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Purpose: The aim of our study was to assess the possible benefits of Therapeutic Magnetic Resonance (TMR) in the treatment of spontaneous perineal lacerations and episiotomies in the postpartum., Methods: We performed a prospective, non-pharmacologic, non-profit, monocentric interventional study on women who had a spontaneous laceration and/or an episiotomy at delivery. The TMR device treatment was accepted by 52 women, while 120 women underwent standard care. Patients were visited 1 day postpartum, before starting the treatment; then a follow-up visit was performed at 3 weeks, 5 weeks, and 3 months after delivery. The main endpoint was the time required for complete healing of the laceration and/or the episiotomy. Secondary endpoints were the prevalence of dehiscence, infections, urinary discomfort, urinary leakage, and the quality of restoration of sexual function., Results: In the treatment group the REEDA score was significantly better both at 3- and 5-weeks postpartum follow-up. At 3 weeks and 5 weeks postpartum, we observed a significantly better outcome in the treatment group for all subjective complaints and perineal complications associated with lacerations and episiotomies. The percentage of patients who scored above the cutoff for sexual dysfunction was significantly better in the treatment group (83.3%) than in the control group (31.8%) (p < 0.001)., Conclusions: With this pilot study, we introduced low dose Pulsating Electromagnetic Fields (PEMFs) as a novel conservative and not pharmacological approach to reduce complications of perineal lesions. Our results demonstrated to significantly improve perineal wound healing and to ameliorate the sexual function in the postpartum., (© 2024. The Author(s).)

Introduction: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy., Methods: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis, and treatment), and sent to all the Italian PCD Centers., Results: Questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow <20 patients, two centers have >40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers, <3 years in three centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75%, 90%, and 40% of centers, respectively. Immunofluorescence is available in five centers. Genetic analysis is offered in 55% of the centers, and in seven centers >50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95% and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics., Conclusions: Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals., (© 2023 Wiley Periodicals LLC.)

Background & Aim: HBV epidemiology is highly heterogeneous and rapidly evolving worldwide: we studied its last two-decades dynamics in a large single center cohort., Methods: In all consecutive HBsAg-positive subjects firstly admitted (2000-2019) at the Pisa-University-Hospital Hepatology-Referral-Center, demographic, virologic and clinical variables were analyzed by admission decade (2000-2009 vs 2010-2019) and origin (Italian vs non-Italian natives)., Results: Of 2003, 1878 (93.7%) subjects were eligible: 1798(95.7%) with HBV-chronic [126(7%) HDV, 72(4%) HCV, 11(0.6%) HIV co-infected] and 80(4.3%) HBV-primary infections (93.7% Italians). Among 1589(88.4%) mono-infected, 496(31.2%) were immigrants, younger than Italians [34.0(5.1-77.1)-52.5(10.0-87.2) years], with female prevalence [204/496(41.1%)-340/1093(31.1%); p<0.001] increasing overtime (14.6-45.0%; p<0.001). Italians aged across decades [50.3(11.1-87.2)-56.2(10.0-86.7) years; p<0.001], HBeAg-positivity remained stable (12.3-14.5%) and acute hepatitis increased (4.0-8.0%; p = 0.003). CHB declined [439/721(60.9%)-320/868(36.9%); p<0.001] whereas HBeAg-negative infection increased [277/626(44.2%)-538/755(71.3%); p<0.001]. Cirrhosis declined [195/721(27.0%)-125/868(14.4%); p<0.001], except in anti-HDV-patients [93/126(73.8%); 42(45.1%) non-Italians], younger than HBV-mono-infected (47.4-57.6 years; p<0.001)., Conclusion: Effective preventive health care policies and immigration flows account for increasing prevalence of HBeAg-negative infection across the last two decades. Antiviral therapy mitigated disease progression in aging Italian CHB but not in CHD patients, mainly young immigrants, emphasizing the unmet need of effective CHD therapies; HBeAg-positive CHB and acute hepatitis B persist in non-vaccinated Italian adults, prompting vaccination in the elderly with risky behaviors., Competing Interests: Conflict of interest Ferruccio Bonino has served as a speaker for Fujirebio, Gilead and Roche. Maurizia Rossana Brunetto has served as a speaker for AbbVie, Gilead, EISAI-MSD and as an advisory board member for AbbVie, Gilead, Janssen, Roche. All other authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) may induce hepatitis B virus (HBV) reactivations in co-infected patients, whose dynamics and outcomes could depend on the phase of HBV infection. We investigated HBsAg and HBV-DNA kinetics in fifteen untreated HBeAg Negative Infection (ENI) (4F-11M, 62.1y) and eight Nucleos(t)ide Analogs (NAs) treated Chronic Hepatitis B (CHB) (3F-6M, 54.8y) with HCV co-infection, receiving DAAs-regimens including Sofosbuvir (13) or not (10). All achieved a sustained virologic response (SVR) and normalized alanine-aminotransferase (ALT). At the direct acting antivirals’ (DAAs) baseline (BL), the HBV-DNA was undetectable (<6 IU/mL) in eight ENI and all CHB, the mean Log-HBsAg was lower in ENI than CHB (0.88 vs. 2.42, p = 0.035). During DAAs, HBV-DNA increased in untreated ENI by >1 Log in five and became detectable in two. Accordingly, mean BL Log-HBV-DNA (0.89) increased at week-4 (1.78; p = 0.100) and at the end of therapy (1.57; p = 0.104). Mean Log-HBsAg decreased at week-4 in ENI (from 0.88 to 0.55; p = 0.020) and CHB (from 2.42 to 2.15; p = 0.015). After DAAs, the HBsAg returned to pre-treatment levels in CHB, but not in ENI (six cleared HBsAg). Female gender and SOF were associated with a greater HBsAg decline. In conclusion, HBV reactivations during DAAs in HCV co-infected ENI caused moderate increases of HBV-DNA without ALT elevations. The concomitant HBsAg decline, although significant, did not modify individual pre-treatment profiles.

In advanced HCC, tyrosine-kinase inhibitors obtain partial responses (PR) in some patients and complete responses (CR) in a few. Better understanding of the mechanism of response could be achieved by the radiomic approach combining digital imaging and serological biomarkers (α-fetoprotein, AFP and protein induced by vitamin K absence-II, PIVKA-II) kinetics. A physic-mathematical model was developed to investigate cancer cells and vasculature dynamics in three prototype patients receiving sorafenib and/or regorafenib and applied in seven others for validation. Overall four patients showed CR, two PR, two stable-disease (SD) and two progressive-disease (PD). The rate constant of cancer cells production was higher in PD than in PR-SD and CR (median: 0.398 vs. 0.325 vs. 0.316 C × day -1 ). Therapy induced reduction of neo-angiogenesis was greater in CR than in PR-SD and PD (median: 83.2% vs. 29.4% and 2.0%), as the reduction of cell-proliferation (55.2% vs. 7.6% and 0.7%). An additional dose-dependent acceleration of tumor vasculature decay was also observed in CR. AFP and cancer cells followed the same kinetics, whereas PIVKA-II time/dose dependent fluctuations were influenced also by tissue ischemia. In conclusion, pending confirmation in a larger HCC cohort, modeling serological and imaging biomarkers could be a new tool for systemic therapy personalization.

Background: Virus, host factors and their interplay influence Hepatitis B surface Antigen serum levels during Hepatitis B Virus (HBV) infection course and treatment., Aim: To study the Pre-S/S circulating quasispecies in a cohort of untreated, HBeAg negative, genotype-D, HBsAg carriers., Methods: We studied 260 carriers: 71 with HBeAg negative infection (ENI; HBV-DNA ≤2000 IU/mL); 42 Grey Zone (GZ; HBV-DNA ≤20 000 IU/mL); 82 chronic hepatitis (CH) and 65 cirrhosis (CI) (HBV-DNA > 20 000 IU/mL). Population sequencing was applied to identify Pre-S/S gene mutations responsible for any amino acid substitution or potential biological/antigenic implications (M-muts) on HBsAg., Results: HBsAg serum levels were lower in ENI + GZ than in CH + CI (2.61 [-1.10/4.06] vs 3.62 [2.41/4.92] log 10 IU/mL, P < 0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log 10 IU/mL, P < 0.001). M-muts were found in 73 (28.1%) cases: 5 (7.0%) ENI, 3 (7.1%) GZ, 26 (31.7%) CH, 39 (60.0%) CI (P < 0.001) and mostly in Pre-S2 (17.6%) than Pre-S1 (5.8%) and Small-S (10.8%; P < 0.001). Overall HBsAg serum levels were higher in carriers with M-muts (3.56 [0.95/4.38] vs 3.17 [-1.10/4.92] log 10 IU/mL, P < 0.001), but comparable in carriers with or without M-mut when considering separately ENI + GZ (2.84 [0.95/3.89] vs 2.61 [-1.10/4.06] log 10 IU/mL, P = 0.330] and CH + CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log 10 IU/mL, P = 0.37). Infection phase (β: 0.422, P < 0.001), age (β: -0.260, P < 0.001), ALT (β: -0.103, P = 0.045), liver stiffness (β: -0.118, P = 0.039) and HBV-DNA (β: 0.384, P < 0.001), but not M-mut were independently associated with HBsAg serum levels., Conclusions: In HBeAg negative, genotype-D, carriers Pre-S/S heterogeneity increases with severity of liver disease, but does not influence HBsAg serum levels, that in low viraemic carriers are associated with an effective control of HBV., (© 2020 John Wiley & Sons Ltd.)

Biologically inspired to mammalian olfactory system, electronic noses became popular during the last three decades. In literature, as well as in daily practice, a wide range of applications are reported. Nevertheless, the most pioneering one has been (and still is) the assessment of the human breath composition. In this study, we used a prototype of electronic nose, called Wize Sniffer (WS) and based it on an array of semiconductor gas sensor, to detect ammonia in the breath of patients suffering from severe liver impairment. In the setting of severely impaired liver, toxic substances, such as ammonia, accumulate in the systemic circulation and in the brain. This may result in Hepatic Encephalopathy (HE), a spectrum of neuro-psychiatric abnormalities which include changes in cognitive functions, consciousness, and behaviour. HE can be detected only by specific but time-consuming and burdensome examinations, such as blood ammonia levels assessment and neuro-psychological tests. In the presented proof-of-concept study, we aimed at investigating the possibility of discriminating the severity degree of liver impairment on the basis of the detected breath ammonia, in view of the detection of HE at its early stage.

In 2016, in order to identify adult patients with sepsis who are likely to have poor outcomes, the Third International Consensus Definitions Task Force introduced a new bedside index, called the quick Sepsis-related Organ Failure Assessment (qSOFA) score. However, these new criteria have not been validated in the pediatric population. In this study, we sought to assess the qSOFA score for children with sepsis, who are being treated outside the pediatric intensive care units. The qSOFA criteria were revised and applied to a study population of 89 pediatric patients with sepsis, admitted in a pediatric tertiary referral center from 2006 to 2016. The analysis of prognostic performance of qSOFA score for the prediction of severe sepsis showed a sensitivity of 46% (95% CI, 27-67%), a specificity of 74% (95% CI, 62-85%), a positive predictive value of 43% (95% CI, 34-52%), and a negative predictive value of 77% (95% CI, 71-82%). The area under ROC curve for qSOFA score ≥ 2 was 0.602 (95% CI 0.492-0.705).Conclusion: The qSOFA score showed a low accuracy to identify children in the pediatric ward at risk for severe sepsis. Clinical tools are needed to facilitate the diagnosis of impending organ dysfunction in pediatric infection outside of the ICU. What is Known: • One of the major challenges for clinicians is to identify and recognize children with sepsis and impending organ dysfunction, in the emergency and in the pediatric department. • In 2016, members of the Sepsis-3 task force proposed qSOFA, an empirically derived score using simple clinical criteria, to assist clinicians in identifying adult patients with sepsis at risk for poor outcome. What is New: • qSOFA demonstrated insufficient clinical value to be recommended as a screening tool for pediatric sepsis outside ICU. • D-dimer level and blood glucose may be useful biomarkers to identify children at risk for severe sepsis.

AimThe aim of this study was to determine the spontaneous closure rate of patent ductus arteriosus at a 2-year follow-up, following failed medical therapy and beyond initial hospital discharge, and to evaluate in-hospital spontaneous or pharmacological closure rates.Materials and methodsA retrospective evaluation was conducted in a cohort of preterm infants admitted to the Neonatal ICU of Ancona between January, 2004 and June, 2013. Inclusion criteria were gestational age between 24+0 and 29+6 weeks or birth weight 1.5 mm, a left atrium-to-aorta ratio >1.4, and/or reversal of end-diastolic flow in the aorta >30% of the anterograde. First-line treatment was intravenous ibuprofen. Intravenous indomethacin was used if ibuprofen failed. Surgical ligation was considered in haemodynamically significant patent ductus arteriosus after medical treatment., Results: A total of 593 infants met the inclusion criteria, and patent ductus arteriosus was diagnosed in 317 (53.4%). Among them, 283 (89.3%) infants had haemodynamically significant patent ductus arteriosus, with pharmacological closure achieved in 228 (80.6%) infants and surgical ligation performed in 20 (7.1%). Follow-up at 24 months was available for 39 (81.3%) of 48 infants with patent ductus arteriosus at the hospital discharge: 36 (92.3%) underwent spontaneous closure, two (5.1%) underwent surgical ligation, and one (2.6%) had a patent ductus arteriosus.DiscussionA significant number of patent ductus arteriosus that fail pharmacological closure undergo spontaneous closure by the age of 2 years. This information should be taken into account when considering surgery or additional attempts of pharmacological closure.

Background & Aims: The difference between the long-term outcome of low-viraemic (HBV-DNA≤20 000-IU/mL, LV-AC) and inactive HBsAg carriers (HBV-DNA≤2000-IU/mL, IC) remains to be defined. We studied prospectively 153 HBeAg-negative HBsAg-carriers with baseline HBV-DNA≤20 000-IU/mL and normal transaminases., Methods: IC, LV-AC or chronic hepatitis B (CHB) (HBV-DNA persistently ≤2000-IU/mL, ≤20 000-IU/mL or >20 000-IU/mL respectively) were diagnosed after 1-year, 3-monthly monitoring. Thereafter IC and LV-AC were followed-up for additional 57.2 (8.5-158.3) months. HBV-DNA, HBsAg, HBV"core-related"Antigen (HBcrAg) and total-anti-HBc were quantified at baseline., Results: After the 1st year diagnostic follow-up CHB [higher HBV-DNA (P=.005), total-anti-HBc (P=.012), ALT (P=.007) and liver-stiffness (P=.021)] was identified in 20 (13.1%) carriers; baseline HBsAg≤1000IU/HBV-DNA≤2000IU/mL excluded the presence of CHB (NPV-100%). Thereafter, during the long-term follow-up none of 87 IC reactivated, 19 (21.8%) cleared HBsAg [older-age (P=.004), lower HBsAg (P<.001), higher yearly HBsAg decline (P<.001)]. Twenty-five of 46 (54.3%) LV-AC remained stable, 20 (43.5%) became IC and 1 (2.2%) developed CHB. The best single-point CHB and IC diagnostic-accuracies were total-anti-HBc (84.2%, NPV-98.2%) and HBV-DNA/total-anti-HBc/HBcrAg combination (89.5%, 93%-sensitivity, 84.8%-specificity) respectively., Conclusions: Viraemia persistently ≤20 000-IU/mL predicts a benign clinical outcome: it was associated with transition to IC in 43% of LV-AC and to Occult HBV Infection in 20% of IC within 5-years. Nevertheless, 13.1% of individuals with low viraemia at presentation develops CHB within 1 year: 1-year HBV-DNA monitoring resulted the most accurate diagnostic approach that can be limited to at least a half of cases by the single point HBV-DNA/HBsAg quantification. The IC-diagnostic-accuracy combining HBV-DNA/total-anti-HBc/HBcrAg needs to be confirmed in further studies., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: The virus/host interplay mediates liver pathology in chronic HBV infection. MiRNAs play a pivotal role in virus/host interactions and are detected in both serum and HBsAg-particles, but studies of their dynamics during chronic infection and antiviral therapy are missing. We studied serum miRNAs during different phases of chronic HBV infection and antiviral treatment., Methods: MiRNAs were profiled by miRCURY-LNA-Universal-RT-miRNA-PCR (Exiqon-A/S) and qPCR-panels-I/II-739-miRNA-assays and single-RT-q-PCRs. Two cohorts of well-characterized HBsAg-carriers were studied (median follow-up 34-52 months): a) training-panel (141 sera) and HBsAg-particles (32 samples) from 61 HBsAg-carriers and b) validation-panel (136 sera) from 84 carriers., Results: Thirty-one miRNAs were differentially expressed in inactive-carriers (IC) and chronic-hepatitis-B (CHB) with the largest difference for miR-122-5p, miR-99a-5p and miR-192-5p (liver-specific-miRNAs), over-expressed in both sera and HBsAg-particles of CHB (ANOVA/U-test p-values: <0.000001/0.000001; <0.000001/0.000003; <0.000001/0.000005, respectively) and significantly down-regulated during- and after-treatment in sustained-virological-responders (SVR). MiRNA-profiles of IC and SVR clustered in the heatmap. Liver-miRNAs were combined with miR-335, miR-126 and miR-320a (internal controls) to build a MiR-B-Index with 100% sensitivity, 83.3% and 92.5% specificity (-1.7 cut-off) in both training and validation cohorts to identify IC. MiR-B-Index (-5.72, -20.43/14.38) correlated with ALT (49, 10/2056 U/l, ρ = -0.497, p<0.001), HBV-DNA (4.58, undetectable/>8.3 Log10 IU/mL, ρ = -0.732, p<0.001) and HBsAg (3.40, 0.11/5.49 Log10 IU/mL, ρ = -0.883, p<0.001). At multivariate analysis HBV-DNA (p = 0.002), HBsAg (p<0.001) and infection-phase (p<0.001), but not ALT (p = 0.360) correlated with MiR-B-Index. In SVR to Peg-IFN/NUCs MiR-B-Index improved during-therapy and post-treatment reaching IC-like values (5.32, -1.65/10.91 vs 6.68, 0.54/9.53, p = 0.324) beckoning sustained HBV-immune-control earlier than HBsAg-decline., Conclusions: Serum miRNA profile change dynamically during the different phases of chronic HBV infection. We identified a miRNA signature associated with both natural-occurring and therapy-induced immune control of HBV infection. The MiR-B-Index might be a useful biomarker for the early identification of the sustained switch from CHB to inactive HBV-infection in patients treated with antivirals.

Middle lobe syndrome in children is a distinct clinical and radiographic entity that has been well described in the pediatric literature. However, issues regarding its etiology, clinical presentation, and management continue to puzzle the clinical practitioner. Pathophysiologically, there are two forms of middle lobe syndrome, namely obstructive and nonobstructive. Middle lobe syndrome may present as symptomatic or asymptomatic, as persistent or recurrent atelectasis, or as pneumonitis or bronchiectasis of the middle lobe and/or lingula. A lower threshold of performing a chest radiograph is warranted in children with persistent or recurrent nonspecific respiratory symptoms, particularly if there is clinical deterioration, in order to detect middle lobe syndrome and to initiate a further diagnostic and therapeutic workup., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Early-onset (EO) pediatric inflammatory bowel diseases (IBD) seem to be more extensive than those with a later onset. To test this hypothesis, we examined the phenotype and disease course of patients with IBD diagnosis at 0 to 5 years, compared with the ranges 6 to 11 and 12 to 18 years., Methods: Anatomic locations and behaviors were assessed according to Paris classification in 506 consecutive patients: 224 Crohn's disease, 245 ulcerative colitis, and 37 IBD-unclassified., Results: Eleven percent of patients were in the range 0 to 5 years, 39% in 6 to 11 years, and 50% in 12 to 18 years. Ulcerative colitis was the most frequent diagnosis in EO-IBD and in 6- to 11-year-old group, whereas Crohn's disease was predominant in older children. A classification as IBD-unclassified was more common in the range 0 to 5 years compared with the other groups (P < 0.005). EO Crohn's disease showed a more frequent isolated colonic (P < 0.005) and upper gastrointestinal involvement than later-onset disease. Sixty-two percent of the patients in the 0 to 5 years range had pancolonic ulcerative colitis, compared with 38% of 6 to 11 years (P = 0.02) and 31% of 12-18 years (P = 0.002) range. No statistical difference for family history for IBD was found in the 3-year age groups. Therapies at the diagnosis were similar for all children. However, at latest follow-up, a significantly higher proportion of younger children were under steroids compared with older groups (P < 0.05). Surgical risk did not differ according to age., Conclusions: EO-IBD exhibits an extensive phenotype and benefit from aggressive treatment strategies, although surgical risk is similar to later-onset disease. A family history for IBD is not common in EO disease.

Crohn's disease (CD) is an inflammatory bowel disease (IBD) that can affect the whole gastrointestinal tract. The ileocolonic variant of CD, an inflammation of both the ileum and the large intestine, accounts for up to 50% of the cases with CD, whereas Crohn's ileitis affecting the ileum is diagnosed in about 30%. Crohn's colitis, which is confined to the large intestine and accounts for the remaining 20%, is difficult to distinguish from the large bowel inflammation seen in patients with ulcerative colitis (UC). The pathogenesis of CD is not yet completely understood. Autoimmunity is one factor that can partake in the triggering or modulation of inflammatory processes in IBD. The major zymogen-granule membrane glycoprotein 2 (GP2) has been recently identified as a major autoantigenic target in CD. Interestingly, GP2 is mainly expressed in the pancreas and has also been demonstrated to be a membrane-anchored receptor of microfold cells in the follicle-associated epithelium. Remarkably, GP2 is overexpressed at the site of CD inflammation in contrast to the one in UC. By utilizing novel enzyme-linked immunosorbent assays for the detection of GP2-specific IgA and IgG, the loss of tolerance to GP2 has been associated with a specific clinical phenotype in CD, in particular with the ileocolonic location of the disease.

Background & Aims: The accurate identification of inactive (serum HBV-DNA persistently or=20,000 IU/mL (AC2): 883 (0.5-7838) vs 4233 (164-82,480) IU/mL, P=.002. HBV infection was less productive in IC and AC1 than AC2 (log10 HBV-DNA/HBsAgsl ratios 0.25 and 0.49 vs 2.06, respectively, P<.001) and in chronic hepatitis than cirrhosis (1.97 vs 2.34, respectively; P=.023). The combined single point quantification of HBsAg (<1000 IU/mL) and HBV-DNA (

Aim: To investigate the usefulness of transient elastography by Fibroscan (FS), a rapid non-invasive technique to evaluate liver fibrosis, in the management of chronic hepatitis B virus (HBV) carriers., Methods: In 297 consecutive HBV carriers, we studied the correlation between liver stiffness (LS), stage of liver disease and other factors potentially influencing FS measurements. In 87 chronic hepatitis B (CHB) patients, we monitored the FS variations according to the spontaneous or treatment-induced variations of biochemical activity during follow-up., Results: FS values were 12.3 +/- 3.3 kPa in acute hepatitis, 10.3 +/- 8.8 kPa in chronic hepatitis, 4.3 +/- 1.0 kPa in inactive carriers and 4.6 +/- 1.2 kPa in blood donors. We identified the cut-offs of 7.5 and 11.8 kPa for the diagnosis of fibrosis >or= S3 and cirrhosis respectively, showing 93.9% and 86.5% sensitivity, 88.5% and 96.3% specificity, 76.7% and 86.7% positive predictive value (PPV), 97.3% and 96.3% negative predictive value (NPV) and 90.1% and 94.2% diagnostic accuracy. At multivariate analysis in 171 untreated carriers, fibrosis stage (t = 13.187, P < 0.001), active vs inactive HBV infection (t = 6.437, P < 0.001), alanine aminotransferase (ALT) (t = 4.740, P < 0.001) and HBV-DNA levels (t = or-2.046, P = 0.042) were independently associated with FS. Necroinflammation score (t = 2.158, > 10/18 vs