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Questions and Answers
What is a significant factor that contributes to the slow decline of HBsAg during nucleos(t)ide analogue therapy?
What is a significant factor that contributes to the slow decline of HBsAg during nucleos(t)ide analogue therapy?
What outcome is typical when nucleos(t)ide analogues are discontinued in patients?
What outcome is typical when nucleos(t)ide analogues are discontinued in patients?
Which treatment was first approved for hepatitis B in 1992?
Which treatment was first approved for hepatitis B in 1992?
What was a major step in the development of HBV therapeutics in 1998?
What was a major step in the development of HBV therapeutics in 1998?
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What common treatment for hepatitis B was recognized as harmful in a randomized controlled trial?
What common treatment for hepatitis B was recognized as harmful in a randomized controlled trial?
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What estimation was made regarding HBsAg clearance under continuous treatment with nucleos(t)ide analogues?
What estimation was made regarding HBsAg clearance under continuous treatment with nucleos(t)ide analogues?
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What kind of therapy was used in the early treatment of hepatitis B during the 1960s and 1970s?
What kind of therapy was used in the early treatment of hepatitis B during the 1960s and 1970s?
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Which medication is noted to be well tolerated even in patients with decompensated cirrhosis?
Which medication is noted to be well tolerated even in patients with decompensated cirrhosis?
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When were the first clinical trials for hepatitis B treatment conducted?
When were the first clinical trials for hepatitis B treatment conducted?
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What was likely necessary to achieve sustained decreases in HBsAg during treatment?
What was likely necessary to achieve sustained decreases in HBsAg during treatment?
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What is the primary characteristic of the Immune Tolerant Phase of Chronic HBV Infection?
What is the primary characteristic of the Immune Tolerant Phase of Chronic HBV Infection?
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Which treatment is not preferred for chronic HBV infection in pediatric patients?
Which treatment is not preferred for chronic HBV infection in pediatric patients?
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How does the persistence of HBV manifest after HBeAg seroconversion?
How does the persistence of HBV manifest after HBeAg seroconversion?
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What has been noted about the global prevalence of HBV infection as of 2020?
What has been noted about the global prevalence of HBV infection as of 2020?
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What is true regarding hepatitis D virus (HDV) in relation to HBV?
What is true regarding hepatitis D virus (HDV) in relation to HBV?
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Which significant advancement in the understanding of HBV occurred in the late 1970s?
Which significant advancement in the understanding of HBV occurred in the late 1970s?
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What was the primary focus of the Nobel Prize awarded to Baruch S. Blumberg in 1976?
What was the primary focus of the Nobel Prize awarded to Baruch S. Blumberg in 1976?
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What is the relationship between HBeAg and HBV infection severity?
What is the relationship between HBeAg and HBV infection severity?
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What are the four major serotypes of HBV that were recognized in the 1980s?
What are the four major serotypes of HBV that were recognized in the 1980s?
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How many genotypes of HBV are recognized today?
How many genotypes of HBV are recognized today?
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Which method was recommended by the WHO to reduce post-transfusion hepatitis in 1970?
Which method was recommended by the WHO to reduce post-transfusion hepatitis in 1970?
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What type of virus is HBV classified as?
What type of virus is HBV classified as?
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What major impact did the discovery of the Australia antigen have on public health?
What major impact did the discovery of the Australia antigen have on public health?
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What is a disadvantage of oral antiviral treatment for HBV?
What is a disadvantage of oral antiviral treatment for HBV?
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What percentage of patients with chronic HBV infection are at risk of early death due to liver cancer or end-stage liver disease?
What percentage of patients with chronic HBV infection are at risk of early death due to liver cancer or end-stage liver disease?
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Which group has the highest risk of developing chronic HBV infection after acute exposure?
Which group has the highest risk of developing chronic HBV infection after acute exposure?
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What is the primary goal of HBV therapy as of 2020?
What is the primary goal of HBV therapy as of 2020?
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Which of the following is NOT a mode of transmission for HBV?
Which of the following is NOT a mode of transmission for HBV?
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What is a reason for the difficulty in completely eradicating chronic HBV infection?
What is a reason for the difficulty in completely eradicating chronic HBV infection?
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What percentage of HBsAg prevalence indicates a high prevalence in a population?
What percentage of HBsAg prevalence indicates a high prevalence in a population?
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Which factor contributes to the debate on nucleos(t)ide analogue treatment for HBV?
Which factor contributes to the debate on nucleos(t)ide analogue treatment for HBV?
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What is a significant risk factor for developing HCC in chronic HBV patients?
What is a significant risk factor for developing HCC in chronic HBV patients?
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Which continent had approximately 3.9 million immigration cases related to HBV from 2002 to 2011?
Which continent had approximately 3.9 million immigration cases related to HBV from 2002 to 2011?
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What is a significant consequence of lamivudine therapy related to drug resistance?
What is a significant consequence of lamivudine therapy related to drug resistance?
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Why does pegylated interferon lead to higher rates of HBeAg and HBsAg loss compared to nucleos(t)ide analogues?
Why does pegylated interferon lead to higher rates of HBeAg and HBsAg loss compared to nucleos(t)ide analogues?
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Which of the following is NOT a notable advantage of the newer nucleos(t)ide analogues approved for hepatitis B?
Which of the following is NOT a notable advantage of the newer nucleos(t)ide analogues approved for hepatitis B?
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Which of the following treatments for chronic hepatitis B has been associated with the potential for reversing fibrotic damage?
Which of the following treatments for chronic hepatitis B has been associated with the potential for reversing fibrotic damage?
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What is one critical limitation of lamivudine therapy for hepatitis B?
What is one critical limitation of lamivudine therapy for hepatitis B?
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What is the primary effect of interferon on HBV as indicated in recent studies?
What is the primary effect of interferon on HBV as indicated in recent studies?
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Which of the following is true regarding pegylated interferon compared to lamivudine?
Which of the following is true regarding pegylated interferon compared to lamivudine?
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What important benefit do telbivudine, entecavir, and tenofovir disoproxil fumarate provide over older treatments?
What important benefit do telbivudine, entecavir, and tenofovir disoproxil fumarate provide over older treatments?
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What does recent research suggest about the effect of interferon on cccDNA?
What does recent research suggest about the effect of interferon on cccDNA?
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In the treatment of chronic hepatitis B, what is one of the primary goals of antiviral therapy?
In the treatment of chronic hepatitis B, what is one of the primary goals of antiviral therapy?
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Study Notes
Hepatitis B
- Hepatitis B virus (HBV) is the causative agent
- HBV biology and disease processes are understood
- Vaccines prevent HBV infection
- Antiviral therapy suppresses HBV replication and prevents liver disease progression
- HBV infection prevalence and associated morbidity/mortality have decreased since 2020
History of HBV
- 1970: World Health Organization recommended screening blood donors for HBsAg, which led to a decline in post-transfusion hepatitis
- Late 1970s/Early 1980s: Molecular biology techniques advanced HBV virology understanding; HBV is DNA-containing and replicates through reverse transcription
- 1972: HBeAg, a new antigen associated with HBV, was discovered; presence associated with infectivity and liver injury
- 1980s: Studies showed some HBeAg-negative patients had high HBV replication levels and continued hepatic inflammation.
- 1980s: Four major serotypes (adw, adr, ayw, ayr) were recognized, later replaced by HBV genotypes. At least 10 genotypes exist, with varying geographical distributions
- The cccDNA (covalently closed circular DNA) has a long half-life in non-dividing hepatocytes and is unaffected by current nucleos(t)ide analogues
HBV Treatment
- Corticosteroids were used in the 1960s/70s, but their harmful effects in chronic hepatitis B patients were noted in later trials.
- Standard interferon was approved as an antiviral treatment for HBV in 1992, though first trials were conducted earlier.
- Lamivudine (1998): major step in HBV therapeutics, but associated with high drug resistance rates.
- Telbivudine, entecavir, and tenofovir disoproxil fumarate were approved (2000-2008) and are characterized by low drug resistance rates.
- Maintain long term suppression
- Enable fibrosis (cirrhosis) reversal
- Pegylated interferon: increased efficacy (2005) and simpler administration but weaker antiviral activity; results in higher rates of HBeAg and HBsAg loss
HBV Screening
- Importance of screening blood donors for HBsAg (1970)
- Screen infants, children and adults exposed to intermediate/high prevalence areas
- Candidates for screening: Persons born in high and intermediate endemic areas; US and European children of immigrants; household and sexual contacts of HBV carriers, injection drug users and individuals with multiple sexual partners or a history of STDs.
- Screening Algorithm: Assess HBsAg (positive/negative), If positive - evaluate for treatment; If negative - Assess anti-HBs (Positive/Negative); If neg = vaccinate, positive= Immune to HBV
HBV Disease Progression
- Acute infection: >90% of infected infants develop chronic disease, <5% of immunocompetent adults progress to chronic disease.
- Chronic infection: 30% of chronically infected individuals develop liver cancer (HCC)
- Liver cirrhosis and liver failure development after years
- Liver transplantation is recommended.
HBV Diagnosis
- HBV diagnosis involves examining serological markers like HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc.
- HBsAg: Marker of chronic HBV infection (found for more than 6 months)
- Anti-HBs: Marker of immunity
- HBeAg: Index of actively replicating viral infection and high infectivity. Appears in recovery or reactivation phase
- Anti-HBe: Indicates recovery phase
- Anti-HBc: Marker for past or possibly current HBV infection
Chronic HBV infection phases
- Immune tolerant phase,
- Immune clearance phase,
- Inactive carrier phase, and
- Reactivation phase
HBV Treatment and Therapy
- Treatment with analogues is often used; maintains viral response in patients and results in some degree of histological improvement in patients
- PEG IFN enhances HBe seroconversion in 36% of patients leading to HBsAg loss
- Treatment Combinations: show promise in achieving synergistic antiviral and immune effects thereby leading to sustained loss of detectable HBV DNA, reduced drug resistance, reduced cccDNA and HBsAg loss.
Important Considerations
- HBV remains a significant global health problem that requires ongoing efforts to reduce prevalence,
- Current and ongoing combination therapy with treatment and therapy for chronic HBV are needed to improve clinical management
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Description
Test your knowledge on the history and factors affecting hepatitis B treatment. This quiz covers key developments in therapies, outcomes of treatments, and significant factors contributing to HBsAg decline during therapy. Challenge yourself with questions about medications, clinical trials, and harmful treatments recognized over the years.
