INTRODUCTION

Acquired immunodeficiency syndrome (AIDS) has become a pandemic, resulting in 25 million deaths and 40 million persons infected with the AIDS virus. The disease prevalence is particularly high in developing countries. The enormity of the problem is highlighted in the sub-Saharan African continent, which represents only 10% of the world’s population, but constitutes 77% of AIDS deaths.

Clinical advances have evolved in consonance with a greater understanding of the virologic and immunologic markers of disease stage, mechanisms of viral transmission and the problem of viral resistance to antiretroviral drugs. Gastrointestinal and hepatobiliary complications are important components of the HIV/AIDS syndrome. They are common and affect most patients with AIDS during the course of their illness.

MALNUTRITION AND CACHEXIA

Survival in AIDS patients is strongly associated with nutritional status. Weight loss is a cardinal feature of AIDS. The factors contributing to weight loss include anorexia, inadequate oral intake, intestinal malabsorption and alterations in metabolism and endocrine dysfunction.

Reduction in oral intake allied to anorexia is a critical factor in weight loss. Malnutrition also has deleterious effects on the immune system. Careful assessment of the patient and the diagnosis, with treatment of systemic illness or upper gastrointestinal disease, usually results in weight gain.

Nutritional supplementation in the form of appetite stimulants and enteral alimentation often leads to a greater feeling of well-being. Total parental nutrition may be indicated in some cases.

CHRONIC DIARRHOEA

Because of the wide spectrum of potential infections that may cause diarrhoea (Table 22.1), it is appropriate to have a systematic approach in investigating the aetiologic agent/s (Figure 22.1; Table 22.2). Weight loss and diarrhoea suggest an opportunistic infection, malabsorption or small bowel bacterial overgrowth. Severe watery diarrhoea suggests cryptosporidiosis. Diarrhoea with nausea and abdominal pain may indicate Giardia, Isospora belli or Mycobacterium avium. Rectal bleeding may indicate viral or bacterial colitis or Kaposi’s sarcoma.

TABLE 22.1 Common causes of diarrhoea in AIDS

FIGURE 22.1 Assessment of diarrhoea in AIDS.

Based on Wilcox CM. AIDS and the gut. In: Weinstein WM, Hawkey CJ, Bosch J, eds. Clinical gastroenterology and hepatology. Philadelphia: Mosby; 2005:8331–6, with permission.

TABLE 22.2 Assessment of diarrhoea in AIDS

A clinical caveat is to assess whether the patient is at risk for an opportunistic infection. The CD4 lymphocyte count is critical to answer the question (see Figure 22.1). If the CD count is less than 100/mm³ (μ/L), opportunistic infections are probable.

Appropriate tests on faeces can facilitate a diagnosis. The initial laboratory investigation is an assessment of microscopy, culture and parasites. Three sampling tests are recommended. If the CD4 lymphocyte count is <200/mm³, then check for cryptosporidia, microsporidia and Clostridium difficile. Blood cultures should be done in febrile patients with a CD4 <100/mm³, including mycobacteria.

Patients are at risk for cytomegalovirus (CMV) when the CD4 count <100/mm³. The diagnosis is established by doing a mucosal biopsy at endoscopy.

The risk for small intestine Mycobacterium avium infection is increased when the CD4 count is <100/mm³. Duodenal biopsy is required to establish the diagnosis. However, if blood cultures are positive for mycobacteria, biopsy is unnecessary and antimicrobial therapy should be initiated. Table 22.3 lists treatment options for diarrhoea as a result of specific pathogens.

TABLE 22.3 Treatment of diarrhoea

N.B. Prior to the advent of HAART, diarrhoea occurred in 90% of AIDS patients.

However, with the inception of HAART, diarrhoea is still frequent but is most often drug-induced or caused by disorders unrelated to HIV infection.

Drug-induced diarrhoea due to the highly active antiretroviral treatment (HAART) regimen is frequent but is usually mild. If no cause of diarrhoea is found, symptomatic therapy is indicated.

HEPATOBILIARY DISEASE

The diagnosis of liver disease should encompass history, physical examination, liver tests and CD4 lymphocyte count (Figure 22.2).

FIGURE 22.2 Evaluation of hepatobiliary disease in AIDS.

CT = computed tomography; ERCP = endoscopic retrograde cholangiopancreatograph; HAART = highly active antiretroviral treatment; LFTs = liver function tests; MRCP = magnetic resonance cholangiopancreatography; MRI = magnetic resonance imaging; US = ultrasound.

Table 22.4 details the spectrum of hepatobiliary disease in AIDS. Opportunistic infections and neoplasms usually involve the liver secondarily through lymphohaematogenous dissemination. Therefore, initial evaluation of blood or bone marrow specimens may provide important information towards a diagnosis.

TABLE 22.4 Spectrum of hepatobiliary disease in AIDS

Hepatitis B, C and D viruses commonly coinfect with HIV and treatment with interferon results in a poor response. It is appropriate to screen HIV-positive patients for hepatitis B and C infection.

With regard to CMV infection, hepatitis and biliary tract disease may be manifestations of the infection. Another important cause of liver function test abnormalities is drug-induced liver injury. The drugs involved include antiretroviral (highly active antiretroviral treatment or HAART) medications, isoniazid, rifampin and trimethoprim-sulfamethoxazole.

Causes of hepatobiliary disease depend on the extent of immunocompromise. If the CD4 count is >500/mm³, hepatic complications usually represent liver specific processes. When the CD4 cell count is <200/mm³, then the liver is usually involved as part of a systemic opportunistic infection due to M. avium complex, fungi or CMV.

Imaging provides further opportunities for establishing a diagnosis. Ultrasonography is a non-invasive imaging procedure for evaluation of the biliary system. Other tests that can be used include magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). CT scan is indicated if a mass lesion is suspected.

Liver biopsy should be considered in patients in whom a treatable cause of parenchymal liver disease is suspected, and when blood cultures and other non-invasive tests do not reveal a cause.

AIDS cholangiopathy presents with epigastric or right upper quadrant pain as well as diarrhoea. It can result in four types of pathology:

The CD4 count is usually below 100/mm³. Typically alkaline phosphatase and gamma-glutamyl transpeptidase are elevated, but these can be normal in 20% of cases. ERCP is diagnostic. If cholangitis or jaundice develops, sphincterotomy at ERCP is helpful.

TREATMENT OF HIV

Initiation therapy is recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/mm³ and before it declines to 200/mm³. A non-nucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with two nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it, or in the event of treatment failure. The virologic target for patients with treatment failure is a plasma HIV-1 RNA level below 50 copies/mL.

SUMMARY

Gastrointestinal and hepatobiliary complications are important components of the HIV/AIDS syndrome, and affect most patients with AIDS during the course of their illness. Anorexia is a frequent risk factor for weight loss, which is a cardinal feature of AIDS. Chronic diarrhoea is frequent. If the CD4 lymphocyte count is less than 100/mm³, opportunistic infections are probable.

Hepatitis B, C and D viruses commonly coinfect with HIV, and treatment with interferon results in a poor response. It is appropriate to screen HIV-positive patients for hepatitis B and C infection. Drug induced injury is an important cause of liver function test abnormalities. If the CD4 cell count is >500/mm³, hepatic complications usually represent liver-specific processes whereas a CD4 cell count <200/mm³ usually indicates that the liver is involved as part of a systemic opportunistic infection.