Hepatitis B virus

Dr. K. G. MaharjanLiver unit, Bir hospital

Introduction• Hepatitis is an inflammation of the liver.• It is usually caused by viral & non viral infections also

due to toxins (alcohol) & drugs (mostly ATT) • In our setup it maybe due to bacterial infection but

may be an autoimmune response as well. • It is characterized by anorexia , jaundice, abdominal

pain, liver enlargement and sometimes fever.• Others , usually bacterial infections leading to HV&IVC

thrombophlebitis, metabolic cause (Wilson disease)• Congestive causes like ( HVOO,IVC disease , CHF)• HBV can lead to cirrhosis and liver cancer.

Introduction• Hepatitis is an inflammation of the liver.• It is usually caused by viral & non viral infections also

due to toxins (alcohol) & drugs (mostly ATT) • In our setup it maybe due to bacterial infection but

may be an autoimmune response as well. • It is characterized by anorexia , jaundice, abdominal

pain, liver enlargement and sometimes fever.• Others , usually bacterial infections leading to HV&IVC

thrombophlebitis, metabolic cause (Wilson disease)• Congestive causes like ( HVOO,IVC disease , CHF)• HBV can lead to cirrhosis and liver cancer.

Viral hepatitis

• The different types of viral hepatitis A,E,(virus transmitted through the faces of an infected person.

• Hepatitis B,C,D are serum hepatitis • Hepatitis F,G, cryptogenic ( caused by a virus

as not identified)• More hepatitis viruses are less common

yellow fever, epstien barr virus(EBV), cytomegalovirus(CMV),

Hepatitis B virus

• HBV is a serious disease ,can cause lifelong infection , liver cirrhosis ,liver cancer , and liver failure ,death.

• HBV is 100 times more infectious than HIV and 10 times more infectious than HCV.

• HBV is a blood borne transmitted ( body fluids , semen, saliva,vaginal fluid (high titers in the blood and lower titer in body fluids)

Hepatitis B virus introductions

• HBV is a 42 nm,double-shelled DNA virus of the class Hepadnaviridae.

• The outer surface membrane contains HBV surface antigen (HBsAg) which also circulates in blood as 22 nm spherical and tubular particles.

HBV virus

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• The inner core of the virus contains HBV core antigen (HBcAg) (HBeAg)

• HBV is a single molecule of partially double –stranded DNA, and DNA- dependent DNA polymerase.

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Risk groups • 1, I/V drug users Health workers • 2, Multiple sex partners• 3,Homosexuals• 4,Infant born to HBV infected mothers• 5,Hemodialysis patients• 6, Areas with high rates of HBV infections• 7,Tatooing

HBV transmitted

• HBV is transmitted by the exchange of blood & body fluids ,eg . Blood, semen, breast milk ,saliva and vaginal secretor fluids , tears.

Epidemiology

• Globally• 50 million new cases per year• 350-400 million chronic carriers 75% in Asia• 520,000 deaths per year

Epidemiology in Nepal

• One epidemiology study in done in nepal• Group;1, Population No. HBsAg • a, Soldiers 922 20 (2.2%)• b, healthy people 232 2 (0.8%)

from districts• c, pregnant women 81 1 (1.2%)• d, blood donors 624 5 (0.8%)• blood donors 168 1 (0.6%)

Continu…….• Group 2,• Hospital staff 792 7 (0.8%)• Student nurses 122 0• Relatives of CLD 388 12 (3.1%)• Patients• Group 3,• Hemophilia 4 1 (25%)• Drug addicts 72 2(3%)• Hemodialysis 41 1(2%)• HBV carriers 49 49(100%)

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• Group 4,• Chronic liver disease 145 57 (39%)• Acute hepatitis 150 14 (9.3%)

Clinical course of hepatitis B infection

Death Recovery

Acute hepatitis

Transient Subclinicalinfection

Acute HBV infection

25% 65%

Cirrhosis

Healthy HBsAgCarrier

Hepatocellular Carcinoma

Chronic Hepatitis

Chronic HBV Infection

1% 99%

100%

10-30% 70-90%10%

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?

HBsAgConfirmation by neutralization

True PositiveALT

Raised Normal

NegativeSearch for other virus

HbcAbAnti-HbcIgM Positive

F/u after 6 monthsNegative

HBeAg

Positive Negative

Liver biopsyHBvDNA

Rx

HBcAbPositive

Liver biopsyHBvDNAAbsent Raised

HBvDNA

RxSearch for other causes of

ALT

Negative

Positive NegativeF/U

HBvDNA F/U

>105ml <105ml

F/URx

Infection

• Acute hepatitis B develops in approximately 30% to 50% of adults at the time of initial infection and is characterized by anorexia, nausea , vomiting and jaundice.

• SGPT raises 2 ½ times• The risk of progression to chronic infection varies with

age , being highest among young children and infants (30%-90%) and lowest among adolescents and adults (2%-6%).

• Rates of progression to cirrhosis and HCC vary according to age at acquisition of chronic infections ,HBeAg status , co infection with HGV,HIV,HCV, and alcohol abuse.

Clinical features

• The first serologic marker to appear following acute infection is HBsAg, which can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks (mode 30-60 days) after exposure to HBV

• HBeAg is generally detectable in patients with acute infections, the presence of HBeAg in serum correlates with higher titers of HBV and greater infectivity.

Continu….

• A diagnosis of acute HBV infection can be made on the basis of the detection of IgM class antibody to HBV core antigen (IgM ,anti-HBc) in serum ,It is generally detectable at the time of clinical onset.

Serological markers ; HBV

• HBsAg: Marker of infection,presence >6months=chronic

• HBeAg: active viral replication,• Anti-HBsAg: indicates recovery and /or

immunity (after vaccine)• Anti-Hbe: inactive viral replication• Anti-HBc: infection or immunity

HBV genotypes• HBV classified into 7 genotypes (A-G)• -a: north america and western europe• B&C: asia• D: southern europe and india• E:&G: africa• F:central and south america and alaska• H: central america• B associated with less HCC, less active and more slowly

progressive liver disease than C• A&B respond better to Interferon than C&D• Genotype does not predict response to oral agents

HBV infection

• Chronic HBV: chronic necroinflammatory liver disease >6month,ALT^,HBeAg-postive or –negative, HBV DNA> 10 x4-5

• Inactive HBsAg carrier : Persistent infection without necroinflammatory disease, ALT normal , HBeAg -negative HBV DNA<10 x 4-5

• Resolved HBV: previous infection without virological ,biochemicalor histological evidence of active disease.

Continu…

• Acute exacerbation HBV: elevated ALT>10 x ULN or >2 x baseline

• Reactivation of HBV: reappearance of necroinflammatory disease in person known to be inactive carrier or resolved HBV

Phases of chronic HBV• Immunotolerant phase: HBeAg- postive; HBV

DNA high (10 x 5-10) ALT normal -candidates for therapy.Immunoactive phase: HBeAg-postive or HBeAg –

negative,HBV DNA high (10 x4-10) ,ALT elevated, symptoms +/-

Non replicative phase :(inactive HBV carrier)HBeAg –negative HBV DNA low(<10 x4 ) ALT

normal, HBsAg may later become undectable.

Liver histology ≥

Routine HBV carriers exam

• Follow-up interval 6 months : Tests : ALT and AST; AFP. USG,

• Inactive HBsAg carrier: If ALT/AST increase , re evaluate

• Chronic hepatitis B: CBC,LFT,HBeAg, anti-HBe

HBV infected mothers

• Hepatitis B immunoglobulin (HBIG 0.5 ml , I/M to new born.

• Hepatitis B vaccination should have been given 12 hours of birth.

Post exposure prophylaxis

• 1, HBIG is required • 2,the first dose of hepatitis B vaccine

immediately, 0 – 1 – 6 months.

Hepatitis B vaccine

• The standard regimen for adult is 10-20mcg initially ( depending on the formulations ) .

• Schedules; 0 -1 -6 months.• Alternative schedules have been approved• 0 -1 -2 -12 months• 0- 7 and 21 days ,plus 12 months• Preferred site vaccine deltoid muscles

Treatment of chronic HBV• Nucleoside/nucleotide analogues: - Entecavir : 0.5-1.0 mg/d• -Lamivudine : 100 mg/d• -Adefovir dipivoxil :10mg/d• -Tenoforvir : 300mg/d• Interferon: interferon alfa-2b 5MU/d or 10MU tiw x 4

months.• Peginterferon alfa-2a (Pegasys) 180 mcg/week x 24-48

weeks.• Liver transplantation ( decompensated chronic HBV

with cirrhosis.

Reference

• Davidson principal and practice of medicine• C.M.D.T• Oxford hand book of medicine• Liver unit, Bir hospital

Thank you

Thank you