Prognostic factors for the survival of patients with AIDS cholangiopathy

OBJECTIVES: AIDS cholangiopathy, once considered to have extremely poor prognosis, is now rarely fatal. This study was designed to assess the survival of patients with AIDS cholangiopathy and investigate prognostic variables, especially in the era of highly active antiretroviral therapy (HAART). METHODS: Ninety-four patients with AIDS cholangiopathy were diagnosed at the San Francisco General Hospital from 1983 to 2001. The mortality status, demographic and clinical variables, and ERCP results were collected through death certificates, chart review, and endoscopic reports. RESULTS: The median survival time from the diagnosis of AIDS and AIDS cholangiopathy was 23 and 9 months, respectively. HAART significantly improved the mortality of patients with AIDS cholangiopathy (hazard ratio [HR] = 0.08, 95% confidence interval [CI] = 0.02-0.35). The presence or history of any opportunistic infection involving the digestive tract, lung, eye, nervous system, skin, or systemic involvement at the time when AIDS cholangiopathy was diagnosed was an indicator of poor prognosis (HR = 3.24, 95% CI = 1.45-7.26); this was especially true for cryptosporidial infection (HR = 2.05, 95% CI = 1.24-3.38). Patients with high serum ALP levels, especially greater than 1000 IU/L or eight times the normal value (HR = 2.69, 95% CI = 1.10-6.60), tended to have a shorter life expectancy than those with normal or slightly elevated serum ALP levels. CD4 lymphocyte counts, type of cholangiopathy, and the performance of sphincterotomy were not correlated with the survival of patients with AIDS cholangiopathy. CONCLUSIONS: HAART administration most likely accounts for the recent dramatic improvement in survival of patients with AIDS cholangiopathy. Underlying immunosuppressive status, reflected by the presence or history of any opportunistic infections, is associated with a worse outcome. Serum ALP levels might be a good clinical indicator for the prognosis of patients with AIDS cholangiopathy.     

Microsporidial AIDS cholangiopathy due to Encephalitozoon intestinalis: case report and review

Microsporidia are increasingly recognized as opportunistic infections in immunodeficient patients, predominantly patients with AIDS. The two microsporidia most commonly associated with disease in AIDS patients are Enterocytozoon bieneusi and Encephalitozoon intestinalis (previously known as Septata intestinalis). The most common clinical presentation of microsporidiosis in AIDS patients is diarrhea, most commonly caused by the Enterocytozoon bieneusi species. Encephalitozoon intestinalis is a recently described species that has been reported to cause disseminated human infection including cholangitis. We report a case of AIDS cholangiopathy that presented with abdominal pain and cholestatic liver tests. Ultrasound examination and ERCP revealed a picture of sclerosing cholangitis. Bile samples obtained at ERCP were negative for microsporidia; stool studies for microsporidia and cryptosporidia were also negative. No organisms were identified on routine light microscopy of the biopsy specimens from the duodenum, ampulla, and bile duct. E. intestinalis spores were demonstrated in the bile duct biopsies, by methylene blue and azure 11 staining and confirmed by electron microscopy. Albendazole therapy was successful in eradicating E. intestinalis with clinical improvement and improvement in CD4 count. However, the cholangiographic picture did not improve and repeat cholangiography revealed progressive bile duct injury. Albendazole therapy was delayed and may have been too late to prevent bile duct damage; the drug had to be approved by the US Food and Drug Administration for compassionate use. This is an unusual case of sclerosing cholangitis caused by an unusual organism and requiring biliary sphincterotomy and stent placement for progressive stricturing despite eradication of the infection.     

Autoimmune cholangiopathy

Currently available evidence is insufficient to classify PBC and AIC as separate diseases. The ultimate answer to the question of whether AIC, defined as AMA-negative PBC with ANA or SMA, is a disease distinct from AMA-positive PBC with or without ANA will require a detailed comparison of etiologic factors and pathogenetic mechanisms, once they are elucidated. It is intriguing to consider the suggestion of Heathcote that the term autoimmune cholangitis be adopted to describe PBC with or without detectable AMA. However, it is improbable that the venerable term PBC will be supplanted. Hepatologists will probably continue to use the terms AIC and AMA-negative PBC interchangeably, with little risk of being misunderstood.     

Epidemiology,determinants,and management of AIDS cholangiopathy:A review

Diseases of the liver and biliary tree have been described with significant frequency among patients with human immunodeficiency virus(HIV), and its advanced state, acquired immunodeficiency syndrome(AIDS). Through a variety of mechanisms, HIV/AIDS has been shown to affect the hepatic parenchyma and biliary tree, leading to liver inflammation and biliary strictures. One of the potential hepatobiliary complications of this viral infection is AIDS cholangiopathy, a syndrome of biliary obstruction and liver damage due to infection-related strictures of the biliary tract. AIDS cholangiopathy is highly associated with opportunistic infections and advanced immunosuppression in AIDS patients, and due to the increased availability of highly active antiretroviral therapy, is now primarily seen in instances of poor access to antiretroviral therapy and medication non-compliance. While current published literature describes well the clinical, biochemical, and endoscopic management of AIDS-related cholangiopathy, information on its epidemiology, natural history, and pathology are not as well defined. The objective of this review is to summarize the available literature on AIDS cholangiopathy, emphasizing its epidemiology, course of disease, and determinants, while also revealing an updated approach for its evaluation and management.     

Ischemic cholangiopathy

Bile ducts are supplied with blood exclusively via hepatic arteries. Obstruction of large arteries is rapidly compensated for by the opening of preexisting intrahepatic or transcapsular collateral arteries, which prevents ischemic damage. Ischemic bile duct injury may occur when small hepatic arteries or the peribiliary vascular plexus are injured, or when all possible arterial blood supplies are interrupted, as is the case in transplanted liver with hepatic artery thrombosis. Most causes of bile duct ischemia are iatrogenic. Systemic diseases involving small hepatic arteries may also be implicated. Depending on the extent and velocity of the arterial obstructive process, ischemic cholangiopathy may present as acute formation of biliary casts, bile duct necrosis, or chronic disease resembling primary sclerosing cholangitis. In many patients, correction of arterial obstruction is not possible. When biliary drainage or reconstruction is not possible or has failed, liver transplantation is the only means of providing potential cure.     

AIDS-related cholangiopathy

Several types of biliary tract abnormality of undertermined origin have been described among AIDS patients. The aims of this study are (1) to evaluate whether biliary tree involvement is in fact one or several homogeneous morphological entities, (2) to specify the role of CMV orCryptosporidium sp. infection, and (3) to evaluate the possible efficacy of treatment. Since ultrasound had revealed abnormality in the biliary tree, 26 consecutive AIDS patients underwent cholangiography. Cholangiograms enabled us to distinguish between two types of biliary tract involvement: (1) gradual and regular stenosis of the terminal portion of the common bile duct associated with dilation but without irregularity of the intrahepatic biliary ducts was present in 27% of our cases, and (2) distal stenosis of the extrahepatic biliary ducts combined with diffuse irregularity of the caliber of the intrahepatic bile ducts was present in 73% of our cases. Concomitant infection by CMV orCryptosporidium sp. was significantly more frequent when intrahepatic duct irregularities were present (94%) than when absent (14%,P<0.001). Anti-CMV treatment and sphincterotomy were unsuccessful in treating anomalies of the intrahepatic biliary tract. Conversely, sphincterotomy caused rapid and lasting disappearance of pain in all our patients. In conclusion, biliary tract involvement in AIDS patients is of two types. CMV infection and infection byCryptosporidium sp. are most frequent when the large intrahepatic ducts are implicated.     

HIV/AIDS cholangiopathy: clinical spectrum, cholangiographic features and outcome in 30 patients

Background and Aims: AIDS cholangiopathy is presently considered rare and has been reported mainly from the West. With the HIV epidemic in India, we have encountered an increasing number of patients. We aimed to study these patients and determine differences from earlier experiences. Methods: We describe the clinical presentation, cholangiographic features, and outcome and determine differences reported in Western literature. Results: From Jan 1999 to May 2009, 30 patients (27 men) with AIDS cholangiopathy were seen. The most common mode of transmission was heterosexual (n = 28) followed by blood transfusion (n = 2). Abdominal pain (n = 20) of biliary origin, was the commonest manifestation followed by an asymptomatic group (n = 6) and a third group (n = 3) with pain due to pancreatitis. Ultrasonography of the abdomen was abnormal in all patients. Papillary stenosis (n = 23) was the most common cholangiographic feature followed by sclerosing cholangitis (n = 5). Abdominal pain resolved reliably and promptly after endoscopic sphincterotomy. Cholangiographic abnormalities regressed during follow up on antiretroviral therapy in 10 patients. Seven patients on anti retroviral therapy developed de novo cholangiopathy, with a precipitous drop in CD4 count of whom two had a worse prognosis. None had Kaposi's sarcoma. Conclusions: In contrast to Western literature, HIV cholangiopathy was seen predominantly in patients who acquired HIV by heterosexual transmission. De novo development of cholangiopathy on antiretroviral therapy may indicate the occurrence of resistance. Papillary stenosis is the most common feature. Abdominal pain resolved with sphincterotomy. Regression of cholangiographic abnormality occurred with anti retroviral medications. Median survival following cholangiopathy diagnosis was 34 months, higher than reported in previous studies.     

Isolated intrahepatic biliary dilatation in a patient with acquired immune deficiency syndrome (AIDS): AIDS cholangiopathy versus incidental unilobar Caroli's disease

We describe a case of possible monolobar Caroli's disease in a patient with acquired immune deficiency syndrome (AIDS) who presented with features of cholangitis. Diagnostic workup, which included endoscopic retrograde cholangiography, revealed focal intrahepatic biliary dilatation confined to the right lobe. The patient subsequently underwent right hepatic lobectomy. Pathology revealed multiple cysts filled with calculi and inflammation in the cyst walls. Special stain results for fungi and acid-fast organisms were negative. The presence of advanced AIDS in this patient raised the possibility of this being a possible manifestation of AIDS cholangiopathy.     

Ischemic cholangiopathy after liver transplantation

Orthotopic liver transplantation (OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have contributed to the current success of OLT, but surgical complications, especially involving the biliary reconstruction, remain a morbid problem. Biliary complications after OLT include leaks and strictures. Strictures may be anastomotic or intrahepatic and diffuse, as seen in cases of hepatic artery thrombosis. Current efforts to expand the limited donor pool include the use of non-heart beating donors. The organ procurement process in these donors entails an increased period of warm ischemia and results with non-heart beating donor grafts have been mixed. It is now appreciated that there is an increased incidence of subsequent diffuse biliary stricturing or "ischemic cholangiopathy" in recipients of these organs. Animal models of this phenomenon and potential therapeutic strategies targeted at ischemic cholangiopathy are being developed with potential applicability to non-heart beating donation and will be the focus of this review.