Keywords: Hepatitis B, Hepatitis C, HIV/AIDS, infection, tumor

Uptake
After adsorption, the coat of the enveloped viruses may fuse with the host cytoplasmic membrane and release the virus genome into the host cell.

Uncoating
The viral genome is then released from its remaining protection inside the host cell.

Genomic Activation
In general, DNA viruses tend to replicate mainly in the nucleus, and RNA viruses mainly in the cytoplasm of the host cell.

Assembly
Assembly of the virus can take place in the nucleus, in the cytoplasm, or at the cell surface.

Release
Release of the new infectious virions is the final stage of replication.

Hepatitis B
Hepatitis B has a DNA genome. The virus replicates in the liver and is shed in large amounts into the blood where its presence is prolonged.  The virus lodges in the hepatocytes and can cause two forms of chronic infection. One is chronic persistent infection, which doesn’t cause liver damage but can result in hepatocellular carcinoma and the other is chronic active hepatitis which causes destruction of the liver tissue which leads to cirrhosis or liver failure.

Hepatitis C
Hepatitis C has a single-strand RNA (ssRNA) genome. It causes a milder form of acute hepatitis than hepatitis B but chances of developing chronic hepatitis are very much higher. This can lead to chronic liver failure or hepatocellular carcinoma.

HIV
Four human retroviruses have been identified. All infect the CD4 bearing cells. These viruses were only discovered in the 1980’s when it became possible to culture T-cells in vitro. HIV 1 is responsible for the AIDS pandemic and HIV 2, which is of lower virulence is largely confined to West Africa.

Pathogenisis
The pathogenesis of AIDS starts with the infection of the CD4 cells, dendritic cells, and macrophages. About 2 to 4 weeks later a flu-like illness occurs. This is followed by a specific immune response and seroconversion takes place. An asymptomatic phase follows, which can last from 2 to 10 years. During this phase most of the virus is cleared from the peripheral blood but viral replication continues in lymphoid tissue. This leads to a gradual loss of CD4 cells and the destruction of the microenvironment of lymphoid tissue. The infected individual starts to suffer from prodromal disorders. Finally a state of gross immunodefiency is reached and the individual has full-blown AIDS.

In the prodromal and final stages of the disease, individuals are prone to a host of opportunistic infections.  These can include protzoal infections (pneumocystis carinii pneumonia, enteritis, encephalitis), fungal infections (candida, cryptococcus neoformans), viral infections (herpes simplex, varicella zoster, cytomegalo virus, leukoencephaly), and bacterial infections (tuberculosis, atypical mycobacterium avium intracellulare, salmonella streptococcus) (1).

Liver Scintigraphy
Liver scintigraphy is the only imaging modality which shows liver function. Although it has a high sensitivity and is useful in the diagnosis of diseases such as cirrhosis, hepatitis and metabolic disorders as well as detecting liver lesions, it is non-specific. Technetium-99m (^99mTc) sulphur or tin colloid and ^99mTc albumin colloid are the most commonly used radiopharmaceuticals, but other imaging agents can also be used such as ^99mTc labeled red blood cells, and Gallium-67 (⁶⁷Ga) citrate to raise the specificity. Liver scintigraphy has largely fallen away because ultrasound and CT have greater specificity.

HIV/AIDS

Lung Complications
Several radiopharmaceuticals have been used to demonstrate pneumocystis carinii pneumonia (PCP) ( 2). These include ⁶⁷Ga citrate, Indium-111 (¹¹¹In) labeled non-specific polyclonal IgG ( 1), and ^99mTc labeled PCP specific monoclonal IgG ( 3 ). ⁶⁷Ga citrate scans have been abnormal in 85-95% of the cases ( 1). A normal chest xray and normal ⁶⁷Ga scan excludes the diagnosis of PCP (1). Where the chest xray is normal and the ⁶⁷Ga scan abnormal the specificity is increased to 100% ( 3). Classical findings on a ⁶⁷Ga scan show diffuse heterogeneous pulmonary uptake that is greater than liver uptake ( 1). However there are other conditions that can result in diffuse lung uptake of varying intensities. This reduces the specificity to 50% ( 1). ¹¹¹In-oxine labeled leukocytes lung scans for PCP have a sensitivity of 40%. They are more sensitive for bacterial pneumonias that are also positive on chest xray. Labeling HIV patients' leukocytes produce certain problems. Firstly these patients have low white cell counts which make labeling difficult and secondly autologous labeling techniques involve venepuncture which carries the risk of needle stick injury to the health care worker ( 1). ¹¹¹In oxine labeled polyclonal IgG has a low specificity for PCP because the label is non-specific ( 3). ^99mTc labeled monoclonal IgG is more specific and has a sensitivity of 86% and a specificity of 87% ( 3). ^99mTc DTPA aerosols are a sensitive marker in early PCP infection when the chest xray may be normal or equivocal but there is a high index of suspicion for PCP. Unfortunately the technique is not specific as other lung infections can show the same pattern on scan. Alveolar clearance of the aerosol can be measured. In normal individuals there is a slow monoexponential clearance. Clearance is rapid and biphasic in severe alveolar damage as seen in PCP and legionella pneumonia ( 3).

⁶⁷Ga has also been used to scan mycobacterium avium intracellulare (MAI). Uptake is lobar and asymmetric, but histoplasmosis will appear similar on scan ( 1). Cytomegalo virus (CMV) will have low grade uptake with perihilar prominence in the lungs and frequently associated multiple organ uptake or eye uptake due to retinitis ( 1) .

Central Nervous System (CNS) Complications
The most common CNS complications in HIV/AIDs patients are toxoplasmosis, primary CNS lymphoma, progressive multifocal leukoenchephalopathy (PML) and HIV encephalopathy ( 1,3). Nuclear medicine imaging of the CNS is limited. Infections will be seen as hypometabolic lesions in Fluorine-18 flurodeoxyglucose (¹⁸F-FDG) PET imaging and lymphomas will show as hypermetabolic lesions ( 3). There is no role for ⁶⁷Ga citrate to play in CNS imaging as it does not cross the intact blood brain barrier adequately ( 1). ¹¹¹In labeled white cells are better for diagnosing infectious lesions ( 1). HIV encephalopathy results from direct infection to the brain tissue primarily involving white matter and subcortical nucleii ( 1). ^99mTc hexamethylpropyleneamine (HMPAO) SPECT images will show typical multifocal perfusion defects affecting the frontal and temporal lobes but the pattern is similar to cocaine abuse and Altzheimers dementia ( 3). ¹⁸F-FDG PET imaging of HIV encephalopathy shows subcortical hypermetabolism in the early stages and cortical and subcortical hypometabolism in the late stage ( 1).

HIV Related Neoplasia
Kaposi' sarcoma is the most common cancer in AIDS patients ( 1). In non-AIDS patients it is an indolent tumor, localised in the skin, but in AIDS patients it is more aggressive and multicentric (1). ⁶⁷Ga scans are usually negative but Thallium-201 (²⁰¹Tl) is taken up avidly by Karposi sarcoma ( 1,3,4). ²⁰¹Tl sequential imaging can help differentiate between infection and Karposi sarcoma. Early images taken between 20 and 60 minutes will be positive for both infection and Karposi sarcoma but the delayed images at 3 hours will show clearance of ²⁰¹Tl from the infectious lesions whilst Karposi sarcoma will still be positive ( 4). ⁶⁷Ga and ²⁰¹Tl imaging are useful in differentiating between Karposi sarcoma, undifferentiated lymphoma and infection (Table 1) ( 4).

Tabla 1. Differential diagnosis using ²⁰¹Tl and ⁶⁷Ga

In the future nuclear medicine may have a role to play in the assessment of the effect of drugs and the delivery of drugs especially in the assessment of the organs affected by disease before and after treatment. There might also be advances in imaging techniques for Kaposi sarcoma to assess the total body tumor load and the assessment of the effect of antiretroviral treatment on the brain (3).