Evaluation of the clinical and economic value of sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C in Spain during the last 5 years.

OBJECTIVE: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) represented a paradigm shift. In 2017, sofosbuvir/velpatasvir (SOF/VEL-Epclusa®) was approved, which showed a high cure rate in all patient, contributing to HCV elimination. The analysis aimed to quantify the clinical and economic value of SOF/VEL in HCV chronic patients since its approval in Spain. METHODS: An economic evaluation was elaborated adapting a Markov model that simulated the lifetime disease progression in of all HCV chronic patients treated with SOF/VEL (30,488 patients) since its launch (5-years), compared to previous therapies. Patients entered the model and were distributed between the fibrosis states (F0-to-F4) in treated and untreated. All patients (100%) were treated with SOF/VEL regardless of their fibrosis, and 49% with previous therapies in ≥F2. The average sustained viral response (SVR) rates 98.9% SOF/VEL versus 61.0% previous therapies. All parameters for the analysis were obtained from real-life data and literature. Only direct healthcare costs associated with disease management were included. The SOF/VEL value was measured as the number of hepatic complications avoided and their associated cost, and hepatic mortality compared to previous therapies. National Health System perspective and a 3% discount rate was applied. RESULTS: SOF/VEL decreased the number of liver complications, avoiding 92% decompensated cirrhosis, 80% hepatocellular carcinomas, and 87% liver transplants, as well as 85% liver-related mortality. Their cost associated was reduced, amounting to savings of 197M€. CONCLUSION: SOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.

Artificial intelligence-assisted identification and retrieval of chronic hepatitis C patients lost to follow-up in the health area of Pontevedra and O Salnés (Spain).

OBJECTIVE: Direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) infection offer an opportunity to eliminate the disease. This study aimed to identify and relink to care HCV patients previously lost to medical follow-up in the health area of Pontevedra and O Salnés (Spain) using an artificial intelligence-assisted system. PATIENTS AND METHODS: Active retrospective search of previously diagnosed HCV cases recorded in the Galician Health Service proprietary health information exchange database using the Herramientas para la EXplotación de la INformación (HEXIN) application. RESULTS AND CONCLUSIONS: Out of 99 lost patients identified, 64 (64.6%) were retrieved. Of these, 62 (96.88%) initiated DAA treatment and 54 patients (87.1%) achieved a sustained virological response. Mean time from HCV diagnosis was over 10 years. Main reasons for loss to follow-up were fear of possible adverse effects of treatment (30%) and mobility impediments (21%). Among the retrieved patients, almost one in three presented advanced liver fibrosis (F3) or cirrhosis (F4) at evaluation. In sum, HCV patients lost to follow-up can be retrieved by screening past laboratory records. This strategy promotes the achievement of HCV elimination goals.

Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. METHODS: 135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. RESULTS: 125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver-kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. CONCLUSIONS: Long-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function.

Patients with severe mental illness and hepatitis C virus infection benefit from new pangenotypic direct-acting antivirals: Results of a literature review.

INTRODUCTION: Hepatitis C virus (HCV) infection is a global health problem that can results in cirrhosis, hepatocellular carcinoma and even death. HCV infection is 3-20-fold more prevalent among patients with versus without severe mental illness (SMI), such as major depressive disorder, personality disorder, bipolar disorder and schizophrenia. Treatment options for HCV were formerly based on pegylated interferon alpha, which is associated with neuropsychiatric adverse events, and this contributed to the exclusion of patients with SMI from HCV treatment, elimination programmes, and clinical trials. Moreover, the assumption of poor adherence, scant access to healthcare and the stigma and vulnerability of this population emerged as barriers and contributed to the low rates of treatment and efficacy. METHODS: This paper reviews the literature published between December 2010 and December 2020 exploring the epidemiology of HCV in patients with SMI, and vice versa, the effect of HCV infection, barriers to the management of illness in these patients, and benefits of new therapeutic options with pangenotypic direct antiviral agents (DAAs). RESULTS: The approval of DAAs has changed the paradigm of HCV infection treatment. DAAs have proven to be an equally efficacious and safe option that improves quality of life (QoL) in patients SMI. CONCLUSIONS: Knowledge of the consequences of the HCV infection and the benefits of treatment with new pangenotypic DAAs among psychiatrists can increase screening, referral and treatment of HCV infection in patients with SMI.

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C.

BACKGROUND & AIMS: Life-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. METHODS: 491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical-biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. RESULTS: During a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01-1.05), age (HR, 1.04; 95% CI, 1.01-1.08) and albumin levels (HR, 0.90; 95% CI, 0.84-0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08-1.37) and albumin (HR, 0.90; 95% CI, 0.84-0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. CONCLUSION: Simple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.

Cardiometabolic effects of direct-acting antivirals in patients with hepatitis C.

Hepatitis C virus (HCV) has long been associated with several extrahepatic manifestations, including increased cardiovascular risk. The emergence of direct-acting antivirals (DAAs) has allowed us to evaluate the potential reversal of these manifestations after successful treatment. Therefore, many studies have provided significant takeaways regarding the positive effect of DAAs therapy on insulin resistance, type 2 diabetes mellitus, cardiovascular disease and atherosclerosis. In contrast, studies have shown detrimental effects on lipid metabolism and indeterminate results regarding renal function and uric acid metabolism. Nevertheless, as more and more patients achieve sustained virological response, the effects of HCV eradication on cardiometabolic processes will be extensively studied, allowing more reliable conclusions on the extent of extrahepatic outcomes.

Sofosbuvir plus glecaprevir/pibrentasvir as salvage therapy after liver transplantation in NS5A inhibitor-experienced patients. A case series.

BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rate higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients. OBJECTIVES: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen. MATERIAL AND METHODS: Retrospective study of 111 liver transplant recipients between January 2018 and December 2020; 18 patients presented with HCV recurrent infection after LT, out of whom three had a history of at least one NS5A inhibitor-based regimen. Salvage therapy with sofosbuvir plus GLE/PIB was started for 12 weeks; baseline characteristics and outcomes were recorded. RESULTS: All three patients (100%) achieved an undetectable HCV viral load 12 weeks after treatment completion. No serious adverse events were observed. CONCLUSION: In our series, sofosbuvir plus GLE/PIB for 12 weeks is an effective and safe salvage therapy after LT in patients previously treated with NS5A inhibitors.

ANTECEDENTES: El tratamiento del virus de la hepatitis C (VHC) crónica con antivirales de acción directa logra tasas de respuesta virológica sostenida superiores a 95 %. Sin embargo, el manejo del fracaso virológico sigue siendo un desafío clínico y la evidencia sobre el retratamiento es limitada, especialmente en poblaciones como los receptores de trasplante hepático (TH). OBJETIVO: Este estudio evaluó el régimen de sofosbuvir más glecaprevir/pibrentasvir (GLE/PIB) en receptores de TH en quienes falló el régimen basado en inhibidores de la proteína no estructural 5A (NS5A). MATERIAL Y MÉTODOS: Estudio retrospectivo de 111 pacientes trasplantados entre enero de 2018 y diciembre de 2020; 18 pacientes presentaron infección recurrente por VHC posterior al TH, tres de ellos tuvieron antecedentes de al menos un régimen basado en inhibidores de NS5A. Se inició terapia de rescate con sofosbuvir más GLE/PIB durante 12 semanas posterior al TH; se registraron las características basales de los pacientes y sus desenlaces. RESULTADOS: En los tres pacientes se logró obtener una carga viral indetectable de VHC a las 12 semanas de finalizar el tratamiento. No se observaron eventos adversos graves. CONCLUSIÓN: En nuestra serie, sofosbuvir más GLE/PIB durante 12 semanas demostró ser una terapia de rescate efectiva y segura posterior al TH en pacientes previamente tratados con inhibidores de NS5A.

Evolution of HCV associated porphyria cutanea tarda after HCV sustained virologic response by direct acting antivirals.

OBJECTIVES: Porphyria cutanea tarda (PCT) is common and usually associated with HCV chronic infection and HFE polymorphisms. Since DAA IFN-free regimens availability, SVR for HCV is nearly a constant and we wonder whether HCV SVR determine PCT evolution. METHODS: Retrospective observational study including patients with HCV associated PCT from the Gastroenterology and Infectious Diseases Departments at our Hospital, treated with DAA (Apr/2015-Apr/2017). Clinical variables of PCT were collected at PCT diagnosis, after PCT treatment, before DAA use and after SVR achievement. UROD activity and C282Y/H63D polymorphisms were registered. SPSS 22.0. RESULTS: 13 HCV-PCT patients included: median age 52.5 years; 4 females; 8 HCV/HIV co-infected (all on undetectable viral load). Classical PCT factors: 12 smoked, 9 alcohol abuse, 6 former IDU. 10 type I PCT and 1 type II PCT. HFE polymorphism: 2 cases with C282Y/H63D; H63D polymorphism in 8. PCT manifestations resolved with PCT treatment in 4 patients, almost completely in 7 patients, 1 patient referred stabilization and one worsened. After DAA treatment all the residual lesions resolved, what always led to specific treatment interruption. CONCLUSIONS: Our series of cases of HCV-associated PCT shows that SVR after DAA treatment leads to PCT resolution. Porphyrin levels are not needed after ending PCT specific treatment interruption when there are no residual skin lesions in HCV-associated PCT.

Evolution of patients with chronic hepatitis C infection with advanced fibrosis or cirrhosis cured with direct-acting antivirals. Long-term follow-up. / Evolución de los pacientes con infección crónica por hepatitis C con fibrosis avanzada o cirrosis curados con antivirales de acción directa. Seguimiento a largo plazo.

AIMS: To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA). PATIENTS AND METHODS: Unicenteric, observational and prospective study. All F3-F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment. Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected. RESULTS: 169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR. The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×103/µL (BV); 163×103/µL (12w)], cholesterol [158mg/dL (BV); 179mg/dL (12w)] and albumin [4.16g/dL (BV); 4.34g/dL (12w)] and a significant decrease in ALT [82UI/L (BV); 23UI/L (12w], AST [69UI/L (BV); 26UI/L (12w)], GGT [118UI/L (BV); 48UI/L (12w)] and bilirrubin [0.9mg/dL (BV); 0.7mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9kPa (BV); 14.8kPa (12w; P<.05]. 8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices. Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence. During follow-up mortality was 9.2%. CONCLUSIONS: There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.

Influence of psychiatric disorders and opioid substitution therapy on hepatitis C treatment with direct-acting antivirals in people who inject drugs. / Influencia de los trastornos psiquiátricos y la terapia de sustitución con opiáceos en el tratamiento del virus de la hepatitis c con antivirales de acción directa en usuarios de drogas por vía parenteral.

INTRODUCTION: The effectiveness of the hepatitis C virus (HCV) treatment seems to be lower in people who inject drugs (PWID). We analyze the influence of various factors as psychiatric disorders and opioid substitution therapy (OST) on the treatment with direct-acting antivirals (DAA) in this collective. PATIENTS AND METHODS: Three hundred thirty-two PWID patients were treated with DAA in 12 Spanish hospitals between 2004 and 2020. They were catalogued in recent and former consumers (if the last consumption was in the last 3 years) and several variables were included, evaluating the effectiveness of the treatment according to the viral load 12 weeks after the end of the treatment with the parameter «sustained viral response¼ (SVR12). RESULTS: 23.4% were recent consumers and 27.7% were on OST. The 41.5% had any diagnosis of psychiatric disorder. SVR12 was 84.04%, ascending to 96.21% when excluded from the analyses the patients lost to follow-up (12.7%). SVR12 was lower due to an increase in the loss to follow-up in recent consumers and other factors like OST, being in prison the last 5 years, naïve patients, generalized anxiety disorder and benzodiazepine consumption. CONCLUSIONS: The effectiveness of the HCV treatment with DAA in PWID is similar than in general population in patients whit an appropriate follow-up. It is important to maintain a closer follow-up in patients on OST, recent consumers and those with psychiatric disorders.

[Effect of winter cover crops on the soil microbiome: a systematic literature review]. / Efecto de los cultivos de cobertura invernales sobre el microbioma del suelo: revisión sistemática de la literatura.

The inclusion of winter cover crops (WCC) in no-till (NT) systems in replacement of bare fallow is a promising alternative to improve soil health and consequently, contribute to environmental sustainability of agricultural systems. This review provides a comprehensive evaluation of the effects of the use of WCC in rotation with summer cash crops under NT systems on the soil microbiome versus bare fallows. A systematic literature search was conducted to evaluate the impact of WCC on microbial parameters indicative of abundance, activity and diversity. Twenty-two papers were selected based on seven combined criteria. The results of this review show that enzyme activities in soil are enhanced with the inclusion of WCC in the rotation, particularly those that include legumes and mix of species. In general, more than half of the analyzed papers report higher microbial biomass in soils with WCC than in bare fallow. Interestingly, the effects of WCC on microbial parameters are independent of the duration of the experiments. However, more basic research is necessary to reduce the heterogeneity of the studies and to better understand the complexity of the interactions between WCC and the soil microbiome.

Hepatitis C-treated patients as a potential source for referral of new cases. / El paciente tratado de hepatitis C como fuente potencial de derivación de nuevos casos.

INTRODUCTION: Direct-acting antivirals (DAAs) are an opportunity for hepatitis C virus (HCV) elimination. Strategies are needed to diagnose new patients and to attract those diagnosed without evaluation. Patients with other chronic viral diseases who receive satisfactory treatment promote referral of other patients for evaluation. Our aim was to evaluate whether patients who have been treated with DAAs would recommend follow-up and treatment to other patients as well as the characteristics that influence this decision. PATIENTS AND METHODS: Two-hundred and 2HCV-infected patients treated with DAAs were included. Patients were asked about whether they knew other infected people and their willingness to share their experience. A general satisfaction survey and a specific HCV satisfaction survey were carried out. Demographic, socioeconomic and HCV infection variables were recorded. RESULTS: Despite the fact that 54.4% of the patients reported knowing others infected, 34.2% would not fully agree to share their experience. The analysis of general and specific satisfaction showed that patients who shared their experience mentioned a perception of greater care from the specialist (4.7±0.4 vs. 4.3±0.6, P=.001) and had more information on treatment expectations (4.6±0.5 vs. 4.0±0.7, P=.001) and social support (4.5±0.7 vs. 4.0±0.8, P=.001). CONCLUSIONS: The perception by treated patients of general satisfaction with the healthcare process and information about benefits influences the degree of recommendation to other infected people. Knowledge about treatment and perception of improvement in health of treated patients should be enhanced as it can contribute to increasing referrals to specialized consultation.

Efficacy of Elbasvir/Grazoprevir in Early Chronic G1/G4 Hepatitis C infection in HIV/HCV co-infected patients with mild fibrosis.

BACKGROUND: Acute hepatitis C virus (AHC) infection is increasingly common among HIV+ men who have sex with men (MSM). Until 2017, the guidelines recommended therapy with pegylated-interferon plus ribavirin with a mild sustained virological response (SVR). This prompted many patients to reject that treatment, at that time, waiting to be treated with better and safer options with new Direct-Acting-Antivirals (DAA). OBJECTIVES: Assess the efficacy and safety of Elbasvir/Grazoprevir to treat recent chronic hepatitis C infection, genotype 1 or 4, in HIV+ MSM patients. METHODS: Prospective, open-labeled, two center, pilot study. SVR is analyzed for treatment with Elbasvir/Grazoprevir (8 weeks in GT1b or 12 in GT1a or GT4) in patients with a recent chronic HCV infection, defined as HCV infection lasting less than 4 years and mild liver fibrosis (liver stiffness <8kPa). RESULTS: Forty-eight patients were included (May 2017-March 2018): 2 GT1b, 24 GT1a and 22 GT4. HCV-RNA>800000UI in 63% and medium liver stiffness 4.9kPa. The SVR was 98%, one patient failed due to poor adherence. 67% of patients had adverse effects, but only 16% treatment related. The most frequent side effects were gastrointestinal (19%), related with the central nervous system (18%), respiratory (16%) and systemic symptoms (15%). During one year of follow-up post-therapy, 4 AHC and 18 patients with sexually transmitted diseases (STD) were diagnosed. CONCLUSIONS: Treatment with Elbasvir/Grazoprevir in this scenario is highly effective and safe. Patients with risky sexual practices must remain linked to the medical care system to detect new STD and HCV reinfection.

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals.

INTRODUCTION: The aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents. PATIENTS AND METHODS: This cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness-spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed. RESULTS: Ninety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p=0.02), spleen stiffness measurement (39.4 vs 46.05; p=0.04), liver stiffness-spleen diameter to platelet ratio score (1.21 vs 2.02; p=0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p=0.04) and variceal risk index (-3.4 vs -1.02; p=0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3kPa for liver stiffness measurement and 27kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance. DISCUSSION: Liver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.

Modification of liver fibrosis, glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents.

INTRODUCTION: There is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels. METHODS: 445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48). RESULTS: The SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3-14.3)kPa at baseline to 6.4 (IQR 4.9-8.9) at SVR48 (p<0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1-3.3) to 1.3 (IQR 0.9-2.0) (p<0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5-1.7) to 0.3 (IQR 0.2-0.4) and from 6.2 (5.0-7.5) to 4.9 (IQR 3.8-5.9) (p<0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172mg/dL and 101.5mg/dL to 191mg/dL and 117.5mg/dL (p<0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7mg/dL at baseline to 127.2mg/dL at SVR48 (p<0.001). DISCUSSION: SVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48.

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus.

INTRODUCTION: Many patients with hepatitis C virus (HCV) have associated comorbidities that require complex treatments. We sought to determine the impact of treatment with direct-acting antiviral agents (DAAs) for HCV on adherence to prescribed concomitant medications for associated comorbidities and to identify predictors of non-adherence to comedications. PATIENTS AND METHODS: HCV-infected patients treated with DAAs in a Spanish hospital between January 2015 and December 2016 and followed-up by the pharmacy unit were included in the study. Adherence to concomitant comedication prescribed before and during HCV therapy with DAAs was compared to adherence during the same number of weeks before DAA initiation. Demographic, clinical and pharmacotherapy variables were analyzed to determine factors associated with non-adherence. A multivariate regression model was created for prediction of non-adherence to concomitant medication. RESULTS: Data from 214 patients using prescribed concomitant therapies were analyzed. Significant reduction on adherence to comedications was observed after initiation of DAA treatment compared with a similar period before therapy initiation (29.9% vs. 36.9%, p=0.032). The univariate analysis showed that polypharmacy and presence of vascular disease were associated negatively with adherence to concomitant medications (87.8%, p=0.006 and 84.7%, p<0.001, respectively). Multivariate analysis indicated that HIV/HBV coinfection was associated with adherence (OR 0.19; 95% CI 0.09-0.39), while polypharmacy was a predictor for non-adherence (OR 4.54; 95% CI 1.48-13.92). DISCUSSION: Adherence to concomitant medications decreases in HCV-infected patients when DAA therapy is initiated. Polypharmacy is a predictor for non-adherence, while HIV/HBV coinfection reduce non-adherence rates. Polymedicated patients on DAAs might benefit from close follow-up and educational programmes to improve their adherence.

Importance of adherence to treatment with direct-acting antivirals in hepatitis C. / Importancia de la adherencia al tratamiento de la hepatitis C con antivirales de acción directa.

The introduction of direct-acting antivirals (DAA) and the implementation of the National Strategic Plan has extended the spectrum of patients suitable for treatment to include practically all affected individuals. There has been a change in patient profile. Most patients are previously untreated, with lesser awareness of the disease, and taking polymedication, and are often under treatment with opioid replacement therapy, are active drug users or have psychiatric comorbidities. This article reviews the most important factors determining the degree of treatment adherence, in particular, drug therapy complexity, the adverse effects of DAA, demographic factors (age, ethnic group, sex, educational level, marital status) and psychosocial factors (beliefs, motivation to take therapy and negative attitude to therapy), as well as the doctor-patient relationship, knowledge/awareness of the disease, and finally comorbidities and drug abuse or abuse of other substances such as alcohol. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.

Optimisation in the multidisciplinary approach to patients with hepatitis C in the era of direct-acting antivirals. / Optimización en el abordaje multidisciplinar del paciente con hepatitis C en la era de los antivirales de acción directa.

The advents of current direct-acting antiviral treatments has revolutionised the therapeutic approach to hepatitis C, increasing cure rates to above 90% and substantially simplifying treatment, which translates into benefits for patients, clinicians and the health system. These new drugs allow cure to be achieved, irrespective of the patient's characteristics, with tolerability similar to that of placebo and few drug reactions with concomitant medication. This in turn improves patients' quality of life and wellbeing. Moreover, these drugs allow multidisciplinary optimisation of the approach to patients with hepatitis C, thus reducing both short- and long-term costs. All these factors facilitate treatment universality, with treatments that are less influenced by specific factors and that allow better results to be obtained in a larger number of patients. Elimination of hepatitis C is now a real possibility. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.

Antiviral treatment does not improve subclinical atheromatosis in patients with chronic hepatitis caused by hepatitis C virus. / El tratamiento antiviral no mejora la ateromatosis subclínica en pacientes con hepatitis crónica por virus de la hepatitis C.

INTRODUCTION: Chronic infection with hepatitis C virus is a risk factor for developing atheromatous plaques, although the possible effect of virus clearance is unknown. Our aim was to determine whether or not subclinical atheromatosis improved and there was any modification in the composition of the plaques 12 months after eradication of hepatitis C virus by direct-acting antiviral agents. MATERIALS AND METHODS: Prospective study that included 85 patients with chronic hepatitis C virus infection in different stages of fibrosis who were on direct-acting antiviral agents. Patients with a cardiovascular history, diabetes and kidney disease were excluded. An arterial ultrasound (carotid and femoral) was performed to diagnose atheromatous plaques (defined as intima-media thickness ≥1.5mm) and the composition (percentage of lipids, fibrosis and calcium with HEMODYN4 software) was analysed at the beginning of the study and 12 months after stopping the therapy. RESULTS: After follow-up no changes were detected in the intima-media thickness (0.65mm vs. 0.63mm, P=.240) or in the presence of plaques (65.9% vs 71.8%, P=.063). There was also no significant change in their composition or affected vascular territory, with an increase in blood lipid profile (P<.001) after 12 months of treatment. These results were confirmed in subgroups by severity of liver disease. DISCUSSION: The eradication of hepatitis C virus by direct-acting antiviral agents does not improve the atheroma plaques and nor does it vary their composition, regardless of liver fibrosis. More prospective studies are needed to evaluate residual cardiovascular risk after virus eradication.

Quality of life in patients with hepatitis C. Importance of treatment. / Calidad de vida en los pacientes con hepatitis C. Importancia del tratamiento.

Chronic hepatitis C virus infection is a systemic disease that impairs the quality of life of affected individuals. The impairment is not only due to physiological factors, such as the non-hepatic manifestations of the disease or certain symptoms such as fatigue, weakness and nausea, but is also due to the substantial psychological impact of the infection. Treatment with direct-acting antivirals (DAA) has been demonstrated to substantially improve patient's quality of life, starting in the initial phases. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.