1. Hepatitis B

2. Chronic Hepatitis B Is a Global Health Problem
HBV infection is the most common chronic viral infection in the world1
Trepo C, pg2053/A
CDC2008, pg6/A (figure 3)
The Hawaiian island:
Vijayadeva V, pge99/A
WHO, pg1/A
HBsAg prevalence
≥8%
2%-7%
<2%
High
Intermediate
Low
An estimated 240 million people worldwide are living with chronic hepatitis B (CHB)2
Map adapted from the CDC.3
HBV=hepatitis B virus.
1. Trepo C, et al. Lancet. 2014;384; ; 2. WHO. Hepatitis B Fact Sheet. July Accessed March 25, 2015; 3. CDC. Morb Mortal Wkly Rep. 2008;57:1-20; 4. Vijayadeva V, et al. Am J Manag Care. 2014;20:e98-e104.

3. Prevalence of CHB in the United States
It is estimated that as high as 2 million persons are living with CHB in the United States1 5%
62.8%
13.5%
14.1%
4.6%
Percentage of foreign-born persons with CHB in the United States who originated from the indicated WHO regions ( )2
Europe
Western Pacific and Southeast Asia
Eastern Mediterranean
Africa
Americas (without US)
WHO regions
Approximately 90% of foreign-born persons with CHB in the United States migrated from regions of intermediate and high endemicity3
WHO=World Health Organization.
1. Cohen C, et al. J Viral Hepatitis. 2011;18: ; 2. Liu SJ, et al. J Immigr Minor Health. 2015;17:7-12; 3. Kowdley KV, et al. Hepatology. 2012;56:

4. CHB in the US: Continuum of Care
2 million have CHB
50,000 receive treatment
600,000 are aware of their infection
500,000 are potentially eligible for treatment
300,000 diagnosed and entered into care
1.4 million people in the US are unaware of their CHB infection
Based on epidemiologic studies in the US. Numbers presented are the upper end of estimated ranges.
Cohen C, et al. J Viral Hepat. 2011;18:

5. Chronic Hepatitis B Can Be Asymptomatic2
Chronic Hepatitis B Can Be Asymptomatic
About 2 out of 3 persons with CHB in the United States are unaware of their infection1
Cohen, pg378/A
CDC, pg1/B
CDC, pg1/B
WHO, pg1/B
CDC, pg1/D
Persons with CHB can be without symptoms for many years2
Unaware of their infection, CHB patients are at risk for transmitting the virus to others and for developing serious liver disease later in life2
Identification and management of CHB-infected individuals can help prevent serious sequelae of chronic liver disease2
1. Cohen C, et al. J Viral Hepat. 2011;18: ; 2. CDC. Morb Mortal Wkly Rep. 2008;57:1-20.

6. Virology of HBV Infection
Busch K, pg1/A
HBV is a partially double-stranded DNA virus which primarily infects liver cells1
Up to 1011 to 1013 virions/day may be produced in an infected person2
Liver inflammation and fibrosis/cirrhosis are consequences of host’s immune response1
The virus can evade the immune system during early phases of infection
Therefore, acute infections are primarily asymptomatic1
The genomic template for active viral propagation, cccDNA, can persist in infected cells, even after clearance of infection marker1
viral envelope
Margeridon-Thermet, pg2701/A
Busch K, pg3/A
polymerase
Busch K, pg2/B,A
DNA
Busch K, pg2/C
Figure adapted from Toronto Centre for Liver Disease. Hepatitis B.
cccDNA=covalently closed circular DNA.
Busch K, Thimme R. Med Microbiol Immunol. 2015;204:5-10; 2. Margeridon-Thermet S, Shafer RW. Viruses. 2010;2:

7. Routes of HBV Transmission
CDC. MMWR pg5/A
CDC. MMWR pg5/C
CDC. MMWR pg5/B
Prolonged close contact (eg, household)
Injection drug use
Sexual contact
Exposure to blood or body fluid
Organ, blood, and semen donors
Hemodialysis
HBV Carrier
Horizontal transmission1
CDC. MMWR pg10/I
CDC. MMWR pg3/A
Buchanan C. pg495/A
Vertical transmission via mother
CDC. MMWR pg5/D
Approximately 25%-50% of acute infections in children aged 1-5 years and <5% in older children and adults progress to CHB1
CDC. MMWR pg5/E; pg8/A
Child
Up to 90% of infants born to HBeAg-positive mothers develop CHB2
HBeAg=hepatitis B e antigen.
CDC. Morb Mortal Wkly Rep. 2008;57: Buchanan C, Tran TT. Clin Liver Dis. 2010;14:

8. Progression and Complications of CHB
Fattovich G. Pg340/A1, A2
0.1%-3%1
Fattovich G. Pg340/C
HCC
Fattovich G. Pg340/B1, B2
10%-17%1
Fattovich G. Pg340/D
Acute Infection
Chronic
Infectiona
Cirrhosis
Liver Transplantation
Death
8%-38%1
Fattovich G. Pg342/A
CDC2008, pg9/A
15%1
Liver Failure (Decompensation)
70%-85%1
Figure adapted from Fattovich G, et al. In: Marcellin P, (ed.) Management of Patients With Viral Hepatitis. Paris: APMAHV; 2004.
aChronic infection is defined as the persistence of positive test results for hepatitis B surface antigen or HBV DNA for at least 6 months.2
Percentages are 5-year cumulative incidence rates.
HCC=hepatocellular carcinoma.
1. Fattovich G, et al. J Hepatol. 2008;48: ; 2. CDC. Morb Mortal Wkly Rep. 2008;57:1-20.

9. Risk Factors Associated With CHB Disease Progression in Asian Patients
Non-HCC Liver Deaths
HCC Development
High level of HBsAg5
HBV genotype C/D5
Precore mutation3
Basal core promoter mutation3
Increased AFP1
Decreased baseline ALT1
Family history of HCC6
Alcohol consumption4
Increased ALT1
Reduced albumin1,2
Reduced platelets1,2
Ascites1
Encephalopathy1
Older age3
Male sex3,4
Cirrhosis2
Increased HBV DNA3,4
HBeAg status1
AFP=alpha fetoprotein.
1. Tong MJ, et al. Dig Dis Sci. 2009;54: ; 2. Tong MJ, et al. Gastroenterol Hepatol. 2006;2:41-47; 3. Tong MJ, et al. World J Gastroenterol. 2006;12: ; 4. Chen C-J, et al. JAMA. 2006;295:65-73; 5. Lin CL, Kao JH. J Gastroenterol Hepatol. 2013;28:10-17; 6. Yang HI, et al. World J Gastroenterol. 2014;20: 9

10. HBV Disease Progression
Chronic HBV Infection1
8%-38%
0.1%-3%
10%-17%
Cirrhosis
HCC
Percentages are 5-year cumulative incidence rates.1
Progression to HBV-related complications depends on multiple risk factors
Host factors
Viral / disease factors
Environmental factors
>40 years of age2
Male gender2
Family history of HCC2,3
African or Asian race2,3
High HBV DNA level2
High HBsAg level4
Prolonged time to HBeAg seroconversion2
Development of HBeAg– CHB2
Genotype C or D2,5
BCP mutations4,5
Elevated ALT2
Presence of fibrosis4 or cirrhosis2
Coinfection with HCV, HDV, or HIV2
Alcohol consumption2
Cigarette smoking2
Aflatoxin2
Obesity and/or diabetes2
ALT=alanine aminotransferase; BCP=basal core promoter; HBeAg=hepatitis B e antigen; HCV=hepatitis C virus; HDV=hepatitis D virus; HIV=human immunodeficiency virus.
Fattovich G, et al. J Hepatol. 2008;43:
Terrault NA, et al. Hepatology Nov 13. [Epub ahead of print].
Trepo C, et al. Lancet. 2014;384:
Burns GS, Thompson AJ. Cold Spring Harb Perspect Med. 2014;4:a
Martin P, et al. Clin Gastroenterol Hepatol. 2015;13:

11. Higher HBV DNA Levels Are Associated With Increased Risk of Cirrhosis and HCC Over Time (REVEAL Study)
Previously Untreated Patients With CHB
Risk of HCC
Cirrhosis1
HCC2
Risk of Cirrhosis
N=3582
N=3653
Adjusted Relative Riska of Cirrhosis
Crude Hazard Ratiob for HCC
<300
10,000-99,999
100, ,999
≥1 million
Copies/mL2
<300
10,000-99,999
100, ,999
≥1 million
Copies/mL1
<60
60-<2000
2000-<20,000
20,000-<200,000
≥200,000
IU/mL3,c
<60
60-<2000
2000-<20,000
20,000-<200,000
≥200,000
IU/mL3,c
Viral Load
Viral Load
aAdjusted for age, sex, cigarette smoking, and alcohol consumption.
bElevated HBV DNA level is a strong risk predictor of HCC, independent of HBeAg, ALT level, and liver cirrhosis; relative risk of an endpoint at any given time.
c1 IU/mL is equivalent to 5-6 copies/mL.
Iloeje UH, et al. Gastroenterology. 2006;130:
Chen CJ, et al. JAMA. 2006;295:65-73.
Martin P, et al. Clin Gastroenterol Hepatol. 2015;13:

12. Serologic Markers of HBV Infection
HBsAg
Hepatitis B Virus
HBV DNA
Trepo C. pg2055/A
Hallmark of infection1
Major tool for screening and diagnosis of CHB (if present ≥6 months3)
Trepo C. pg2055/B
Niederau C. pg11596/B
Measure of viral load; indicates ongoing viral replication1
Correlates with infectivity4 and risk of major liver disease2
CDC2008, pg9/A
Kao JH. Pg556/A
Niederau C. pg11597/A
Kao JH. Pg555/A
Anti-HBs
Kao JH. Pg555/D
Kao JH. Pg555/B
Kao JH. Pg555/C
Antibody to HBsAg4
Marker of immunity to HBV4
Only detectable marker of successful immunization4
HBeAg
Anti-HBc
Marker of risk of transmission of infection4
Antibody to HBV core antigen4
Marker of prior exposure4
IgM anti-HBc is a marker of recent infection4
anti-HBs=antibody to HBsAg; anti-HBc=antibody to hepatitis B core antigen; IgM=immunoglobulin M.
1. Trepo C, et al. Lancet. 2014;384: Niederau C. World J Gastroenterol. 2014;20: CDC. Morb Mortal Wkly Rep. 2008;57:1-20; 4. Kao JH. Expert Rev Gastroenterol Hepatol. 2008;2:

13. Serologic Profiles of Progression from Acute Infection to CHB
Progression from acute infection to chronic hepatitis B
CDC2008. pg4/A
Titer
HBeAg
anti-HBe
Acute (6 months)
Chronic (years)
Weeks after exposure 4 8 12 16 20 24 28 32 36 52
Years
IgM anti-HBc
Total anti-HBc
HBsAg
CDC, pg3/E
CDC, pg3/F
Antigens and antibodies associated with HBV infection include HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe
Serologic assays are available to test for these markers
CDC. Morb Mortal Wkly Rep. 2008;57;1-20.

14. PC/BCP Mutation Reactivation
Course of HBV Infection
HBsAg+
HBsAg−
HBeAg+
2 million have CHB
Anti-HBe+
Anti-HBe+
HBV DNA
ALT
50,000 receive treatment
Immune
Tolerant
Immune
Activation
Low
Replicative
Reactivation
Remission
Minimal Inflammation
Active Inflammation
Mild Inflammation
Active Inflammation
Inactive
Figure adapted from Tong MJ, et al.1
PC/BCP Mutation Reactivation
Wild-type
Reactivation
CHB follows a variable clinical course – not all patients will go through each phase (including remission)2
ALT=alanine aminotransferase; anti-HBe=antibody to HBeAg; HBeAg=hepatitis B e antigen; HBsAg=hepatitis B surface antigen; PC/BCP=precore/basal core promoter.
1. Tong MJ, et al. Dig Dis Sci. 2011;56: ; 2. Martin P, et al. Clin Gastroenterol Hepatol. 2015;13:

15. Immune Tolerant: High HBV DNA Levels at the Onset of CHB
Anti-HBe
HBeAg
HBsAg+
HBsAg–
HBV DNA
ALT
Sarin SK, Kumar M, pg213/C
Croagh, pg10397/A
Croagh, pg10397/B
Burns GS, pg4/B
Croagh, pg10397/C
Immune tolerant
Liao B, pg6/A
Immune clearance
Inactive carrier
Reactivation
Resolution
Croagh, pg10398/A
Often seen in perinatally infected children; may last for several decades1
In infection acquired during childhood or in adult, the phase is short or absent2
Very high serum HBV DNA levels and HBeAg positivity with very low rate of HBeAg seroclearance1,3
Normal ALT levels with minimal or absence of inflammation or fibrosis1
A recent retrospective study showed that, despite having normal ALT, a substantial number of HBeAg+ Asian/Chinese patients had significant fibrosis4
As older age may predict adverse outcomes, it is important to monitor older immune tolerant patients who show minimally or intermittently elevated ALT1
1. Croagh CMN, Lubel JS. World J Gastroenterol. 2014;20: ; 2. Sarin Sk, Kumar M. In: Shetty L, Wu GY (eds). Clinical Gastroenterology: Chronic Viral Hepatitis. Totowa, NJ: Humana Press. 2009; ; 3. Burns GS, Thompson AJ. Cold Spring Harb Perspect Med. 2014;4:a024935; 4. Liao B, et al. PLoS ONE. 8:e78672.

16. Immune Clearance: Fluctuating HBV DNA Levels With Active Liver Damage
Anti-HBe
HBeAg
HBsAg+
HBsAg–
HBV DNA
ALT
Croagh, pg10398/B
Burns GS, pg4/C,A
Croagh, pg10398/C
Immune clearance
Immune tolerant
Inactive carrier
Reactivation
Resolution
Burns GS, pg4/D
Burns GS, pg5/C
Burns GS, pg5/D
Lok ASF, pg23/O, pg24/A
Keeffe EB, pg1328/A
Intermittent or persistent elevation of ALT levels and high HBV DNA levels1
Typically occurs during the 2nd and 3rd decades of life; may last for years, leading to progressive liver damage2
Presence of necroinflammation on liver biopsy and varying degrees of fibrosis are the result of immune-mediated liver damage1
HBeAg seroconversion is a serologic marker of the end of the immune clearance phase2
10%-20% of patients will have annual spontaneous HBeAg seroconversion
Patients with active liver disease in the immune clearance phase are potential candidates for treatment2-4
Croagh CMN, Lubel JS. World J Gastroenterol. 2014;20: ; 2. Burns GS, Thompson AJ. Cold Spring Harb Perspect Med. 2014;4:a024935;
3. Lok ASF, McMahon BJ. Hepatology. 2009;50:1-36; 4. Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6:

17. Inactive Carrier: Low HBV DNA Levels with Minimal Liver Damage
Anti-HBe
HBeAg
HBsAg+
HBsAg–
HBV DNA
ALT
Croagh, pg10400/A
Sarin SK, pg214/A
Sarin SK, pg214/B
Inactive carrier
Immune tolerant
Immune clearance
Reactivation
Resolution
Trepo C, pg2057/C
Characterized by HBeAg seroconversion, suppression of HBV DNA (low or undetectable), and normalization of ALT1
Usually mild hepatitis and minimal fibrosis, but more severe liver damage, including cirrhosis, may have already accumulated from the preceding immune clearance phase2
The term “healthy carrier” is an erroneous term, as a significant proportion of patients may have high viral load, hepatic fibrosis, and other liver-related complications such as HCC2
20%-30% of patients will experience reactivation after HBeAg seroconversion3
1. Croagh CMN, Lubel JS. World J Gastroenterol. 2014;20: ; 2. Sarin SK, Kumar M. In: Shetty K, Wu GY (eds). Clinical Gastroenterology: Chronic Viral Hepatitis. Totowa, NJ: Humana Press. 2009; ; 3. Trepo C, et al. Lancet. 2014;384:

18. Reactivation and Resolution: Reactivation of Viral Replication and Resolving Infection
Anti-HBe
HBeAg
HBsAg+
HBsAg–
HBV DNA
ALT
Trepo C, pg2057/A
Sarin SK, pg215/A
Sarin SK, pg215/C
Trepo C, pg2057/B
Lok ASF, pg24/B,C
Keeffe EB, pg1329/A
Reactivation
Resolution
Immune tolerant
Immune clearance
Inactive carrier
Burns GS, pg5/A
Croagh, pg10401/B
Reactivation may occur spontaneously or due to immunosuppression1,2
Patients with reactivation of HBV replication are usually older, with more advanced liver disease2
Those with active disease have increased risk of liver cirrhosis and HCC1
Treatment is recommended for HBeAg-negative CHB patients who experience HBV reactivation3,4
HBsAg loss may occur in 0.5%-2% of Western patients and 0.1%-0.8% of Asian populations annually; this is considered resolution of hepatitis B5,6
Some patients may still have detectable HBV DNA in serum and are vulnerable to reactivation5
1. Trepo C, et al. Lancet. 2014;384: ; 2. Sarin SK, Kumar M. In: Shetty K, Wu GY (eds). Clinical Gastroenterology: Chronic Viral Hepatitis. Totowa, NJ: Humana Press. 2009; ; 3. Lok ASF, McMahon BJ. Hepatology. 2009;50:1-36; 4. Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6: ; 5. Croagh CMN, Lubel JS. World J Gastroenterol. 2014;20: ; 6. Burns GS, Thompson AJ. Cold Spring Harb Prespect Med. 2014;4:a

19. HBV Infection Can Be Prevented
Involves simple blood tests for serologic markers of infection1
Screen for HBV Infection
Trepo C, pg2054/A
Trepo C, pg2054/A
Trepo C, pg2054/A
CDC, 2006, pg1/A
Asian liver center, pg7/A
Asian liver center, pg7/D
Asian liver center, pg7/B
Asian liver center, pg7/C
CDC, 2006, pg1/A
Identify CHB-infected patients1,2
Identify unprotected patients for HBV vaccination1,2
Counsel to prevent transmission of infection to others
Provide appropriate medical management
Hepatitis B vaccination is the most effective measure to help prevent HBV infection and its consequences3
It is important to screen for HBV infection before vaccination1
1. Asian Liver Center Physician’s Guide to Hepatitis B. Accessed March 25, 2015; 2. CDC. Morb Mortal Wkly Rep. 2008;57:1-20; 3. CDC. Morb Mortal Wkly Rep. 2006;55:1-33.

20. Alignment of HBV Screening Recommendations From USPSTF, CDC, and AASLD
Lefevre ML. pg59/A
CDC. MMWR pg10/a
Lok ASF. Pg2/A
People born in regions with prevalence of HBV infection of ≥2%1-3
US-born people not vaccinated as infants whose parents were born in regions with prevalence of HBV infection of ≥8%1-3
Household and sexual contacts of persons with HBV infection1-3
All pregnant women2-4
Men who have sex with men1-3
Injection drug users1-3
Individuals infected with human immunodeficiency virus (HIV)1-3
People with certain medical conditions2,3,5
Needing immunosuppressive therapy
Undergoing hemodialysis
Lefevre ML. pg59/A
CDC. MMWR pg10/B
Lok ASF. Pg2/B
CDC. MMWR pg10/C
Lok ASF. Pg2/B
USPSTF pg1/A
Lefevre ML. pg59/A
CDC. MMWR pg11/A
Lok ASF. Pg2/B
LeFevre ML. pg59/A
CDC. MMWR pg10/D
Lok ASF. Pg2/B
LeFevre ML. pg59/A
CDC. MMWR pg11/B
Lok ASF. Pg2/B
LeFevre ML. pg59/A
CDC. MMWR pg10/E
Lok ASF. Pg2/B
CDC. MMWR pg10/F,G
Lok ASF. Pg2/B
USPSTF. Consumer Fact Sheet. P1/A
For a complete list of screening recommendations, please see:
LeFevre ML; USPSTF. Ann Intern Med. 2014;161:58-66.
CDC. Morb Mortal Wkly Rep. 2008;57:1-20.
Lok ASF, McMahon BJ. Hepatology. 2009;50(3):1-36.
USPSTF. Ann Intern Med. 2009;150:
USPSTF. Consumer Fact Sheet. May Accessed March 25, 2015.
AASLD=American Association for the Study of Liver Diseases.
CDC=Centers for Disease Control and Prevention.
USPSTF=United States Preventative Services Task Force.

21. + − HBV Screening Tests Screening Tests1,2
Screening tests for virologic markers of HBV infection include HBsAg, anti-HBs, and anti-HBc1,2
Keeffe EB. Pg1319/AA
Keeffe EB. Pg1319/AA
CDC-Serologic test, pg1/A
Screening Tests1,2
HBsAg
Anti-HBs
Anti-HBca
Interpretation
Recommended
Follow-up + −
Acute or chronic infectionb
Contact patient for evaluation and further testing
Patient has immunity from previous infection
Follow up as appropriatec,d
Patient has immunity from vaccination
No further action required
Patient is at-risk for HBV infection
Vaccinate
CDC, serologic test, pg1/B
CDC2008, pg9/A
Keeffe EB, pg1334/A
Bruix J, pg3/B
aAnti-HBc refers to total anti-HBc.2
bPatient is chronically infected if HBsAg+ for ≥6 months.3
cPatients who are anti-HBc positive should be monitored closely during and after the administration of cytotoxic chemotherapy for signs of HBV reactivation.1
dPatients with cirrhosis may need to be monitored for hepatocellular carcinoma per the AASLD guidelines.4
1. Keeffe EB, et al. Gastroenterol Hepatol. 2008;6: ; 2. CDC. Interpretation of Hepatitis B Serologic Test Results. Updated December 11, Accessed March ; 3. CDC. Morb Mortal Wkly Rep. 2008;57:1-20; 4. Bruix J, Sherman M. Hepatology. 2011;53. guideline_documents/HCCUpdate2010.pdf. Accessed March 25, 2015.

22. Populations recommended for HBV vaccination by the CDC1
CDC – hepatitis B in short, pg1/A-C, pg2/A
All newbornsa
All unvaccinated children and adolescents through 18 years of age
All unvaccinated adults at risk for infection and those requesting protection from HBV infection
CDC, 2006, pg10/A
CDC, 2006, pg10/B
Primary vaccination consists of 3 intramuscular doses given at 0, 1, and 6 months2
A full 3-dose vaccine series is associated with immunity in >90% of healthy adults2
CDC, 2005, pg13/A
>90%
5 months
1 month
75%
30%-55%
with protective
immunity
First dose (0 month)
Second dose (1 month)
Third dose (6 months)
aInfants born to HBsAg-positive mothers should also receive hepatitis B immune globulin ≤12 hours of birth.3
1. CDC. Vaccination and Immunizations: Hepatitis B In-Short. February 2, Accessed March 25, 2015; 2. CDC. Morb Mortal Wkly Rep. 2006;55:1-33; 3. CDC. Morb Mortal Wkly Rep. 2005;54:1-33.

23. Serological diagnoses of 240 self-declared vaccinated Korean adults1
Significant Disparity Between Self-Reported Vaccination and Actual Immunity
A recent study showed significant disparity between self-reported vaccination and actual immunity1
Navarro N. pg5/B
60.4%
Immune due to vaccination 2%
Infected
26.3%
Immune due to natural infection
10.8%
Susceptible
0.4% Other
Chu D. pg454/A
History of vaccination has been cited as one of the main reasons for not ordering screening2,a
Vaccination is not beneficial for already infected or immune (resolved acute infection) persons3
HBV screening is important to avoid false perception of protection1 and unnecessary vaccination3
Navarro N. pg5/A
Asian liver center. Pg7/E
Asian liver center. Pg7/E
Navarro N. pg6/A
Navarro N. pg 5/A,B
Serological diagnoses of 240 self-declared vaccinated Korean adults1
aData based on a survey of 217 Asian/Asian American primary care practitioners from New York, Los Angeles, San Francisco, Houston, and Chicago areas.2
1. Navarro N, et al. BMC Infect Dis. 2014;14:269; 2. Chu D, et al. Gut Liver. 2013;7: ; 3. Asian Liver Center Physician’s Guide to Hepatitis B. Accessed March 25, 2015.

24. Medical Management of CHB
Initial evaluation of patients should include a thorough history and physical examination, followed by laboratory tests
Keeffe EB. Pg1318/B
Keeffe EB. Pg1319/A
Pretreatment Evaluation and Initial Follow-Up
History and physical examination
Evaluation tests
Risk factors for viral hepatitis
Risk factors for HIV coinfection
Duration of infection
Route of transmission
History of alcohol use
Presence of comorbid diseases
Family history of liver cancer
Serial testing for HBV DNA and ALT (6-month period)
HBeAg and anti-HBe
Liver function tests
Tests for antibodies to HAV, HCV, HDV, and HIV
HBV genotype
Screen for HCC in high-risk patients
Liver biopsya
Urinalysis
aNoninvasive methods for assessing fibrosis may be helpful on a case-by-case basis.
Patients should also be counseled on risk of transmission, screening of family members, vaccination of at-risk household and sexual contacts, and family planning
HAV= hepatitis A virus; HCV=hepatitis C virus; HDV=hepatitis D virus.
Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6:

25. Existing CHB Guidelines and Algorithms Overview
HBV DNA (IU/mL)
AASLD >20,000
ALT (U/L)
AASLD >2x ULNa or biopsy (+)
AASLD >20,000 or >2000 if biopsy (+)
US Treatment Algorithm ≥2000
US Treatment Algorithm >ULNa or TE*/biopsy (+)
EASL >2000
EASL >ULNa and biopsy (+)
APASL ≥20,000
APASL ≥2x ULNa or biopsy (+)
APASL >2x ULNa or biopsy (+)
APASL ≥2000
HBeAg+
HBeAg−
aULN for US Treatment Algorithm (2015) and AASLD (2009): 30 U/mL (men) and 19 U/mL (women); ULN for EASL (2012): 40 U/mL; ULN for APASL (2012): dependent on the laboratory reference.
AASLD=American Association for the Study of Liver Diseases; APASL=Asian Pacific Association for the Study of the Liver; EASL=European Association for the Study of the Liver; *TE=transient elastography; ULN=upper limit of normal.
1. Lok ASF, McMahon BJ. Hepatology. 2009;50:1-36; 2. Martin P, et al. Clin Gastroenterol Hepatol. 2015;13: ; 3. EASL. J Hepatol. 2012;57: ; 4. Liaw YF, et al. Hepatol Int. 2012;6: 25

26. Asian American Treatment Algorithm Indicators for Monitoring
HBeAg+
HBeAg−
Immune Tolerant
HBV DNAa >2000 IU/mL
ALT ≤ ULNb
Inactive Carrier
HBV DNA ≤2000 IU/mL
ALT ≤ ULNb
MONITOR
HBeAg+
HBeAg−
Compensated
Cirrhosis
Undetectable HBV DNA
Any ALT level
Compensated
Cirrhosis
Undetectable HBV DNA
Any ALT level
aHBV DNA usually copies/mL.
bALT normal range is based on local laboratory reference range.
Tong MJ, et al. Dig Dis Sci. 2011;56:

27. Asian American Treatment Algorithm Indicators for Treatment
HBeAg+
HBeAg−
Chronic Hepatitisa
HBV DNA >2000 IU/mL
ALT > ULNb
Chronic Hepatitisa
HBV DNA >2000 IU/mL
ALT > ULNb
TREAT
HBeAg+
HBeAg−
Compensated
Cirrhosisc
Detectable HBV DNA
Any ALT level
Compensated
Cirrhosisc
Detectable HBV DNA
Any ALT level
aLiver biopsy grade 1-3 and/or stage 1-3.
bALT normal range is based on local laboratory reference range.
cPatients with decompensated cirrhosis should be treated regardless of HBV DNA and ALT levels, and immediately referred to a liver transplant center.
Tong MJ, et al. Dig Dis Sci. 2011;56:

28. Asian American Treatment Algorithm Indicators for “Gray Zone” Considerations
HBeAg−
Chronic Hepatitis
HBV DNA >2000 IU/mL
ALT ≤ ULN
HBeAg+
Chronic Hepatitis
HBV DNA ≤2000 IU/mL
ALT > ULN
ASSESS
GRAY ZONE
CONSIDERATIONS
HBeAg−
Chronic Hepatitis
HBV DNA ≤2000 IU/mL
ALT > ULN
Tong MJ, et al. Dig Dis Sci. 2011;56:

29. Conduct liver biopsy if possible. If not, calculate Risk Impact Scorea
Asian American Treatment Algorithm Risk Assessment for Patients in the “Gray Zone”
Total Score
Conduct liver biopsy if possible. If not, calculate Risk Impact Scorea
Risk Factors
Impact Score
Age ≥40 yr 1
Male gender
Male ALT >30 U/L
or Female ALT >19 U/L
Basal core promoter mutation 2
HCC in first-degree relative 3
Albumin ≤3.5 g/dL or
Platelets ≤130,000 mm3
Total Score
____ points ≥3
<3
HBV DNA
>2000 IU/mL
HBV DNA
≤2000 IU/mL
Recommend
Treatmentb
Monitor
aThis scoring system is based on expert opinion and warrants further clinical experience and validation.
bPlease see reference for detailed information on first- and second-line antiviral treatment choices.
Adapted from Tong MJ, et al. Dig Dis Sci. 2011;56: 29

30. Monitoring of CHB Patients on Treatment
Asian American Treatment Algorithm On-Treatment Monitoring of HBV DNA, ALT, and Serologic Markers
HBV DNA
Every 3 months until undetectable
Every 3-6 months thereafter
Monitoring of CHB Patients on Treatment
ALT
Every 3 months until normalization
Every 3-6 months thereafter
HBeAg+
HBeAg
Every 6 months until negative –
Anti-HBe +
Once sustained suppression of HBV DNA is achieved
HBsAg
Every 12 months
HBeAg−
Tong MJ, et al. Dig Dis Sci. 2011;56: 30

31. Asian American Treatment Algorithm When to Stop Treatment
Stopping Treatment
HBeAg+
Treat until seroconversion to anti-HBe
Continue with consolidation therapy for at least 1-2 years
After stopping therapy, monitor for relapse
Seroreversion to HBeAg positivity
Reappearance of HBV DNA
ALT elevation
HBeAg−
Continue antiviral treatment for life
If HBsAg becomes negative, then treatment may be stopped
Monitor closely for relapse
Cirrhosis
Continue antiviral treatment for life
Tong MJ, et al. Dig Dis Sci. 2011;56:

32. Asian American Treatment Algorithm HCC Surveillance in Asian Americans With CHB
AFP
Abdominal ultrasound
Surveillance
Tests
Surveillance
Interval
Every 6 months
Surveillance
Candidates
High-risk patients
Cirrhosis
HCC in blood relatives
Low- to moderate-risk patientsa
Inactive carriers
Immune tolerant patients
HBsAg+ males <40 years, females <50 years
Patients with HBsAg loss (especially in patients with cirrhosis)
aIf clinically active chronic hepatitis, cirrhosis, or other risk factors for HCC are present in these patients.
Tong MJ, et al. Dig Dis Sci. 2011;56:

33. Summary
In the US, the majority of CHB patients are unaware of their infections1
Cohen C, pg378/A
Keeffe EB, pg1317/A; pg1318/A’
The clinical course of CHB consists of the immune tolerant, immune clearance, inactive carrier, reactivation, and resolution phase2
Not all patients will go through every phase of infection; however, CHB patients are at risk for serious liver disease2,3
Keeffe EB, pg1318/A
CDC2008, pg1/B
Rajbhandari R, pg76/A
Asian Liver Center, pg7/C
CDC2008, pg1/D
HBV screening is important to identify chronically infected persons who may need treatment and to allow for intervention to reduce transmission to others4
HBV screening consists of simple blood tests for serologic markers of infection5
Screening, vaccination, and appropriate management of persons with CHB are important steps to help prevent hepatitis B and its liver complications3
1. Cohen C, et al. J Viral Hepatitis. 2011;18: ; 2. Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6: ; 3. CDC. Morb Mortal Wkly Rep. 2008;57:1-20; 4. Rajbhandari R, Chung RT. Ann Intern Med. 2014;161:76-77; 5. Asian Liver Center Physician’s Guide to Hepatitis B. Accessed March 25, 2015.