Dataset Information

Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil.

ABSTRACT:

Background

Hepatitis D virus (HDV), which requires the presence of hepatitis B virus (HBV), is a deadly yet neglected disease that rapidly leads to liver cancer and disease-induced mortality. This co-dependence creates complex transmission dynamics that make it difficult to predict the efficacy of interventions aimed at HBV and/or HDV control in endemic regions, such as certain municipalities of Brazil, where up to 65% of HBV-infected persons are co-infected.

Methodology

We created a mathematical model that captures the joint transmission dynamics of HBV and HDV, incorporating mother-to-child, sexual and household transmission. With an aim to minimize the number of total infections and disease-induced mortality in 2027, we then determined optimal strategies for Brazil and its sub-regions under a constrained budget, which was dynamically allocated among HBV and HDV screening, HBV and HDV treatment, HBV newborn and adult vaccination, and awareness programs. Three treatment options were considered, namely: Tenofovir, PEGylated-Interferon, and nucleic acid polymers (NAP).

Results

The additional cost of HDV screening and the use of a more expensive PEGylated-Interferon are offset by not wasting resources on treating co-infected persons with Tenofovir. The introductory price of NAP treatment must be less than $16,000 per course to become competitive with Tenofovir and PEGylated-Interferon in Brazil.

Conclusion

Additional screening for HDV is beneficial, even in a low HBV and HDV endemic regions of Brazil. We recommend PEGylated-Interferon, wherever possible, for both HBV and HDV. If PEGylated-Interferon is not available in abundance, PEGylated-Interferon for co-infections and 4-year Tenofovir treatment for mono-infections is recommended.

SUBMITTER: Goyal A

PROVIDER: S-EPMC6128631 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil.

Goyal Ashish A Romero-Severson Ethan Obie EO

PloS one 20180907 9

<h4>Background</h4>Hepatitis D virus (HDV), which requires the presence of hepatitis B virus (HBV), is a deadly yet neglected disease that rapidly leads to liver cancer and disease-induced mortality. This co-dependence creates complex transmission dynamics that make it difficult to predict the efficacy of interventions aimed at HBV and/or HDV control in endemic regions, such as certain municipalities of Brazil, where up to 65% of HBV-infected persons are co-infected.<h4>Methodology</h4>We create ...[more]

PMID: 30192887

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Project description:Time series of gene expression arrays before and during treatment of Hepatitis C; days 0, 1, 2, 7, 14 and 28 for 69 participants (IDs 1 through 69 are used). Treating chronic hepatitis C using peginterferon alpha and ribavirin leads to sustained clearance of virus and clinical improvement in approximately 50% of patients. Response rates are lower among patients with genotype 1 than with genotypes 2 and 3 and among African American ( AA) compared to Caucasian (CA) patients. Using DNA microarrays, gene expression was assessed in a group of 33 African American and 36 Caucasian American patients with chronic hepatitis C, genotype 1 during the first 28 days of treatment. Results were examined with respect to treatment responses and to race. Patients showed a response to treatment at the gene expression level in RNA isolated from PBMC irrespective of degree of decrease in hepatitis C virus (HCV) RNA levels. However, gene expression responses were relatively blunted in patients with poor viral response (< 1.5 log10 IU/ml decrease at 28 days) compared to those in patients with a marked (> 3.5 log10 decrease) or intermediate (1.5 to 3.5 log10 decrease) response. The number of genes that were up- or down-regulated by peginterferon and ribavirin treatment was fewer in patients with a poor response compared to those with an intermediate or marked viral response. However AA patients had a stronger interferon response than CA patients in general. The induced levels of known ISGs such as OAS, MX1, IRF-7 and the toll like receptor TLR-7 was lower in poor response patients than in marked or intermediate response patients. Thus, the relative lack of viral response to interferon therapy of hepatitis C is associated with blunted interferon cell signaling. No specific regulatory gene could be identified as responsible for this global blunting or racial differences. Experiment Overall Design: Eligible patients were naÃ¯ve to interferon and ribavirin treatment, had detectable HCV RNA in serum, and nearly all had a liver biopsy performed within the previous 18 months showing chronic hepatitis. Only patients who were born in the United States and designated themselves as âAfrican American/Blackâ or âCaucasian/Whiteâ were eligible. The clinical protocol called for participants to be treated for up to 48 weeks with peginterferon alpha-2a (Pegasysâ¢, Roche Pharmaceuticals Nutley, NJ) in a dose of 180 Âµg weekly by self-administered subcutaneous injection and ribavirin (Copegusâ¢, Roche) orally in a dose of 1000 or 1200 mg daily based on body weight of less than 75 kg or equal to or greater than 75 kg. Peripheral blood mononuclear cells (PBMC) were collected from patients before treatment (day 0) and on days 1 (after the initial supervised injection of peginterferon), 2, 7, 14 and 28. From the Virahep-C cohort, 72 patients who did not have dose reductions of either peginterferon or ribavirin in the first 28 days of treatment were selected such that 12 patients were included in each race (CA, AA) by virological response category. The three categories of response were: marked, defined as a decrease in HCV RNA levels of more than 3.5 log10 IU/ml or to undetectable on day 28; intermediate, defined as a decrease of 1.4 to 3.5 log10 IU/ml on day 28; and poor, defined as less than 1.4 log10 IU/ml decline on day 28 relative to baseline. These definitions were made a priori in an attempt to analyze the biological basis for virological responses. Of these, adequate RNA was not obtained from 3 patients to provide gene expression information. Of these 72, 69 were analyzed.

Dataset Information

Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil.

Background

Methodology

Results

Conclusion

Publications

Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil.

Similar Datasets

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