Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis C.

BACKGROUND: Primary analysis of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial showed long-term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis. AIM: To assess the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms and sexual health in HALT-C patients. METHODS: A total of 517 HALT-C patients received peginterferon alfa-2a (90 microg/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores and symptoms were serially assessed by repeated-measures analyses of covariance. RESULTS: Patients with cirrhosis (n = 427) reported lower general well-being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome. CONCLUSION: Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164).

Evolution of hepatitis C virus NS5A region in breakthrough patients during pegylated interferon and ribavirin therapy*.

Investigating the evolution of the hepatitis C viral (HCV) genome in the small number of patients that experience viral breakthrough might shed light on the problem of resistance to interferon therapy. Within the HCV genome, sequence diversity of the viral nonstructural 5A protein-coding region (NS5A) has been linked to interferon responsiveness. We analysed the temporal sequence changes within NS5A in genotype 1a patients: 6 breakthrough (BT), 12 sustained virologic responders (SVR) and 12 non-responders (NR), all of whom had received full dose peg-interferon and ribavirin therapy. The entire NS5A region was amplified by reverse transcription (RT)-PCR followed by direct sequencing of serum samples from baseline and three on-treatment time points for each group. Comparing baseline sequences with week 12 and later time points, BT patients resembled SVR patients in having a higher number of amino acid substitutions at week 12 than NR patients; however, the number of amino acid substitutions in this group decreased at and after BT. Substitutions were focused in the V3 and flanking regions in BT patients but not in SVR patients. The high number of substitutions in NS5A in both BT and SVR groups suggests that selective pressure is associated with viral response to therapy. Our results provide evidence that amino acid substitutions within the NS5A coding region may reflect a host response that drives selective pressure for viral adaptation.

Age-related eye diseases: impact of hormone replacement therapy, and reproductive and other risk factors.

In Western countries, age-related macular degeneration is the leading cause of legal blindness in the population over 60 years of age, and cataract is the leading cause of visual impairment worldwide. Because postmenopausal women are living longer, they have a greater probability of developing a variety of age-related visual disorders. As the population ages, the physical and emotional toll of these ailments, as well as the burden on the health care system, will escalate. Currently, interventional therapy for age-related macular degeneration is limited to a small subpopulation of patients who can benefit from laser treatment, whereas surgery is the only effective treatment for cataract. The need for other therapeutic options and preventive measures remains a major challenge for the future. Studies among women have suggested that exposure to estrogens is associated with a reduction in risk of developing ocular diseases associated with aging. This article addresses the epidemiology of age-related macular degeneration and cataract, focusing on the specific risks for women, and discusses factors that may influence development or progression of these visual disorders.

Do age-related macular degeneration and cardiovascular disease share common antecedents?

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss and blindness in elderly Americans. The etiology of this condition remains unknown and treatment options are limited. Some epidemiological findings point to a cardiovascular risk profile among persons with AMD. Documented risk factors for cardiovascular disease (such as age, smoking, hypertension, hypercholesterolemia, post-menopausal estrogen use, diabetes, and dietary intake of fats, alcohol and antioxidants) have also been associated with AMD in some studies. This raises the possibility that the causal pathways for cardiovascular disease and AMD may share similar risk factors. Future research on this hypothesis could lead to important insights into etiologic factors for AMD. Research could also identify modifiable risk factors and suggest new treatment options which could prevent AMD, slow its progression, or reduce visual loss. Susceptible individuals could then be targeted for improved health promotion and disease prevention measures for this disabling and highly prevalent disorder.

The epidemic of Acanthamoeba keratitis: where do we stand?

PURPOSE: To review from a historical perspective the recent epidemic of Acanthamoeba keratitis and its association with the use of contact lenses and to provide a summary of recent techniques that have allowed earlier diagnosis and treatment. METHODS: The authors reviewed available literature on Acanthamoeba keratitis from 1973 to the present, with emphasis on the history of the epidemic and its association with contact lenses, identification of risk factors, preventive measures, and current diagnostic techniques. We also estimated the annual incidence of Acanthamoeba keratitis during 1985 through 1987 from available data. RESULTS: Before the popularization of soft-contact-lens wear, Acanthamoeba keratitis was extremely rare; however, an epidemic began in the early 1980s, and the number of cases increased dramatically beginning in 1984. By 1985, the association of this infection with the use of contact lenses was firmly established, and in 1987, the infection was shown to occur more commonly among men, as well as in contact-lens wearers who failed to disinfect their lenses as frequently as recommended, swam while wearing lenses, or used homemade instead of commercially prepared saline solution. Adoption of "disposable" contact lenses in the late 1980s did not decrease the risk of Acanthamoeba keratitis, and concerns remain regarding the effectiveness of some contact-lens disinfectants; however, recent advances in diagnosis and treatment have improved the prognosis. The annual incidence during 1985 through 1987 was conservatively estimated at 1.65 to 2.01 cases per million contact-lens wearers. It is unclear whether the incidence is declining. CONCLUSION: Acanthamoeba keratitis has now been recognized worldwide, and there are clear associations of this infection with improper contact-lens hygiene, particularly contact with water. Recent methods allow earlier diagnosis and thus improved outcomes. The epidemic provides a valuable lesson on how a new technology can be associated with unforeseen complications and exemplifies how rapid dissemination of epidemiologic information can aid in controlling an emergent epidemic.