chronic hepatitis

1. Chronic
Hepatitis B

2. Introductio
n
•
• Human hepatitis B virus belongs to the family of Hepadnaviridaeof small,
enveloped,
Chronic hepatitis B virus infection is when the patient is HBsAg seropositive for more
than 6
Chronic infection may develop in nearly half of children infected with HBV before the age of
6 years and in <5% of individuals infected as adults
The virus replicates in the host and assembles exclusively in the hepatocytes and virionsare
released non-cytopathicallythrough the cellular secretory pathway
month
s
–
primarily hepatotropicDNA
viruses
–
Chronic hepatitis B is defined as chronic necro-inflammatory liver disease due to persistent hepatitis B virus
infection

3. Signs and
Symptoms
•
•
The majority of acute viral hepatitis infections are
asymptomaticor they can cause an anicteric illness that
may not be diagnosed as hepatitis
Symptomatic hepatitis B will depend on the mode and
time of transmission
– Vertical transmission from mother to child is
almost always asymptomatic; other routes of
transmission are more likely to produce
symptomatic disease (30% of cases transmitted

4. 1) PreictericPhase
Nonspecificsystemic symptoms (egmyalgia, nausea, vomiting, fatigue, malaise with
discomfort in the right upper quadrant of the abdomen)
•Altered sense of smell or taste, coryza, photophobia, headache, cough, diarrhea, dark
urine
and serum sickness-like syndrome
•Hepatomegaly, splenomegaly and lymphadenopathy may be seen on physical exam
2) Icteric Phase
Jaundice, usually noted after onset of fever or upon lysisof fever
Development of symptoms of hepatic encephalopathy (egconfusion, drowsiness within 8
weeks of symptoms or within 2 weeks of onset of jaundice)
•Hypoglycemia, prolonged prothrombintime (PT)
3) Fulminant
Hepatitis

5. Histor
y
Important points in the clinical history of patients with suspected viral
hepatitis
•Contacts with jaundiced patients
•IV drug use
•History of blood transfusion
•Surgery or hospitalizations
•Family history of chronic liver disease
• Occupation
•Food and water sources
•Alcohol use

6. Serological
Tests
•
•
•
•
–
Anti-HBc(anti-core antibody) is the 1st antibody to appear in the serum and is a marker of
natural
immunity
Usually characterized by the presence of hepatitis B surface antigen (HBsAg) which suggests
infectivity
HBV DNA tests for HBV replication and aids in the evaluation of treatment efficacy with
antiviral agents New biomarkers of HBV infection are:
–
–
–
–
Anti-HBs is produced following a resolved infection and is the only hepatitis B virus (HBV) antibody marker
present after immunization
This may be negative at the time that the patient is evaluated for acute hepatitis B since viral replication may
have already ceased
Its presence indicates an immune response against HBV within liver cells and is a specific marker of acute
hepatitis B infection Presence of anti-HBcIgMis diagnostic for acute HBV infection but may occur during a flare of
chronic hepatitis B
Viral covalently closed circular DNA (cccDNA) -shown to persist in the liver of infected patients even after long-term
nucleotide analogue therapy and even after HBsAgloss and seroconversion; used in clinical trials evaluating treatment
concepts to cure HBV infection
–Hepatitis B core-related antigen (HBcrAG) -helpful in defining the phase of chronic HBV infection especially in the HBe-
negative
patients as well as predicting the long-term HCC risk
–Circulating HBV RNA
Persistence of HBsAgfor at least 6 months indicate chronic
infection
• Hepatitis B e antigen (HBeAg) is a marker of active viral
replication

8. •
•
•
–
Prothrombintime (PT), international normalized ratio (INR), renal
function
tests
Noninvasivetests such as the aminotransferase/platelet ratio index
(APRI)
or fibrosis-4 (FIB-4)may be used to assess the degree of hepatic
fibrosis
Other lab tests that are recommended in patients suspected to have
viral hepatitis:
Liver function tests (LFTs)
– Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT)
–
Serum bilirubin, alkaline phosphatase
(ALP)
Transient elastographymay be an option for patients with
contraindications to liver biopsy
•

9. Evaluatio
n
If patient meets criteria for chronic hepatitis B:
Liver biopsy must be done:
•to grade stage of liver diseaseas chronic
hepatitis
B may evolve to cirrhosis and hepatocellular
cancer
•Liver biopsy is essential in determining disease
activityin cases of inconclusive biochemical and
HBV markers

10. Phases of Chronic
Hepatitis B
1) HBeAg-positive Chronic HBV Infection (Immune-tolerant)
•Presence of serum HBeAg
•Very high levels of HBV DNA
•ALT persistently within the normal range (<19 U/L for females and <30 U/L in males) or minimally elevated
•Minimal or no liver necroinflammationor fibrosis
•Frequently occurred and prolonged in patients infected perinatallyand is associated with preserved HBV
specific T
cell function at least until young adulthood
•Patients at this stage are highly contagious because of the high levels of HBV DNA
2) HBeAg-positive Chronic Hepatitis B (Immune-clearanceHBeAg-positive)
•Presence of serum HBeAg
•High levels of HBV DNA
•Elevated ALT
•Moderate to severe liver necroinflammationand accelerated progression of fibrosis
•Usually occurs in patients infected during adulthood
•Patients may have HBeAgseroconversionand HBV DNA suppression that progress to HBeAg-negative

11. Absence of serum HBeAgusually with detectable anti-HBe
Persistent or fluctuating moderate to high levels of serum
HBV DNA Fluctuating or persistently elevated ALT
There is liver necroinflammationand fibrosis
3) HBeAg-negative Chronic HBV Infection (Inactive Carrier/Immune Control)
•Absence of serum HBeAg
•Undetectable or low (<2,000 IU/mL) HBV DNA levels
•Normal ALT
•Minimal liver necroinflammationand variable fibrosis as a result of previous hepatic injury during the
HBeAg-
positive immune-active phase
•Low risk of progressing to cirrhosis or HCC but progression to chronic hepatitis B may occur
5) HBsAg-negative (Occult HBV Infection)
•Serum negative HBsAgand positive antibodies to HBcAgwith or without detectable antibodies to HBsAg
•Normal ALT
•Usually, but not always, undetectable serum HBV DNA
•Liver has frequently detectable HBV DNA (cccDNA)
•Several studies have shown that almost all patients with occult HBV infection have normal liver
biochemistry and
minimal or no liver necroinflammationand fibrosis
•However, it may still be associated with the development of liver cirrhosis and HCC
•
•
•
•
• Associated with low rates of spontaneous disease
remission
4) HBeAg-negative Chronic Hepatitis B (HBeAg-negative Immune
Reactivation/Escape)

14. MANAGEMEN
T

15. General
management
1) Serologic screening of chronic Hepatitis B virus infection amongst patient’s family
members
2) Prevention of transmission of Hepatitis B virus to others :
-Ensure that their sexual partners are vaccinated
-No sharing of toothbrushes and razors
-Cover open wounds
-No donation of body parts
-Clean blood spills with bleach/detergents
Note: Hepatitis B virus transmission is nottransmissible through:
• Sharing of utensils, food or kissing as part of social greetings
• Participating in all activities including contact sports
• Social interaction with others (e.g. in schools, day care centres)
3) Prevention of super-infection -Unless contraindicated, hepatitis A vaccination should be
given to
prevent superimposed acute hepatitis A in patients with chronic hepatitis B virus infection.

16. Specific
management
Management of patients with chronic hepatitis B should be tailored according to the patients’ clinical
state of liver disease(compensated versus decompensated liver disease) as well as their virologicand
biochemical (i.e. the liver function test, in particular the serum transaminase levels) status.

21. Selection of antiviral drug for CHB:
• In all adults, adolescents and children aged 12 years or older in whom antiviral therapy is indicated, the
NAs which have a high barrier to drug resistance (tenofovir or entecavir) are recommended.
• In woman of childbearing age Tenofovir may be preferred as the drug of choice in the eventuality of a
pregnancy. Entecavir is not recommended in pregnancy.
• Tenofovir is preferred in patients who have been exposed to lamivudine who have a potential for
Entecavir resistance.
• Entecavir is recommended in children aged 2–11 years.
• Entecavir may be preferred over Tenofovir in:
• Age > 60 years; bone disease due to chronic steroid use or use of other medications that worsen bone
density,
• history of fragility fracture, osteoporosis; altered renal function with eGFR < 60 mL/min/1.73 m2 or
albuminuria
• > 30 mg/ 24 hr or moderate dipstick proteinuria or Low phosphate (<2.5 mg/dL) or in patient on
hemodialysis

23. Monitorin
g
•
•
Monitor patient to ensure that fulminant liver failure
does not develop
Monitor liver function tests (LFT) every 1-4 weeks until
normal; ALT every 3-6 months if patient did not meet
criteria for treatment
Further monitoring of HBV DNA every 3-6 months in
non- responders is recommended to recognize
delayed response and to plan retreatment if required
Monitor for hepatocellular carcinomain high-risk
patients
every 6-12 months using ultrasound and alpha-
fetoprotein
•
•