{"id":2404,"date":"2018-10-13T12:50:24","date_gmt":"2018-10-13T12:50:24","guid":{"rendered":"https:\/\/www.mybiosource.com\/learn\/?p=2404"},"modified":"2023-03-04T12:31:47","modified_gmt":"2023-03-04T12:31:47","slug":"std-series-hepatitis-coinfection-in-hiv-patients","status":"publish","type":"post","link":"https:\/\/www.mybiosource.com\/learn\/std-series-hepatitis-coinfection-in-hiv-patients\/","title":{"rendered":"STD Series: Hepatitis Coinfection in HIV Patients"},"content":{"rendered":"

Table of Contents<\/strong><\/span><\/h2>\n

I. Introduction<\/strong>
\n\u2022 HBV infection among HIV patients globally
\n\u2022 Need for screening HIV individuals for HBV infection
\nII. Progression of HBV in stages<\/strong>
\nIII. Impact of HIV on the HBV Infection<\/strong>
\n\u2022 Increased levels of HBV DNA and low clearance rate of e antigen (HBeAg)
\n\u2022 High risk of HBV infection advancing faster to cirrhosis, liver cancer, and end-stage liver disease
\n\u2022 Associated with the frequent flares of hepatic transaminases
\nIV. Diagnosing hepatitis B in HIV-infected individuals<\/strong>
\n\u2022 HBsAg, HBcAb, and previous HBV vaccination assessment
\n\u2022 ALT level and abnormal liver enzymes
\n\u2022 Determination of HBeAg
\n\u2022 Ultrasound and other evaluations
\nV. ART in HBV\/HIV coinfected patients<\/strong>
\n\u2022 Treatment for HBV and antiretroviral drugs for HIV
\n\u2022 Hepatoxicity associated with antiretroviral medications
\n\u2022 Use of antiretroviral therapy with active agents
\n\u2022 Treatment of HBV with ART
\n\u2022 Treatment of HBV in the absence of ART<\/p>\n

\n

Hepatitis B<\/span> virus (HBV<\/span>) is a double-stranded DNA multiplying in hepatocytes<\/span> and is considered one of the common infections among HIV<\/span> individuals globally. With the increase in the rate of HBV<\/span> infection among HIV<\/span> patients and the common routes of transmission, HIV<\/span> individuals should be screened for HBV<\/span> infection with HBsAg testing.\u00a0 As the HBV<\/span> DNA can continue to remain in the liver throughout an individual\u2019s life, those with cAb positivity are at the risk of reactivation of HBV<\/span> infection even when the sAB test appears positive.<\/p>\n

Globally, an estimated 2.6 million HIV<\/span> individuals are co-infected with HBV<\/span> and around 25-36% co-infection with HBV<\/span> occurs in the high endemic<\/span> parts of the world. According to the Centers for Disease Control and Prevention<\/span> (CDC), in the United States, around 10% of HIV<\/span> people also have HBV<\/span>.<\/p>\n

Progression of HBV in stages<\/strong><\/p>\n

Individuals with a weakened immune system<\/span> such as HIV<\/span> population will progress to have a chronic infection which is indicated in four stages;<\/p>\n

Immune tolerance<\/em> (stage 1): a short-lived phase among adults where HBV<\/span> multiplies to a high viral load<\/span> with the immune system not responding very well.<\/p>\n

Active immune response<\/em> (stage 2): the immune system continues to attack the infected cells in the liver. This phase can last for just a few weeks or continue for years or decades causing liver damage deteriorating over time.<\/p>\n

Inactive carriage<\/em> (stage 3): in a process known as seroconversion<\/span>, the body develops antibodies against HBV<\/span> so the virus is not reproduced freely. Individuals are also at the risk of liver cancer.<\/p>\n

\u2018e\u2019-antigen-negative chronic active hepatitis<\/span><\/em> (stage 4): individuals lack the \u2018e\u2019-antigen, presenting moderate levels of viral multiplication with inflammation of the liver and presenting a very high risk of cirrhosis<\/span> and liver cancer.<\/p>\n

Impact of HIV on the HBV Infection<\/strong><\/p>\n

Individuals with HIV<\/span> and chronic HBV<\/span> co-infection present increased levels of HBV<\/span> DNA and low clearance rate of e antigen (HBeAg<\/span>). Co-infected individuals are at high risk of HBV<\/span> infection advancing faster to cirrhosis<\/span>, liver cancer and end-stage liver disease than those with only HBV<\/span> infection. The co-infection also is associated with the frequent flares of hepatic transaminases, that can develop with IRIS<\/span> (immune reconstitution inflammatory syndrome) because of ART<\/span> or the development of resistance to HIV<\/span>\/HBV<\/span> treatment.<\/p>\n

Diagnosing hepatitis B in HIV-infected individuals<\/strong><\/p>\n

As the initial assessment, all HIV<\/span> individuals should be tested for HBsAg, for hepatitis B<\/span> core antibodies (HBcAb) and assessed for previous HBV<\/span> vaccination.<\/p>\n

ALT level<\/strong> \u2013 increased ALT is indicative of liver inflammation and ALT level three times more than normal is associated with cirrhosis<\/span> risk while abnormal liver enzymes for three months indicates HBV<\/span> treatment should be initiated.<\/p>\n

Determination of HBeAg<\/span><\/strong> \u2013 Positive HBeAg<\/span> present high HBV<\/span> DNA and negative patients also can have a progressive liver disease, however, in both circumstances, measurement of HBV<\/span> DNA should be done.<\/p>\n

Ultrasound and other evaluations<\/strong> \u2013 Ultrasound of the liver can detect cirrhosis<\/span>, steatosis and maybe early hepatocellular carcinoma<\/span> (HCC<\/span>), a common type of liver cancer. Individuals with liver cirrhosis<\/span> can also have serum<\/span> alpha-fetoprotein<\/span> (AFP) assessment to identify HCC.<\/p>\n

Histological evaluation<\/strong> \u2013 liver biopsy may present several advantages such as assessment of necrosis<\/span>, inflammation and fibrosis.<\/p>\n

ART in HBV\/HIV coinfected patients<\/strong><\/p>\n

Generally, the treatment for HBV<\/span> is the antiviral<\/span> drugs that either stops or delay the effects of liver damage. Several of the antiretroviral drugs as treatment for HIV<\/span> infection can also slow the progression of the disease by decreasing the viral load<\/span>. However, some degree of hepatoxicity has been associated with the majority of antiretroviral medications along with the HBV<\/span> infection, acting as an independent risk factor for the development of hepatoxicity. Also, these co-infected individuals are at risk for HBV<\/span> immune reconstitution inflammatory syndrome that is characterized by a paradoxical hepatitis<\/span> flare.<\/p>\n

According to a study reported at the 20th<\/sup> Conference on Retroviruses on Opportunistic Infections<\/span>, the use of antiretroviral therapy<\/span> with active agents such as tenofovir, 3TC (lamivudine, Epivir<\/em>) and FTC (emtricitabine<\/span>, Emtriva<\/em>) can act against both HBV<\/span> and HIV<\/span> thus reducing the chance of becoming infected with HBV<\/span> (acting a HBV<\/span> pre-exposure prophylaxis \u2013 PrEP). Hence, the need for vaccination against HBV<\/span> is also reduced when taking these drugs.\u00a0<\/strong><\/p>\n

Treatment of HBV with ART<\/strong><\/p>\n

As one or more HBV<\/span>-active agents are present in most of the HIV<\/span> treatment (eg, emtricitabine<\/span> (FTC), tenofovir (TDF<\/span>), lamivudine<\/span> (3TC)), an indication for HBV<\/span> infection should be initiated on fully active ART<\/span> containing HBV<\/span>-active nucleoside\/nucleotide analogues. Any HIV<\/span>\/HBV<\/span> co-infected individual with an indication for ART<\/span> should initiate on HIV<\/span> treatment that contains effective anti-HBV<\/span> treatment. As the first-line of effective treatment for HBV<\/span>, the combination of TDF<\/span> with 3TC or FTC is recommended. In case TDF<\/span> cannot be tolerated by the patient, entecavir can be used as the alternative treatment.<\/p>\n

Treatment of HBV in the absence of ART<\/strong><\/p>\n

U.S Department of Health and Human Services guidelines recommends that an active ART<\/span> should be initiated as the treatment for HBV<\/span> among HIV<\/span>\/HBV<\/span> co-infected individuals even if they don\u2019t have an indication for HIV<\/span> treatment. With the adefovir as the treatment for HBV<\/span> only, even a low-dose could have anti-HIV<\/span> activity. Pegylated interferon could be an option here, but the long-term treatment is not possible due to poor tolerability and toxicity.<\/p>\n

Treatment prospects <\/strong><\/p>\n

Drugs as the treatment of HBV<\/span> infection among individuals with HIV<\/span>;<\/p>\n

Tenofovir disoproxil fumarate<\/em> \u2013 when used in combination with lamivudine<\/span>, it is effective in reducing the viral load<\/span> of both HIV<\/span> and HBV<\/span><\/p>\n

Lamivudine<\/em> \u2013 active against HIV<\/span> and prevents HBV<\/span> replication in most of the cases<\/p>\n

Emtricitabine<\/em> \u2013 similar to lamivudine but when used as monotherapy, HBV<\/span> resistance can develop rapidly<\/p>\n

Entecavir<\/em> \u2013 active against both HIV<\/span> and HBV<\/span> but not recommended for treatment of HBV<\/span> infection among HIV<\/span> patients not receiving ART<\/span><\/p>\n

Adefovir dipivoxil<\/em> \u2013 nucleoside analog reverse transcriptase<\/span> inhibitor active against HBV<\/span> although a warning was indicated against the use as monotherapy in HIV<\/span>\/HBV<\/span> co-infected individuals<\/p>\n

Interferon-alfa<\/em> \u2013 Interferon-alfa 2a or 2b or Peg IFN-alfa 2a are used for HBV<\/span> mono-infected individuals. Studies suggest a decrease in the response rate in HIV<\/span>\/HBV<\/span> co-infected individuals; however, it may be used if an agent not active against HIV<\/span> is required.<\/p>\n

Guidance for treatment of individuals with HBV and HIV co-infection<\/strong><\/p>\n

    \n
  1. Initiation of ARVT for all co-infected patients that should include two drugs with activity against HBV<\/span> regardless of their CD4<\/span> count<\/li>\n
  2. Those already receiving effecting ART<\/span> but does not include drug against HBV<\/span> should change treatment to include TDF<\/span> and TAF with emtricitabine<\/span> or lamivudine<\/span>.<\/li>\n
  3. If ART<\/span> regime is changed, effective drugs used against HBV<\/span> must not be discontinued without substituting with another drug<\/li>\n
  4. Dose adjustment of TDF<\/span>-emtricitabine-inclusive regimes if creatinine<\/span> clearance appears <50mL\/min<\/li>\n<\/ol>\n

    References<\/strong><\/p>\n

      \n
    1. http:\/\/annals.org\/aim\/article-abstract\/705952\/hepatitis-b-patients-hiv-infection-relationship-aids-patient-survival<\/a><\/li>\n
    2. https:\/\/www.cdc.gov\/hiv\/pdf\/library\/factsheets\/hiv-viral-hepatitis.pdf<\/a><\/li>\n
    3. http:\/\/www.aidsmap.com\/Hepatitis-B\/page\/1506084\/<\/a><\/li>\n
    4. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2928468\/<\/a><\/li>\n
    5. http:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b<\/a><\/li>\n
    6. https:\/\/aidsinfo.nih.gov\/understanding-hiv-aids\/fact-sheets\/26\/89\/hiv-and-hepatitis-b<\/a><\/li>\n
    7. https:\/\/grants.nih.gov\/grants\/guide\/pa-files\/PA-17-278.html<\/a><\/li>\n
    8. https:\/\/www.hivguidelines.org\/hiv-care\/hbv-hiv-coinfection\/#tab_6<\/a><\/li>\n
    9. https:\/\/aasldpubs.onlinelibrary.wiley.com\/doi\/10.1002\/hep.29800<\/a><\/li>\n
    10. http:\/\/hivinsite.ucsf.edu\/InSite?page=kb-05-03-04#S5X<\/a><\/li>\n
    11. http:\/\/www.euro.who.int\/__data\/assets\/pdf_file\/0011\/91937\/E90840_Chapter_7.pdf<\/a><\/li>\n<\/ol>\n

       <\/p>\n","protected":false},"excerpt":{"rendered":"

      Table of Contents I. Introduction \u2022 HBV infection among HIV patients globally \u2022 Need for screening HIV individuals for HBV infection II. Progression of HBV in stages III. Impact of HIV on the HBV Infection \u2022 Increased levels of HBV DNA and low clearance rate of e antigen (HBeAg) \u2022 High risk of HBV infection […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"off","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[31],"tags":[44,13],"class_list":["post-2404","post","type-post","status-publish","format-standard","hentry","category-news","tag-hepatitis","tag-hiv"],"_links":{"self":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2404","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/comments?post=2404"}],"version-history":[{"count":0,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2404\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/media?parent=2404"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/categories?post=2404"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/tags?post=2404"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}