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Background and Objectives : Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods : We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results : We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions : Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy.

Background and Objectives : Sarcopenia is commonly associated with liver cirrhosis and predicts clinical outcome. Our aim was to identify the changes in skeletal muscle index (SMI) on computed tomography (CT) examination, as a quantitative marker of sarcopenia, in patients with HCV-related cirrhosis after direct acting antivirals (DAAs) treatment and to assess predictive factors for the evolution of SMI. Materials and Methods: This is a single center retrospective study in patients with HCV-related compensated cirrhosis who obtained sustained virological response (SVR) after DAAs. CT examinations were performed in 52 patients before and within 5-24 months after treatment. The total muscle area ( TMA ) of abdominal muscle at the level of third lumbar vertebra (L3) was measured at baseline and after SVR. The L3-SMI was calculated from TMA divided by body height squared (cm 2 /m 2 ). We assessed changes in L3-SMI after SVR according to baseline body mass index (BMI) and laboratory data. Predictive factors were assessed by linear regression model. Results: Patients with L3-SMI above the gender-specific cut-off value at baseline had higher values of serum creatinine (median 0.73) compared to patients with low L3-SMI (median 0.68, p = 0.031). After SVR, 14 patients showed increase of L3-SMI, and 38 patients had a decrease of L3-SMI. BMI in the decreased L3-SMI group was significantly lower (median 26.17) than those without decreased L3-SMI (median 28.84, p = 0.021). ALT values in the decreased L3-SMI group (median 66.5) were significantly lower than those without a decrease in L3-SMI (median 88, p = 0.045). Conclusions: Low creatinine serum level correlates with sarcopenia. SMI was partially influenced by the viral clearance. Lower BMI and ALT serum levels at baseline were predictive for no benefit in terms of muscle mass dynamics. Understanding all the mechanisms involved in sarcopenia and identifying the most vulnerable patients could ensure optimal adapted care strategies.

Background and Aims: The 12-week regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (OPrD) has shown high efficacy and tolerability in clinical trials for the treatment of chronic hepatitis C virus (HCV). The shorter 8-week regimen has been recently incorporated into clinical guidelines and on-label indications, but real-world evidence on its use is limited. Given this knowledge gap, the AMETHYST study aimed to evaluate the effectiveness of the 8- and 12-week regimens of OPrD in treatment-naive patients with HCV with mild to moderate liver fibrosis in Romanian clinical practice., Methods: This was a secondary data collection study analyzing data from a 1-year Patient Support Program in HCV in Romania. Patients received OPrD treatment for 8 or 12 weeks. The effectiveness endpoint was sustained virologic response 12 weeks post-treatment (SVR12)., Results: A total of 1,835 treatment-naive patients with HCV with mild or moderate fibrosis were included in the study. Of these, 426 and 1,375 completed the 8-week and 12-week regimens, respectively. SVR12 was 98.1% in the 8-week treatment group and 98.7% in the 12-week treatment group., Conclusion: The study provides real-world evidence that 8-week and 12-week treatment regimens of OPrD are highly effective in treatment-naive patients with HCV with mild to moderate liver fibrosis.

Background and Aims: Ledipasvir/Sofosbuvir (LDV/SOF) with or without Ribavirin (RBV) has shown good results in terms of efficacy and safety in clinical trials in advanced liver cirrhosis, but real-life data are still needed in order to confirm this profile. We investigated the efficacy and safety of LDV/SOF in a large Romanian population with liver cirrhosis and genotype 1b hepatitis C virus (HCV)., Methods: We analyzed a multicentric retrospective cohort enrolling 349 patients with decompensated liver cirrhosis due to HCV who received LDV/SOF±RBV 12/24 weeks (301/48). Patients were included between 2017-2018, all with genotype 1b. Main inclusion criteria were liver cirrhosis and detectable HCV RNA. The cases were followed-up monthly during therapy and 12 weeks after the end of therapy., Results: The cohort included 60% females with a median age of 61, 16% interferon (IFN) pre-treated, 53% with comorbidities, 40/53/7 % with Child Pugh A/B/C, 4% with virus B co-infection and 8% with previously treated hepatocellular carcinoma. Mean initial MELD score was 11.92 (6.82÷ 24.5). Six patients were lost during follow-up. Sustained virologic response (SVR) in intention-to-treat was reported in 85.1%. Predictive factors of SVR in decompensated cirrhosis were female gender (p=0.01), advanced age (p<0.001), lower bilirubin levels (p=0.002) and lower CTP score (p=0.02). In patients with CTP score B or C low bilirubin levels (p=0.003), low INR (p<0.001), increased platelet count (p=0.04), low CTP score (p<0.001), lack of encephalopathy (p=0.02), serum albumin >3.5g/dl (p=0.002) predicted improvement of liver function. Serious adverse events were reported in 16/349 (4.6%), most of them due to severe liver decompensation (9/16)., Conclusions: LDV/SOF±RBV proved to be highly efficient in our difficult to treat population with 85.1% SVR.

Introduction: Alisporivir (ALV) (previously known as Debio 025) is a potent, pangenotypic host-targeting antiviral oral agent acting on cyclophilin A, which is necessary for HCV replication. Areas covered: This article reviews the therapeutic efficacy and safety of ALV for the treatment of HCV infection. Expert opinion: Direct-acting antivirals (DAAs) have revolutionized the HCV antiviral treatment paradigm with success rates well above 95% for all HCV genotypes. However, challenges still remain in certain patient populations such as those who have developed resistance and have experienced multi-DAA failure. To cure HCV infection, a treatment regimen must combine antiviral potency and a high barrier to resistance. ALV fulfills this need as shown by the studies evaluating its clinical efficacy. Nevertheless, ALV missed the chance to be included in the HCV treatment armamentarium after the FDA halted clinical studies following reports of serious side effects (three cases of pancreatitis, one lethal). However, it is possible that ALV could still be considered for HCV-infected non-cirrhotic patients that are infected with a multiresistant virus or with HCV genotype 3, although it must be said that the drug industry would be reluctant to invest in new antivirals if the current clinical need is effectively met.

Advanced age has been a major limitation of interferon-based treatment for chronic hepatitis C virus (HCV) infection because of its poor response and tolerability. Direct-acting antiviral (DAA) drug regimens are safe and highly effective, allowing administration of treatment also in elderly. This study aims to assess the efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with ribavirin for the treatment of patients aged ≥70 years with HCV genotype 1b compensated cirrhosis.A total of 1008 patients with HCV genotype 1b compensated cirrhosis were prospectively treated with PrOD + ribavirin for 12 weeks, between December 2015 and July 2016. Sustained virologic response 12 weeks after the end of treatment (SVR12), adverse effects (AEs), comorbidities, discontinuation, and death rates were recorded. Efficacy and safety of therapy were assessed in patients aged ≥70 years and compared with data from patients <70 years.There were 117 patients aged ≥70 years, preponderantly females (58.9%), mean age 73.3 ± 2.8 years (range 70-82), and 37 (31.6%) were treatment-experienced. Comorbidities were reported in 60.6% of patients ≥70 years and in 39.8% of those <70 years (P < .001). SVR12 rates based on intention-to-treat and per-protocol analyses were 97.4% and 100%, respectively, in patients ≥70 years, compared to 97.8% and 99.6%, respectively, in patients <70 years (P = ns and P = ns). Severe AEs were reported in 4 (3.4%) patients ≥70 years, compared to 23 (2.6%) in those <70 years (P = ns). One death was recorded in a patient aged 79 years (0.9%) and 6 deaths (0.8%) in those <70 years (P = ns).Treatment with PrOD + ribavirin in patients 70 years of age or older with HCV genotype 1b compensated cirrhosis proved as effective, safe, and well tolerated, as it did in younger patients., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Ombitasvir/Paritaprevir/ritonavir/Dasabuvir (OBV/PTV/r+DSV) is one of the elective direct-acting antivirals (DAAs) recommended by international guidelines and the only one covered by the National Insurance System in Romania until November 2016. Our aim was to present the first prospective Romanian cohort evaluating the effectiveness and safety in clinical practice of this 3DAA combination in patients with HCV genotype-1b Child A liver cirrhosis., Methods: 681 patients received OBV/PTV/r+DSV+RBV for 12 weeks and were assessed clinically and biologically at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained viral response, SVR)., Results: Per protocol, EOT virological response was 99.8% and SVR12 rate was 99.4%. Adverse events were present in 36.4% of patients. Permanent discontinuation of 3DAA regimen due to side effects was reported in 11 patients (1.6%). In 47.6% (185/389) of patients, Transient Elastography values were >20kPa (defined as clinically significant portal hypertension, CSPH) at baseline. Independent variables associated with CSPH were: baseline cholesterol level (p=0.003), platelet count <120,000/mm³ (p=0.02), MELD score (p=0.01). Liver stiffness measurement has significantly improved between baseline (26.6+/-12.7kPa) and SVR12 (21.6+/-11.8kPa) (p<0.0001). The same was true for APRI score (2.66+/-0.15 at baseline vs 0.85+/-0.02 at SVR12, p<0.0001) and FIB4 score (5.53+/-0.28 vs 3.24+/-0.08, p<0.0001), but not for Lok score (0.57+/-0.01 vs 0.63+/-0.01, p<0.0001)., Conclusions: We report a high efficacy of the 3DAA regimen in a homogeneous compensated HCV genotype-1b liver cirrhosis population, in a real-life setting. Noninvasive fibrosis scores significantly improved at SVR12.

Background and Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country., Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus., Recommendations: We present here the second part of the Society's recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure., Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania.

Background and Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country., Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus., Recommendations: We present here the first of the two parts of our Society's recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules., Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.

Background: We did a phase 3 study in previous non-responders with chronic hepatitis C virus (HCV) genotype 1 infection and compensated liver disease that related to the standard of care for these patients at the time this study was initiated. We investigated whether simeprevir is non-inferior in terms of efficacy to telaprevir, each in combination with peginterferon alfa-2a and ribavirin., Methods: We did this randomised, double-blind, phase 3 trial at 169 investigational sites in 24 countries. We enrolled adults (≥18 years) with chronic HCV genotype 1 infection, compensated liver disease, and plasma HCV RNA higher than 10 000 IU/mL who were null or partial responders during at least one previous course of peginterferon alfa-2a and ribavirin treatment. We randomly assigned (1:1) patients (stratified by HCV genotype 1 subtype [1a plus other/1b] and previous treatment response [partial or null]) to receive simeprevir (150 mg once a day) plus telaprevir placebo (three times a day 7-9 h apart) or telaprevir (750 mg three times a day) plus simeprevir placebo (once a day) in combination with peginterferon alfa-2a and ribavirin for 12 weeks followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. The primary efficacy endpoint was sustained virological response 12 weeks after end of treatment (SVR12) in the intention-to-treat and the per-protocol population. We compared groups with the Cochran-Mantel-Haenszel test. We established a non-inferiority margin of 12%. Adverse events were reported descriptively. This trial is registered with ClinicalTrials.gov, number NCT01485991., Findings: Patient screening began on Jan 19, 2012, and the last visit was on April 7, 2014. We included 763 patients (472 previous null responders [62%]). Simeprevir and peginterferon alfa-2a and ribavirin was non-inferior to telaprevir and peginterferon alfa-2a and ribavirin for SVR12 (54% [203/379] vs 55% [210/384]; difference -1·1%, 95% CI -7·8 to 5·5; p=0·0007). SVR12 was achieved in 70% (101/145) versus 68% (100/146) of previous partial responders and 44% (102/234) versus 46% (110/238) of previous null responders with simeprevir and peginterferon alfa-2a and ribavirin and telaprevir and peginterferon alfa-2a and ribavirin treatment, respectively. We recorded differences between treatment groups in simeprevir or telaprevir-related adverse events (69% [261/379] in the simeprevir group vs 86% [330/384] in the telaprevir group), serious adverse events (2% [8/379] vs 9% [33/384]), and adverse events leading to simeprevir or telaprevir discontinuation (2% [7/379] vs 8% [32/384])., Interpretation: Simeprevir once a day with peginterferon alfa-2a and ribavirin was well tolerated in HCV genotype 1-infected previous non-responders and was non-inferior to telaprevir, thus providing an alternative treatment in areas of the world where all-oral HCV regimens are not available or accessible., Funding: Janssen., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background & Aims: TG4040 is a modified vaccinia Ankara (MVA) virus that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase II open-label study to determine the efficacy, safety, and immunotherapeutic properties of TG4040 in combination with pegylated interferon α-2a and ribavirin (PEG-IFNα/RBV) in patients with chronic HCV infection., Methods: Treatment-naive patients with HCV genotype 1 infection were assigned randomly to 1 of the following groups: PEG-IFNα/RBV for 48 weeks (group A, n = 31), PEG-IFNα/RBV for 4 weeks followed by PEG-IFNα/RBV for 44 weeks with 6 injections of TG4040 (group B, n = 63), or TG4040 for 12 weeks (7 injections) followed by PEG-IFNα/RBV for 48 weeks with 6 injections of TG4040 (group C, n = 59). The primary end point was complete early virologic response (cEVR), defined as HCV-RNA level less than 10 IU/mL after 12 weeks of PEG-IFNα/RBV treatment., Results: In group C, 64.2% of evaluable patients achieved cEVR, compared with 30.0% in group A and 45.9% in group B (P = .0003 for group C vs A). A higher percentage of patients achieved a sustained virologic response 24 weeks after therapy ended in group C (58.2%) than in groups A (48.4%) or B (50.8%). HCV- and MVA-specific T-cell responses were observed predominantly in group C. As expected, most patients given injections of TG4040 developed anti-MVA antibodies. The combination of TG4040 and PEG-IFNα/RBV was reasonably well tolerated. However, PEG-IFNα-associated thrombocytopenia developed in 3 patients who carried the class II HLA allele DRB01*04., Conclusions: A higher percentage of patients with chronic HCV infection who received immunotherapy with TG4040 followed by TG4040 and PEG-IFNα/RBV achieved a cEVR compared with patients who received only PEG-IFNα/RBV therapy. These findings show that immunotherapies that activate T cells are effective in patients with chronic HCV infection. ClinicalTrials.gov number, NCT01055821., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus (HCV) cohort., Methods: Patients with chronic HCV were randomized to receive interferon-based therapy for 24 (genotypes 2/3) or 48 (genotype 1) wk. FibroSURE™ (FS) was assessed at baseline and at week-12 post-treatment follow-up. Baseline biopsy for METAVIR was assessed by a single pathologist. FibroScan(®) transient elastography (TE) was performed during treatment in a patient subset., Results: Two thousand and sixty patients (n = 253 in Asia) were classified as METAVIR F0-1 (n = 1682) or F2-4 (n = 378). For F2-4, FS (n = 2055) had sensitivity and specificity of 0.87 and 0.61, respectively, with area under the receiver-operating curve of 0.82; corresponding values for TE (n = 214) and combined FS/TE (n = 209) were 0.77, 0.88 and 0.88, and 0.93, 0.68 and 0.88. Overall FS/TE agreement for F2-4 was 71% (κ = 0.41) and higher in Asians vs non-Asians (κ = 0.86 vs 0.35; P < 0.001). Combined FS/TE had 97% accuracy in Asians (n = 33). Baseline FS (0.38 vs 0.51, P < 0.001) and TE (8.0 kPa vs 11.9 kPa, P = 0.006) scores were lower in patients with sustained virological response than in nonresponders, and were maintained through follow-up., Conclusion: FS and TE may reliably differentiate mild from moderate-advanced disease, with a potential for high diagnostic accuracy in Asians with chronic HCV.

Aim: The study was designed to evaluate the efficacy and safety of peginterferon alpha-2a in HBeAg-positive chronic hepatitis B patients, nonresponders or relapsers after previous lamivudine or standard interferon therapy., Methods: This prospective, national, multicentric, open label, not randomized trial enrolled 43 HBeAg-positive chronic hepatitis B patients with detectable HBsAg for at least 6 months prior to screening, positive HBeAg and negative anti-HBe, serum HBV DNA levels of at least 500,000 copies/mL by PCR assay, elevated ALT up to 10 x ULN, no response or relapse after previous lamivudine or standard interferon therapy. All eligible patients received pegIFN alpha-2a 180 micrograms weekly for 48 weeks with 24 weeks treatment free follow-up. There were two main efficacy assessments: HBeAg seroconversion and viral supression below 100,000 copies/mL., Results: HBeAg seroconversion rate at the end-of-treatment was 4.65% (n=2; p less than 0.05) increasing to 11.62% 24 weeks after end of therapy (n=5; p less than 0.05). The rate of viral supression at levels below 100,000 copies/mL was 23.25% (n=10; p less than 0.05) at end-of-treatment, and 16.3% (n=7; p less than 0.05) at end of follow-up. ALT normalization was obtained in 20.9% (p less than 0.05) of patients at end-of-treatment, the percentage being significantly higher - 37.2% (p less than 0.05) at the end of follow-up., Conclusions: Even in a difficult-to-treat patient population with HBeAg-positive chronic hepatitis B, peginterferon alpha 2a proved to be efficient in a defined proportion of patients. The increase in HBeAg seroconversion rate from end-of-treatment (4.65%) to the end of follow-up period (11.62%) also proves the benefits of prolonged immunological effect of pegIFN alpha 2a.

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]

Objectives: The current study aimed at evaluating the association between metabolic syndrome (MeS) in patients with hepatitis C virus (HCV) liver cirrhosis (compensated, genotype, 1b) and changes after sustained viral response (SVR) following a 12-week therapy with paritaprevir, ritonavir, ombitasvir, dasabuvir, and ribavirin (PrOD+R). Methods: The current multicenter retrospective study included 809 patients diagnosed with compensated HCV cirrhosis (child class A), all 1b genotype treated for 12 weeks with direct acting antiviral agents - PrOD+R - regimen (according to the protocol practiced in Romania) and achieved SVR. The parameters of MeS (according to the definition of the International Diabetes Federation) were collected from medical records before and 12 weeks after the treatment. The results were collected in a central database and analyzed with SPSS 18.0. Statistical analysis used both descriptive and analytical methods with a significance level of 95% (CI 95%). Results: Out of the 809 patients, 105 (13%) demonstrated 3 out of the 5 criteria for MeS. Based on the MeS criteria, the commonest parameters were abnormal glycaemia (54.1%), followed by visceral obesity (38.6%), raised triglycerides (26.1%), high blood pressure (12.1%), and a low high-density lipoprotein (HDL)-cholesterol (4.6%). The re-assessment of MeS parameters after SVR showed favourable changes, which were statistically significant: a siginficanttly lower serum triglyeride level (182.32 vs. 153.50 mg/dL, P = 0.001), lower systolic arterial blood pressure (130.57 vs. 124.85 mmHg; P = 0.001), lower diastolic arterial blood pressure (80.26 vs. 78.42 mmHg; P = 0.001) and lower glyceamic levels (130.06 vs. 120.71 mg/dL; P = 0.001), as well as a significant rise in HDL-cholesterol levels (48.61 vs. 50.50 mg/dL; P = 0.003). Abdominal circumference was the only parameter, which did not change after SVR. Following the changes sustained after SVR, 26.7% of the patients no longer fulfilled the minimum 3 criteria for MeS. No correlation was observed between the presence of MeS and the risk of severe adverse events, but it was noted that 37.5% of the patients who decompensated, 66.7% of the ones who developed hepatocarcinoma and 100% of the ones that died of abnormal glycaemic levels. Conclusions: Hyperglycemia, and not MeS, is associated with HCV compensated liver cirrhosis genotype 1b, and is a risk factor for severe adverse events. The attainment of SVR through PrOD+R regimen results in short-term improvements in MeS parameters. [ABSTRACT FROM AUTHOR]