Table of Contents
Definition of AIDS Cholangiopathy
Patients with AIDS can develop an abnormality of liver enzymes and sclerosing cholangitis. Alkaline phosphatase (ALP) level is usually elevated, while the CD4 count is always < 200/mm3. This form of sclerosing cholangitis is believed to be related to opportunistic infections in AIDS and is known as AIDS cholangiopathy.
Epidemiology and Etiology of AIDS Cholangiopathy
AIDS cholangiopathy is a fatal complication of AIDS that has become very rare since the introduction of highly active antiretroviral therapy (HAART). The median survival after the diagnosis of AIDS cholangiopathy is about 9 months. Patients who are HIV positive are expected to develop some liver abnormalities, but the diagnosis of AIDS cholangiopathy is reserved for patients with sclerosing cholangitis.
The most common etiology of AIDS cholangiopathy is infectious. Opportunistic infections of the biliary system are responsible for AIDS-related cholangitis and sclerosing cholangitis in this group of patients.
The most commonly identified organisms are cryptosporidium and cytomegalovirus, which can be isolated from the bile. Enterocytozoon bieneusi can also be identified in the bile of some patients with unexplained AIDS cholangiopathy.
Pathophysiology and Clinical Presentation of AIDS Cholangiopathy
Patients with AIDS cholangiopathy have a very low CD4 count that is less than 200/mm3, which puts them at risk of opportunistic infections. Opportunistic infections of the biliary system result in scarring and elevated levels of liver enzymes, such as alkaline phosphatase. Eventually, sclerosing cholangitis ensues, and patients can develop chronic liver disease.
No definite pathogen is identified in half of the patients. It affects AIDS patients with low CD4 counts (<135/mm3). The possible causative organisms are:
- Cytomegalovirus (CMV)
- Herpes simplex virus (HSV)
- Cryptosporidium parvum
- Mycobacterium avium complex
There are four pathological patterns:
- Combination of sclerosing cholangitis and papillary stenosis (50%)
- Isolated intrahepatic sclerosing cholangitis–like appearance (20%)
- Isolated papillary stenosis (15%)
- Long-segment extrahepatic duct stricture +/- concurrent intrahepatic disease (15%)
Symptoms of AIDS Cholangiopathy
Patients with AIDS cholangiopathy usually present with right upper abdominal pain and elevated liver enzymes. Abdominal pain is usually associated with nausea, vomiting, and fever. Jaundice is rarely seen in AIDS cholangiopathy.
Diagnostic Work-up for AIDS Cholangiopathy
The incidental finding of an elevated alkaline phosphatase level in a patient with AIDS can be a presenting feature of AIDS cholangiopathy. A complete blood count always reveals a CD4 count < 200 cells/mm3 and usually lower than 100 cells/mm3. Other hepatic enzyme levels can be abnormal in patients with AIDS cholangiopathy, but this finding is not specific. Bilirubin level is usually normal, hence there is typically no jaundice present on physical examination.
Transabdominal ultrasound is indicated as an initial diagnostic tool in the evaluation of patients for whom the differential diagnosis of AIDS cholangitis is being considered.
Findings consistent with sclerosing cholangitis on transabdominal ultrasound include:
- Dilated intrahepatic bile ducts
- Thickening of the common bile duct wall
If any of these findings are identified in a patient with AIDS, endoscopic retrograde cholangiopancreatography (ERCP) is indicated.
ERCP is the gold-standard diagnostic modality for AIDS cholangiography. Sclerosing cholangitis, intrahepatic sclerosing cholangitis, and extrahepatic bile duct strictures are usually evident on ERCP in patients with AIDS cholangiopathy. It enables clinicians to extract a sample for small-bowel biopsy to identify the causative organism. An abnormal ultrasonography study is highly predictive of an abnormal ERCP result in patients with AIDS cholangiopathy.
Other less commonly used imaging modalities include computerized tomography (CT) scanning and hepatobiliary scintigraphy. CT scanning of the biliary system can reveal intrahepatic ductal dilation, but it is not sensitive enough to diagnose increased wall thickness of the extrahepatic bile duct. Hepatobiliary scintigraphy can identify intrahepatic and extrahepatic sclerosing, stenotic, and dilatation abnormalities.
Treatment of AIDS Cholangiopathy
A holistic approach to treating AIDS cholangiopathy is critical and includes:
- Diet and lifestyle modifications
- Antimicrobial and antiviral therapy
- Palliative pain control, when appropriate
Current consensus is that AIDS cholangiopathy is infectious in origin, hence diet modifications are not very beneficial. As a preventive measure, sexual education about safe-sex practices can lower the risk of HIV infection and AIDS.
Unfortunately, patients with AIDS cholangiopathy do not benefit from antimicrobial therapy unless the etiology is related to cryptosporidium infection. A few studies have reported clinical improvement and bile clearance of oocysts in patients with AIDS cholangiopathy due to cryptosporidium infection when intravenous paromomycin followed by oral letrazuril was given.
Gastrointestinal symptoms related to cryptosporidium infection, such as diarrhea and abdominal pain, may be alleviated with antimicrobial therapy.
There is no current treatment for patients with cytomegalovirus-related AIDS cholangiopathy. Patients who develop cholecystitis as a complication of AIDS cholangiopathy may benefit from treatment with trimethoprim-sulfamethoxazole because the most commonly implicated organism is Cyclospora cayetanensis, which is sensitive to this antibiotic combination.
The best treatment to lower the risk of AIDS cholangiopathy is HAART, which improves immune function in patients with HIV infection. Additionally, patients with cryptosporidiosis benefit from HAART as it was shown to eradicate the organism oocysts in the stool.
HAART can also eradicate cryptosporidiosis oocysts from the bile in patients with AIDS cholangiopathy. HAART, especially if a protease inhibitor is included, is also effective in patients with AIDS cholangiopathy who did not respond to antimicrobial therapy as it cannot reduce biliary tract damage.
HAART is not only effective in treating AIDS cholangiopathy but can also lower the risk of AIDS and AIDS-defining disease. HAART also results in an improvement in liver function, as manifested by a decrease in alkaline phosphatase level and a reduction in the diameter of the intrahepatic and extrahepatic bile duct system.
Therapeutic ERCP is indicated for patients who have stenosis in the papilla of Vater as urgent biliary decompression and drainage is usually needed. Unfortunately, ERCP does not affect survival in patients with AIDS cholangiopathy, and HAART is the only treatment that was found to directly increase survival.
ERCP usually results in significant improvement in symptoms attributed to AIDS cholangiopathies, such as abdominal pain and fever, but it is not known to affect liver chemistry or decrease alkaline phosphatase levels.
Finally, patients with AIDS cholangiopathy may develop medically intractable abdominal pain. In these situations, a celiac plexus block may be beneficial for pain relief. However, this interventional treatment is typically reserved for patients with AIDS-related sclerosing cholangitis associated with papilla of Vater stenosis that is unresponsive to narcotics or ERCP treatment.
Ursodeoxycholic acid may have a role in treating intrahepatic ductal sclerosis and cholestasis.
Patients with acalculous cholecystitis related to AIDS cholangiopathy might benefit from laparoscopic cholecystectomy, particularly when ERCP, HAART, and antimicrobial therapy are ineffective.