Diagnosis and management of chronic hepatitis b infection(word)
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Transcript of Diagnosis and management of chronic hepatitis b infection(word)
DIAGNOSIS AND MANAGEMENT OF CHRONIC HEPATITIS B INFECTIONPresented by: Dr. Himanshu Rana (JR-3)
Moderated by: Dr. S. K. SonkarMD (Assistant Professor)Screening population
• Individual from high/intermediate prevalence areas• Household contacts• IV drug abusers• Polygamous or H/O STD• Men sex with men• Inmates of correction facilities• Chronically elevated ALT/AST• HCV/HIV +ve • Patients on hemodialysis • Pregnancy• Immunosuppressive therapy
Prevention• Carriers to be counseled for prevention of transmission• HBV negative contacts should receive vaccination• Pregnancy – Tenofovir in 3rd trimester if DNA > 107 IU/ml to reduce transmission*• Newborns to receive HBIg and vaccination at delivery• Post vaccination response testing
– Infants of carrier mothers at 9 to 15 months– Annually for chronic hemodialysis patients
Assessment of HBV positive subjects• Primary care invetigations
– HBeAg/ anti HBeAg – HBV DNA level– Anti HCV– Anti HDV– Anti HIV– IgG HAV– ALT/AST/GGT/serum albumin/ total bilirubin/ PT/ full blood counts
• Secondary care investigations– Transient elastography – Liver biopsy
Goals of treatment• Prevention of long-term negative clinical outcomes (eg, cirrhosis, HCC, death) by durable
suppression of HBV DNA• Remission of liver disease• Primary treatment endpoint
– Sustained decrease in serum HBV DNA level to low or undetectable• Secondary treatment endpoints
– Decreased or normalize serum ALT – Induce HBeAg loss or seroconversion – Induce HBsAg loss or seroconversion – Improve liver histology
Management (adults)
Children and young people• DNA levels >2000 IU/ml / abnormal ALT– liver biopsy*• When to start!!!
– DNA levels >2000 IU/ml / abnormal ALT* or– Significant fibrosis on biopsy
• METAVIR stage ≥ F2 or• Ishak stage ≥ 3
• Fibroscan is not recommended in childrenTreatment sequence**
• Peginterferon α-2a initial treatment in all*• Tenofovir and Entecavir as second line in all*• Prophylaxis to be started before starting immunosuppressive therapy and continue till 3
months after sero-conversion
* Except in pregnancy, breast feeding, decompensated chronic liver disease ** NICE clinical guidelines, The Guidelines Manual, June 2013; 9-10
• Telbivudine & Adefovir not recommended• If already on Adefovir – continue as per treating physician• If already on Telbivudine change to
– Entecavir for -ve h/o lamivudine resistance– Tenofovir for +ve h/o of lamivudine resistance
When to Consider PegIFN ?• Favorable predictors of response[1,2]
Fibroscan
>11kPa
Treatment
6 – 10 kPaBiopsy
< 6 kPa
DNA level >2000 IU/ml*Abnormal ALT levels*
DNA level <2000 IU/ml*Normal ALT levels*Annual follow up
Adults > 30 yrs age
Treatment
Adults < 30 yrs age
Necroinflammation and Fibrosis on biopsy
Treatment
No necroinflammation and Fibrosis on biopsy
Annual follow up
= Biopsy
* 2 consecutive tests conducted 3 months apart
– Low HBV DNA– High ALT– Genotype A or B > C or D[3-5]
• Specific patient demographics[1,2]
– Generally young people– Absence of comorbidities
• Patient preference[1,2] • Concomitant HCV infection
Definition of Response to Antiviral Therapy
Response Definition
Primary nonresponse* ↓ in serum HBV DNA by < 2 log10 IU/mL after ≥ 24 wks of therapy
Biochemical response ↓ in serum ALT to within the normal range
Virologic response↓ in serum HBV DNA to undetectable levels by PCR andloss of HBeAg in patients who were initially HBeAg positive
Virologic relapse↑ in serum HBV DNA of 1 log10 IU/mL after discontinuation of treatment in ≥ 2 determinations > 4 wks apart
Histologic response↓ in histology activity index by ≥ 2 points andno worsening of fibrosis score compared to pretreatment liver biopsy
Complete response Fulfill criteria of biochemical and virologic response and HBsAg loss
First Line therapy
Decompensated liver disease
PegIFN α-2a
24 weeksHBV DNA ↓ by 2 log10 &/orHBsAg > 20,000 IU/ml in HBeAg +ve or HBsAg has not ↓ in HBeAg -veYes No
Stop 1st line Continue for next 24 weeksAssess for HBeAg seroconversion
at 48 weeksStart 2nd line
• Hepatitis B+C co infection → Peg IFN + Ribavirin • Hepatitis B+D co infection → Peg IFN for 48 weeks → Continue treatment & evaluate
response annually(consider stopping treatment if no↓ in HDV RNA after 24 – 48weeks)
Management of Patients With HIV Coinfection• HBV/HIV-coinfected patients who require HBV therapy should be treated[1]
– Liver biopsy should be considered in patients with fluctuating or mildly elevated ALT (1-2 x normal)
Not on HAART or not Anticipated to Antiretroviral Therapy*
Planning Antiretroviral Therapy (HBV+HIV)
Already Receiving Antiretroviral Therapy
Antiviral therapy that does not target HIV, eg: pegIFN or ADV or entacavir
Although telbivudine does not target HIV, should not be used
That are effective against both viruses:( TDF + LAM) 0R (Emtricitabine+TDF) preffered
If regimen does not include drug active against HBV, may be treated with pegIFN, ADV or entacavir.
If LAM resistance, add TDF or adefovir
Children and young people
2 nd line therapy
History of Lamivudine resistance
+ ve - ve
Tenofovir Entecavir
Significant fibrosis or Abnormal ALT
48 weeks of PegIFN α-2a Consider stopping after 24 wks ifHBV DNA ↓ by 2 log10 &/orHBsAg > 20,000 IU/mlHBV DNA
+ ve - ve2nd line Stop
Prophylaxis in immunosupressive therapy
PRE-EXPOSURE PROPHYLAXIS
Recombivax HB Dose (mcg) Engerix-B Dose (mcg)
HBeAg +ve HBeAg –ve
TenofovirFor 48 wks
DNA +veDNA -ve
48 wks
Tenofovir/ Entecavirfor 48 wks
DNA +veH/o Lamivudine resistance +veEntecevir
H/o LamivudineResistance -veLamivudine
Stop treatment 12 months after HBeAg seroconversion
DNA +veConsider swithching
Stop treatment 12 months after HBsAg seroconversion& HBV DNA -ve
CirrhosisContinueindefinite
Non cirrhoticStop after 12 months
HBsAg +ve
HBV DNA > 2000 IU/mlHBV DNA < 2000 IU/ml
Entecavir/Tenofovir < 6 months – Lamivudine*> 6 months – Entecavir/Tenofovir
HBsAg –ve & anti-HBc +ve
Not on Rituximab On Rituximab
Start LamivudineAnti-HBs +ve
Anti-HBs -veDNA < 2000 IU/ml- Lamivudine*DNA > 2000 IU/ml- Entecavir/Tenofovir
No prophylaxis
* Change to tenofovir if HBV DNA +ve after 3 months
Infants and children (<11 years of age) 0.5 ml (5) 0.5 ml (10)
Adolescents 11-19 years 0.5 ml (5) 0.5 ml (10)
Adults >20 years 1.0 ml (10) 1.0 ml (20)
Post-exposure prophylaxsis• Perinatal exposure of infants : single dose of HBIG, 0.5 mL, IM in thigh immediately after
birth, followed by complete course of three injections of recombinant hepatitis B vaccine to be started within first 12 hours of life.
• Direct percutaneous inoculation or transmucosal exposure to HBsAg-positive blood or body fluids : single IM dose of HBIG, 0.06 mL/kg, as soon as possible, followed by complete course of hepatitis B vaccine within the first week.
• For those exposed by sexual contact : single IM dose of HBIG, 0.06 mL/kg, within 14 days of exposure, followed by complete course of hepatitis B vaccine.
Management of Antiviral-Resistant HBV
Treatment Strategy
Lamivudine resistance Add adefovir or tenofovir Stop lamivudine and switch to tenofovir/emtricitabine
Adefovir resistance Add lamivudine
Stop adefovir and switch to tenofovir/emtricitabine Switch to or add entecavir
Entecavir resistance Switch to tenofovir or tenofovir/emtricitabine
Telbivudine resistance Add adefovir or tenofovir Stop telbivudine and switch to tenofovir/emtricitabine
Tenofovir resistance May add entecavir, telbivudine, lamivudine, or emtricitabine
Prevention and Monitoring of Resistance
Prevention
Avoid unnecessary treatment
Initiate potent antiviral that has low rate of drug resistance or use combination therapy
Switch to alternative therapy in patients with primary nonresponse
Monitoring
Test for serum HBV DNA (PCR) every 3-6 mos during tx
Check for medication compliance in patients with virologic breakthrough
Confirm antiviral resistance with genotypic testing
Screening for HCC• High risk to be screened every 6-12 months – USG• AFP is used where USG is not available• HIGH risk subjects
– Asian men over 40 yrs age– Asian women over 50 yrs age– Cirrhotics– Family history of HCC– Africans over 20 yrs age– Any carrier >40 yrs with DNA >2000 IU/ml or intermittent or persistent ALT elevation
Questions1. Which of the following drugs have been suggested as first line therapy as per the EASLD
guidelines 2012 for the management of chronic hepatitis B?a. Tenofovirb. Adefovirc. Interferon alphad. Peg-IFN alpha
ANS: d2. Which of the following drugs is an absolute contraindication for Peg-IFN alpha therapy?
a. Chronic renal failureb. Treated pulmonary tuberculosisc. Ischemic heart diseased. Decompensated liver disease
Ans: d3. Which of the following related to hepatitis B infection is true?
a. Around 99% cases of infection resolve after an episode of acute hepatitisb. Newborn to HBsAg positive mothers develop life threatening fulminant hepatitisc. IgM antiHBc is always negative in acute reactivation of chronic hepatitis B virusd. Patient to be started on immunosuppressive therapy are not required for screening
of Hep B infectionAns: c
4. Which of the following is false?a. Fibroscan measures the stiffness of liver in kilopascals by measuring the shear stress
produced.b. Fibroscan scores of >11kpa are diagnostic of significant fibrosisc. Liver biopsy should be used in patients with score >11kpa for guiding therapy.
d. All patients with chronic hepatitis B related liver disease must be subjected to fibroscan.
Ans: c5. Which of the following is not correct regarding treatment of hepatitis B infection?
a. Tenofovir can be used as 2nd line treatment in all chronic Hep B infection regardless of HBeAg status.
b. First line therapy of IFN alpha should be used in all indicated Heatitis B patients for at least 24 – 48 weeks before switching to 2nd line therapy
c. Tenfovir should be used in patient with history positive for lamivudine resistanced. Ribavirin should be added to Peg IFN alpha in patients with Hepatitis C coinfection as
first line treatment.Ans: b