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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