Sickle cell disease is one of the common hemoglobinopathies in the Eastern Province of Saudi Arabia, where the frequency of Sickle cell trait can reach as high as 25% in some areas[1-3
]. One of the common manifestations of SCD is jaundice, which can be caused by a variety of hepatobiliary diseases including CJ[3-5
]. There are certain causes of CJ that are SCD related. One of these causes is intrahepatic sickling of RBC[4,5,9
]. This is also called hepatic crisis or hepatic sequestration (sickle cell hepatopathy)[4,5
]. This can lead to cholestasis and a clinical picture that can resemble extrahepatic bile duct obstruction which causes diagnostic and therapeutic dilemmas. Sickle cell intrahepatic cholestasis on the other hand is a more serious condition, characterized by acute onset of hepatomegaly, hyperbilirubinemia, coagulopathy, and acute liver failure[4,5
]. Early identification of these is important as the process of sickling can be reversed by hydration and simple, or in severe cases, exchange blood transfusion. There is also a high frequency of cholelithiasis and choledocholithiasis in patients with SCD[3,6-8
]. The frequency of cholelithiasis in patients with SCD is variable, ranging from 4% to 55%, and this increases with age[2,3,6-8
]. In the general population with cholelithiasis, the incidence of common bile duct (CBD) stones has been reported to be 10%-15%, whereas in those with SCD it ranges from 18%-30%[10,11
]. Due to this high incidence, routine intraoperative cholangiography has been advocated[10
]. With the recent advances in laparoscopic cholecystectomy (LC), exclusion of CBD stones prior to LC is of great importance. ERCP has been shown to be valuable, both for the diagnosis and management of CBD stones, in patients with SCD who are undergoing or have undergone LC[12-14
]. ERCP is also of great importance in evaluating SCD patients with CJ, whether this is due to intrahepatic or extrahepatic causes. Ultrasound is a simple, non invasive imaging technique, and although gallstones and intrahepatic and extrahepatic bile duct dilatation are readily detected by ultrasound, common bile duct stones might be missed. ERCP, on the other hand, is more invasive but is the procedure of choice in suspected cases of extrahepatic bile duct obstruction. It provides direct visualization of the biliary tree and demonstrates the site and nature of the obstruction in more than 90% of patients. ERCP also provides therapeutic interventions, including endoscopic sphincterotomy and stone extraction, dilatation of strictures, and placement of stents and biliary drainage catheters[15-19
]. This was the case in our series, where we found ERCP valuable both as a diagnostic and therapeutic procedure. The majority of bile duct stones (95.4%) in our series were removed via ERCP. ERCP however was normal and unnecessary in a significant number of our patients (27%) with SCD and CJ. This was specially so in those who presented with CJ only (53.2%). These patients most likely had CJ secondary to intrahepatic sickling of RBC. Hepatic crisis and hepatic sequestration resemble each other clinically, and the only differentiating point between the two is a sudden drop in hematocrit, as well as a sudden increase in liver size in those with hepatic sequestration[4,5
]. Sickle cell intrahepatic cholestasis, on the other hand, is a more serious and often fatal complication of SCD where there is widespread intrahepatic sickling within the liver sinusoids leading to their blockage, vascular stasis with hepatic ischemia, and the striking feature is the highly elevated plasma bilirubin level[4,5,12,13
]. It is possible that our patients with CJ and normal ERCP represent a benign variant of intrahepatic cholestasis or a form of what is called benign hyperbilirubinemia[5
]. All our patients had hyperbilirubinemia, but their plasma AST, ALT and alkaline phosphatase levels were only moderately elevated. To support this, these patients subsequently recovered with conservative treatment including observation, hydration and, where indicated, blood transfusion. To overcome this and decrease the number of patients with normal ERCP, patients with CJ only should be evaluated further prior to ERCP, including endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP). However, these investigations are not readily available, and in these situations a period of observation and conservative management is to be advocated.
We found an interesting group of patients with SCD and CJ who had dilatation of the bile ducts without an obstructive cause (24.6%). There are several causes for bile duct dilatation, such as CBD stones, tumor of the head of pancreas or Ampulla of Vater, and tumors or masses at the porta hepatis. None of our patients had an obstructive cause for the bile duct dilatation. The exact etiology of this dilatation is not known. However, we think this is a form of cholangiopathy that is a consequence of sickling in the end arteries of the biliary arterial tree leading to hypoxia and dilatation[16,17
]. The bile ducts are supplied via the hepatic arteries and ischemic bile duct injury might occur when these vessels are injured or occluded. This will ultimately result in ischemic stricture of the bile ducts. This however, depends on the extent and velocity of the occlusive process. In patients with SCD, we feel that the occlusion, which is usually not complete, is of the peribiliary vascular plexus and is a result of sickling within these vascular channels. This will ultimately lead to hypoxia of the bile ducts leading to their dilatation rather than ischemia and stricture formation. This is SCD cholangiopathy and the extent of this is also variable, as was demonstrated in our series. We found patients with bile duct dilatation limited to the common bile duct, but there were also those who had dilatation involving both extra and intrahepatic bile ducts (Figures and ). Documenting this is of great importance, as these patients need to be followed up regularly for the possibility of developing bile duct stones. Cunningham, in a study of the common hepatic duct diameter in SCD patients, found only two patients with clinically silent enlargement based on ultrasonic evaluation of 95 patients[20
]. Their patients, in contrast to our patients, were young with a mean age group of 16.8 years. Taking in consideration the high frequency of biliary sludge and the possibility of bile duct stones formation in these patients, 42 (76.4%) of our patients with dilated bile ducts without an obstructive cause had endoscopic sphincterotomy, as this could obviate the future development of bile duct stones (Figure ). Thus, the value of endoscopic sphincterotomy in this group of patients needs to be evaluated further, as endoscopic sphincterotomy is not without complications.
ERCP showing biliary sludge in a patient with SCD. An arrow indicates the site of biliary sludge.