Faculty Bibliography

The life expectancy of HIV seropositive persons is approaching the life expectancy of those who are uninfected with HIV. Hepatitis C virus (HCV) infection has emerged as a worldwide epidemic. Given the similar transmission route between HCV and HIV, there has been an explosion in the number of individuals infected with both viruses. Because of the successful introduction of antiretroviral therapy, patients are more susceptible to new opportunistic infections such as HCV. HCV leads to a more rapid progression to end-stage liver disease in patients with HIV, and the morbidity and mortality related to HCV in co-infected patients is on the rise. Therefore, it has become imperative to treat both HIV and HCV in co-infected patients. The primary goal of HCV therapy is permanent eradication of the virus. Secondary goals include reduction in hepatic fibrosis progression, development of decompensated cirrhosis, and hepatocellular carcinoma. Early studies using standard interferon-alfa for the treatment of HCV in co-infected individuals were discouraging, as poor outcomes, high discontinuation rates, and severe adverse events were observed. The current standard of care for treatment of HCV is pegylated-interferon and ribavirin. New studies have recently demonstrated a higher sustained virologic response rate and a better adverse event profile than previously reported in co-infected patients. As a result, we recommend considering all co-infected patients for HCV therapy while watching closely for unique treatment-related toxicities. The treatment of HCV in co-infected patients should be a high priority for all providers

Because the life expectancy of patients infected with HIV has been prolonged, liver diseases have assumed far greater importance as a cause of morbidity and mortality in these patients. Given the shared risks of transmission, patients who have HIV often are coinfected with hepatotrophic viruses such as hepatitis C and hepatitis B. Further, antiretroviral therapy (ART) used by patients who have HIV is often hepatotoxic, contributing to liver damage. With increasing immunosuppression caused by AIDS, patients who have HIV have to deal with these issues and the increased risk of infection with opportunistic viral, fungal, bacterial, and protozoal pathogens. In addition, steatosis and lipodystrophy now are recognized more commonly in patients who have HIV, particularly in the setting of ART. Thus, understanding of liver diseases in the setting of HIV infection becomes an important focus in caring these individuals. There have been numerous advances in the treatment of liver disease in patients who have HIV, particularly in treating viral hepatitis C and B. This article reviews various liver manifestations in patients who have HIV and the recent advances in diagnostic and therapeutic options

OBJECTIVES: This study assessed the rates and course of depressive symptomatology and neurocognitive deficits in hepatitis C virus (HCV) patients undergoing interferon treatment, and explored possible predictors of depression and neurocognitive deficits. DESIGN: In order to obtain objective assessments of depression, and to evaluate cognitive impairment, a 72-week prospective study, comprising 48 weeks of treatment and 24 weeks of post-treatment follow-up was utilized. METHODS: A total of 50 HCV patients were assessed at baseline, and 14 times during pegylated interferon plus ribavirin treatment. Patients were also assessed on four timepoints after the termination of treatment. All patients have previously been treated for hepatitis C infection with interferon and were judged to be treatment resistant in these treatments. Depression was assessed using the Center for Epidemiological Studies Depression (CES-D) questionnaire, and patients were interviewed regarding problems with memory, attention and concentration. RESULTS: Eighty-two per cent of interferon-treated patients developed severe enough depressive symptoms to meet the CES-D criteria for possible major depressive disorder (MDD). Possible MDD onset was most frequent by the first week of treatment, and almost all possible MDD cases were observed by week 8. More severe depressive symptoms at baseline were associated with higher depressive symptoms during interferon treatment. Thirty per cent of patients complained about cognitive problems. In half of these patients cognitive impairments were still reported after the termination of treatment. There was no association between depression during interferon treatment and subjective cognitive complaints. CONCLUSIONS: The findings suggest that depression and cognitive impairments are frequent and persistent side-effects of interferon treatment in treatment-resistant patients

BACKGROUND: Survival in HIV infection has improved dramatically in the last decade due to antiretroviral therapy (ART). Due to shared routes of transmission, HCV is found in approximately 30% of HIV infected patients. HCV infection has emerged as a major issue in this population as manifest by a major increase in liver-related mortality. ART-associated hepatotoxicity has been demonstrated to occur more frequently in co-infected individuals and may be severe or fatal in some instances. Thus treatment of HCV has become a priority in HIV infected individuals. OBJECTIVES: The main aims of this review are to summarise and illustrate the current evidence based management of anti-HCV therapy in HIV-infected patients. METHODS: A systematic review of the literature was performed using Pubmed and Medline searches. CONCLUSION: All HIV-infected patients should be screened for HCV infection via anti-HCV antibody and HCV RNA polymerase chain reaction. If HCV infection is present, treatment should be considered in those patients with evidence of liver inflammation and fibrosis. Recent studies have demonstrated the safety and efficacy of anti-HCV therapy in HIV-infected individuals with pegylated interferon and ribavirin combination therapy. HCV genotype is predictive of response to therapy and increasing the duration of therapy to 48 weeks has proven to be more effective in patients with genotypes 2 and 3. HCV treatment with interferon based therapy is associated with many unique side effects and toxicities in this population of which the clinician must be aware

The most common chronic blood-borne infection in the United States is caused by hepatitis C virus. An estimated 3.9 million people (1.8%) in the United States have been infected with the hepatitis C virus, excluding certain subpopulations who are at high risk for hepatitis C virus infection. Among these subpopulations are an estimated 255,000 (15%) of prison inmates and 175,000 (22%) of homeless people. Prevalence of hepatitis C virus infection is also high among veterans (6.6% overall and even higher among homeless veterans). The single most important risk factor for hepatitis C virus infection is injection drug use; up to 90% of illicit injection drug users are infected with hepatitis C virus. This review describes the prevalence of hepatitis C virus in special populations and discusses the treatment options for patients with severe disease, transplant recipients, and patients at high risk for infection. Close monitoring and management of therapeutic side effects are required to assist these patients in adhering to therapy.

Anemia and decreased health-related quality of life (HRQL) are common in patients receiving combination therapy of interferon alfa (IFN) and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. In a randomized, prospective study evaluating the effectiveness of epoetin alfa in maintaining RBV dose, alleviating anemia, and improving HRQL in anemic (Hb < or = 12 g/dL) HCV-infected patients receiving combination therapy, patients receiving epoetin alfa had significant improvements in HRQL compared with placebo. In this study, 185 patients were randomized to 40,000 units of epoetin alfa subcutaneously weekly or placebo for an 8-week double-blind phase (DBP), followed by an 8-week open-label phase during which all patients received epoetin alfa. To further assess the impact of epoetin alfa on HRQL, post hoc analyses were conducted in the same patient population to compare the HRQL of these patients at randomization with norms of other populations, and to determine the critical relationship between hemoglobin (Hb) levels and HRQL. Mean HRQL scores of anemic HCV-infected patients receiving combination therapy at randomization were significantly lower than those of both the general population and patients who had other chronic conditions. Patients receiving epoetin alfa who had the greatest Hb increases from randomization to the end of the DBP also had the largest improvements in HRQL. Hb improvement was an independent predictor of HRQL improvement in these patients. In conclusion, epoetin alfa provided clinically significant HRQL improvement in HCV-infected patients receiving IFN/RBV therapy.