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Aims: We aimed to compare the diagnostic performance of two 2D-Shear Wave Elastography (2D-SWE) techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection using Transient Elas-tography (TE) as reference., Material and Methods: We enrolled 208 consecutive patients with chronic HCV infection, in which liver stiffness (LS) was evaluated in the same session using two 2D-SWE techniques: 2D-SWE.GE and 2D-SWE.SSI using TE as the method of reference. LS measurements were considered failures when no value was obtained after 10 attempts., Results: Valid LSMs were obtained in 95.6% (199/208) of cases by 2D-SWE.GE, 92.7% (193/208) of cases by 2D-SWE.SSI, and in 94.7% (197/208) of cases by TE (p>0.05). The mean LS values by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI: 10.3±3.8 kPa vs. 15±10.4 kPa (p<0.0001). 2D-SWE.GE LSMs correlated better with TE than 2D-SWE.SSI (r=0.75, p<0.0001 vs. r=0.57, p<0.0001, z test p=0.0012). Linear regression analysis showed a moderate correlation between LSMs obtained by 2D-SWE.GE and 2D-SWE.SSI (r=0.63, R2=0.4, P<0.0001). Pairwise comparison of receiver operating characteristics curves (ROC) found no significant differences between 2D-SWE.GE and 2D-SWE.SSI in identifying F≥2 fibrosis (0.97 vs. 0.96, P = 0.5650), F≥3 (0.97 vs. 0.95, P = 0.2935), or F=4 (0.97 vs. 0.96, p = 0.6914)., Conclusions: Both 2D-SWE techniques had good feasibility for the noninvasive assessment of liver fibrosis. LS values obtained by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI. No significant differences were found between both methods in staging liver fibrosis in patients with chronic HCV.

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.

The study compared the diagnostic performance of two shear-wave elastography techniques, elastography point quantification (ElastPQ) and 2-D shear-wave elastography by General Electric (2-D-SWE.GE), for the non-invasive assessment of liver fibrosis in a cohort of patients with chronic hepatitis C virus (HCV) infection, using transient elastography (TE) as the reference method. There was no significant difference between the feasibility rates of TE, ElastPQ and 2-D-SWE.GE (p = 0.507). A good correlation was found between the liver stiffness (LS) values obtained using the two elastographic methods (r = 0.78). The mean LS values obtained using the ElastPQ technique were significantly higher than those obtained using 2-D-SWE.GE (12.1 ± 7.3 kPa vs. 10.4 ± 4.0 kPa, p < 0.0001). Pairwise comparisons of receiver operator characteristics curves between 2-D-SWE.GE and ElastPQ have shown that there are no significant differences in their performance for staging F ≥ 2 fibrosis (p = 0.89), F ≥ 3 fibrosis (p = 0.76) and F = 4 fibrosis (p = 0.86) in patients with chronic HCV infection., Competing Interests: Conflict of interest disclosure The authors declare no competing interests., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Aims: Our aim was to assess the diagnostic performance of transient elastography (TE) and Virtual Touch Quantification (VTQ), a point Shear Wave Elastography (pSWE) technique, using Acoustic Radiation Force Impulse (ARFI) technology, for liver fibrosis assessment, as compared to percutaneous liver biopsy (LB), in patients with chronic hepatitis B or C., Methods: We analyzed 157 patients (80 with chronic hepatitis B and 77 with chronic hepatitis C) with reliable liver stiffness (LS) measurements, in whom we compared TE and VTQ to the LB performed during the same session (evaluated according to the Metavir scoring system: F0-F4). LS was assessed by TE (FibroScan, EchoSens, Paris, France) and VTQ using the Siemens Acuson S2000TM ultrasound system (Siemens AG, Erlangen, Germany). We defined reliable LS measurements as the median value of 10 measurements with an IQR/M <30% for both TE (obtained using the M probe) and VTQ. The areas under receiver operating characteristic curves (AUROCs) were used to assess the diagnostic performance of TE and VTQ. Correlation analysis determined the relationship between LSM values and liver histology., Results: On LB 31 (19.7%) patients had no fibrosis, 35 (22.3%) had F1, 43 (27.4%) had F2, 28 (17.8%) had F3 and 20 (12.7%) had cirrhosis. The mean size of the liver specimen in LB was 27 mm. A strong, linear correlation (Spearman ρ=0.826; p<0.001) with 95% confidence interval for rho (0.769- 0.870), was found between the TE and VTQ measurements. By comparing the AUROC curves, TE and VTQ had similar predictive values for the presence of F≥1 Metavir: AUROC TE=0.876, AUROC VTQ=0.832, p=0.358, for F≥2 Metavir: AUROC TE=0.826, AUROC VTQ=0.862, p=0.313, for F≥3 Metavir: AUROC TE=0.907, AUROC VTQ=0.880, p=0.434 and for F=4 Metavir: AUROC TE=0.981, AUROC VTQ=0.974, p= 0.423., Conclusions: Both methods, TE and VTQ (pSWE) offer excellent diagnostic accuracy for liver fibrosis assessment in patients with chronic hepatitis B or C with similar performance.

Hepatitis B virus may reactivate in patients with chronic hepatitis C treated with direct-acting antivirals. The aim of this study was to investigate the risk of hepatitis B virus (HBV) reactivation in HBV + hepatitis C virus (HCV)-co-infected patients with compensated liver cirrhosis treated with paritaprevir/ombitasvir/ritonavir, dasabuvir with ribavirin. We reviewed prospectively gathered data from a national cohort of 2070 hepatitis C virus patients with compensated liver cirrhosis who received reimbursed paritaprevir/ombitasvir/r, dasabuvir with ribavirin for 12 weeks from the Romanian National Health Agency during 2015-2016. Twenty-five patients in this cohort were HBs antigen positive (1.2%); 15 untreated with nucleotide analogues agreed to enter the study. These patients were followed up: ALT monthly, serology for HBV and DNA viral load at baseline, EOT and SVR at 12 weeks. Hepatitis B virus (HBV)-co-infected patients were all genotype 1b and 52% females, with a median age of 60 years (51 ÷ 74); 76% were pretreated with peginterferon + ribavirin; 72% were with severe necroinflammatory activity on FibroMax assessment; 40% presented comorbidities; and all were HBe antigen negative. Hepatitis C virus (HCV) SVR response rate was 100%. Hepatitis B virus (HBV)-DNA viral load was undetectable in 7/15 (47%) before therapy, and for the other 8 patients, it varied between below 20 and 867 IU/mL. Five patients (33%) presented virological reactivation (>2 log increase in HBV-DNA levels) during therapy. One patient presented with hepatitis associated with HBV reactivation, and two started anti-HBV therapy with entecavir. Hepatitis B virus (HBV) virological reactivation was present in 33% in our patients. Generally, HBV-DNA elevations were mild (<20 000 IU/mL); however, we report one case of hepatitis associated with HBV reactivation., (© 2018 John Wiley & Sons Ltd.)

Background: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile., Material and Methods: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12)., Results: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 10 5 /mm 3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03)., Conclusions: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients., Conclusion: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272)., (© 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

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: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania., Methods: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address., Results: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanta (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramures (8.8/105) (p<0.001)., Conclusions: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta.

Background and Aims: Liver stiffness (LS) measurement by Transient Elastography (TE) has been widely accepted as a tool for fibrosis assessment. The aim of this study was to assess LS dynamics in a group of patients with HCV liver cirrhosis after interferon free treatment (IFT)., Methods: This two-center clinical trial included 225 patients with compensated HCV cirrhosis (all genotype 1b), who received IFT for 12 weeks. All patients were evaluated by means of TE at the beginning and at the end of treatment (EOT), and a subgroup (170 patients) also 12 weeks after EOT; all of them had sustained viral response (SVR). Reliable LS measurements (LSM) were defined as a median value of 10 valid LSM, with IQR <30% and SR >/=60%. Both M and XL probes were used. For diagnosing cirrhosis we used a cut-off value of 12kPa as proposed by the Tsochatzis meta-analysis. We considered a decrease or increase of more than 10% in LSM as being significant., Results: Out of 225 subjects, reliable measurements were obtained in 93.7%, so that the final analysis included 211 patients. The mean LS values decreased significantly after IFT: 26.4+/-11.7 vs. 23.5+/-13.3 kPa (p=0.01). Most patients, 59.2% (125/211) presented more than 10% decrease in LS values, 24.1% (51/211) had stable LS values, while in 16.4% (35/211) cases, the LS values increased. In the subgroup of 170 patients with LSM also performed 12 weeks after EOT (SVR), the mean LS values were significantly lower as compared to baseline: 21.3+/-11 kPa vs. 27.4+/-11.9 kPa (p<0.0001) and also as compared to EOT: 21.3+/-11 kPa vs. 23.7+/-13.3 kPa (p<0.0001)., Conclusion: In our patients with HCV liver cirrhosis, the mean LS values evaluated by TE significantly decreased after antiviral treatment at EOT and also 12 weeks after EOT as compared to baseline. Overall, about 60% of patients had LS values at EOT lower than at baseline, while 12 weeks after EOT about 75% of patients had LS values lower than at baseline.

The aim of this study was to evaluate the diagnostic performance of a point shear wave elastography using ARFI technique - ElastPQ, in patients with B and C chronic hepatopathies, using Transient Elastography (TE) as the reference method, since it is a validated method for liver fibrosis assessment., Subjects and Methods: the study included 228 consecutive subjects with chronic hepatopathies (26% HBV, 74% HCV) from whom 51% had liver cirrhosis. Liver stiffness (LS) was evaluated in the same session by means of 2 elastographic methods: TE (FibroScan, EchoSens) and ElastPQ (Affinity, Philips) techniques. For TE 10 valid LS measurements were performed for each patient and the median value was calculated. Reliable LS measurements by TE (M or XL probe) were considered the median value of 10LS measurements with a success rate ≥60% and an interquartile range <30%. For ElastPQ we calculated the median value of 10LS measurements in the liver parenchyma, at least 1cm below the capsule, avoiding large vessels. For differentiating between stages of liver fibrosis we used the TE cut-off values published in the Tsochatzis meta-analysis: significant fibrosis (F≥2)- 7.0kPa, severe fibrosis (F≥3)- 9.5kPa and for liver cirrhosis (F=4)-12kPa (Tsochatzis et al., 2011). The areas under the receiver operating characteristic curve (AUROCs) were used to assess the diagnostic performance of ElastPQ, correlations between ElastPQ and TE were evaluated., Results: Valid LS measurements were obtained in 90.7% (207/228) cases by means of TE and in 98.7% (225/228) cases with ElastPQ. In the final analysis 205 patients were included. The ElastPQ values ranged from 2.32 to 44.07kPa (median=10.42kPa). Based on TE cut-off values (Tsochatzis et al., 2011) we divided our cohort into 4 groups: F0-F1:61/205 (29.8%); F2: 14/205 (6.8%); F3: 15/205 (7.3%); F=4: 115/205 (56.1%). The best cut-off values for discriminating, significant, severe fibrosis and cirrhosis were 7.2, 8.5 and 8.9kPa, respectively. The AUROCs were calculated considering TE as the reference method: 0.94 for significant fibrosis (F≥2), 0.97 for severe fibrosis (F≥3) and 0.97 for cirrhosis (F=4). In our cohort there was a strong correlation between measurements obtained by Transient Elastography and ElastPQ (r=0.85, p<0.001)., Conclusions: ElastPQ seems to have a good diagnostic accuracy for staging liver fibrosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: To evaluate how often do we "miss" chronic hepatitis C patients with at least significant fibrosis (F&gt;/=2) and those with compensated cirrhosis, by using Acoustic Radiation Force Impulse (ARFI) elastography cut-off values proposed by meta-analysis., Material and Methods: Our study included 132 patients with chronic hepatitis C, evaluated by means of ARFI and liver biopsy (LB), in the same session. Reliable measurements were defined as: median value of 10 liver stiffness (LS) measurements with a success rate&gt;/=60% and an interquartile range interval&lt;30%. For predicting F&gt;/=2 and F=4 we used the LS cut-offs proposed in the last published meta-analysis: 1.35 m/s and 1.87 m/s, respectively., Results: Reliable LS measurements by means of ARFI were obtained in 117 patients (87.9%). In our study, 58 patients (49.6%) had LS values &lt;1.35 m/s; from these 75.8% had F&gt;/=2 in LB. From the 59 patients (50.4%) with LS values&gt;/=1.35 m/s, only 6.8% had F0 or F1 in LB. Also, in our study, 88 patients (75.3%) had LS values &lt;1.87 m/s; from these only 2.2 % had F4 in LB. From the 29 patients (24.7%) with LS values&gt;/=1.87 m/s, 41.3% had F4 in LB. Both for prediction of at least significant fibrosis and liver cirrhosis, higher aminotransferases levels were associated with wrongly classified patients, in univariate and multivariate analysis., Conclusions: ARFI elastography had a very good positive predictive value (93.2%) for predicting the presence of significant fibrosis and excellent negative predictive value (97.8%) for excluding the presence of compensated liver cirrhosis.

Unlabelled: HCV is an important cause of renal disease. Taal and Brenner have identified risk factors for CKD and have suggested that these risk factors be incorporated into a renal risk score analogous to the Framingham cardiovascular score. Given the high HCV-renal disease comorbidity, we sought to assess risk factors for CKD in patients with HCV chronic hepatitis., Methods: One hundred-seventeen patients with HCV chronic hepatitis (mean age: 50.68 +/- 9.14 years; 86 female and 31 male) hospitalized in the Department of Hepatology during 2009 were enrolled into the study. All patients were assessed for the risk factors for CKD proposed by Taal and Brenner: albuminuria, diabetes mellitus, hypertension, obesity, anemia, hypercholesterolemia, hypertriglyceridemia, nephrotoxins, primary renal disease, associated urological disorder, cardiovascular disease and family history of CKD. Renal function (GFR-CKD-Epi) was also evaluated., Statistical Analysis: Pearson's correlation coefficient and Odds Ratio (OR) was performed using SPSS17 and Epi 3.2.2., Results: The prevalence of albuminuria was 21.36%, of hypertension was 20.51%, of obesity was 21.36%, and hypercholesterolemia was present in 41.02% of the cases. Renal function was as follows: 10.25% (12/117) of the patients had a GFR < 60 mL/min/1.73 sqm.; 64.95% (76/117) of the patients had a GFR between 60-89 mL/min/1.73 sqm.; and 24.78% (29/117) had a GFR > or = 90 mL/min/1.73 sqm., Conclusions: Our study shows that HCV chronic hepatitis is associated with renal function impairment in a high percentage of patients. Prominent risk factors for CKD are present in these patients, such as albuminuria, hypertension, obesity, and hypercholesterolemia, which need to be actively searched and addressed therapeutically.

Background and Objective: Chronic hepatitis C represents an important health problem. The aim of our meta-analysis was to establish the role of reference single nucleotide (rs) 12979860 allele of interleukin-28B (IL28B) CC versus CT+TT genotype (the most researched allele of IL28B) as a predictor of sustained virological response (SVR) in patients with chronic hepatitis C treated with triple therapy., Methods: The PubMed, MEDLINE, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases as well as abstract books from important gastroenterology and hepatology meetings were searched for all studies published until 15 July 2012 that analysed the relationship between the polymorphism of IL28B and SVR in patients with chronic hepatitis C, genotype 1, treated with pegylated interferon + ribavirin + direct antiviral agents (telaprevir or boceprevir). The following keywords were used: IL28B polymorphism, chronic hepatitis C, sustained virological response, SVR, triple therapy, telaprevir, boceprevir., Results: Odds ratios (ORs) with 95 % confidence intervals were pooled from five study populations (1,641 cases) using a random-effects model. The SVR rate was significantly higher in patients with the CC genotype of IL28B than in those with non-CC genotypes (CT and TT): OR = 3.91 (95 % CI 2.11-7.28), p < 0.0001. Higher SVR rates were obtained in chronic hepatitis C patients with the CC genotype of IL28B, regardless of their therapeutic status (naïve patients: OR = 3.99 [95 % CI 1.67-9.51], p < 0.0001; and previously treated ones: OR = 2.15 [95 % CI 1.35-3.43], p = 0.001)., Conclusion: IL28B polymorphism seems to influence the SVR rate in patients with chronic hepatitis C treated with triple therapy, but further studies are needed to clarify the mechanism and the influence of other factors on the SVR rates.

Our study tried to identify the factors associated with discordance between liver stiffness values assessed by acoustic radiation force impulse (ARFI) elastography and histologic fibrosis in 106 chronic hepatitis C patients. Liver biopsy (LB) and ARFI measurements were performed in the same session. A discordance of at least two stages of fibrosis in the Metavir scoring system between ARFI results and LB was defined as significant. The performance of ARFI elastography was assessed using the following cut-offs: F1-1.19 m/s, F2-1.34 m/s, F3-1.55 m/s and F4-1.80 m/s. Discordance of at least two stages of fibrosis between ARFI results and histologic assessment were observed in 31.7% of the patients. In an univariate analysis, female sex (p = 0.004), interquartile range interval (IQR) ≥30% (p = 0.04), high alanine aminotransferases (p = 0.008) and high aspartate aminotransferases levels (p = 0.003) were associated with discordances. In a multivariate analysis, the female sex (p = 0.006) and IQR ≥30% (p = 0.004) were associated with discordances. Therefore, IQR parameter should be used for ARFI measurements., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Aim: The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C., Patients and Methods: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5-10 valid measurements, expressed in meters/second - m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6-10 valid measurements, expressed in kiloPascals - kPa)., Results: Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r=0.654) was found between ARFI measurements and fibrosis (p<0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 - cut-off>1.19 m/s (AUROC=0.779), F ≥ 2 - cut-off>1.33 m/s (AUROC=0.792), F ≥ 3 - cut-off>1.43 m/s (AUROC=0.829), F=4 - cut-off>1.55 m/s (AUROC=0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r=0.728 vs. 0.689, p=0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p=0.01) and fibrosis (F ≥ 1, METAVIR) (p=0.01)., Conclusion: ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Our aim was to compare liver stiffness (LS) measurements by means of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in patients with chronic hepatitis B and C, according to the severity of fibrosis. We also compared the correlation strength of ARFI and TE measurements with liver fibrosis. We included 53 patients with hepatitis B and 107 with hepatitis C in which liver biopsy, ARFI and TE measurements were performed in the same session. The mean LS values measured with ARFI were similar in patients with chronic hepatitis B and C and depended on the stage of fibrosis. The correlation strength of LS measurements by ARFI and by TE with fibrosis was similar in chronic hepatitis B and C patients. In conclusion, for the same stage of fibrosis, the mean LS values by ARFI were similar in patients with chronic hepatitis B and C. ARFI had similar predictive value with TE in both chronic viral hepatitis., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Introduction: HBV and HCV chronic hepatitis can be accompanied by secondary renal disease. In addition, these patients receive antiviral drugs with potential nephrotoxicity. It is known that interferon (IFN) therapy in HCV-infected kidney transplant recipients is followed by rejection of the transplant in 50% of the cases. Ribavirin is contraindicated in hemodialyzed patients and in patients with a GFR <50 ml/min/1.73 m(2). IFN therapy requires dosage reduction and close monitoring in patients with a GFR <50 ml/min/1.73 m(2) and in patients with end stage renal disease. The aim of our study was to assess the nephrotoxicity of antiviral drugs in patients with chronic hepatitis by measuring three renal biomarkers: urinary albumin, N-acetyl-β-D-glucosaminidase (NAG) and α 1-microglobulin, as well as glomerular filtration rate (GFR-MDRD4) before and at 6 months of therapy., Methods: Fifty-five patients (28 male and 27 female, with a mean age of 47.85 ± 12.03 years) with chronic hepatitis (40 patients with HCV, 13 patients with HBV, 1 patient with HBV+HCV, and 1 patient with HBV+HDV) were enrolled into the study. Different antiviral drug associations were used on a case-by-case basis. The 40 patients with HCV chronic hepatitis received either Peg-IFN-α 2a+Ribavirin (37 patients) or Peg-IFN-α 2b+Ribavirin (3 patients). The 13 patients with HBV chronic hepatitis received Peg-IFN-α 2a (9 patients), Lamivudine (2 patients), Entecavir (1 patient), or Adefovir (1 patient). The patient with HBV+HCV chronic hepatitis received Peg-IFN-α 2a+Ribavirin. The patient with HBV+HDV chronic hepatitis received IFN-α 2a. Urinary albumin (ELISA), NAG (colorimetrical method), α 1-microglobulin (ELISA), and serum creatinine were measured before and at 6 months of antiviral therapy. Urinary markers were expressed as either mg/gCr (for albumin and α 1-microglobulin) or U/gCr (for NAG). Statistical analysis (Pearson's correlation coefficient, paired t-test and χ(2)-test) was performed., Results: At 6 months of therapy urinary albumin/gCr did not increase significantly: 16.58 ± 23.39 vs. 15.85 ± 24.96 mg/gCr before therapy, p = 0.87. Urinary NAG/gCr did not increase significantly: 4.21 ± 3.37 vs. 3.83 ± 3.2 U/gCr before therapy, p = 0.53. Urinary α 1-microglobulin/gCr was almost unchanged: 4.38 ± 4.47 vs. 4.38 ± 3.57 mg/gCr before therapy, p = 0.99. The GFR did not decline significantly: 92.41 ± 22.21 vs. 94.59 ± 36.1 ml/min/1.73 m(2) before therapy, p = 0.7. Ten patients (18.18%) were albuminuric before therapy, and 14 patients (25.45%) were albuminuric at 6 months of therapy, a non-significant increase (p = 0.35). We found a correlation between urinary albumin/gCr and NAG/gCr and between urinary albumin/gCr and α 1-microglobulin/gCr both at baseline and at 6 months of therapy: r = 0.54, p = 0.0005; r = 0.29, p = 0.03; r = 0.51, p = 0.0005; and r = 0.4, p = 0.002, respectively. In the patient receiving Adefovir, a known nephrotoxic drug, two of the three biomarkers (urinary albumin/gCr and NAG/gCr) increased, most notably NAG/gCr. Both HCV and HBV chronic hepatitis therapy were associated with non-significant changes in renal biomarker excretion and GFR., Conclusions: With the exception of Adefovir, all of the drug associations used in this study were safe.

Aim: To find out if by combining 2 ultrasound based elastographic methods: acoustic radiation force impulse (ARFI) elastography and transient elastography (TE), we can improve the prediction of fibrosis in patients with chronic hepatitis C., Methods: Our study included 197 patients with chronic hepatitis C. In each patient, we performed, in the same session, liver stiffness (LS) measurements by means of TE and ARFI, respectively, and liver biopsy (LB), assessed according to the Metavir score. 10 LS measurements were performed both by TE and ARFI; median values were calculated and expressed in kilopascals (kPa) and meters/second (m/s), respectively. Only TE and ARFI measurements with IQR < 30% and SR ≥ 60% were considered reliable., Results: On LB 13 (6.6%) patients had F0, 32 (16.2%) had F1, 52 (26.4%) had F2, 47 (23.9%) had F3, and 53 (26.9%) had F4. A direct, strong correlation was found between TE measurements and fibrosis (r = 0.741), between ARFI and fibrosis (r = 0.730) and also between TE and ARFI (r = 0.675). For predicting significant fibrosis (F ≥ 2), for a cut-off of 6.7 kPa, TE had 77.5% sensitivity (Se) and 86.5% specificity (Sp) [area under the receiver operating characteristic curve (AUROC) 0.87] and for a cut-off of 1.2 m/s, ARFI had 76.9% Se and 86.7% Sp (AUROC 0.84). For predicting cirrhosis (F = 4), for a cut-off of 12.2 kPa, TE had 96.2% Se and 89.6% Sp (AUROC 0.97) and for a cut-off of 1.8 m/s, ARFI had 90.4% Se and 85.6% Sp (AUROC 0.91). When both elastographic methods were taken into consideration, for predicting significant fibrosis (F ≥ 2), (TE ≥ 6.7 kPa and ARFI ≥ 1.2 m/s) we obtained 60.5% Se, 93.3% Sp, 96.8% positive predictive value (PPV), 41.4% negative predictive value (NPV) and 68% accuracy, while for predicting cirrhosis (TE ≥ 12.2 kPa and ARFI ≥ 1.8 m/s) we obtained 84.9% Se, 94.4% Sp, 84.9% PPV, 94.4% NPV and 91.8% accuracy., Conclusion: TE used in combination with ARFI is highly specific for predicting significant fibrosis; therefore when the two methods are concordant, liver biopsy can be avoided.

Background: Patients with HCV liver cirrhosis are a category difficult to treat. The aim of this study was to establish the sustained virological response (SVR) rates in HCV patients with liver cirrhosis treated with standard of care therapy (Pegylated Interferon and Ribavirin for 48 weeks in genotypes 1 and 4 and 24 weeks in genotypes 2 and 3)., Methods: Searching the PubMed, Medline, Lilacs, Scopus, Ovid and Medscape databases we identified all the articles published until February 2011 that included only HCV cirrhotic patients. These studies evaluated the SVR after standard of care treatment: Pegylated Interferon alpha 2a (doses ranging between 135-180 µg/week) or Pegylated Interferon alpha 2b (1 or 1.5 µg/kg/week) and Ribavirin (doses ranging between 800-1200 mg/day). We used the following key words: HCV, liver cirrhosis, sustained virological response (SVR)., Results: The overall SVR rate was 33.3% (95%CI-confidence interval=30.6-36.2%). SVR was significantly higher in patients with genotypes 2 and 3 (422 patients) as compared to those with genotypes 1 and 4 (692 patients): 55.4% (95%CI=50.7-60.1) versus 21.7% (95%CI=18.7-25), p < 0.0001., Conclusion: The overall SVR rate in cirrhotic patients treated with standard of care therapy is 33.3%, but lower in cases affected by genotypes 1 and 4 (21.6%) which makes them a priority regarding the development of more potent drugs for effective treatment.

Purpose: Chronic viral hepatopathies can be evaluated through invasive or noninvasive methods. The aim of this paper was to assess the indications and results of transient elastographic (TE) evaluation of the liver in patients with chronic viral hepatitis and cirrhosis., Materials and Methods: We retrospectively assessed all the liver stiffness measurements (LSM) (FibroScan®) performed over a two-year period (2007 - 2009)., Results: 3,459 TE evaluations were made mainly for the assessment of: HCV hepatitis, HBV infection (chronic hepatitis and inactive HBV carriers), biviral hepatitis (B + C or B + D), cirrhosis and in 176 normal subjects (to establish the normal values of LSM). From the 3,459 FS evaluations, we could not obtain valid LSM in 183 cases (5.3 %). 93.9 % of the patients in the failure group were overweight (BMI > 25 kg/m²). In 527 cases (16 %) the SR (success rate = number of valid measurements/total number of measurements) was < 60 %. TE reproducibility was analyzed in 287 cases. The ICCs for the three operators were 0.985, 0.949, and 0.874 respectively, and the overall ICC was 0.982. 596 cases of cirrhosis were evaluated. A cut-off value of 23.3kPa was found to predict the presence of at least grade 2 esophageal varices., Conclusion: LSM by means of TE is a promising noninvasive evaluation method, which can be used in numerous clinical situations, some in which its value is well established (suspicion of LC, predicting significant fibrosis) and some in which its value is less known (HBV chronic hepatitis, inactive HBV carriers or severity of portal hypertension)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To assess the values of liver stiffness (LS) in patients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis., Methods: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan®-Echosens®) and liver biopsy was performed in the same session (assessed according to the Metavir score)., Results: According to the Metavir score of the 140 HBV patients: one had F0, 32 had F1, 67 had F2, 33 had F3 and 7 had F4. Of the 317 HCV patients: 5 had F0, 34 had F1, 146 had F2, 93 had F3 and 39 had F4. For the same severity of fibrosis, the mean values of LS in HBV patients were similar to those in HCV patients: F1, 6.5 ± 1.9 kPa vs 5.8 ± 2.1 kPa (P = 0.0889); F2, 7.1 ± 2 kPa vs 6.9 ± 2.5 kPa (P = 0.3369); F3, 9.1 ± 3.6 kPa vs 9.9 ± 5 kPa (P = 0.7038); F4, 19.8 ± 8.6 kPa vs 17.3 ± 6.1 kPa (P = 0.6574). A significant direct correlation between LS measurements and fibrosis was found in HCV patients (Spearman's r = 0.578, P < 0.0001), as well as in HBV patients (r = 0.408, P < 0.0001). The correlation was more significant in HCV than in HBV patients (Fisher's Z-test, Z = 2.210, P = 0.0271)., Conclusion: In our group, the mean values of LS in patients with chronic B hepatitis were similar to those in patients with chronic HCV hepatitis, for the same stage of fibrosis. Also, LS was correlated with the severity of fibrosis both in HBV and HCV chronic hepatitis patients.

Background and Aim: The current standard of care in chronic HCV genotype 1 hepatitis is the combination of pegylated interferon (PegIFN) with ribavirin for 48 weeks. The aim of our paper was to verify if there are significant differences regarding the sustained virologic response (SVR) in patients treated with PegIFN alfa-2a vs. those treated PegIFN alpha-2b, both in combination with ribavirin., Method: We performed a retrospective study on 507 patients with chronic viral C hepatitis treated with PegIFN alpha-2a 180 microg/kg/week or PegIFN alpha-2b 1.5 microg/kg/week plus ribavirin in the recommended doses according to weight, following the current treatment guidelines. We evaluated the SVR defined as PCR RNA-HCV undetectable 24 weeks after the end of treatment., Results: There were no differences regarding the baseline characteristics among the subgroups of patients treated with PegIFN alpha-2a or PegIFN alpha-2b concerning the pretreatment viral load (p=0.2445), the severity of fibrosis (p=0.2403), the mean age of the patients (p=0.9597) and the women/men ratio (p=0.2087). The SVR rates in patients treated with PegIFN alpha-2a were similar to those in patients treated with PegIFN alpha-2b: 208/338 (61.5%) vs. 94/169 (55.6%) (p=0.2129)., Conclusion: Sustained virologic response rates were similar in HCV genotype 1 patients treated with PegIFN alpha-2a and with Peg-IFN alpha-2b.

Background: Patients with mild hepatitis C have a significant risk of disease progression at medium- and long-term follow-up and should be considered for antiviral therapy., Aim: To evaluate the rate of sustained viral response (SVR) and predictive factors of SVR in HCV genotype 1 patients with mild hepatitis C (fibrosis stage F0/F1) treated with combination antiviral therapy., Methods: 260 naïve patients were followed-up during 72 weeks in three referral hepatology centers between 2004 and 2006. Univariate and multivariate logistic regression analysis was conducted., Results: Early virological response was 88.1% and SVR was 74.2%. In the univariate analysis, SVR was associated with young age (p=0.001), very low (< or = 400,000 IU/mL) baseline viremia (p=0.03) and high aminotransferase levels (p=0.04) and was not associated with gender, body mass index, inflammatory activity, steatosis, ribavirin and peginterferon dose changes, premature cessation of therapy. Multivariate analysis identified the following independent predictors of SVR: age <50 years (p=0.0009), viral load < or = 400,000 IU/mL (p=0.03) and aminotransferase level >2 times normal value (p=0.02)., Conclusions: Genotype 1 HCV patients with mild hepatitis have a high rate of SVR, similar to genotype non-1. Young age, very low viremia and significant hepatocytolisis are independent predictors of SVR in patients with mild hepatitis.

Unlabelled: The aim of our paper was to assess the prevalence of anti HCV antibodies among diabetics from Romania., Material and Method: We performed two studies: a prospective randomized one, on 559 diabetics from Timişoara, and a second, retrospective-descriptive one, on 625 diabetics from Petroşani, who were tested for anti HCV antibodies., Results: I. In Timişoara, 559 diabetics were prospectively evaluated, 4.5% (25p.) were anti HCV positive. There were no statistically significant differences between the proportions of type I DM in the anti HCV positive group (4%-1p.) as compared to the entire group (12%-67p.) (p=0.3429), nor in the F: M ratio, 1.3:1 vs. 1.5:1 (p=0.838). II. In Petroşani, 625 diabetics were retrospectively evaluated, 7.7% (48p.) were anti HCV positive. There were no significant differences between the proportions of type I DM in the anti HCV positive group (6%-3p.) vs. the entire group (8%-53p.) (p=0.788), nor in the F: M ratio, 1.7:1 vs. 1.7:1 (p=1)., Conclusion: The prevalence of anti HCV antibodies among diabetics from Romania is rather high (4.5% in a randomized prospective trial and 7.7% in a retrospective descriptive trial) so that this special population (especially type II DM) should be screened for HCV infection, even if the aminotransferases are normal.

Aim: To compare the liver stiffness (LS) measurement by transient elastography (TE) to the liver biopsy (LB)-considered the "gold standard" in the evaluation of patients with chronic hepatitis C., Methods: During a period of 12 mo, we evaluated 199 consecutive patients with chronic hepatitis due to hepatitis C virus (HCV), in which LB and LS assessments (by means of TE) were performed during the same session., Results: Out of 199 patients, a valid measurement of the LS could not be obtained in 8. The mean value of LS in the cohort of 191 valid measurements was 8.45 +/- 4.96 kPa, ranging from 2.3 to 38 kPa. The mean value of LS in patients with significant fibrosis at biopsy (161 patients with F >= 2 according to Metavir) was 9.02 +/- 5.15 kPa, significantly higher than in patients with no or mild fibrosis (30 patients with F < 2 Metavir): 5.39 +/- 1.81 kPa (P < 0.0001). For a cut-off value of 6.8 kPa, the LS had a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6% and a specificity of 93.3% for the presence of significant fibrosis (at least F2 Metavir), with a diagnostic performance of 77.3% (AUROC 0.773). Using this cut-off value, we reached the best discrimination between absence of fibrosis/mild fibrosis (F < 2 Metavir) and the presence of moderate to severe fibrosis (F >= 2 Metavir)., Conclusion: In patients with chronic hepatitis due to HCV, a cut-off value of 6.8 kPa measured by TE can differentiate between significant fibrosis and absent or mild fibrosis, with a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6%, a specificity of 93.3%, and a diagnostic performance of 77.3%.

Aim: To evaluate the response to pegylated-interferon alpha 2a in chronic hepatitis C patients on chronic haemodialysis., Methods: Ten patients with chronic C hepatitis were enrolled in this study. All had increased aminotransferases for more than 6 mo, positive antiHCV antibodies and positive PCR HCV-RNA. We administrated Peg-Interferon alpha 2a 180 microg/wk for 48 wk. After 12 wk of treatment we evaluated the biochemical and early virological response (EVR). At the end of the treatment we evaluated the biochemical response and 24 wk after the end of the treatment we evaluated the sustained virological response (SVR). We monitored the side-effects during the treatment., Results: Two patients dropped out in the first 12 wk of treatment and 2 after the first 12 wk of treatment. After 12 wk of treatment, 7 out of 8 patients had biochemical response and EVR and 1 had biochemical response but persistent viremia. We had to reduce the dose of pegylated-interferon to 135 mug/wk in 2 cases. Three out of 6 (50%) patients had SVR 24 wk after the end of the treatment. Intention-to-treat analysis showed that 3 out of 10 patients (30%) had SVR. Side-effects occurred in most of the patients (flu-like syndrome, thrombocytopenia or leucopoenia), but they did not impose the discontinuation of treatment., Conclusion: After 12 wk of treatment with Peg-Interferon alpha 2a (40 ku) in patients on chronic haemodialysis with chronic C hepatitis, EVR was obtained in 87.5% (7/8) of the cases. SVR was achieved in 50% of the cases (3/6 patients) that finished the 48 wk of treatment.

Background: Pegylated interferons (Peg-IFNs) represent, in association with Ribavirin, the first line of treatment in chronic C viral hepatitis. The AIM of our paper was to compare the efficacy of Peg-IFN alpha 2a (Pegasys) and Peg-IFN alpha 2b (PegIntron) in a group of patients from the Department of Gastroenterology in Timisoara., Material and Method: 116 patients with chronic C viral hepatitis were treated. The patients were randomized in chronological order (1:1), so that 58 patients were treated with Peg-IFN alpha 2a 180 microg/kg/week + Ribavirin (group 1) and 58 were treated with Peg-IFN alpha 2b 1.5 microg/kg/week + Ribavirin (group 2). Ribavirin was administered in the recommended doses, according to weight. The mean age was: group 1 -- 49.3 years, group 2 -- 50.9 years (p=0.37). Group 1 consisted of 37 women and 21 men and group 2 of 44 women 14 men (p=0.22). In group 1, 48 patients were naïve (N1), 7 were relapsers after previous treatment (RL1) and 3 non-responders to previous treatment (NR1). In group 2, 33 patients were naive (N2), 18 relapsers (RL2) and 7 non-responders (NR2). After 12 weeks of treatment we evaluated the early virological response (EVR), defined as a drop in the viral load with 2 logs compared to the baseline viremia., Results: The following EVR rates were found: in group 1 (Pegasys) - 82.2% (48/58); in group 2 (PegIntron) -- 67.2% (39/58) (p=0.08). There were also no significant statistical differences between the response rates in the subgroups: naïve patients [89.6% vs. 75.2%, p = 0.61], relapsers [57.1% vs. 66.6%, p = 0.67] and non responders [33.3% vs. 28.6%, p = 1]., Conclusion: Our head to head comparative study showed that there are no statistically significant differences in the EVR between the patients treated with Peg-IFN alpha 2a and Peg-IFN alpha 2b.

The aim of the study was to evaluate the response to Pegylated Interferon alpha2a (40 kDa) in patients on chronic haemodialysis with chronic C hepatitis. 10 patients were enrolled in this study (4 males and 6 females). All had increased aminotransferases, anti HCV antibodies and PCR HCV-RNA positive. We administrated Peg-Interferon alpha2a 180 microg/week for 48 weeks. One patient was excluded from the study because of lack of compliance. We had to stop the treatment in one patient due to complications after surgery. After 12 weeks of treatment we evaluated the biochemical and virological response. We continued with Peg-Interferon until 48 weeks. Six patients finished the treatment. After 12 weeks of treatment with Peg-Interferon alpha 2a (40 kDa) in patients on chronic haemodialysis with chronic C hepatitis, the virological response (HCV-RNA absent by PCR) was obtained in 87.5% (7/8) of the cases. All patients who finished the 48 weeks of treatment had normal transaminases (biochemical response) (6/6). We had to reduce the dose of Peg-Interferon in only 2 cases. Even if side-effects occurred in most of the patients (flu-like syndrome, thrombocytopenia or leucopenia) they did not impose the discontinuation of treatment. The sustained response will be established by determining PCR RNA-HCV 6 months after the end of the treatment.