A. Introduction. Gastrointestinal illness is common among HIV-infected patients. Esophagitis, enterocolitis, and hepatobiliary disease can thus frequently occur.
B. Esophagitis. Esophagitis usually presents with dysphagia, odynophagia, or a substernal sensation of pain or burning.
a. Causes of HIV-related esophagitis. Common causes include the following:
2. Cytomegalovirus (CMV)
3. Herpes simplex virus (HSV)
1. Aphthous ulcers
2. Pill-induced esophagitis
b. Approach to the patient
i. Empiric antifungal therapy. Patients with symptoms of esophagitis and oral thrush are usually treated empirically for candidal esophagitis given this is the most common pathogen. Fluconazole (often 200 mg orally once daily) may be administered for 2–3 weeks. A rapid improvement in symptoms is expected; thus, failure to improve should prompt further testing and/or reconsideration of the diagnosis.
ii. Upper endoscopy is usually indicated for patients without oral thrush or for those unresponsive to empiric antifungal therapy. Abnormal areas on endoscopy should be biopsied and sent for pathology as well as viral and fungal cultures. Viral and fungal esophagitis can coexist. Aphthous ulcers are an important consideration in patients with negative cultures and pathology.
i. Fungal esophagitis
1. Fluconazole is usually the first-line treatment unless fluconazole-resistant Candida is suspected. A newer antifungal agent (such as an echinocandin or voriconazole) may be necessary in patients with resistant species.
2. Maintenance therapy may be given as one-half of the treatment dose (e.g., fluconazole, 100 mg once daily).
ii. Viral esophagitis
1. CMV esophagitis is usually treated with ganciclovir (usually 5 mg/kg intravenously twice daily for 2–3 weeks). The maintenance dose is often 5 mg/kg intravenously daily. New oral agents (valganciclovir) have a role in maintenance therapy.
2. HSV esophagitis is usually treated with acyclovir. Intravenous therapy may be necessary in patients who are unable to swallow or in those who are very ill (e.g., in patients with esophageal bleeding or fevers or those who cannot tolerate oral treatment).
3. Noninfectious esophagitis including aphthous ulcers may be treated with steroids (often prednisone, 40 mg orally daily for 2 weeks followed by a taper) or thalidomide.
C. Enterocolitis. More than 40% of HIV-positive patients develop diarrhea at some time during their illness.
a. Causes of HIV-related enterocolitis
i. Opportunistic infection
1. Bacteria. Salmonella, Shigella, Yersinia, Escherichia coli, and Campylobacter are common causes of acute diarrhea in HIV-positive patients. Clostridium difficile is an important consideration even in patients without recent exposure to antibiotics.
2. Protozoa. Commonly implicated organisms include Entamoeba histolytica, Giardia lamblia, Cryptosporidium, Microsporidia, and Cystoisospora belli.
3. Viruses. CMV and adenovirus are common causes of enterocolitis in HIV-infected patients.
4. Mycobacterium avium complex (MAC) can cause diarrhea; however, stool is frequently colonized with this organism in the absence of disease.
ii. AIDS-associated enteropathy is a diagnosis of exclusion. It is not known whether this entity is directly caused by HIV.
b. Approach to the patient
i. Laboratory studies
1. Stool culture should be performed to rule out bacterial infection.
2. Stool ova and parasites (O&P). Multiple samples may be sent to increase the yield. The evaluation for Cryptosporidium and Microsporida are enhanced by an acid-fast stain and a modified trichrome stain, respectively.
3. Testing for C. difficile toxin.C. difficile may be a commonly missed diagnosis and should be looked for in both immunocompromised and immunocompetent patients in the appropriate settings.
4. Routine blood cultures for Salmonella should be considered. In patients with CD4 counts <50 cells/µL, mycobacterial blood cultures for MAC should be obtained.
ii. Endoscopy is often necessary when symptoms continue and no etiology has been identified.
1. CMV is a very common pathogen that is often missed by the initial screening studies.
2. Colonoscopy with biopsy (followed by upper endoscopy with small bowel biopsy if colonoscopy findings are normal) should be performed.
i. Specific therapy depends on the causative organism. Most bacterial causes of enterocolitis are fluoroquinolone susceptible, but increasing resistance is reported, particularly with Campylobacter.
ii. Oral vancomycin is first-line treatment for C. difficile. Metronidazole, tinidazole, or nitazoxanide can be used to treat Giardia. Cystoisospora responds to trimethoprim-sulfamethoxazole (TMP-SMX). Amebiasis can be treated with metronidazole plus paromomycin. Cryptosporidium and Microsporidia are challenging to treat and tend to respond poorly, although nitazoxanide or albendazole, respectively, may be effective.
D. Hepatobiliary Disease. Elevated transaminases, alkaline phosphatase, and bilirubin are common findings in HIV-infected patients. These abnormalities may be clinically insignificant and asymptomatic but may also be the initial indication of opportunistic infections and neoplastic disease or dangerous drug toxicity.
a. Causes of HIV-related hepatic parenchymal disease.
i. Viruses, including hepatitis B, hepatitis C, and CMV
ii. Disseminated MAC and, less commonly, Mycobacterium tuberculosis infection
iii. Fungal infections including histoplasmosis
iv. Malignancy including lymphoma, Kaposi’s sarcoma, and hepatocellular carcinoma
1. Sulfa drugs, isoniazid, rifampin, and fluconazole are known causes of hepatitis. Usually, a hepatocellular (i.e., transaminase elevation) picture predominates.
2. Many antiretroviral medications have been associated with transaminase elevations. Of these, the most serious is hepatitis due to nevirapine (a nonnucleoside reverse transcriptase inhibitor), which can lead to fulminant hepatic failure.
3. Nucleoside reverse transcriptase inhibitors can cause hepatic steatosis in association with lactic acidosis leading to a transaminitis. If not recognized early, the lactic acidosis may be fatal.
vi. Peliosis hepatis from Bartonella henselae or Bartonella quintana
b. Causes of HIV-associated obstructive biliary tract disease
i. Sclerosing cholangitis (i.e., AIDS cholangiopathy) often presents with right upper quadrant pain accompanied by significant elevation in alkaline phosphatase level that is out of proportion to transaminase elevations. Biliary involvement with CMV or Cryptosporidium is commonly associated with AIDS cholangiopathy, whereas Microsporidia and MAC are less common causes.
ii. Remember that the protease inhibitors indinavir and atazanavir can also cause an asymptomatic unconjugated hyperbilirubinemia as side effects of treatment. In fact, compliance with these drugs can often be checked by examining unconjugated bilirubin levels.
c. Approach to the patient
i. Patient history. A medication history should be obtained to identify potentially hepatotoxic medications. Pain should be carefully characterized, including location and relationship to food.
ii. Physical examination. As always, a careful physical examination should be performed, looking for cutaneous and other manifestations of disease such as drug rash, skin lesions suggestive of Kaposi’s sarcoma or fungal infection, and lymphadenopathy.
As a rough guide, drugs and viral hepatitis tend to present acutely with a transaminitis-predominant pattern, whereas many of the other listed etiologies are more likely to show an alkaline phosphatase–predominant pattern.
iii. Laboratory studies. After obtaining the history, performing the examination, and obtaining initial liver chemistries, categorize whether the patient is presenting predominantly with obstructive or infiltrative disease (elevations of alkaline phosphatase out of proportion to transaminases) or a hepatocellular picture (transaminases elevated out of proportion to alkaline phosphatase) and whether the process is acute or chronic. This categorization can help direct your workup. As a rough guideline, drugs and viral hepatitis tend to present with hepatitis, whereas many of the other listed etiologies are more likely to show an alkaline phosphatase–predominant pattern.
1. Liver studies (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, fractionated bilirubin).
2. Hepatitis A, B, and C serologies should be obtained.
3. Blood cultures for MAC, fungi, and Bartonella species may be ordered.
4. If hepatic steatosis with lactic acidosis is a consideration, obtain a serum lactate level.
5. A urine Histoplasma antigen may be diagnostic of disseminated histoplasmosis.
6. Serum quantitative CMV studies should be obtained (CMV DNA by polymerase chain reaction).
7. Stool studies for Cryptosporidium, Microsporidia should be sent.
iv. Imaging studies. Although initial evaluation may uncover a potential etiology, it is often unclear whether that disease is an incidental finding or the cause of the hepatobiliary process. Imaging studies are often performed to rule out other disorders (e.g., lymphoma).
1. Ultrasound may be especially useful for evaluating the bile ducts and is therefore often chosen for patients in whom biliary obstruction is suspected. Early ultrasound is important to delineate whether a patient needs surgical evaluation (e.g., gallstone-related hepatitis or jaundice) versus medical management.
2. Computed tomography (CT). A CT scan provides better resolution of the liver parenchyma and is useful for patients suspected of having parenchymal disease.
3. Endoscopic retrograde cholangiopancreatography (ERCP) may be used for the diagnosis and treatment of sclerosing cholangitis. In this disease, intraluminal irregularities of the bile ducts are often accompanied by distal narrowing of the common bile duct (i.e., papillary stenosis). Biliary brushings for culture and cytology can be obtained during the procedure.
v. Liver biopsy may be considered for patients with a negative evaluation and persistent symptoms.
d. Treatment depends on the cause. In patients with sclerosing cholangitis, papillary sphincterotomy may provide symptomatic benefit by improving biliary drainage.
Suggested Further Readings
Acharya C, Dharel N, Sterling RK. Chronic liver disease in the human immunodeficiency virus patient. Clin Liver Dis 2015;19:1–22.Find this resource:
Cohen J, West AB, Bini EJ. Infectious diarrhea in human immunodeficiency virus. Gastroenterol Clin North Am 2001;30:637–64. (Classic Article.)Find this resource:
Tonolini M, Bianco R. HIV-related/AIDS cholangiopathy: pictorial review with emphasis on MRCP findings and differential diagnosis. Clin Imaging 2013;37:219–26.Find this resource: