Hepatitis: Management

Uchenna Ijoma
Clinical evaluation

Relevant history Clinical examination

• Risk factors • Chronic hepatitis is usually
• Family history asymptomatic
• Alcohol intake • Recurrent jaundice
• Hepatomegaly
• Features of liver
decompensation
Laboratory evaluation
• HBV serological profile • Liver imaging
• HBV viral load Ultrasound, CT,, MRI
• HCV viral load / Genotyping • Assesment of fibrosis
• HBsAg quantification* Transient elastography (Fibroscan)
• LFT APRI score
• Serum proteins FIB-$ score ,, others
• Electrolytes , urea creatinine • Liver biopsy + histology
• Others
 Liver biopsy
• Percutaneous: blind or image guided, transjugular,
laparscopic open surgical.
• Menghini needle, trcut, automated biopsy guns.
• Intercostal, subcostal routes,
• Indications
• Precautions
• Complications
• Contraindications

03/13/2025 Lecture series in Medicine 4

The phases of chronic hepatitis B
Immune Immune Immune Immune
tolerance clearance control escape

HBeAg+ve HBeAg–ve
< >< >
HBV-DNA

ALT

HBeAg +ve Inactive (carrier) HBeAg –ve active

chronic hepatitis state* chronic hepatitis

Slide 8
 Disease Classification Update (EASL 2017)
HBeAg+ HBeAg-

New Chronic Chronic

Chronic Infection Chronic Hepatitis
terminology Infection Hepatitis
Old Immune tolerant Immune reactive Inactive Carrier HBeAg- CHB
terminology
HBsAg High High/intermediate Low Intermediate

HBeAg Positive Positive Negative Negative

HBV DNA >107 IU/mL 104-107 IU/mL <2000 IU/mL >2000 IU/mL

ALT Normal Elevated Normal Elevated

Liver None/minimal Moderate/severe None/minimal Moderate/severe

Disease
Summary of HBV biomarkers
HBV Marker Significance
HBsAg Evidence of HBV infection
HBeAg High infectivity, infection with wild
type of HBV
Anti-HBe Evidence of convalescence
Anti-HBs Evidence or presence of immunity
Anti-HBc (IgM) Acute/Current HBV infection
Anti-HBc (IgG) Previous or resolved HBV infection
HBV DNA Marker of viraemia, infectivity and
response to therapy
Assessment of Liver Disease

• Liver function tests

• HBV DNA
• HBsAg quantification
• Imaging (USS, CT Scan and/or MRI)
• Non-Invasive methods of evaluation of fibrosis- APRI score , FIB-4,
Fibroscan
• Liver biopsy
• Other relevant tests, e.g. HAV, HIV,HCV,HDV
 Goals of Treatment

• Virologic/Serologic Response
• HBsAg loss (ultimate goal)
• Decrease in serum HBV DNA to undetectable levels
• HBeAg loss and seroconversion to anti-HBe
• Biochemical Response
• Decrease in ALT levels to normal
• Histological Response
• Decrease in inflammation and fibrosis (METAVIR or similar)
• Prevent development of cirrhosis (and associated complications), hepatic
failure, and hepatocellular carcinoma
Who to treat……
• HBeAg positive and HBeAg negative chronic hepatitis (new
classification)
• Presence of liver fibrosis/ cirrhosis
• Family history of HBV complications in a first degree
relative
• Need to undergo immunosuppressive therapy
Treatment recommendations

Nucleoside RESISTANCE
DOSE DURATION ROUTE INDICATION REMARKS
Analogues BARRIER

Life-long, or
Low risk of until loss of High viral Watch out for
Tenofovir 300mg dly P.O
resistance HBsAg/HBeAg load Nephrotoxicity
positivity

Life-long , or Maybe
0.5mg dly
Low risk of until loss of High viral used in
Entecavir resistance
Lamivudine
HBsAg/HBeAg
P.O
load place of
naïve
positivity Tenofovir
 Treatment recommendations

Interferons Resistance Dose Duration Route Indication Remarks

Barrier
Pegylated Not 180mcg 48 weeks SC Low viral load, For finite duration
Interferons applicable wkly High ALT of therapy, Higher
HBsAg loss &
Higher HBeAg
seroconversion
 Interferons vs Nuceot(s)ide analogues
Interferon vs. Nucleos(t)ide Analogues

• Peg-IFN
• Advantages: Finite, low rates of HBsAg loss, absence of resistance
• Disadvantages: Moderate antiviral effect, low tolerability, high risk for adverse
events, contraindicated in decompensated cirrhosis and pregnancy,
subcutaneous injections

• Nucleos(t)ide Analogues
• Advantages: Potent antiviral effect, high tolerability, safety, no
contraindications for treatment, regression of fibrosis/cirrhosis over time
• Disadvantages: Unknown duration of treatment, rare HBsAg loss, resistance
risk (lower with Entecavir/Tenofovir)
 Prevention
 Minimize alcoholic beverages
 Proper screening of blood & blood products
 Use of sterile needles
 Observe standard universal precaution at all times.
 Unsafe sexual habits
 Proper hygiene
 Avoid use of local concoctions
 Immunization

03/13/2025 Lecture series in Medicine 14

 Hepatitis B Vaccine
First vaccine against a major human cancer,
introduced in 1982
Good results in Taiwan, Saudi Arabia, Egypt.
introduced in NPI in 2003

 Vaccine recommended in
All those aged 0-18
Those at high risk

 Infants: several options that depend on status of the

mother

 Adults
* 0,1, 6 months
HBV Post Exposure Prophylaxis (PEP)

• Wash wounds with soap/water; flush mucous membranes with water

• Screen source (HBsAg, anti-HCV, HIV)
• Test exposed individual: HBsAg, anti-HBs, anti-HBs (IgG)
• PEP active/passive immunization
• HBIG and HBV vaccine [0,1,6 months]
• Source exposure HBsAg-positive or unknown
• HBIG repeated at 1 month
• Source exposure HBeAg-positive, has high HBV DNA, or if information is unknown
• Post vaccination serologic testing can be done 1-2 months after vaccination series
 Recommended Postexposure Prophylaxis for Percutaneous Exposure to
Hepatitis B Virus*

Vaccination and antibody Treatment when source is

National Clinicians’ Post-exposure Prophylaxis Hotline (PEPline): 1.888.448.4911

status of exposed person
HBsAg† positive HBsAg negative Not tested or infection
status unknown
Unvaccinated HBIG‡ X 1; Initiate hepatitis B Initiate hepatitis B vaccine
Initiate hepatitis B series
series series

Known Responder§
No treatment No treatment No treatment

Known non-responder, No treatment; consider If known high-risk source, treat

HBIG X 1 and initiate
Previously Vaccinated

no revaccination revaccination for future as if source were HBsAg

revaccination
protection positive.

Known non-responder to If known high-risk source, treat

initial & revaccination HBIG X 2 – second dose one
No treatment as if source were HBsAg
month after the first
series positive

Antibody response
unknown Test exposed person for Test exposed person for anti-
anti-HBs|| HBs||
-If adequate¶, no treatment No testing, no treatment -If adequate¶, no treatment
-If inadequate¶, HBIG X 1 and -If inadequate¶, vaccine booster
vaccine booster dose# dose#

* Postexposure recommendations apply ≤7 days after exposure. Modified from:

† Hepatitis B surface antigen Pickering L, eds. “Red Book 2000 Report of the Committee on Infectious
‡ Hepatitis B immune globulin (0.06 mL/kg administered intramuscularly) Diseases, 25th ed.” 2000, American Academy of Pediatrics, p. 302.

§ Person with anti-HBs antibody level of 10 mIU/mL

Atkinson W, Wolfe C, eds. “Epidemiology and Prevention of Vaccine-Preventable
|| Antibody to hepatitis B surface antigen Diseases, 7th ed.” Jan 2002, DHHS-CDC, p.185.
¶ Adequate response is anti-HBs 10mIU/mL; inadequate response is anti-HBs<10mIU/mL
#The person should be evaluated for antibody response after the vaccine booster dose. For persons who received HBIG, anti-HBs testing should be done when passively
acquired antibody from HBIG is no longer detectable (eg, 4-6 mo); if they did not receive HBIG, anti-HBs testing should be done 1-2 months after the vaccine booster dose.
If anti-HBs is inadequate (<10mIU/mL) after the vaccine booster dose, 2 additional doses should be administered to complete a 3-dose reimmunization series.
 Hepatitis C

03/13/2025 Lecture series in Medicine 18

 Goals of
Natural History HCV
Management
• Mode of infection • To achieve a sustained virologic
• Risk factors for disease response (SVR) = cure
progression • To prevent progression to
• Age, alcohol, co-infections cirrhosis, liver failure and
• Generally, asymptomatic acute hepatocellular carcinoma
phase • To prevent transmission of HCV
• Majority of acute infections infections
become chronic • To improve quality of life
• Long term duration of cirrhosis
before HCC
 Investigations to decide treatment
• HCV viral load
• Genotyping and subtyping
• Assessment of liver disease
Liver fibrosis and cirrhosis:
liver biopsy
non invasive markers of fibrosis

March 13, 2025 WACP and RCP gastroenterology training 20

Pre-treatment assessment: lab-based tests

Liver/Renal Function Assessment:

• AST, Platelet Count => APRI Score
 informs prioritization of treatment (if necessary), treatment duration and need for
specialist referral
• Creatinine => calculate GFR
 impaired renal function should be managed by a specialist
• Additional: FBC, complete LFT/RFT panels
Genotyping *
There are 6 recognized genotypes of HCV: 1, 2, 3, 4, 5 and 6
*HCV genotyping should be done to determine optimal treatment only if pan-
genotypic treatment regimens are un-available.
Goal of HCV Treatment

• When patients receive proper HCV treatment and achieve cure, they can reduce their
risk of HCC by 70% and all-cause mortality by 50%.
• Sustained Virological Response (SVR) = the absence of detectable HCV RNA in the
blood at least 12 weeks after treatment is completed
• SVR is how we define cure of HCV
• SVR is usually associated with resolution of liver disease in patients without cirrhosis
• Highlights the importance of early treatment
• Data suggests that cirrhotic patients who attain SVR are at reduced risk of HCC and mortality
than untreated patients/those who do clear the virus
• Recommend determination of SVR 12 weeks after the end of treatment = SVR12
• Note: treatment does not protect against subsequent re-infection.
HCV Therapeutic Timeline
Ledipasvir*
Paritaprevir**
Ombitasvir**
Sofosbuvir & Dasabuvir**
Simeprevir Daclatasvir
Telaprevir &
Boceprevir
First all oral
GT 1
First all oral Velpatasiv
GT 2 & 3
Interferon + RBV
Voxilaprevir

Interferon 48W

2015 2016/17
 Standard of care for HCV treatment

SOC before 2011 SOC after 2011

Drug regimen Duration of treatment Drug regimen Duration of treatment

PEG INF + Ribavarin 24 or 48 months Triple therapy: Telaprevir:

(SVR 40%-50%) depending on PEG ING+ Ribavarin 12 weeeks followed
genotype by 12 to 40 weeks of
+bocepreir (SVR 63%- PEG/RIBA
66%) Boseprevir:
24-44 weeks after 4
Or weeks PEG/RIBA lead-
Telaprevir (SVR 65%- in
75%)

March 13, 2025 WACP and RCP gastroenterology training 24

Newer regimens

• Sofosbuvir/daclatasvir

• Sofosbuvir/velpatasvir

• Sofosbuvir/velpatasvir/voxliprevir

• Glecaprevir/pibrentasvir: newest, advocated for 8 weeks

therapy
HCV Post Exposure Prophylaxis (PEP)

• Wash wounds with soap/water; flush mucous membranes with water

• Screen source (HBsAg, anti-HCV, HIV)
• Test exposed individual: anti-HCV
• PEP active/passive immunization for HBV (if persons is unvaccinated)
• HBIG and HBV vaccine [0,1,6 months]
• Source exposure HBsAg-positive or unknown
• HBIG repeated at 1 month
• Source exposure HBeAg-positive, has high HBV DNA, or if information is unknown
• Post vaccination serologic testing can be done 1-2 months after vaccination series
 For the Future……..
HBV HCV
• Novel biomarkers for HBV • DAAs awaiting approval
• cccDNA targeting ;
destabilization, silencing, HBxx
Inhibition
• C(p)AMS
• Therapeutic vaccines
• DAAs

March 13, 2025 WACP and RCP gastroenterology training 27

 WHO Global Health Sector
Strategy on Viral Hepatitis 2016
- 2021
28 May 2016: The first of
its kind, WHO publishes a
global strategy aiming for
elimination of viral
hepatitis as a public health
threat by 2030

Source: WHO Global Health Sector Strategy on viral hepatitis. Available at:
https://apps.who.int/gb/ebwha/pdf_files/WHA69/A69_32-en.pdf?ua=1 {Accessed August 2016}
Consequences of Hepatitis