HBV 2010

HBV 2010AMCOLIAN ALUMNI : 

HBV 2010AMCOLIAN ALUMNI TARGET AUDIENCE 20 GASTROENTEROLOGIST

HBV 2010AMCOLIAN ALUMNI : 

HBV 2010AMCOLIAN ALUMNI TARGET AUDIENCE 50 CONSULTANTS

HBV 2010AMCOLIAN ALUMNI : 

HBV 2010AMCOLIAN ALUMNI TARGET AUDIENCE 100 POST GRADUATE STUDENTS

HBV 2010AMCOLIAN ALUMNI : 

HBV 2010AMCOLIAN ALUMNI TARGET AUDIENCE 400 UNDER GRADUATE STUDENTS

MAJORITY IS AUTHORITY : 

MAJORITY IS AUTHORITY

HBV 2010AMCOLIAN ALUMNI : 

HBV 2010AMCOLIAN ALUMNI FACTS THAT SHOULD BE KNOWN TO GENERAL PHYSICIANS AND UNDER GRADUATE STUDENTS PROF DR GHIAS UN NABI TAYYAB FRCP, FCPS, FACG

Hepatitis B Dane particle : 

05/02/2009 Hepatitis B Dane particle HBsAg HBcAg HBeAg ds DNA Polymerase

Spectrum of Disease : 

Spectrum of Disease Acute HBV infection 90% neonates 25–30% children <10% adults Progressive chronic hepatitis Cirrhosis HCC Death Decompensated cirrhosis Inactivecarrier state EASL Consensus Guidelines. J Hepatol 2003;Lok, McMahon. Hepatology 2004 (AASLD Guidelines) Chronic infection 15–40% Fulminant hepatic failure ~2%

Symptoms and Sequelae of Chronic Infection : 

Symptoms and Sequelae of Chronic Infection During chronic infection: elevation of serum ALT levels cirrhosis: cannot be cured, but progress can be stopped if active replication is considerably reduced compensated cirrhosis: liver cirrhosis but residual liver function decompensated cirrhosis: considerable reduction in liver function HCC – HBV is the leading cause of HCC worldwide death: severe liver damage resulting in liver failure Hoofnagle, di Bisceglie. N Engl J Med 1997

Slide 10: 

< < > > HBeAg +ve HBeAg -ve/ anti-HBe +ve ALT HBV-DNA Normal/ mild CH Moderate/severe CH Moderate/severe CH Normal/mild CH Cirrhosis Inactive-carrier state HBeAg –ve CHB HBeAg +ve CHB Immune tolerance Immune clearance Low replicative phase Reactivation phase Cirrhosis 109–1010 cp/mL 107–108 cp/mL <105 cp/mL >105 cp/mL Inactive cirrhosis Stages of Chronic Hepatitis B (CHB) Infection Adapted from Fattovich. Sem Liver Dis 2003

Slide 11: 

Immune escape < < > > HBeAg+ve HBeAg–ve ALT HBV-DNA Inactive (carrier) state HBeAg –ve active chronic hepatitis HBeAg +ve chronic hepatitis Immune tolerance Immune clearance Immune control Characteristic phases of CHB infection

Natural History of HBV: Development of HBeAg-negative CHB : 

HBeAg-positive HBeAg-negative/ anti-HBe-positive Natural History of HBV: Development of HBeAg-negative CHB Brunetto. J Hepatol 1991

Diagnosis of HBV Infection: Using Serum Markers : 

Infection Replication Three steps of serological diagnosis Diseaseactivity Serum markers HBsAg, anti-HBc, anti-HBe HBeAg, HBV DNA ALT 1 2 3 Diagnosis of HBV Infection: Using Serum Markers

Slide 14: 

monitor monitor Who should be considered for treatment?

Spectrum of Disease : 

Spectrum of Disease Acute HBV infection 90% neonates 25–30% children <10% adults Progressive chronic hepatitis Cirrhosis HCC Death Decompensated cirrhosis Inactivecarrier state EASL Consensus Guidelines. J Hepatol 2003;Lok, McMahon. Hepatology 2004 (AASLD Guidelines) Chronic infection 15–40% Fulminant hepatic failure ~2%

HBV is a Dynamic Disease : 

HBV is a Dynamic Disease

Treatment Options : 

Treatment Options

Conventional Quackery : 

Conventional Quackery

State Sponsored Quackery : 

State Sponsored Quackery Prime Minister HBV Control Program

Medical Quackery : 

Medical Quackery Placebo drugs in the absence of monitoring Or A proper understanding of Natural history of CHB

What happens in the absence of a proper intervention : 

What happens in the absence of a proper intervention

In about 10 -15 years : 

In about 10 -15 years CHRONIC HBV INFECTION

ORAT TIMES : 

ORAT TIMES

& in 20-30 years time : 

& in 20-30 years time Hepatocellular Carcinoma

WHAT ARE OUR TARGETS? : 

WHAT ARE OUR TARGETS?

HBsAg seroconversion: the‛champion’ among clinical endpoints : 

HBV DNA Suppression HBeAg Seroconversion HBsAg Seroconversion 1 3 2 HBsAg seroconversion: the‛champion’ among clinical endpoints THREE TARGETS OF ANTI VIRAL TREATMENT IN CHB

WHAT IS IDEAL? : 

WHAT IS IDEAL?

WHAT IS IDEAL? : 

WHAT IS IDEAL? HBsAg seroconversion

WHAT IS IDEAL? : 

WHAT IS IDEAL? HBsAg seroconversion Success is there!

WHAT IS IDEAL? : 

WHAT IS IDEAL? HBsAg seroconversion Success is there! Though limited

What is achievable in most of patients? : 

What is achievable in most of patients?

Slide 32: 

HBV DNA Suppression HBeAg Seroconversion HBsAg Seroconversion 1 3 2 THREE TARGETS OF ANTI VIRAL TREATMENT IN CHB

Secondary end points of interventions in CHB : 

Secondary end points of interventions in CHB

Secondary end points of interventions in CHB : 

Secondary end points of interventions in CHB Normalization of ALT Reduction of Fibrosis ? Risk reduction of HCCA

We have yet to learn a lot : 

We have yet to learn a lot

Educate your patient : 

Educate your patient Natural history Life style Protection from Hep E and Hep A Diet Drugs Alcohol Family vaccination

Goals of HBV Therapy : 

Goals of HBV Therapy

Primary Goal of Hepatitis B Therapy: Preventing Cirrhosis, HCC, and Death : 

Primary Goal of Hepatitis B Therapy: Preventing Cirrhosis, HCC, and Death Prolonged viral suppression is associated with Reduction in necroinflammation, fibrosis, and cirrhosis Reduction in decompensation Reduction in rates of HCC Reduction in mortality Durable Suppression of HBV Replication Impact of viral suppression on liver disease outcomes

Who to Treat : 

Who to Treat

Who Should Be Treated? : 

Who Should Be Treated? Not a question of who to treat but when: treat now or monitor and treat later when indicated All HBV carriers are potential treatment candidates A patient who is not a treatment candidate now can be a treatment candidate in the future Changes in HBV replication status and/or activity/stage of liver disease Availability of new and better treatments

What to Treat With : 

What to Treat With

Therapy for Chronic Hepatitis B: 2009 : 

1992 2009 and beyond… IFN alfa ADV LdT 1998 2002 2005 ETV PegIFN alfa-2a TDF Clevudine* Combination Rx? 2006 Therapy for Chronic Hepatitis B: 2009 *not FDA approved for the treatment of HBV

What to Treat With : 

Decision to treat IFN (PegIFN alfa-2a) Nucleos(t)ide analogues What to Treat With

Advantages and Disadvantages of PegIFN : 

Advantages and Disadvantages of PegIFN

Advantages and Disadvantages of Nucs : 

Advantages and Disadvantages of Nucs

How should our patients be treated? : 

How should our patients be treated? Benefits Risks Patient’s age and preference Timing? HBV genotype ? Co-morbid illness Costs? Likelihood of sustained response Severity of liver disease Side effects Drug resistance Balancing the facts

Proper Patient Selection Is Key : 

3/21/02 PegIFN best in the following patient groups Younger than 60 years of age and otherwise healthy Baseline HBV DNA ≤109 copies/mL Baseline ALT > 2-3 x ULN HBV genotype A or B Absence of cirrhosis Nucleos(t)ide analogue best in the following patient groups Adult of any age Baseline HBV DNA ≥ 2 x 108 IU/mL Baseline ALT > 5 x ULN Any HBV genotype Cirrhosis with or without decompensation HBsAg(+) chemotherapy patient Proper Patient Selection Is Key Perrillo RP. Hepatology. 2006;43:S182-S193.

Criteria to Guide Choice of Therapy : 

Criteria to Guide Choice of Therapy Anticipated duration of therapy Resistance profile important for oral agents Long-term treatment needed if HBeAg negative Baseline viral load Seroconversion unlikely with IFN if HBV DNA >108 Genotype Superior response to PEG IFN with genotype A Histology PEG IFN to be avoided in cirrhotic patients

Criteria to Guide Choice of Therapy : 

Criteria to Guide Choice of Therapy IFN vs PEGIFN PEGIFN preferred. 7 vs 1 injection/week If non-affording for PEGIFN,use IFN Lamivudine Should no longer be used as a single agent Adefovir Once tenofovir becomes available,it will no longer be used Telbivudine Strong viral suppressant but intermediate resistance rate(approx.22% at 2yrs).Should only be used with the road-map concept. Entecavir,Tenofovir Drugs of first choice as a single agent therapy

Management of HBV during pregnancy : 

Management of HBV during pregnancy

Pregnancy Category of FDA-Approved Treatments for Chronic HBV : 

Pregnancy Category of FDA-Approved Treatments for Chronic HBV Drugs [package insert].

Slide 52: 

FDA Classification of Drug Safety During Pregnancy FDA. Available at: http://www.fda.gov/fdac/features/2001/301_preg.html. Accessed October 20, 2008.

Recommendations for HBV-Infected Women Who Desire Pregnancy : 

Recommendations for HBV-Infected Women Who Desire Pregnancy Women with mild liver disease, low viremia Pregnancy before treatment Women with moderate liver disease, no cirrhosis Treatment before pregnancy; if response, stop treatment before pregnancy Women with advanced liver disease Treatment before and during pregnancy; continue treatment after delivery Women with mild liver disease, very high viremia Treatment in last trimester with “B” category drug Wedemeyer H, et al. Dtsch Med Wochenschr. 2007;132:1775-1782. EASL Clinical Practice Guidelines. J Hepatol. In press.

Thank You : 

Thank You