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High-calorie diet (often tolerated best in morning) Intravenous hydration and parenteral nutrition Avoidance of alcohol and drugs metabolized by the liver Avoidance of drugs that may produce adverse reactions (e.g., cholestasis) Bile-salt sequestrant resins, if severe pruritus Cholestyramine: up to 4 g PO 4 times daily
Antiviral therapy
Nucleoside analogues In rare instances of severe acute hepatitis B, treatment with a nucleoside analogue has been successful.
Liver transplantation
Liver transplantation is indicated in the rare cases of Fulminant hepatic failure and Grade III or IV encephalopathy.
Prevention
Recommends screening certain high-risk groups and vaccinating those who are not already immune or infected
Pregnant women Persons born in hyperendemic areas Men who have sex with men Injection drugs users Patients on dialysis HIV-infected patients Family and household contacts of HBV-infected persons
Persons with HCV infection Person who require immunosuppressive or cytotoxic therapy
Vaccination
Recombinant hepatitis B vaccine Vaccine components and administration
2 available vaccines: 10 g IM or 20 g IM Half dose for children 40-g dose for patients receiving hemodialysis and immunocompromised adults Given at 0, 1, and 6 months Deltoid, not gluteal, injection
Duration of protection
At least 5 years in ~8090% of immunocompetent vaccine recipients At least 10 years in ~6080% of immunocompetent vaccine recipients Booster vaccinations are indicated only for: Immunosuppressed individuals who no longer have detectable anti-HBs Immunocompetent persons who sustain percutaneous HBsAgpositive inoculations after losing detectable anti-HBs Dialysis patients whose anti-HBs antibody levels fall below 10 mIU/mL
Postexposure prophylaxis
Hepatitis B immune globulin: 0.06 mL/kg IM
1. Immediately after NEEDLESTICK, followed by a complete course of hepatitis B vaccine to begin within the first week Within 14 days of SEXUAL EXPOSURE followed by a complete course of hepatitis B vaccine to begin within the first week For PERINATAL EXPOSURE of infants born to an HBsAg-positive mother, a single 0.5-mL IM dose should be given immediately after birth in combination with a complete course of 3 injections of hepatitis B vaccine to be started within the first 12 hours of life.
2.
3.
8. Tests to screen for HCC 9. Consider liver biopsy to grade and stage liver disease for patients who meet criteria for chronic hepatitis
Total Anti-HBc
Negative Positive Negative Positive Positive Positive
IgM Anti-HBc
---Negative Positive --
Anti-HBs
Negative Positive Positive Negative Negative Negative
Interpretation
Susceptible; offer vaccination Immune due to natural infection Immune due to hepatitis B vaccination Chronic HBV infection Acute HBV infection Unclear; could be any one of the following: 1. Resolved infection (most common) 2. False-positive anti-HBc; susceptible 3. Low-level chronic infection 4. Resolving acute infection
Resolved hepatitis B
HBeAg-Negative CHB
2000 - 2 x 107
HBeAg
ALT Other observations Treatment candidate?
Positive
Normal Liver biopsy typically normal or minimal findings No
Positive
Elevated or fluctuating Active inflammation on liver biopsy Yes
Negative
Normal HBsAg may become undetectable No
Negative
Elevated or fluctuating Active inflammation on liver biopsy
Yes
<
HBeAg+
><
HBeAg-/anti-HBe+ (precore/core promoter variants) > 2000 IU/mL < 2000 IU/mL
>
HBV DNA
2x 11 IU/mL 2 x 10 108 200,000 - 2 x 109 IU/mL
<
HBeAg+
><
HBeAg-/anti-HBe+ (precore/core promoter variants) > 2000 IU/mL < 2000 IU/mL
>
HBV DNA
2x 11 IU/mL 2 x 10 108 200,000 - 2 x 109 IU/mL
ALT
<
HBeAg+
><
HBeAg-/anti-HBe+ (precore/core promoter variants) > 2000 IU/mL < 2000 IU/mL
>
HBV DNA
2x 11 IU/mL 2 x 10 108 200,000 - 2 x 109 IU/mL
ALT
Normal/mild CH
Moderate/severe CH Cirrhosis
Moderate/severe CH Cirrhosis
<
><
HBeAg-/anti-HBe+ (precore/core promoter variants) > 2000 IU/mL < 2000 IU/mL
>
ALT
Normal/mild CH
Moderate/severe CH
Normal/mild CH
Moderate/severe CH
Adefovir
Decision to treat
Nucleos(t)ide analogues
Hepatitis
web study
What is Pegylation?
Covalent attachment of polyethelene glycol to peptide Increases hydrodynamic size Prolonged circulation, delayed renal clearance.
Hepatitis
web study
Nucleos(t)ide analogues
Lamivudine
Adefovir
Entecavir
Telbivudine
Tenofovir
Hepatitis
web study
Route
SQ SQ PO PO PO PO PO
*Dose adjustment needed if eGFR < 50 mL/min. Persons coinfected with HIV should receive 150 mg BID. Should only be used in combination with other antiretrovirals. Lok AS, et al. Hepatology. 2009;50:661-662.
Tenofovir (TDF)
Hepatitis
web study
Safety & tolerability Efficacy (potency) Barrier to resistance (durability) Safety & tolerability
Efficacy (potency)
Finite duration
Hepatitis
web study
Finite course of therapy No resistance Higher rate of HBeAg loss in 1 yr Higher rate of HBsAg loss with short duration therapy*
SQ administration Frequent AEs Contraindicated in patients with cirrhosis, in pregnancy, with acute hepatitis B, and who are immunosuppressed
*Particularly for HBeAg-positive patients with genotype A infection. Recent case report of lactic acidosis in severe liver failure.
Lok AS. Hepatology. 2010;52:743-747. Buster EH, et al. Gastroenterology. 2008;135:459-467. Lange CM, et al. Hepatology. 2009;50:2001-2006.
Hepatitis
web study
Agent
Peginterferon[1] Lamivudine[1-4] Adefovir[5] Telbivudine[3] Entecavir[2]
*Median follow-up.
n
72 55 61 43 39 45 55 70
1. Lau GKK, et al. N Engl J Med. 2005;352:2682-2695. 2. Gish RG, et al. Gastroenterology. 2007;133:14371444. 3. Poynard T, et al. EASL 2008. Abstract 706. 4. Dienstag JL, et al. Hepatology. 2003; 37:748-755. 5. Wu IC, et al. Clin Infect Dis. 2008;47:1305-1311. Hepatitis
web study
Hepatitis
web study
"HBV DNA levels decreased over time in patients infected with genotypes A, B or D," the study authors concluded.
"However, highly active genotype C or D infection often remained highly active, implying a risk for progressive liver damage."
Hepatitis
web study
Lok AS, McMahon BJ. Hepatology. 2009;50:661-662. Chronic Hepatitis B: Update 2009, Lok ASF, McMahon BJ, www.aasld.org. Copyright@2009. American Association for the Study of Liver Diseases, Reproduced with permission of the American Association for the Study of Liver Diseases.
ALT < 1 x ULN HBV DNA < 2000 IU/mL Q 3 mos ALT x 3, then Q 6-12 mos if ALT still < 1 X ULN
ALT 1-2 x ULN HBV DNA 2000-20,000 IU/mL Q 3 mos ALT and HBV DNA Consider biopsy if persistent Rx as needed
ALT 2 x ULN HBV DNA 20,000 IU/mL Treat if persistent Liver biopsy optional
Lok AS, McMahon BJ. Hepatology. 2009;50:661-662. Chronic Hepatitis B: Update 2009, Lok ASF, McMahon BJ, www.aasld.org. Copyright@2009. American Association for the Study of Liver Diseases, Reproduced with permission of the American Association for the Study of Liver Diseases.
HBeAg Loss
100 80 60
HBeAg Seroconversion
26
30
21
40 20 22 12-18
23
21
22-27 21
NA
ETV TDF PegIFN
PegIFN
Lok AS, et al. Hepatology. 2007;45:507-539. Lau GK, et al. N Engl J Med. 2005;352:2682-2695. Marcellin P, et al. N Engl J Med. 2003;348:808-816. Chang TT, et al. N Engl J Med. 2006;354:1001-1010. Lai CL, et al. N Engl J Med. 2007;357:2576-2588. Marcellin P, et al. N Engl J Med. 2008;359:2442-2455. Janssen HL, et al. Lancet. 2005;365;123-129.
80 Outcome (%)
77 68 68 65 49-56 39
~ 80 72 74 69
60 48 40 41-75
53
*No/short duration consolidation treatment among LAM- and ETV-treated patients; most patients treated with ADV and LdT had consolidation.
HBeAg Positive
76 67
100 80 60
HBeAg Negative
88 90 93 63
60-73
51-63
PegIFN
TDF PegIFN
*By PCR-based assay (LLD ~ 50 IU/mL) except for some LAM studies. Lok AS, et al. Hepatology. 2007;45:507-539. Lok AS, et al. Hepatology. 2009;50:661-662.
Drug Generation
1st
LAM
24%
38%
49%
67%
70%
2nd 3rd
0% 4% 0.2% 0%
3% 17% 0.5% 0%
11% 1.2% 0%
18% 1.2%
29%
1.2%
1.2%
EASL. J Hepatol. 2009;50:227-242. Tenny DJ, et al. EASL 2009. Abstract 20. Marcellin P, et al. AASLD 2009. Abstract 481. Heathcote E, et al. AASLD 2009. Abstract 483.
b. HBeAg-negative chronic hepatitis BTreatment should be continued until the patient has achieved HBsAg clearance.
Definition
in serum HBV DNA by < 2 log10 IU/mL after 24 wks of therapy in serum ALT to within the normal range in serum HBV DNA to undetectable levels by PCR and loss of HBeAg in patients who were initially HBeAg positive in serum HBV DNA of 1 log10 IU/mL after discontinuation of treatment in 2 determinations > 4 wks apart in histology activity index by 2 points and no worsening of fibrosis score compared to pretreatment liver biopsy Fulfill criteria of biochemical and virologic response and HBsAg loss
Virologic response
Virologic relapse Histologic response Complete response
EASL1
Compensated cirrhosis Antiviral therapy if HBV DNA +, regardless of ALT
AASLD2
Antiviral therapy if ALT >2 x ULN or if HBV DNA >2,000 IU/mL
APASL4
Antiviral therapy with IFN (if no hepatitis flare) or NAs* if HBV DNA >2,000 IU/mL
Decompensated cirrhosis*
1. EASL. J Hepatol 2009; 50:22742; 2. Lok & McMahon. Hepatology 2009; 50:136; 4. Liaw Y-F, et al. Hepatol Int 2008; 2:26383.
Treatment duration
Long-term treatment
Can discontinue in HBeAg-positive patients with confirmed HBeAg seroconversion and 6 mos consolidation therapy Can discontinue in HBeAg-negative patients with confirmed HBsAg clearance
Preferred therapies
(LAM or LdT) + (ADV or TDF); TDF or ETV monotherapy*
Treatment should be coordinated with transplantation center IFNs should not be used in decompensated cirrhosis
Treatment duration
Lifelong treatment recommended
*Clinical data documenting safety and efficacy of TDF or ETV monotherapy in decompensated cirrhosis are lacking.
Lok AS, et al. Hepatology. 2009;50:661-662.
After birth
Breastfeeding not associated with transmission 2 May be related to scarification, other parenteral exposures
From 20-32 wks antepartum HBsAg-positive pregnant women, HBV DNA > HBV DNA > 6 x 106 copies/mL
To 4 weeks postpartum
All infants received HBV vaccine series and HBIG (200 IU, single dose)
No Rx (n = 92) 13.04
P Value .004
--Lower risk of postpartum ALT flare in telbivudine group (7.45% vs 18.48%; P = .025) --Postpartum ALT flare in 12.73% of telbivudine-treated patients after treatment discontinuation at Week 4 --No cases of severe hepatitis (ALT > 10 x upper limit of normal)
Han G AASLD 2010 Abstract 212.
Recent reports suggest that lamivudine therapy during the last trimester of pregnancy in pregnant HBsAg-positive women with high levels of viremia reduces the risk of intrauterine and perinatal transmission of HBV if given in addition to passive and active vaccination by HBIg and HBV vaccination.
Tenofovir or tenofovir with emtricitabine or entecavir could be considered. Although apparently safe, these protocols require further confirmation.
Active co-infection with HDV is confirmed by the presence of detectable HDV RNA, immuno-histochemical staining for HDV antigen, or IgM anti-HDV.