Melissa Osborn

Subdural empyema and other suppurative complications of paranasal sinusitis

Suppurative intracranial infection, including meningitis, intracranial abscess, subdural empyema, epidural abscess, cavernous sinus thrombosis, and thrombosis of other dural sinuses, are uncommon sequelae of paranasal sinusitis. A high index of suspicion is necessary to identify these serious complications. We present a patient with subdural empyema in whom the diagnosis was delayed, followed by a discussion of suppurative complications of sinusitis. The case shows the rapid progression of subdural empyema, which represents a true neurosurgical emergency requiring prompt diagnosis and management.

Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection

ABSTRACT A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8+ T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8+ T cells during the acute and chronic stages of infection. Although HCV-specific CD8+ T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8+ T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8+ T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the “death phase” of HCV-specific CD8+ T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection, at the site of infection in the liver, a substantial frequency of caspase 9-mediated T-cell death was also present. This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections.

Safety and efficacy of entecavir for the treatment of chronic hepatitis B

Entecavir is a cyclopentyl deoxyguanosine analog that was approved for the treatment of the hepatitis B virus (HBV) in 2005. In Phase III trials, it showed potent HBV suppression with drops of 6- to 7-log copies/mL in HBV DNA at 1 year. In addition, rates of genotypic resistance in nucleos(t)ide-naïve patients are low, reaching only 1.2% after 6 years. Safety and efficacy have been established in compensated cirrhosis and HIV-coinfected patients. Studies in decompensated cirrhosis also show efficacy. Because of potent viral suppression and a large genetic barrier to resistance, entecavir is now a first-line choice in most HBV treatment guidelines and has become an integral part of the HBV treatment armamentarium.

Acute hepatitis C and HIV coinfection

Hepatitis C is a common infection worldwide, but acute infection is often asymptomatic and difficult to diagnose. People coinfected with HIV and hepatitis C might progress to chronic liver disease more quickly. We present a case of a man infected with HIV with sexually acquired acute hepatitis C and discuss the immunology, natural history, and epidemiology of acute hepatitis C and coinfection with HIV. Several recent reports have documented acute hepatitis C among men who have sex with men who engage in high risk sexual practices and often have concomitant genital ulcer disease. We review treatment options for the medical management of acute hepatitis C and coinfection with HIV.

Safety and efficacy of telbivudine for the treatment of chronic hepatitis B.

Telbivudine was recently approved for the treatment of chronic hepatitis B. Phase III studies indicated its antiviral potency with 6- to 6.5-log copies/mL reductions in hepatitis B DNA levels at year 1, comparable to other potent agents such as entecavir or tenofovir. Genotypic resistance rates, however, reached 25% at year 2 in hepatitis B e-antigen positive subjects and 11% in hepatitis B e-antigen negative subjects, preventing it from becoming a preferred first-line drug for hepatitis B. Furthermore, its signature resistance mutation (a change from methionine to isoleucine at position 204 in the reverse transcriptase domain of the hepatitis B polymerase) also confers cross-resistance to entecavir, lamivudine, and emtricitabine. Telbivudine is well tolerated, with elevations in creatine phosphokinase being the most common abnormality observed in clinical trials. Most often, elevations were asymptomatic. Future research in hepatitis B will focus on the best ways to use existing therapies, including telbivudine, sequentially or in combination in order to maximize viral suppression and minimize the development of antiviral resistance.