Biliary Atresia

00:01 Hello there. In this talk, we're going to discuss biliary atresia.

00:05 So, when your bile ducts go away and you get yellow.

00:09 Biliary atresia is fibrosis of the extrahepatic biliary tree.

00:13 And it can occur diffusely.

00:16 It can occur in focal lesions and it can occur for genetic basis or it can occur because of inflammation or infection.

00:26 In the embryonic form, this is basically primary agenesis.

00:31 The bile tree never really developed. It's present at birth and it's associated often with other congenital anomalies such as flipped visceral situs inversus or polysplenia, multiple fragmented portions of the spleen, intestinal malrotation or congenital heart disease.

00:49 The neonatal form of biliary atresia is the most common.

00:53 The vast majority of babies will have this if they're going to have atresia.

00:57 It's usually just involving the biliary tree, so, none of the other organs mentioned previously.

01:04 And initially, the bile, the biliary tree is normal but then, there will be progressive obliteration either diffusely or in focal areas and that's commonly due to either infections or immune disease.

01:18 If there's complete obliteration which occurs in, unfortunately, the vast majority of cases, this is non-correctible.

01:25 We're going to have to do something like a total liver transplant as we'll talk about at the end.

01:30 If it's surgically correctible, that may be there's focal disease that is amenable to the surgeon cutting out the defect and reanastomosing things or to stenting that focal area of obliteration.

01:43 The epidemiology of this, so, overall, not all that common.

01:47 About one in 10,000 to 15,000 live births for reasons that are probably genetically related, it is more common in Eastern Asian populations, although, there's a worldwide distribution.

01:59 In terms of the pathophysiologic, there may be genetic factors.

02:02 So, the embryonic version is almost certainly driven by primary defects in the genesis of the biliary tree.

02:12 The secondary or neonatal versions of this are often due to inflammation.

02:17 Autoimmune disease with macrophages making tumor necrosis factor that can cause bile epithelium injury or cytotoxic T-lymphocytes that can kill bile epithelium or autoantibodies that can kill bile epithelium.

02:33 All those will lead to, in most cases, a progressive atresia of the biliary tree.

02:41 Viral infections can be a major driver for this. It may underlie some of these so called autoimmune atresias.

02:47 And then, toxins can also clearly damage the biliary epithelial cells.

02:55 The clinical presentation. So, it may be present at birth.

02:58 That's the embryonic form but it may appear, and that's more commonly, over the first initial weeks.

03:04 And the baby at the beginning seems to have a completely normal appetite and normal growth.

03:09 But then, there is a progressive insidious onset of jaundice.

03:14 There is bilirubinuria, meaning that because we're not able to get the bile out of the liver and into the GI tract, we're excreting it in the conjugated form into the bloodstream and it's being urinated away. So, there will be darker urine.

03:33 The stools may be light colored or acholic.

03:36 They'll be clay colored because we're not dumping our conjugated bilirubin into the stool.

03:42 There will often be hepatomegaly secondary to the inflammation.

03:46 And then, with associated portal hypertension, we may have splenomegaly.

03:52 Making the diagnosis. So, first and foremost, it's going to be looking at the bilirubin levels.

03:58 And we will see elevated totals, so, above one to 1.5 milligrams per deciliter and it's going to be predominantly direct.

04:06 So, the liver is able to do its job. It's able to conjugate the bilirubin.

04:10 It's just not able to excrete it because the biliary tree is gone.

04:15 There will also be elevated alkaline phosphatase and elevated alk phos is a really good marker for biliary tree obstruction.

04:22 So, and it may be large biliary tree or even enterohepatic but we'll measure alkaline phosphatase.

04:29 Overall, the ALT and AST are only mildly, if elevated at all.

04:33 And it's going to be because we're not really damaging the hepatocytes until we get the very high levels of bilirubin.

04:41 And so, there's not much release of those transaminases.

04:46 Ultrasonography may give us a sense of the dilation of the bile duct, the entire tree.

04:53 You can also do ERCP, the endoscopic retrograde cholangiopancreatography that will show either diffused or focal areas of obstruction.

05:03 A percutaneous liver biopsy can be done to rule out other potential causes.

05:09 It will show proliferation of the bile ducts. That's kind of the response when there's obstruction.

05:16 Bile ducts reduplicate in an effort to kind of find a new way to get their product out.

05:20 The lobular architecture will be relatively intact. There will be minimal amounts of hepatocyte damage.

05:26 And how do we manage this? Well, if there are focal lesions, we can resect them or stent them.

05:32 If it's diffuse, at least in the perinatal, the early childhood period, we can do a so called Kasai procedure and that's where we will put in a shunt that goes between the portal tract and the bowel and that will allow us to dump the contents of the biliary tree directly into the GI tract.

06:00 But the only definitive therapy is liver transplant. With that, bile or biliary atresia.