Impact of hepatitis C virus eradication with direct-acting antivirals on glycidic metabolism

ABSTRACT Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.

Improving Diagnosis of Hepatitis C Virus Infection Using Hepatitis C Core Antigen Testing in a Resource-Poor Setting

Abstract INTRODUCTION: We compared the hepatitis C virus (HCV) core antigen test with the HCV RNA assay to confirm anti-HCV results to determine whether the HCV core antigen test could be used as an alternative confirmatory test to the HCV RNA test. METHODS: Sera from 156 patients were analyzed for anti-HCV and HCV core antigen using a chemiluminescent microparticle immunoassay (Architect i2000SR) and for HCV RNA using the artus HCV RG RT-PCR Kit (QIAGEN) in a Rotor-Gene Q instrument. RESULTS: The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 77.35%, 100%, 100%, and 89.38%, respectively. HCV core antigen levels showed a good correlation with those from HCV RNA quantification (r =0.872). However, 13 samples with a viral load of less than 4000 IU/mL were negative in the HCV core antigen assay. All gray-zone reactive samples were also RNA positive and were positive on repeat testing. CONCLUSIONS: The Architect HCV core antigen assay is highly specific and has an excellent positive predictive value. At the present level of sensitivity (77%), the study is still relevant in a low-income setting in which most of the HCV-positive patients would go undiagnosed, since HCV RNA testing is not available and/or not affordable. HCV core antigen testing can also help determine the true burden of infection in a population, considering the fact that almost 50% of the anti-HCV positive cases are negative for HCV RNA.

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.

Rare Occurrence of Type lll Membranoproliferative Glomerulonephritis in a patient with Hepatitis C in Sustained Virologic Response Phase

@#Hepatitis C virus (HCV) infection is known to cause acute and chronic active hepatitis. In addition, HCV also has systemic disorder involvement that links to various extra-hepatic complications. We report a case of a patient which has been diagnosed to have Hepatitis C Genotype 3A who has been started on antiviral. He achieved end treatment response and sustained virologic response. During routine follow up, he experienced acute kidney injury. Renal biopsy showed type III membranoproliferative glomerulonephritis. His proteinuria improved greatly with the addition of angiotensin converting enzyme inhibitor. This case highlights the possibility of appearance of HCV related glomerulonephritis in patient who has sustained virological response.

Comparison of simeprevir versus telaprevir plus pegylated interferon alfa and ribavirin in patients with hepatitis C virus genotype 1 infection——a meta-analysis / 中华传染病杂志

Objective To compare the efficacy and safety of simeprevir-based (SMV) or telaprevir-based (TVR) triple therapy [SMV + Pegylated interferon alfa (PegIFNα) and ribavirin (RBV) versus TVR + PegIFNαand RBV] in patients with hepatitis C virus (HCV) genotype 1 infection .Methods A systematic literature searching was conducted in multiple online databases to identify relevant studies .The sustained virologic response rate at 12 (SVR12) and 24 weeks (SVR24) after end of the treatment were used as the efficacy endpoints .The rate of treatment related adverse events (AEs) ,discontinuation due to AEs and overall treatment discontinuation were used as safety endpoints . Patients were divided into multiple subgroups according to the previous treatment history to further compare the efficacy of the two treatment regimen .Statistical analyses were performed using the RevMan 5 .3 software .The Jajad score scale and the Newcastle-Ottawa scale were employed to evaluate the quality of included studies .Results A total of 5 clinical studies including 1666 HCV genotype 1 patients were included in this study .The pooled results showed that SVR12 rates in SMV group and TVR group were 67 .6％ and 68 .3％ , respectively .There was no significant difference in overall SVR12 rate between SMV and TVR groups (OR=0 .95 ,95％ CI:0 .76 -1 .18 , P=0 .65) .There was no significant heterogeneity among studies (P=0 .84 ,I2 = 0％ ) .For SVR24 rate ,the average SVR24 rate in SMV group was 78％ ,which was lower than that in TVR group of 84％ .However ,there was no significant difference in overall SVR24 rate between SMV and TVR groups (OR=0 .71 ,95％ CI:0 .42-1 .20 ,P=0 .20) .Meanwhile ,there was no significant heterogeneity among studies (P= 0 .69 ,I2 = 0％ ) .The subgroup analysis also showed that there was no significant difference in efficacy between SMV and TVR-based triple therapy for treatment-native patients ,prior partial response ,relapse ,and prior null response patients (all P>0 .05) .However , the pooled analysis indicated that both SMV-based and TVR-based triple therapies were most effective for the treatment-naive patients(SMV :85 .7％ ,TVR :85 .6％ ) .For the safety endpoints ,the incidence rate of anemia was significant lower in SMV group compared to TVR group (OR=0 .30 ,P<0 .001) .For the rate of overall treatment discontinuation ,there was no statistically significant difference between SMV and TVR group (OR=0 .48 ,P=0 .12) .Conclusions This meta-analysis suggests that the efficacy of SMV-based triple therapy is non-inferior to TVR-based triple therapy .However ,the SMV-based triple therapy is more tolerable and has a lower incident rate of anemia and discontinuation due to AEs compared to TVR-based triple therapy .

Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon

Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.

Research progress on direct-acting antiviral agents(DAAs)in treatment of hepatitis C / 中华临床感染病杂志

In recent years,great progress has been made in treatment of patients with HCV infection with direct-acting antiviral agents (DAAs).Up to now,twelve kinds of oral DAAs and three kinds of combination regimens have been approved by the U.S.Food and Drug Administration and European Medicines Agency to treat chronic HCV infection.This article reviews the research progress of DAAs in treatment of hepatitis C,including the name of DAAs,drug targets,therapy regimen,clinical efficacy and adverse effects.

Association of interleukin‑28B rs12979860 and rs8099917 polymorphisms with sustained viral response in hepatitis C virus genotype 1 and 3 infected patients from the Indian subcontinent.

Background: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) have been shown to impact treatment responses in hepatitis C virus (HCV) infected patients. The association of these polymorphisms with sustained viral response (SVR) has been studied in HCV genotype 3 infected patients in India, but not in genotype 1. Objectives: This study aimed to determine the association of IL28B gene polymorphisms and other host and viral factors with treatment response in patients with HCV genotype 1 and 3 infection. Materials and Methods: DNA from 42 HCV‑infected patients on antiviral therapy was analysed for the IL28B polymorphisms using polymerase chain reaction‑restriction fragment length polymorphism (PCR‑RFLP). Bidirectional sequencing was performed on a subset of samples for verification of PCR‑RFLP results. Information on age, weight, height, diabetic status, pre‑treatment viral load and alanine aminotransferase (ALT) levels was obtained from clinical records. The IL28B genotypes and the other factors were analysed for their association with SVR. Results: The frequency distribution of rs12979860 CC/CT/TT genotypes was found to be 66.7%, 26.2% and 7.1%, respectively. For rs8099917 genotype, the TT/GT/GG distribution was 73.8%, 21.4% and 4.8%, respectively. SVR was seen in 61.9% of cases (55.6% in genotype 1 and 62.5% in genotype 3). CC genotype at rs12979860 and TT genotype at rs8099917 were significantly higher in responders (P = 0.013 and 0.042, respectively). Lower baseline ALT and rapid viral response were also found to be associated with SVR. On logistic regression analysis, CC genotype at rs12979860 emerged as the most powerful predictor of treatment response. Conclusion: IL28B polymorphisms are strong predictors of SVR in patients from the Indian subcontinent infected with HCV genotype 3 and genotype 1.

Induction with ribavirin in a relapsing patient with chronic HCV hepatitis

In this case, a new possible strategy for treatment of hepatitis C virus (HCV) relapsing patients is described. The target of anti-HCV therapy is sustained viral response, but strategies for improving sustained viral response in relapsing patients would be useful, and ribavirin is crucial for obtaining viral response. Six weeks of induction therapy with ribavirin were used to improve efficacy of standard combined antiviral therapy in a patient relapsing to standard therapy. In the present case, the patient had undergone a retreatment with the same regimen with the exception of the six-week induction period with ribavirin. Use of induction therapy with ribavirin in this case has allowed for a sustained viral response without prolonging the interferon exposure time in retreatment.

The effects of individualized therapeutic programs on chronic hepatitis C and the influential factors of virological response / 中华内科杂志

Objective To investigate the effect of individualized therapeutic programs with combination of interferon and ribavirin (RBV) in chronic hepatitis C (CHC) and study the influential factors of virological response rates.Methods A total of 139 patients with CHC were enrolled and given the intensive treatment doses of interferon and RBV according to their basic clinical condition.At the treatment of 0,4,12,24 weeks,the end of treatment and 24 weeks after treatment stop,the serum HCV RNA was determined.Timely adjustment to dosage and time periods was made according to the virological response to treatment,and the predictive value of rapid virological response (RVR) and complete early virological response (cEVR) for sustained virological response (SVR) were analyzed.Results At the 4th week of treatment,the level of serum HCV RNA was monitored in 120 patients,and 84.2％ (101/120) of patients obtained RVR; among them,90.7％ (88/97) obtained SVR.The virus load of patients obtained RVR at pretherapy was lower than that of patients didn't obtained RVR [(5.883±1.246) lg copies/ml vs (6.502±0.693)lg copies/ml,P =0.034].The RVR rate of initial treatment patients with PEG-IFNα-2a [87.8％(79/90)]was significantly higher than that of retreatment patients with PEG-IFNα-2a [65.0％ (13/20)](P =0.031).At the 12th week of treatment,the level of serum HCV RNA was monitored in 132 patients,and 92.4％ (122/132) of patients obtained cEVR; among them,90.8％ (108/119) obtained SVR.The SVR rate of patients obtained cEVR was significantly higher than that of patients didn't obtained cEVR (5/9) (P =0.007).There was no significant difference between the cEVR rate of initial treatment patients [94.7％ (90/95)]and retreatment patients [85％ (17/20)]with PEG-IFNα-2a (P =0.158).Conclusions cEVR was predictor of SVR.Individualized therapy can increase the obtaining probability of RVR,cEVR and SVR.Adjusting drug dose timely and extending treatment period of HCV RNA-negative based on virological response to treatment are important in CHC individualized therapy.

Hepatitis C: adherencia al tratamiento: consulta de hígado del Hospital Miguel Pérez Carreño Caracas / Hepatitis C: adherence to treatment in the population liver clinic Hospital

La adherencia o cumplimiento terapéutico es la realización del tratamiento de la hepatitis C con dosis suficientes de Interferon pegilado y Ribavirina durante el tiempo previsto, es decir 80% de las dosis inicialmente indicada, en el 80% del tiempo establecido. El objetivo de esta investigación fue determinar la adherencia al tratamiento en el grupo seleccionado, el cumplimiento de la terapia depende de varios factores que incluyen: paciente, efectos colaterales, personal médico y paramédico y todo aquello que impida reducir dosis o interrumpir la terapia. En este trabajo se revisaron 41 historias del archivo interno de la consulta de hígado del Hospital Miguel Pérez Carreño a quien se le indico tratamiento con Peg-Interferon y RBV por diagnostico de Hepatitis C, independientemente del genotipo. Se tomaron en cuenta los siguientes parámetros: sexo, edad, morbilidad asociada, efectos colaterales, motivo para suspender terapia, % de pacientes que culminaron tratamiento, etc. Se utilizo procesador Word y Excel, y análisis estadístico simple. El hallazgo primordial fue que aproximadamente solo el 29% culmino la terapia. La conclusión de esta revisión es entender la importancia de profundizar la relación médico-paciente y la conformación del equipo multidisciplinario como punto indispensable para lograr la adherencia al tratamiento y por ende una respuesta viral sostenida, objetivo primordial de la terapia.

Adherence or compliance to therapy is to apply the treatment for Hepatitis C, with the maximum dosage of Pegylated Interferon and Ribavirin along the foreseen period, i.e. 80% of the dosage initially prescribed during 80% of the established time. The completion of this objective depends on numerous factors: 1. Relating to Patients: a) patient’s education and understanding to realize the consequences of the disease and b) encouraging the patient to comply with the therapy. 2. Inherent to the treatment itself: a) appropriate management of adverse effects and b) drug tolerance of the patient. 3. Setting up a multidisciplinary team: medical doctor, nurse, psychologist, hematologist, etc. which positively influence the attitude of patient preventing dose reduction and drop-out of therapy. In this paper we reviewed 41 patient’s medical records from the internal archive of the Hepatic Department, Miguel Pérez Carreño Hospital. Those patients were treated with Peg-Interferon and RBV (Ribavirin) due to Hepatitis C diagnosis, independently on the genotype. The following parameters were taken into account: gender, age, associate morbidity, side effects, reasons for suspending therapy, % of patients who completed therapy, etc. Word processor and Excel were used and the simple statistical analysis. With the fundamental finding that, approximately, only the 29% of patients culminated the therapy. Reviewing this series allowed us to assess the importance of deepen the doctor-patient relationship, as well as setting up a multidisciplinary team, as an essential point in order to achieve the adherence to treatment and, therefore, a sustained viral response: the paramount objective of the therapy.

How sustained is sustained viral response in patients with hepatitis C virus infection.

Background Sustained virological response (SVR) is achieved in a high proportion of patientswith chronic hepatitis C infection, particularly those with genotype 2 or 3 HCV infection. However, data on long-term durability of virological response in patients who achieve SVR are limited. Aim To evaluate the long-term durability of virological response in patients who have achieved SVR with interferon-based combination therapy. Methods One hundred patients with chronic HCV infection who had obtained SVR after IFN and ribavirin combination therapy were followed up for up to 8 years with annual HCV RNA testing. Results During a followed up of 6 months to 8 years, 8 of 100 patients with initial SVR developed late relapse of HCV infection. Relapse was more common in patients who had cirrhosis (5/28 [18%] vs. (3/72 [4%] with no cirrhosis; p=0.037). Conclusion SVR is durable in most patients, but some patients do have late relapse; long term follow up may be particularly important in a subset of patients with HCV infection who have liver cirrhosis.

Infection with hepatitis C virus genotype 3 - Experience of a tertiary health care centre in south India.

To analyse the response rate and the predictive values of virological, biochemical and histological factors on HCV antiviral therapy in HCV genotype 3 infected patients, we retrospectively studied 21 HCV genotype 3 infected patients, who underwent HCV antiviral therapy. Low (57%) sustained viral response (SVR) rate and significant association of SVR with normalization of alanine transaminase (ALT) levels were observed in our study. Absence of early viral response (EVR) showed high (80%) predictive value on SVR. Absence of EVR and normalisation of the ALT levels can predict the outcome of HCV antiviral therapy.

Improvement of steatosis after interferon therapy in HCV genotype 4 is related to weight loss.

Introduction Hepatic steatosis is common in patients with chronic hepatitis C virus (HCV) infection, and its occurrence may be related to both host and viral factors. Relationship between improvement in steatosis and response to anti-viral treatment remains unclear. This study assessed the factors associated with steatosis in patients infected with genotype 4 HCV, and to correlate degree of changes in steatosis with host factors and response to treatment. Methods Records of 175 patients with chronic genotype 4 HCV infection, who had received interferon and ribavirin combination therapy, were reviewed retrospectively to extract data on body mass index (BMI), presence of diabetes mellitus, and liver histology findings. Paired BMI data and liver biopsies (pre- and 24-weeks post-treatment) were available in 86 patients. Baseline steatosis and its changes (before and after treatment) were the dependent variables in a univariate and multivariate analyses. Results Steatosis was found in 88/175 (50.3%) of baseline biopsies. Its presence was related to baseline BMI (r=0.33, P<0.01), but not with viral load, or grade of liver inflammation or fibrosis. On follow up, improvement in steatosis was significantly associated with degree of weight loss but not with response to anti-viral treatment. Conclusion Steatosis is common in genotype 4 HCV infection, and its presence appears to be related to high BMI, but not to viral load or degree of liver injury.