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.

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.

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.

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

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.

Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in Hepatitis C Monoinfection Compared to Hepatitis C/Human Immunodeficiency Virus Coinfection in a Community Care Setting

BACKGROUND/AIMS: Limited data exist comparing the safety and efficacy of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human immunodeficiency virus (HIV) coinfected patients in the real-world clinic practice setting. METHODS: All HCV monoinfected and HCV/HIV coinfected patients treated with DAAs between January 2014 and October 2017 in community clinic settings were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks (SVR12) after treatment, and adverse reactions were compared between the groups. RESULTS: A total of 327 patients were included in the study, of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a statistically significant difference observed in SVR12 when comparing HCV monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005). However, there were no significant factors identified as a predictor of a reduced response. The most common adverse effect was fatigue (27%). No significant drug interaction was observed between DAA and antiretroviral therapy. None of the patients discontinued the treatment due to adverse events. CONCLUSIONS: In a real-world setting, DAA regimens have lower SVR12 in HCV/HIV coinfection than in HCV monoinfection. Further studies involving a higher number of HCV/HIV coinfected patients are needed to identify real predictors of a reduced response.

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

Objective@#To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C.@*Methods@#Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded.@*Results@#108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin.@*Conclusion@#Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.

Consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C / 中华肝脏病杂志

Approved direct-acting antiviral agents (DAA ) in chronic hepatitis C were introduced. Metabolism and pharmacokinetics data of DAAs were analyzed. Comorbidity and concomitant medications of chronic hepatitis C (CHC) patients were extracted from Chinese Health Insurance database. Drug-drug interactions (DDIs) were calculated by integrated above data and confirmed by using Liverpool DDI website. Based on those data, experts propose consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C, including pre-treatment, on-treatment, and post-treatment.

Prevalence of pre-existing direct-acting antiviral agents resistance-associated variants in genotype 1 HCV/HIV co-infected patients / 上海交通大学学报（医学版）

Objective: To investigate the prevalence of pre-existing direct-acting antiviral agents (DAAs) resistance associated variants (RAVs) in genotype 1 hepatitis C virus (HCV)/ human immunodeficiency virus (HIV) co-infected patients. Methods: All NS3 and NS5B HCV sequences in genotype 1 HCV/HIV co-infected patients were retrieved from NCBI GenBank database. And sequences were aligned and analyzed using software MEGA 5.0. Results: In total, the overall prevalence of DAAs RAVs in NS3 region was high (26.06% and 38. 18%, respectively), no matter in genotype 1a or genotype 1b. In genotype 1a, the high prevalence of RAVs mainly presented in the position Q80 (8.45%). In genotype 1b, S122 RAV was most observed (36.36%). It is worth noting that, RAVs in NS5B region were rare observed (0.77%) in this study, especially as no RAV was detected in any sequence of genotype 1a patients. Conclusion: The prevalence of pre-existing RAVs is high in NS3 region but rare in NS5B region in HCV/HIV co-infected patients, suggesting that NS5B inhibitors based combination regions are a better choice for HCV/HIV co-infected patients.

Advances in combination therapy of ombitasvir and dasabuvir for chronic hepatitis C virus genotype 1 infection / 中华肝脏病杂志

Since 2014, the United States and Europe has approved all oral, interferon free- regimens that combine with direct-acting antiviral agents. Hence, the sustained virological response rate of patients with chronic HCV genotype 1 infection has improved over 90%, and the treatment modalities has introduced a new era. These drugs, ombitasvir and dasabuvir, received customary authorization of Food and Drug Administration in 2015 and are the first combined direct-acting antiviral agents for treating HCV genotype 1 infection. It has superior application prospects in China because of its high-sustained virological response rate and safety profile. This article reviews the pharmacokinetics, drug interactions, efficacy and safety of this therapeutic regimen.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. @*Methods@#An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. @*Results@#A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. @*Conclusion@#Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

Application of direct antiviral drugs in special patients with HCV infection / 中华肝脏病杂志

Patients with HCV infection can develop decompensated cirrhosis, hepatocellular carcinoma (HCC), even liver failure. As a result, efficient antiviral treatment is very essential to prevent HCV-related disease progression. Newly developed direct-acting antiviral agents (DAAs) have shown safety profile, favorable tolerability, and relatively short duration, which provide an opportunity to expand the number of patients who can be treated for HCV infection. There is a need for further clinical observation and summaries for DAAs in a real world. In the era of DAAs, special patients with HCV infection still get lots of attention from doctors. This review aims at the application of DAAs in patients with HCV infection, combined with chronic kidney diseases, hepatocellular carcinoma, HBV/HCV co-infection, HIV/HCV co-infection, post liver transplantation, pregnancy, children, lymphoma and retreatment.

Prevalence of pre-existing direct-acting antiviral agents resistance-associated variants in genotype 1 HCV/HIV co-infected patients / 上海交通大学学报（医学版）

Objective·To investigate the prevalence of pre-existing direct-acting antiviral agents (DAAs) resistance associated variants (RAVs) in genotype 1 hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients.Methods·All NS3 and NSSB HCV sequences in genotype 1 HCV/HIV co-infected patients were retrieved from NCBI GenBank database.And sequences were aligned and analyzed using software MEGA 5.0.Results·In total,the overall prevalence of DAAs RAVs in NS3 region was high (26.06％ and 38.18％,respectively),no matter in genotype 1a or genotype 1b.In genotype 1a,the high prevalence of RAVs mainly presented in the position Q80 (8.45％).In genotype lb,S122 RAV was most observed (36.36％).It is worth noting that,RAVs in NS5B region were rare observed (0.77％) in this study,especially as no RAV was detected in any sequence of genotype 1a patients.Conclusion·The prevalence of pre-existing RAVs is high in NS3 region but rare in NS5B region in HCV/HIV co-infected patients,suggesting that NS5B inhibitors based combination regions are a better choice for HCV/HIV co-infected patients.

Research progress on antiviral therapy in severe hepatic impairment patients and special population with HCV infection / 中华临床感染病杂志

The research and development of direct-acting antiviral agents (DAAs) for hepatitis C achieved significant results in the last decade .DAAs is highly effective in treatment of hepatitic C patients with convenience and safety , and the sustained virological response of DAAs is over 90％, which will greatly contribute to achieving the WHO's goal of eliminating hepatitis C by 2030.The European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD) and WHO all updated guidelines for diagnosis and treatment of hepatitis C in 2018, which will play a positive role for the management of hepatitis C globally .This article reviews the related guidelines and literature on prevention and treatment of hepatitis C , and summarizes the advantages of antiviral therapy for severe hepatic impairment patients and special population with HCV infection .

Clinical advances on danoprevir and triple therapy of danoprevir with Peg IFN and ribavirin regimen in treatment of chronic hepatitis C / 中华临床感染病杂志

So far, thirty-seven clinical trials of danoprevir in treatment of chronic hepatitis C (CHC)have been completed globally,in which more than 2 600 patients were involved.The clinical trials among Chinese patients with genotype 1 CHC showed that the sustained virologic response(SVR)rate reached to 97.0% after twelve-week treatment of danoprevir combined with PR regimen(Peg IFN and ribavirin), and the safety was good.

Direct acting antiviral agent for Chinese patients with chronic hepatitis C genotype 1b infection——a real world experience / 中华传染病杂志

Objective To evaluate the effectiveness and safety of direct-acting antiviral agents (DAA) treatment in Chinese chronic hepatitis C (CHC) patients with genotype (GT) 1b HCV infection in a real world setting .Methods The consecutive GT1b CHC Chinese patients treated with sofosbuvir (SOF) plus daclatasvir (DCV) (n＝62) or SOF plus ledipasvir (LDV) (n＝171) were enrolled from July 2014 to December 2016 at 302 Military Hospital of China .The treatment duration for all the patients was 12 weeks .All the clinical parameters were measured at baseline and then 4-weekly till 12 weeks after the end-of-treatment (EOT ).Baseline clinical characteristics ,treatment efficacy ,safety and tolerance were compared .Serum HCV RNA concentration was detected by means of COBAS TaqMan assay with a lower detection limit of 15 IU/mL ,and liver stiffness was measured using FibroScan?.Sustained virologic response (SVR) was defined as HCV RNA under the lower limit of quantification 12 weeks after EOT (SVR12).Students′t-test ,pearson χ2 test ,Spearman rank correlation analysis and Fisher exact test were used for comparison between groups when appropriate .Results Among 233 patients ,173 cases had baseline HCV RNA level ≥ 6 .0 lg IU/mL and 97 cases hade liver stiffness measurement (LSM )≥17.5 kPa.The baseline liver inflamation ,liver fibrosis ,and HCV RNA load of patients in the two groups were not significantly different (all P＞0 .05).The HCV RNA of all the 233 patients was undetectable at the end of 12-week treatment ,while 2 patients relapsed after 12 weeks of EOT with the overall SVR12 of 99.1% .HCV RNA decline was significantly faster in patients with lower LSM than those with higher LSM (ρ＝0 .233 ,P＝0 .001) ,and SVR12 was higher in those with lower LSM .In terms of other clinical characteristics of SOF+DCV and SOF+LVD groups ,alanine transaminase declined from (68 .0 ± 60 .1) and (70 .1 ± 56 .1) U/L to (21 .1 ± 10 .9) U/L and (15 .3 ± 9 .5) U/L ,respectively ,total bilirubin declined from (21 .3 ± 17 .3) and (18 .2 ± 14 .0) μmol/L to (13 .2 ± 6 .7) and (10 .2 ± 4 .6) μmol/L , respectively ,AFP declined from 19 .6 (10 .6 ,62 .3) and 15 .0 (12 .0 ,25 .0) μg/L to 6 .5(4 .5 ,18 .7) and 7 .8(5 .3 ,15 .4) μg/L ,respectively ,LSM declined from 17 .6 (8 .9 ,25 .4) and 15 .7 (7 .8 ,23 .9) kPa to 13.9(6 .5 ,21 .4) and 9 .1(5 .6 ,19 .9) kPa ,respectively ,serum album elevated form (37 .5 ± 5 .8) and (38 .7 ± 5 .5) g/L to (41 .3 ± 4 .7) and (42 .8 ± 5 .1) g/L ,respectively ,platelet elevated from (120.9 ± 78 . 2)×109/L and (136 .6 ± 65 .8 )× 109/L to (139 .5 ± 71.8 )× 109/L and (149 .7 ± 71.4 )× 109/L , respectively .Reports of adverse events were low in both groups .Conclusions Both SOF + DCV and SOF/LDV therapy are highly effective with ＞ 98% of SVR12 and reduce LSM value significantly with good safety for CHC GT1b Chinese patients .

2017 Korean Association for the Study of the Liver (KASL) Clinical Practice Guidelines of Chronic Hepatitis C: What's New? / 대한소화기학회지

With the advent of highly effective direct-acting antiviral agents (DAA), the treatment of hepatitis C virus infections continues to change. The Korean Association for the Study of the Liver updated guidelines for the management of hepatitis C were revised in 2015 in accordance with the introduction of new DAA into practice and a results of domestic and overseas research in late 2017. More effective and convenient DAAs are also recommended for each genotype depending on the presence of cirrhosis and treatment experience. DAA treatment in patients with chronic kidney disease is feasible. The treatment guidelines for DAA failure are also presented. The guidelines need to be revised constantly as new drugs are developed and the results of clinical research and experience accumulate.

Consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C / 中华肝脏病杂志

Approved direct-acting antiviral agents (DAA ) in chronic hepatitis C were introduced. Metabolism and pharmacokinetics data of DAAs were analyzed. Comorbidity and concomitant medications of chronic hepatitis C (CHC) patients were extracted from Chinese Health Insurance database. Drug-drug interactions (DDIs) were calculated by integrated above data and confirmed by using Liverpool DDI website. Based on those data, experts propose consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C, including pre-treatment, on-treatment, and post-treatment.