Efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in treatment of patients with genotype 3B HCV/HIV infection / 临床肝胆病杂志

ObjectiveTo investigate the efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in Chinese patients with genotype 3B HCV/HIV infection. MethodsA total of 299 patients with genotype 3B HCV/HIV infection who attended The Third People’s Hospital of Kunming from January 2017 to December 2020 were enrolled and treated with sofosbuvir/velpatasvir alone or in combination with ribavirin for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment （SVR12） and adverse reactions. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the Agresti-Coull method was used to evaluate the 95% confidence interval （CI） of SVR12； univariate and multivariate non-conditional logistic regression analyses were used to investigate the influencing factors for SVR. ResultsThe 299 patients with genotype 3B HCV/HIV infection had a mean age of 43.92±6.84 years， among whom the male patients accounted for 77.3% （231/299）， the patients with liver cirrhosis accounted for 36.5% （109/299）， the patients with a history of antiviral therapy accounted for 13.4% （40/299）， and the patients receiving sofosbuvir/velpatasvir combined with ribavirin accounted for 27.8% （83/299）. The overall SVR was 87.0% （260/299） for all patients， and there was no significant difference in SVR12 between the patients receiving sofosbuvir/velpatasvir alone and those receiving sofosbuvir/velpatasvir combined with ribavirin （87.5% vs 85.5%， χ2=0.203， P=0.653）. There was a significant difference in SVR12 between the patients without liver cirrhosis and those with liver cirrhosis （90.0% vs 81.7%， χ2=4.256， P=0.039）， and the patients receiving antiviral therapy for the first time had a significantly higher SVR12 than the treatment-experienced patients （93.4% vs 45.0%， χ2=71.670， P<0.001）. The univariate and multivariate logistic regression analyses showed that platelet count （odds ratio ［OR］=0.957， 95%CI： 0.931 — 0.984， P=0.002）， liver stiffness measurement （OR=1.446， 95%CI： 1.147 — 1.822， P=0.002）， and experience in treatment （OR=13.807， 95%CI： 2.970 — 64.174， P=0.001） were independent influencing factors for SVR in patients with genotype 3B HCV/HIV infection. There were 41 cases of serious adverse events， all of which occurred within 2 weeks after antiviral therapy， and 28 cases were resolved without drug withdrawal or active treatment， while 13 cases were not resolved after active treatment and were resolved after the antiviral drugs were stopped for 2‍ ‍—‍ ‍5 days， with no similar reactions observed when the drugs were used again after remission. ConclusionSofosbuvir/velpatasvir alone or in combination with ribavirin has relatively good efficacy and safety in patients with genotype 3B HCV/HIV infection.

Advances in laboratory testing methods and strategies for hepatitis C virus infection / 临床肝胆病杂志

Laboratory testing for hepatitis C virus （HCV） infection provides an important basis for the identification and diagnosis of patients with HCV infection. With the continuous development of HCV testing in recent years， the performance of reagents has been significantly improved， and new testing service strategies have emerged and gradually been applied in clinical practice. This article summarizes the laboratory testing methods and strategies for HCV infection in China and globally， as well as the testing methods for HCV infection， and analyzes the influence of new methods and strategies on the prevention and control of HCV infection in China. Timely and accurate laboratory testing methods and effective and feasible testing strategies may help to realize the early identification， early diagnosis， and early treatment of HCV infection and ultimately achieve the strategic goal of eliminating viral hepatitis as a major public health threat by 2030.

Hepatitis C virus infection and organ transplantation / 临床肝胆病杂志

In recent years， rapid progress has been made in strategies for the prevention and treatment of hepatitis C virus （HCV） in organ transplant candidates and recipients， and although HCV infections no longer threaten transplantation outcomes in liver or non-hepatic solid organ transplantation， they remain a focus of research. Since hepatitis C is still a leading cause of death worldwide due to decompensated cirrhosis， liver failure， and hepatocellular carcinoma， appropriate organ transplantation is needed to improve survival rate and quality of life. With the increase in HCV-positive solid organ donors in recent years and the fact that the demand for organs still greatly exceeds organ supply， as well as the development of direct-acting antiviral agents， transplantation of HCV-viraemic organs into HCV-naïve recipients will significantly increase transplantation rates and reduce waitlist mortality. The efficacy of current HCV therapies has created an important opportunity to improve the survival rate of patients with end-organ failure by enhancing access to organ transplantation and reducing waitlist mortality.

Micro-elimination of hepatitis C virus infection in the hemodialysis population / 临床肝胆病杂志

The hemodialysis population is increasing year by year in China. Due to the specific nature of hemodialysis treatment， the prevalence and incidence rates of hepatitis C virus （HCV） infection in hemodialysis patients are much higher than the general population. In order to achieve the WHO’s initiative to eliminate HCV by 2030 and realize the micro-elimination of HCV in the hemodialysis population， standard infection control and hand hygiene procedures should be implemented to cut off the route of iatrogenic infection， especially to prevent the outbreak of HCV infection in hemodialysis centers. Screening for HCV infection should be conducted for patients newly admitted to the hemodialysis center or transferred to another hemodialysis center， and regular screening should be conducted for patients receiving maintenance hemodialysis to identify new HCV infections in the early stage. It is also necessary to collaborate with specialists and provide direct-acting antiviral therapy for hemodialysis patients with HCV infection.

Orbital mucosa-associated lymphoid tissue (MALT) lymphoma as the initial presentation in patients with hepatitis C virus infection

ABSTRACT Hepatitis C virus infection may be implicated in 12.7% of ocular adnexal marginal zone lymphomas. We present the first case of an orbital-systemic mucosa-associated lymphoid tissue lymphoma that responded to hepatitis C virus medical treatment. A 62-year-old male with a right-sided orbital mass was diagnosed with stage IIA orbital marginal zone lymphoma in addition to hepatitis C virus infection based on clinical, imaging, laboratory, and histological examinations. The systemic and orbital responses were achieved 1 year after undergoing hepatitis C virus treatment with glecaprevir/pibrentasvir. The association between the hepatitis C virus infection and orbital-systemic mucosa-associated lymphoid tissue lymphoma is relevant. Accordingly, patients with orbital mucosa-associated lymphoid tissue lymphoma should be assessed for hepatitis C virus seroreactivity for therapeutic and prognostic purposes.

Brazilian registry for the elimination of hepatitis C in dialysis units: a call to action for Nephrology / Registro brasileiro para eliminação da hepatite C nas unidades de diálise: um chamado para a Nefrologia

Abstract Infection by the hepatitis C virus is more prevalent in patients on dialysis than in the general population in Brazil, and has been associated with worse outcomes. Current therapy for hepatitis C is highly effective, safe, and widely available in Brazil, with coverage provided to dialysis patients with chronic kidney disease, which makes the elimination of hepatitis C a viable target. The Brazilian Society of Nephrology, the Brazilian Society of Hepatology, and the Brazilian Liver Institute developed the "Brazilian Registry for the Elimination of Hepatitis C in Dialysis Units". This project aims to identify, treat, and monitor the response to treatment of patients on chronic dialysis infected with the hepatitis C virus in Brazil. This article presents the issue and invites Brazilian nephrologists to rally around the achievement of a significant goal.

Resumo A infecção pelo vírus da hepatite C é mais prevalente em pacientes em diálise do que na população geral no Brasil e implica um pior prognóstico. O tratamento atual para hepatite C é altamente eficaz, seguro e disponível no país, inclusive para a população de pacientes crônicos em diálise, o que torna a eliminação do vírus da hepatite C uma meta viável. A Sociedade Brasileira de Nefrologia, a Sociedade Brasileira de Hepatologia e o Instituto Brasileiro do Fígado desenvolveram o "Registro Brasileiro para Eliminação da Hepatite C nas Unidades de Diálise". O projeto visa identificar pacientes em diálise crônica com vírus da hepatite C no Brasil, além de tratar e monitorar a resposta virológica após o tratamento. Este breve artigo apresenta o problema e convida os nefrologistas brasileiros a unirem forças nesse objetivo comum.

Efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide combined with sofosbuvir/velpatasvir in treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and its influence on blood lipid levels / 临床肝胆病杂志

Objective To investigate the efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/c/F/TAF) combined with sofosbuvir/velpatasvir (SOF/VEL) in the treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and the changes in blood lipid levels. Methods This prospective cohort study was conducted among 10 previously untreated chronic hepatitis C patients with HIV/HCV co-infection who attended Department of Infectious Diseases in Tangdu Hospital from July 2019 to May 2021 and achieved continuous HIV suppression after antiretroviral treatment (ART). As for anti-HIV therapy, the ART regimen was switched to the E/c/F/TAF regimen for 32 weeks, and for anti-HCV therapy, the SOF/VEL regimen was started since week 4 after switching and lasted for 12 weeks. Related indices were monitored before and after switching to E/c/F/TAF for anti-HCV therapy and SOF/VEL for anti-HCV therapy, including body weight, body mass index, HCV genotype, alpha-fetoprotein, liver stiffness measurement, CD4 + T cell count, CD4 + T/CD8 + T ratio, hepatic and renal function parameters, blood lipids, HIV RNA, HCV RNA, SVR12, SVR24, and adverse reactions. The Mann-Whitney U test was used for comparison of continuous data between two groups, and a Spearman correlation analysis was performed. Results After 4 weeks of treatment with E/c/F/TAF, 10 patients (HCV genotypes 2a and 1b) had HIV RNA below the lower limit of detection (20 IU/ml) and a significant reduction in albumin ( Z =-2.801, P =0.003 7), with the other indices remaining stable, and the patients reported significant improvements in the adverse events of anti-HIV therapy with the former ART regimen. After 4 weeks of E/c/F/TAF combined with SOF/VEL, the patients had HCV RNA below the lower limit of detection (15 IU/ml), and both SVR12 and SVR24 reached 100%; after 12 weeks of anti-HCV therapy, there were significant reductions in alanine aminotransferase ( Z =-2.732, P =0.004 8) and aspartate aminotransferase ( Z =-2.501, P =0.010 7) and significant increases in total cholesterol (TC) ( Z =-2.797, P =0.003 9) and low-density lipoprotein cholesterol (LDL-C) ( Z =-2.343, P =0.018 5), with a significantly positive correlation between them ( r =0.87, P < 0.001), and all the other indices were normal. Conclusion For previously untreated chronic hepatitis C patients with HIV/HCV co-infection, switching to E/c/F/TAF combined with SOF/VEL has good efficacy, tolerability, and safety, and the combination of the two regimens can avoid drug interaction, achieve a high HCV cure rate, and maintain HIV suppression. Transient increases in TC and LDL-C are observed during combination treatment, which suggests dyslipidemia caused by HCV infection and the pharmacological action of this regimen.

Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone / 临床肝胆病杂志

Objective To investigate the difference in naturally occurring resistance-associated variants (RAVs) between the patients with HIV/HCV co-infection and those with HCV infection alone by detecting the drug resistance loci associated with HCV NS3/4A protease and NS5A inhibitors. Methods A total of 246 patients with HIV/HCV co-infection or HCV infection alone who were hospitalized or attended the outpatient service in Guangzhou Eighth People's Hospital, Guangzhou Medical University, from January 2016 to January 2020 were enrolled in this study. Serum samples were collected and next-generation sequencing (Illumina platform, PE250) was used for sequencing. The two groups of patients were compared in terms of RAVs associated with NS3/4A protease and NS5A inhibitors approved in China, and the drugs for analysis included asunaprevir/daclatasvir (ASV/DCV) and elbasvir/grazoprevir (EBR/GZR) for HCV genotype 1b and glecaprevir/pibrentasvir (GLE/PIB) for pan-genotypes. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 246 serum samples included in this study, 239 samples (97.2%) were successfully amplified by PCR and sequenced, with 102 samples from the patients with HIV/HCV co-infection and 137 from the patients with HCV infection alone. The analysis of RAVs associated with ASV/DCV and EBR/GZR showed that Y56F, Q80K/L, and S122N/R/T associated with ASV and GZR and L31M and Y93H associated with DCV and EBR were observed in patients with HIV/HCV (genotype 1b) co-infection or HCV (genotype 1b) infection alone; 2 patients with HIV/HCV co-infection had the RAVs of Y56F+Y93H associated with EBR/GZR, and 2 with HCV infection alone had the RAVs of Q80L+L31M and Y56F+Y93H, respectively, associated with EBR/GZR, with no significant difference in RAVs between the two groups (both P > 0.05). The analysis of RAVs associated with GLE/PIB for pan-genotypes showed that 3 patients with PIB-associated Y93H RAV were observed among the patients with HCV genotype 3a infection, among whom 2 had HIV/HCV co-infection and 1 had HCV infection alone ( P =0.590), and in addition, no RAVs associated with GLE/PIB were observed. Conclusion There is no significant difference in naturally occurring RAVs associated with HCV NS3/4A protease and NS5A inhibitors between the patients with HIV/HCV co-infection and those with HCV infection alone.

Selection dynamics of HCV genotype 3 resistance-associated substitutions under direct-acting antiviral therapy pressure

ABSTRACT The chronic hepatitis C (CHC) treatment is currently based on the use of direct-acting antivirals (DAAs), and patients infected with hepatitis C virus genotype 3 (GT3) have emerged as a more difficult-to-cure population. The NS5A inhibitor daclatasvir (DCV) and sofosbuvir (SOF), an NS5B viral polymerase inhibitor, are among the drugs that compose more effective and safer treatment regimens. The virus genetic variability is related to resistance-associated substitutions (RASs) that adversely impact DAAs effectiveness. The aims of this study were to analyze the association of NS5A and NS5B RASs and other clinical factors with DAAs regimens effectiveness in patients with GT3 CHC infection. This was a prospective cohort study performed in a Brazilian university hospital. Individuals older than 18 years with GT3 CHC treated with SOF + DCV ± ribavirin (RBV) or SOF + peginterferon (PEG) + RBV were included. Blood samples were collected at baseline and post-treatment. A total of 121 patients were included. Sustained virological response rates were 87.6% for the SOF + DCV ± RBV group and 80.0% for the SOF + PEG + RBV arm. Cirrhosis, prior treatment with interferon/PEG + RBV, and baseline NS5A RAS were associated with higher risk of treatment failure. The NS5A analysis suggested that A30K, Y93H, and RAS at site 62 were related to failure. Interestingly, a likely compensatory effect was shown between A30K and A62T. Emergence of Y93H was always associated with RAS at position 62. The RASs dynamics comprehension is an important tool to indicate more effective treatment for GT3 patients.

Hepatitis crónica por virus C: evaluación de los pacientes tratados con antivirales de acción directa en el sistema público de Chile / Evaluation of patients with virus C hepatitis treated with direct-acting antivirals in the Chilean public system

Background Direct-acting antivirals (DAA) allowed a radical change in the treatment of hepatitis C virus (HCV), achieving the elimination of the virus or sustained viral response (SVR) in > 95% of patients, with good tolerance and few adverse effects. Aim To characterize the treated population and evaluate the efficacy of DAA treatment in the Chilean public health system. Material and Methods: Retrospective analysis of data sheets of pa- tients with chronic HCV infection collected by the Ministry of Health of Chile between 2016 and May 2019. Results Two hundred and fifty-five patients with a mean age of 59 years (51% males) were collected. Genotype 1b was predominant, 72% patients had a diagnosis of cirrhosis at the beginning of treatment. Sofosbuvir-Velpatasvir was predominantly used in 56%. SVR was achieved in 92% of cases, only 4% persisted with detectable load at 24 weeks. A significant decrease in alanine aminotransferase values (88 and 31 U/L respectively, p < 0.01) and a significant increase in plasma albumin (3.7 and 3.9 mg/dl respectively, p = 0.02) were observed. The comparative analysis of MELD-Na before and after treatment did not show a signifi- cant variation (10.8 and 10.4 respectively, p = 0.34). Conclusions These patients treated with DAAs presented SVR rates comparable with national and international data.

Caracterización de pacientes con Hepatitis C en el servicio de hemodiálisis. Cienfuegos 2019 / Characterization of patients with hepatients with hepatitis c in the hemodialysis service.Cienfuegos 2019

RESUMEN Fundamento: La infección por el virus de la Hepatitis C ha sido reconocida como problema de salud a nivel mundial. Objetivo: Determinar las características de los pacientes con Hepatitis C que reciben tratamiento en el servicio de hemodiálisis del Centro Especializado Ambulatorio de Cienfuegos, en el periodo de enero a agosto del 2019. Metodología Se realizó un estudio observacional, descriptivo, longitudinal retrospectivo con los 54 pacientes en hemodiálisis portadores de Hepatitis C. Las variables utilizadas fueron: edad, sexo, lugar de procedencia, tipo de acceso vascular y tiempo en tratamiento. Se utilizó como fuente de información la base de datos del Centro Provincial de Higiene, Epidemiología y Microbiología en Cienfuegos. Resultados: El mayor porcentaje de personas con Hepatitis C se concentró entre los 50 a 54 años; siendo la edad promedio 53 años, sobresalió el sexo masculino para un 84.93%, y predominó el municipio de Cienfuegos como lugar de residencia. En relación al tipo de acceso vascular, la fístula arterio -venosa aportó el 98.14%, mientras el tiempo de tratamiento que prevaleció fue de más de 3 años para un 77.8%. Conclusiones La Hepatitis C en el servicio de hemodiálisis mostró un comportamiento similar a lo descrito en la literatura.

ABSTRACT Background Infection by the hepatitis c virus has been recognized as a health problem worldwide. Objective: To determine the characteristics of patients with hepatitis C receiving treatment in the Hemodialysis Service of the Cienfuegos Specialized Outpatient Center from January 2019 to August 2019. Methodology An observational, descriptive, longitudinal retrospective study was carried out with the 54 Hemodialysis patients with Hepatitis C. The variables used were: age, sex, place of origin, type of vascular access and time in treatment. The database of the Provincial Center for Hygiene, Epidemiology and Microbiology in Cienfuegos was used as a source of information. Results The highest percentage of people with hepatitis C was concentrated between 50 to 54 years old; The average age being 53 years, the male sex stood out for the 84.93%, with the municipality of Cienfuegos predominating as the place of residence. Regarding the type of vascular access, the arterio-venous fistula contributed the 98.14%, while the treatment time that prevailed was more than 3 years for the 77.8%. Conclusions: Hepatitis C in the hemodialysis service showed a similar behavior as described in the literature.

Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy / Remissão de doença hepática e renal a longo prazo induzida pelo HCV após terapia antiviral de ação direta

Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.

Advances in direct-acting antiviral therapy for liver transplant recipients with HCV-related hepatocellular carcinoma / 临床肝胆病杂志

The launch of direct-acting antiviral agents is a milestone in the treatment of hepatitis C, but further studies are needed to explore its specific timing and effectiveness in liver transplantation for HCV-related hepatocellular carcinoma (HCC). This article summarizes related guidelines, consensus statements, and recommendations in China and globally and the advantages of different treatment timing strategies. Furthermore, a retrospective analysis of related studies is performed to investigate the controversial topic of the impact of direct-acting antiviral agents on the recurrence rate of HCV-related HCC after liver transplantation, and it is pointed that direct-acting antiviral agents can reduce the risk of HCC recurrence in liver transplant recipients with HCV-related HCC. The selection of treatment timing should consider various factors such as liver function, waiting time for donors, and utilization of HCV-positive organs.

Advances in direct-acting antiviral therapy for liver transplant recipients with HCV-related hepatocellular carcinoma / 临床肝胆病杂志

The launch of direct-acting antiviral agents is a milestone in the treatment of hepatitis C, but further studies are needed to explore its specific timing and effectiveness in liver transplantation for HCV-related hepatocellular carcinoma (HCC). This article summarizes related guidelines, consensus statements, and recommendations in China and globally and the advantages of different treatment timing strategies. Furthermore, a retrospective analysis of related studies is performed to investigate the controversial topic of the impact of direct-acting antiviral agents on the recurrence rate of HCV-related HCC after liver transplantation, and it is pointed that direct-acting antiviral agents can reduce the risk of HCC recurrence in liver transplant recipients with HCV-related HCC. The selection of treatment timing should consider various factors such as liver function, waiting time for donors, and utilization of HCV-positive organs.

Hepatitis aguda por virus C: reporte de siete casos en centro de referencia en Chile

Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV / Associação entre polimorfismo do gene da interleucina-6 e regulação do ferro em pacientes em hemodiálise infectados pelo HCV

ABSTRACT Backgrounds: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. Method: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. Results: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. Conclusions: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

RESUMO Introdução: A hepcidina está associada à patogênese da anemia por insuficiência renal crônica, considerada um estado inflamatório crônico e também infecção por HCV. A IL-6 estimula a liberação de hepcidina a partir do fígado, suprime a captação intestinal de ferro e libera ferro das reservas internas. Método: Para detectar a associação entre o polimorfismo do gene IL-6 e os marcadores de anemia, 80 pacientes em hemodiálise (HD) [40 pacientes em HD, negativos para HCV; e 40 em HD, positivos para HCV] foram avaliados por exames químicos de rotina e hemograma completo, além da avaliação da hepcidina sérica, parâmetros do ferro [ferro sérico e ferritina sérica] e marcadores de hepatite C. O polimorfismo da IL-6 -174G/C foi determinado por MS-PCR, enquanto os polimorfismos de IL-6 -597G/A e -572 G/C foram detectados por PCR-SSP. Resultados: A hepcidina não esteve significativamente elevada em pacientes com HCV em comparação com pacientes em hemodiálise negativos para HCV. Uma diferença estatisticamente significativa foi detectada entre os pacientes em HD HCV negativos comparados aos positivos nas frequências de IL-6 -174 G/C e -597 G/A (P≤ 0,01 e P≤ 0,001, respectivamente). Por outro lado, foi relatada uma diferença não significativa entre pacientes em HD HCV negativos e positivos nas frequências de IL-6 -572 G/C. Conclusões: Nosso estudo indicou que os polimorfismos de IL-6 -174 G/C e -597 G/A podem desempenhar um papel na suscetibilidade ao HCV em pacientes em HD. Ainda necessitamos de estudos prospectivos adicionais em uma população maior para confirmar nossos achados.

Combined ns5a & ns5b nucleotide inhibitor therapy for patients with chronic hepatitis c with stage 5 chronic kidney disease on hemodialysis / Terapia inibidora de nucleotídeo NS5A& NS5B combinada para pacientes com hepatite C crônica com doença renal crônica em estágio 5, em hemodiálise

ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é a infecção viral hepática mais comum que afeta pacientes em hemodiálise de manutenção. O tratamento da infecção crônica por HCV no estágio 4 e 5 da doença renal crônica inclui uma combinação de elbasvir/grazoprevir e glecaprevir/pibrentasvir, que não estão disponíveis em muitos países. OBJETIVO: Portanto, realizamos este estudo para procurar a segurança e eficácia da terapia combinada de sofosbuvir nesta população de difícil tratamento. MÉTODOS: Realizamos um estudo de centro único, prospectivo e aberto, no qual pacientes com doença renal crônica em estágio 5 em hemodiálise de manutenção com infecção por HCV. Um total de 18 pacientes foi incluído. Sofosbuvir com daclatasvir ou ledipasvir foi usado de acordo com o genótipo por 12 semanas. O HCV RNA, genótipo, elastografia transitória foi considerado para cada paciente. O HCV RNA foi quantificado na 4ª semana, 12ª semana e 12 semanas após o tratamento para procurar uma resposta virológica sustentada. RESULTADOS: A infecção por genótipo 1 foi observada em 12 (66,7%) pacientes, seguido pelo genótipo 3 em 4 (22,3%), em um paciente do genótipo 2 e em outro, 5. O valor mediano do HCV RNA foi de 2.35.000 IU/mL. Na elastografia transitória, todos tinham rigidez hepática de <9.4 KPa. Todos os pacientes tinham RNA HCV <15 IU/mL na 4ª e 12ª semana de tratamento e 12 semanas após o tratamento. Não foi observada nenhuma alteração significativa na hemoglobina, eGFR e rigidez hepática. CONCLUSÃO: A dose completa sofosbuvir ou seja, 400 mg, em combinação com inibidores NS5A daclatasvir ou ledipasvir foi considerada segura e eficaz em pacientes com doença renal em estágio final, que estão em manutenção hemodiálise.

Full-length sequencing and baseline resistance-associated substitution of hepatitis C virus subtype 3b / 临床肝胆病杂志

ObjectiveTo investigate the application of next-generation sequencing (NGS) in determining the full-length sequence and baseline resistance-associated substitution (RAS) of hepatitis C virus (HCV) subtype 3b. MethodsNucleic acid was extracted from plasma of a HCV RNA-positive blood donor, and after sequence-independent amplification, a sequencing library was constructed and NGS was performed using Illumina Hiseq. Bioinformatics methods were used to analyze full-length HCV sequence, viral genotype, and baseline RAS to direct-acting antivirals (DAAs). ResultsA total of 8.4 Gb data with more than 56 million reads were obtained. The full-length HCV sequence was obtained by bioinformatics analysis, with an average sequencing depth of 488 007 and a genotype of 3b subtype. A total of 12 RASs were identified in HCV amino acid sequence, i.e., Y56H, Q80K, Q80R, and A156G located in NS3, M28G, Q/A30G, Q/A30K, L31F, L31M, and Y93H located in NS5A, and S282T and V321A located in NS5B, among which Q/A30K and L31M located in NS5A had high frequencies of 99.16% and 98.37%, respectively, while the other 10 RASs had low frequencies of ＜0.5%. ConclusionNGS can be used to determine the full-length sequence and genotype of HCV subtype 3b and identify baseline RASs, which has great significance in the epidemiological study of HCV subtype 3b and the development of DAA treatment regimens.

Drug resistance of direct-acting antivirals in genotype 2/3 hepatitis C virus / 临床肝胆病杂志

Since the development of direct-acting antivirals (DAAs) for hepatitis C virus(HCV), more than 95% of the patients with hepatitis C can be cured, but a very small proportion of patients still face treatment failure. There are many reasons for treatment failure, among which HCV genotype and resistance-associated substitutions (RASs) in virus genes show a certain impact. This article mainly introduces the RASs associated with the NS5B and NS5A gene fragments in genotype 2/3 HCV, summarizes the distribution of RASs, and compares the difference in the distribution of RASs between previously untreated chronic hepatitis C patients and patients with treatment failure.

Value of combined determination of hepatitis C virus genotype, AFP-L3, and P53 antibody in the diagnosis of hepatitis C virus-related hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the value of combined determination of hepatitis C virus (HCV) genotype, the alpha-fetoprotein variant AFP-L3, and P53 antibody in HCV-related hepatocellular carcinoma (HCV-HCC). MethodsA total of 84 patients with HCV-HCC who were diagnosed in our hospital from January 2016 to December 2019 were enrolled as HCV-HCC group, and 84 patients with benign liver diseases (hepatitis C and HCV liver cirrhosis) were enrolled as control group. The PCR-reverse dot blot hybridization technique was used to determine HCV genotype, ELISA was used to measure P53 antibody, and electrochemical luminescence was used to measure AFP-L3. The t-test and the Kruskal-Wallis H test were used for comparison between two groups; the chi-square test was used for comparison of categorical data between two groups. The logistic regression analysis and the receiver operating characteristic (ROC) curve were used to compare the value of each index in the diagnosis of HCV-HCC. ResultsCompared with the control group, the HCV-HCC group had a significantly higher proportion of patients with HCV 1b genotype or AFP-L3 and a significantly higher level of P53 antibody (χ2=5714, Z=-9.27, Z=-9.92, all P＜0.05). The logistic regression analysis showed that HCV genotype, AFP-L3, and P53 antibody had significant effects on HCV-HCC (all P＜0.05). The above indices were fitted to establish a model of Logit(Y)=-3.881+0031XAFP-L3(%)+0.043XP53+1218XHCV genotype, in which Y was the positive probability value of combined determination. In the screening of HCV-HCC, Y had a significantly larger area under the ROC curve than HCV genotype (0.945 vs 0.758, Z=6.17, P＜0001), AFP-L3 (0.945 vs 0.863, Z=3.97, P＜0.001), and P53 antibody (0.945 vs 0.887, Z=3.07, P=0.002). Y had higher AUC (0.945), sensitivity (90.90%), specificity (94.00%), positive predictive value (93.80%), negative predictive value (9116%), and diagnostic accuracy (92.44%) than each index alone. ConclusionHCV 1b genotype, AFP-L3, and P53 antibody level are associated with the risk of HCV-HCC, and the combined determination of the three indices has important clinical significance in the early diagnosis of HCV-HCC.