Friday, December 2, 2022

Hepatitis B Treatment Antiviral Drugs

What Is Hepatitis B

Pharmacology – ANTIVIRAL DRUGS (MADE EASY)

Hepatitis B is caused by a virus that infects the liver. It is one of the most common vaccine-preventable diseases affecting travellers and can cause either acute or chronic infection.

About 90 to 95 percent of adults with acute hepatitis B infection will clear the virus on their own within six months, and develop lifelong protection against it.

Some people are unable to clear the virus, and develop chronic hepatitis B. Untreated chronic hepatitis B can later develop into serious health problems. Children under four years old are at particular risk of chronic hepatitis B, because only up to 10% will clear the virus.

Emergency Hepatitis B Treatment

See your GP as soon as possible if you think you may have been exposed to the hepatitis B virus.

To help stop you becoming infected, they can give you:

  • a dose of the hepatitis B vaccine you’ll also need 2 further doses over the next few months to give you long-term protection
  • hepatitis B immunoglobulin a preparation of antibodies that work against the hepatitis B virus and can offer immediate but short-term protection until the vaccine starts to take effect

These are most effective if given within 48 hours after possible exposure to hepatitis B, but you can still have them up to a week after exposure.

Treatment For Chronic Hepatitis B

If blood tests show that you still have hepatitis B after 6 months, your doctor may recommend medication to reduce the risk of complications of hepatitis B and regular tests to assess the health of your liver.

Treatment is usually offered if:

  • your immune system is unable to control the hepatitis B by itself
  • there’s evidence of ongoing liver damage

Hepatitis B medications can help keep the virus under control and stop it damaging your liver, although they will not necessarily cure the infection and some people need lifelong treatment.

The main medicines for chronic hepatitis B include peginterferon alfa 2-a and antiviral medicines.

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What Are The Alternatives To The Treatment

Vaccination is the best and the only alternative for the hepatitis B virus. Also, the other best option is to be safe from your end and always have protected sex and do not abuse drugs. Do not share needles and if possible get the vaccination when you are young. Also, lead a healthy lifestyle with a proper diet intake.

Identification Of Novel Drug Targets

Management of Hepatitis B in Pregnancy

New drugs targeting novel targets are needed to develop true combination therapies and step toward a cure of HBV infection. Several targets and novel compounds are currently being evaluated in in vitro and in vivo experimental models, which could potentially complement NA or IFN-based therapy .

Schematic representation of various classes of anti-HBV molecules on the Hepatitis B virus life cycle. Compounds in development for chronic hepatitis B can be seen at www.hepb.org/professionals/hbf_drug_watch.htm. cccDNA, covalently closed circular DNA ER, endoplasmic reticulum hNTCP, human sodium taurocholate cotransporting polypeptide pgRNA, pregenomic RNA rcDNA relaxed circular DNA.

A more general manner to inhibit HBV protein functions would be to prevent their translation by degrading viral RNAs. In this respect, the use of antisense or small interfering RNAs could represent a POC approach to show that inhibiting the expression of viral proteins in the first place could inhibit viral replication or restore functions otherwise inhibited by viral protein . Hence, one could inhibit the production of HBx, HBc, as well as viral secreted protein and obtain multiple antiviral effects. But using siRNAs in vivo and delivering them to the entire liver to target all infected cells remains a therapeutic challenge, although major progress has recently been made in that area.

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Hbv Drugs Not Recommended

Other HBV treatment regimens include telbivudine used in addition to a fully suppressive ARV regimen, or adefovir used in combination with 3TC or FTC and a fully suppressive ARV regimen.20,25,26 However, data on these regimens in persons with HBV/HIV coinfection are limited. In addition, these regimens are associated with higher rates of HBV treatment failure and a higher incidence of toxicity when compared to regimens containing TDF, TAF, or entecavir. These toxicities include increased risk of renal disease with adefovir-containing regimens and increased risk of myopathy and neuropathy with telbivudine-containing regimens. Therefore, the Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents does not currently recommend adefovir or telbivudine for patients with HBV/HIV coinfection.

What Treatments Are Available For Chronic Hepatitis B

Hepatitis B

Hepatitis B treatment is based on the results of blood tests, age, and the degree of scarring in the liver. Hepatitis B treatment is recommended for patients with very active virus and an inflamed liver. People with chronic hepatitis B and cirrhosis also may be candidates for treatment.

Treatment involves taking an oral antiviral medication. In some cases, injections may be used.

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Hepatitis B And Pregnancy

The American College of Obstetricians and Gynecologists , the US Preventive Services Task Force , and the World Health Organization recommend routine prenatal screening for hepatitis B surface antigen in all pregnant womenduring every pregnancyregardless of previous test results or vaccinations. Pregnant women at risk for hepatitis B infections should be specifically targeted for vaccination. The risk of transmission of hepatitis B associated with amniocentesis is low. WHO further recommends all pregnant women undergo testing at least once for HIV and syphilis in addition to that for HBsAg and as early as possible in the pregnancy.

It is recommended that all infants receive their first dose of hepatitis B vaccine as soon as possible after birth , followed by two or three doses to complete the primary series.

To prevent maternal-fetal HBV transmission, a conditional WHO recommendation is that HBsAg-positive gravida who have an HBV DNA 5.3 log10 IU/mL receive tenofovir prophylaxis beginning the 28th week of pregnancy until at least birth. This is in addition to the three-dose hepatitis B vaccination in all infants, including a timely birth dose. When antenatal HBV DNA testing is not available, HBeAg testing can be used as an alternative study to determine eligibility for tenofovir prophylaxis to prevent mother-to-child transmission of HBV.

Question : Discontinuing Compared To Continuing Antiviral Therapy In Hbeag

Pharmacology 879 a AntiViral Drugs Viral Classification Non RetroVirus Herpes Influenza Hepatitis

Two observational studies, compared patients with chronic hepatitis B who stopped therapy after HBeAg seroconversion to those who continued to receive antiviral therapy. For both studies, the median duration of therapy leading to HBeAg seroconversion was 21 months, median follow-up after stopping therapy was 40 months, and median duration of consolidation treatment after HBeAg seroconversion was 12 months. Characteristics and risk of bias for both studies are illustrated in Tables and .

Compared to continued antiviral therapy, very low-quality evidence suggests increased risk of relapse of viremia in patients who stopped antiviral therapy with no effect on ALT flares. The rate of HBeAg seroreversion was 8% after a median of 6 months in 1 study, with a cumulative incidence of 9% at 5 years in another study. No clinical outcomes were reported. The quality of evidence was very low due to increased risk of bias, indirectness, and imprecision. Additional noncomparative and indirect evidence is summarized in the Supporting Information.

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Referral To And Assessment By Specialist Care For Pregnant Women Who Are Identified As Hepatitis B Surface Antigen

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What the quality statement means for service providers, healthcare professionals and commissioners

Service providersHealthcare professionalsCommissioners

What the quality statement means for patients, service users and carers

Pregnant women who are found to have hepatitis B infection

Definitions of terms used in this quality statement

Specialist care assessment
Equality and diversity considerations
  • have a history of substance misuse
  • ave recently arrived as a migrant, asylum seeker or refugee
  • have difficulty speaking or understanding English
  • are aged under 20 years
  • have experienced domestic abuse

Antiviral Treatment Endpoints And Prognosis Improvement

The above studies confirmed that HBV DNA inhibition and HBeAg seroconversion can both improve prognosis. However, long-term NA maintenance treatment is required for patients who only achieve HBV DNA inhibition. HBeAg seroconversion can not only improve prognosis but also lead to safe drug withdrawal in some patients therefore, this endpoint is important to achieve in clinical practice. For patients who cannot achieve HBeAg seroconversion, long-term HBV DNA inhibition should be maintained to delay disease progression and await the development of new drugs, which is also an acceptable option. Additionally, different percentages of relapses were present in patients with HBeAg seroconversion, 20%-40% could revert to HBeAg-positive CHB and 10%-20% could revert to HBeAg-negative CHB. Even after converting to inactive HBsAg carriers , 20%-40% may revert to HBeAg-negative CHB, and HCC incidence and liver-related mortality in these patients were both higher than those for HBsAg-negative healthy controls . Therefore, HBsAg clearance should be the goal for the treatment of CHB.

However, it should be noted that HBsAg clearance does not indicate virus eradication. Due to the presence of cccDNA, it is possible for HBV reactivation in patients treated with immunosuppressants, cytotoxic drugs and hormones. Therefore, we refer to HBsAg clearance as a clinical cure or functional cure, which is the highest treatment endpoint that can be achieved by current treatment methods.

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Who Is Eligible For The Treatment

Anyone who is diagnosed with the hepatitis B virus and anyone who feel that they might have contracted the virus through unsafe sex or contact injections have to undergo the treatment. In case you have an acute condition- meaning that the virus is short lived, you might not have to undergo the treatment. Changing your lifestyle patterns and having plenty of fluids and dietary changes are more than enough.

Advice On Physical Activity Diet And Alcohol

Hepatitis B Reactivation with Hepatitis C Treatment

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Service providersHealthcare professionalsCommissionersPeople with non-alcoholic fatty liver disease

Definitions of terms used in this quality statement

Advice on physical activity, diet and alcohol
  • be offered advice on physical activity and diet if they are overweight or obese, in line with NICEs guidelines on obesity and preventing excess weight gain
  • be advised that there is some evidence that exercise reduces liver fat content
  • be advised that, if they drink alcohol, it is important to stay within the governments recommended limits for alcohol consumption.

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Management Of Treatment Failure

Assessment of Treatment Adherence

Good adherence to anti-HBV therapies is important for maintaining maximal suppression of HBV replication . Poor adherence can result in substantially reduced plasma drug levels, depending on the number of doses missed and the half-life of the drug, and can result in increased viral replication . Investigation of adherence to NA therapy in patients with CHB has shown that nearly 40% may not be fully adherent this significantly impacts on the rates of viral suppression . Low-level viral replication associated with nonadherence increases the pressure on the potency of the NA, and consequently increases the risk of selecting for resistance. Specific treatment adherence questionnaires and drug concentration monitoring can be useful for the management of patients. The level of education, type of health insurance, cultural factors, as well as low copayment for medications can significantly impact medication adherence. Thus, programs on patient counseling and on medication adherence to improve effectiveness of antiviral therapy in clinical practice are recommended.

Management of treatment failure

Treatment Adaptation According to Cross-Resistance

Management of Antiviral Drug Resistance

Are The Results Of The Treatment Permanent

Once you are vaccinated, you will not have a chance of getting the virus. For others who have undergone the treatment options, you would not have the symptoms again, but still, the damage to your liver in some cases can be permanent. It depends on how far the virus has affected your liver and how your body has responded to the treatment.

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Selection Of Patients For Treatment

The persistence of HBV despite treatment often necessitates long durations of therapy. Therefore, the decision to treat must balance the risk of liver-related morbidity and mortality in the future with the likelihood of sustained response to treatment. The development of antiviral resistance is a major obstacle in long-term viral suppression hence, therapy should be initiated only when the benefits outweigh the risks.

Initial evaluation of HBV carriers should include assessment of HBV replication: HBeAg and HBe antibody , and quantitative HBV DNA level and activity/stage of liver disease: ALT, indicators of liver synthetic function , and evidence of portal hypertension . A liver biopsy is the only reliable method to assess histological damage, but is not necessary in all cases. High risk carriers should also be screened for HCC.

Figure 1

Modified American Association for the Study of Liver Disease algorithm for treatment of non-cirrhotic hepatitis B. ULN, upper limit of normal IFN, interferon-alfa LAM, lamivudine ADV, adefovir ETV, entecavir NA, nucleoside analogues PCR, polymerase chain reaction wks, weeks mos, months. In patients who meet only a single criterion, optimal management is not clear liver biopsy may be useful in defining histological necroinflammatory activity.

Screening for HCC is indicated for patients who have cirrhosis, men over the age of 40 and women over the age of 50, and those with a family history of HCC.

What Is My Risk

Treatment of Hepatitis Part 3 – Hepatitis B (HBV) Treatment

Your risk depends of several factors: destination, length of stay, what you do when you are travelling and whether you have direct contact with blood or other body fluids. In certain destinations, your risk may be higher, as some areas have higher numbers of people with chronic hepatitis B in the general population.

The risk increases with certain activities, such as unprotected sex, sharing needles, tattooing and acupuncture.

Aid and health care workers and anyone who receives medical or dental care with unsterilized or contaminated equipment in a country where hepatitis B occurs are also at greater risk.

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Choosing Oral Antivirals Versus Peginterferon

A primary decision point when choosing an initial therapy in a patient with chronic hepatitis B is whether to use an oral antiviral agent or an interferon-based agent . When an interferon-based agent is used, peginterferon is clearly preferred over interferon, primarily due to more convenient dosing, improved efficacy, and better tolerance. Thus, the following discussion will focus on comparing oral antivirals with peginterferon.

The availability of safe, well-tolerated, highly potent, oral antivirals that have a high genetic barrier to drug resistance, when taken together with the key disadvantages of peginterferon, have made the oral antivirals the preferred treatment for most individuals with chronic HBV infection. The oral antivirals have similar efficacy as peginterferon after 48 to 52 weeks of therapy for persons positive for hepatitis B e Ag and those negative for HBeAg . Long-term follow-up studies have shown that sustained treatment with oral antiviral therapy in persons with chronic HBV markedly reduces the risk of developing cirrhosis, decompensated liver disease, and hepatocellular carcinoma . There are also long-term follow-up studies that suggest interferon or peginterferon treatment for chronic HBV reduces the risk of HCC and improves survival, but these data are less robust than with oral antivirals, especially with peginterferon.

Monitoring People With Chronic Hepatitis B Infection Who Do Not Meet The Criteria For Antiviral Treatment

Quality statement

Rationale

Quality measures

Structure

Data source:

Process

Data source:

What the quality statement means for service providers, healthcare professionals and commissioners

Service providersHealthcare professionalsCommissioners

What the quality statement means for patients, service users and carers

People with chronic hepatitis B infection

Definitions of terms used in this quality statement

Chronic hepatitis B infection
Recommended intervals for monitoring
  • Adults with HBeAg-positive disease in the immune-tolerant and immune-clearance phases .
  • Adults with inactive chronic hepatitis B .
  • Children and young people .
  • Children, young people and adults with HBeAg or HBsAg seroconversion after antiviral treatment .
Monitoring people with chronic hepatitis B infection who meet the criteria for antiviral treatment

Equality and diversity considerations

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What Does It Mean To Have A Successful Treatment What Is A Sustained Virologic Response

In an untreated state, the hepatitis C virus infects the cells of the liver and then continuously lives there, making copies of itself that circulate in the bloodstream. Antiviral medications can destroy the ability of the virus to reproduce, so the amount of virus in the bloodstream then decreases. The amount of virus in the blood is measured by aviral load.

Treatment is successful when the viral load drops toundetectablelevels, which means the virus cannot be detected in the bloodstream at all. The viral load becomes undetectable during treatment and remains undetected after treatment has ended. If there is still no detectable virus in the blood 12 weeks after the end of the treatment, the treatment was successful. This is called a Sustained Virologic Response .

A patient who has achieved an SVR is considered to be cured of the hepatitis C virus.

Treatment Of Finite Duration With Peg

Management of Occupational Exposure to HIV

This strategy is intended to achieve a sustained off-treatment virological response. A 48-wk course of Peg-IFN- is mainly recommended for HBeAg-positive patients with the best chance of anti-HBe seroconversion. It is practically the only option that may offer a chance for sustained off-treatment response after a finite duration of therapy. In HBeAg-negative patients, Peg-IFN- therapy can achieve on-treatment viral suppression, but is followed by virological relapse after treatment cessation in many patients.

Finite-duration treatment with an NA is achievable for HBeAg-positive patients who seroconvert to anti-HBe on treatment. However, treatment duration is unpredictable before therapy as it depends on the timing of anti-HBe seroconversion and the treatment continuation after anti-HBe seroconversion. Anti-HBe seroconversion may not be durable after NAs discontinuation in a substantial proportion of these patients, therefore requiring close virologic monitoring after treatment cessation. Even after NA treatment prolongation for an additional 12 mo after anti-HBe seroconversion, a durable off-treatment response can be expected in 40%80% of these patients.

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