Discussion HBV Flare AWACC 2009. Pathogenesis of HBV CLDx Hepatic damage predominantly immune...

DiscussionDiscussion

HBV FlareHBV Flare

AWACC 2009AWACC 2009

Pathogenesis of HBV CLDxPathogenesis of HBV CLDx

Hepatic damage Hepatic damage predominantly predominantly immune mediated - cytotoxic T cellsimmune mediated - cytotoxic T cells

HBV specific peptides presented on HBV specific peptides presented on the infected liver cell surface the infected liver cell surface recognized by Ag specific CD8 T cells recognized by Ag specific CD8 T cells hepatocellular inflammation and hepatocellular inflammation and necrosis. necrosis.


Natural history in face of HIV:Natural history in face of HIV:

Higher rates of hepatitis HBeAg Higher rates of hepatitis HBeAg positivitypositivity

Higher levels of HBV DNAHigher levels of HBV DNA

Lower ALT levelsLower ALT levels

Reduced necroinflammatory Reduced necroinflammatory activity on histologyactivity on histology

More rapid progression of liver More rapid progression of liver disease.disease.


Definition of HBV IRISDefinition of HBV IRISRapid worsening of LFTRapid worsening of LFT

Soon after commencement of HAARTSoon after commencement of HAART

Evidence of immune reconstitution (decrease Evidence of immune reconstitution (decrease VL, increase CD4 count)VL, increase CD4 count)

Absence of alternate explanation:Absence of alternate explanation:– Hepatotoxic effects of treatmentHepatotoxic effects of treatment– Withdrawal of HBV active agentWithdrawal of HBV active agent– Resistance of HBV to HBV active agentResistance of HBV to HBV active agent– Superimposed, unrelated acute liver disease Superimposed, unrelated acute liver disease


HBV IRISHBV IRIS

Immune reconstitution is a Immune reconstitution is a “double-edged sword” in “double-edged sword” in patients infected with HBV. patients infected with HBV. – Hepatocyte injuryHepatocyte injury– Viral clearance.Viral clearance.


Chronic Asymptomatic HBV infectionChronic Asymptomatic HBV infectionIs a result of a fine balance between viral Is a result of a fine balance between viral replication and intensity of immune response to replication and intensity of immune response to virusvirus

Acute Flare

Due to alteration in balance:Treatment interruption / withdrawal

HBV resistance to treatment

Immune reconstitution (favorable)AWACC 2009AWACC 2009

How to prevent How to prevent flaresflares

Know HBV status !Know HBV status !


How to prevent flaresHow to prevent flaresControl active HBV replication.Control active HBV replication.

The most prudent approach would The most prudent approach would be combination of 3TC &TDF: be combination of 3TC &TDF:

More effective at reducing HBV VL More effective at reducing HBV VL

↓ ↓ risk of HBV drug risk of HBV drug ΩΩ (50% - 2 yrs, 90% - (50% - 2 yrs, 90% - 4 yrs)4 yrs)

Particular care with significant Particular care with significant underlying liver diseaseunderlying liver disease. .


Take Home MessageTake Home Message

Cannot Cannot commencecommence HAART without the HAART without the knowledge of your patients HBV statusknowledge of your patients HBV status

Cannot Cannot withdrawalwithdrawal HAART without knowledge HAART without knowledge of your patients HBV status.of your patients HBV status.

Must be aware of the dual purposes of Must be aware of the dual purposes of lamivudine, tenofovir, and emtricitabinelamivudine, tenofovir, and emtricitabine

If suspect underlying liver disease then need If suspect underlying liver disease then need to evaluate patient furtherto evaluate patient further


Discussion HBV Flare AWACC 2009. Pathogenesis of HBV CLDx Hepatic damage predominantly immune...

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