USPSTF Draft HBV Screening Recommendations: Suggested comments for physicians
Draft Recommendation Statement
Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults:
Preventive Services Task Force Recommendation Statement DRAFT
Summary of Recommendation and Evidence
Section entitled, “Summary of Recommendation and Evidence,”
 In cases where children come from a country with mid- to high- prevalence, individuals may be
vaccinated without being screened first for HBV prior to vaccination. The common assumption
with these individuals is that they are protected from HBV, when they may not be if they have
already been infected or exposed. Therefore, I encourage the USPSTF to review the literature for
HBV screening in infants, children and adolescents and include this caveat in the recommendations.
Rationale
Importance
Section entitled, “Rationale: Importance,”
 The prevalence estimates noted are underestimates. A number of reports and studies estimate the
total prevalence of chronic HBV (CHB) in the U.S. to be as high as 2.2 million.1,2,3,4 In addition,
compared to the CDC estimate of 375,000-975,000 foreign-born persons with CHB, a prominent
2012 study estimated that a total of 1.32 million foreign-born persons live with hepatitis B in the
U.S. have methodological challenges that would lead to a potential underestimation of disease.5
Studies have also shown estimates for institutionalized and homeless persons living with CHB vary
widely and therefore the total estimates may be even higher.6
Detection
 No comments
Benefits of Detection and Early Intervention
Section entitled, “Rationale: Benefits of Detection and Early Intervention,”
 In the statement, “The USPSTF found adequate evidence that HBV vaccination is effective at
decreasing disease acquisition,” the phrase “in high-risk groups” should be included.

When assessing the association between improvement in intermediate outcomes following antiviral
therapy and improvement in clinical outcomes, the USPSTF should also look at the results of the
study done by Hosaka et al. on the effect of long-term entecavir treatment on HCC with individuals
with chronic HBV.7
Harms of Detection and Early Intervention
 No comments
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USPSTF Assessment
 No comments
Clinical Considerations
Patient Population Under Consideration
Section entitled, “Clinical Considerations: Patient Population Under Consideration,”
 The patient population under consideration should also include those in high-risk groups who were
vaccinated but not tested for HBV prior to vaccination.
Assessment of Risk

There needs to be a distinction between those at high-risk of acquiring hepatitis B as adults
compared with those at high-risk of having chronic hepatitis B because of transference of the virus
in infancy/childhood.

I encourage the USPSTF to simplify the guidelines in testing the foreign-born. The concern is that
confusion will arise between Table 1 in the draft recommendations, as compared with the list
provided below Table 1 of countries with 8% endemicity or above, taken from the Kowdley et al.
article.8 Table 3 from the 2008 MMWR report by Weinbaum et al. provides a classification system
that will be easier for primary care providers, to prevent confusion about whom to test.9

High-risk groups for HBV screening denoted by the USPSTF should also include those individuals
who are co-infected with HCV. Studies indicate that among HCV-infected cohorts, exposure to
HBV infection can reach up to 35% and 3.5%-5.6% can be actively co-infected (with or without
HIV).10,11 Co-infection with HBV and HCV can significantly increase and speed up the risk of
serious liver disease, including liver cancer.12,13 Occult HBV in patients with chronic HCV has
been noted to produce an over two-fold increased risk for HCC. Shi et. al. conducted a metaanalysis of studies investigating the risk of developing HCC in patients with occult HBV, including
eight prospective studies and eight retrospective studies.14 They found that patients with both
occult HBV and chronic HCV had an over two-fold increased risk for HCC in comparison to
patients with chronic HCV alone. In addition to being associated with increased risk for HCC,
there was an association reported by Chang et. al. between occult HBV and worse disease-free
Hep B United: Comments for USPSTF Hepatitis B Screening Recommendations 2014
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survival after treatment for HCC with resection.15 These data suggest a possible role for treatment
of occult HBV especially in patients with chronic HCV, to reduce the risk of HCC.
After identifying HCV patients who are also HBsAg positive, anti-HBV therapy should be applied.
For those who are HBsAg negative, vaccination for HBV is recommended.

A differentiation must be outlined between Tables 1 and 2. Table 1 refers to those who are at highrisk of having chronic HBV. However, Table 2 notes those who are at highly susceptible to acquire
HBV. The individuals who are at risk and are susceptible to HBV infection should be tested and
then vaccinated. Those with current infection should be linked to care. Additionally, guidance must
be included here to mark the difference between those individuals who are at high-risk for chronic
hepatitis B and those who are vaccinated before being tested and thought to be protected when they
may have the virus. For these high-risk cases, individuals should be tested although they have been
vaccinated.

In the statement, “[t]he prevalence of HBV infection is low in the general U.S. population, and
most infected individuals do not develop complications,” I advise the USPSTF to use other wording
instead of “most,” as up to 25-45% of chronically infected individuals will die prematurely from
cirrhosis or HCC depending on gender.16
Screening Tests
Section entitled, “Clinical Considerations: Screening Tests,”
 The statement in the report “Diagnosis of chronic HBV infection is characterized by persistence of
HBsAg, HBV DNA, and total anti-HBc for at least 6 months” should be revised. Chronic HBV
infection is diagnosed with the presence of HBsAg for greater than 6 months, regardless of level of
HBV DNA or presence of anti-HBc. HBV DNA is not a specific indicator of chronic infection, but
an indicator of actively replicating virus. In addition, total core anti-HBc is only a marker of past
exposure, and does not indicate chronic infection – once a person is exposed to HBV virus, antiHBc generally remains positive for life – this marker cannot distinguish between acute and chronic
HBV infection.17 Since HBV is incurable, once a patient has anti-HBc, they have HBV DNA in
their liver for their lifespan, with the future risk of reactivation. There is no benefit to vaccinating
patients who are anti-HBc positive. Studies have shown that there is a “booster” effect for anti-HBs
titers in anti-HBc positive individuals, yet no clinical benefit of this “boosting” has been
demonstrated.
Treatment
Antiviral Regimens
 No comments
Vaccination
Section entitled, “Clinical Considerations: Treatment: Vaccination,”
 I would like the last statement of this passage, “[t]he CDC recommends that persons who are tested
for HBV infection receive the first dose of the vaccine at the same medical visit as screening,” to be
removed from this document. This is known as “incident to” vaccination or “draw and dose”.
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Although this method of testing and vaccination has been proven to be effective in certain settings,
e.g. developing countries, this method is dependent on many factors. Anti-HBc is found in 15-65%
of high-risk populations. If the anti-HBc is positive, these patients do not benefit from vaccine.18
The other, more effective method for most settings in the US, tests for HBsAg, anti-HBc, and antiHBs to provide a complete profile on a patient’s HBV status. People who are HBsAg positive need
to be linked to care, possible treatment and surveillance as well as education about risk for HCC
and cirrhosis as well as infectivity. Although people with core antibody have been exposed, there is
no proven benefit to providing the vaccine even if they have the surface antibody, as they already
have the HBV virus infection and have low levels of persistent virus in their hepatocytes.
Therefore, the only people who need vaccines are those who are HBsAg negative, anti-HBc
negative, and anti-HBs negative. The latter model structure shows cost-effectiveness. Additionally,
in developing countries, less than 70% of babies get their birth dose of HBV vaccine in less than 24
hours. When the HBV vaccine is used without HBIG, which is the case in most countries due to the
cost of HBIG, the protective effect of the HBV vaccine to prevent transmission is rapidly lost, as
the administration time is greater than 24 hours.19
Other Considerations
Research Needs and Gaps
Section entitled, “Other Considerations: Research Needs and Gaps,”
 To minimize confusion, I recommend that this section be placed at the end of the document.

As mentioned earlier, language needs to be included in this recommendation statement that
differentiates the different methods of “incident to” vaccination.

A distinction and explanation between acute HBV acquired through high-risk behavior
(susceptibility), as opposed to acquiring HBV as an infant/child in a moderate/high endemic
country and then immigrating to the US (high-risk) could be very helpful for primary care
providers.
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Discussion
Burden of Disease
Section entitled, “Discussion: Burden of Disease,”
I ask that the USPSTF differentiates and highlights the differences between the data mentioned the
declining incidence of acute HBV infection in the U.S., as opposed to the high prevalence of chronic
HBV infection in risk groups, the latter of which is the basis for this recommendation.
In reference to the first paragraph, about acute HBV infection:
 The 2,890 cases reported in the text refer to the reported cases of acute (incident) HBV
infection in 2011. This is the actual number of cases meeting the CDC case definition, reported
by health professionals to health departments, which in turn reported these numbers to
CDC. Including adjustments for under-diagnosis and underreporting, CDC notes that
the estimated number of acute HBV cases in 2011 is 6.5 times that figure (i.e., about 19,000
cases). In 2007, the estimated number of acute HBV cases was about 40,000. The CDC did not
intend to include cases of chronic HBV infection among foreign-born persons who entered the
U.S. during that year in question with chronic disease to be part of incidence calculations.

Incidence rates for reported cases of acute HBV infection were highest for black, non-Hispanic
persons (race/ethnicity), higher for men than for women, and were highest for those aged 30-39.20
In reference to the second paragraph, about chronic HBV infection:
 Prevalence of chronic HBV has been estimated as high as 2.2 million.21 It was estimated that from
2004-2008, 53,800 cases of chronic HBV were from immigrants coming to the U.S., and 3,800 new
U.S. acquired cases in each year, totaling 57,600 cases per year.22 Mitchell et al. also note in their
study that 25% of these cases (14,000 individuals), will develop fatal complications from HBV
infection if not provided with proper clinical management. The study also states that the majority of
deaths (95% or 13,110 cases) due to complications would be in immigrants with chronic HBV
infection.
Scope of Review
 No comments
Accuracy of Tests
 No comments
Intermediate Outcomes
 No comments
Clinical Outcomes
 No comments
Association Between Intermediate and Clinical Outcomes
Section entitled, “Discussion: Effectiveness of Early Detection and Treatment: Association Between
Intermediate and Clinical Outcomes,”
 In reference to the last study mentioned in this section, due to improved liver function, patients
tolerate the procedure better and have greater chances of survival, in contrast to HBeAg negative
Hep B United: Comments for USPSTF Hepatitis B Screening Recommendations 2014
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patients, who tend to have more advanced liver disease. There were many studies done to support
this claim.23,24,25,26,27,28,29,30,31,32,33,34
HBV Vaccination
 No comments
Harms of Screening and Treatment
 No comments
Estimate of Magnitude of Net Benefit
 No comments
How Does Evidence Fit With Biological Understanding?
Section entitled, “How Does Evidence Fit With Biological Understanding?”
 I recommend that the USPSTF change this language to reflect the fact that the risk of chronic
infection is inversely proportional to the age of acquisition.35
Update of the Previous USPSTF Recommmendation
 No comments
Recommendations of Others
 No comments
Levi J, Pastorfield C, Segal LM, Cimons M. HBV & HCV: America’s Hidden Epidemics. Trust for America’s
Health. Washington, D.C. September 2010: 1-42.
2
Gish RG, Gadano AC. Chronic hepatitis B: Current epidemiology in the Americas and implications for management.
J Viral Hepat 2006; 13: 787-98.
3
Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born
persons living in the United States by country of origin. Hepatology 2012; 56: 422-433.
4
Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW; Centers for Disease
Control and Prevention (CDC). Recommendations for identification and public health management of persons with
chronic hepatitis B virus infection. MMWR Recomm Rep. 2008 Sep 19; 57(RR-8): 1-20.
5
Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW; Centers for Disease
Control and Prevention (CDC). Recommendations for identification and public health management of persons with
chronic hepatitis B virus infection. MMWR Recomm Rep. 2008 Sep 19; 57(RR-8): 1-20.
6
Solomon L, Flynn C, Muck K, Vertefeuille J. Prevalence of HIV, syphilis, hepatitis B, and hepatitis C among
entrants to Maryland correctional facilities. J Urban Health. 2004; 81: 25-37.
7
Hosaka T, Suzuki F, Kobayashi M, Seko Y, Kawamura Y, Sezaki H, Akuta N, Suzuki Y, Saitoh S, Arase Y, Ikeda K,
Kobayashi M, Kumada H. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with
hepatitis B virus infection. Hepatology. 2013; 58(1): 98-107.
8
Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born
persons living in the United States by country of origin. Hepatology 2012. 56(2): 422-433.
9 Weinbaum CM, Williams I, Mast EE, Wang SA, et al. Recommendations for Identification and Public Health
Management of Persons with Chronic Hepatitis B Infection. MMWR 2008; 57 (RR08): 1-20.
1
Hep B United: Comments for USPSTF Hepatitis B Screening Recommendations 2014
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10 Tyson
GL1, Kramer JR, Duan Z, Davila JA, Richardson PA, El-Serag
HB.http://www.ncbi.nlm.nih.gov/pubmed/23505059 Prevalence and predictors of hepatitis B virus coinfection in
a United States cohort of hepatitis C virus-infected patients. Hepatology. 2013 Aug;58(2):538-45.
11
Hepatitis-B virus infection predicts mortality of HIV and hepatitis C virus coinfected patients. Teira R; VACH
Study Group. AIDS. 2013 Mar 13; 27(5): 845-8.
12 Perumalswami PV, Bini EJ. Epidemiology, natural history, and treatment of hepatitis B virus and hepatitis C virus
coinfection. Minerva Gastroenterol Dietol. 2006 Jun;52(2):145-55.
13 Cho LY, Yang JJ, Ko KP, Park B, Shin A, Lim MK, Oh JK, Park S, Kim YJ, Shin HR, Yoo KY, Park SK.
Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: systematic review and meta-analysis. Int
J Cancer. 2011 Jan 1. 28(1): 176-84.
14
Shi Y, Wu YH, Wu W, Zhang WJ, Yang J, Chen Z. Association between occult hepatitis B infection and the risk of
hepatocellular carcinoma: A meta-analysis. Liver Int. 2012;32(2):231-22.
15
Chang ML, Lin YJ, Chang CJ, et al. Occult and overt HBV co-infections independently predict postoperative
prognosis in HCV-associated hepatocellular carcinoma. PLoS One. 2013;8(6):e64891.
16
Lok, A. S., & McMahon, B. J. (2001). Chronic hepatitis B. Hepatology, 34(6), 1225-1241.
17
Lok, A. S., & McMahon, B. J. (2001). Chronic hepatitis B. Hepatology, 34(6), 1225-1241.
18
Mat O, Mestrez F, Beauwens R, Muniz-Martinez MC, Dhaene M. Primary high-dose intradermal hepatitis B
vaccination in hemodialysis: cost-effectiveness evaluation at 2 years. Hemodial Int. 2006 Jan; 10(1): 49-55.
19
World Health Organization, Expanded Programme on Immunization, Department of Immunization, Vaccines, and
Biologicals. Practices to improve coverage of the hepatitis B birth dose vaccine. Geneva, Switzerland: January 2013.
20
Centers for Disease Control, National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention, Division of
Viral Hepatitis. Viral Hepatitis Surveillance: United States, 2011.
21
Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born
persons living in the United States by country of origin. Hepatology 2012. 56(2): 422-433.
22 Mitchell T, Armstrong GL, Hu DJ, Wasley A, Painter JA. The Increasing Burden of Imported Chronic Hepatitis
B---United States, 1974-2008. PLoS ONE 6(12): e27717. doi: 10.1371/journal.pone.0027717.
23
Liaw, Y. F., J. J. Sung, W. C. Chow, G. Farrell, C. Z. Lee, H. Yuen, et al. 2004. Lamivudine for patients with
chronic hepatitis B and advanced liver disease. N. Engl. J. Med. 351:1521–1531.
24
Matsumoto, A., E. Tanaka, A. Rokuhara, K. Kiyosawa, H. Kumada, M. Omata, et al. 2005. Efficacy of lamivudine
for preventing hepatocellular carcinoma in chronic hepatitis B: a multicenter retrospective study of 2795 patients.
Hepatol. Res. 32:173–184.
25 Eun, J. R., H. J. Lee, T. N. Kim, and K. S. Lee. 2010. Risk assessment for the development of hepatocellular
carcinoma: according to on-treatment viral response during long-term lamivudine therapy in hepatitis B virusrelated liver disease. J. Hepatol. 53:118–125.
26
Hosaka T, Suzuki E, Kobayashi M, Seko Y, Kawamura Y, Sezaki H, Akuta N, Suzuki Y, Saitoh S, Arase Y, Ikeda
K. Kobayashi M, Kumada H. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients
with hepatitis B virus infection. Hepatology 2013; 58:98-107.
27 Piao CY, Fujioka S, Iwasaki Y, Fujio K, Kaneoshi T, Araki Y,Hashimoto K, Senoch T, Terada R, Nishida T,
Kabashi H, Sakaguchi K et al. Lamivudine treatment in patients with HBV-related hepatocellular carcinoma
using an untreated, matched control cohort. Acta Med Okayama 2005; 59: 217–24.
28 Kuzuya T, Katano Y, Kumada T, Hirooka Y, Itoh A, Ishigami M,Hayashi K, Honda T, Goto H. Efficacy of antiviral
therapy with lamivudine after initial treatment of hepatitis B virus-related hepatocellular carcinoma. J
Gastroenterol Hepatol 2007; 22:1929–35.
29 Kubo S, Tanaka H, Takemura S, Yamamoto S, Hai S, Ichikawa T, Kodai S, Shinkawa H, Sakeguchi H, Tamori A,
Habu D, Nishiguchi S. Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in
patients with active replication of hepatitis B virus. Hepatol Res 2007; 37: 94–100.
30 Kim BK, Park JY, Kim DY, Kim JK, Choi JS, Moon BS, Han KH, Chon JY, Moon YM, Ahn SH. Persistent hepatitis B
viral replication affects recurrence of hepatocellular carcinoma after curative resection. Liver Int. 2008:28:393401.
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31 Hann HW, Bergin D, Coben R, DiMarino AJ.
Prevention of new hepatocellular carcinoma with concomitant
antiviral therapy in chronic hepatitis B patients whose initial tumor was successfully ablated. Int. J. Cancer
2011: 128, 740–743.
32 Chan ACY, Chok KSH, Yuen WK, Chan SC, Poon RTP, Lo CM, Fan ST. Impact of Antiviral Therapy on the
Survival of Patients After Major Hepatectomy for Hepatitis B Virus–Related Hepatocellular Carcinoma. Arch
Surg. 2011; 146: 675-81.
33 Wu C-Y, Chen y-J, Ho HJ, Hsu T-C, Kuo KN, Wu M-S, Lin J-T. Association between nucleoside analogues and
risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA 2012;
308:1906-13.
34 Hann HW,Coben R,Brown D,Needleman L, Rosato E, Min A, Hann RS, Park KB, Dunn S, DiMarino AJ. A longterm study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular
carcinoma (HCC) following local tumor ablation. Cancer Med 2014; doi: 10.1002/cam4.197.
35
Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW; Centers for Disease
Control and Prevention (CDC). Recommendations for identification and public health management of persons with
chronic hepatitis B virus infection. MMWR Recomm Rep. 2008 Sep 19; 57(RR-8): 1-20.
Hep B United: Comments for USPSTF Hepatitis B Screening Recommendations 2014
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