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Flashcards in Hepatitis & Liver Disease Deck (74):
1

What is the risk of perinatal transmission of HAV?

0% - There is no perinatal transmission of HAV.

2

Can pregnant women be vaccinated against HAV?

The inactivated HAV vaccine can be safely used for prevention, including during pregnancy if a patient is at risk for HAV exposure. Two doses IM (Havrix 1 mL [50 U] or Vaqta 1 g [1440 U]), given 6 to 12 months apart, are needed to confer immunity. HA vaccine is also available in combination with HB vaccine. Immunity after vaccination lasts >10 years.

3

How should pregnant woman with an exposure to HAV be treated?

Exposed pregnant women can receive immune globulin injections, which are >85% effective in preventing HAV infection if given within two weeks of exposure. The standard intramuscular dose of immune globulin IS 0.02 mg/kg. The HAV vaccine series should also be initiated.

4

What is the therapy for acute HAV infection?

The vast majority of hepatitis A virus (HAV) infections are self-limited. Therapy is supportive.

5

Symptoms of HAV infection

Fever, malaise, decreased appetite, nausea, abdominal discom- fort, dark urine, jaundice.

6

How is HAV transmitted?

Fecal/oral contact with infected person or contaminated food/ water; rarely from blood transmission. Most U.S. cases are from person-to-person or sexual contacts or transmission during outbreaks.

7

Average HAV incubation period?

28 (15-49 days)

8

What are the complications/chronic sequelae of HAV?

Mortality is <0.3%. Chronic carrier state does not exist.

9

Diagnosis of HAV

HAV IgM and IgG. HAV IgM is detectable 5 to 10 days before the onset of symptoms and usually decreases to undetectable concentrations within six months after recovery. Consider rest of hepatitis workup. Check AST/ ALT, bilirubin.

10

Where are the HAV endemic areas?

High: Mexico, South America, Africa, Middle EastIntermediate: Asia

11

Is breast-feeding permitted in women with HAV?

Not contraindicated

12

Who should receive the HAV vaccine?

International travelersChildren in endemic areasIntravenous drug usersIndividuals who have occupational exposure (e.g., workers in a primate laboratory)Residents and staff of chronic care institutions Individuals with liver diseaseHomosexual menIndividuals with clotting factor disorders

13

What is the vertical transmission rate of HBV in women with HBeAg+?

95.00%

14

What is the vertical transmission rate of HBV in women who are HBsAg+ but HBeAg-?

25.00%

15

What is the vertical transmission rate of acute HBV in the third trimester?

90.00%

16

Without intervention, what percent of newborns infected with HBV develop chronic hepatitis? How many develop complications?

90%, with 25% of chronic HBV carriers eventually dying of complications (cirrhosis, hepatocellular cancer)

17

What vaccines do newborns born to women with HBV receive? Efficacy?

HBIg, HB vaccine, within 12 hrs of birth, prevents 90% of neonatal HBV infection

18

Is breastfeeding contraindicated in HBV+ mothers?

Breast-feeding is not contraindicated, as long as the mother is HBeAg- and HIV-, and the newborn receives appropriate immunoprophylaxis.

19

Labs for serologic diagnosis of acute HBV

HBsAg+, HBcAb+, HBcIgM+, HBsAb‰ÛÒ

20

Labs for serologic diagnosis of chronic HBV

HBsAg+ >6 months, HBsAb‰ÛÒ

21

Differential diagnosis of hepatitis

Hepatic A, B, or C virusCytomegalovirus (CMV)Epstein‰ÛÒBarrVaricella (VZV)Coxsackie BHerpes (HSV)RubellaAutoimmune

22

Diagnosis of newborn HBV

Detection of persistent (e.g., >9 months of age) HBsAg. Only HbsAb is attributable to newborn vaccination: HBcAb arises only as the result of actual HBV infection.

23

Symptoms of acute HBV

Only 30% to 50% of patients acutely infected have symptoms such as loss of appetite, malaise, nausea, and vomiting. About 10% have jaundice. The onset is usually insidious.

24

Natural history of HBV infection

One-third of the world‰Ûªs population (two billion people) have been infected with HBV: 90% have complete resolution, while about 10% overall develop chronic HBV infection; but this incidence is 90% in children 5 years old. About 25% of HBV chronic infection patients die of liver disease (4000/yr in the United States, >1 million/yr world-wide‰ÛÓ0.5% mortality)

25

HBV vaccine efficacy

The vaccine is about 95% effective against HBV.

26

HBV incubation period

60-90 days

27

HBV antigens

‰ÛÏs‰Û surface‰ÛÓinfected. If present >6 months = chronic HBV infection‰ÛÏc‰Û‰ÛÓcore‰ÛÏe‰Û‰ÛÓinfectious

28

HBV antibodies

‰ÛÏs‰Û‰ÛÓimmune‰ÛÏc‰Û‰ÛÓcovers ‰ÛÏwindow‰Û period, and usually precedes HBsAb conversion

29

Risk of chronic HBV infection

About 5% of HBV infections become chronic. This can lead to cirrhosis, hepatocellular carcinoma, and death.

30

Interpret this HBV panel:HbsAg -Anti-HBc -Anti-HBs -Vertical transmission rate?

Susceptible0%

31

Interpret this HBV panel:HbsAg -Anti-HBc +Anti-HBs +Vertical transmission rate?

Immune bc of natural infxn0%

32

Interpret this HBV panel:HbsAg -Anti-HBc -Anti-HBs +Vertical transmission rate?

Immune bc of HB vaccine0%

33

Interpret this HBV panel:HbsAg +Anti-HBc +Anti-HBc IgM +Anti-HBs -Vertical transmission rate?

Acutely infectedFirst trimester: 10% Third trimester: 90% HBeAg -: 10‰ÛÒ20% HBeAg +: 90%

34

Interpret this HBV panel:HbsAg +Anti-HBc +Anti-HBc IgM -Anti-HBs -Vertical transmission rate?

Chronically infectedHBeAg -: 2‰ÛÒ10% HBeAg +: 90%

35

Interpret this HBV panel:HbsAg -Anti-HBc +Anti-HBs -

Four interpretations possible:1. May be recovering from acute HBV infection2. May be distantly immune and test is not sensitive enough to detect very low level of anti-HBs in serum 3. May be susceptible with false-positive anti-HBc4. May be an undetectable level of HBsAg present in the serum and the person is actually a carrier

36

Blood transfusion HBV transmission risk

1/137,000 transfused units of screened blood

37

HBV risk factors

Intravenous drug abuseSexually transmitted diseasesMultiple sex partnersHouse contactsMetal institution/prisonAcupuncture are other risk factorsHBV-infected patients are at higher risk of HIV and HCV infections.

38

Complications of HBV

-Ninety percent of patients resolve the infection (clear the s and e Ag) and develop HBsAb-10% develop chronic HB (maintain HBsAg). Of these, most are asymptomatic with normal liver function tests (LFTs), and no HBV detectable by PCR. -The other 15% to 30% of chronic HB has persistent viral replication: these patients can develop cirrhosis and hepatocellular cancer. Mortality is 0.5% to 1%. This is more common in pts coinfected with HCV or HIV.

39

Lamivudine for HBV - efficacy, dosing

-FDA category B- >95% efficacy to achieve <150,000 HBV DNA, 167% HbeAg negativity-Can reverse cirrhosis of the liver. Given usually as 100 mg from 28 weeks to one month after birth in HBV carrier mothers, has been associated with a significant decrease in the HBV mother-to- child transmission

40

How to treat HBV exposure in pregnancy

Check serologies, LFTs. If HBsAg- and sAb-, give HBIg and begin the HB vaccine series (preferably within 24 hours of exposure): this combination will prevent 75% of transmission. Must give HBIg within 14 days of sexual contact. Repeat HBIg within one month if blood or mucous membrane exposure.

41

What is HDV?

Incomplete RNA virus, which can super- infect 20% to 25% of chronic HBV-infected patients. HDV infection worsens chronic HBV infection, so that 25% may die from disease. If HBV is prevented, HDV infection is prevented too. HDV has no effect on pregnancy or fetus/ neonate.

42

Presence of HBeAg indicates:

Active viral replication and a high level of infectivity.

43

When should you start lamivudine treatment for HBV in pregnancy, if the pt has had a previous perinatal transmission?

28 weeksHBV DNA >/= 200,000 IU/mL or >10^6 copies/mL

44

When should you start lamivudine treatment for HBV in pregnancy, if the pt has NOT had a previous perinatal transmission?

28 weeksHBV DNA >/= 2,000,000 IU/mL or >10^7 copies/mL

45

In clinical trials, effect of lamivudine prophylaxis on perinatal HBV transmission with lamivudine prophylaxis decreases by?

The overall effect favored lamivudine prophylaxis when these studies were combined (RR 0.31, 95% CI 0.15-0.63).

46

Definition of chronic HCV infection

HCV IgG+ with detectable HCV RNA

47

Definition of chronic active HCV infection

Chronic HCV infxn + abnl LFTs

48

Diagnosis of mother-to-infant transmission of HCV

Positive neonatal serum HCV RNA on 2 occasions, 3-4 mos apart, after the infant is 2 mos old, and/orAnti-HCV detected after 18 mos of age

49

Risk factors for vertical transmission of HCV

Coinfection with HIV, high maternal viral load

50

Evaluation of HCV positive pregnant women

HCV RNA viral loadHBsAgHepatitis A antibodyLFTsHIVGI referralSTD screening

51

Which vaccines should be given to pts with HCV infection?

HAV, HBV, if nonimmune - coinfection has additive morbidity

52

Treatment of HCV in nonpregnant adults

Combo antiviral therapy - alpha interferon, ribavirin. Cannot be used during or immed prior to pregnancy, bc ribavirin is teratogenic. Should be started postpartum for same indications as other nonpregnant adults.

53

Delivery mode in HCV+ women

C/S should be reserved for obstetrical indications in HCV+ but HIV- women

54

Is breastfeeding contraindicated in women with HCV?

Only if coinfected with HIV

55

Symptoms of HCV infection

75% asymptomatic. Symptoms = malaise, fever, abd pain, jaundice.

56

HCV incubation time

30-60 days

57

Natural history of HCV infaction

Chronic HCV (+RNA) develops in 50-75% of adult/pediatric pts. Chronic active disease (abnl LFTs) develops in at least 20% of chronic HCV infection.

58

Risk factors for HCV infection

Screening only recommended in women with risk factors:History of intravenous drug abuseHistory of blood transfusion or exposure to blood productsHistory of multiple STDsHIV infectionHepatitis B viral infectionSexual partner who abuses intravenous drugs or has HIV, HBV, or HCV infectionThree or more lifetime sexual partnersIncarcerationHistory of body piercing and tattooingRecipient of organ transplants before 1992Unexplained elevated transaminasesPatient or staff members involved in chronic dialysis programsParticipant in in vitro fertilization programs from anonymous donors

59

Complications of chronic HCV

Cirrhosis (10-20%)Hepatocellular carcinoma (1-5%)

60

How does HIV-HCV coinfection affect vertical transmission?

-Greatly increases vertical transmission-HAART has been shown to decrease HCV transmission in coinfected women-HIV coinfected women delivered by C/S were 60% less likely to have an HCV-infected child than those delivered vaginally

61

Does vertical transmission of HCV correlate with mode of delivery?

#NAME?

62

CVS, amniocentesis & HCV infection

Amniocentesis does not appear to significantly increase the risk (8), but very few studies have addressed this. If amniocentesis is requested, transplacental needle insertion should be avoided. There are no data regarding CVS and in utero transmission: appropriate counseling should be undertaken if an HCV-infected woman requests CVS, and the availability of amniocentesis should be discussed as a potentially less-invasive and vasodisruptive procedure.

63

Effect of chronic active hepatitis in pregnancy

Increased incidence of preterm delivery, intrauterine growth restriction, small for gestational age, and NICU admission

64

Work-up of pregnant woman with +HCV IgG

HCV RNA viral loadHepatitis B surface antigenHepatitis A antibodyLiver function testingHIV screeningGastroenterology referralSTD screeningVaccination against HAV and/or HBV should be administered if the woman is nonimmune for either or both, to avoid the comorbidities of superimposed hepatitis viral infections, which can be substantial.

65

Diagnosis of HCV infection

The diagnosis is best confirmed by serologic testing. The initial screening test should be an EIA. The confirmatory test is a recombinant immunoblot assay (RIBA ). Seroconversion may not occur for up to 16 weeks after infection. In addition, although these immunologic tests have been available for many years, they still do not consistently and precisely distinguish between IgM and IgG antibody.

66

Risk of perinatal transmission of HCV

Per Creasy: If low serum concentration of HCV RNA and HIV-, risk is < 5%. If RNA concentration high or HIV+, rate may approach 25%. EB MFM:Anti-HCV only (RNA negative) 1‰ÛÒ2% Viremic (HCV RNA positive) 4‰ÛÒ6% HIV positive 19‰ÛÒ40% HIV negative 3‰ÛÒ5% Anti-HCV and injection drug use 9%

67

What is hepatitis G?

Caused by an RNA virus that is related to the hepatitis C virus. Hepatitis G is more prevalent, but less virulent, than hepatitis C. Many patients who have hepatitis G are coinfected with hepatitis A, B, C, and/or HIV. Coinfection with hepatitis G does not adversely affect the prognosis of these other infections.

68

Symptoms of hepatitis G

Most pts are asymptomatic.

69

Diagnosis of hepatitis G

PCR for virus, ELISA for antibody

70

Does hepatitis G cause a carrier state? Is it perinatally transmitted?

Hepatitis G can cause a chronic carrier state, and perinatal transmission has been documented. However, the clinical effectsof infection in both mother and baby appear to be minimal.Patients should not routinely be screened for this infection, and no special treatment is indicated even if infection is confirmed.

71

Conditions associated with cholestasis:

Hepatitis C
Autoimmune hepatitis
Primary biliary cirrhosis

72

Which antibiotics can exacerbate cholestasis?

Erythromycin
Flucloxacillin
Amoxicillin w/ clavulanic acid

73

Recurrence rate of cholestasis

40-90%

74

First line treatment for cholestasis

Ursodiol 500 mg BID, may be increased