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Hepatitis
Hepatitis B – Recent Developments in Therapy
Jennifer Price and Zhiping Li
Division of Gastroenterology and Hepatology, Johns Hopkins University
Abstract
Hepatitis B is a global health problem that affects millions of people and causes over 1 million deaths every year. The goals of hepatitis B
therapy are to prevent disease progression and improve patient survival and quality of life. Currently, many experts agree that patients with a
high hepatitis B viral load should be treated, because the risks of hepatitis B disease progression and complications are associated with HBV
viral load. The treatment options include interferon injection and oral nucleotide and nucleoside analogues. In this article, we discuss recent
developments in who should be treated for hepatitis B, treatment strategies and special conditions associated with hepatitis B treatment.
Keywords
HBV, hepatitis B, therapy, viral load, peginterferon alpha-2a, lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir
Disclosure: The authors have no conflicts of interest to declare.
Received: 11 June 2009 Accepted: 30 June 2009
Correspondence: Zhiping Li, Johns Hopkins University, 912 Ross Bldg, 720 Rutland Ave, Baltimore, MD 21205, US. E:
zhipingli@jhmi.edu
Infection with hepatitis B virus (HBV) is a significant global public Some chronic HBV patients are infected with mutations in the pre-core
health problem. It is estimated that 350 million people worldwide are and/or basal core promoter regions, leading to a decrease or loss of
chronically infected with HBV and that one-third of the world’s HBeAg expression.
11
These patients have low rates of spontaneous
population has evidence of exposure to the virus.
1
Sequelae of remission and a high risk of liver disease progression.
11
It is therefore
chronic infection with hepatitis B (CHB) include end-stage liver important to distinguish them from inactive carriers; hence, serial
disease and hepatocellular carcinoma (HCC), and have been monitoring of HBV DNA and alanine aminotransferase (ALT) for all
associated with over 1 million deaths per year.
2–4
HBsAg-positive, HBeAg-negative individuals is recommended.
The natural history of HBV infection is a dynamic process involving Goals of Treatment
interactions between host, viral and external factors. HBV infection The overall goal of treatment of CHB is to improve survival through
therefore results in a range of clinical manifestations with varying remission of liver disease and prevention of cirrhosis, liver failure and
risk of progression. This natural history can be divided into four HCC. This is accomplished by maintaining sustained suppression of
distinct phases, which are not necessarily sequential or HBV replication. Therefore, reduction of HBV DNA levels is the primary
experienced by all patients. First, the ‘immune-tolerant’ phase is parameter used to evaluate treatment response. Loss of HBeAg,
characterised by high levels of viraemia with minimal elevation or development of anti-HBe, loss of HBsAg, development of anti-HBs,
normal level of aminotransferase and minimal inflammation on normalisation of ALT and improvement in liver histology are additional
histology. This phase is more frequent and more sustained during goals of therapy.
infection early in life.
5,6
Second, during the ‘immune-reactive’ phase,
HBV DNA levels and replication are low. Unlike the immune-tolerant Deciding Who to Treat
stage of infection, this phase is associated with histological There are currently seven approved medications for adults with HBV
evidence of liver disease and more rapid disease progression. It may infection in the US and Europe. Treatment is indicated in patients with a
also be referred to as the ‘immune-clearance’ phase.
1,2,7
Third, rapid decline in liver function, patients with cirrhosis and patients with
transition into the ‘inactive carrier’ stage often occurs with hepatitis CHB who plan to initiate immunosuppressive therapy and therefore are
B e antigen (HBeAg) seroconversion. The inactive carrier stage is at risk of reactivating their infection.
12
Patients with chronic HBV
characterised by very low or undetectable HBV DNA. Hepatitis B infection should be evaluated for treatment; choosing who among them
surface antigen (HBsAg) may be lost in 1–3% of patients; however, to treat remains a challenge. Guidelines to assist this decision focus on
even these individuals can experience disease reactivation.
8
Finally, three parameters: HBeAg status, ALT levels and HBV DNA levels.
approximately one-third of inactive carriers will enter the
‘reactivation’ phase of the disease, which is characterised by Traditionally, the American Association for the Study of Liver Disease
fluctuating high levels of HBV DNA and aminotransferases.
9,10
Other (AASLD) and other organisations have relied heavily on ALT thresholds to
patients directly transition into this phase from the immune reactive guide treatment decisions. More recently, however, data have suggested
stage upon HBeAg seroconversion. that truly normal aminotransferases are significantly lower than current
38 © TOUCH BRIEFINGS 2009
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