Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil

Introduction and objectivesDirect 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.Materials and methodsAll 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).Results3939 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.ConclusionSOF-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.     

Asynchronous electronic consultation between primary care and specialized care proved effective for continuum of care for viraemic hepatitis C patients

IntroductionIt has been proposed that primary care diagnose and treat hepatitis C virus (HCV) infection. However, a care circuit between primary and specialized care based on electronic consultation (EC) can be just as efficient in the micro-elimination of HCV. It is proposed to study characteristics and predictive factors of continuity of care in a circuit between primary and specialized care.MethodsFrom February/2018 to December/2019, all EC between primary and specialized care were evaluated and those due to HCV were identified. Variables for regression analysis and to identify predictors of completing the care cascade were recorded.ResultsFrom 8098 EC, 138 were performed by 89 (29%) general practitioners over 118 patients (median 50.8 years; 74.6% men) and were related to HCV (1.9%). Ninety-two patients (78%) were diagnosed > 6 months ago, and 26.3% met criteria for late presentation. Overall, 105 patients required assessment by the hepatologist, 82% (n = 86) presented for the appointment, of which 67.6% (n = 71) were viraemic, 98.6% of known. Finally, 61.9% (n = 65) started treatment. Late-presenting status was identified as an independent predictor to complete the care cascade (OR 1.93, CI 1.71–1.99, p < 0.001).ConclusionCommunication pathway between Primary and Specialized Care based on EC is effective in avoiding significant losses of viraemic patients. However, the referral rate is very low, high in late-stage diagnoses, heterogeneous, and low in new diagnoses. Therefore, early detection strategies for HCV infection in primary care are urgently needed.     

Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease

Background and aimsThe advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a ‘real-world’ cohort of patients with CKD.MethodsWe performed an observational single-arm multi-centre study in a large (n = 198) cohort of patients with stage 1–3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15 IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities.ResultsThe average baseline eGFR (CKD-EPI equation) was 70.06 ± 20.1 mL/min/1.72 m²; the most common genotype was HCV 1b (n = 93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n = 40), simeprevir ± daclatasvir (n = 2), and sofosbuvir-based combinations (n = 147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures – eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n = 12), which required discontinuation or dose reduction of ribavirin in some cases (n = 6); deterioration of kidney function occurred in three (1.7%).ConclusionsAll-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a ‘real–world’ clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population.     

Impact of hepatitis virus infection on arterial calcification among incident hemodialysis patients

BackgroundThe impact of hepatitis virus infection on arterial calcification (AC) was not studied.ObjectiveTo study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection.Cases and methods172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin.Results86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group.In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P < 0.001 in all).HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6 ± 0.66 vs. 5.45 ± 0.77 mg/dL, 36.4 ± 7.2 vs. 44.1 ± 8.69, and 348 ± 65.4 vs. 405.9 ± 83.2 pg/mL, P < 0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group.ConclusionHCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.     

Treatment of chronic hepatitis C in patients with chronic kidney disease with Sofosbuvir-basead regimes

BackgroundTo analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD).MethodsA retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %.ResultsThirty-five patients were treated. The mean age was 52.1 ± 10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8 ± 28.6 and 63.7 ± 28.3 ml/min pre- and post-treatment respectively (p > 0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function.ConclusionSofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.     

Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment‐naïve,noncirrhotic HCV genotype 3‐infected patients

Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed‐dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR+GZR was assessed in HCV GT3‐infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment‐naïve, noncirrhotic HCV GT3‐infected patients. Randomized patients received open‐label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV. The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy (SVR12). SVR12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR+GZR+RBV for 12 weeks or 18 weeks, respectively. On‐treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance‐associated substitutions (RASs) with a >five‐fold shift in potency occurred in the NS3 region in six (35%) patients and in the NS5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR+GZR+RBV was suboptimal in HCV GT3‐infected patients due to a high rate of on‐treatment virologic failure and treatment‐emergent RASs which demonstrates an inadequate barrier to the development of GT3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR+GZR+RBV in GT3‐infected patients.clinicaltrials.gov: NCT01717326.     

Sofosbuvir-based regimens for HCV in stage 4–stage 5 chronic kidney disease. A systematic review with meta-analysis

BackgroundHepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4–5 CKD.Study aims and designWe performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4–5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses.ResultsThirty clinical studies (n = 1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I² = 99.8%) and 0.09 (95% CI, 0.05; 0.13, I² = 84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I² = 73.3%) (P < 0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, −0.01; 0.04, I² = 16.1%). Common serious adverse events were anemia (n = 26, 38%) and reduced eGFR (n = 14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I² = 80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I² = 95.8%). Six studies (n = 69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found.ConclusionsSOF-based regimens appear safe and effective in patients with stage 4–5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.     

Patient journey of individuals tested for HCV in Spain: LiverTAI,a retrospective analysis of EHRs through natural language processing

ObjectivesLimited screening and delays in diagnosis and linkage-to-care are barriers for hepatitis C virus (HCV) elimination. The LiverTAI study focused on patients tested for HCV using AI technologies to describe their demographic and clinical characteristics and pre-testing patient journeys, reflecting clinical practice in hospitals.Patients and methodsLiverTAI is a retrospective, secondary analysis of electronic health records (EHRs) from 6 tertiary Spanish hospitals, extracting unstructured clinical data using natural language processing (NLP) EHRead® technology. Adult subjects with an HCV testing procedure from January 2014 to December 2018 were grouped according to HCV seropositivity and viremia.ResultsFrom 2,440,358 patients, 16,261 patients were tested for HCV (13,602 [83.6%] HCV seronegative; 2659 [16.4%] seropositive). Active HCV viremia appeared in 37.7% (n = 1003) of patients, 18.6% (n = 494) had negative viremia, and 43.7% (n = 1162) unknown viremia. Patient journeys showed core departments (Gastroenterology, Internal Medicine, and Infectious Disease) and others including Emergency perform ample HCV testing in Spanish hospitals, whereas Medical Oncology lags. Patients were PCR-tested and genotyped significantly faster in core departments (p < .001).ConclusionsOur results highlight hospital departments responsible for HCV testing. However, further testing was sub-optimal during the study period. Therefore, we underscore the need for HCV screening and reflex testing to accelerate diagnosis and linkage-to-care.     

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

IntroductionThere 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.Methods445 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).ResultsThe 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 172 mg/dL and 101.5 mg/dL to 191 mg/dL and 117.5 mg/dL (p < 0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7 mg/dL at baseline to 127.2 mg/dL at SVR48 (p < 0.001).DiscussionSVR 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.     

Evaluation of the liver condition in chronic hepatitis C virus patients with and without vasculitis

Aim of the workThe association between hepatitis C virus (HCV)-related vasculitis and severe hepatic fibrosis is a controversial issue. In this study, we aimed to evaluate the liver affection in a group of patients with HCV-related vasculitis and a control group with chronic HCV infection without vasculitis.Patients and methodsTwenty-six HCV associated vasculitis patients (22 females, 4 males) with a mean age of 51.9 ± 8.5 years (range 36–72 years) and a control group including 20 age- and sex matched HCV infected patients without any extra-hepatic autoimmune manifestations were recruited in this study. All patients and controls were evaluated by routine biochemical tests, conventional ultrasonography and Fibroscan.ResultsThe mean disease duration in patients with vasculitis and the control group was 7.5 ± 7.3 and 4.1 ± 3.6 years, respectively (p = 0.062). Mean aspartate aminotransferase, bilirubin and international normalized ratio (INR) values were higher in the control group (p = 0.036, 0.041 and 0.017, respectively). Hepatomegaly was found in 11 (42.3%) vasculitis patients and 17 (85%) controls (p = 0.006), while portal hypertension was found in 4 (15.4%) vasculitis patients and 9 (45%) controls (p = 0.046). On Fibroscan, eleven vasculitis patients (42.3%) had mild to moderate liver fibrosis (F1–2), and 10 (38.5%) had severe liver fibrosis (F3–4), while only one patient (5%) of the control group had mild, and 17 (85%) had severe liver fibrosis (p = 0.002).ConclusionPatients with chronic HCV infection without vasculitis have worse liver functions and more advanced liver fibrosis than those with HCV related vasculitis.     

Sofosbuvir-based antiviral therapy in patients with recurrent HCV infection after liver transplant: A real-life experience

Introduction and aimRecurrent HCV infection after liver transplant (LT) has a negative impact on graft and patient survival. The aim of this study is to describe the efficacy and safety of sofosbuvir (SOF-based) regimens in the treatment of recurrent HCV after liver transplant (LT).Materials and methodsThis retrospective study included 68 adults with recurrent HCV infection after LT, treated with different SOF-based regimens between March 2015 and December 2016. The choice of regimens, their duration and use of ribavirin (RBV) was made by the treating physician. The efficacy of antiviral treatment was assessed based on the sustained viral response obtained 12 weeks after the end of treatment (SVR12), according to an intention-to-treat analysis.ResultsThe most frequent HCV genotypes were 1 and 3 (n = 35, 51.4% and n = 31, 45.6%, respectively). Only 22 patients were treatment naïve (32.3%) and 7 had cirrhosis (10.2%). SOF + daclatasvir (DCV) was the most commonly used regimen (n = 63, 92.6%). Most patients used RBV (n = 56, 82.3%) and were treated for 12 weeks (n = 66, 97%). Overall SVR12 was 95.5% (65/68 patients). Three patients had virologic failure. Three patients had serious adverse events, however, no one discontinued treatment prematurely. RBV-related anaemia was the most frequent adverse event (n = 34, 50%). Four patients had severe cellular graft rejection after HCV elimination, while immunosuppression remained stable.ConclusionSOF-based therapy is highly effective and safe to treat HCV recurrence after LT. Cellular graft rejection following the successful treatment of HCV needs further investigation.     

Pharmacoeconomic analysis of the treatment of chronic hepatitis C with peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin in Spain

BackgroundAn independent meta-analysis of randomized comparative trials of peginterferons alfa-2a and alfa-2b, both combined with ribavirin, analyzed the probability of achieving a sustained virological response (SVR).ObjectiveTo estimate the long-term cost-effectiveness of treatment of patients with chronic hepatitis C with peginterferon alfa-2a (180 μg/week) plus ribavirin (800–1200 mg/day) vs. alfa-2b (1.5 μg/kg/week) plus ribavirin (800–1400 mg/day), from the perspective of the Spanish National Health System.MethodsA Markov model was developed with 7 health states to simulate lifetime disease progression. SVR was calculated from the meta-analysis data. Transition probabilities and health state utilities were obtained from published literature. Direct healthcare costs were obtained from the drug catalog, while costs of disease-related complications were obtained from published studies and healthcare cost database. Costs were expressed in 2010€. The annual discount rate applied was 3.5% for both costs and benefits.ResultsSVR rate for treatment with alfa-2a was higher than with alfa-2b; the differences were 6.0%, 7.6% and 8.7% for all genotypes, genotypes 1/4 and genotypes 2/3, respectively. Each patient would gain 0.469, 0.600 and 0.685 life-years and 0.155, 0.198 and 0.227 quality-adjusted life-years with alfa-2a vs. alfa-2b, for the respective genotypes. The cost saving per patient treated with alfa-2a would be €705, €672 and €1900, for all genotypes and for genotypes 1/4 and 2/3, respectively, alfa-2a being dominant.ConclusionsAccording to the present model, treatment of patients with chronic hepatitis C with peginterferon alfa-2a is cost-effective compared with peginterferon alfa-2b, both combined with ribavirin.     

Frecuencia de sustituciones relevantes asociadas a resistencia en la región NS5A a elbasvir en el virus de la hepatitis C en pacientes con genotipo 1a en España

Resistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q30H + Y93H (n = 4) and Q30R + Y93H (n = 2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients.     

HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment: The ITAL-C network study

BackgroundSustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D’Amico might provide new insights on timing for antiviral therapy.MethodsWe investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n = 575) or cirrhosis (n = 2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines.ResultsThe SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients.ConclusionOur findings support the use of DAAs in patients with advanced cirrhosis (stages 3–5) who are at greatest risk and have the most to gain from therapy.     

Influencia de la puntuación MELD basal en la eficacia del tratamiento de la hepatitis C con sofosbuvir y simeprevir

Introduction

There are few published studies on predictors of response to treatment with sofosbuvir and simeprevir in HCV patients.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

BackgroundTolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment.MethodsA multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment.Results308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis.ConclusionTreatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.     

A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients: The TT4 randomized trial

BackgroundRapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4).Method267 naïve HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n = 180) or current standard-of-care (SoC, n = 87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2 log₁₀ at week 12 or detectable HCV-RNA at week 24 discontinued treatment.ResultsBoth groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25 ± 15 vs. 36 ± 12.1 weeks], and for subgroups: G1 [35.3 ± 16.7 vs. 47.3 ± 2.6 weeks], G2 [18.3 ± 7.5 vs. 24 ± 2.8 weeks], G3 [15.2 ± 8.7 vs. 22.8 ± 3 weeks] and G4 [26.9 ± 13 vs. 48 weeks].ConclusionsIn HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction.     

Cribado de infección por virus de la hepatitis B y C en pacientes hospitalizados con infección por SARS-CoV-2

AimsTo evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients.MethodTransversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1 st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection.ResultsIn this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0–104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC + patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19).ConclusionScreening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.     

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study

IntroductionImmune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients.MethodsA multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months.ResultsTwenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225–525 ng/mL) in 14 (15.2%) patients and low (ATP < 225 ng/mL) in 78 (84.8%); no patients had a strong response (ATP ≥ 525 ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p = 0.043). Similar acute rejection rates were recorded in patients with mean ATP ≥ 225 vs. <225 ng/mL during the study period (7.1% vs. 9.1%, p = 0.81).ConclusionAlthough ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.     

Impact of sustained viral response in the evolution of minimal hepatic encephalopathy: A prospective pilot study

Introduction and aimsTo determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE.Materials and methodsWe performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment.Results64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p < 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p < 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04).ConclusionWe found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.