basic modules for hbv · 2018. 12. 12. · natural history of chronic hepatitis b chronic hepatitis...
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1 |World Health Organization
Western Pacific Region
Basic modules for HBVBasic modules for HBV
2 |World Health Organization
Western Pacific Region
HBV Module 1Hepatitis B serological markers
and virology
HBV Module 1Hepatitis B serological markers
and virology
3 |World Health Organization
Western Pacific RegionWHO guideline 2015
Who is at risk for chronic HBV infection ?Who is at risk for chronic HBV infection ? Age is a key factor in determining the risk of chronic
hepatitis B infection
80‐90% of infants infected during the first year of life
30‐50% of children infected before the age of 6 years
Less than 5% of otherwise healthy persons who are
infected as adults
20‐30% of adults who are chronically infected will
develop cirrhosis and/or liver cancer.
4 |World Health Organization
Western Pacific Region
Who to test for chronic HBV and HCV infectionWho to test for chronic HBV and HCV infection There are several possible approaches to testing for HBV
and HCV infection
General population testing
Focused or targeted testing of specific high‐risk groups
Routine antenatal clinic (ANC) testing
“Birth cohort” testing
Blood donor screening
GUIDELINES ON HEPATITIS B AND C TESTING (WHO 2017) P38‐39
5 |World Health Organization
Western Pacific Region
Initial assessment for chronic hepatitis B and CInitial assessment for chronic hepatitis B and C
HBV HCVChronic infection HBsAg Anti‐HCVAcute infection Anti‐HBc IgM HCV RNA, HCcAg etc.
(without anti‐HCV antibody, excluding other hepatitis viruses)
6 |World Health Organization
Western Pacific Region
Additional assessment for chronic hepatitisAdditional assessment for chronic hepatitis
HBV HCVSerological markers
Anti‐HBs/anti‐HBc antibodiesHBe antigen, Anti‐HBe,
HBV DNA
HCV RNAHCV genotype
Severity Aminotransferase (AST/ALT)Bilirubin, albumin, alkaline phosphatase (ALP)
Staging Liver biopsyNon‐invasive tests
‐APRI, FIB‐4, FibroTest, Transietn elastography
7 |World Health Organization
Western Pacific Region
Serological pattern of chronic HBV infectionSerological pattern of chronic HBV infection
GUIDELINES ON HEPATITIS B AND C TESTING (WHO 2017) P22
8 |World Health Organization
Western Pacific Region
How to test for chronic HBV infectionHow to test for chronic HBV infection(A) Single assay
(HBs seroprevalence ≥0.4%)
(B) Two assays(HBs seroprevalence <0.4%)
GUIDELINES ON HEPATITIS B AND C TESTING (WHO 2017) P53
9 |World Health Organization
Western Pacific Region
HBV Module 2Hepatitis B transmission and
prevention
HBV Module 2Hepatitis B transmission and
prevention
10 |World Health Organization
Western Pacific Region
Transmission routes of HBVTransmission routes of HBV Vertical: Mother to child
Horizontal: Young children, household contacts
Sexual
Health‐care associated
Blood products
Unsafe injections
Medical procedure (i.e. Needle stick injury)
Persons who inject drugs (PWID)
Organs and tissue transplantation
11 |World Health Organization
Western Pacific Region
Prevention of HBV infectionPrevention of HBV infectionVaccination*
Childhood vaccination• Primary 3-dose vaccination• Timely birth dose
High risk groups Catch‐up programs
Other measures Screening of blood and blood products Injection safety Occupational safety Harm reduction interventions Safe sex
* Is the key intervention to prevent chronic HBV infection(occurs following infection during infancy and childhood)
12 |World Health Organization
Western Pacific Region
Infant and neonatal hepatitis B vaccinationInfant and neonatal hepatitis B vaccination Vaccination is the mainstay of Hepatitis B prevention
Infant and neonatal hepatitis B vaccination
The hepatitis B vaccination is the mainstay of
hepatitis B prevention
WHO recommends birth dose (BD) and 3rd dose
(B3) of hepatitis B vaccination
The complete vaccine series induces protective
antibody levels in >95% of infants and children.
13 |World Health Organization
Western Pacific Region
Dose Protection
1 16%‐40%2 80%‐95%3 98%‐100%
Protection* in Infants by HBV Vaccination DoseProtection* in Infants by HBV Vaccination Dose
* Protection defined as anti‐HBs antibody titer of 10 mIU/mL or higherNote: Preterm infants less than 2 kg respond to vaccination less often
14 |World Health Organization
Western Pacific Region
HBV Module 3Natural history of Hepatitis B
HBV Module 3Natural history of Hepatitis B
15 |World Health Organization
Western Pacific Region
Consequences of HBV infectionConsequences of HBV infectionHepatitis B virus infection
Acute infection(short duration: <6 mo)
Chronic infection(duration >6 mo)
Asymptomatic
Acute viral hepatitis
Acute liver failure
Chronic hepatitis B
Cirrhosis: compensated
Cirrhosis: decompensated
16 |World Health Organization
Western Pacific Region
Serological pattern of acute HBV infectionSerological pattern of acute HBV infection
GUIDELINES ON HEPATITIS B AND C TESTING (WHO 2017) P22
17 |World Health Organization
Western Pacific Region
Natural history of chronic hepatitis BNatural history of chronic hepatitis B
Chronic hepatitis B
Immune‐tolerant phase
Immune‐active phase
Immune‐control phase
Reactivation phase
Immune clearance (cure)
18 |World Health Organization
Western Pacific Region
Natural history of chronic hepatitis BNatural history of chronic hepatitis B
Chronic hepatitis B
Immune‐tolerant phase
Immune‐active phase
Immune‐control phase
Reactivation phase
Immune clearance (cure)
Phases that need anti‐viral drug treatment
Phases that DO NOT need anti‐viral drug treatment
Cirrhosis with any of the phases
19 |World Health Organization
Western Pacific Region
Infection persistent
HBe(+) chronic hepatitis HBsAg (+), Anti‐HBc (+)
HBeAg (+), HBV DNA highALT high
HBe(‐) chronic hepatitis HBsAg (+), Anti‐HBc (+)
HBeAg (‐), HBV DNA low(‐high)ALT normal‐high
Inactive carrierHBsAg (+), Anti‐HBc (+)
HBeAg (‐), HBV DNA (‐)‐lowALT normal
Liver cirrhosis
Liver failureLiver cancer
Death
Clinical clearanceHBsAg (‐), Anti‐HBs (‐)
Anti‐HBc (+), HBV DNA (‐)ALT normal
Natural history of HBV infection (chronic phase)Natural history of HBV infection (chronic phase)
20 |World Health Organization
Western Pacific Region
Serological pattern of chronic HBV infectionSerological pattern of chronic HBV infection
GUIDELINES ON HEPATITIS B AND C TESTING (WHO 2017) P22
21 |World Health Organization
Western Pacific Region
HBV Module 4Assessment of liver fibrosis
HBV Module 4Assessment of liver fibrosis
22 |World Health Organization
Western Pacific Region
Fibroscan®(http.myliverexam.com/en/lexamen‐fibroscan.html)
AST; aspartate aminotransferase ALT; alanine aminotransferaseAPRI; aspartate aminotransferase‐to‐platelet ratio indexFIB‐4; fibrosis‐4 score
Assessing the degree of liver fibrosisAssessing the degree of liver fibrosis Non‐invasive tests
Components Requirements Cost
APRI AST, platelets Simple serum andhematology test +
FIB‐4 Age, AST, ALT, Platelets
FibroTest gGT, haptoglobin, bilirubin,A1apoprotein, α2‐macroglobulin
Specialized tests atdesigned laboratories ++
Fibroscan ® Transient elastography Dedicated equipment +++
GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION (WHO 2015)
23 |World Health Organization
Western Pacific Region
Transient elastography (Fibroscan)Transient elastography (Fibroscan)
24 |World Health Organization
Western Pacific Region
Transient elastography (Fibroscan)Transient elastography (Fibroscan)
Transducer sends a mechanical shearwave
Large explored volume(at least 100 times more than biopsy)
Monitor display of Fibroscan
25 |World Health Organization
Western Pacific Region
FibroscanFibroscan
Advantages Easy, non‐invasive Can be done in outpatient or community settings Takes <10 minutes to perform Health‐care staff can be easily trained
Limiting factors High cost of equipment Equipment needs regular maintenance/calibration by trained
personnel No universal cut‐off values for specific stages of fibrosis Difficult to measure in very obese
26 |World Health Organization
Western Pacific Region
The Child‐Turcotte‐Pugh Classification systemThe Child‐Turcotte‐Pugh Classification systemPoints 1 2 3
Encephalopathy None Minimal(grade1 or 2)
Advanced(grade 3 or 4)
Ascites Absent Controlled Refractory
Total bilirubin(μmol/L)(mg/dL)
<34 (<2) 34‐51 (2‐3) >51 (>3)
Albumin(g/dL) >3.5 2.8‐3.5 <2.8
Prothrombin time (seconds) or PT‐INR*
<4 or <1.7 4‐6 or 1.7‐2.3 >6 or >2.3
Child‐Pugh Class A: 5‐6 pointsChild‐Pugh Class B: 7‐9 pointsChild‐Pugh Class C: 10‐15 points
*PT‐INR ; prothrombin time international normalized ratio
27 |World Health Organization
Western Pacific Region
HBV Module 5Treatment for Chronic Hepatitis B
HBV Module 5Treatment for Chronic Hepatitis B
28 |World Health Organization
Western Pacific Region
WHO guidelinesWHO guidelines
Assessment for treatment
Monitoring
Stopping treatment
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Western Pacific Region
Why should we treat HBV infectionWhy should we treat HBV infection Delay the progression of cirrhosis (Improve liver fibrosis)
Reduce the incidence of hepatocellular carcinoma
↓
Improve long‐term survival and QOL
Key outcomes
Sustained ALT normalization
Sustained undetectable HBV DNA
HBeAg seroconversion / HBsAg seroconversion
Reversion of fibrosis stage
GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION (WHO 2015)
30 |World Health Organization
Western Pacific Region
1. Natural history of HBV infection
2. Clinical assessment of persons with chronic hepatitis B
3. Why to treat for HBV
4. Who to treat for HBV
5. How to treat for HBV
6. How to monitor during treatment for HBV
7. When to stop treatment for HBV
Clinical management of HCV infectionClinical management of HCV infection
31 |World Health Organization
Western Pacific Region
Which patients should we treat for HBVWhich patients should we treat for HBV
GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION (WHO 2015) P36‐37
Optimal timing of treatment for HBV is still debated.
HBV HCV• Cirrhosis• High risk of disease progression to
cirrhosis and hepatocellular carcinoma, such as…
Older than 30 years Persistently abnormal ALT levels High level HBV replication
• All patients
32 |World Health Organization
Western Pacific Region
Populaiton
HBsAg‐
Non cirrhotic patients aged <30
Normal(<19 F, <30 M)
<2,000
Treatment Deferred
HBsAg+
Non cirrhotic patients aged >30
Fluctuating
2,000‐20,000
Treatment Deferred
Cirrhotic patients or APRI >2
Persistently elevated
>20,000
Treatment Deferred
Treatment Deferred
Treatment Deferred
Treatment Recommended
Treatment Recommended
CIRRHOSIS
No Treatment Required
Summary of WHO Recommendation Summary of WHO Recommendation ALT HBV DNAHBsAg
33 |World Health Organization
Western Pacific Region
1. Natural history of HBV infection
2. Clinical assessment of persons with chronic hepatitis B
3. Why to treat for HBV
4. Who to treat for HBV
5. How to treat for HBV
6. How to monitor during treatment for HBV
7. When to stop treatment for HBV
Clinical management of HBV infectionClinical management of HBV infection
34 |World Health Organization
Western Pacific Region
How to treat HBV infectionHow to treat HBV infection Antiviral agents
Interferon (IFN), Pegylated (PEG) ‐IFN
Nucleos(t)ide analogue (NA) ‐ Tenofovir, Entecavir
Lifelong treatment is generally required
Clearance of HBsAg (=Cure) is rare
High rate recurrence in treatment discontinuation
Optimal timing of discontinuation remains unclear
Patient’s motivation is essential
GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION (WHO 2015)
35 |World Health Organization
Western Pacific Region
Antiviral agents for HBVAntiviral agents for HBVAntiviral agent Potency against
HBV Resistance barrier Antivity against HIV Cost
Interferons Moderate Not applicable Moderate High
Tenofovir High High HighLow (high in HongKong and other Asian countries)
Entecavir High High Weak High
Emtricitabine Moderate Low High Low
Telbivudine High Low Unclear High
Lamivudine Moderate‐high Low High Low
Adefovir Low Moderate None(at 10mg dose) High
GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION (WHO 2015) P21
36 |World Health Organization
Western Pacific Region
WHO recommendation: choice of drugWHO recommendation: choice of drug
GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION (WHO 2015)
In all adults, adolescents and children aged 12 years or older in whom antiviral therapy is indicated, the nucleos(t)ide analogues which have a high barrier to drug resistance (tenofovir or entecavir) are recommended.
Entecavir is recommended in children
37 |World Health Organization
Western Pacific Region
Drug doseDrug dose Adults Entecavir 0.5 mg/day oral
Tenofovir 300 mg/day oral
Children need dose modification
38 |World Health Organization
Western Pacific Region
HBV Module 6Monitoring for Chronic Hepatitis B
HBV Module 6Monitoring for Chronic Hepatitis B
39 |World Health Organization
Western Pacific Region
Need for monitoringNeed for monitoring
All need monitoring (irrespective of need for treatment)
HBsAg +ve
Defertreatment
Notreatment
Starttreatment
40 |World Health Organization
Western Pacific Region
Who should we monitor and whyWho should we monitor and why
All patients with chronic HBV and HCV infection
More frequent monitoring is recommended for:
Persons who do not yet meet the criteria for treatment
Persons on treatment or following treatment cessation
Monitoring is essential to confirm
Adherence, toxicities
Treatment effect ‐ ALT, HBsAg, HBeAg, HBV DNA
Hepatocellular carcinoma – Ultrasound and AFP testing
GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION (WHO 2015) P64
41 |World Health Organization
Western Pacific Region
How to monitor?How to monitor?
42 |World Health Organization
Western Pacific Region
How to monitor?How to monitor? At least annually: ALT
HBsAg, HBeAg, HBV DNA levelAPRIAdherence to treatmentDrug adverse events (renal function)
More frequent In those who do not clearly meet criteria for treatment Following treatment discontinuation
Surveillance for hepatocellular cancer
43 |World Health Organization
Western Pacific Region
How to monitor HBV infected patientsHow to monitor HBV infected patients: every 12 mos
Disease progression/ treatment response
: every 12 monthsMonitoring for
treatment toxicities
: every 6 monthsDetection of liver cancer(cirrhosis / family history)
Adherence Renal function Ultrasound
ALT, HBV DNA, HBeAg Risk factors for renal dysfunction α‐fetoprotein
Non‐invasive test
Baseline 6month 12month 18month 24month…
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