HEPATITIS B INFECTION

1. HEPATITIS B
DR. SSENYONGA DOMINIC
MBChB

2. Introduction
• Hepatitis B is a viral infection that attacks the liver and can cause
both acute and chronic disease
• HBV infection is a public health problem in several regions.
• Burden is highest in the WHO Western and African Region, where
116 million and 81 million people respectively are chronically
infected as compared to 14 million and 5 million in the WHO
European and Americas Regions respectively
• WHO estimates that 296 million people were living with chronic
hepatitis B infection in 2019, with 1.5 million new infections each
year.
• Sub-Saharan Africa, is a highly endemic area, with a prevalence rate
of between 8% and 18%,
• In 2019, hepatitis B resulted in an estimated 820 000 deaths, mostly
from cirrhosis and hepatocellular carcinoma.

4. HBV in Uganda
• 9 out of every 10 people in Uganda do not know their HBV
status.
• Prevalence of HBV infection among adults stands at 4.3%
(5.6% among men and 3.1% among women) down from 10.3%
in 2005.
• Highest in Northern region with 4.6% in mid North and 4.4% in
North East and3.8% in West Nile.
• Rest of the country with a range of 0.8% in South West region
to 2.7% in East Central region (UPHIA 2016)
• UBTS data indicates that the trend of Hepatitis B virus among
blood donors has increased from 1.9% in 2012/13 to 2.3% in
2016/17. The highest rates being registered in Arua (4.98%)
and 4.21% in Mbale

5. Figure: The
distribution of
chronic hepatitis B
infection in the
country as shown
below (UPHIA,
2016)

6. Key Definitions
• Acute hepatitis B: New-onset hepatitis B infection that
may or may not be symptomatic and usually lasts < 6
months from time of onset. It is usually self limiting.
• Chronic hepatitis B: Persistence of hepatitis B surface
antigen(HBsAg) for six months or more after acute
infection with HBV.
Note that this definition does not refer to liver disease but
HBV infection. This means chronic HBV infection does not
mean chronic liver disease.
6

7. 7
Child-to-Child
Contaminated Needles
Sexual Contacts
Healthcare Worker-occupational
Blood Transfusion
Only 6% of people
infected over the age
of 5 become
chronically infected
 90% of infected
infants become
chronically
infected
Vertical Transmission Horizontal Transmission
Transmission of HBV
CDC Viral hepatitis B fact sheet.
Lee. N Engl J Med. 1997;337:1733-1745.
Lavanchy. J Viral Hepat. 2004;11:97-107.
Host
Mother
Infant
Recipient
7

8. Chronic
Cirrhosis
ESLD, HCC
Natural history of HBV
HBV
infection
“Healthy
carrier”
“resolved”
Within 6
months
• 94% of
adults
• 10% infants
• Natural history of chronic HBV infection and disease is complex and highly variable
Takes 30-40 yrs for
perinatally infected
Factors Influencing Natural
History
• Age at infection
• Host immune status
• Gender
• HBV viral load
• Co-infection with HCV, HDV,
HIV
• Alcohol use
• , HDV or HIV
8

12. Jaundice (gulsot)
Weakness (svaghed)
Fatigue (træthed)
Malaise (utilpashed)
Anorexia (mistet appetiten)
Nausea (kvalme)
Vomiting (opkastning)
Myalgia (muskelsmerter)
Arthralgia (ledsmerter)
Abdominal pain (mavesmerter)
Hepatomegaly (hepatomegali/enaleret lever )
Splenomegaly (splenomegali/forstørret milt )
Dark urine (mørk urin)
Low-grade fever
Acute infection may cause nonspecific symptoms and clinical
signs, such as:
Approximately 5 percent of adults acutely infected with
HBV progress to chronic infection and stay in preclinical
phase for decades
Clinical presentation- Acute hepatitis B
12
gulsot

13. Clinical presentation- Chronic hepatitis B
Compensated cirrhosis
• No ascites, no varices
Decompensated cirrhosis
• Portal hypertension
• Ascites
• Esophageal /gastric varices
• Spontaneous bacterial
peritonitis
• Hepatic encephalopathy
• Hepato-renal syndrome
• Hepatocellular carcinoma
13

14. Chronic Hepatitis B Work-up
• HBV serology
• Liver enzymes (ALT, AST, Albumin,
GGT, ALP)
• Viral load for HBV DNA by PCR
• Alpha fetoprotein monitoring
• Hepatic imaging – US or CT scan
• Liver biopsy
• Others as appropriate
• CBC (APRI score)
• HIV
• HCV
• HDV
• Urine HCG
• RFT
APRI Calculation: APRI is a non-invasive
marker of hepatic fibrosis
APRI = (AST/ULN x 100) / Platelet count
NB:
• AST is the patients test result in IU/L
• ULN - upper limit of normal for AST
in the lab where the LFT was done.
• Unit of measure for platelets is 109/L
• APRI >2 signifies significant hepatic
fibrosis
14

15. Other Routine Laboratory tests
• Complete Blood Counts
• Haemoglobin r/o anaemia
• White cell count r/o infection
• Platelets High ?low > affects clotting of blood
• Urea / Electrolytes & Creatinine
• Important to know renal function if Tenofovir is to be considered for
treatment.

16. Laboratory tests –Liver specific
• Prothrombin Time index (PTI) Range (85-100%). Coagulation profile
(clotting) of blood deteriorates with increasing damage of liver
• International Normalized ratio (INR); used in determining period it
takes blood to clot. Range (0.8–1.1) and gets higher with increased
clotting time
• Alpha fetoprotein (AFP) –tumourmarker. (Range 10 –20ng/mL)
• Elevation >500 ng/mL in patients with liver cancer (In pregnant
women it rises but <500)

17. Imaging studies
• Ultrasound scan of abdomen-Screen for Hepatocellular carcinoma
• Liver fibroscan – transient elastography
• Superior to ultrasound for detection of liver scarring.
• Can determine liver cirrhosis or advanced fibrosis.

18. Management of Hepatitis B
REQIURES;
Thorough assessment of disease activity
Close monitoring for disease flares regardless
of antiviral initiation.

20. Therapeutic Options
• Nucleos(t)ide analogues
• Interferon
• However, the clinician must facilitate appropriate counselling to
ensure safe and adherence to treatment.

21. Current treatment guidelines
• Based on disease stage, as determined by;
• - HBV viral load
• - serologic status
• - degree of liver injury

22. Goals and endpoints of therapy
*Often represents a partial immune control of the chronic HBV infection;
†Achieved in most patients with long-term suppression of HBV replication;
‡Indicates profound suppression of HBV replication and viral protein expression
EASL CPG HBV. J Hepatol 2017;67:370–98
HBV has no cure, so why treat?
Goals
• Improve survival and quality of life by preventing disease progression to cirrhosis and HCC
• Prevent MTCT of hepatitis B reactivation,
• Prevent and treat HBV-associated extrahepatic manifestations
• Treatment is indicated in approximately 30% of persons with chronic HBV infection
Recommendations
Main endpoint
• Induction of long-term suppression of HBV DNA I 1
Valuable endpoint
• Induction of HBeAg loss (± anti-HBe seroconversion) in HBeAg-positive patients with
chronic hepatitis B*
II-1 1
Additional endpoint
• ALT normalization (biochemical response)† II-1 1
Optimal endpoint
• HBsAg loss (± anti-HBs seroconversion)‡ II-1 1
Grade of evidence Grade of recommendation

23. Indications for treatment
*Defined by HBV DNA >2,000 IU/ml, ALT >ULN and/or at least moderate liver necroinflammation or fibrosis;
†Defined by persistently normal ALT and high HBV DNA levels;
‡Even if typical treatment indications are not fulfilled
EASL CPG HBV. J Hepatol 2017;67:370–98
• Primarily based on the combination of 3 criteria
• HBV DNA, serum ALT and severity of liver disease + (APRI score Ugandan guidelines)
Recommendations
Should be treated (confirmed HBsAg positive > 6 months) plus
• With HBeAg-positive or -negative chronic hepatitis B* I 1
• With cirrhosis, any detectable HBV DNA, regardless of ALT level I 1
• With HBV DNA >20,000 IU/mL and ALT >2x ULN, regardless of severity of histological
lesions
• APRI score >2 and HIV (Ugandan guidelines)
II-2 1
May be treated
• Patients with HBeAg-positive chronic HBV infection†
>30 years old, regardless of severity of liver histological lesions
III 2
Can be treated
• Patients with HBeAg-positive or -negative chronic HBV infection and family history of HCC
or cirrhosis and extrahepatic manifestations‡
III 2
Grade of evidence Grade of recommendati

24. Current treatment strategies for chronic hepatitis B
*Stopping NAs after some years might be considered in selected cases; †Psychiatric, neurological, endocrinological; ‡Uncertainties regarding kidney function, bone diseases for some NAs; §Decompensated disease, comorbidities
etc.; ‖Dose adjustments in patients with eGFR <50 ml/min are required for all NAs except for TAF (no dose recommendation for TAF in patients with CrCl <15 ml/min who are not receiving haemodialysis); ¶Depending on baseline
characteristics; **Slowly increases with treatment time in HBeAg-positive patients (a plateau in serological responses has been observed beyond treatment Year 4), usually very low in HBeAg-negative patients; ††So far no TDF or
TAF resistance development has been detected
EASL CPG HBV. J Hepatol 2017;67:370–98
Features Entecavir(ETV), Tenofovir (TDF, TAF), PegIFNα
Route of administration Oral Subcutaneous injections
Treatment duration Long-term until HBsAg loss* 48 weeks
Tolerability High Low
Long-term safety concerns Probably not‡ Very rarely persistence of
on-treatment AEs†
Contraindications None‖ Many§
Strategy Inhibition of viral replication Induction of a long-term immune control
Level of viral suppression Universally high Moderate
Effect on HBeAg loss Low in first year, moderate over long term Moderate¶
Effect on HBsAg levels Low** Variable¶
Risk of relapse after treatment
cessation
Moderate if consolidation treatment provided after HBeAg
seroconversion. High for HBeAg-negative disease
Low for those with sustained response
6–12 months after therapy
Early stopping rules No Yes
Risk of viral resistance Minimal to none†† No

25. What to treat with
• TDF and Entecavir are recommended 1st line drugs
• Entecavir in children aged 2-11 years (who weigh at least 10 Kg) should be given entecavirat
0.02mg/Kg ( the medication is available in 0.5 and 1mg strength)
• TDF for adolescents > 12 years and adults weighing at least 30 kg
• TAF has similar efficacy with increased renal and bone safety compared to TDF (await future
guidance on availability)
• Adefovir, lamivudine; telbivudine – not recommended as monotherapy because low resistance barrier
• In renal disease, patients should be on entecavir
• In case of elevated creatinine, all those initially on TDF should be switched to entecavir, if
seen at a lower facility patients requiring this switching should be referred to a RRH for
further evaluation of their disease
• HIV and HBV co-infected patients
• antiretroviral therapy (ART) should be initiated as per the most recently approved national
HIV guidelines
• At least 2 drugs active against both HIV and HBV i.e. Tenofovir + lamivudine should be
included in the ART combination 25

26. Monitoring of patients currently not treated
EASL CPG HBV. J Hepatol 2017;67:370–98
• Patients with no current indication of antiviral therapy should be
monitored
• Periodical assessments of serum ALT, HBV DNA and non-invasive
markers for liver fibrosis (Ultrasound/fibroscan)
Recommendations
Follow-up at least every 3–6 months
• HBeAg-positive chronic HBV infection, <30 years old
II-2 1
Follow-up at least every 6–12 months
• HBeAg-negative chronic HBV infection and serum HBV DNA <2,000 IU/ml
II-2 1
Follow-up every 3 months for the first year and every 6 months thereafter
• HBeAg-negative chronic HBV infection, serum HBV DNA ≥2,000 IU/ml
III 1
Grade of evidence Grade of recommendation

27. HBV treatment discontinuation
• Treatment if indicated is largely LIFE-LONG
• Hepatitis B treatment can be discontinued in patients with;
• No cirrhosis (baseline APRI score <2)
• Sero-conversion (loss of HBeAg and its replacement with anti-
HBeAb),
• Undetectable HBV viral loads
• Persistently normal ALT
• When this seroconversion occurs, treatment should be
continued for another 12 months after which it can be
stopped
• These individuals should also be monitored since recurrence
can occur
• Regardless of prior HBeAg status, treatment can be stopped27

28. Follow up tests after treatment initiation
Lab test for
diagnosis and
monitoring
Baseline
entry into
care
If S Ag test is
Positive but
before deciding
to treat
Before
Initiation or
switching
treatment
Every 6
months
Every year Per
Need
HBsAg  .  
CBC: Platelet count   
LFT: AST & ALT    
HBV DNA Viral load
(if available)
  
HBeAg  (if positive
at treatment
initiation)
(if positive at
treatment
initiation)
RFT & Urinalysis    
HIV testing  (if initially HIV
negative.)

Abd. US - Liver   
Alfa-feto protein   
Clinical evaluation  .     
28

29. Serological tests for Hepatitis B if HBsAg is
positive
• Hepatitis B blood test serological marker that varies in acute and chronic viral
liver infection
• Hepatitis B surface antigen (HBsAg)
• First serological marker to appear in acute infection 1-9 weeks after exposure
• Present in both acute and chronic Hepatitis B.
• Hepatitis B core antigen (HBcAg) not detected in serum but its antibody Anti-HBc
through immunoglobulins.
• Antibody to HBsAg (Anti–HBs), positive after vaccination or resolved infection
• HBsAg, anti-HBc, anti-HBs are All negative = Patient susceptible to HBV and must
be vaccinated.

30. Cont.
• Hepatitis B e-antigen HBeAg positive in active infection; (anti-HBe) is a marker of
resolution of acute illness.
• IgM anti-HBc –Immunoglobulin M is seen in new infection and declines in 6-9months.
• A flare up or acute exacerbation can result in positive anti HBc in chronic Hepatitis B
• IgG anti HBc -Remains positive indefinitely as a marker of past HBV Infection
• HBV DNA -quantifies level of infectivity and indicates viral replication. Levels (<2000
IU/ml) not treated
• PCR -Polymerase chain reaction assay detects genome of HBV and the specific genotype
A-H of Hepatitis B.
• (Hepatitis B test, MekaroonkamolP; Hepatitis B test, Medscape Feb 2020 Davidson SA;
BMJ May 2014. Vol

32. THANK YOU SO MUCH
FOR YOUR TIME