AIDS CHOLANGIOPATHY PDF

AIDS cholangiopathy is a biliary syndrome in patients with AIDS. This entity is diagnosed on the basis of clinical features, raised alkaline phosphatase, evidence. AIDS cholangiopathy is a well-documented biliary syndrome in severely immunocompromised AIDS patients[9]. It occurs when strictures in the. As it was suspected that the patient suffered from AIDS cholangiopathy, further laboratory studies were obtained. A stool study for Isospora ova.

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Diseases of the liver and biliary tree have been described with significant frequency among patients with human immunodeficiency virus HIVand its advanced state, acquired immunodeficiency syndrome AIDS.

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 anti-retroviral therapy and cholantiopathy non-compliance.

While current published literature describes well the clinical, biochemical, and cholanfiopathy 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 cholangikpathy its evaluation and management.

Though a declining phenomenon in the Western world, acquired immunodeficiency syndrome AIDS -related cholangiopathy has been shown to cause significant burden and remains an important etiology of hepatobiliary pathology in those affected with human immunodeficiency virus HIV. While it is linked to advanced immunosuppression in AIDS patients, particularly in those with extremely low CD4 counts and opportunistic infections, as well as those with drug-resistant HIV infection, it is also seen in developing countries due to less available anti-retroviral therapy, decreased awareness, and medication non-compliance.

Human immunodeficiency virus HIV is a global pandemic and it has been estimated that 37 million people are infected with it aidd. Acquired immunodeficiency syndrome AIDS is associated with high morbidity and mortality due to increased risk of opportunistic infections and malignancy[ 1 ].

HIV affects the hepatic parenchyma and biliary tree, leading to liver inflammation and biliary strictures.

According to observational cohort studies published by the D. It has been well established that HIV directly affects hepatocytes, Kupffer cells, and endothelial cells[ 6 ].

Abnormalities in liver chemistries are common among HIV-infected persons, cholangipathy in the absence of hepatitis B and C infections. Mechanisms by which HIV exerts its effect on hepatocytes include but are not limited to: Liver diseases in HIV are generally classified into three main categories.

The first group consists of diseases associated with immunosuppression, including AIDS cholangiopathy, acalculous cholangiopathyy, AIDS-related neoplasms non-Hodgkin lymphoma and Kaposi sarcomaand vanishing bile duct syndrome.

AIDS Cholangiopathy.

The cholangiopsthy category involves worsening of co-infection with cholangiopxthy B and C viruses, encompassing accelerated liver damage and progression of fibrosis.

It occurs when strictures in the biliary tract develop due to opportunistic infections, leading to biliary obstruction and cholestatic liver damage[ 10 ]. The condition was first recognized in by Pitlik et alds 11 ] and Guarda et al[ 12 ] among cholangiopahty humans.

Following these reports, investigations of right upper quadrant pain and elevated liver enzymes in severely immunocompromised AIDS patients revealed several opportunistic pathogens, implicating the pathogenesis of AIDS cholangiopathy[ 13 ].

Furthermore, Schneiderman et al[ 14 ] published a case series in highlighting the endoscopic appearance of papillary stenosis involving the intrahepatic and extrahepatic biliary tree and associated with sclerosing cholangitis. InCello identified four patterns of cholangiographic features resembling primary sclerosing cholangitis PSCincluding papillary stenosis, long extrahepatic strictures, acalculous cholecystitis, and intrahepatic and extrahepatic sclerosing lesions[ 15 ].

Several case series and reviews choalngiopathy published highlighting the clinical, biochemical, and endoscopic management of AIDS-related cholangiopathy. Still, little is known about its epidemiology and natural history, as well as the determinants of its pathology in developed and developing countries. In this review article, we will focus on the epidemiology, determinants, and management of AIDS related cholangiopathy. Actual data on the incidence and prevalence of AIDS-related cholangiopathy is largely lacking, especially from developing countries.

To date, approximately cases are reported in the literature-mostly before the introduction of HAART.

Although rarely reported in developed countries, AIDS-related cholangiopathy remains an important differential of cholestatic liver disease in HIV-infected patients, attributable to resistance to the first line antiretroviral medications[ 17 ]. Meanwhile, it is still a problem in developing countries due to poor access to HAART, decreased awareness about the disease, and medication non-compliance[ 18 ]. AIDS-related cholangitis is most commonly reported in young men who have sex with men with a mean age of 37 years[ 21 ].

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Conversely, it is more common in heterosexual men in developing counties and rarely associated with Kaposi sarcoma[ 22 ]. Opportunistic infections of the biliary tract associated with advanced immunosuppression in AIDS has been well documented in the literature.

Sources of samples for diagnosis include: Epidemiological studies show that C. However, cholangiopathy is only reported in the immunocompromised state associated with AIDS.

The incidence of C. This pathogen is still the most common infectious cause of AIDS cholangiopathy in patients who either do not have access to medications or have documented resistance to first-line HAART. It has been proposed that HIV and C.

The mechanism by which C. FasL protein expression in the cytoplasm of the cultured hepatocyte and its translocation is enhanced by the HIV-1 Tat protein. In addition, the HIV-1 Tat protein causes release of full-length FasL in infected cells; consequently, apoptotic cell death in uninfected cholangiocytes leads to damage of the biliary epithelia, which occurs almost exclusively in patients infected with HIV[ 2627 ].

Another proposed mechanism of pathology is autonomic nerve damage in the intestine caused by C. Here, the damage is usually found in the arterioles close to the biliary canals, rather than within biliary epithelial cells.

It has been postulated that CMV causes vascular injury leading to ischemic damage[ 15 ]. Microsporidia is another opportunistic pathogen that has been found to be associated with AIDS cholangiopathy in immunocompromised hosts.

A series of 20 cases reported by some researchers showed that E. Another study published by Pol et al[ 29 ] found this pathogen in the biliary samples of all 8 patient studies[ 30 ]. There are several other pathogens implicated in AIDS cholangiopathy, but are less well-described.

Iads is a well-known opportunistic pathogen in AIDS patients associated with chronic diarrhea; however, its association with AIDS cholangiopathy is relatively aivs 31 ]. In some cases, multiple pathogens are involved in the pathogenesis[ 32 ]. Clearly, there are several opportunistic infections associated with the development of cholangiopathy in AIDS, with the most common being C.

Clinical, biochemical and imaging studies necessary for the diagnosis of AIDS related cholangiopathy are as follows:.

The clinical presentation of AIDS cholangiopathy is variable, ranging from asymptomatic disease to severe right upper quadrant pain associated with nausea, vomiting, and diarrhea. Presence of papillary stenosis is the primary determinant of abdominal pain severity.

Less common presenting features include fever and jaundice, usually seen with complete bile duct obstruction.

International Journal of Hepatology

When present, fevers are usually low-grade, but spiking high-grade fevers can be seen with superimposed bacterial cholangitis. Substantial weight loss is also seen commonly, while pruritus is uncommon. On physical examination, abdominal tenderness and hepatomegaly are reported in some case reports[ 213334 ]. Elevated liver enzymes, especially markedly elevated alkaline phosphatase and gamma-glutamyl transferase GGTis the most common biochemical abnormality associated with AIDS cholangiopathy.

Obstruction of the smaller branches of the biliary tree cholanguopathy to granulomatous infiltration from disseminated MAC is cholzngiopathy possible underlying explanation. Only mild to moderate elevation has been observed in other liver chemistries such as alanine aminotransferase and aspartate aminotransferase.

Serum bilirubin may remain normal or elevated, depending cholanviopathy the severity of papillary duct stenosis.

In approximately one-fourth of patients, the presentation of AIDS cholangiopathy is subtle and not associated with any biochemical abnormalities despite the evidence of cholangiographic abnormalities on imaging studies[ 3536 ]. Microscopically, the changes of AIDS cholangiopathy are usually consistent with sclerosing cholangitis[ 37 ]. Being cost-effective, sonography is an ideal screening imaging modality in an HIV-infected patient suspected to have hepatobiliary pathology.

Another commonly seen abnormality is the presence of hyperechoic echogenic nodules at the distal end of the CBD, which represents edema of the papilla of Vater noted on ERCP[ 3839 ]. Contrast-enhanced multidetector computed tomography: Computed tomography CT scans are used widely to evaluate causes cholaniopathy acute and chronic abdominal pain, such as acute pancreatitis in HIV-infected patients. Abdominal CT scans with contrast provide detailed information about hepatic and pancreatic parenchyma and vasculature.

In HIV cholangitis, findings of intrahepatic and extrahepatic biliary ductal dilatation in the absence of external compression from malignant masses are seen commonly[ 40 ]. In addition, the risk of complications seen more in Cholangiopthy such as iatrogenic pancreatitis, duodenal perforation, hemorrhage, and cholangiopatht cholangitis are rare. Currently, MRCP is preferred over ERCP unless there is need for diagnostic and therapeutic procedures, such as brushing, sphincterotomy, or placement of stents due to biliary strictures.

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According to the published literature, the most common cholangiographic finding in AIDS cholangiopathy is papillary stenosis, which is a smoothly tapered cholanfiopathy at the distal cholangiipathy of the CBD at the level of the hepatopancreatic ampulla. In two-thirds of cases, papillary stenosis is present either alone or in combination with intrahepatic ductal dilatation and multifocal intrahepatic biliary strictures with alternating normal segments, or saccular dilatations.

AIDS Cholangiopathy.

Symptomatic treatment with opioids such as morphine and CT-guided celiac plexus block has been effective in alleviating abdominal pain[ 44 ].

Treatment of opportunistic infections is surprisingly ineffective cohlangiopathy halting the progression of sclerosing cholangitis and papillary stenosis. Cryptosporidium, by far the most common pathogen implicated in the pathogenesis of AIDS cholangitis, has no effective eradication therapy[ cholangiopatjy ]. In a few studies, paromomycin, azithromycin, and more recently nitazoxanide have been used without promising results[ 4647 ].

Intravenous gancyclovir and foscarnet are also not beneficial for treatment of CMV-related cholangitis[ 48 ]. Though albendazole has been used with some success in disseminated Enterocytozoon intestinalis infection including cholangitis, the therapeutic effect seems to be transient[ 49 ]. Trimethoprim-sulfamethoxazole for cyclopora has been used with little success[ 50 ].

Cholangiopahy is recommended with oral trimethoprim-sulfamethoxazole in addition to ivermectin for isospora[ 51 ]. Use of ursodeoxycholic acid URSO in AIDS cholangiopathy is associated with symptomatic improvement in abdominal pain and normalization of alds chemistries after sphincterotomy for chopangiopathy stenosis[ 52 ].

The data regarding improvement in clinical symptoms and radiological findings after HAART initiation is conflicting. While most case series studies show improvement in abdominal pain, normalization of liver chemistries, and decrease in the progression of intrahepatic and extrahepatic biliary involvement, a case described by Imai et al[ 54 ] showed that intrahepatic biliary duct stenosis progressed even after the timely initiation of HAART[ 55 ].

Endoscopic sphincterotomy usually provides symptomatic relief of abdominal pain in cholangitis associated with papillary stenosis by decompressing the bile ducts and improving drainage in the biliary tree.

The aics of endoscopic sphincterotomy has been evaluated in multiple case series. Endpoints of follow-up evaluation were improvement in pain score and cholestasis, decrease in the biliary dilatation, and decreased progression of sclerosing cholangitis.

According to the prospective study published by Cello et al[ 56 ], ERCP sphincterotomy was associated with significant improvement cholantiopathy pain scores up to at least 9 mo of follow-up.

However, there was no significant improvement in the level of alkaline phosphatase, and progression of intrahepatic sclerosing cholangitis was observed. These findings are supported by chooangiopathy other studies as well. Though experience is limited, there have been reports of successful biliary stent use in patients with both long and proximal strictures[ 57 ].

The survival of patient with AIDS cholangiopathy is generally poor because of disease association with advanced stages of immunosuppression and the presence of multiple opportunistic infections.

Remarkable improvement was reported in the median survival of the patients with AIDS cholangiopathy during the last decade, including reports of up to 34 mo median survival.

According to the prospective study published by Ko[ 60 ], the factors associated with poor prognosis in AIDS cholangiopathy include history or presence of opportunistic infections, and elevation in the level of alkaline phosphatase eight times above the upper limit of normal.

CD4 count, severity of cholangiopathy, and sphincterotomy for decompression of the biliary tract each have no effect on mortality. In the same study, factors associated with improved survival of the patient but became insignificant after adjusting for confounding factors were older age 30 years or olderthe absence of opportunistic infection, diagnosis of AIDS afterand AIDS cholangiopathy after So far, the primary complications reported to be caused by AIDS-related cholangiopathy are development of cholangiocarcinoma and progression of sclerosing cholangitis despite appropriate treatment.

Chronic biliary infection from opportunistic pathogens seen in AIDS cholangiopathy initiate the dysplastic process in the biliary epithelium, leading to development of cholangiocarcinoma.