Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil

ABSTRACT Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

Effect evaluation of medical insurance policy for hepatitis C DAA drugs based on patient survey / 中国药房

OBJECTIVE To provide reference for the prevention and treatment of hepatitis C and the formulation and improvement of medical insurance payment policy for direct-acting antiviral （DAA） drugs. METHODS An questionnaire survey was conducted among the patients who received hepatitis C treatment in a third-grade class-A hospital in Sichuan province from 2019 to 2020 and enjoyed Chengdu medical insurance policy. The patients’ hepatitis C treatment and satisfaction with the medical insurance policy for DAA drugs were compared before and after DAA drugs were included in the medical insurance list. RESULTS A total of 203 patients effectively responded among 644 investigated patients. In terms of treatment plans， although there were significant differences in the treatment plan between patients who saw a doctor in 2019 and 2020 （P＜0.05）， the vast majority of patients were cured within the course of treatment （200 cases， 98.52%）， and there were no obvious adverse reactions （193 cases， 95.07%）. In terms of economic burden， the out-of-pocket costs and economic burden of patients treated with DAA drugs in 2020 were significantly lower than those treated with DAA drugs in 2019 （P＜0.05）； in terms of patient services， 78.82% of patients received expert consultation services from designated medical institutions， but 9.85% of patients still did not receive any patient services provided by the hospital. In terms of satisfaction with outpatient reimbursement policy， the overall satisfaction of patients who saw a doctor in 2020 （95.37%） was significantly higher than those who saw a doctor in 2019 （81.05%）（P＜0.05）. CONCLUSIONS The surveyed patients with hepatitis C obtain good efficacy after DAA drugs treatment， and are satisfied with the medical insurance policy of DAA drugs， but the standardized management of patient services in designated medical institutions is insufficient.

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

Abstract Introduction The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. Patients and methods This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. Results One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p< 0.001). Conclusions Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.

Efficacy and safety of using DAAs to treatment the special populations with chronic hepatitis C / 中国热带医学

@#Abstract:Chronic hepatitis C (CHC) is a global health problem, which is prevalent all over the world. China is a low epidemic area. Hepatitis C virus (HCV) is mainly transmitted through blood, and nowadays, intravenous drug addicts are the key population for the prevention and treatment of hepatitis C. HCV has multiple genotypes and gene subtypes, and the distribution of these genotypes and gene subtypes varies significantly among the regions of the world. Nowadays, the treatment of hepatitis C has entered the era of direct-acting antiviral agents, which have high efficacy and safety in the general population. However, when special populations use direct-acting antiviral agents to treatment hepatitis C, we don't know how its efficacy and safety will be. The special populations include children, adolescents, drug users, HCV/HBV co-infected patients, HCV/HIV co-infected patients, and patients who have comorbidity of HCV and chronic kidney disease. This review will discuss the efficacy and safety of using direct-acting antiviral agents to treat hepatitis C in these special populations.

HCV evolution and positive selection sites of HCV NS5B region among intravenous drug users in Guangdong / 中国输血杂志

【Objective】 To learn the situation of the evolution process of HCV virus population and the selection pressure of HCV NS5B in intravenous drug users (IDUs) in Guangdong. 【Methods】 141 blood samples from hepatitis C virus (HCV) RNA-positive blood donors and 58 from HCV patients in Guangdong were randomly collected for HCV NS5B sequence amplification, combined with HCV NS5B sequences from blood donors and IDUs obtained by sequencing previously(between 2009 and 2011). Homology analysis was performed by Molecular Evolutionary Genetics Analysis (MEGA) software, evolutionary analysis were performed by Bayesian Evolutionary Analysis Sampling Trees (BEAST) software package. Selection pressure analysis was performed on sequences isolated from IDUs by Datamonkey online software package with Mixed Effects Model Evolution (MEME) method, and the population expansion of species were analyzed using Tajima and Fu neutrality test by Arlequin software. 【Results】 The comparison results of internal homology among different subtypes of IDUs in this group were as follows : HCV-3b had the highest homology (97%), followed by HCV-3a (96%), HCV-6a (95%) and HCV-1b (94%); HCV evolution rate analysis showed that HCV-1b had the fastest evolution rate [2.17E-03 substitutions/site/year (y/y/y)], followed by HCV-3b (2.12E-0 y/y/y), HCV-3a (1.58E-03 y/y/y) and HCV-6a (1.28E-03 y/y/y). The analysis on effective population of HCV: 1980~1990 was rapid growth period for HCV-6a, 1990~1995 period for HCV-1b, and 2000~2007 period for HCV-3a. HCV population genetic characteristics was as follows: HCV-1b, 3a, 3b and 6a experienced population expansion, among which 3a and 3b were the most obvious. As to the analysis of HCV selection pressure, two positive selection sites (235 and 243)were found in the 339 nucleotide fragment of the NS5B sequence in injecting drug users, but mutation only occurred at position 316 [mutation rate 1.24% (14/1 130)] among 5 direct antiviral drug (DAA) sites in this gene. 【Conclusion】 The evolution of HCV-3b in Guangdong has showed an obvious trend of population expansion, with a high proportion and homology especially in the local IDUs. HCV-3b should be the focus of HCV prevention and control in this region. Given that the positively selected sites of the HCV NS5B gene region of IDUs in Guangdong are non-DAA binding sites, DAA is expected to demonstrate a good effect on these patients.

Long-term prognosis of patients with hepatitis C virus-related hepatocellular carcinoma receiving direct-acting antiviral: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo systematically evaluate the difference in recurrence-free survival rate, hepatocellular carcinoma (HCC) recurrence rate, all-cause mortality rate, and liver-related mortality rate between hepatitis C-related HCC patients receiving oral direct-acting antiviral (DAA) and those receiving non-DAA (NDAA) treatment regimen. MethodsCNKI, Wanfang Data, VIP, CBM, PubMed, Embase, and Cochrane Library were searched for Cohort studies of DAA in the treatment of hepatitis C-related HCC patients published before December 2020, and quality assessment and meta-analysis were performed. ResultsA total of 10 cohort studies were included in this study, with 3108 patients in total. The meta-analysis showed that compared with NDAA regimen, DAA treatment significantly increased recurrence-free survival rate (risk ratio ［RR］=1.38, 95% confidence interval ［CI］: 1.10-1.72, P=0.005) and significantly reduced HCC recurrence rate (RR=0.52, 95%CI: 0.42-0.63, P＜0.000 01), all-cause mortality rate (RR=0.42, 95%CI: 0.32-0.55, P＜0.000 01), and liver-related mortality rate (RR=0.37, 95%CI: 0.18-0.76, P=0.007) in hepatitis C-related HCC patients. ConclusionDAA treatment is beneficial and safe for hepatitis C-related HCC patients.

Treatment of chronic hepatitis C in patients with chronic kidney disease with Sofosbuvir-basead regimes

ABSTRACT Background: To analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD). Methods: A retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %. Results: Thirty-five patients were treated. The mean age was 52.1 ± 10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8 ± 28.6 and 63.7 ± 28.3 ml/min pre- and post-treatment respectively (p > 0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function. Conclusion: Sofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.

Clinical outcomes of patients with chronic hepatitis C after generic direct-acting antiviral treatments in Vietnam: A retrospective analysis

Objective: To evaluate the outcomes of generic direct-acting antiviral treatments for chronic hepatitis C in Vietnam. Methods: The medical records of 522 patients (median 45 years; Female, 25.3%) with chronic hepatitis C treated at a tertiary hospital in northern Vietnam in 2016 were retrospectively reviewed. Results: Female patients were significantly older than male patients (median 52, IQR 41-59 vs. 43 years, IQR: 39-55; P<0.001). Among 522 patients, 49.4% were infected with hepatitis C virus (HCV) genotype 6, followed by 1a (19.0%), 1b (13.0%), and 3 (5.9%). Coinfection with hepatitis B virus or human immunodeficiency virus was noted in 5.8% and 3.1% of patients, respectively. Patients were treated with ledipasvir/sofosbuvir with or without ribavirin (70.9%), sofosbuvir/pegylated-interferon + ribavirin (13.2%), daclatasvir/ sofosbuvir with or without ribavirin (12.5%), or sofosbuvir/ribavirin (3.4%), and 96.4% (n=503) completed the direct-acting antiviral treatment. No patient discontinued treatment due to adverse event(s). A sustained virologic response 12 weeks after the end of the treatment (SVR12) was evaluated in 62.6% of patients. Overall sustained virologic response 12 weeks after the end of the treatment was 98.7% regardless of HCV genotypes or direct-acting antiviral regimens. The severity of liver stiffness was significantly decreased from 10.2 to 6.3 kilopascals measured by transient elastography by the treatment (P<0.001). Among patients who completed the directacting antiviral treatment, 17.7% returned for further follow-ups after SVR12. Conclusions: In Vietnam, the current generic direct-acting antiviral treatment for chronic hepatitis C was effective regardless of HCV genotypes and direct-acting antiviral regimens with the attenuation of liver stiffness. It is feasible to implement direct-acting antiviral treatment to cure chronic hepatitis C patients at any liver fibrosis stages in Vietnam.

Systematic Review of the Economics of the Second-generation Direct-acting Antiviral Agents in the Treatment of Hepatitis C / 中国药房

OBJECTIVE：To systematically evaluate the pharmacoeconomic research of the second-generation direct-acting antiviral agents （DAAs）in the treatment of hepatitis C ，and to provide methodological suggestions for economic research ，and to provide decision-making reference for the adjustment of medical insurance catalogues and market access. METHODS ：Retrieved from PubMed ，EMbase，the Cochrane library ，CNKI，Wanfang database and VIP ，the pharmacoeconomic researches of the second-generation DAAs for hepatitis C were collected during Jan. 2015-Jan. 2020. The quality of included studies were evaluated with the checklist about Consolidated Health Economics Evaluation Reporting Standards （CHEERS），and the data were extracted and analyzed quantitatively. RESULTS ：A total of 14 studies were included ，and the standard coincidence rate ranged from 79.2％ to 95.8％；the overall quality was relatively high. Thirteen （92.9％）studies had compared the economics of different treatment schemes from the perspective of the payer by using the Markov model and the lifetime study time limit. Compared with the second-generation DAAs treatment schemes based on sofosbuvir ，all the research results showed that Ombitasvir combined with Dasabuvir（3D），EBR/GZR and GLE/PIB were more economical in the target countries ；single factor sensitivity analysis showed that the research results were more sensitive to the three parameters of drug price ，drug SVR rate and health status utility value. CONCLUSIONS：Among the second-generation DAAs for hepatitis C ，the three regimens of 3D，EBR/GZR and GLE/PIB are more economical. It is recommended that future research on the economics of medicines for hepatitis C adopted dynamic model and the research perspective of the whole society to carry out direct high-quality economic research on a variety of DAAs ；at the same time，considered the effects of drug price ，drug SVR rate and health status utility value on the robustness of basic analysis results in sensitivity analysis in order to increase the credibility of the research results.

Clinical outcomes of patients with chronic hepatitis C after generic direct-acting antiviral treatments in Vietnam: A retrospective analysis

Objective: To evaluate the outcomes of generic direct-acting antiviral treatments for chronic hepatitis C in Vietnam. Methods: The medical records of 522 patients (median 45 years; Female, 25.3%) with chronic hepatitis C treated at a tertiary hospital in northern Vietnam in 2016 were retrospectively reviewed. Results: Female patients were significantly older than male patients (median 52, IQR 41-59 vs. 43 years, IQR: 39-55; P<0.001). Among 522 patients, 49.4% were infected with hepatitis C virus (HCV) genotype 6, followed by 1a (19.0%), 1b (13.0%), and 3 (5.9%). Coinfection with hepatitis B virus or human immunodeficiency virus was noted in 5.8% and 3.1% of patients, respectively. Patients were treated with ledipasvir/sofosbuvir with or without ribavirin (70.9%), sofosbuvir/pegylated-interferon + ribavirin (13.2%), daclatasvir/ sofosbuvir with or without ribavirin (12.5%), or sofosbuvir/ribavirin (3.4%), and 96.4% (n=503) completed the direct-acting antiviral treatment. No patient discontinued treatment due to adverse event(s). A sustained virologic response 12 weeks after the end of the treatment (SVR12) was evaluated in 62.6% of patients. Overall sustained virologic response 12 weeks after the end of the treatment was 98.7% regardless of HCV genotypes or direct-acting antiviral regimens. The severity of liver stiffness was significantly decreased from 10.2 to 6.3 kilopascals measured by transient elastography by the treatment (P<0.001). Among patients who completed the directacting antiviral treatment, 17.7% returned for further follow-ups after SVR12. Conclusions: In Vietnam, the current generic direct-acting antiviral treatment for chronic hepatitis C was effective regardless of HCV genotypes and direct-acting antiviral regimens with the attenuation of liver stiffness. It is feasible to implement direct-acting antiviral treatment to cure chronic hepatitis C patients at any liver fibrosis stages in Vietnam.

An eye on hepatitis C: a review / O olho na hepatite C: uma revisão

ABSTRACT This review aims to caution ophthalmologists about the ocular consequences leading to the diagnosis of hepatitis C virus infection. In addition, in this context, the effects of old and new drugs are discussed in the ophthalmological setting. The importance of early diagnosis and the curative treatment of the disease has been reported in the national and international literature, demonstrating that its progression has important implications for daily clinical and surgical ophthalmological practice. Despite the scarcity of studies on new direct-acting antiviral drugs, fewer side effects of these drugs have been shown when compared with conventional interferon treatment with or without ribavirin. The ophthalmologist's risk of becoming infected, as demonstrated by the presence of the virus in ocular structures, and the possibility of contamination, is also discussed.

RESUMO Esta revisão objetiva alertar os oftalmologistas sobre as consequências oculares que levam ao diagnóstico da infecção pelo vírus da Hepatite C. Além disso, neste contexto, os efeitos de drogas antigas e novas são discutidos no cenário oftalmológico. A importância do diagnóstico precoce e do tratamento curativo da doença tem sido relatada na literatura nacional e internacional, demonstrando que sua progressão tem implicações importantes para a prática oftalmológica diária. Apesar da escassez de estudos sobre novos medicamentos antivirais de ação direta, foram demonstrados menos efeitos colaterais desses medicamentos quando comparados ao tratamento convencional com interferon, com ou sem ribavirina associado ou não à rivabirina. O risco do oftalmologista de se infectar, como demonstrado pela presença do vírus nas estruturas oculares, e a possibilidade de contaminação, também é discutido.

Tratamiento de infección crónica por virus de hepatitis C en niños, ¿perspectiva hacia la curación o lejos de la meta? / Treatment of chronic hepatitis C virus infection in children, prospect towards cure or far from the goal?

Resumen La infección por el virus de hepatitis C es un problema global de salud pública; en México aproximadamente 2 % de la población se encuentra infectada. En niños, los datos de prevalencia son variables según la edad, pero se estima que 0.1 a 2 % de los niños presenta infección crónica por virus de hepatitis C, cuya principal vía de transmisión es la perinatal. Actualmente existen antivirales de acción directa aprobados en adultos con una tasa de respuesta viral sostenida superior a 95 %; sin embargo, en niños aún son pocos los estudios que confirman su seguridad y efectividad. Aunque todavía estamos lejos de la meta, avanzamos rápidamente hacia un tratamiento óptimo de curación también para pacientes pediátricos.

Abstract Infection with hepatitis C virus is a global health problem; in Mexico, approximately 2% of the population is infected. In children, data on prevalence are variable according to the age group, but 0.1-2% of children are estimated to have chronic infection with hepatitis C virus, the main way of transmission of which is perinatal. Currently, there are direct-acting antiviral agents approved in adults that offer a sustained viral response rate higher than 95%; however, in children there are still only few studies confirming their safety and effectiveness. Although we are still far from the goal, we are rapidly advancing towards an optimal curative treatment also for pediatric patients.

Real-world study of paritaprevir/ritonavir-ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China / 中华肝脏病杂志

Objective@#To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients.@*Methods@#A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data.@*Results@#80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment.@*Conclusion@#In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.

Effects of direct-acting antiviral agents on the frequency of myeloid-derived suppressor cells in patients with chronic hepatitis C / 中华传染病杂志

Objective@#To investigate the effects of direct-acting antiviral agents (DAA) therapy on the frequency of myeloid-derived suppressor cells (MDSC) and their subset of monocytic myeloid-derived suppressor cells (M-MDSC) in chronic hepatitis C (CHC) patients.@*Methods@#A total of 32 treatment-naive CHC patients and 16 healthy controls were recruited at Third Affiliated Hospital of Sun Yat-Sen University from June 2016 to June 2017. The peripheral blood mononuclear cells (PBMC) were separated from the peripheral blood of patients with CHC before DAA therapy, at four weeks after DAA therapy, at 12 weeks after DAA therapy and 12 weeks after the end of DAA therapy. The frequencies of MDSC and M-MDSC were detected by the flow cytometer. The t test, U test and chi-square test was employed to analyze the data.@*Results@#All the 32 treatment-naive patients achieved the rapid virological response and no virological breakthrough was observed. Before DAA therapy, the frequency of MDSC in CHC patients was 2.18%, which was higher than healthy individuals (0.60%; Z=-4.593, P<0.01), and positively correlated with the plasma levels of hepatitis C virus (HCV) RNA (r=0.688, P<0.01) and aspartate aminotransferase (r=0.735, P<0.01). After four weeks of DAA therapy, the frequency of MDSC decreased significantly to 1.07%, with no statistical significance compared to the controls (Z=-1.221, P>0.05). However, at 12 weeks after DAA therapy, the MDSC frequency increased, with statically significance compared to the controls (1.64% vs 0.60%, Z=-3.117, P=0.002). At 12 weeks after the end of DAA therapy, the MDSC frequency had decreased to 1.29% again, with no statistical significance compared to the controls (Z=-1.387, P=0.664). The changes of M-MDSC frequency were slightly different. Before DAA therapy, the frequency of M-MDSC in CHC patients was higher compared to healthy controls (1.66% vs 0.81%, Z=-2.745, P<0.01). The frequencies of M-MDSC were 0.91%, 1.09% and 1.10% at four, 12 weeks after DAA and 12 weeks after the end of DAA therapy, respectively. The differences were not statistically significant compared to the controls (Z=-0.589, -1.028 and -0.486, respectively, all P>0.05).@*Conclusion@#Immune status of the peripheral MDSC and M-MDSC can return to normal after DAA therapy in CHC patients.

Effects of direct-acting antiviral agents on the frequency of myeloid-derived suppressor cells in patients with chronic hepatitis C / 中华传染病杂志

Objective To investigate the effects of direct-acting antiviral agents (DAA) therapy on the frequency of myeloid-derived suppressor cells (MDSC) and their subset of monocytic myeloid-derived suppressor cells (M-MDSC) in chronic hepatitis C (CHC) patients.Methods A total of 32 treatment-naive CHC patients and 16 healthy controls were recruited at Third Affiliated Hospital of Sun Yat-Sen University from June 2016 to June 2017.The peripheral blood mononuclear cells ( PBMC) were separated from the peripheral blood of patients with CHC before DAA therapy , at four weeks after DAA therapy , at 12 weeks after DAA therapy and 12 weeks after the end of DAA therapy.The frequencies of MDSC and M-MDSC were detected by the flow cytometer.The t test, U test and chi-square test was employed to analyze the data.Results All the 32 treatment-naive patients achieved the rapid virological response and no virological breakthrough was observed . Before DAA therapy, the frequency of MDSC in CHC patients was 2.18%, which was higher than healthy individuals (0.60%; Z＝-4.593, P＜0.01), and positively correlated with the plasma levels of hepatitis C virus (HCV) RNA (r＝0.688, P＜0.01) and aspartate aminotransferase (r＝0.735, P＜0.01).After four weeks of DAA therapy, the frequency of MDSC decreased significantly to 1.07%, with no statistical significance compared to the controls ( Z＝-1.221, P＞0.05).However, at 12 weeks after DAA therapy , the MDSC frequency increased , with statically significance compared to the controls (1.64%vs 0.60%, Z＝-3.117, P＝0.002).At 12 weeks after the end of DAA therapy , the MDSC frequency had decreased to 1.29%again, with no statistical significance compared to the controls ( Z ＝-1.387, P ＝0.664).The changes of M-MDSC frequency were slightly different.Before DAA therapy, the frequency of M-MDSC in CHC patients was higher compared to healthy controls (1.66%vs 0.81%, Z＝-2.745, P＜0.01).The frequencies of M-MDSC were 0.91%, 1.09% and 1.10% at four, 12 weeks after DAA and 12 weeks after the end of DAA therapy , respectively.The differences were not statistically significant compared to the controls (Z＝-0.589,-1.028 and -0.486, respectively, all P＞0.05).Conclusion Immune status of the peripheral MDSC and M-MDSC can return to normal after DAA therapy in CHC patients.

A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.@*Methods@#Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.@*Results@#132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.@*Conclusion@#Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Dual herpes virus reactivation complicated with encephalitis caused by direct-acting antiviral agents

@#Direct-acting antiviral agents (DAAs) have been the mainstream treatment of hepatitis C because of tolerability and efficacy. A 67-year-old man presented with acute drowsiness preceded by headache after starting DAAs (sofosbuvir and velpatasvir) for treatment of hepatitis C. Herpes zoster and herpes simplex stomatitis were noted. Later, HSV-1 encephalitis was diagnosed based on positive HSV1-PCR of CSF, while other tests were negative including HSV2-PCR, syphilis, culture of bacteria, tuberculosis and fungus. Further study showed the presence of concomitant Sjögren syndrome. The patient recovered well with the combination of intravenous acyclovir and steroid. Immune reconstitution inflammatory response (IRIS) may be the most important mechanism of this patient’s severe illness. In conclusion, severe CNS infection instead of just peripheral nervous system involvement may occur due to herpes virus reactivation caused by DAAs. Screening of autoimmune markers may be considered before DAA therapy

Efficacy of precision therapy with direct-acting antiviral drugs for patients with chronic HCV genotype 1b infection / 中华临床感染病杂志

Objective To evaluate the efficacy of precision therapy with direct-acting antiviral drugs (DAAs) for patients with chronic HCV gene type 1b infection.Methods One hundred and thirteen patients with chronic HCV genotype 1b infection admitted in the Department of Infectious Diseases of First Hospital of Shanxi Medical University from January 2018 to July 2019 were enrolled,including 89 patients with chronic hepatitis and 24 patients with cirrhosis.Different DAAs therapeutic schedule were taken based on liver function, kidney function, complication and treatment costs.Seventy-two patients were treated with pan-genotype drugs, including 43 patients treated with Sofosbuvir and Velpatasvir (SOF+VEL), 13 treated with Sofosbuvir and Ribavirin ( SOF +RBV), and 16 treated with Sofosbuvir and Daclatasvir ( SOF +DCV).Forty one patients were treated with specific genotype DAAs , including 15 treated with Ombitasvir and Dasabuvir (OBV+DSV), and 26 treated with Elbasvir and Grazoprevir tablets (EBR+GZR).Pair t test and Chi-square test were used to compare virological response rate , the liver function and the adverse reactions were observed.Results The super-rapid virological response (SRVR) rate with DAAs treatment at 1 week was 88.5%(100／113),and the rapid virological response ( RVR) at 4 weeks of treatment was 98.2%(111／113).There was no significant differences in SRVR and RVR among the patients treated with five treatment regimens (χ2 ＝5.95 and 1.04,P＞0.05), all the patients obtained complete early virological response (CEVR) at 12 weeks and sustained virological response ( SVR12) at 12 weeks after treatment. Besides, there were no significant differences in SRVR and RVR between pan-genotype and gene-specific drugs (χ2 ＝0.03 and 0.17, P＞0.05),both CEVR and SVR12 reached 100% in all patients.The liver transaminase levels were improved in patients undergoing pan-genotype or gene-specific drugs treatment. Mild adverse reactions were observed in 5 cases, hemolysis occurred in 1 patient and it was cured after replacement of drugs.Conclusion Both pan-genotype and specific genotypes of DAAs can achieve high virological response rates.Genotypic testing should be performed before antiviral therapy , in order to accurately select treatment options and to save costs.

Characteristics of chronic hepatitis C in the elderly and the progress of antiviral therapy / 中华临床感染病杂志

Elderly patients have become a special concern in the management of hepatitis C .Their HCV exposure time is long and the risk of liver disease and extrahepatic complications is high .With the advent of direct antiviral drugs (DAA), the treatment of chronic hepatitis C has been significantly improved , and the cure rate of virology can be more than 90% in the elderly patients , with a high safety.However, elderly patients often have more underlying diseases and the drug use will be more complicated , resulting in drug interaction ( DDI) and increasing the challenge of treatment management.This article reviews the requirements for comprehensive evaluation of elderly patients before DAA treatment , including liver and kidney function, combined drug use and potential DDI.The monitoring of adverse events and DDI , and the countermeasures are also discussed in the article.

Recent update of the 2017 Korean Association for the Study of the Liver (KASL) treatment guidelines of chronic hepatitis C: Comparison of guidelines from other continents, 2017 AASLD/IDSA and 2016 EASL

The paradigm for the treatment of chronic hepatitis C (CHC) has been changed due to the development of direct acting antivirals (DAAs) of hepatitis C virus (HCV). The high sustained virologic response rate and ease of administration makes the DAAs approach ideal to contribute to the complete eradication of HCV. Currently, treatment options for individual patients vary depending on the genotype or subtype of HCV, presence or absence of liver cirrhosis, previous experience of antiviral treatment or resistance associated substitutions. Because of drug avalilability, cost-effectiveness, preference, compliance and greater possibility of desirable effects and presumed patient-important outcomes may vary between countries, treatment options for individual patients are different. The review focuses on the comparing the current treatment options for CHC in other continents with the 2017 Korea Association for the Study of the Liver guidelines.