Portal hypertension in children and young adults with biliary atresia

Abstract

Objective: Biliary atresia (BA) frequently results in portal hypertension (PHT), complications of which lead to significant morbidity and mortality. The Childhood Liver Disease Research and Education Network was used to perform a cross-sectional multicentered analysis of PHT in children with BA.

Methods: Subjects with BA receiving medical management at a Childhood Liver Disease Research and Education Network site were enrolled. A priori, clinically evident PHT was defined as "definite" when there was either history of a complication of PHT or clinical findings consistent with PHT (both splenomegaly and thrombocytopenia). PHT was denoted as "possible" if one of the findings was present in the absence of a complication, whereas PHT was "absent" if none of the criteria were met.

Results: A total of 163 subjects were enrolled between May 2006 and December 2009. At baseline, definite PHT was present in 49%, possible in 17%, and absent in 34% of subjects. Demographics, growth, and anthropometrics were similar amongst the 3 PHT categories. Alanine aminotransferase, γ-glutamyl transpeptidase, and sodium levels were similar, whereas there were significant differences in aspartate aminotransferase (AST), AST/alanine aminotransferase, albumin, total bilirubin, prothrombin time, white blood cell count, platelet count, and AST/platelet count between definite and absent PHT. Thirty-four percent of those with definite PHT had either prothrombin time >15 seconds or albumin <3 g/dL.

Conclusions: Clinically definable PHT is present in two-thirds of North American long-term BA survivors with their native livers. The presence of PHT is associated with measures of hepatic injury and dysfunction, although in this selected cohort, the degree of hepatic dysfunction is relatively mild and growth is preserved.

Trial registration: ClinicalTrials.gov NCT00061828.

Figure 1

Age distribution at enrollment. The number of BA subjects of the cohort of 163 in each age range is indicated in this bar graph.

Figure 2

A: Presence of clinical characteristics or history of complications of PHT at enrollment. The percentage of the BA subjects who reported ascites, esophageal variceal bleeding (EV Bleed), hepatopulmonary syndrome (HPS), splenomegaly [spleen tip > 2 cm below the costal margin], thrombocytopenia [Platelet count (plt) < 150k] or both (Spleen + Plt) are noted. Subjects could have more than one characteristic or complication so that the total is greater than 100%. B: Venn diagram of the factors determining presence of Definite PHT. The factor associated with definite PHT is represented by each ellipse and is described by the text next to the ellipse. The interrelationship of the features is indicated by the overlap of the ellipses and the number with the overlapping sections. For example, following the left-most ellipse of Ascites, only 4 of the 14 reported ascites alone, while 1 each reported ascites+ EV bleed and ascites + HPS + EV bleed, while none of the 8 subjects with HPS had HPS + ascites. In 56 subjects PHT was absent and in 27 it was possible (not shown). Sizes of the ellipses do not correlate with the number of subjects. EV = esophagogastric variceal hemorrhage; HPS = hepatopulmonary syndrome.

Figure 2

A: Presence of clinical characteristics or history of complications of PHT at enrollment. The percentage of the BA subjects who reported ascites, esophageal variceal bleeding (EV Bleed), hepatopulmonary syndrome (HPS), splenomegaly [spleen tip > 2 cm below the costal margin], thrombocytopenia [Platelet count (plt) < 150k] or both (Spleen + Plt) are noted. Subjects could have more than one characteristic or complication so that the total is greater than 100%. B: Venn diagram of the factors determining presence of Definite PHT. The factor associated with definite PHT is represented by each ellipse and is described by the text next to the ellipse. The interrelationship of the features is indicated by the overlap of the ellipses and the number with the overlapping sections. For example, following the left-most ellipse of Ascites, only 4 of the 14 reported ascites alone, while 1 each reported ascites+ EV bleed and ascites + HPS + EV bleed, while none of the 8 subjects with HPS had HPS + ascites. In 56 subjects PHT was absent and in 27 it was possible (not shown). Sizes of the ellipses do not correlate with the number of subjects. EV = esophagogastric variceal hemorrhage; HPS = hepatopulmonary syndrome.

Figure 3

A–C: Correlation of history of presence of ascites (3A), esophageal variceal bleed (3B) or hepatopulmonary syndrome (3C) with current platelet count and spleen span below the costal margin. The presence (filled circles) or absence (open circles) of a history of ascites (3A), EV bleed (3B) or HPS (3C) for each subject relative to platelet count (y-axis) and spleen size (cm below the costal margin, x-axis) is shown. The horizontal line represents a platelet count of 150,000, and the vertical line a spleen size of 2 cm below the left costal margin. Thus, individuals whose data points fall to the right of a spleen size of 2 cm (x-axis) and below a platelet count of 150,000 (y-axis) are in the definite PHT category. Note that a large majority of subjects with complications fall within this part of the graph.

Figure 3

A–C: Correlation of history of presence of ascites (3A), esophageal variceal bleed (3B) or hepatopulmonary syndrome (3C) with current platelet count and spleen span below the costal margin. The presence (filled circles) or absence (open circles) of a history of ascites (3A), EV bleed (3B) or HPS (3C) for each subject relative to platelet count (y-axis) and spleen size (cm below the costal margin, x-axis) is shown. The horizontal line represents a platelet count of 150,000, and the vertical line a spleen size of 2 cm below the left costal margin. Thus, individuals whose data points fall to the right of a spleen size of 2 cm (x-axis) and below a platelet count of 150,000 (y-axis) are in the definite PHT category. Note that a large majority of subjects with complications fall within this part of the graph.

Figure 3

A–C: Correlation of history of presence of ascites (3A), esophageal variceal bleed (3B) or hepatopulmonary syndrome (3C) with current platelet count and spleen span below the costal margin. The presence (filled circles) or absence (open circles) of a history of ascites (3A), EV bleed (3B) or HPS (3C) for each subject relative to platelet count (y-axis) and spleen size (cm below the costal margin, x-axis) is shown. The horizontal line represents a platelet count of 150,000, and the vertical line a spleen size of 2 cm below the left costal margin. Thus, individuals whose data points fall to the right of a spleen size of 2 cm (x-axis) and below a platelet count of 150,000 (y-axis) are in the definite PHT category. Note that a large majority of subjects with complications fall within this part of the graph.

Figure 4

4A and 4B: Distribution of WBC (4A) and Platelet count (4B) relative to PHT status and presence or absence of complications of PHT. Individual value of WBC count (4A) and platelet count (4B) for those individuals defined with Absent, Possible or Definite PHT. Subjects without any history of complication (defined as either ascites, EV bleed or HPS) are represented as open circles, those with complications as filled circles. Box and whisker plots overlay the data. The heavy bar represents the median, the box indicates the 25^th and 75^th percentile, and the whiskers span 99% of the data if the data were normally distributed.

Figure 4

4A and 4B: Distribution of WBC (4A) and Platelet count (4B) relative to PHT status and presence or absence of complications of PHT. Individual value of WBC count (4A) and platelet count (4B) for those individuals defined with Absent, Possible or Definite PHT. Subjects without any history of complication (defined as either ascites, EV bleed or HPS) are represented as open circles, those with complications as filled circles. Box and whisker plots overlay the data. The heavy bar represents the median, the box indicates the 25^th and 75^th percentile, and the whiskers span 99% of the data if the data were normally distributed.