Status of clinical research in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts / 器官移植

Antiviral therapy for chronic hepatitis C virus (HCV) infection has entered the era of direct antiviral agent (DAA), and up to 95% of patients could be clinically cured. Under this circumstance, HCV infection has gradually changed from relative contraindication to surgical indication for kidney transplantation. However, at present, the number of kidney transplantation from HCV-infected donors or recipients has been rarely reported in China. The short-term follow-up data of HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts in other countries have confirmed that DAA yields high cure rate and safety in the treatment of HCV infection, and recipients could obtain favorable short-term survival and allograft outcome. However, the long-term safety of HCV-infected kidney transplantation remains to be validated by clinical trials with large sample size and long-term follow-up. In this article, the virological clearance, allograft outcome and safety of DAA use in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts under the intervention of DAA were investigated, aiming to evaluate clinical safety and efficacy of this pattern of kidney transplantation and deepen the understanding of safe use of HCV-positive organs.

Research progress on the application of liver transplantation in HIV combined with HCV positive patients / 器官移植

With the advent of highly active antiretroviral therapy (HAART), acquired immune deficiency syndrome (AIDS) has gradually evolved from an incurable terminal disease to a controllable chronic disease. Due to the extended survival of AIDS patients, chronic renal failure and (or) chronic liver failure have become the main cause of death, and AIDS patients with chronic liver failure are constantly complicated with hepatitis C virus (HCV) infection. Human immunodeficiency virus (HIV) infection was previously considered as a contraindication for liver transplantation. With the deepening of medical cognition and improvement of surgical management experience, the quantity of HIV positive liver transplantation recipients has been steadily elevated and high long-term survival rate has been achieved. Nevertheless, the 3-, 5-, and 10-year survival rates after liver transplantation of HIV combined with HCV positive patients remain extremely low. In this article, the development of liver transplantation in HIV positive patients, the disease progression of HIV combined with HCV positive patients, and the treatment for the recurrence of viral hepatitis C after the operation were summarized.

Guidelines for the prevention and treatment of hepatitis C (2019 version) / 中华肝脏病杂志

In order to standardize and update the prevention, diagnosis and antiviral therapy of hepatitis C and to achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat by 2030, Chinese Medical Association, the Chinese Society of Hepatology, and the Society of Infectious Diseases organized relevant native experts in 2019 to revise the guideline for the prevention and treatment of hepatitis C (2019 version) based on the basic, clinical and prophylactic research progress of hepatitis C infection at home and abroad, combined with the present actual situation of our country, so as to provide an important basis for the prevention, diagnosis and treatment of hepatitis C.

Guidelines for the prevention and treatment of hepatitis C (2019 version) / 中华肝脏病杂志

In order to standardize and update the prevention, diagnosis and antiviral therapy of hepatitis C and to achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat by 2030, Chinese Medical Association, the Chinese Society of Hepatology, and the Society of Infectious Diseases organized relevant native experts in 2019 to revise the guideline for the prevention and treatment of hepatitis C (2019 version) based on the basic, clinical and prophylactic research progress of hepatitis C infection at home and abroad, combined with the present actual situation of our country, so as to provide an important basis for the prevention, diagnosis and treatment of hepatitis C.

Re-treatment with peginterferon-ribavirin and direct antiviral agents of patients with chronic hepatitis C after failure of intensified treatment / 中华实验和临床病毒学杂志

Objective@#To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied.@*Methods@#Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded.@*Results@#The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild.@*Conclusions@#The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.

Influences of daclatasvir plus asunaprevir therapy on CD4+and CD8+T cell functions in patients with chronic hepatitis C / 中华微生物学和免疫学杂志

Objective To investigate the changes in CD4+and CD8+T cell functions in patients with chronic hepatitis C in response to daclatasvir plus asunaprevir therapy. Methods A total of 21 HLA-A2-restricted patients with chronic hepatitis C virus ( HCV) genotype 1b infection were enrolled in this study. All patients were treated with daclatasvir plus asunaprevir for 24 weeks. Peripheral blood samples were collected at baseline, 4 and 24 weeks post-therapy. CD4+and CD8+T cells were sorted and purified. Cytokines secreted by CD4+T cells were measured by flow cytometry. CD8+T cells were co-cultured with HCV cell culture ( HCVcc)-infected Huh7. 5 cells in both direct and indirect contact co-culture systems. The cytolytic and non-cytolytic functions of CD8+T cells were analyzed by measuring the levels lactate dehy-drogenase and cytokines in the supernatants of cell culture. Results The virological and biochemical re-sponse rates were 71. 43% (15/21) and 77. 78% (14/18) at 4 weeks post-therapy, respectively. Both rates reached 100% at 24 weeks post-therapy. Secretion of IFN-γ, TNF-α and IL-17 by CD4+T cells was significantly enhanced at 4 and 24 weeks in response to daclatasvir plus asunaprevir therapy. In contrast, IL-10 secretion by CD4+T cells did not change notably post-therapy. However, no significant differences in cy-tokine secretion were found between patients with and without virological response at 4 weeks post-therapy. Daclatasvir plus asunaprevir therapy increased the percentage of dead cells in direct contact co-culture system of CD8+T cells and HCVcc-infected Huh7. 5 cells at 4 and 24 weeks post-therapy. However, it did not af-fect the cytotoxity of CD8+T cells in indirect contact co-culture system. Moreover, IFN-γ expression in both direct and indirect contact co-culture systems was significantly increased at 4 and 24 weeks post-therapy. There was also a notable increase in the expression of TNF-α in direct contact co-culture system, while no remarkable change in TNF-α expression was detected in indirect contact co-culture system. No significant differences in cytolytic and non-cytolytic activities of CD8+T cells were found between patients with virologi-cal and without virological response at 4 weeks post-therapy. Conclusion Daclatasvir plus asunaprevir ther-apy achieves high clinical cure rate in patients with chronic hepatitis C. Inhibition of HCV replication con-tributes to the improvement of CD4+and CD8+T cell functions.