Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Cytomegalovirus infection in renal transplantation: clinical aspects, management and the perspectives / Infecção pelo citomegalovírus no transplante de rim: aspectos clínicos, manejo e perspectivas

Cytomegalovirus infection is one of most frequent infectious complications after renal transplantation, and can be classified as primo-infection, when the transmission occurs through the graft, or reactivation, when the recipient is cytomegalovirus seropositive. After transplantation, cytomegalovirus can appear as an infection, when the patient presents with evidence of viral replication without symptoms or disease, which has two clinical spectra: typical viral syndrome or invasive disease, which is a less common form. Their effects can be classified as direct, while the disease is developed, or indirect, with an increase of acute rejection and chronic allograft dysfunction risks. Diagnosis must be made based on viremia by one of the standardized methods: antigenemia or PCR, which is more sensitive. The risk factors related to infection after transplantation are the serologic matching (positive donor and negative recipient) and anti-lymphocyte antibody drugs. One of the strategies to reduce risk of disease should be chosen for patients at high risk: preemptive treatment or universal prophylaxis. Recent clinical research has described ganciclovir resistance as an emergent problem in management of cytomegalovirus infection. Two types of mutation that cause resistance were described: UL97 (most frequent) and UL54. Today, sophisticated methods of immunologic monitoring to detect specific T-cell clones against cytomegalovirus are used in clinical practice to improve the management of high-risk patients after renal transplantation.

A infecção pelo citomegalovírus é uma das principais complicações após o transplante de rim, podendo ser classificada em primoinfecção, quando a transmissão ocorre por meio do enxerto, ou em reativação, quando o receptor é soropositivo. Do ponto de vista clínico, pode se apresentar como infecção, na ausência de sintomas, ou como doença, com dois diferentes espectros: a síndrome viral típica ou, menos comumente, a doença invasiva. Os efeitos podem ser diretos, que é o desenvolvimento da doença, ou indiretos, como aumento no risco de rejeição aguda e de disfunção crônica do enxerto. O diagnóstico deve ser feito por pesquisa de viremia por meio de um dos dois métodos padronizados: antigenemia ou PCR − sendo essa última a mais sensível. Os fatores de risco relacionados com a infecção após o transplante são o match sorológico (doador positivo e receptor negativo) e o uso de anticorpos antilinfócitos. Uma das estratégias de redução de risco de doença deve ser escolhida após o transplante nos pacientes de alto risco: tratamento preemptivo ou profilaxia. Recentemente, linhas de pesquisa clínica têm apontado a resistência ao ganciclovir como um problema emergente no manejo da infecção pelo citomegalovírus. Duas formas de mutação que causam resistência são descritas: UL97, que é a mais frequente, e a UL54. Atualmente, sofisticados métodos de monitorização imunológica, como a detecção de clones específicos de células T contra o citomegalovírus podem ser utilizados na prática clínica para o melhor manejo após o transplante renal dos pacientes de alto risco.

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0 percent (n = 17) and 9.0 percent (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3 percent vs. 25.0 percent). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0 percent vs. 12.0 percent, and hyperbilirubinemia, 20.0 percent vs. 1.6 percent, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.

Situación actual de la hepatitis B en Chile / Present situation of hepatitis B in Chile

Background: Hepatitis B virus infection generates carriers and 8 percent will evolve to a chronic phase. Aim: To perform a compilation of studies on hepatitis B in Chile and other sources of information to estímate the impact of this disease in our country. Material and methods: Published and unpublished evidence about the infection, in the general population and risk groups in our country, was compiled and reviewed critically. Informal interviews to experts, revisión of the mandatory notification book of the Ministry of Health and collection of data from laboratories that study hepatitis B virus, were also carried out. Results: The seroprevalence of chronic carriers in blood donors is nearly O.3 percent. Among risk groups such as health care personnel, the figure is O.7 percent, among homosexuals 29 percent, among HIV positive patients 30 percent, among sexual workers 2 percent and among children with chronic hemodialysis, 9 percent. Prevalence rate according to notified cases in 2004 was 1.8 x 100,000 habitants. Detection of viral hepatitis B surface antigen in ¡aboratories occurs in 0.2 percent of donors and 1.396 of non donors. Conclusions: The seroprevalence of hepatitis B virus, the lack of notification, and the introduction of hepatitis B vaccine to our Regular Program of Immunizations, are arguments to develop in Chile a hepatitis B and C surveillance system.

Impairment of cytomegalovirus-specific cellular immune response as a risk factor for cytomegalovirus disease in transplant recipients: [review]

Human cytomegalovirus (CMV) infection is common in most people but nearly asymptomatic in immunocompetent individuals. After primary infection the virus persists throughout life in a latent form in a variety of tissues, particularly in precursor cells of the monocytic lineage. CMV reinfection and occurrence of disease are associated with immunosuppressive conditions. Solid organ and bone marrow transplant patients are at high risk for CMV disease as they undergo immunosuppression. Antiviral treatment is effective in controlling viremia, but 10-15 percent of infected patients can experience CMV disease by the time the drug is withdrawn. In addition, long-term antiviral treatment leads to bone marrow ablation and renal toxicity. Furthermore, control of chronic CMV infection in transplant recipients appears to be dependent on the proper recovery of cellular immunity. Recent advances in the characterization of T-cell functions and identification of distinct functional signatures of T-cell viral responses have opened new perspectives for monitoring transplant individuals at risk of developing CMV disease.