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Lipids, Hepatitis, HIV. Dr. Felix Hernandez M.D. Cholesterol. Test Range and Collection Total, serum Desirable: <200 mg/dL Borderline: 200–239 mg/dL High risk: >240 mg/dL
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Lipids, Hepatitis, HIV • Dr. Felix Hernandez M.D.
Cholesterol • Test Range and Collection • Total, serum • Desirable: <200 mg/dL • Borderline: 200–239 mg/dL • High risk: >240 mg/dL • Fasting specimen is required for LDL-C determination. HDL-C but total cholesterol can be measured with nonfasting specimen. • Physiologic Basis • Cholesterol level is determined by lipid metabolism, which is in turn influenced by heredity, diet, and liver, kidney, thyroid, and other endocrine organ functions. Screening for total cholesterol (TC) may be done with nonfasting specimens, but a complete lipoprotein profile or LDL cholesterol (LDL-C) determination must be performed on fasting specimens. • TC, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) are directly measured.
Cholesterol • Interpretation • Increased in: Primary disorders: polygenic hypercholesterolemia, familial hypercholesterolemia (deficiency of LDL receptors), familial combined hyperlipidemia, familial dysbetalipoproteinemia. Secondary disorders: hypothyroidism, uncontrolled diabetes mellitus, nephrotic syndrome, biliary obstruction, anorexia nervosa, hepatocellular carcinoma, Cushing syndrome, acute intermittent porphyria. Drugs: corticosteroids. • Decreased in: Severe liver disease (acute hepatitis, cirrhosis, malignancy), hyperthyroidism, severe acute or chronic illness, malnutrition, malabsorption (eg, HIV), extensive burns, familial (Gaucher disease, Tangier disease), abetalipoproteinemia, intestinal lymphangiectasia. • The recommended LDL-C intervention goals are <100 mg/dL for high-risk patients (eg, patients with CHD), <130 mg/dL for moderate-risk patients ( 2 risk factors), and <160 mg/dL for low-risk patients (no or 1 risk factor).
Triglycerides • Test Range and Collection • serum (TG) • <165 mg/dL • Fasting specimen required. • Physiologic Basis • Dietary fat is hydrolyzed in the small intestine, absorbed and resynthesized by mucosal cells, and secreted into lacteals as chylomicrons. • Triglycerides in the chylomicrons are cleared from the blood by tissue lipoprotein lipase. • Endogenous triglyceride production occurs in the liver.
Triglycerides • Interpretation • Increased in: Hypothyroidism, diabetes mellitus, nephrotic syndrome, chronic alcoholism (fatty liver), biliary tract obstruction, stress, familial lipoprotein lipase deficiency, familial dysbetalipoproteinemia, familial combined hyperlipidemia, obesity, the metabolic syndrome, viral hepatitis, cirrhosis, pancreatitis, chronic renal failure, gout, pregnancy, glycogen storage diseases types I, III, and VI, anorexia nervosa, dietary excess. Drugs: -blockers, cholestyramine, corticosteroids, diazepam, diuretics, estrogens, oral contraceptives.
Triglycerides • Interpretation • Decreased in: Tangier disease ( -lipoprotein deficiency), hypo- and abetalipoproteinemia, malnutrition, malabsorption, parenchymal liver disease, hyperthyroidism, intestinal lymphangiectasia. Drugs: ascorbic acid, clofibrate, nicotinic acid, gemfibrozil. • If serum is clear, the serum triglyceride level is generally <350 mg/dL. • Elevated triglycerides are now considered an independent risk factor for coronary artery disease, and a major risk factor for acute pancreatitis, particularly when serum triglyceride levels are >1000 mg/dL. • Triglycerides >1000 mg/dL can be seen when a primary lipid disorder is exacerbated by alcohol or fat intake or by corticosteroid or estrogen therapy.
Hepatitis A • Test Range and Collection • serum (Anti-HAV) • Negative • Physiologic Basis • Hepatitis A is caused by a nonenveloped 27-nm RNA virus of the enterovirus-picornavirus group and is usually acquired by the fecal–oral route. IgM antibody is detectable within 1 week after symptoms develop and persists for 6 months. IgG antibody appears 4 weeks later than IgM and persists for years. • Interpretation • Positive in: Acute hepatitis A (IgM), convalescence from hepatitis A (IgG).
Hepatitis B • Test Range and Collection • serum (HBsAg) • Negative • Physiologic Basis • In hepatitis B virus infection, surface antigen is detectable 2–5 weeks before onset of symptoms, rises in titer, and peaks at about the time of onset of clinical illness. • Generally it persists for 1–5 months, declining in titer and disappearing with resolution of clinical symptoms. • Interpretation • Increased in: Acute hepatitis B, chronic hepatitis B (persistence of HBsAg for >6 months, positive HBcAb [total]), HBsAg-positive carriers. • May be undetectable in acute hepatitis B infection. • First-line test for the diagnosis of acute or chronic hepatitis B. If positive, no other test is needed.
Hepatitis B • Test Range and Collection • serum (HBsAb, anti-HBs) • Negative • Physiologic Basis • Test detects antibodies to hepatitis B virus (HBV), which are thought to confer immunity to hepatitis B. Because several subtypes of hepatitis B exist, there is a possibility of subsequent infection with a second subtype. • Interpretation • Increased in: Hepatitis B immunity due to HBV infection or hepatitis B vaccination. • Absent in: Hepatitis B carrier state, nonexposure. • Test indicates immune status. It is not useful for the evaluation of acute or chronic hepatitis.
Hepatitis B • Test Range and Collection • serum (HBcAb, anti-HBc) • Negative • Physiologic Basis • HbcAb (IgG and IgM) will be positive (as IgM) about 2 months after exposure to hepatitis B. Its persistent positivity may reflect chronic hepatitis (IgM) or recovery (IgG). • Interpretation • Positive in: Hepatitis B (acute and chronic), hepatitis B carriers (high levels), prior hepatitis B (immune) when IgG present in low titer with or without HBsAb. • Negative: After hepatitis B vaccination. • HBcAb (total) is useful in evaluation of acute or chronic hepatitis only if HBsAg is negative. An HBcAb (IgM) test is then indicated only if the HBcAb (total) is positive. • HBcAb (IgM) may be the only serologic indication of acute HBV infection.
Hepatitis C • Test Range and Collection • serum (HCAb) • Negative • Physiologic Basis • Detects antibody to hepatitis C virus, which is a single-stranded RNA virus of the Flaviviridae family. • Current screening test (ELISA) detects antibodies to proteins expressed by putative structural (HC34) and nonstructural (HC31, C100-3) regions of the HCV genome. The presence of these antibodies indicates that the patient has been infected with HCV, may harbor infectious HCV, and may be capable of transmitting HCV. • A recombinant immunoblot assay (RIBA), equivalent to Western blot, is available as a confirmatory test.
Hepatitis C • Interpretation • Increased in: Acute hepatitis C (only 20–50%; seroconversion may take 6 months or more), posttransfusion chronic non-A, non-B hepatitis (70–90%), sporadic chronic non-A, non-B hepatitis (30–80%), blood donors (0.5–1%), non–blood-donating general public (2–3%), hemophiliacs (75%), intravenous drug abusers (40–80%), hemodialysis patients (1–30%), male homosexuals (4%). • Seropositivity for hepatitis C documents previous exposure, not necessarily acute infection.
Hepatitis C • Test Range and Collection • Negative (detection limit: 50 IU/mL, assay-specific) • HCV-RNA • Physiologic Basis • Detection of HCV-RNA is used to confirm current infection and to monitor treatment with interferon-a (with or without ribavirin). • Interpretation • Positive in: Hepatitis C. • A negative result does not rule out the presence of PCR inhibitors in the patient specimen or hepatitis C virus RNA concentrations below the level of detection by the assay.
Hepatitis D • Test Range and Collection • serum (anti-HDV) • Negative • Physiologic Basis • This antibody is a marker for acute or persisting infection with the delta agent, a defective RNA virus that can only infect HBsAg-positive patients. • HBV plus hepatitis D virus (HDV) infection may be more severe than HBV infection alone. Antibody to HDV ordinarily persists for about 6 months following acute infection. Further persistence indicates carrier status. • Interpretation • Positive in: Hepatitis D. • Test only indicated in HBsAg-positive patients. Chronic HDV hepatitis occurs in 80–90% of HBsAg carriers who are superinfected with delta, but in less than 5% of those who are coinfected with both viruses simultaneously.
HIV • Test Range and Collection • serum • Negative • Physiologic Basis • This test detects antibody against the human immunodeficiency virus-1 (HIV-1), the etiologic agent of the vast majority of all HIV infections in the US. • Antibodies become detectable approximately 22–27 days after acute infection. Early detection is crucial for the institution of highly active antiretroviral therapy (HAART). • HIV antibody test is considered positive only when a repeatedly reactive enzyme immunoassay (EIA) is confirmed by a Western blot (WB) analysis. Immunofluorescent antibody test (IFA) is also performed in some laboratories for screening and/or as a substitute for WB. • Rapid HIV antibody tests are available and provide timely detection of antibody to HIV in cases of needle stick injury or exposure to potentially HIV-contaminated materials.
HIV • Interpretation • Positive in: HIV infection: EIA sensitivity >99% after first 2–4 months of infection, specificity 99%. When combined with confirmatory test, specificity is 99.995%. • The CDC recommends that all pregnant women be offered HIV testing. • There are at least three rapid HIV tests approved by the US FDA and available in the US: OraQuick Rapid HIV-1 Antibody Test, Reveal Rapid HIV-1 Antibody Test, and Uni-Gold Recombigen HIV Test.