The Impact of Ethnicity on Hepatitis C Virus Treatment Decisions and Outcomes
ABSTRACT Hepatitis C virus infection is a major public health concern. Approximately 4 million people are reported to be infected with the virus in the United States, and the annual death rate due to HCV-associated decompensated liver failure or hepatocellular carcinoma is estimated to be approximately 18,000 within the next decade. Therapeutic success, as measured by a sustained virologic response, is approximately 50 % in G1 patients with pegylated-interferon/ribavirin-based therapies. Independent studies have reported significant variation in response rates depending on the ethnicity or race of the patient, though the underlying reasons are not well understood. Historically, ethnic populations have been underrepresented in most large clinical trials of HCV therapies, even though these populations have disproportionately high rates of HCV infection. Recent clinical trials have investigated genetic variations in key biological pathways that may underlie the mechanisms responsible for the different rates of HCV clearance and treatment outcomes in ethnic populations treated with pegylated-interferon/ribavirin. However, as novel direct-acting antiviral drugs are added to, and eventually replace, existing treatment regimens, the role of the innate immune response in determining treatment outcomes will diminish. Socioeconomic and biological factors can impact rates of HCV infection, disease progression, and treatment outcomes in minority populations. Improved access to health care, novel antiviral treatments, and a better understanding of the host factors that contribute to disparities in treatment outcomes are expected to result in optimized treatment paradigms that directly target the virus, leading to improved outcomes for all patients.
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ABSTRACT: The hepatitis C virus (HCV), the main cause of morbidity and mortality, is endemic worldwide. HCV causes cirrhosis and other complications that often lead to death. HCV is most common in underdeveloped nations, with the highest prevalence rates in Egypt. Tumor suppressor gene (P53) induces the expression of apoptotic antigen-1 gene (APO-1) by binding to its promoter for mediating apoptosis; an important mechanism for limiting viral replication. This study aims at investigating the impact of P53 72 Arg/Pro and APO-1 -670 A/G polymorphisms on HCV genotype 4a susceptibility. Two hundred and forty volunteers were enrolled in this study and divided into two major groups; 160 HCV infected patient group and 80 healthy control group. HCV patients were classified according to Metavir scoring system into two subgroups; 72 patients in F0/1-HCV subgroup (patients with no or mild fibrotic stages) and 38 patients in F3/4-HCV subgroup (patients with advanced fibrotic stages). Quantification of HCV-RNA by qRT-PCR and fibrotic scores as well as genotyping of HCV-RNA, P53 at 72 Arg/Pro, and APO-1 at -670 A/G were performed for all subjects. It was resulted that F0/1-HCV patients have significant differences of P53 at 72 (Pro/Pro and Arg/Arg) genotypes and dominant/recessive genetic models as well as APO-1 -670 A/A genotype and dominant genetic model as compared to F3/4-HCV patients. Moreover, HCV patients have significant differences of P53 at 72 (Pro/Pro) genotype and recessive genetic model as well as APO-1 -670 A/A genotype and dominant genetic model as compared to those of healthy individuals. Finally, it was concluded that P53 rs 1042522 (Pro/Pro and Arg/Arg) genotypes and APO-1 rs 1800682 A/A genotype may be potentially used as sensitive genetic markers for HCV genotype 4a susceptibility.Gene 08/2014; 550(1). DOI:10.1016/j.gene.2014.08.011 · 2.08 Impact Factor
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ABSTRACT: We examined risk factors associated with Hepatitis C virus (HCV) infection among opioid-dependent patients enrolled into medication-assisted therapy (buprenorphine or methadone) to determine factors affecting chronic infection. Patients (N=1,039) were randomized as part of a larger, multisite clinical trial sponsored by the National Drug Abuse Treatment Clinical Trials Network assessing liver function. HCV status was first assessed with an antibody screen; if positive, then current infection was determined with an antigen screen testing for detectable virus. Patients were classified as HCV negative, HCV positive but have cleared the virus, or as having chronic HCV. Logistic regression analysis was used to examine demographic and behavioral correlates of the three groups. Thirty-four percent of patients were classified with chronic infection and 14% had evidence of prior infection with apparent clearing of the virus. Chronic infection was associated with recent injection drug use and cocaine use. Chronic HCV infection was also associated with being older and Hispanic. Age, ethnicity, and current drug use increase the likelihood of being chronically infected with HCV. Strategies targeting high risk subgroups can aid in preventing further disease escalation.Journal of Community Health 03/2015; DOI:10.1007/s10900-015-0016-2 · 1.28 Impact Factor