{"id":2353,"date":"2018-10-12T14:50:40","date_gmt":"2018-10-12T14:50:40","guid":{"rendered":"https:\/\/www.mybiosource.com\/learn\/?p=2353"},"modified":"2024-04-04T07:56:23","modified_gmt":"2024-04-04T07:56:23","slug":"std-series-a-brief-curation-of-developments-related-to-hepatitis-b-and-hepatitis-c","status":"publish","type":"post","link":"https:\/\/www.mybiosource.com\/learn\/std-series-a-brief-curation-of-developments-related-to-hepatitis-b-and-hepatitis-c\/","title":{"rendered":"STD Series: A brief curation of developments related to Hepatitis B and Hepatitis C"},"content":{"rendered":"

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

I. Introduction <\/strong>
\n\u2022 World Hepatitis Day and its significance
\n\u2022 Global concern for chronic hepatitis B virus infection
\n\u2022 Importance of HBV cure research
\nII. Novel Therapeutic Strategies for HBV Cure <\/strong>
\n\u2022 Combination of antiviral approaches
\n\u2022 Pre-clinical studies on mice and their promising results
\n\u2022 Antiviral therapy goal and combination of peginterferon and nucleotide analog
\nIII. Insights into the Immune System Responses for HBV Cure <\/strong>
\nIV. Viral Biomarkers for Monitoring Chronic Hepatitis B Virus Infection <\/strong>
\nV. Conclusion<\/strong><\/p>\n

\n

It is widely known that hepatitis B<\/span> virus (HBV<\/span>) and hepatitis C<\/span> virus (HCV) are among the most common blood-borne pathogens worldwide. Both viruses can lead to chronic infection leading to complications associated with liver-related morbidity and mortality. Chronic HBV<\/span> infection is the leading cause of hepatocellular carcinoma<\/span> (HCC) worldwide, while chronic HCV is the number one cause in the United States (US). More than 350 million individuals suffer from chronic HBV<\/span> infection with one million deaths annually worldwide and it is estimated that more than 150 million individuals are chronically infected with HCV worldwide.<\/p>\n

Hepatitis B and updates<\/u><\/p>\n

Hepatitis B<\/span> consists of a partially double-stranded relaxed circular DNA (rcDNA) genome. Upon entry into human hepatocytes<\/span>, rcDNA is subsequently converted to a tightly coiled plasmid-like covalently closed circular DNA (cccDNA) in the host nucleus. cccDNA is unusually stable and is able to avoid DNA-sensing cellular machinery. The production of tolerogenic proteins<\/span> (HBsAg and hepatitis B<\/span> e-antigen [HBeAg]) can lead to T-cell exhaustion. Patients recover from HBV<\/span> infection still harbour cccDNA in hepatocyte nuclei for life acting as a reservoir for reactivation of viral genome replication when these patients undergo immunosuppressive<\/span> therapies.<\/p>\n

At present, there are seven treatments approved for chronic HBV<\/span> infection: two formulations of interferon (interferon alfa-2b, peginterferon alfa-2a) and five nucleos(t)ide agents. Interferon mainly has immunomodulatory effects and whereas nucleos(t)ide analogues (NA) work by inhibiting the reverse transcriptase<\/span> activity of HBV<\/span> polymerase<\/span>, thereby suppressing viral replication<\/span>. The current nucleos(t)ide agents approved for use are lamivudine, telbivudine, entecavir (ETV), adefovir dipivoxil and tenofovir disoproxil fumarate (TDF<\/span>). The preferred first-line treatment choices among the oral nucleosides\/nucleotides<\/span> are entecavir and tenofovir because of their superior efficacy.<\/p>\n

\u201cOur results suggest that for healthier patients, TDF<\/span> and [Baraclude] are comparable [chronic HBV] treatment choices regarding renal safety,\u201d\u00a0Sam Trinh, BS,<\/strong>\u00a0from Stanford University Medical Center in California, and colleagues wrote. \u201cHowever, for those with moderate renal impairment or over 60 years old, renal outcomes with TDF<\/span> may be worse while improvement can be expected for patients treated with [Baraclude].\u201d Baraclude is <\/em>entecavir, Bristol-Myers Squibb.<\/em><\/p>\n

In routine practice, standard interferon alfa-2b has largely been replaced by peginterferon alfa-2a<\/span>. While the implementation of HBV<\/span> vaccine<\/span> has led to a decline in the incidence of new HBV<\/span> infection, the prevalence of chronic HBV<\/span> infection still remains high as these therapies also do not affect cccDNA, and thus cannot lead to a true cure of chronic HBV<\/span> infection.<\/p>\n

\u201cIn the United States, about 1,800 death certificates annually list hepatitis B<\/span> virus (HBV<\/span>) as an underlying or contributing cause of death,\u201d researchers wrote. \u201cHowever, accurately quantifying mortality related to hepatitis<\/span> is difficult because of the prolonged period between infection and death and because death is not always linked to underlying infection. … Underestimating the true prognosis of [chronic hepatitis B (CHB)] infection may have real consequences for patients.<\/em><\/p>\n

Hepatitis C and updates<\/u><\/p>\n

HCV<\/span> has been classified into six major genotypes (1\u20136) and are found to be distributed in different geographical locations. Genotype 1 is predominantly found in North American and European populations. Genotype 3 is the second most common genotype and accounts for the majority of infections in Asia, while North African and Middle Eastern populations are typically infected with genotype 4 virus.<\/p>\n

For more than 20 years Interferon<\/span> therapy was the mainstream treatment. The combination of interferon with ribavirin<\/span> improved Sustained virologic response (SVR) rates by up to 40%, with greater success in genotype 2 and 3 patients. SVR is considered achieved after the treatment course when the HCV RNA<\/span> is below the lower limit of quantification<\/span>. Development of pegylated interferon and its co-administration with ribavirin further increased SVR rates to 80% in genotype 3 patients, but remained under 50% for genotype 1 patients.<\/p>\n

Inside the host cell HCV encodes a large polyprotein that is cleaved by both host and viral proteases<\/span> to produce ten viral proteins<\/span>. This includes structural proteins<\/span> (core, E1 and E1 glycoproteins<\/span>), integral membrane protein<\/span> (p7) and non-structural proteins<\/span> (NS2, NS3, NS4A, NS4B, NS5A, NS5B). Non-structural proteins<\/span> are essential for their replication, assembly and export. Inhibition of the non-structural (NS) proteins<\/span> has become the major target in the development of direct-acting antiviral (DAA) agents. DAA\u2019s is a shorter treatment course than interferon therapy and cure rates exceeding 90% in many populations. The most recent guidelines by the American Association for the Study of Liver Diseases<\/span> (AASLD) and the Infectious Diseases Society of America<\/span> (IDSA) recommend DAAs as the primary treatment for all genotypes of HCV.<\/p>\n

Hepatitis B\u00a0and\u00a0hepatitis C\u00a0are among the most common causes of liver disease, according to the\u00a0Centres for Disease Control and Prevention (CDC)<\/a>\u00a0\u2014 but having both viruses at the same time significantly increases risk of liver damage. Patients with co-infection have higher incidents of liver cancer, liver failure, and the need for\u00a0liver transplantation. The viruses act together to cause more inflammation and scarring of the liver, compared to mono-infection.<\/p>\n

Coinfection of HBV<\/span> and HCV<\/u><\/p>\n

In people with both HBV<\/span> and HCV, the two viruses seem to interact and keep each other in check. HBV<\/span> DNA viral load is often low or undetectable and HCV is typically the main driver of active liver disease. But when hepatitis C<\/span> is cured with DAAs, HBV<\/span> has an opportunity to reactivate, often indicated by a rapid increase in HBV<\/span> DNA and ALT liver enzyme levels and sometimes jaundice<\/span>. In severe cases it can lead to fulminant hepatitis<\/span>, liver failure and death. This phenomenon may not have been apparent in the interferon era because interferon alfa is active against both viruses.<\/p>\n

The American Association for the Study of the Liver (AASLD) and Infectious Diseases Society of America (IDSA) issued new recommendations for HBV<\/span>\/HCV co-infected patients in a September 16 update to its\u00a0HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C<\/span>, available at\u00a0www.hcvguidelines.org<\/a>.<\/em><\/p>\n

The revised recommendation states:<\/em><\/p>\n