Real-life data on the HCV treatment with direct-acting agents in patients with decompensated cirrhosis are scarce. Study to investigate the effectiveness and safety of sofosbuvir-containing regimens in a prospective cohort of patients with HCV decompensated cirrhosis. A total of 150 patients were enrolled (64% male, 84% genotype 1 with a mean age of 61 ± 9 years). The median MELD was 12, and 79% were Child-PughB. Most patients were treated with sofosbuvir and daclatasvir (98%) with ribavirin in 27%. The overall intention to treat SVR12 was 91% (137/150). The most frequent adverse event was anemia (17%), 73% associated with ribavirin. Twenty-one (14%) patients experienced renal dysfunction, 81% AKI I, and 1 discontinued treatment. Thirty-five (23%) patients presented at least 1 infectious episode, mainly respiratory tract infection (29%). Thirty-three patients (22%) had at least 1 episode of cirrhosis decompensation throughout treatment, particularly worsening of previous ascites in 19%. Nine patients died, and among those, 7 patients died from sepsis. The probability of decompensation in 28, 90 and 180 days was 4%, 19% and 25%. During treatment, infection (OR 2.24; 95 CI 1.09-4.61; P = .03) was a predictor of cirrhosis decompensation, and baseline MELD and CHILD ≥ B8 were both associated with infection. In decompensated cirrhosis, the overall virological response was high with mild adverse events. However, this population had a high frequency of liver-associated decompensation and infections.

Hepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs).

To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil.

This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a P value of < 0.05 was considered significant.

The mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, P = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, P = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, P = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060-1.233, P = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, P = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, P = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, P = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence.

Treatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.

The efficacy of direct-acting antivirals (DAAs) in the treatment of chronic hepatitis C (CHC) in liver transplant recipients is poorly understood, and several factors, including immunosuppression, drug interactions, elevated viraemia, and intolerance to ribavirin (RBV), can reduce cure rates. We conducted a real-life study on liver transplant recipients with CHC treated with a combination of sofosbuvir (SOF) and daclatasvir (DCV) or simeprevir (SIM), with or without RBV, followed-up for 12 to 24 weeks. The treatment effectiveness was assessed by determining the sustained virological response (SVR) rates at 12 or 24 weeks after the treatment cessation. Eighty-four patients were evaluated, with a mean age of 63.4 ± 7.4 years, HCV genotype 1 being the most prevalent (63.1%). Nineteen patients (22.7%) had mild fibrosis (METAVIR < F2) and 41 (48.8%) significant fibrosis (METAVIR ≥ F2). The average time between liver transplantation and the start of treatment was 4 years (2.1-6.6 years). The SOF + DCV regimen was used in 58 patients (69%). RBV in combination with DAAs was used in seven patients (8.3%). SVR was achieved in 82 patients (97.6%), and few relevant adverse events could be attributed to DAA therapy, including a patient who stopped treatment due to a headache. There was a significant reduction in ALT, AST, GGT and FA levels, or the APRI index after 4 weeks of treatment, which remained until 12/24 weeks post-treatment. DAA treatment of CHC in liver-transplanted patients achieved a high SVR rate and resulted in the normalization of serum levels of liver enzymes.

Disturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy.

Clinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays.

Cohort included 33 patients (59.5 ± 9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ± 15 years, 54.5% females). Before treatment, HCV patients presented higher MMP-9/TIMP-1 levels (P < 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P < 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P < 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators.

Our data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.

After DAA treatment for chronic hepatitis C infection, peripheral monocyte subsets from patients who achieved sustained virological response (SVR) reduced compared to healthy control. Improvement in inflammatory parameters and liver stiffness has been observed. However, little is known about the long-term impact of DAA treatment on peripheral monocyte subsets and immune mediators levels.

We aimed to examine peripheral monocyte subsets and immune mediators levels in Brazilian chronic HCV patients after long-term successful IFN-free SOF-based treatment.

We analyzed CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes and 27 immune mediators by flow cytometry and analysis of multiple secreted proteins assay, respectively, in monoinfected chronic HCV patients receiving IFN-free sofosbuvir-based regimens followed before treatment, at SVR and one year after the end of treatment (1y).

Twenty-one biomarkers decreased significantly at 1y and 55-80 % of patients this reduction at 1y. Experimented patients presented a greater modulation of immune mediators at 1y. HLA-DR expression significantly decreased on CD14++CD16- and CD14++CD16+ monocytes at 1y when compared to SVR.

Successful DAA therapy did not modify monocyte subsets frequency but reduced monocyte activation at 1y and sustained the downregulation and restoration of circulating immune mediators, indicating that long-term reversal of inflammation status could occur after HCV eradication.

Between 70 and 170 million people worldwide are infected with hepatitis C virus (HCV) which frequently causes chronic liver disease and cirrhosis. There are several genotypes and many subtypes of HCV. Direct-acting antiviral agents are effective at eradicating HCV in the vast majority of patients, producing much higher cure rates than were seen with interferon and ribavirin regimens only a few years ago. The chapter reviews the epidemiology and virology of HCV infection. Treatment regimens are complex but a straightforward approach to selection of patients, choice of direct-acting antiviral agents and follow-up is presented.

Coronaviruses are a group of enveloped viruses with non-segmented, single-stranded, and positive-sense RNA genomes. In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Wuhan City, China. The World Health Organization (WHO) declared the coronavirus outbreak as a global pandemic in March 2020. Fever, dry cough and fatigue are found in the vast majority of all COVID-19 cases. Early diagnosis, treatment and future prevention are keys to COVID-19 management. Currently, the unmet need to develop cost-effective point-of-contact test kits and efficient laboratory techniques for confirmation of COVID-19 infection has powered a new frontier of diagnostic innovation. No proven effective therapies or vaccines for SARS-CoV-2 currently exist. The rapidly increasing research regarding COVID-19 virology provides a significant number of potential drug targets. Remdesivir may be the most promising therapy up till now. On May 1, 2020, Gilead Sciences, announced that the U.S. Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for the investigational Remdesivir as a potential antiviral for COVID-19 treatment. On May 7, 2020, Gilead Sciences, announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval of Veklury® (Remdesivir) as a treatment for SARS-CoV-2 infection, the virus that causes COVID-19 acute respiratory syndrome, under an exceptional approval pathway. Also, Corticosteroids are recommended for severe cases only to suppress the immune response and reduce symptoms, but not for mild and moderate patients where they are associated with a high-risk side effect. Based on the currently published evidence, we tried to highlight different diagnostic approaches, side effects and therapeutic agents that could help physicians in the frontlines.

In recent years the management of hepatitis C virus infection and the possibility of its eradication have been researched due to the importance that they represent in the health of the world population. Obtaining data that help to cope with this pathology improves the quality of life of those affected by it. The present study evaluated the effectiveness of direct-acting antiviral therapies provided by the Brazilian Ministry of Health in accordance to the Clinical Protocol and Therapeutic Guidelines of 2015.

To evaluate the epidemiological profile of patients with chronic hepatitis C and the rate of sustained virologic response using direct-acting antivirals of all individuals that attended the referral service for the treatment of chronic hepatitis C at the Hospital of the Federal University of Rio Grande.

This was an observational, retrospective/prospective study with all patients with chronic hepatitis C who had their treatments available from December 2015 to August 2017 according to the criteria of the Clinical Protocol and Therapeutic Guidelines of 2015. In the first phase, the clinical and demographic variables of all individuals enrolled in a treatment for hepatitis C were selected and collected from the Reference Service database. In the second phase, treatment data were collected. The outcome variable, sustained virologic response, was defined as an undetectable viral load on the blood test three months after the end of treatment. The descriptive and bivariate analyzes were performed with Pearson's chi-square and Fisher's Exact test, adopting a P value ≤0.05 in the SPSS 20 software.

Of the 252 participants in the study, 228 (90.5%) had a sustained virologic response, 55.2% were male with an average age of 58.6 years (SD±9.1). Genotype 1 was the most prevalent, observed in 54.4% of the participants, and 87.4% of the patients had moderate/advanced hepatic fibrosis. After the statistical analysis, it was observed that the individuals with genotype 3 and moderate/advanced hepatic fibrosis had lower sustained virologic response rate (P=0.05 and P=0.04, respectively).

It was observed that the use of direct-acting antivirals, in comparison to previous therapeutic regimens, increases the sustained virologic response, reaching all patients with mild fibrosis. This study provides information that helps in the hepatitis C treatment by showing that prescribing early treatment for patients without hepatic fibrosis and/or genotype 3 virus could increase therapeutic effectiveness.

Direct-acting antivirals have revolutionized hepatitis C treatment, also for patients with chronic kidney disease (CKD), but some controversy exists regarding the use of sofosbuvir (SOF) in patients with glomerular filtration rate (GFR) <30 mL/min.

To evaluate the efficacy and safety of these regimens for hepatitis C treatment of patients with CKD and after renal transplantation, as well as the impact of SOF on renal function in non-dialysis patients.

All patients with hepatitis C and CKD or renal transplant treated with direct-acting antivirals at a referral center in Brazil between January 2016 and August 2017 were included. Efficacy was evaluated based on viral load (HCV RNA) and a sustained virological response (SVR) consisting of undetectable RNA 12 and/or 24 weeks after the end of treatment (SVR12 and SVR24) was defined as cure. Safety was determined by adverse events and ribavirin, when combined, was administered in escalating doses to all patients with GFR <60 mL/min. The impact of SOF on renal function was determined by the measurement of baseline creatinine during and after the end of treatment and its increase was evaluated using the Acute Kidney Injury Network (AKIN) classification.

A total of 241 patients (52.7% females) with a mean age of 60.72±10.47 years were included. The combination of SOF+daclatasvir was the predominant regimen in 75.6% of cases and anemia was present in 28% of patients who used ribavirin (P=0.04). The SVR12 and SVR24 rates were 99.3% and 97.1%, respectively. The treatment was well tolerated and there were no major clinically relevant adverse events, with the most prevalent being asthenia (57.7%), itching (41.1%), headache (40.7%), and irritability (40.2%). Among conservatively treated and renal transplant patients, oscillations of creatinine levels (AKIN I) were observed in 12.5% of cases during treatment and persisted in only 8.5% after the end of treatment. Of these, 2.0% had an initial GFR <30 mL/min and this percentage decreased to 1.1% after SOF use. Only 0.5% and 1.6% of the patients progressed to AKIN II and AKIN III elevation, respectively.

The direct-acting antivirals were safe and efficacious in CKD patients treated with SOF-containing regimens, with the observation of high SVR rates, good tolerability and few severe adverse events. The combination with ribavirin increased the risk of anemia and the administration of escalating doses seems to be useful in patients with GFR <60 mL/min. In patients with GFR <30 mL/min, SOF had no significant renal impact, with serum creatinine returning to levels close to baseline after treatment.

To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens.

A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow-up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors.

A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08-3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38-4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78-18.30]). Treatment efficacy was 98.1%.

Direct-acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.

Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil.

All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR).

3939 patients (60% males, mean age 58±10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation.

SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.

Hepatitis C virus is known to be highly dependent of lipid metabolism to infect new cells and replicate.

To investigate lipid and apolipoprotein profile in chronic HCV patients according to treatment response.

Patients recruited from the Hepatitis Treatment Center at Niteroi (Brazil) who received interferon (IFN)-based therapies were separated into two groups, those who achieved sustained virological response (SVR) or not (non-SVR). Another group of patients treated with IFN-free direct-acting antiviral (DAA) therapies was followed from before starting the treatment until one year after therapy. Triglycerides, total cholesterol and fractions were determined by colorimetric and/or electrophoresis techniques. Lecithin cholesterol acyltransferase (LCAT) activity and serum levels of apolipoproteins A1, A2, B, C2, C3 and E were assessed by enzymatic and multiplex assays, respectively.

We studied 114 patients, and SVR was reached in 28 (39.4%) patients treated with IFN-therapy and in all (100%) patients who received DAA. Non-SVR patients (n = 43) presented altered liver parameters post-treatment. Levels of total cholesterol, LDL-C, VLDL-C and triglycerides were significant higher in SVR group. In contrast, LCAT activity and HDL-C levels were elevated in non-SVR patients. Only apolipoproteins B, C2 and C3 levels were increased in SVR group. The follow-up of SVR-DAA patients (n = 43) revealed a significant and progressive increase in serum levels of total cholesterol, LDL-C, VLDL-C and triglycerides.

After a successful treatment, chronic hepatitis C patients experienced a reestablishment of lipid metabolism. Our results suggest that the monitoring of serum lipids could be a practical and routine laboratory tool to be applied during the treatment follow-up.

Sofosbuvir(SOF)-based regimens have been administrated with excellent efficacy in chronic hepatitis C. Few uncontrolled ("real-life") studies consider the assessment of renal function when evaluating their post-treatment outcomes. This study aims to evaluate renal biomarkers in a "real-life" experience with chronic hepatitis C patients treated with SOF therapy in a long-term follow-up.

Serum and urinary biomarkers were analysed before, at the end of therapy (EoT), after 12 weeks (sustained virological response-SVR) and one year (1y) post-treatment. Patients were categorized according to baseline glomerular filtration rate (GFR-cut-off 45 mL/min/1.73 m² ).

Ninety-four patients with a mean age of 59.9 ± 8.5 years were included; 98.9% of patients reached SVR. Significant improvement in renal biomarkers was observed in patients with GFR ≥45 mL/min/1.73 m² , as indicated by a progressive increase in mean GFR values until 1y. No evidence of tubular dysfunction was identified. Patients with baseline GFR <45 mL/min/1.73 m² did not experience alterations in renal biomarkers; however, a mean change of +10.7 in GFR values was observed. We noticed significant upper stage transition in the CKD classification, and 58.7% of patients achieved G1 stage at 1y (P < .0001).

In a "real-life experience" of a Brazilian centre, SOF therapy appears to guarantee renal safety for patients with chronic hepatitis C followed until one year after treatment.

This study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients.

This was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response.

A total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p<0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response.

The results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.