CHRONIC HEPATITIS B

GENERAL PRACTIONER PERSPECTIVE

DR PANKAJ INGALE
MD , DNB (GASTROENTEROLOGY)
Consultant Gastroenterologist

AMRAVATI INSTITUTE OF GASTROENTEROLOGY

A complete solution for Liver and GI health care
 Hepatitis B infection

• Caused by Hepatitis B virus (HBV)

– An enveloped DNA virus that infects the liver,
causing hepatocellular necrosis and
inflammation
• Can be either acute or chronic
• Associated illness ranges in severity from
asymptomatic to symptomatic, progressive
disease
Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. WHO. 2015. Accessed on 12th Dec 2016. Available at:
http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf
 Hepatitis B infection: Acute HBV

• Acute hepatitis B
– A self-limiting disease
– Acute inflammation and hepatocellular necrosis
– Anicteric hepatitis: the predominant form of
expression
– Case fatality rate of 0.5–1%

Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107.
 Hepatitis B infection: CHB

• Chronic hepatitis B (CHB)

– Persistence of hepatitis B surface antigen
(HBsAg) for six months or more

– Major complications of CHB

• Cirrhosis
• Hepatocellular carcinoma (HCC)

Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107.
 Structure of Hepatitis B virus
• DNA and surrounding proteins
• Structure
– Core protein – hepatitis B core antigen (HBcAg)
– Envelope or surface protein – HBsAg
– Another protein (has elements of core protein) – HBeAg

• HBsAg and HBeAg – important role in management of hepatitis B

• HBV has a strong preference for liver cells

– Enters cells and uses the reproductive machinery of liver cells to replicate,
does not kill infected cells

• Liver injury results from body’s immune response to the infection

– Characterized by ALT elevations
Case - 1
Staff nurse in ICU gets needle prick from HBsAg
+ve patient. She has not had prior vaccination.

• Risk of getting infection?

• Post exposure prophylaxis?

• If she had completed vaccination;

what should be the
advise ?
 Needle Prick Transmission

• Needle stick injury from hep. B +ve pt.

– Susceptible (non vaccinated) individual – 23% - 62%
• ‘e’ positive – 37% - 62%
• ‘e’ negative – 23% – 37%
MMWR 2001 (CDC Guidelines 2001)
MMWR 2008 (CDC Guidelines 2008)
 Parenteral - IV drug abusers, health workers are
at increased risk.

 Sexual - sex workers and homosexuals are

particular at risk.

 Perinatal (Vertical) - mother(HBeAg+) →

infant.
 Concentration of Hepatitis B Virus
in Various Body Fluids

Low/Not
High Moderate Detectable

blood semen urine

serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
 Post Exposure Prophylaxis
HBIG (0.06 ml/kg) & hepatitis B vaccine
Unvaccinated
(3)
Previously vaccinated:

Responder No treatment

HBIG ? 2 doses (one month apart)

Non-responder OR
HBIG ? 1 dose & Revaccination

Test for anti HBs

Antibody response If adequate * - No treatment
unknown If inadequate (†) – HBIG ? 1 dose & vaccine
booster
 Adaptive Immune response to HBV

• HBsAg – first antigen to appear

• HBcAg – released along with HBsAg,

concentration declines rapidly.

• HBeAg - peaks at wk 16 and

undetectable by wk 24.

• HbsAg antibodies - are final

antibodies and signifies full recovery
and lifelong immunity
 CASE 2
• Asymptomatic, 26 yrs old engineer goes for blood donation.
Detected to be HBsAg +ve
• How do we evaluate ?
 Diagnosis of CHB

• Initial evaluation of CHB patients

– A thorough history and physical examination
• risk factors for coinfection,
• alcohol use, and
• family history of HBV infection and liver cancer

• Laboratory tests
– Assessment of liver disease activity and function,
– HBeAg/Anti Hbe/DNA PCR
– HCV, HDV, or HIV in those at risk

Terrault NA, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016; 63(1):261-83 .
 Investigations
• LFT
– SGOT 19
– SGPT 22
– Albumin 4.0
– Globulin 3.2
– Bilirubin 0.8

• HBeAg +ve
• HBeAb -ve
• HBV DNA PCR > 2,00,000 IU /ml
• USG Normal
Possible Outcomes of HBV Infection

Acute hepatitis B infection

3-5% of adult-acquired 95% of infant-

infections acquired infections
Chronic HBV infection

Chronic hepatitis

12-25% in 5 years
Cirrhosis
6-15% in 5 years 20-23% in 5 years

Hepatocellular Liver failure

carcinoma

Death Liver transplant

Death
 Phases of CHB infection

Terrault NA, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016; 63(1):261-83.
Natural History of Chronic Hepatitis B
Case - 3
Mrs. K, 35 yrs/female, asymptomatic, 23rd Feb 12.
• HBsAg incidentally detected, HBeAg +ve
• Father & Brother, HBsAg +ve
• Husband HBsAg –ve, vaccinated
• Serum Bilirubin 0.8 mgm
• SGOT 35 IU/ml, SGPT 40 IU/Lit
• Serum Proteins 7.2 gms Alb 4.0 gms,
Glob 3.2 gms
• Haemogram – Normal, Platelets - Normal
• USG – Normal
HBV DNA PCR done
High viral load 80,226 IU/ml
 LIVER ENZYMES
• Liver enzymes – Updates in normal level
– Men - 30 IU/L
– Women - 19 IU/L
Daniele Prati, Ann Intern Med.2002;137:1-9

• Raised enzymes s/o necro-inflammation

• Mortality
– ALT 20 – 29 RR 2.9 (Compared to ALT < 20)
– ALT 30 – 39 RR 9.5 (Compared to ALT < 20)

Lai et al 2005, Nguven et al 2005

Natural History of Chronic Hepatitis B
 CHB: Treatment indications

Treatment indications for noncirrhotic HBeAg-positive chronic

HBV-infected patients
Sarin SK et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10:1–98.
 How to evaluate ?

a) Fibroscan
b) AST / Platelet ratio
c) Fibro test
d) Liver biopsy
e) Follow up
•Periportal & interphase hepatitis
•Focal confluent necrosis
•Spotty necrosis
•Portal inflammation
•Fibrosis
•HAI 8
 WHY DID WE DO BIOPSY ?
• Majority of Asians with Chr HBV have N LFT
– 1/3 chr hepatitis on histology.
(Lok ASF et al 1992)

• Meta - analysis of Chronic Hep B (Pnalt)

• Significant hist activity (Fibrosis > 2, Infl > 2)
– Overall - 22.5 %
– HBe antigen +ve – 12.2 %
– Anti Hbe +ve– 23.7 %
DDW May 2011 Abstract Mo 1075
 What does the FibroScan®
examination consist of?
You lie on your back, with your right arm raised behind your head.
Physician applies a water-based gel to the skin and places the probe
with a slight pressure
• The examination includes 10 consecutive measurements made at the
same location
• The result is delivered at the end of the examination, it’s a number
which can vary from 1.5 to 75 kPa.
 What the clinician needs to know?

Clinical Gastroenterology and Hepatology 2015;13:27–36

 TREAT
OR
OBSERVE
???
NEED FOR TREATMENT
 Why do we need to treat Hepatitis B ?

• Life time risk of significant complications – 40 %

– Cirrhosis
– Hepatocellular carcinoma
– Death
• Repeated acute exacerbations of necroinflammation
– Progression of fibrosis
• Seen in 21 % - 36 % of untreated group within 1 year

– Fibrosis  Cirrhosis
• (Mortality at 5 years - 16% compensated, 65.86% decompensated)

– HCC Risk 60 times > if HBsAg + HBeAg +ve

AIMS OF MANAGEMENT
• Suppress HBV replication (VR)
HBeAg Anti HBe
DNA PCR –ve
• Normalization of liver enzymes (BR)
• Improvement in liver – histology (HR)
￬ in HAI > 2 points
• Biochemical + Virological response

+ Disappearance of HBsAg (CR)

What are the treatment options ?

1. Peg interferon
2. Interferon
3. Lamuvidine
4. Adefovir
5. Entecavir
6. Telbivudine
7. Tenofovir
CASE 4
• Mr. J, 50 Yrs, BMI 25
• Symp. Cholelithiasis
• Lap. Chole
– HBsAg +ve, HBeAg –ve
• SGOT - 65 IU, SGPT - 70 IU
• Sr. Bili - 1 mg
• Sr. Proteins – N
• Haemogram – N
• HCV – ve/ HDV – ve/ Non alcoholic / Non diabetic / No drugs
– PCR 1925 IU/ml
Natural History of Chronic Hepatitis B
 CHB: Treatment indications

Treatment indications for noncirrhotic HBeAg-negative

chronic
Sarin SK et al. Asian-Pacific clinical practice guidelines HBV-infected
on the management patients
of hepatitis B: a 2015 update. Hepatol Int 2016;10:1–98.
 CHB in pregnancy

• Infants of all HBsAg-positive women should

receive immunoprophylaxis
– HBV vaccination + hepatitis B immunoglobulin

• AASLD suggests antiviral therapy to reduce the

risk of perinatal transmission of hepatitis B in
HBsAg-positive pregnant women with an HBV
DNA level >200,000 IU/mL

Terrault NA, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016; 63(1):261-83.
 Factors to Consider in Initiating
Anti-HBV Therapy

 HBV DNA levels

 ALT levels
 HBeAg status
 Cirrhosis vs no cirrhosis
 Compensated vs decompensated disease
 SUMMARY
• Treatment is initiated if patient has acute liver failure/severe
acute hepatitis

• Compensated cirrhosis, treatment is initiated even in patients

with HBV DNA levels less than 2000 IU/mL

• For patients without cirrhosis, treatment is recommended if

HBV DNA level is greater than 20,000 IU/mL and ALT level is
greater than 2 times the ULN
 SUMMARY

• Patients in the gray zone, liver biopsy is recommended,

particularly if they are older than age 40

• Difficulty in predicting which patient with cirrhosis will develop

HCC

• ENTECAVIR Vs TENOFOVIR