Antiviral Medications For Hepatitis B

Hepatitis B World Prominence

Hepatitis B virus causes the disease Hepatitis. Hepatitis is considered to be the leading cause of liver cancer worldwide . Hepatitis B virus can be found in almost every region of the world but is most prevalent in countries where the virus is endemic. HBV is endemic in some countries located in Asia, Africa, South America, and the Caribbean.

Approximately two billion people have been infected with HBV which means almost 1 out of 3 people have been infected. Every year an estimated 1.5 million people will become newly infected and roughly 10% of those individuals will go undiagnosed. Every year, an estimated 820,000 people die from Hepatitis B infection and related HBV complications.

The spread of Hepatitis B virus in the western world occurs most often through sexual intercourse or needle sharing by intravenous drug users . IVDU show the highest rate of HBV infection in Europe and North America. There are also higher rates of Hepatitis B infection among men who have sex with men . Risk of being infected with HBV increases with having multiple sex partners.

What Do The Panels Test Indicators Mean

-ALAT : An enzyme produced by the liver and released into the bloodstream when the liver is damaged. Therefore, high levels of ALAT suggest liver damage.

-ASAT : An enzyme produced by the liver, with elevated levels of ASAT suggesting liver damage.

Anti-HBs : Hepatitis B virus caused by type B virus a common cause of cirrhosis. The test detects the surface antigen of the hepatitis B virus.

Anti-HBc IgM: Is the core antigen of the hepatitis B virus, with a positive test indicating hepatitis B infection

Anti-HBc IgG: The antigen appears after 6 months since Anti-HBc IgM disappears to show that the body has been exposed to the hepatitis B virus for over 6 months. At this point, the disease may have disappeared or become chronic.

Anti-HCV: Hepatitis C virus caused by type C virus a common cause of cirrhosis. The test detects antibodies against hepatitis C.

Stopping Antiviral Treatment In Chronic Hepatitis B

The investigators aim to study the virological and immunological profile in patients who stopped long-term NA therapy, with or without post-NA cessation flare. In addition, the investigators would like to investigate the effect of mild flare after monitored NA-cessation on subsequent virological activity and HBsAg seroclearance.

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Antiviral Therapy For Hcc Patients Undergoing Locoregional Therapy

For patients ineligible for surgical resection or transplantation, locoregional therapy can be potentially curative, and can offer palliative control for inoperable tumors. The effect of LRT on HBV replication, and the effect of antiviral therapy in this setting are not well defined. Transarterial chemoembolization is widely used, and can be effective in reducing tumor progression, with improvement in survival. The delivery of highly concentrated chemotherapy using LRT results in a high intra-tumor concentration of cytotoxic drugs. Although systemic chemotherapy can be associated with HBV reactivation, it is likely that chemotherapy delivered by TACE poses a far less risk. The lipiodol that is widely used to deliver the drug to the tumor allows for the drug to remain concentrated in the tumor for longer periods, thereby reducing the systemic effect. In addition, the risk of HBV reactivation is dependent on the type of chemotherapeutic agent used. Although doxorubicin can cause HBV reactivation, the risk is likely relatively lower than chemotherapy regimens that contain rituximab and high dose steroid.

What Is Chronic Hepatitis B

You have chronic hepatitis B when the virus is active in your body for more than 6 months. The virus can damage liver cells and cause your liver to become swollen and tender.

Most people who have chronic hepatitis B don’t have symptoms. But they can still pass the infection to other people, especially the people they live with or have sex with, unless they receive treatment that gets rid of the virus.

Most people with chronic hepatitis B don’t develop serious problems. But about 15 to 25 people out of 100 who have the infection will die of cirrhosis or liver cancer.footnote 1 When there is a lot of the virus in your body, your chance of having these problems is greater. Sometimes, chronic hepatitis B can lead to severe liver damage. If this happens, you may need a liver transplant.

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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.

Key Points About Drug

• Drug-induced hepatitis is a redness and swelling of the liver.
• It is a rare condition caused by harmful amounts of certain medicines, vitamins, herbal remedies, or food supplements.
• In most cases, you may be taking a medicine for several months before it reaches a toxic level and affects your liver.
• You may also get the condition if you take too much of some medicines, such as acetaminophen. This can happen quickly.
• You must stop taking the medicine that is causing the disease.

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The Role Of Oral Antiviral Therapy In Hepatitis B

James Fung1,2,3Kenneth S.H. Chok2,3,4

1Department of Medicine, The University of Hong Kong, Hong Kong, China.

2The Liver Transplant Center, Queen Mary Hospital, Hong Kong, China.

3State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.

4Department of Surgery, The University of Hong Kong, Hong Kong, China.

Correspondence Address: Dr. James Fung, Department of Medicine, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China. E-mail: jfung@gastro.hk

Received: First Decision: Revised: Accepted:

This is an open access article licensed under the terms of Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, as long as the original author is credited and the new creations are licensed under the identical terms.

When Can Hepatitis B Patients Stop Taking Antivirals Experts Finally Have Some Answers

With the help of antivirals, many patients today have undetectable viral load , a relatively healthy liver and cleared the hepatitis B e antigen . So when can they consider stopping their daily entecavir or tenofovir pill?

For years, experts have admitted the endgame of antiviral treatment has been ill-defined. While antivirals reduce viral load and the risk of liver damage, they rarely cure people. Recently, after years of observing patients and with the help of better diagnostic tools, experts are getting better at identifying when might be safe to stop.

Historically, in addition to reducing viral load to undetectable levels, the goals of antiviral treatment were:

• Triggering HBeAg seroconversion: About 21 percent of HBeAg-positive patients with liver damage treated with either tenofovir or entecavir for 12 months are able to lose the hepatitis B e antigen and develop the e antibody . This HBeAg seroconversion indicates the immune system is fighting the infection and slowing viral replication.
• And reducing liver damage and even clearing the hepatitis B surface antigen : About 1-3 percent of patients treated with antivirals lose HBsAg after years of treatment. This is called a functional cure. Unfortunately, if you have HBeAg-negative hepatitis B, only 1-2 percent of you will lose HBsAg after five to eight years of antiviral treatment.*

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Treatment For Acute Hepatitis B

If youre diagnosed with hepatitis B, your GP will usually refer you to a specialist, such as a hepatologist .

Many people do not have any troublesome symptoms, but if you do feel unwell, it can help to:

• get plenty of rest
• take over-the-counter painkillers, such as paracetamol or ibuprofen, for tummy pain
• maintain a cool, well-ventilated environment, wear loose clothing, and avoid hot baths or showers if itching is a problem
• take medication, such as metoclopramide, to stop you feeling sick, and chlorphenamine to reduce itching your doctor can give you a prescription for these if necessary

Most people recover completely in a couple of months, but youll be advised to have regular blood tests to check that youre free of the virus and have not developed chronic hepatitis B.

What Treatments Are Available For Viral Hepatitis

Many medications are available for the treatment of chronic HBV and HCV infection. For chronic HBV infection, there are several antiviral drugs. People who are chronically infected with HBV require consistent medical monitoring to ensure that the medications are keeping the virus in check and that the disease is not progressing to liver damage or cancer.

There are also antiviral medications available for HCV treatment and new treatments have been approved in recent years. Many antiviral HCV treatments can cure more than 90 percent of people who take them within 8 to 12 weeks. HCV treatment dramatically reduces deaths, and people who are cured are much less likely to develop cirrhosis or liver cancer. However, not everyone infected with HCV needs or can benefit from treatment. NIDA researchers have identified genes that are associated with spontaneous clearance of HCV. These genes also enable people who are unable to clear HCV on their own to respond more favorably to treatment medications. This new information can be used to determine which patients can benefit most from HCV treatment. More studies must be done, but this is a first step to personalized medicine for the treatment of HCV.

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Antiviral Therapy For Chronic Hbv Infection With Persistently Normal Alanine Aminotransferase: Controversy And Consensus

• 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
• 2Department of Infection, Affiliated Hospital of Southwest Medical University, Luzhou, China
• 3Department of Infectious Diseases, The First People’s Hospital of Ziyang City, Ziyang, China
• 4Department of Infectious Diseases, People’s Hospital of Deyang City, Deyang, China
• 5Department of Infectious Diseases, The Second People’s Hospital of Neijiang, Neijiang, China

How Are Hepatitis B And C Treated

Hepatitis B: Not all patients with chronic hepatitis B infection require treatment. At Yale Medicine, specialists decide on an individual basis whether a patient is an appropriate candidate for treatment. Generally, patients require treatment when their hepatitis B virus level is high, and when laboratory tests demonstrate significant inflammation or injury to the liver.

There are currently seven approved drugs for hepatitis B, two of which are considered to be first-line treatments. These drugs are oral pills taken once daily, and while theyre very effective at suppressing the virus to very low or undetectable levels over the long term, they are not considered curative.

Therefore, the goal of treatment is to control the virus long-term and decrease the risk of hepatitis B related complications such as cirrhosis and liver cancer.

Hepatitis C: For the greater part of the last 20 years, treatment of hepatitis C required the use of a chemotherapy-like injection drug called interferon, which has been associated with serious side effects and a low cure rate. Fortunately, advances in hepatitis C treatments within the last three years now allow for the use of oral medications that are significant improvements in terms of safety and effectiveness.

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Improving The Hbsag Clearance Rate By Optimizing Antiviral Treatment

Previous studies concluded that HBsAg level is a marker for determining the safety of drug withdrawal after patients achieve HBeAg seroconversion. It was generally believed that drugs can be withdrawn safely from patients with HBsAg < 1000 IU/mL. Liu et al systematically reviewed 11 studies comprising 1716 patients, aiming to determine the effects of HBsAg level on NA withdrawal in Asian CHB patients. The study found that among patients with HBsAg < 100 IU/mL, after more than 1 year of drug withdrawal and follow-up, 9.1%-19.6% of patients had virologic relapse , and 15.4%-29.4% patients had clinical relapse . The results indicated that although HBsAg is very low in patients undergoing NA treatment, the relapse rate after drug withdrawal is still high. However, if patients with low levels of HBsAg were treated properly, they could achieve HBsAg clearance. Therefore, the goal of antiviral treatment should not be limited to lack of relapse after drug withdrawal. HBsAg clearance is the most effective way to reduce relapse and improve prognosis.

Pattern of different antiviral treatment regimens. IFN: Interferon NA: Nucleoside analogue.

Antiviral Therapy For Patients With Untreatable Hcc

For patients with advanced HCC not amenable to treatment, the role of antiviral therapy is limited. Patients will succumb to disease progression arising from the tumor rather than from HBV infection. Therefore, the life expectancy and quality of life is unlikely to be improved with antiviral therapy. Those already on antiviral therapy should remain on treatment, as there may still be chance of severe flare with cessation of therapy. For those not on antiviral therapies with advanced HCC for palliation, commencing antiviral therapy at this juncture will be futile for the overwhelming majority. Even in the setting of high viral load and elevated transaminases, it may be difficult to confirm that it is due to HBV-related hepatitis rather than locally advanced infiltrative disease. The decision for antiviral therapy in this setting should be made on a case-by-case basis, taking into account the tumor stage and life expectancy of the patient.

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Clinical Consequences Of Antiviral Resistance

The development of antiviral resistance is generally associated with worse clinical outcomes. In a landmark trial that randomized patients with bridging fibrosis or cirrhosis to either lamivudine or placebo to prevent liver disease progression, lamivudine was shown to delay the development of liver disease progression by 50 percent during a median period of 32 months of treatment.55 Patients who developed lamivudine resistance had less benefit compared to those without resistance, but they still experienced fewer adverse outcomes compared to placebo-treated patients.55 Whether patients with resistance would have developed worse outcomes with longer duration of follow-up remains to be determined. In another study evaluating the long-term histological benefits of lamivudine, the effectiveness of therapy was negated by the development of lamivudine resistance.56 Patients who received lamivudine continuously for 3 years and who had no evidence of drug resistance were more likely to demonstrate histological improvement and less likely to show deterioration compared to those who developed resistance.56 Patients with lamivudine resistance for more than 2 years were least likely to demonstrate histological improvement . Lower rates of HBeAg loss and seroconversion were reported in patients receiving lamivudine treatment following the development of resistance.57

Management Of Antiviral Resistance

Management of antiviral resistance has been shaped by several important concepts which have emerged in recent years. Earlier alteration of therapy after the emergence of virological breakthrough has been associated with better long-term virological outcome. In a study to assess whether the timing of administration of rescue therapy influenced virological outcome, adefovir rescue therapy was initiated either at the time of detection of just genotypic resistance or at the time of genotypic and biochemical breakthrough in patients treated with lamivudine.64 At 2 years after instituting adefovir rescue therapy, the virological response was 100% in patients who were treated at the time of detection of genotypic resistance but only 78% in those who presented with both genotypic and biochemical breakthrough suggesting a more favorable clinical outcome with early implementation of rescue therapy.64

Therapy should be altered immediately in patients with cirrhosis if they develop drug resistance because of a higher risk for hepatic decompensation should a hepatitis flare occur. Finally, the choice of rescue therapy for a patient with drug-resistant HBV should be based on the cross-resistant profile of the mutations present, the potency of available agents against these mutations and the presence of other co-morbid conditions such as renal insufficiency.

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Key Points To Remember

• Some people with chronic hepatitis B don’t develop serious problems and can live active, full lives without treatment. But others may develop severe liver damage. If this happens, you may need a liver transplant.
• Treatment may not be an option for everyone who has hepatitis B, because antiviral medicines cost a lot and may not work for everyone.
• Experts recommend antiviral medicines if you have high levels of both the hepatitis B virus and liver enzymes in your blood for at least 6 months or if you have liver disease.
• Some antiviral medicines that stop or slow the growth of the hepatitis B virus can have serious long-term side effects. And some can make you feel sick while you are taking them.
• You may not need to take antiviral medicines if you have normal or only slightly higher-than-normal levels of liver enzymes in your blood and a biopsy shows no signs of liver damage.
• People who have had an organ transplant or who drink too much alcohol or use illegal drugs may not be able to take some antiviral medicines.
• You will probably need to take medicine for many years. And you’ll need to have regular exams and blood tests to see if the virus is still active in your body and to find out how well your liver is working.