Volume 144, Issue 1, Pages 112-121.e2 (January 2013) Characteristics of Congenital Hepatic Fibrosis in a Large Cohort of Patients With Autosomal Recessive Polycystic Kidney Disease  Meral Gunay–Aygun, Esperanza Font–Montgomery, Linda Lukose, Maya Tuchman Gerstein, Katie Piwnica–Worms, Peter Choyke, Kailash T. Daryanani, Baris Turkbey, Roxanne Fischer, Isa Bernardini, Murat Sincan, Xiongce Zhao, Netanya G. Sandler, Annelys Roque, Daniel C. Douek, Jennifer Graf, Marjan Huizing, Joy C. Bryant, Parvathi Mohan, William A. Gahl, Theo Heller  Gastroenterology  Volume 144, Issue 1, Pages 112-121.e2 (January 2013) DOI: 10.1053/j.gastro.2012.09.056 Copyright © 2013 AGA Institute Terms and Conditions

Figure 1 Schematic representation of fibrocystin/polyductin, the protein encoded by the PKHD1 gene, with positions of the mutations identified in our cohort indicated. Missense mutations are listed above and frameshifting mutations are listed below the bar. Domains of the protein are color coded as follows: pink, transmembrane; orange, TMEM2 homology; green, TIG/TIG-like (immunoglobulin-like fold shared by plexins and transcription factors). Gastroenterology 2013 144, 112-121.e2DOI: (10.1053/j.gastro.2012.09.056) Copyright © 2013 AGA Institute Terms and Conditions

Figure 2 Findings on abdominal imaging in patients with ARPKD and CHF. (A) USG showing severely increased echogenicity of the liver. (B) Color Doppler USG showing multiple vessels at the porta hepatis with a patent portal vein (arrow) resembling the cavernomatous transformation. (C) MRI showing enlarged left lobe and multiple intrahepatic biliary cysts as well as splenomegaly. (D) MRI showing enlarged left lobe of the liver extending to the left subdiaphragmatic area. (E) MRI showing large collaterals (arrow) between the spleen and the liver, in addition to splenomegaly and multiple small liver cysts. (F) Anterior coronal MRI section showing patent umbilical vein (arrow). Gastroenterology 2013 144, 112-121.e2DOI: (10.1053/j.gastro.2012.09.056) Copyright © 2013 AGA Institute Terms and Conditions

Figure 3 Artist's rendering and MRCP images showing the spectrum of biliary abnormalities in ARPKD. (A) Drawing of a normal liver. MRCP is normal except for an enlarged gallbladder. s, stomach. (B) Enlarged extrahepatic CBD and gallbladder. MRCP also shows dilated intrahepatic peripheral ducts. The kidney (k) is enlarged due to diffuse microcystic disease. (C) Fusiform and small cystic dilatations of peripheral and central intrahepatic bile ducts as well as fusiform dilatation of the extrahepatic CBD (arrow) and large gallbladder. (D) Fusiform and macrocystic intrahepatic and extrahepatic dilatations and enlarged gallbladder. All patient livers were abnormally shaped with a disproportionately large left lobe as indicated in the artist's rendering (B–D). Gastroenterology 2013 144, 112-121.e2DOI: (10.1053/j.gastro.2012.09.056) Copyright © 2013 AGA Institute Terms and Conditions

Figure 4 Serum albumin level and renal glomerular function showed no correlation with severity of PH, whereas PT and platelet count showed significant correlation with PH. (A) Serum albumin level did not decrease with worsening PH assessed by spleen volume (y = 4.2515x−0.016, R2 = 0.0164, P = .6386). (B) Platelet count displayed a negative correlation with spleen volume (y = 4903x−0.593, R2 = 0.6487, P < .0001). (C) PT increased with worsening PH measured by spleen volume (y = 0.0019x + 12.842, R2 = 0.51, P < .0001). (D) Renal GFR did not show a good correlation with severity of PH based on spleen volume, although there was a trend (y = 14.205x0.3025, R2 = 0.1021, P = .0225). Gastroenterology 2013 144, 112-121.e2DOI: (10.1053/j.gastro.2012.09.056) Copyright © 2013 AGA Institute Terms and Conditions

Figure 5 (A) SL/H ratio plotted against age. The black line indicates the upper limit of normal range, and the red line is the mean in healthy individuals. Patients whose SL/H ratio was greater than the upper limit of normal were classified as having splenomegaly. (B) SL/H ratio correlated inversely with platelet count (R2 = 0.42, P < .0001). (C) SL/H ratios of patients with missense mutations and with truncating mutations were similar (P = .73). (D) SL/H ratio correlated with APRI (R2 = 0.19, P = .0002). Gastroenterology 2013 144, 112-121.e2DOI: (10.1053/j.gastro.2012.09.056) Copyright © 2013 AGA Institute Terms and Conditions

Supplementary Figure 1 Score card of spectrum of liver echogenicity on USG, including (A) normal and (B) mildly, (C) moderately, and (D) severely increased liver echogenicity. Gastroenterology 2013 144, 112-121.e2DOI: (10.1053/j.gastro.2012.09.056) Copyright © 2013 AGA Institute Terms and Conditions

Supplementary Figure 2 Abdominal MRI of patients with ARPKD with various severities of liver and kidney disease. (A) Six-year-old girl (patient 23; Supplementary Table 1) with spleen volume of 760 mL and enlarged cystic end-stage kidneys; GFR was 22 mL/min/1.73 m2. (B) Nine-year-old girl (patient 43) with markedly increased spleen volume of 1219 mL and decreased GFR of 32 mL/min/1.73 m2. Her enlarged cystic kidneys, similar to those of patient 23, are not seen on this anterior coronal image. (C) Seven-year-old boy (patient 51.1) with spleen volume of 681 mL. His mild kidney disease is limited to parts of the medulla, and his GFR is normal. (D) This 39-year-old woman (patient 60) required a renal transplant at 36 years of age. Her spleen volume at 39 years of age was only mildly increased at 270 mL. (E) This 24-year-old woman (patient 10.2) had a mildly increased spleen volume at 272 mL in association with moderate renal disease affecting the entire medulla but only parts of the cortex. The GFR was decreased at 55 mL/min/1.73 m2. (F) This 14-year-old girl (patient 26.2) was diagnosed at 14 years of age by imaging performed due to family history; she had a normal-sized spleen at 190 mL and mild renal disease in association with a normal GFR. Gastroenterology 2013 144, 112-121.e2DOI: (10.1053/j.gastro.2012.09.056) Copyright © 2013 AGA Institute Terms and Conditions