ABCs of Hepatitis Bruce D. Askey, MS, ANP-BC Associate Lecturer Fitzgerald Health Education Associates, Inc. North Andover, MA Adult Nurse Practitioner Dept. of Hepatology/Gastroenterology Guthrie Clinic Sayre, PA/Ithaca, NY

Objectives Having completed the learning activities, the participant will be able to: –Examine serology aspects of hepatitis. –Interpret serological components of the hepatitis profile. –Outline recommended follow-up serologies for a patient with hepatitis.  Fitzgerald Health Education Associates, Inc. 2

Hepatitis Inflammation of the liver –Presents with elevation of liver enzymes Infectious or noninfectious –Acute or chronic 3  Fitzgerald Health Education Associates, Inc.

Symptoms of Hepatitis Jaundice/pruritus Scleral icterus 4  Fitzgerald Health Education Associates, Inc.

Symptoms of Hepatitis (continued) Acholic stools Dark colored urine Right upper quadrant abdominal pain Fatigue Anorexia/nausea Elevated liver enzymes 5  Fitzgerald Health Education Associates, Inc.

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Hepatocellular Enzymes ALT (Alanine aminotransferase), AST (Aspartate aminotransferase): Increase with hepatocellular inflammation Measure of severity of hepatocellular inflammation –Severe elevations (>5 X ULN) often result from toxins (meds, infection, herbals) or shock liver AST elevations in excess of ALT elevations often occur with alcohol use 8  Fitzgerald Health Education Associates, Inc.

Liver Panel: Acute Hepatitis C AST 1005 (N U/L) ALT 1310 (N 7-56 U/L) Alk. phos. 194 (N U/L) Total bili 11.1 (N mg/dL) ( µmol/L { µmol/L}) 9  Fitzgerald Health Education Associates, Inc.

Direct bili 5.3 (N mg/dL) (90.63 µmol/L { µmol/L}) Albumin 4.1 (N g/dL) (41 g/L {34-50 g/L}) INR 1.12 ( )  Fitzgerald Health Education Associates, Inc. 10 Liver Panel: Acute Hepatitis C (continued)

Infectious Hepatitis Hepatitis A Hepatitis B Non-A, non-B –Hepatitis C –Hepatitis D –Hepatitis E –Hepatitis G –Hepatitis ? 11  Fitzgerald Health Education Associates, Inc.

Hepatitis A Occurs worldwide –Vaccine-preventable disease (VPD) Incubation period: 2-6 weeks –Contagious during this time Does not become chronic: 3-6 month recovery Management is supportive Rarely fatal: Can lead to liver failure if: –Cirrhosis –Hepatitis B or C coinfection 12  Fitzgerald Health Education Associates, Inc.

Hepatitis A: Transmission Spread via the “fecal-oral route” –Up to 50% of U.S. cases result from international travel: Mexico and parts south ¹ ¹ Klevens RM, Miller JT, Iqbal K, et al. The evolving epidemiology of hepatitis a in the United States: incidence and molecular epidemiology from population-based surveillance, Arch Intern Med 2010; 170:  Fitzgerald Health Education Associates, Inc.

Hepatitis A: Transmission (continued) Sexual and household contact Male-male activity Food and water borne Daycare centers Drug use with contaminated equipment Perinatal transmission has not been shown 14  Fitzgerald Health Education Associates, Inc.

Hepatitis A: Pregnancy Premature contractions Placental separation Premature rupture of membranes Vaginal bleeding Preterm labor ¹Elinav, E, et al. Acute hepatitis A infection in is associated with high rates of gestational complications and preterm labor. Gastroenterology 2006; 130(4):  Fitzgerald Health Education Associates, Inc.

Hepatitis A: Serology Hepatitis A Antibody (Anti-HAV antibody) Total antibody only indicates a history of exposure but does not differentiate between past or current infection –IgM (MISERY) Indicates current infection Present at the onset of symptoms Usually clears several months later but may persist for years –IgG (GONE) Indicates immunity Indicates past or recent infection Remains present for years, possibly lifelong

Hepatitis A: Serology (continued)  Fitzgerald Health Education Associates, Inc. 17

Hepatitis E Fecal-oral route of transmission Incubation: 2-8 weeks Vaccination has been developed but is not commercially available in the U.S. Not generally seen in the U.S. Occurs –Asia –Africa –Middle East –Central America 18  Fitzgerald Health Education Associates, Inc.

Hepatitis E Rarely chronic –Organ transplant –Chronic immunosuppression Management is supportive 19  Fitzgerald Health Education Associates, Inc.

Hepatitis E: Pregnancy Up to 20% maternal fatality¹ Pregnant women with symptomatic acute hepatitis E have worse fetal and obstetric outcomes than pregnant women with other forms of symptomatic acute viral hepatitis ² ¹ Hamid,SS, et al. Fulminant hepatic failure in pregnant women: acute fatty liver or acute viral hepatitis?. Journal of Hepatology 1996; 25(1):20. ² Patra, S, et al. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Annals of Internal Medicine. 2007; 147(1):  Fitzgerald Health Education Associates, Inc.

Hepatitis E: Serology Fecal or serum polymerase chain reaction (PCR) Hepatitis E virus IgM antibody No commercial testing is available in the U.S. –May be available at research centers – 21  Fitzgerald Health Education Associates, Inc.

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Comparing HBV and HCV HBV –DNA virus –Found in all body fluids –Commonly sexually transmitted –Transmitted through sharing drug paraphernalia –Vaccine-preventable disease Lok, A & McMahon, J Chronic Hepatitis B: Update Hepatology. 50(3):  Fitzgerald Health Education Associates, Inc.

Comparing HBV and HCV (continued) HCV –RNA virus –Found primarily in the blood –Rarely sexually transmitted –Transmitted through sharing drug paraphernalia –Vaccine not available Ghany, M, et al Diagnosis, Management and Treatment of Hepatitis C: An update. Hepatology. 49(4):  Fitzgerald Health Education Associates, Inc.

Hepatitis C The most common chronic blood-borne infection in the U.S. –#1 reason for liver transplant in the U.S % will develop cirrhosis years after exposure Up to 5% will develop liver cancer 85% of those exposed will clear spontaneously but retain the hepatitis C antibody. Leading cause of death in HIV patients –4 million Americans have HCV. Wise, M, et al., Hepatology. 2008;47:  Fitzgerald Health Education Associates, Inc.

Symptoms of HCV Acute infection (<6 months) –Generally asymptomatic but jaundice occurs in 20% of cases Chronic infection (>6 months) –Generally asymptomatic but may have elevated liver enzymes Advanced disease –Ascites, varices, encephalopathy 26  Fitzgerald Health Education Associates, Inc.

Risk Factors for HCV Clotting factors prior to 1987 –85% Injection drug use –80% Hemodialysis –10-20% Multiple sex partners –4-6%  Fitzgerald Health Education Associates, Inc. 27

Risk Factors for HCV (continued) Sexual contact with infected partner –2-3% Blood transfusion prior to July 1992 –5% Infants born to infected women –4-7%  Fitzgerald Health Education Associates, Inc. 28

Risk Factors for HCV (continued) Organ recipients prior to 1992 –5% Healthcare workers (needle stick, etc.) –2% Ghany, M, et al Diagnosis, Management and Treatment of Hepatitis C: An update. Hepatology. 49(4):  Fitzgerald Health Education Associates, Inc. 29

Possible Risk Factor  Fitzgerald Health Education Associates, Inc. 30

Diagnosis of Hepatitis C Health history –Most reliable method available to assess risk Physical exam –Not reliable!!! Abnormal liver enzymes (ALT) –Not reliable!!! 31  Fitzgerald Health Education Associates, Inc.

Hepatitis C antibody –Indicates exposure (15% have cleared) Hep C RNA by PCR (HCV RNA test [Heptimax ® ]) –Indicates current infection –Viral load (benchmark) Ghany, M, et al Diagnosis, Management and Treatment of Hepatitis C: An update. Hepatology. 49(4):  Fitzgerald Health Education Associates, Inc. 32 Diagnosis of Hepatitis C (continued)

Who to Screen Anyone with a risk factor for hepatitis C Anyone with elevated liver enzymes Kuritzky L, et al. Family Practice Recertification. 2006; 28(2)  Fitzgerald Health Education Associates, Inc.

Who to Screen (continued) Those born between (baby boomers) should be offered a 1 time screening for hepatitis C. –5 times more likely than other adults to have hepatitis C –75% of adults with hepatitis C are baby boomers. Source  Fitzgerald Health Education Associates, Inc.

Serologic Tests Hepatitis C antibody Hepatitis C RNA Hepatitis C genotype 35  Fitzgerald Health Education Associates, Inc.

Serologic Tests (continued) Hepatitis C antibody –Screening test for exposure to HC –Immune cell that is made to fight off HC –All of those exposed will generate an antibody but 15% will clear the virus. –85% of those with an antibody will be currently infected. Ghany, M, et al Diagnosis, Management and Treatment of Hepatitis C: An update. Hepatology. 49(4):  Fitzgerald Health Education Associates, Inc.

Hepatitis C RNA –“Viral load” –Indicates current infection –Value does not correlate with degree of liver damage or clinical symptoms. Ghany, M, et al Diagnosis, Management and Treatment of Hepatitis C: An update. Hepatology. 49(4):  Fitzgerald Health Education Associates, Inc. Serologic Tests (continued)

Hepatitis C genotype –There are 6 forms (genotypes) of HC –Genotype 1 is the most common in the U.S. –With current therapies the response rates are similar regardless of genotype Flamm SL. JAMA. 2003; 289:  Fitzgerald Health Education Associates, Inc. Serologic Tests (continued)

HCV Screening Algorithm

Case Study Mr. J is a 43-year-old who presents to you as a new patient for primary healthcare needs. As part of his health history, he reveals that he had a blood transfusion in What test should be drawn that would indicate exposure to hepatitis C? 40  Fitzgerald Health Education Associates, Inc.

Hepatitis C antibody is positive. What is the percentage chance that he is currently infected? What test would indicate current infection with hepatitis C? 41  Fitzgerald Health Education Associates, Inc.

Viral Load Testing Indicates Current Infection What test will determine duration of treatment and chance of responding? 42  Fitzgerald Health Education Associates, Inc.

Hepatitis B The data and information for this section has been obtained from the following AASLD treatment guideline for management of chronic hepatitis B: Lok, A & McMahon, J Chronic Hepatitis B: Update Hepatology. 50(3):  Fitzgerald Health Education Associates, Inc.

Hepatitis B >95% of adults will clear the virus within 6-12 months of infection. Around 90% of infants will not clear the virus. –Hepatitis B immunoglobulin (HBIg) and hepatitis B vaccination at birth will improve this to 10%. 44  Fitzgerald Health Education Associates, Inc.

Hepatitis B: Serology Hepatitis B surface antigen (HBsAg) –Indicates current infection Hepatitis B surface antibody (HBsAb) –Indicates immunity Previous infection with clearance Vaccination May reactivate if immunosuppressed 46  Fitzgerald Health Education Associates, Inc.

Hepatitis B core antibody (HBcAb) –Immune response to the hepatitis B core antigen –Does not indicate immunity without the presence of HBsAb –IgM Acute infection (M=MISERY) –IgG Old infection (G=GONE) 47  Fitzgerald Health Education Associates, Inc. Hepatitis B: Serology (continued)

Hepatitis B e antigen (HBeAg) –“Pre-core” –Indicates active viral replication –Correlates with increased infectivity and liver injury Hepatitis B e antibody (HBeAb) –Immune response to HBeAg –Lower viral replication, infectivity and damage 48  Fitzgerald Health Education Associates, Inc. Hepatitis B: Serology (continued)

“Precore mutant” “Core promoter protein” Terms to indicate a mutant strain of hepatitis B that is replicating in a HBeAg negative, HBeAb positive patient Hepatitis B viral DNA –The amount of virus present/milliliter of blood 49  Fitzgerald Health Education Associates, Inc. Hepatitis B: Serology (continued)

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Hepatitis D (The Delta Virus) Can exist only in the presence of hepatitis B –Immunization against hepatitis B also provides immunity against hepatitis D. Can cause an acute hepatitis in those with chronic hepatitis B 53  Fitzgerald Health Education Associates, Inc.

Hepatitis D: Serology Must have current hepatitis B infection –Hepatitis B surface antigen positive –If acute, hepatitis B core IgM positive Hepatitis D antigen –Not available in the U.S. Hepatitis D RNA positive 54  Fitzgerald Health Education Associates, Inc.

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 Fitzgerald Health Education Associates, Inc. 57 End of Presentation Thank you for your time and attention. Bruce D. Askey, MS, ANP-BC Website:

 Fitzgerald Health Education Associates, Inc. 58 All websites listed active at the time of publication.