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Introduction: Recent research points to a link between chronic hepatitis C virus (HCV) infection and cardiovascular disease, especially carotid atherosclerosis, and suggests that HCV clearance may impact cardiovascular outcomes., Aim: To determine if viral eradication by the new oral direct-acting antiviral (DAA) agents has benefit regarding carotid atherosclerosis, peripheral artery disease (PAD), steatosis, and liver fibrosis., Patients, Materials and Methods: We conducted a prospective study on 168 patients diagnosed with chronic HCV infection or HCV-related cirrhosis. They were all treated with DAAs, with sustained virological response (SVR). Laboratory data, vibration-controlled transient elastography (VCTE), carotid intima-media thickness (IMT) measurement, and ankle-brachial index (ABI) were recorded in all patients., Results: We found an average IMT of 1.22±0.2 mm, with a variance range from 1.14±0.19 mm in the mild and moderate fibrosis (≤F2) group to 1.29±0.25 mm in the severe fibrosis (≥F3) group. Also, patients with severe fibrosis (≥F3) present a more critical decrease of IMT values, with the carotid thickness affecting only 18.2% of individuals in the follow-up period. At the baseline, the best values of ABI were recorded in patients having F1-F2 fibrosis stage (mean value 1.02±0.19). Instead, in the group with severe fibrosis, the average value of ABI was lower (0.91±0.16) at the baseline, with a significant increase at SVR evaluation (p<0.001)., Conclusions: Our research highlights the beneficial effect of viral eradication on both carotid atherosclerosis and PAD, especially in those with advanced fibrosis and cirrhosis.

Introduction : The development of direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection has completely transformed the management of this disease. The advantages of using DAA therapies include high efficacy (sustained virological response (SVR) rate >95%) with minimal side effects, good tolerability, easy drug administration (once daily oral dosing), and short duration of treatment (8-12 weeks). This transformative nature of DAA therapy underpins the goal of the World Health Organization to eliminate HCV infection as a public health threat by 2030. Areas covered : This review seeks to address the current status of DAA therapies, including recent developments, current limitations, and future challenges. Expert opinion : The current DAA regimens, with their high effectiveness and safety profiles, have changed patient perception of HCV infection from a disease that requires complex evaluation and long-term monitoring to a disease that can be cured after one visit to the general practitioner. Despite the remarkably high success rate of DAAs, few patients (4-5%) fail to obtain SVR even after treatment. Five years ahead, the landscape of HCV treatment will undoubtedly continue to evolve, and more pan-genotypic treatment options will be available to all patients.

Background and Aims: Elimination of hepatitis C worldwide is more feasible if micro-elimination screening strategies are adopted. We aimed to screen hepatitis C virus (HCV) in specific high-risk populations in certain sub-regions of Romania and link them to antiviral treatment., Methods: A multicenter prospective study was conducted among the hospitalized or ambulatory adult patients from March 2019 to March 2020 in more than 20 medical institutions from 4 Romanian cities (Bucharest, Iasi, Timisoara, Cluj-Napoca). A rapid diagnostic test for HCV diagnosis was performed to all admitted patients and the positive ones were sent to gastroenterology departments for confirming the active infection, staging and treatment prescription., Results: In total, 25,141 subjects signed the informed consent and were consequently enrolled into the study. The prevalence of anti-HCV antibodies was 1.39% (95%CI: 1.25-1.54) and increased with the number of risk factors presented by one subject. There was a positive association between the presence of anti-HCV antibodies and female gender (p<0.001), rural area of residence (p<0.001), advanced age (p<0.001), as well as a negative association with the education level (p<0.001)., Conclusions: In a hospital-based screening micro-elimination program in Romania, HCV prevalence was lower than previously reported. This is a first step towards a cost-effective screening in a well-defined group of persons at risk and provides sufficient capacity to deliver access to HCV treatment and linkage to care in Romania.

Direct acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, achieving high rates (≥ 95%) of sustained virological response, with a good safety profile and high compliance rates. Consequently, it had been expected that viral clearance will reduce morbidity and mortality rates, as well as the risk of hepatocellular carcinoma (HCC). However, since 2016, concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy, which led to an avalanche of studies with contradictory results. We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aims: The purpose of this study was to assess the changes in hepatic morphology evaluated by computed tomography (CT) examination in patients with hepatitis C virus (HCV)-related compensated cirrhosis who achieved sustained virologic response (SVR) after direct-acting antivirals (DAAs) treatment. Methods: CT examination was performed in 56 patients with HCV-related compensated cirrhosis before and within 6-18 months after the treatment with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir. The liver CT changes were assessed by measuring liver volume, caudate-right lobe ratio (C/RL), hepatic vessels diameters, periportal widening space, and right posterior notch. Portal trunk, splenic and superior mesenteric vein diameters, as well as spleen volume were assessed as part of portal hypertension. Results: Right hepatic vein diameter was significantly wider after treatment (median: 8.12 mm; IQR: 4.20) than before treatment (median: 6.36 mm; IQR: 3.94) z = -3.894; p < 0.001. The liver volume was significantly higher prior to the treatment (median: 1786.77 mm 3 ; IQR: 879.23) than after treatment (median: 1716.44 mm 3 ; IQR: 840.50), z = -1.970; p = 0.049. Splenic volume was considerably higher before treatment (median: 564.79 mm 3 ; IQR: 342.54) than after (median: 474.45 mm 3 ; IQR: 330.00), z = -2.500; p = 0.012. The other parameters, such as C/RL, periportal space widening, and right hepatic notch showed no significant changes. Conclusions: SVR in patients with HCV-related compensated cirrhosis treated with DAAs is associated with some improvements of hepatic morphology detectable by CT, the most constant being the increase of right hepatic vein diameter.

Chronic hepatitis C infection is a systemic disease that affects over 71 million patients all over the world and it is to be considered nowadays as a new cardiometabolic risk factor. This study aimed to evaluate the weight and metabolic changes after viral eradication in patients with hepatitis C virus (HCV) infection. We conducted a prospective study between October 2017 to December 2021, in a tertiary care center, in which we included 132 patients with HCV or cirrhosis. All patients received treatment with direct antivirals (DAAs) and achieved sustained viral response at 12 weeks (SVR12). During the study, clinical laboratory data and Fibroscan examinations were recorded in all patients. The study group was evaluated at the initiation of antiviral treatment, at SVR12, and within an average follow-up period of 6 months to 12 months after the previous evaluation. Evaluation at SVR12 and the data recorded in the post-SVR surveillance period show a further increase in BMI compared with baseline measurements with a statistically significant difference (27.11 ± 3.22 vs. 27.415 ± 3.03 vs. 28.04 ± 1.11 kg/m2, p = 0.012). The same observation was noticed for waist circumference (WC) at post-SVR evaluation (87.6 ± 13.1 vs. 88.4 ± 13.6 cm, p = 0.031). Moreover, the study population registered an increase in the average total cholesterol (TC) values at post-SVR evaluation (177.01 ± 42.2 mg/dL, p = 0.014) compared to baseline. In addition, the serum level of triglycerides had been modified after viral clearance, with a minimal decrease in the mean values of triglycerides (TGD) at SVR-12 assessment (133.48 ± 41.8 mg/dL, p = 0.78), followed by a significant increase to the mean value of 145.4 ± 47.2 mg/dL (p = 0.026) in the third evaluation. Our study highlights that HCV eradication does not improve the lipid profile in the short term, and these patients still have an additional cardiovascular risk factor due to high levels of TC, TGD, and weight gain. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection induces hepatic steatosis due to viral and host factors. However, information regarding the effects of direct-acting antivirals (DAAs) therapy on liver steatosis and fibrosis is limited. Vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) represents a non-invasive method, which has been used in the last few years for the detection of hepatic steatosis and fibrosis before and at a sustained virological response at 12 weeks (SVR12). The aim of this study was to assess the modifications of liver steatosis and fibrosis in HCV-infected patients who achieved SVR12. Consecutive patients with chronic HCV infection that were treated with DAAs in a tertiary gastroenterology center from Romania were included. Demographics, laboratory data, and VCTE evaluation were recorded in all patients. Patients with previous hepatic decompensation and those who did not achieve SVR were excluded. Two hundred and eighty patients (67.1% females) who achieved SVR12 were included. Regarding the changes in biological parameters, including liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced to normal levels at SVR12 compared to the baseline (28.72 ± 24.71 U/L vs. 40.72 ± 27.34 U/L for ALT, p < 0.013 and 27.21 ± 11.15 U/L vs. 33.35 ± 23.37 U/L for AST, p = 0.029). On the contrary, the levels of triglycerides increased significantly from the baseline to SVR12 (124.03 ± 113.49 mg/dL to 153.78 ± 94.53, p = 0.004). Regarding hepatic steatosis by CAP evaluation, at SVR12, 186 (66.4%) of the individuals had a CAP score of ≥248 dB/m, an increase of 4.6% from the baseline. After viral eradication with DAAs, we observed an increase in hepatic steatosis. Hence, a long-term follow-up is mandatory to identify HCV-infected patients with hepatic steatosis post-SVR and the risk factors for more severe outcomes. [ABSTRACT FROM AUTHOR]

Background: Considering the excellent safety profile and the high efficacy rates, great benefits were expected with the availability of the new direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV) infection. Following the publication of two articles in 2016 on the high incidence rates of HCC following DAAs, several papers revealed contradictory results, thereby casting shadows on the role of DAAs in hepatocarcinogenesis. Objectives: The present study aimed to assess the incidence and risk factors of HCC in patients with HCV genotype 1b infection and compensated cirrhosis with the sustained virological response (SVR) following DAAs. Methods: This multicentric prospective study encompassed 479 patients with HCV genotype 1b compensated cirrhosis treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) +/- ribavirin (RBV) for 12 weeks in two tertiary centers in Northeastern Romania. The patients were prospectively followed up in the Institute of Gastroenterology Iasi, Romania, from November 2015 to December 2020. Results: During the follow-up period (mean 60.11-3.87 months), 23 patients (4.8%) developed HCC. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 1.1, 1.9, and 2.6%, respectively. At the time of the diagnosis, 15 patients (65%)had a single tumor, 12 patients (52.2%)were within the Milan criteria, and nine persons (39%) had Barcelona liver cancer stage 0-A. In this regard, the mean AFP level was 35.3-93.1 ng/mL. A multivariate analysis, age above 65 years, and a cutoff point of AFP≥ 10 ng/mL at the end of treatment were independent factors associated with HCC. A majority of the patients (n = 11, 47.8%) received curative treatment by surgical resection. In this study, histopathological examination identified a moderately differentiated tumor (G2) in 5 patients, five patients had a poorly differentiated tumor (G3), and only one patient had a well-differentiated tumor (G1). Conclusions: Our study revealed no evidence of the high incidence rate of HCC after the long-term follow-up of patients with HCV-related liver cirrhosis and SVR following DAA treatment. However, the cumulative 5-year risk remained above the cutoff point, and this makes the HCC screening cost-effective. The HCC occurrence appears to be associated with aging and a moderately increased AFP level at EOT (≥ 10 ng/mL). [ABSTRACT FROM AUTHOR]

Introduction. Despite the high efficacy of direct acting antivirals (DAAs) in curing chronic HCV infection, there is a concern regarding a more aggressive phenotype of hepatocellular carcinoma (HCC) after DAA treatment. Although there are many clinical cohort studies that have evaluated the incidence and recurrence of HCC in these patients, data on the tumor characteristics of HCC after DAAs are not sufficient to establish a clear conclusion. A promising index was recently developed for the evaluation of HCC aggressiveness (AGI) which comprises 4 tumor-related parameters: maximum tumor diameter (MTD), number of tumor nodules, portal vein thrombosis (PVT) and serum AFP levels. Aim. We aimed to investigate the usefulness of AGI in assessing the pattern of HCV-related HCC after DAAs and the predictive value in survival. Material&methods. We carried out a retrospective comparative observational study in which we included patients treated with DAAs for HCV infection and diagnosed with HCC in the Institute of Gastroenterology and Hepatology from Iași, Romania, between January 1st, 2017 and December 31, 2019. Patients were matched based on age and sex with a historic cohort consisting of patients with HCV-related HCC without DAA therapy. Based on AGI, patients were divided into three aggressiveness classes: class A (low aggressiveness), B (intermediate aggressiveness) and C (high aggressiveness). Results. Among the 124 patients with chronic HCV infection diagnosed with HCC, 66 (53.2%) patients were males and 58 (46.8%) were female, with a mean age of 62.38 ± 9.88 years. According to DAAtreated and DAA-naive status, patients were divided into 2 groups: the DAA group included 30 treated patients and the non-DAA group included 94 DAAnaive patients. In the DAA group, the frequency of single HCC was much higher (73.3%) than in naïve patients (53.2%) (p = 0.052), as well as smaller tumor sizes (41.07 ± 18.116mm vs. 61.79 ± 34.477mm, p=0.001) and lower rates of malignant PVT (20% vs. 36%, p = 0.146). According to AGI, class B was the most frequently observed (42.6%) in DAA-naïve patients, followed by class A (31.9%) and class C (25.5%), whilst in DAA-treated patients the most frequent was class A (46.7%), closely followed by class B (40.0%), and class C in 13.3% of cases. The 3-year survival probability for AGI class A vs. B vs. C was 66.9% vs 40.2% vs 8.4%; p=0.001, from the time of diagnosis by Kaplan-Meier plot. There was a significantly higher survival rate in the DAA group compared to DAA-naïve patients (75.3% vs. 52.4%, p = 0.008). [ABSTRACT FROM AUTHOR]