receive cme abim moc points · 4/16/2020 6 current standard of care 1. screening for hbv 2. goals...

4/16/2020

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American College of Gastroenterology

4/16/2020

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MOC QUESTION

If you plan to claim ABIM MOC Points for this activity, you will be asked to: Please list specific changes you will make in your practice as a result of the information you received from

this activity.

Include specific strategies or changes that you plan to implement.THESE ANSWERS WILL BE REVIEWED.

ACG Virtual Grand Rounds

Join us for upcoming Virtual Grand Rounds!

Week 5: Refractory GERD: New Options for Treatment 2020Philip O. Katz, MD, MACGApril 23, 2020 at Noon EDT

Week 6: Celiac Disease: 10 Things Every Clinician Should Know Amy S. Oxentenko, MD, FACGApril 30, 2020 at Noon EDT

Visit gi.org/ACGVGR to Register

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Register Now at gi.org/ACGVGR

Presenter: Nancy S. Reau, MD, FACG Research Support: Genfit, Intercept, ShireConsultant: Abbott, AbbVie, Gilead, Merck

Moderator: Mitchell L. Shiffman, MD, FACGAdvisory Board: AbbVie, Gilead, Intercept, Mallinckrodt, ShionogiResearch Grant: Conatus, CymaBay, Dova, Enanta, Gilead, InterceptRoyalties: SlackSpeakers Bureau: AbbVie, Daiichi Sankyo, Eisai, Gilead, Intercept, Shionogi

Disclosures:

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Hepatitis B Update

Nancy S. Reau, MD, FACG

Chief, Section of Hepatology

Richard B. Capps Chair of HepatologyRush University Medical Center

Agenda

• General overview of HBV Treatment Guidelines

• Highlight treatment conundrums in hepatitis B infection

• Introduce future directions in HBV management

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Epidemiology and Public Health Burden

1. EASL CPG HBV. J Hepatol 2017;67:370–98; 2. Schweitzer A, et al. Lancet 2015;386:1546–55; 3. Ott JJ, et al. Vaccine 2012;30:2212–9; 4. GBD 2013 Mortality and Causes of Death Collaborators. Lancet 2015;385:117–71; 5. Coppola N, et al. Euro Surveill 2015;20:30009; 6. Hampel A, et al. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz2016;59:578–83; 7. Chen C‐L, et al. J Hepatol 2015;63:354–63.

• Worldwide ≈250 million chronic HBsAg carriers2,3

• 686,000 deaths from HBV‐related liver disease and HCC in 20134

Increasing prevalence in some European countries:5,6

• Migration from high endemic countries

HBsAg prevalence, adults (1949 years), 20053

<2%24%57%≥8%Not applicable

Decreasing prevalence in some endemic countries, e.g. Taiwan7

Possible reasons:• Improved

socioeconomic status

• Vaccination • Effective treatments

Despite the risk, access to timely diagnosis and treatment is limited globally…

WHO. Global Hepatitis Report 2017. Available at: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/ (accessed May 2019)

257

221.7

0

50

100

150

200

250

300

Infected Diagnosed Started treatment

Only 9% of infected individuals globally are diagnosed and only 8% of those start treatment

Per

son

s (m

illio

n)

9% 8%

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Current Standard of Care

1. Screening for HBV

2. Goals of therapy

3. Indications for treatment

4. Treatment strategies

5. Endpoints of therapy



2. Goals of therapy




Screening: 1. HBsAg + anti‐HBs2. Anti‐HBs‐ Negative should be vaccinated3. Anti‐HBc not routine but has a role with HIV, HD, Donation and

Immune suppression4. Counsel HBsAg positive on transmission

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*Including needle‐sharing contacts of HBsAg‐positive persons;†Those who are seronegative should receive hep B vaccine.

AST: aspartate aminotransferase; CDC: Centers for Disease Control; USPSTF: US Preventative Service Task Force; MSM: men who have sex with men; ESRD: persons with end‐stage renal disease; PEP: postexposure prophylaxis

Risk factorsUSPSTF 2014

CDC 2008

AASLD 2018

Persons born in region with ≥2% prevalence

US‐born persons not vaccinated as infants whose parents were born in regions with ≥8% prevalence

†

MSM †

PWID †

HIV‐positive †

Household and sexual contacts of HBV‐infected persons *†

Requiring immunosuppressive therapy

ESRD, including haemodialysis patients †

Persons with elevated ALT or AST †

Persons who are the source of blood or body fluid exposure that might require PEP †

Pregnant women †

Infants born to HBV‐infected mothers †

Groups Recommended for HBV Screening

Terraut NA, et al. Hepatology 2018;67:1560–99; Terrault NA, et al. Hepatology 2016;63:261–83; Abara WE, et al. Ann Intern Med 2017;167:794–805; Lefevre ML. Ann Intern Med 2014;161:58–66; Weinbaum CM, et al. Hepatology 2009;49(5 Suppl):S35–S44

Risk factorsUSPSTF 2014

CDC 2008 AASLD 2018

Blood and tissue donors

Persons with chronic liver disease, e.g. HCV *

Persons who are not in a long‐term, mutually monogamous relationship *

Persons seeking evaluation or treatment for a STD *

At‐risk health care and public safety workers *

Residents and staff of facilities for developmentally disabled persons *

Travelers to countries with intermediate or high prevalence of HBV infection *

Inmates of correctional facilities *

Unvaccinated persons with diabetes who are aged 19–59 years *

Groups Recommended for HBV Screening (cont’d)

*Those who are seronegative should receive Hep B vaccine.STD: sexually transmitted disease

Terraut NA, et al. Hepatology 2018;67:1560–99; Terrault NA, et al. Hepatology 2016;63:261–83; Abara WE, et al. Ann Intern Med 2017;167:794–805; Lefevre ML. Ann Intern Med 2014;161:58–66; Weinbaum CM, et al. Hepatology 2009;49(5 Suppl):S35–S44.

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HBV Serology Interpretation and Management

Screening test resultsInterpretation Management

HBsAg Total/IgG anti‐HBc Anti‐HBs

+ + ‐/+ Current infectionCounselling, evaluation, management, treatment, and HCC risk assessment and surveillance; refer household and sexual contacts for HBV screening and vaccination

‐ + + Prior infection with immune controlNo transmission risk; HBV dormant in the liver; reactivation risk on immunosuppressive medications

‐ + ‐Prior infection, occult* infection, or false‐positive anti‐HBc (< 0.2%)

If immunocompetent†, counsel as prior infection above; if immunocompromised, check HBV DNA for occult infection

‐ ‐ + Immune from prior vaccination Protected for life. No need for booster vaccine

‐ ‐ ‐ Susceptible Vaccinate‡

*Occult HBV infection is defined by the presence or detectable HBV DNA in persons who are HBsAg-negative. Patients with occult HBV infection should be managed similarly to those with current infection.†Consider HBV vaccination for persons not from an area of intermediate or high endemicity, as this may represent a false-positive anti-HBc result. The false-positive anti-HBc is <2/1000, using current assays.‡Groups at high risk for HBV transmission and immunocompromised persons should be assessed for response to vaccination with a PVST of anti-HBs between 1–2 months after the final dose of the vaccine. A challenge vaccine dose or full vaccine series followed by PVST may be given to persons from high-risk groups with documentation of complete vaccination but not PVST.

Slide Courtesy of Amy S Tang, MD, National Hepatitis B Task Force PVST: post‐vaccination serology test.



2. Goals of therapy




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Goals of Therapy

• Improve survival and quality of life by preventing disease progression and HCC

• Prevent mother‐to‐child transmission, reactivation, and extrahepatic manifestations

Recommendations

Main endpoint• Induction of long-term suppression of HBV DNA

I 1

Valuable endpoint• Induction of HBeAg loss (± anti-HBe seroconversion)

in HBeAg-positive patients with chronic hepatitis B*II-1 1

Additional endpoint • ALT normalization (biochemical response)†

II-1 1

Optimal endpoint • HBsAg loss (± anti-HBs seroconversion)‡

II-1 1

Grade of evidence Grade of recommendation

*Often represents a partial immune control of the chronic HBV infection;†Achieved in most patients with long-term suppression of HBV replication;‡Indicates profound suppression of HBV replication and viral protein expression.EASL CPG HBV. J Hepatol. 2017;67:370–98.



2. Goals of therapy




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HBeAg positive HBeAg negative

Phase 1 Phase 2 Phase 3 Phase 4 Phase 5

Chronic HBV infection

Chronichepatitis B

Chronic HBV infection

Chronichepatitis B

Resolved HBV infection

HBsAg HighHigh/

intermediateLow Intermediate Negative

HBeAg Positive Positive Negative Negative Negative

HBV DNA >107 IU/mL 104–107 IU/mL <2,000 IU/mL* >2,000 IU/mL <10 IU/mL‡

ALT Normal Elevated Normal Elevated† Normal

Liverdisease

None/minimalModerate/

severeNone

Moderate/severe

None§

Immune tolerant

Immune ActiveHBeAg positive

CHBInactive CHB

Immune ActiveHBeAg negative

CHBResolved

Nomenclature Differs by Guideline

*HBV DNA levels can be between 2,000 and 20,000 IU/mL in some patients without signs of chronic hepatitis;†Persisitently or intermittently, based on traditional ULN (~40 IU/L). ‡cccDNA can frequently be detected in the liver;§Residual HCC risk only if cirrhosis has developed before HBsAg loss. EASL CPG HBV. J Hepatol 2017;67:370–98 Terrault NA, et al. Hepatology 2018;67:1560–99;

Chronic HBVinfection

Chronic hepatitis B

EASL

AASLD

qHBsAg<1000 IU/mL

Management of CHB in Patients Without Cirrhosis

Threshold for treatment5

APASL (2015)1 EASL (2017)2US algorithm

(2015)3AASLD (2018)4

HBV DNA, IU/mLHBeAg positiveHBeAg negative

>20,000>2000

>2000>2000

≥2000≥2000

>20,000≥2000

ALTULN for malesULN for females

>2 x ULN40 IU/mL40 IU/mL

>ULN40 IU/L40 IU/L

>ULN30 IU/L19 IU/L

≥2 x ULN35 U/L25 U/L

1. Sarin APASL HBV guidelines. Hepatol Int 2016;10:1; 2. EASL. J Hepatol 2017;67:370; 3. Martin. Clin Gastroenterol Hepatol 2015;13:2071; 4. Terrault. Hepatology 2018;67:1560; 5. Clinical options. Available at clinicaloptions.com (accessed June 2019)

May be treated

• Patients with HBeAg-positive chronic HBV infection† >30 years old, regardless of severity of liver histological lesions

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ELEVATED ALT >ULN SIGNIFICANTLY INCREASES RISK OF LIVER‐RELATED COMPLICATIONS

≥45

>30

>20

ALT level (U/L)

Significantly increases risk of developing cirrhosis and HCC1,2

Significantly increases risk of significant liver disease (presence of inflammation and fibrosis) and mortality3

Significantly increases risk of liver disease mortality (20 for women and 30 for men)4

Risk of liver-related complications

1. Iloeje UH, et al. Gastroenterology. 2006;130:678-686; 2. Chen CJ, et al. JAMA. 2006;295:65-73; 3. Wang H, et al. PLoSONE. 2013;8:e80585; 4. Shim JJ, et al. Liver Int. 2018 Jan 27. [epub ahead of print]; 5. Martin P, et al. Clin Gastroenterol Hepatol. 2015;13:2071-2087; 6. Terrault NA, et al. Hepatology. 2018 February 5. Epubahead of print.

AASLD=American Association for the Study of Liver Diseases; ULN=upper limit of normal; USTA=US Treatment Algorithm.

>40

Recommended ALT ULN

men

USTA 20155

30 U/Lwomen19 U/L

men

AASLD 20186

35 U/L 25 U/Lwomen!



2. Goals of therapy




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“In most people... treatment does not cure hepatitis B infection, but only suppresses the replication of the virus. Therefore, most people who start

hepatitis B treatment must continue it for life.”

– World Health Organization2

19984

LAM

20025

ADV

20056,7

ETV, PEG‐IFN

20068

LdT

20089

TdF

201610

TAF

Because CHB endures, management must account for the changing needs of patients1-3

CHB Therapy Has Changed Over the Years

adefovir dipivoxil; ETV, entecavir; LAM, lamivudine; LdT, telbivudine; PEG-IFN, peginterferon alfa-2a.1. Terrault NA, et al. Hepatology. 2016;63(1):261-283; 2. WHO Hepatitis B Fact Sheet. Updated July 2016; 3. EASL HBV Clinical Practice Guidelines.J Hepatol. 2012;57(1):167-185; 4. Epivir-HBV® FDA approval letter. December 8, 1998; 5. Hepsera® FDA approval letter. September 20, 2002; 6. Baraclude® FDA approval letter. May 13, 2005; 7. Pegasys® FDA biologics license approval letter. May 13, 2005; 8. Tyzeka® FDA approval letter. October 25, 2006; 9. Viread FDA approval letter. August 11, 2008; 10. VEMLIDY [package insert]. Foster City, CA: Gilead Sciences, Inc; November 2016.

*Evidence level I, grade of recommendation 1; †Collation of currently available data – not from head-to-head studies;‡No evidence of resistance has been shown after 8 years of TDF treatmentEASL CPG HBV. J Hepatol 2017;67:370–98

Cumulative incidence of HBV resistance to NAs in pivotal trials in NA-naïve patients with CHB†

24

38

49

6770

03

11

18

29

4

17

0.50.21.2

0 0 0 0 0 0 00

10

LAM

20

30

40

50

ADV TBV ETV TDF† TAF

60

70

801 year2 years3 years4 years5 years

3 first line oral therapies

Prevention of resistance should rely on the use of first‐line NAs with a high barrier to resistance*

Preferred regimens : PEG, ETV, TDF and TAF

NOT recommended: LAM, ADV and TBV

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Indications for selecting ETV or TAF over TDF*

*TAF should be preferred to ETV in patients with previous exposure to NAs; †ETV dose needs to be adjusted ifeGFR <50 ml/min; no dose adjustment of TAF is required in adults or adolescents (aged ≥12 years and ≥35 kg body weight) with estimated CrCl ≥15 ml/min or in patients with CrCl <15 ml/min who are receiving haemodialysisEASL CPG HBV. J Hepatol 2017;67:370–98

Age • >60 years

Bone disease

• Chronic steroid use or use of other medications that worsen bone density

• History of fragility fracture• Osteoporosis

Renal alteration†

• eGFR <60 ml/min/1.73 m2

• Albuminuria >30 mg/24 h or moderate dipstick proteinuria• Low phosphate (<2.5 mg/dl)• Haemodialysis

TAF vs. TDF for HBV: Change in eGFR

Agarwal K, et al. J Hepatol 2018;68:67281

Median change from baseline in eGFR over 96 weeks TAF 25 mg (n=866) vs. TDF 300 mg (n=432)

TAFTDF

TAF: -1.2

TDF: -4.8p<0.001

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TAF vs. TDF for HBV: change in BMD

Agarwal K, et al. J Hepatol 2018;68:67281

Median change from baseline in BMD over 96 week TAF 25 mg (n=866) vs. TDF 300 mg (n=432)

TAF

TDF

Hip SpineTAF

TDFp<0.001 p=0.80

Monitoring Patients Treated with ETV, TDF or TAFRecommendations (monitoring)ALT and serum HBV DNA*• All patients treated with NAs q3–4 months for first year then q6 months

Renal monitoring†

• Patients at risk of renal disease treated with any NA • All patients treated with TDF, regardless of renal risk

Switch to ETV or TAF‡

• Should be considered in patients on TDF at risk of development of and/or with underlying renal or bone disease

Recommendations (long‐term surveillance)HCC surveillance recommended• All patients under effective long‐term NA therapy

HCC surveillance mandatory• All patients with cirrhosis or with moderate or high HCC risk scores at the onset of NA therapy

*Liver function tests should be performed every 3–4 months during the first year and every 6 months thereafter. Serum HBV DNA should be determined every 3–4 months during the first year and every 6–12 months thereafter; †Including at least eGFR and serum phosphate levels. Frequency of renal monitoring can be every 3 months during the first year and every 6 months thereafter, if no

deterioration. Closer renal monitoring is required in patients who develop CrCl <60 ml/min or serum phosphate levels <2 mg/dl; ‡Depending on previous LAM exposureEASL. J Hepatol 2017;67:370–398

AASLD: HBsAg-positive adults at high risk for HCCAsian or black men > 40 yrs of age; Asian women > 50 yrs of ageFirst-degree relative with history of HCC Coinfection with HDV

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2. Goals of therapy




Discontinuation of NA Treatment

EASL CPG HBV. J Hepatol 2017;67:370–98

Long‐term therapy with NAs is usually required: HBV eradication is not usually achieved

Recommendations

NAs should be discontinued • After confirmed HBsAg loss (± anti-HBs seroconversion)

II-2 1

NAs can be discontinued• In HBeAg-positive patients, without cirrhosis, who achieve stable HBeAg

seroconversion and undetectable HBV DNA and complete ≥12 months of consolidation therapyClose post-NA monitoring is warranted

II-2 2

NAs may be discontinued • In selected HBeAg-negative patients, without cirrhosis, who achieve long-term (≥3

years) virological suppression, if close post-NA monitoring can be guaranteedII-2 2


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References (6-16)*Assessed 6 months after completion of 12 months of therapy.†Assessed after 3 years of continuous therapy.‡Assessed after 2 years of continuous therapy.§HBV DNA <2,000-40,000 IU/mL for peg-IFN; <60 IU/mL for entecavir and tenofovir disoproxil fumarate; <29 IU/mL for tenofovir alafenamide.llHBV DNA <20,000 IU/mL for peg-IFN; <60 IU/mL for entecavir and tenofovir disoproxil fumarate; <29 IU/mL for tenofovir alafenamide.¶ALT normalization defined by laboratory normal rather than ≤35 and ≤25 U/L for males and females. Terrault, et al. Hepatology. Vol. 67, No.4. 2018.

HBeAg Positive Peg-IFN* Entecavir†Tenofovir

Disoproxil Fumarate†

Tenofovir Disoproxil Fumarate†

Tenofovir Alafenamide‡

Tenofovir Alafenamide‡Entecavir

90-91 (<50-60 IU/mL) 93 (<60 U/mL) 90 (<29 IU/mL)

61 (<50-60 IU/mL) 76 (<60 IU/mL) 73 (<29 IU/mL)

Peg-IFN

32-36 22-25

21-22 21 18

81

<1

1

22

68

76

8

68-81

4-5

78-88

0-1 0

59

29-3634-52

2-711 (at 3 years posttreatment)

46 (at 3 years posttreatment)

30-42 (<2,000-40,000 IU/mL)8-14 (<80 IU/mL)

43 (<4,000 IU/mL)19 (<80 IU/mL)

% HBeAg loss

% HBsAg loss

% HBsAg loss

Table 2. Efficacy of Approved First-Line Antiviral Therapies in Adults with Treatment-Naïve Chronic Hepatitis B and Immune-Active Disease (Not Head-to-Head Comparisons)

HBeAg Negative

% HBeAg seroconversion

% HBV-DNA suppression(cutoff to define HBV-DNA suppression)§

% HBV-DNA suppression(cutoff to define HBV-DNA suppression)ll

% Normalization ALT

% Normalization ALT¶

Discontinuation of NA Treatment

EASL CPG HBV. J Hepatol 2017;67:370–98

Long‐term therapy with NAs is usually required: HBV eradication is not usually achieved

Recommendations

NAs should be discontinued • After confirmed HBsAg loss (± anti-HBs seroconversion)

II-2 1

NAs can be discontinued• In HBeAg-positive patients, without cirrhosis, who achieve stable HBeAg

seroconversion and undetectable HBV DNA and complete ≥12 months of consolidation therapyClose post-NA monitoring is warranted

II-2 2

NAs may be discontinued • In selected HBeAg-negative patients, without cirrhosis, who achieve long-term (≥3

years) virological suppression, if close post-NA monitoring can be guaranteedII-2 2


AASLD: HBeAg negative: indefinite therapy; if considering discontinuation in patients with mild disease, discuss risks and defer to center with expertise

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Fewer Relapses With Longer Duration of Consolidation After HBeAg Seroconversion

1. Kuo. Scand J Gastroenterol. 2010;45:75. 2. Dai. J Antimicrob Chemother. 2013;68:2332.

< 12 mos(n = 39)

12‐18 mos(n = 41)

> 18 mos(n = 21)

Duration of ConsolidationMaintained Response

†6 M

os

After Therapy Cessation (%)[2]

< 6 mos(n = 47)

6‐12 mos(n = 46)

> 12 mos(n = 31)

Duration of Consolidation

26

39

71

*No HBeAg seroreversion or HBV DNA increase to > 105 copies/mL. †HBeAg seroconversion and undetectable serum HBV DNA.

Maintained Response* 2 Yrs

After Therapy Cessation (%)[1]

100

80

60

40

20

0

100

80

60

40

20

0

2923

48

Age at HBeAg Seroconversion Predicts Durability of Sustained Response

1. Pan. PLoS One. 2013;8:e68568. 2. Song. World J Gastroenterol. 2012;18:6277.

Group C: > 40 yrs AND < 15 mos consolidation

Group B: ≤ 40 yrs OR ≥ 15 mos consolidation

Group A: ≤ 40 yrs AND ≥ 15 mos consolidation

Mos After Treatment Cessation

Virologic Recurrence

[2]

Group A vs C: P = .014

≤ 37 yrs

> 37 yrs

P = .045

Follow‐up (Mos)

Cumulative Relapse Rate[1]

1.0

0.8

0.6

0.4

0.2

0

0 10 20 30 40 50 0 6 12 18 24 30 36

1.0

0.8

0.6

0.4

0.2

0

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Current Conundrums in Standard of Care

1. Do I treat acute HBV?

Acute HBV• >95% immunocompetent adults recover spontaneously

– Do not routinely treat symptomatic acute HBV– Verify HBsAg loss after 6‐12 months

• Severe Acute Hepatitis B: consider therapy with ETV/TdF or TAF– Tbili >3 mg/dL, INR >1.5, HE or ascites

• LAM studies: improved HBV DNA but no difference in biochemical improvement or HBsAg loss– Hepatic encephalopathy– Serum bilirubin >10.0 mg/dL– INR >1.6

Terrault NA, et al. Hepatology. [online ahead of print February 5, 2018]. doi: 10.1002/hep.29800.

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2. How do I prevent MTCT

2017 TDFLAM, LdT

Second trimester of pregnancy

HBV DNA >2x105 IU/mL, HBsAg levels> 4 logs IU/mL

2018 TDFLAM, LdT

28-32 weeks of gestation

HBV DNA >2×105 IU/mL.

APASL 2015 TDF,LdT

28-32 weeks of gestation

HBV DNA>106–7 IU/mL

Recommendations from Association Guidelines forPreventing HBV MTCT

TDF Preferred

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Algorithm for the Management of Chronic Hepatitis B During Pregnancy

Recommend all infants to receive HBIG and HBV vaccination series

(1st dose of vaccine and HBIG within 12 hours of birth)

Cirrhosis / stage IV fibrosis

or severe hepatitis flareNo

Monitoring without treatment. Test HBV DNA at end of the 2nd trimester

HBV DNA > 200,000 IU/mL, or threatened pre-term labor, or previous child has

immunoprophylaxis failure

Maternal HBV DNA < 200,000

IU/mL

TDF/LAM/LTD at beginning of the

3rd trimester

Monitoring without

treatment

Yes

TDF therapy throughout the entire pregnancy

Consultation: breastfeeding is recommended (Use TDF if

treatment is needed)

TDF, tenofovir-DF; LAM, lamivudine; LTD, telbivudine; HBIG, hepatitis B immunogloburin

No

Give TDF up to delivery (or 1‐3

mos postpartum); 3TC and

telbivudine are alternatives

Terrault. Hepatology. 2018;67:1560. Zhang. Hepatology. 2014;60:468.




3. Role of qHBsAg

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Role of qHBsAg

• HBeAg‐negative patients:

– qHBsAg <1,000 IU/mL and HBV DNA <2,000 IU/mL suggest inactive CHB

– qHBsAg<1,000 IU/mL predicts spontaneous HBsAg clearance

• Predicts treatment response:

– Peg‐IFN: qHBs @ week 12

• HBeAg positive: qHBsAg<1,500 IU/mL 57% for HBeAg seroconversion and 18% for HBsAg loss (no decline high assoc w/ failure)

– NA: HBeAg negative

• >1 log decline in qHBsAg predicted increased loss of HBsAg,

• qHBsAg level<100 IU/mL sustainable off‐treatment response after 3+ years consolidation therapy


Role of qHBsAg

• HBeAg‐negative patients:

– qHBsAg <1,000 IU/mL and HBV DNA <2,000 IU/mL suggest inactive CHB

– qHBsAg<1,000 IU/mL predicts spontaneous HBsAg clearance

• Predicts treatment response:

– Peg‐IFN: qHBs @ week 12

• HBeAg positive: qHBsAg<1,500 IU/mL 57% for HBeAg seroconversion and 18% for HBsAg loss (no decline high assoc w/ failure)

– NA: HBeAg negative

• >1 log decline in qHBsAg predicted increased loss of HBsAg,

• qHBsAg level<100 IU/mL sustainable off‐treatment response after 3+ years consolidation therapy


• HBsAg quantitation can be useful in managing patients receiving peg‐INF therapy.

• HBsAg quantitation is not recommended for the routine testing or follow‐up of patients with CHB

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3. Role of qHBsAg

4. How do I follow patients I don’t have on therapy

Warning:There are a lot of these patients

They get lost to follow‐up

Monitoring Patients Not on Therapy: HBeAg +


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Monitoring Patients Not on Therapy: HBeAg (‐)

• Normal ALT + HBV DNA <2,000 IU/mL– Test ALT +/‐ HBV DNA q3 months for a

year then 6‐12 months

– Check HBsAg status at 6‐12 month intervals

• HBV DNA >2,000 IU/mL + ALT <2x ULN– Assess histology treat if F2

– Treat especially if >40 yo


Monitoring in Other Groups

Monitoring Patients Not on Therapy: HBsAg Loss

• ALT and HBV‐DNA monitoring no longer required

• HCC screening if cirrhosis, FMHx of HCC or long duration of infection (>40 years for men, >50 years for women if infected at young age)

HBV DNA <2,000 IU/mL with elevated ALT

• Evaluate for other liver diseases, especially HDV


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NA-Induced HBsAg Loss is Durable

Kim et al Abstract 0198Implications for clinical practice:: HBsAg loss is a durable and safe endpoint for stopping therapy

50

40

30

20

10

0

0 12 24 36 48 60 72 84

Cumulative Risk of HCC development (%

)

Follow-up duration (months)No. at risk

NUC‐continuation

NUC‐discontinuation

HR=0.53 (95% CI, 0.12–2.23), log‐rank p=0.3850

40

30

20

10

0

0 12 24 36 48 60 72 84

Cumulative

Risk of HBsA

g‐Reversion (%)

145

131

129

121

100

97

62

67

44

51

34

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145

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114

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Follow-up duration (months)

HR=0.45 (95% CI, 0.12–1.76), log‐rank p=0.24

Retrospective analysis of patients who stopped or continued NA after HBsAg loss Evaluated incidence of HBsAg sero‐reversion and HCC

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NA-Induced HBsAg Loss is Durable

Kim et al Abstract 0198Implications for clinical practice:: HBsAg loss is a durable and safe endpoint for stopping therapy

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0 12 24 36 48 60 72 84

Cumulative Risk of HCC development (%

)

Follow-up duration (months)No. at risk

NUC‐continuation

NUC‐discontinuation

HR=0.53 (95% CI, 0.12–2.23), log‐rank p=0.3850

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Cumulative Risk of HBsA

g‐Reversion (%)

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Follow-up duration (months)

HR=0.45 (95% CI, 0.12–1.76), log‐rank p=0.24

Retrospective analysis of patients who stopped or continued NA after HBsAg loss Evaluated incidence of HBsAg sero‐reversion and HCC

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3. Role of qHBsAg

4. How do I follow patients I don’t have on therapy

5. TDF vs ETV

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Overview of TDF vs ETV on HCC incidence in CHB Patients: AASLD 2019

The Future of HBV

• Cure: Elimination of all forms of potentially replicating HBV

• Functional Cure: HBV DNA is not detectable after completion of a finite course of treatment with HBsAg loss and decreased risk of HCC

• Partial Cure: Detectable HBsAg but HBV DNA negative after completion of finite therapy

Liang, et al. Hepatology. 62(6) 2015.

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Gastroenterology 2019 156, 311-324DOI: (10.1053/j.gastro.2018.07.057)

1. Entry and uncoating2. Nucleocapsid transported to nucleus3. Partially ds rcDNA repaired4. cccDNA bound to chromatin5. cccDNA transcribed into pgRNA6. pgRNA reverse transcribed into HBV

DNA and mRNA7. mRNA translated into proteins8. Nucleocapsid assembled in cytoplasm

(pgRNA+ core + polymerase)9. pgRNA reverse transcribed into DNA10. Enveloped and secreted

HBV Life Cycle

Conclusions

• Therapy is recommended for those with chronic hepatitis B (elevated ALT, HBV DNA >2,000 in HBeAg negative and >20,000 IU/mL in HBeAg positive)

• Treatment is also recommended in those at high risk for progression and cancer

• Medications with a high barrier for resistance are recommended as first line therapy

• Regular monitoring for response and adverse events is necessary

• We may start to use the word cure in the discussion of HBV management

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How to Receive CME and ABIM MOC Points

LIVE VIRTUAL GRAND ROUNDS WEBINAR

ACG will send a link to a CME & ABIM MOC evaluation to all attendees on the live webinar.

ABIM Board Certified physicians need to complete their MOC activities by December 31, 2020 in order for the MOC points to count toward any MOC requirements that are due by the end of the year. No MOC credit may be awarded after March 1, 2021 for this activity.

ACG will submit MOC points on the first of each month. Please allow 3-5 business days for your MOC credit to appear on your ABIM account.

ABIM MOC QUESTION

If you plan to claim ABIM MOC Points for this activity, you will be asked to: Please list specific changes you will make in your practice as a result of the information you received from

this activity.

Include specific strategies or changes that you plan to implement.THESE ANSWERS WILL BE REVIEWED.

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Register Now at gi.org/ACGVGR

ACG Virtual Grand Rounds

Join us for upcoming Virtual Grand Rounds!

Week 5: Refractory GERD: New Options for Treatment 2020Philip O. Katz, MD, MACGApril 23, 2020 at Noon EDT

Week 6: Celiac Disease: 10 Things Every Clinician Should Know Amy S. Oxentenko, MD, FACGApril 30, 2020 at Noon EDT

Visit gi.org/ACGVGR to Register

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giondemand.com

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gi.org/COVID19

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receive cme abim moc points · 4/16/2020 6 current standard of care 1. screening for hbv 2. goals...

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