4.1 Congenital 

Caroli's disease (congenital intrahepatic biliary dilation) is a rare condition in which saccular, dilated segments of the intrahepatic bile ducts lead to stone formation, recurrent cholangitis and hepatic abscesses with sepsis. Episodes of abdominal pain, fever and jaundice may onset at any age, most commonly in childhood or young adult life.

Cholangiography reveals the irregularly dilated segments of the intrahepatic bile ducts that connect with the main ducts. The common duct is normal. Endoscopy (or surgery) can remove some stones but does little for the process that affects small bile ducts in the liver. If involvement is unilateral, partial hepatectomy can be curative. Otherwise, management is conservative, using antibiotics for infectious complications of the duct system. These recurrent episodes of cholangitis sometimes progress to secondary biliary cirrhosis, portal hypertension and eventually cholangiocarcinoma. Partial hepatectomy of an affected segment sometimes is feasible. Liver transplantation may become necessary in other cases.

Congenital hepatic fibrosis frequently accompanies Caroli's disease (perhaps reflecting a developmental defect of the small interlobular ducts). It clinically presents as portal hypertension with esophageal varices in children. Liver biopsy is diagnostic, revealing broad bands of fibrous tissue entrapping bile ducts but no cirrhosis (i.e., no regeneration). Liver transplantation may be necessary in complicated cases.

Choledochal cyst is a congenital dilation of a portion of the common bile duct, which may form a diverticulum in the intraduodenal segment. This congenital cystic anomaly can be associated with Caroli's disease: both represent a spectrum of defective budding and cannulation from the primitive foregut. Presentation may be as cholestasis in infants, or intermittent jaundice, pain and fever (cholangitis) later in young adults. Complications include chronic obstruction leading to biliary cirrhosis and the development of ductal carcinoma. Diagnosis is provided by ultrasound or CT scan and verified by endoscopic cholangiography. Surgery involves excising the cyst and re-establishing biliary drainage with a biliary-enteric anastomosis.

Alagille's syndrome is a marked reduction in intrahepatic (actually interlobular) bile ducts. Although it is believed to be congenital, being inherited in an autosomal dominant pattern, presentation may be as a neonatal jaundice or as cholestasis in older children. There are associated triangular facies, cardiovascular anomalies (e.g., pulmonary artery stenosis) and vertebral body abnormalities. Outcome is variable, depending upon the attendant anomalies and the severity of the liver disease.

Biliary atresia is a common cause of neonatal cholestatic jaundice. Although congenital (appearing at birth), it is not inherited. Complete absence of the extrahepatic bile ducts reflects either an arrest in remodeling of the ductal plate in utero or, more probably, an inflammatory destruction of the formed bile ducts during the postpartum period. The latter process is evident by an inflammatory infiltrate in the portal tracts and, in some, features of neonatal hepatitis, perhaps initiated by a viral infection. Large duct obstruction then leads to small duct injury within the liver and hence secondary biliary cirrhosis. Severe cholestasis develops in the neonatal period. The stools are pale and the urine is dark and devoid of urobilinogen. Cholestatic features predominate, with the development of steatorrhea, skin xanthoma, bone disease and failure to thrive. Surgery is usually necessary to confirm the diagnosis and attempt some form of biliary drainage. In some, existence of a patent hepatic duct or dilated hilar ducts potentially allows correction of the obstruction by anastomosis to the small intestine (e.g., a Roux-en-Y choledochojejunostomy). Much more common is an absence of patent ducts; dense fibrous tissue encases the perihilar area and precludes conventional surgery. Such obliteration of the proximal extrahepatic biliary system requires the Kasai procedure. A conduit for biliary drainage is fashioned by resecting the fibrous remnant of the biliary tree and anastomosing the porta hepatis to a Roux-en-Y loop of jejunum. With either surgery, most children eventually develop chronic cholangitis, hepatic fibrosis/cirrhosis and portal hypertension. When the child is larger, hepatic transplantation dramatically improves the prognosis.

4.2.1 CHOLANGITIS

Cholangitis is any inflammatory process involving the bile ducts, but common usage implies a bacterial infection, usually above an obstructive site. The presence of bacteria in the biliary tree plus increased pressure within the system results in severe clinical features of cholangitis (suppurative cholangitis). Any condition producing bile duct obstruction is liable to cause bacterial infection of bile. Most commonly, this takes the form of a common duct stone (Section 2.3), a benign biliary stricture (trauma from biliary surgery, ischemia following liver transplantation or sclerosing cholangitis), stasis in a congenital biliary cyst (Section 4.1), a parasite residing in the ducts (Clonorchis sinensis, Opisthorchis viverrini or Fasciola hepatica), an occluded biliary stent or extrinsic compression from a diseased papilla or pancreas. A less likely cause of infection is neoplastic obstruction. The difference relates to the high-grade, fixed obstruction of neoplasms versus the intermittent blockage with a stone or an inflammatory stricture. Such intermittent blockage allows retrograde ascent of bacteria; the stone may act as a nidus for infection. The bacteria are commonly thought to ascend the biliary tree (hence the term "ascending cholangitis"), but may enter from above via the portal vein or from periductular lymphatics.

In acute bacterial cholangitis, particularly if severe, the classical Charcot's triad of intermittent fever and chills, jaundice and abdominal pain may be followed by septic shock. Most cases are less severe and life-threatening; jaundice may be absent. Mild cases may respond to antibiotics and conservative measures. Investigation and decompression of the biliary system are mandatory in all patients, whether by ERCP, percutaneous transhepatic cholangiography or surgery.

Primary sclerosing cholangitis is a chronic cholestatic syndrome of unknown etiology characterized by progressive inflammation of the intra- and extrahepatic bile ducts. The entity may appear either alone or in association with inflammatory bowel disease, particularly ulcerative colitis. Primary sclerosing cholangitis may precede inflammatory bowel disease and runs a separate course, not being cured by colectomy. The patchy scarring (sclerosis) leads to fibrotic narrowing and eventually obliteration of the bile ducts. Like other organs, the biliary tract exhibits a limited number of responses to injury: here it responds with diffuse strictures and segmental dilations. Periductal inflammation and fibrosis in the portal areas, termed "pericholangitis", probably represents the intrahepatic extension of this process. The basis may be an infectious agent, an enterohepatic toxin or an immunological attack on the biliary epithelium.

Diffuse stricturing also occurs in secondary sclerosing cholangitis, which may complicate a biliary obstruction from a common duct stone, biliary stricture or cholangiocarcinoma, or some AIDS-related infections.

The presentation in primary sclerosing cholangitis is insidious in most cases, with fatigue, pruritus or just an elevated alkaline phosphatase level. In others, acute cholangitis develops with obstructive jaundice, pruritus, abdominal pain and fever. Biliary stagnation leads to pigment stones. Eventually, secondary biliary cirrhosis supervenes with portal hypertension, pronounced cholestasis and progressive liver failure. Antimitochondrial antibody is negative. ERCP provides the diagnosis, showing thickened bile ducts with narrowed, beaded lumens.

Therapeutic trials of corticosteroids and immunosuppressive agents (for the presumed immunologically mediated inflammatory process), penicillamine (to mobilize copper, because this potentially toxic material accumulates in cholestasis) and proctocolectomy in patients with inflammatory bowel disease have all failed. As some patients may be asymptomatic for a decade, only careful observation is warranted early on. Recurrent bacterial cholangitis requires antibiotics. Predominantly large-duct strictures respond to endoscopic or transhepatic dilation and stent placement. Evaluation of ursodeoxycholic acid (which helps the pruritus but may not change the disease process), cyclosporine, methotrexate and colchicine awaits good clinical trials. Some 10-15% of patients develop cholangiocarcinoma, creating a diagnostic challenge. Primary sclerosing cholangitis is a frequent indication for liver transplantation that has a good outcome.

Benign tumors (adenomas, papillomas, cystadenomas) are rare causes of mechanical biliary obstruction.

Adenocarcinoma, the most common malignancy, is uncommon in the Western world. Predisposing factors are chronic parasitic infestations of the biliary tract (e.g., a liver fluke, such as Clonorchis sinensis or Opisthorchis viverrini), congenital ectatic lesions (Caroli's disease, choledochal cyst) and primary sclerosing cholangitis.

Jaundice and pruritus are common, but the presentation is varied. Cholestasis and weight loss eventually develop. There may be a deep-seated, vague pain localized in the right upper quadrant of the abdomen, in contrast to the severe pain of biliary colic and the septic picture of cholangitis. Indeed, cholangitis is not a feature if no biliary manipulations have been performed, such as an ERCP-placed stent. Hepatomegaly is frequent. A distended, nontender gallbladder may occasionally be palpated, feeling like a small rubber ball, if the common duct is obstructed below the entry of the cystic duct ("Courvoisier's sign"). Obstruction produces dilation of the biliary tree that can be readily detected on ultrasound or CT scan. Cholangiography, usually by ERCP, should reveal the diagnosis. This slow-growing tumor presents late. The terminal event is usually hepatocellular failure. Palliation using biliary stents placed across strictures sometimes helps. Occasionally, a distal common duct lesion is amenable to curative surgery. Transplantation does not provide a good outcome.