Research on expression of Toll-like receptors and IFN-α in HCV infected patients with different clinical outcomes / 中国热带医学

@#Abstract: Objective To investigate the changes in expression of Toll-like receptor 3 (TLR3) and interferon-α (IFN-α) in patients with different clinical outcomes of hepatitis C virus (HCV) infection treated with direct-acting antiviral agents (DAAs), and to explore the relationship between the expression of TLR3 and IFN-α with the clinical outcomes of HCV infection. Methods A total of 149 HCV infected patients who received initial treatment were selected from Hainan General Hospital between September 2020 and August 2022. The patients were divided into two groups: chronic hepatitis C (CHC) group (n=129) and liver cirrhosis (LC) group (n=20). Additionally, 28 volunteers were selected as the control group during the same period. All patients with HCV infection were first treated with Sofosbuvir/Vipatavir tablets for 12 weeks. Blood samples were collected at 0, 4, 12, 24 and 48 weeks after treatment. Liver function indicators were detected by enzyme-linked immunosorbent assay (ELISA), while TLR3 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction (qRCR), IFN-α was detected by Luminex multiplex cytokine assays. Measurement data subject to normal distribution were represented by x±s, and t test was used between groups. Compare differences between groups. Results TLR3 mRNA in CHC group was higher than that in LC group and control group at baseline (P<0.05). After 4 weeks of DAAs treatment, TLR3 mRNA in CHC and LC groups was significantly up-regulated (P<0.05). TLR3 mRNA in the CHC group was gradually down-regulated to the level of the control group at 12, 24, and 48 weeks. In addition, IFN-α expression gradually increased with prolonged treatment, while it decreased in the LC group. The liver inflammation indicators in both the CHC and LC groups partially recovered after treatment with DAAs. Conclusions TLR3 is involved in viral clearance and chronic inflammatory response. The expression difference of TLR3 in patients with different clinical outcomes of HCV infection after DAAs treatment may be related to the severity of the disease.

Cost-utility Analysis of the Pan-genotypic Direct-acting Antivirals in the Treatment of Chronic Hepatitis C Infection / 中国药房

OBJECTIVE：To evaluate the cost-utility of the pan-genotypic direct-acting antivirals （DAAs）in the treatment of patients with chronic hepatitis C infection ，and to provide pharmacoeconomic evidence for relevant health care decisions. METHODS：A Markov model was established from a societal perspective with newly diagnosed chronic hepatitis C patients in China as the target population ，and analyzed quality-adjusted life years （QALYs）and incremental cost-utility ratios （ICERs）of patients with chronic hepatitis C with sofosbuvir/velpatasvir ，glecaprevir/pibrentasvir，sofosbuvir+coblopasvir. Sensitivity analysis was used to verity the robustness of the results. RESULTS ：Glecaprevir/pibrentasvir increased QALYs by 0.002 1 and costs by 25 021 RMB，compared to sofosbuvir/velpatasvir ；its ICERs was 12 129 031 yuan/QALY（willingness to pay threshold was 70 892 yuan/QALY），which had no cost-utility ；glecaprevir/pibrentasvir need to cut down the price by 64.65％ to have cost-utility. Sofosbuvir+coblopasvir increased QALYs by 0.002 0 and saved costs by 515 yuan，so it was the optimal regimen which was cost-saving. Sensitivity analysis showed that SVR rates and drug prices were the most influential factors. The probability of having cost-utility for sofosbuvir+coblopasvir was higher than glecaprevir/pibrentasvir. CONCLUSIONS ：Glecaprevir/pibrentasvir need to reduce the price to achieve better affordability. Sofosbuvir+coblopasvir shows economical advantage.

Efficacy and Safety of Daclatasvir and Asunaprevir in Patients with Hepatitis C Virus Genotype 1b Infection on Hemodialysis

BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)

Antiviral Regimens for the Patients with Chronic Hepatitis C Virus Complicated with Cirrhosis / 中国药师

The efficacy of patients infected with hepatitis C virus complicated with cirrhosis is not promising after treated with present standard therapy. With more and more new drugs against hepatitis C virus, many new regimens for the patients with chronic hepatitis C virus complicated with cirrhosis have come forth. Because the adverse reactions of the first generation HCV protease inhibi-tors telaprevir and boceprevir are severe, they are not recommended to be used in the patients with chronic hepatitis C virus complicated with cirrhosis. The other drugs, such as simeprevir, sofosbuvir and ledipasvir show good efficacy in the patients with chronic hepatitis C virus complicated with cirrhosis, however, the sustained virological response ( SVR) in the patients with chronic hepatitis C virus complicated with cirrhosis is lower than that in the patients with chronic hepatitis C virus without cirrhosis. Therefore, the regimens should be optimized in the future to narrow the gap in SVR.

Hepatitis C Virus Infection and Coronary Arteriosclerosis: The Growing Evidences.

Arteriosclerosis is a chronic inflammatory vascular pathology that features a leading cause of coronary artery disease contributing to significant mortality and reduced quality of life. The recent identification of the possible role of infections in the initiation of a serious of inflammatory events represents an interesting development towards the better understanding of immune mediated vascular injury and premature atherosclerosis in patients with chronic HCV infection. A number of factors related to chronic HCV infection have been hypothesized to contribute to arteriosclerosis. The current review displays some of the aspects of interaction between the chronic viral infection, the immune system and cytokine networks and its relation to the increased risk of coronary artery disease.

Contribuição da ultrassonografia para o diagnóstico das alterações histopatológicas presentes na hepatite C crônica, com ênfase na esteatose hepática: Parte I / Contribution of ultrasonography to the diagnosis of chronic hepatitis C histopathological changes, with emphasis on hepatic steatosis: Part I

OBJETIVO: Avaliar a contribuição da ultrassonografia no estudo das alterações histopatológicas encontradas na hepatite crônica pelo vírus C, com ênfase para a esteatose hepática. MATERIAIS E MÉTODOS: Foram comparados os resultados dos exames ultrassonográficos do fígado de 192 pacientes portadores de hepatite crônica pelo vírus C, com os achados histopatológicos dos fragmentos obtidos por biópsia hepática. Todos os exames ultrassonográficos obedeceram a um mesmo protocolo, sendo analisados os seguintes critérios: ecogenicidade, ecotextura e atenuação. Os pacientes foram agrupados considerando-se os com alterações ultrassonográficas e os sem alterações ultrassonográficas, sendo comparados com as alterações histopatológicas presentes. RESULTADOS: Entre as alterações histopatológicas presentes, apenas os graus 0 e 3 de alteração arquitetural e a esteatose hepática apresentaram diferença estatística significante entre os dois grupos. Dentre os critérios ultrassonográficos avaliados, a atenuação foi o que apresentou melhor correlação com a esteatose hepática. CONCLUSÃO: Os resultados do trabalho demonstraram que, em pacientes com hepatite crônica pelo vírus C, a ultrassonografia apresentou limitações à caracterização das alterações histopatológicas, apresentando concordância regular com o diagnóstico de esteatose hepática. Destaca-se a capacidade do método em mostrar a probabilidade de inexistência de esteatose hepática, tendo em vista a especificidade de 77,9 por cento e o valor preditivo negativo de 95,5 por cento.

OBJECTIVE: To evaluate the role of ultrasonography in the assessment of histopathological changes in patients with chronic hepatitis C, with emphasis on hepatic steatosis. MATERIALS AND METHODS: Liver ultrasonography results were compared with histopathological findings of liver biopsy of 192 patients with chronic hepatitis C virus infection. All the US examinations followed a single protocol, analyzing the following aspects: echogenicity, echotexture and attenuation. The patients sample was divided into two groups as follows: patients with sonographic changes and patients with no sonographic changes. Sonographic findings of both groups were compared with histopathological findings after liver biopsy. RESULTS: Statistically significant intergroup differences were observed just regarding architectural changes grades 0 and 3 and hepatic steatosis. Attenuation was the sonographic criterion that was best correlated with hepatic steatosis. CONCLUSION: The results of the present study demonstrate that, in patients with chronic hepatitis C, ultrasonography has limitations in the characterization of histopathological changes, with an intermediate rate of agreement with the diagnosis of hepatic steatosis. Considering the specificity of 77.9 percent and the negative predictive value of 95.5 percent, the authors highlight the capacity of the method to demonstrate the probability of absence of hepatic steatosis.

Completion of Chronic Hepatitis C Virus Treatment in Interferon-Induced Major Depressive Disorder with Psychotic Features

Interferon (IFN)-associated psychiatric disorders can be managed without interruption to hepatitis C virus (HCV) treatment. The limited number of cases in the literature reporting psychotic depression as an adverse drug reaction to IFN resulted in discontinuation of HCV therapy. The author reports a case of a 49 year-old man with chronic HCV genotype 1a treated with pegylated interferon-alpha and ribavirin developing major depressive disorder with psychotic features. The patient was successfully treated with both an antidepressant and antipsychotic for this suspected IFN-associated adverse drug effect while continuing 12 months of uninterrupted HCV treatment and subsequently achieving sustained hepatitis C virological response. Although IFN can cause distressing psychiatric disturbances, appropriate treatment with psychotropic agents and careful monitoring allows patients to be maintained on a full course of HCV treatment.