MANAGEMENT OF BLOOD- BORNE VIRAL HEPATITIS

ANNABELLE D MARIE101303061

B27 F1

DIAGNOSIS

Serological Marker Interpretation

HBsAg General marker of infection

HBsAb Document recovery and or immunity to HBV

anti-HBcIgM marker of acute infection

HBeAg active replication of virus and infectiveness

Anti- Hbe virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV

HBV-DNAindicates active replication of virus more accurate than HBeAg especially in cases of escape mutants. Used for monitoring response to therapy

Role of HBV DNA

• Not used for diagnostic purposes, but for when we're planning to start the treatment.

• Useful for monitoring response to treatment

• Other tests:

• - LFT

• - Baseline investigations

So far, ok?

Principles of treatment

• Acute hepatitis B infection does not usually require treatment..

• Early antiviral treatment may be required in <1% of patients whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised

• Chronically infected individuals with persistently elevated serum ALT and HBV DNA levels are candidates for therapy to reduce risk of cirrhosis, liver cancer (20-30yrs to develop) and liver failure.

Phases of chronic Hepatitis B infection

Immunotolerant phase

viral loads are high and transmission is commonpoor immune response (normal liver enzyme)near normal liverrisk of developing viral resistance outweigh any benefits of early therapy

Immunoactive phase

Immune response engages with the virushigh level viral replicationliver inflammationserum transaminases increase, often to more than 2 times upper limit of normalrapidly progresses to cirrhosis and liver cancerTreatment is beneficial

ImmunosurveillanceA heterogenous group of patientsdiffering risk of disease reactivation and progressionin some patients, prolonged quiescent period with very low risk of disease progression. In others, more active HbeAg negative disease characterised by fluctuating viraemia and LFTsFor patients who develop abnormal LFT or have higher viral loads, a liver biopsy and then consider treatment options

Name 3 drugs used to treat Hep B?

• Immunomodulators: Interferon alpha and pegylated interferon- Intron A

• L-nucleoside analogues Lamivudine - Epivir HBV, Telbivudine

• Nucleotide analogues- Adefovir dipivoxil- Hepsera, Tenofovir disoproxil fumarate.

• Cyclopentanes- Entecavir*

Indications for therapy

• ALT>2 times upper limit of normal

• HBeAg positive

• HBV DNA titre of at least 10 000copies/mL

• Documentation of severity of inflammation and fibrosis (not mandatory)

Interferons

1st line for HBeAg+ve pt

When there is an active inflammatory response that can be augmented by cytokine therapyPt with low viral load and ALT>2x upper limitActs by augmenting the native immune response

Adv: No resistance developsDisad: weekly subcutaneous injection, flu like symptomsS/E: fatigue, depression, irritability, bone marrow suppression, thyroid disease

Response: 35% lose e antigen after 4-6 months of treatment.

Lamivudine

Nucleoside analogueInhibits DNA polymerase (reverse transcriptase) and suppresses HBV DNA levelsCan improve liver function in patients with decompensated cirrhosis and may prevent need for transplantDisadv: YMDD variants- DNA polymerase mutants form after 9 monthslong term use is associated with high rate of resistance (70-80%) after 4-5 years

Response: loss of 23% HBeAg at end of 1 year

Adefovir

Nucleotide analogue. Inhibts DNA PolymeraseReduces HBeAg by 3-4 logs, enhances seroconversion and leads to histo improvementUseful in lamivudine resistant patients and patients in immmunoescape phase (HBeAg negative)Resistant rates lower than with lamivudine (only 2%) at 2 years but increase to 18% at 3yrs, 29% at 5yrsRelapse on stopping medication

Entacavir

D.O.C in adultsMore effective than lamivudine and adefovir in reducing viral loadHigh barrier to resistance (<1%)Resistance requires mutations at more than one site within the HBV polymerase geneResistance rates are very high in patients with pre-existing lamivudine resistance

NB: It is contraindicated in HIV patients not on HAART because it has anti- HIV action

Tenofovir, Telmivudineand Emcitabine

have anti-HIV efficacyStill in clinical trial

How to assess response to therapy?

• Normalisation of ALT• Decreased inflammation series with no

worsening or improvemnet of fibrosis on histology

• Clearance of HBeAg, seroconvesion to HBeAb

• Clearance of HBsAg, seroconversion to anti-HBs

• Decreased serum levels of HBV DNA

HEPATITIS C VIRUS

coco de mer

Serology and virology

• It takes 6-12 weeks for antibodies to appear in blood following acute infection eg needlestick injury

• Hepatitis C RNA can be identified in blood as early as 2-4 weeks after infection.

• Active infection is confirmed by presence of hepatitis C RNA in anyone who is antibody positive.

• Anti-HCV antibodies persist in serum even after viral clearance, whether spontaneous or post treatment

• Liver function test– Normal or show fluctuating

serum transaminases between 50 and 200IU/L

– Jaundice only appears in end stage cirrhosis

• Liver histology– Stage the degree of liver

damage– Degree of inflammation and

fibrosis can be scored histologically

Treatment

• Pegylated Alpha 2b Interferon- S.C, weekly• Synthetic nucleotide analogue: Ribavirin- oral • Protease inhibitors?• Q. What is the main side effect of

– oral ribavirin?

– IFN alpha?

haemolytic anemia, teratogenicity

flu-like symptoms, irritability and depression, nausea, vomiting, BP changes, thyroid problems

Genotypes

Response to therapy• Virological relapsers

– serum HCV RNA undetectable at the end of treatment, but detectable afterwards

• Virological non responders– seru, HCV RNA is still detectable at the end of

treatment

• Sustained viral eradication– serum HCV RNA undetectable even after 6

months after stopping therapy

Cured: loss of virus from serum 6 months after completing therapy= sustained virological response (SVR)

Role of Liver transplantation

• In both Hep B and Hep C, liver transplanation is indicated in decompensated cirrhosis

• However, infection tends to recur in the graft*

• Use of post liver transplant prophylaxis with Lamivudin and Hep B Immunoglobulins has reduced reinfection rate to 10% and increased 10 year survival to 80%.

PREVENTION• Vaccination- 0, 1, 6- Engerix

– if mother is HBsAg negative– if mother is HBsAg positive?

• Hepatitis B Immunoglobulin (HBIG)• Screening blood donors, blood and

body fluid precautions• PEP• No vaccine in existance for

HepatitisC.

References• CDC• Malaysian Medical Council; Guideline on Blood

Borne Viral Infections Last updated 22nd Nov 2011• NICE Guidelines: Hepatitis B (chronic): Diagnosis

and management of chronic hepatitis B in children, adolescents and adults.

• Malaysian Society of Gastroenterology and Hepatology- Management of Hepatitis C

• Pediatric on call• Davidson's Principles of Practice of Medicine 21st

Edition• WHO.int/hiv/mediacentre/news/

whd2015_preventhepatitis/en/