Low Hepatitis C Virus Viral Load Research Articles

Interferon- α Treatment of Hepatitis C Patients with Psychiatric Disorders

Gastroenterologists make clinical risk-benefit assessments when offering interferon-α based therapies (IFN) to treat Hepatitis C virus (HCV) infection. The fear of precipitating or worsening psychiatric co-morbidity is a frequent trigger for psychiatric consultation to address the probability of IFN-induced neuropsychiatric adverse effects. Several risk factors are thought to increase the risk of IFN emergent psychiatric co-morbidity and include the following: a previous history of any psychiatric illness; a family history of psychiatric illness; and a history of suicidal ideation. In contrast to the variable influence of these psychiatric risk factors, the decreased likelihood of sustained virologic response (SVR) from HCV in response to IFN is associated with several predictive and additive factors. We propose a comprehensive assessment model that integrates both the psychiatric and medical factors pertaining to HCV treatment. Case 1 (Figure 1): IFN is clearly indicated in the case of a 35 YO slender white women with no history of psychiatric illness who is infected with a low HCV viral load of either genotype 2 or 3. Case 2 (Figure 1): In the absence of advancing cirrhosis IFN should be delayed in the case of a 50 YO obese African American man with history of psychosis and substance use disorder who is infected with a high viral load of HCV genotype 1. Ongoing psychiatric follow-up is certainly indicated when a patient has one or more psychiatric risk factors. In cases where a low estimated likelihood of SVR from HCV is combined with an intermediate to low probability of psychiatric adverse effects an evaluation incorporating the patient's IFN treatment preferences can help sway the decision. This model is intended to assist clinicians in making an individualized and balanced risk-benefit analysis incorporating HCV-disease specific factors as well the potential for psychiatric complications prior to offering IFN treatment. [figure 1]Figure

Antigen-specific immune responses and liver histology in HIV and hepatitis C coinfection

To test the hypothesis that antigen-specific interferon (IFN)gamma responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV). Cellular immune responses were studied in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy. We measured HCV-specific and recall responses in peripheral blood mononuclear cells using IFNgamma and interleukin (IL)-10 ELISpots, and correlated these immune responses with liver histology. The relationship of immunologic, virologic and clinical variables to inflammation and fibrosis was modeled using recursive partitioning. There were significant negative correlations between inflammatory scores and IFNgamma production in response to the HCV proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also correlated with higher IFNgamma production in response to NS5 and summed HCV proteins. Higher IFNgamma production in response to Candida was significantly associated with lower inflammatory and fibrosis scores. In multivariable models, factors associated with severe fibrosis were lower IFNgamma responses to Candida and summed HCV proteins. Factors associated with severe inflammation were detectable HIV viral load and lower HCV viral load, while predictors of mild inflammation included undetectable HIV viral load and higher IFNgamma response to Candida. In this cohort of subjects coinfected with HIV and HCV, antigen-specific IFNgamma responses are correlated with milder inflammation and fibrosis. Immunological responses best predicted severity of fibrosis, while clinical variables and recall antigen responses best predicted severity of inflammation.

Interferon-α Treatment of Hepatitis C Patients With Psychiatric Illness

Sir: The clinical management of individuals with comorbid chronic hepatitis C virus (HCV) infection and psychiatric illness is a substantial public health problem.1 At least 50% of patients with HCV suffer from at least 1 psychiatric illness.2,3 Furthermore, the prevalence of HCV in patients with psychiatric illness (10%–20%)1 is 5 to 10 times that in the general U.S. population (2%). Recent advances in the treatment of HCV and the introduction of interferon-α–based therapies in combination with ribavirin have resulted in viral clearance (complete eradication of HCV; absent HCV viral load 6 months after HCV treatment is completed) rates of 50% to 59% of patients with HCV genotype 1 (70% of the U.S. HCV-infected population) and 80% to 90% of patients with HCV genotypes 2 and 3 (20%–30% of the U.S. HCV-infected population).4,5 These viral clearance rates, however, may not be applicable to the HCV-infected population with comorbid psychiatric illness, since most large HCV treatment trials4,5 have excluded patients with any history of psychiatric or substance use disorders. The practice of excluding patients with HCV and psychiatric illness from interferon-α treatment is stigmatizing and will result in substantial morbidity and mortality for a vulnerable population no less deserving of treatment than HCV patients without psychiatric illness. Recently, gastroenterologists have started evaluating patients with HCV and comorbid psychiatric illness and making a risk-benefit assessment for interferon-α treatment. Fearing the precipitation or worsening of preexisting psychiatric illness with interferon-α treatment, gastroenterologists call upon consultant psychiatrists to assist in making a risk assessment regarding the probability of interferon-α–induced neuropsychiatric adverse effects. Several risk factors are thought to increase the probability of interferon-α–emergent neuropsychiatric adverse effects6: a history of any psychiatric illness, a history of substance abuse, a family history of psychiatric illness, and a history of suicidal ideation. The ability to predict the variable interferon-α–induced neuropsychiatric adverse effects, however, remains modest at best due to the lack of systematic large-scale data and the exclusion of patients with psychiatric illness from HCV clinical trials.7 In contrast to the variable influence of these psychiatric risk factors, the decreased likelihood of viral clearance in response to interferon-α is associated with several well-established predictive and additive factors including male gender, African American race, increased body mass index, advanced age (> 40 years), higher HCV viral load, coinfection with human immunodeficiency virus, and HCV genotype 1.8 I propose a comprehensive clinical risk-benefit model (Figure 1) integrating factors pertaining to the likelihood of viral clearance in response to interferon-α and the probable risk of interferon-α–induced neuropsychiatric adverse effects. Figure 1. Risk-Benefit Model for Interferon-α Treatment of Hepatitis C Patients Integrating the Risks of Neuropsychiatric Adverse Events and the Likelihood of Viral Clearance A 35-year-old slender white woman with no history of psychiatric illness who is infected with a low HCV viral load of either genotype 2 or 3 would be a candidate for interferon-α treatment (represented by case 1 in Figure 1). In the case of a 50-year-old obese African American man with a history of psychosis and a substance use disorder who is infected with a high viral load of HCV genotype 1 (represented by case 2 in Figure 1), interferon-α should be delayed in the absence of advancing cirrhosis. While these 2 cases present clinical scenarios at the opposite ends of the risk-benefit spectrum, the risk-benefit profile in the majority of patients with HCV and psychiatric comorbidities is in an intermediate zone. Prophylactic treatment with psychotropics might be offered if the woman in case 1 had a history of major depressive disorder and was infected with a low viral load of HCV genotype 1. Biopsy-demonstrated cirrhosis might be a compelling reason to attempt interferon-α treatment in case 2. Ongoing psychiatric follow-up is certainly indicated when a patient has 1 or more of the psychiatric risk factors listed above. In cases in which a low estimated likelihood of viral clearance of HCV is combined with an intermediate to low probability of psychiatric adverse effects, an evaluation incorporating the patient's interferon-α treatment preference and available psychosocial support can influence the treatment decision. Use of an evidence-based approach in selecting patients for interferon-α treatment is paramount when endeavoring to treat patients with HCV and comorbid psychiatric illness in order to minimize the morbidity and mortality associated with interferon-α (i.e., suicide). This model is intended to assist clinicians in making an individualized and balanced risk-benefit analysis incorporating HCV–disease specific factors as well the potential for psychiatric complications prior to offering interferon-α treatment.

Human leukocyte antigen phenotypes and hepatitis C viral load

After hepatitis C virus (HCV) infection, 55% to 85% of patients become chronic carriers. HCV-RNA could be detected in the sera of these patients though the viral load varies. Various factors may be involved in determining the viral load. In this study, we want to investigate the relationship between human leukocyte antigen phenotypes and hepatitis C viral load. One hundred and sixty HCV-RNA positive subjects were investigated in this study. We have analyzed 160 HCV-RNA positive subjects and found that lower HCV viral load is significantly associated with HBsAg-positivity (P = 0.017) but not age, gender, or mixed infection (infection with different HCV genotypes). One hundred and fifty-four HBsAg-negative subjects were further analyzed to explore the relationship between human leukocyte antigen (HLA) phenotypes and HCV viral load. Subjects with certain HLA alleles (A*34, B*56, DRB1*1502) have significantly lower viral load than those without these alleles (P = 0.0074, 0.0039 and 0.016, respectively) while those with HLA-B*4001 have significantly higher viral load (P = 0.0026). Furthermore, lower viral load was significantly associated with HLA-DRB1 heterozygosity in subjects with HLA-B heterozygosity (P = 0.048). Our data suggests a role for host immunogenetic factors in determining viral load during HCV infection.