant polycystic kidney disease (ADPKD). Many individuals affected with ADPKD possess polycystic livers as a common extrarenal manifestation. We performed whole exome sequencing in a female with autosomal dominant polycystic liver disease (ADPLD) without kidney cysts and established the presence of a heterozygous missense variant (c.677G>C p.(Gly226Ala)) in ALG9. In silico pathogenicity prediction and 3D protein modeling determined this variant as pathogenic. Loss of heterozygosity is regularly seen in liver cyst walls. Immunohistochemistry indicated the absence of ALG9 in liver tissue from this patient. ALG9 expression was absent in cyst wall lining from ALG9- and PRKCSH-caused ADPLD patients but present in the liver cyst lining derived from an ADPKD patient with a PKD2 variant. Thus, heterozygous pathogenic variants in ALG9 are also associated with ADPLD. Somatic loss of heterozygosity of the ALG9 enzyme was seen in the ALG9 patient but also in ADPLD patients with a different genetic background. This expanded the phenotypic spectrum of ADPLD to ALG9.

BACKGROUND: Hepatic transcatheter arterial embolization (TAE) has become an accepted treatment option for patients with symptomatic autosomal dominant polycystic kidney disease (ADPKD) who also have polycystic liver disease and who are not good candidates for surgery. However, indications for TAE and long-term outcome with it are still unclear.
METHODS: Retrospective cohort study.
METHODS: Symptomatic patients with ADPKD with polycystic liver disease who underwent hepatic TAE, June 2001 to December 2012, at Toranomon Hospital and whose liver volume data were available were studied (N=244; 56% on dialysis therapy, none with kidney transplants). Mean age was 55 ± 9 (SD) years, and mean liver volumes were 8,353 ± 2,807 and 6,626 ± 2,485 cm(3) in men and women, respectively. Target arteries were embolized from the periphery using platinum microcoils.
METHODS: Sex-specific quartiles (6,433, 8,142, and 9,574 cm(3) in men and 4,638, 6,078, and 8,181 cm(3) in women) of total liver volume pretreatment.
RESULTS: All causes of mortality were obtained from medical records, followed up until July 31, 2013.
METHODS: Laboratory values were measured before TAE and 1, 3, 6, and 12 months after. Organ volumes were measured pretreatment, then 6 and 12 months after, by summing the products of the organ areas traced in each computed tomographic image.
RESULTS: Liver/cyst volume decreased to 94.7% (95% CI, 93.5%-95.8%) at 6 months and 90.8% (95% CI, 88.7%-92.9%) at 12 months of pretreatment volumes. Serum protein and hematocrit values improved significantly without liver damage. Survival was significantly better for patients with liver volume ≤ 9,574 cm(3) (men) and ≤ 8,181 cm(3) (women) than for those with larger livers (5-year survival, 69% and 48%; P=0.02). Infection and liver failure caused most deaths, especially in patients with larger livers.
CONCLUSIONS: Referral bias and lack of control group.
CONCLUSIONS: Hepatic TAE appears to be a safe and less invasive option for patients with symptomatic polycystic liver, especially those contraindicated for surgical treatment (eg, with malnutrition or on dialysis therapy), improving both hepatic volume and nutrition.