Hepatitis b a silent threat to all in India-its management

Hepatitis b a silent threat to all in India-its management

1. Training of Trainers on
Clinical Management of Viral
Hepatitis

2. Learning objectives
At the end of this session, the learners shall understand and
know:
•Clinical and laboratory assessment of HBV-infected persons
•Antiviral drugs available for treatment of HBV infection
•Treatment and follow-up strategies recommended for HBV
•Identify the appropriate treatment strategy for a particular
patient with HBV infection

3. National Guidelines: India

4. Consequences of HBV infection
Hepatitis B virus infection
Acute infection
(short duration: <6 mo)
Chronic infection
(duration >6 mo)
Asymptomatic
Acute viral hepatitis
Acute liver failure
Chronic hepatitis B
Cirrhosis: compensated
Cirrhosis: decompensated

5. Natural history of chronic hepatitis B
Chronic hepatitis B
Immune-
tolerant
phase
Immune-active
phase
Immune-control
phase
Reactivation
phase
Immune
clearance
(cure)

6. Natural history of chronic hepatitis B
Chronic hepatitis B
Immune-
tolerant
phase
Immune-active
phase
Immune-control
phase
Reactivation
phase
Immune
clearance
(cure)
Cirrhosis with any of the phases

7. Natural history of chronic hepatitis B
Chronic hepatitis B
Immune-
tolerant
phase
Immune-active
phase
Immune-control
phase
Reactivation
phase
Immune
clearance
(cure)
Phases that need anti-viral drug treatment
Phases that DO NOT need anti-viral drug treatment
Cirrhosis with any of the phases

8. Algorithm for management of HBV infection-
WHO
Assessment for treatment
Monitoring
Stopping treatment

9. •Host liver injury
–Serum alanine aminotransferase (ALT) Pattern (and not one value)
•Viral status
–HBeAg, anti-HBe antibody
–HBV DNA quantitative assay IU/mL
•Presence/absence of cirrhosis
–Compensated cirrhosis Biopsy, APRI (>2.0)
FIB-4, Fibroscan, Fibrotest
–Decompensated cirrhosis Ascites
Hepatic encephalopathy
Variceal bleed
Jaundice
Pre-treatment assessment

10. Population
Summary of Recommendation -NVHCP
HBsAg
Guidelines for Roll out of Hepatitis B Diagnosis and management in India, NVHCP, MoH, 2019

11. Population
HBsAg −ve
HBsAg +ve
Summary of Recommendation
HBsAg
Guidelines for Roll out of Hepatitis B Diagnosis and management in India, NVHCP, MoH, 2019

12. Population
HBsAg −ve
HBsAg +ve
No Treatment
Required
Summary of WHO Recommendation
HBsAg
Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection (WHO 2015): P36-37

13. Population
HBsAg −ve
Non-cirrhotic
HBsAg +ve
Cirrhosis or
APRI >=2; FIB-
4>= 3.25
No Treatment
Required
Summary of WHO Recommendation
ALT HBV DNAHBsAg
Guidelines for Roll out of Hepatitis B Diagnosis and management in India, NVHCP, MoH, 2019
Fibrosis/age

14. Population
HBsAg −ve
Non-cirrhotic
HBsAg +ve
Cirrhosis or
APRI >=2; FIB-
4>= 3.25
Treatment
Recommended
No Treatment
Required
Summary of WHO Recommendation
ALT HBV DNAHBsAg
Guidelines for Roll out of Hepatitis B Diagnosis and management in India, NVHCP, MoH, 2019
Fibrosis/age
Irrespective of age, ALT, HBeAgor DNA

15. Guidelines for Roll out of Hepatitis B Diagnosis and management in India, NVHCP, MoH, 2019

16. What is normal ALT?
•Suggested upper limits for normal (ULN)
–Men: up to 30 U/L
–Women: up to 19 U/L
•However, the local laboratory’s reference range should be
used

17. What is a persistently normal/elevated ALT?
•The persistently elevated ALT under the program is defined as
at least 2 values four weeks apart in the last 6 months, which
are above the upper limit of normal.
NVHCP Guidelines, 2019

18. Need for monitoring
All need monitoring
(irrespective of need for treatment)
HBsAg +ve
Defer
treatment
No
treatment
Start
treatment

19. Monitoring
The disease is complex and has sequelae, resolution as well as
drugs side effects. Hence, three types of monitoring is
necessitated
•Monitoring for disease progression and treatment response in
persons with CHB prior to, during and post-treatment
•Monitoring for tenofoviror entecavirside-effects
•Monitoring for hepatocellular carcinoma

20. How to monitor?
•At least annually: ALT
HBsAg, HBeAg, HBV DNA level
APRI
Adherence to treatment
Drug adverse events (renal function)
•More frequent
–In those who do not clearly meet criteria for treatment
–Following treatment discontinuation
•Surveillance for hepatocellular cancer

21. :every 12 mo
Disease progression
/ treatment response
:every 12 months
Monitoring for treatment
toxicities
:every 6 months
Detection of liver cancer
(cirrhosis / family history)
Adherence Renal function Ultrasound
ALT, HBV DNA, HBeAg Risk factors for renal dysfunctionα-fetoprotein
Non-invasive tests
Baseline 6month 12month 18month 24month…
How to monitor?

22. How to treat?

23. Drugs to treat HBV infection
•There are various antiviral agents recommended for
treatment of CHB.
Adults
Children

24. Selection of antiviral drugs for CHB
•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.

25. Entecavir preferred over tenofovir
•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

26. •Tenofovir alafenamide fumarate ( TAF) is the drug of choice in
patients with reduced renal function or bone disease bone
toxicities, where entecavir is contraindicated
•Drugs with a low barrier to resistance (lamivudine, adefovir or
telbivudine) are available but not recommended as they lead
to drug resistance.
•Despite the inconvenience of injections and side effects
PegIFN may be considered in a sub group of non cirrhotics
where a finite therapy might achieve a sustained response.

27. Counseling and patient Preparedness
Key points prior to initiation of therapy
•Preparing to start treatment: Patients should be counseled
about the indications for treatment, including
–the likely benefits and side-effects,
–willingness to commit to long-term treatment, and
–need to attend for follow-up monitoring both on and off
therapy;
–the importance of full adherence for treatment to be both
effective and reduce the risk of drug resistance; and
–cost implications.
•Measurement of baseline renal function and assessment of
baseline risk for renal dysfunction should be considered in all
persons prior to initiation of antiviral therapy

28. Monitoring for tenofovir and entecavir toxicity
•Renal function should be monitored annually in persons on
long-term tenofovir or entecavir therapy, and growth
monitored carefully in children.
•Measurement of baseline renal function includes: serum
creatinine (Cr) levels, and calculation of creatinine clearance
(CrCl)/estimated glomerular filtration rate (eGFR) using the
Cockcroft–Gault (CG)
•CG formula: eGFR = (140 –age) x (weight in kg) x 0.85 (if
female) / (72xCr in mg/dL)

29. Dose Adjustment for Tenofovir

30. Monitoring for hepatocellular carcinoma (HCC)
Routine surveillance for HCC with abdominal ultrasound and
alpha-fetoprotein testing every six months is recommended for:
•Persons with cirrhosis, regardless of age or other risk factors
•Persons with a family history of HCC
•Persons aged over 40 years (lower age may apply according to
regional incidence of HCC), without clinical evidence of
cirrhosis (or based on APRI score ≤2), and with HBV DNA level
>2000 IU/mL (where HBV DNA testing is available).

31. Duration of treatment
•Cirrhosis or APRI >2.0Lifelong treatment
•Discontinuation may be considered exceptionally in those
without cirrhosis (or APRI < 2.0 in adults) and all of the
following:
–Can be followed carefully long-term for reactivation
–If HBeAg loss and seroconversion to anti-HBe, and maintained
for one year
–Persistently normal ALT
–Persistently undetectable HBV DNA

32. Issues in patients with
HBV infection

33. Issues in patients with chronic HBV infection
Q.1 Acute versus chronic infection
Q.2Chronic hepatitis versus liver cirrhosis
Q.3 No cirrhosis: Decide about treatment
Q.4 Cirrhosis: compensated versus decompensated
Q.5 When to treat? How to treat?
Q.6 How to follow-up?

34. Q.1: Acute versus chronic hepatitis
History & examination
•Prodrome
•Risk factor for recent exposure
•Jaundice
•Past history of liver disease
•Previous HBsAg status
Investigations
•Very high ALT/AST (>8-10X upper limit of normal)
•IgM anti-HBc
•No feature of cirrhosis / portal hypertension / decompensation

35. Acute HBV
•Usually self-limiting
•HBsAg clears in 95% in adults
•Rarely leads to chronic hepatitis (depends on age at infection)
•Rarely causes fulminant hepatitis

36. Age at HBV infection and natural history

37. Acute HBV infection vs acute liver failure
Acute viral hepatitis
(AVH-B)
Acute liver failure
(ALF-B)
Prodromal symptoms Present
Sudden jaundice Present
Liver size Hepatomegaly Small size liver
Encephalopathy Absent Present
SGPT/SGOT Markedly elevated
IgM anti-HBc Positive
PT prolongation Absent Present

38. Q.2: Chronic hepatitis versus liver cirrhosis
History & examination
Feature of cirrhosis / portal hypertension / decompensation
i.e. ascites, edema, encephalopathy, variceal bleed
Investigations
Hemogram >>> pancytopenia (hypersplenism)
LFT >>> Low serum albumin, PT prolongation
USG >>> Features of cirrhosis (next slide)
Fibroscan >>> Higher liver stiffness indicates cirrhosis
Endoscopy >>> Varices
Liver biopsy >>> Degree of fibrosis
Non-invasive markers>>> APRI (AST-platelet ratio index)

39. Q.2: Chronic hepatitis versus liver cirrhosis
Indicators of cirrhosis/portal hypertension on USG
Liver
Shrunken size
Nodular surface
Irregular margins
Splenomegaly (>11 cm)
Portal vein dilatation (>12 mm)
Venous collaterals
Coarse echotexture

40. Q.3: Treat or not, if no cirrhosis
History & examination
None
Investigations
ALT (SGPT) and AST (SGOT)
HBeAg and anti-HBe
HBV DNA quantitative
Follow-up
ALT monitoring for 6-12 months

41. Q.4: Compensated versus decompensated
History
•Ascites, edema
•Hepatic encephalopathy
•Variceal bleed
Investigations
•Total serum bilirubin
•Prothrombin time (INR)
Definition of decompensation
•Total bilirubin > 2.5 x ULN +INR >1.5
•Encephalopathy
•Ascites

42. Decompensated cirrhosis
Decompensation: presence of one of the following features
a)Ascites
b)Hepatic encephalopathy
c)Total bilirubin >2.5 x ULN* + prolonged prothrombin time
(>3 second prolongation or INR** >1.5)
d)Variceal bleed
* Upper limit of normal
** International Normalized Ratio

43. Summary
•Patients with acute hepatitis B do not need treatment
•In patients with chronic hepatitis B, try to identify whether
–Chronic HBV vs cirrhosis
–Compensated vs decompensated cirrhosis
•Those with cirrhosis (compensated or decompensated) need anti-
viral drug treatment
•Patients with chronic HBV and no cirrhosis need individualized
decision about treatment
•Starting antiviral drugs is easy, but the treatment is often life-long
•All patients need monitoring for hepatocellular cancer; those on
treatment also need periodic assessment for drug efficacy/toxicity