HBsAg seroclearance in NA-treated patients

International Symposium on Hepatology 2017 & 30th Annual Scientific Meeting

Dr Grace Lai-Hung WongMBChB (Hons, CUHK), MD (CUHK), MRCP, FHKCP, FHKAM (Medicine)

Professor, Institute of Digestive DiseaseThe Chinese University of Hong Kong

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Disclosures

• Advisory committee member: Gilead

• Speaker: AbbVie, Bristol-Myers Squibb, Echosens & Furui, Gilead, Janssen, Roche

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CAN CHRONIC HEPATITIS B BE CURED?

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Cure of chronic hepatitis B• Functional cure

– HBsAg seroclearance +/-seroconversion• Absolute or complete cure

– Absence of cccDNA

Liu et al.Gut 2014. Block et al.Antiviral Res 2013.

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HBV DNA vs. HBsAg

HBV-DNA(virions)

HBV replication

qHBsAgvirions + defective particles

cccDNA transcription/mRNA translation

Chan HL et al., J Hepatol. 2011;55:1121-31.

HBV replication

Serum HBV DNA: a marker of

HBV replication

Serum HBsAg: a marker of transcriptionally

active cccDNA*HKASLD HKASLD

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HBsAg seroclearance Treatment goal of chronic hepatitis B

APASL 2016, EASL 2017, AASLD 2016Yuen MF, et al. Gastroenterology 2008

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Benefits of HBsAg seroclearance

• p Hepatic decompensation

• p HCC

• n Survival

• p Levels of cccDNA

• As close to cure as we can expect to achieve in

chronic hepatitis B

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HBsAg seroclearance – what’s new

1. Durability of HBsAg seroclearance

2. Risk factors of HCC after HBsAg seroclearance

3. Management of CHB patients with HBsAg

seroclearance

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DURABILITY OF HBSAG SEROCLEARANCE

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Durability of HBsAg seroclearance in untreated and NA-treated patients

Yip TC, Wong GL, et al. J Hepatology 2017 (in press)HKASLD HKASLD

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Both spontaneous and NA-induced HBsAg seroclearance are durable

5-year cumulative rate of HBsAg seroclearance:

spontaneous 88.1%NA-induced 92.2%

log-rank test, P=0.964

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Presence of anti-HBs increases durability of spontaneous HBsAg seroclearance, but not NA-induced one

Yip TC, Wong GL, et al. J Hepatology 2017 (in press)

Spontaneous NA-induced

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None of patients who had received consolidation therapy for 12 months or more developed HBsAg seroreversion

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Summary

• NA-induced HBsAg seroclearance is as durable as that

occurs spontaneously.

• HBsAg seroconversion, i.e. the presence of anti-HBs is

not essential for maintaining HBsAg seroclearance after

NA treatment.

• Consolidation therapy for 12 months or more may

minimize the risk of HBsAg seroreversion.

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RISK FACTORS OF HCC AFTER

HBSAG SEROCLEARANCE

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HK data – 1,680 patients in ETV/TDFBaseline HBsAg level and HCC

Cirrhosis No Cirrhosis

N = 415P = 0.933

N = 1,265P = 0.08

The were a trend that baseline HBsAg level predicts HCC in non-cirrhotic patients.

Wong GL, et al. Gastroenterology 2013;144:933-44.HKASLD HKASLD

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HBsAg level in HCC risk score

Yang HI, et al. Clin Gastroenterol Hepatol. 2016;14:461-468.e2.HKASLD HKASLD

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HBsAg seroclearance in patients on NAs

Original cohort: 110 HBsAg seroclearance; 5299 controlsPropensity score matching: 93 HBsAg seroclearance; 372 controls

Kim et al. Gut 2014;63:1325Wong VW et al. Gastroenterology 2014;147:1435

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Yip TC,……Wong GL. J Hepatology 2017 Nov;67(5):902-908.HKASLD HKASLD

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Age and gender on HCC development

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Cox proportional hazard model

Model Variable Univariate analysis Multivariate analysis

HR 95% CI P HR 95% CI P

1 Age>50 4.49 1.79-11.27 0.001 4.31 1.71-10.84 0.002

Male 2.59 1.30-2.15 0.007 2.47 1.24-4.91 0.01

2 Age (per yr) 1.04 1.02-1.07 <0.001 1.05 1.02-1.07 <0.001

Male 2.59 1.30-2.15 0.007 2.55 1.28-5.07 0.007

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3 risk levels of HCC after HBsAg seroclearance

Highest riskMale > 50

Intermediate riskDĂůĞ�чϱϬFemale >50

Lowest (no) risk&ĞŵĂůĞ�чϱϬ

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Summary – age and gender on HCC risk after HBsAg seroclearance

• Cumulative risk of HCC development after HBsAg

seroclearance = 1.5% in 5 years

• Age >50 years and male gender are independent risk

factors for HCC

• Male patients who clear HBsAg at age >50 years have

significant risk of HCC (2.5% in 5 years)

• Female patients who clear HBsAg before age of 50 have

very low risk of HCC (0% in 5 years)

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DM increases HCC risks Good glycemic control reduces HCC risk

Yip TC,……Wong GL. APDW 2017

DM on HCC risk after HBsAg seroclearance

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MANAGEMENT OF PATIENTS WITH

HBSAG SEROCLEARANCE

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Monitoring of patients with HBsAg seroclearance

• In general, no need further evaluation

• In case of suspicion of liver disease (e.g. elevated ALT level or

suspicion of liver cirrhosis)

– Check anti-HBc ± HBV DNA

– Exclude other liver diseases (e.g. co-infection with HCV, alcohol, NAFLD)

• If detectable HBV DNA (usually low titre)

– Yearly LFT and HBV DNA

– Fibroscan to exclude cirrhosis (esp. if age >50)

– Antiviral if HBV DNA +ve AND cirrhosis

– HCC screening not essential unless the patient is cirrhotic or had HBsAg

seroclearance in males after the age of 50HKASLD HKASLD

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HBsAg seroclearance – can it be occult HBV infection?

• HBsAg negative

• Detection of HBV DNA in the serum or the liver

• Anti-HBs and anti-HBc may be positive or negative

• In real life, anti-HBc is often the marker for possible occult

HBV infection

Raimondo et al. J Hepatol 2008;49:652HKASLD HKASLD

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Immunosuppressants and risk of reactivation of occult HBV infectionAgent Risk (%)

B cell-depleting agents (e.g. rituximab) >10

TNF-ɲ inhibitors (e.g. infliximab) 1

Tyrosine kinase inhibitors (e.g. imatinib) 1

Doxorubicin and epirubicin 1-10

Azathioprine, 6-MP, methotrexate <<1

Systemic corticosteroids

Moderate to high dose >4 weeks 1-10

Moderate to high dose <1 week <<1

Low dose >4 weeks <1

Perrillo et al. Gastroenterology 2015;148:221

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Conclusions• HBsAg seroclearance is as durable

– ~90% in 5 years

– NA-induced ~ spontaneous

• In NA-induced HBsAg seroclearance, presence of

anti-HBs does not affect durability.

• Females of age <50 would be of minimal risk of HCC

after HBsAg seroclearance.

• Good glycemic control in DM patients reduces HCC risk

after HBsAg seroclearance. HKASLD HKASLD

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Database team, Institute of Digestive Disease, CUHK

Thank you for your attention!

Grace Lai-Hung WongInstitute of Digestive DiseaseThe Chinese University of Hong KongE-mail: wonglaihung@cuhk.edu.hk

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HBsAg seroclearance in NA-treated patients · HBV-DNA (virions) HBV replication. q. HBsAg virions +...

Transcript of HBsAg seroclearance in NA-treated patients · HBV-DNA (virions) HBV replication. q. HBsAg virions +...

HBsAg seroclearance in NA-treated patients · HBV-DNA (virions) HBV replication. q. HBsAg virions +...

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Transcript of HBsAg seroclearance in NA-treated patients · HBV-DNA (virions) HBV replication. q. HBsAg virions +...

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