
Hepatitis B infection: An Under- Recognized Problem in Oncology Atif Zaman MD MPH Professor of Medicine Division of Gastroenterology and Hepatology. Case Presentation. 66 year old male who presented for evaluation of severe shoulder and chest pain.
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Hepatitis B infection: An Under- Recognized Problem in OncologyAtif Zaman MD MPHProfessor of MedicineDivision of Gastroenterology and Hepatology
In accord with ORS.41675 related to QA, Teaching & Supervision of Medical Staff Physicians
In accord with ORS.41675 related to QA, Teaching & Supervision of Medical Staff Physicians
WHEN…
In accord with ORS.41675 related to QA, Teaching & Supervision of Medical Staff Physicians
In accord with ORS.41675 related to QA, Teaching & Supervision of Medical Staff Physicians
In accord with ORS.41675 related to QA, Teaching & Supervision of Medical Staff Physicians
In accord with ORS.41675 related to QA, Teaching & Supervision of Medical Staff Physicians
In accord with ORS.41675 related to QA, Teaching & Supervision of Medical Staff Physicians
Prevalence of HBsAg
High ≥ 8%
Intermediate 2% to 7%
Low < 2%
World Health Organization. Hepatitis B Fact Sheet. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2012. New York: Oxford University Press; 2012.
Modified from Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20.
Immune Control
(Nonreplicative)
Immunotolerance
Immune Clearance
HBV DNA
HBeAg+ HBeAg- HBeAb+
HBsAg+ HBsAg- HBsAb+
ALT
5-30 Yrs
Mos-Yrs
Mos-Yrs
Infection
Yim HJ, et al. Hepatology. 2006;43:S173-S181.
Immune Control
(Nonreplicative)
Immunotolerance
Immune Clearance
HBV DNA
HBsAg+ HBsAg- HBsAb+
ALT
5-30 Yrs
Mos-Yrs
Mos-Yrs
Infection
Yim HJ, et al. Hepatology. 2006;43:S173-S181.
cccDNA
Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
T cell
T cell
Do You Ever Really Get Rid of HBV?cccDNA
Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
T cell
T cell
Along Comes Immune SuppressionHIV
Steroids
Chemotx
cccDNA
Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
T cell
T cell
Along Comes Immune SuppressionHIV
Steroids
Chemotx
cccDNA
Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758.
HBeAg+ HBeAg- HBeAb+
HBeAg+
Immunotolerance
Immune Clearance
HBV DNA
ALT
5-30 Yrs
Mos-Yrs
Mos-Yrs
Infection
Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
HBeAg+ HBeAg- HBeAb+
HBeAg+
Immunotolerance
Immune Suppression
Immune Clearance
HBV DNA
ALT
5-30 Yrs
Mos-Yrs
Mos-Yrs
Infection
Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
HBeAg+ HBeAg- HBeAb+
HBeAg+
Immunotolerance
Immune Suppression
Immune Reconstitution
Immune Clearance
HBV DNA
ALT
5-30 Yrs
Mos-Yrs
Mos-Yrs
Infection
Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
Definition
Clinically
Hoofnagle JH. Hepatology. 2009;49(5 suppl):S156-S165.
Yeo W, et al. Hepatology. 2006;43:209-220.
Hepatitis
Interruption of chemotherapy
Yeo W, et al. Hepatology. 2006;43:209-220.
1. Kim MK, et al. Korean J Intern Med. 2007;22:237-243.2. Yeo W, et al. J Med Virol. 2003;70:553-561.
100 patients with NHL undergoing CHOP; 27 HBsAg positive
100
80
60
48
HBsAg Patients (%)
40
22
20
4
4
0
HBV
Reactivation
Jaundice
Nonfatal
Liver Failure
Death
Lok AS, et al. Gastroenterology. 1991;100:182-188.
Yeo W, et al. Hepatology. 2006;43:209-220.
ACE
100
PACE
73*
80
68
*P < .05
60
46
44*
HBsAg Patients (%)
38
36
35
40
*
28*
13
20
4
0
HBV
Reactivation
ALT
> 10 x ULN
Jaundice
Complete
Remission
Survival
at 4 Yrs
Prednisolone increased risk and severity of HBV reactivation
but trend toward improved NHL outcome
Cheng AL, et al. Hepatology. 2003;37:1320-1328.
Artz AS, et al. J Clin Oncol. 2010;28:3199-3202.
Artz AS, et al. J Clin Oncol. 2010;28:3199-3202.
Lok AS, et al. Hepatology. 2009;50:661-662.
CDC[2,3] & EASL[4] recommend screening ALL
patients prior to starting chemotherapy
1. Lok AS, et al. Hepatology. 2009;50:661-662. 2. Weinbaum CM, et al. MMWR Recomm Rep. 2008:57(RR-8):1-20. 3. Weinbaum CM, et al. Hepatology. 2009:49(suppl 5):S35-S44. 4. EASL. J Hepatol. 2012;57:167-185.
Chart Review
of Actual Screening (208 Pts at Single
Institution)[2]
Self-Reported HBV Screening
Practices of 131 US Oncologists[1]
100
80
62
60
HBV Screening (%)
40
24
14
14
20
0
None
High Risk
All
ActualScreening Rate
Few oncologists routinely screen all patients initiating chemotherapy for HBV
1. Khokhar OS, et al. Chemotherapy. 2009;55:69-75. 2. Lee R, et al. Curr Oncol. 2010;17:32-38.
Knowledge About HBV ScreeningAmong Oncologists
100
80
60
Proportion of Oncologists (%)
40
20
0
Recognize Country of Origin as No. 1 Risk Factor
Aware of HBVGuidelines
High-risk screening requires recognition of high-risk population
Lee R, et al. ASCO 2010. Abstract 6147.
1. EASL. J Hepatol. 2012;57:167-185. 2. Lok AS, et al. Hepatology. 2009;50:661-662. 3. Weinbaum CM, et al. Hepatology. 2009:49(suppl 5):S35-S44. 4. Artz AS, et al. J Clin Oncol. 2010;28:3199-3202.
100
Preemptive LAM
75
Survival Free From Hepatitis Due to HBV Reactivation
50
P = .002 by log-rank test
On-demand LAM
(if HBV DNA increased)
25
0
0
10
20
30
40
Wk
Pts at Risk, nPreemptive LAM
On-demand LAM
1515
1213
1010
94
62
Lau GK, et al. Gastroenterology. 2003;125:1742-1749.
100
On-demand group: start LAM if ALT > 1.5 x ULN
Preemptive group: start LAM on Day 1 of CHOP
80
60
48
HBsAg Patients (%)
36
40
20
20
8
8
0
0
0
0
HBV Reactivation and Hepatitis Flare
HBV Reactivation and ALT >10 x ULN
HBV Reactivationand Jaundice
Death
(After ChemoTx)
Preemptive antivirals decrease HBV reactivation
Hsu C, et al. Hepatology. 2008;47:844-853.
EASL. J Hepatol. 2012;57:167-185. Lok AS, et al. Hepatology. 2009;50:661-662.
EASL. J Hepatol. 2012;57:167-185. Lok AS, et al. Hepatology. 2009;50:661-662.
Manzano-Alonso ML, et al. World J Gastroenterol. 2011;17:1531-1537.
Yeo W, et al. Hepatology. 2006;43:209-220. Papamichalis P, et al. Clin Res Hepatol Gastroenterol. 2012;36:84-93.
40
CHOP (n = 25)
CHOP-R (n = 21)
30
24
Proportion of Anti-HBc Positive, HBsAg-Negative Patients (%)
20
10
5
0
0
0
HBV-Related
Death
HBV Reverse
Seroconversion
Risk of reactivation with rituximab significant in anti-HBc positive
Yeo W, et al. J Clin Oncol. 2009;27:605-611.
Yeo W, et al. J Clin Oncol. 2009;27:605-611.
1. Lau GK, et al. Bone Marrow Transplant. 1997;19:795-799. 2. Hui CK, et al. Blood. 2005;106:464-469.3. Onozawa M, et al. Transplantation. 2005;79:616-619. 4. Lau GK, et al. J Infect Dis. 1998;178:1585-1591.
**If observation is chosen, monitor liver tests, HBsAg and HBV DNA q1-3 months