Pharmacotherapy of Hepatitis B
PST 06106
Basic Pharmacotherapy
Session 28: Pharmacotherapy of Hepatitis B
Learning Objectives
By the end of this session students are expected to be able to:
Define hepatitis B
Explain pathophysiology of hepatitis B
Explain the clinical presentation of hepatitis B
Outline diagnosis of hepatitis B
Describe pharmacological treatment of hepatitis B
Describe the monitoring of hepatitis b therapy
Activity: Buzzing
What is Hepatitis
B ?
Definition of
Hepatitis B
Hepatitis
B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV).
It can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer.
HBV is transmitted sexually, parenterally, and
perinataly
.
In areas of high HBV prevalence, perinatal transmission from mother to infant is most common, whereas in areas of intermediate prevalence, horizontal transmission from child to child is most common.
Sexual contact, both homosexual and heterosexual, and injection drug use are the predominant forms of transmission in low-endemic countries
Pathophysiology of Hepatitis B
The life cycle of HBV is complex but, essentially, it acts as a stealth virus by evading the immune system.
During the first stage of infection, the HBV
virion
(virus particle) attaches to a liver cell (hepatocyte) then penetrates the hepatocyte’s cytoplasm
The HBV
virion
is uncoated, which means that
nucleocapsids
can move into the hepatocyte’s nucleus and convert the DNA to covalently closed circular DNA (
cccDNA
) – a double-stranded DNA structure
The
cccDNA
is very stable and can stay in the host nucleus for many months in chronic disease
Pathophysiology of Hepatitis
B Cont…
The virus makes copies of itself in a process that lacks “proof reading ability”, which allows the virus to mutate
The newly formed HBV
virions
are released into the bloodstream, from where they invade other hepatocytes and repeat the replication process.
It is thought that HBV causes inflammation and progressive fibrosis in the infected liver by triggering the immune system to attack the hepatocytes
Clinical Presentation And Diagnosis Of Hepatitis B
The majority of acute HBV infections are also asymptomatic but around 30% of adults will present with the following symptoms;
Signs and symptoms
Easy fatigability, anxiety, anorexia, and malaise
Ascites, jaundice, variceal bleeding, and hepatic encephalopathy can manifest with liver
decompensation(loss of brain function when a damaged liver doesn't remove toxins from blood
)
Clinical Presentation And Diagnosis Of Hepatitis
B Cont…
Signs and
symptoms….
Hepatic
encephalopathy is associated with hyper excitability, impaired mentation, confusion,
obtundation
(loss of consciousness), and eventually coma(a period of prolonged unconsciousness)
Vomiting and seizures
Clinical Presentation And Diagnosis Of Hepatitis B Cont…
Laboratory tests
Presence of hepatitis B surface antigen >6
mo
Intermittent elevations of hepatic transaminase (alanine transaminase
Liver biopsies for pathologic classification as chronic persistent hepatitis, chronic active hepatitis, or cirrhosis
Activity
: Brainstorming
What
is the treatment of Hepatitis B infection??
Pharmacological Treatment Of Hepatitis B
HBV infections are not curable; rather, the goals of therapy are to increase the chances for
seroclearance
, prevent disease progression to cirrhosis and HCC, and to minimize further injury in patients with ongoing liver damage
.
Pharmacological treatment includes
;
Tenofovir
(PO) 300mg once daily for life
OR
Entecavir
(PO) 0.5mg–1mg once daily for life
OR
Lamuvidine
(PO) 100mg once daily for life
Pharmacological Treatment Of Hepatitis
B Cont….
Prophylaxis against HBV can be achieved by vaccination or by passive immunity in
postexposure
cases with hepatitis B immunoglobulin.
Vaccination is the most effective strategy to prevent infection
Monitoring Of Hepatitis B Therapy
Response to therapy is monitored by;
Biochemical (normalization of ALT levels),
Histologic examination of liver cells from biopsy (a minimum 2-point decrease in histology activity compared with baseline biopsy), and
Virologic
response (undetectable serum HBV DNA levels and loss of HBeAg in HBeAg-positive patients).
Maintenance of viral suppression is defined as durability of response.
In HBeAg-positive patients, successful therapy includes loss of HBeAg status and seroconversion to anti-HBeAg.
Key Points
Hepatitis
B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV).
It can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer
HBV infections are not curable; rather, the goals of therapy are to increase the chances for
seroclearance
, prevent disease progression to cirrhosis and HCC, and to minimize further
Evaluation
What
is Hepatitis B?
What is the pathophysiology of
Hepatitis B?
What are the signs and symptoms of Hepatitis B?
How is the treatment of
Hepatitis B?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
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