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The MARS post-marketing, observational study evaluates glecaprevir/pibrentasvir in a large population of Italian patients who are infected with HCV. Achievement of SVR12 was the primary endpoint in the overall population and by subpopulations of interest (treatment-naïve and treatment-experienced patients, subjects infected with different HCV genotype/sub-genotype, cirrhotic and non-cirrhotic patients, patients with different severity of fibrosis, patients with an APRI score ≥1, subjects with comorbidities, HIV-coinfected patients, elderly patients and people who use drugs). Safety and quality of life (assessed by SF-36 and Work Productivity and Activity Impairment) were also evaluated. The SVR12 rate was 99.4% (319/321; 95% CI: 97.8–99.8%) in the core population with sufficient follow-up (n = 321), 99.7% (289/290) in 8-week treated patients, and high (>96%) across subgroups. Only three patients (0.9%) had treatment-related adverse events that led to treatment discontinuation. In total, 30.1% of patients showed an improvement of ≥2.5 points in the Physical Component Summary of the SF-36 from baseline to the end of treatment, and this figure raised to 37.5% with the achievement of SVR12. Corresponding values for MCS were 42.2% and 42.8%, respectively. Glecaprevir/pibrentasvir is safe and effective across subpopulations who are underserved in clinical trials. [ABSTRACT FROM AUTHOR]

Since most patients with hepatitis C virus (HCV) infection now receive treatment irrespective of liver disease severity, special attention to patient quality of life (QoL), including psycho-social aspects, is required. No QoL questionnaire is specific for patients with HCV. To develop and validate a short Italian questionnaire (HepaDisk) assessing the QoL of patients affected by HCV with intuitive graphic results that is understandable by patients and physicians. A questionnaire, drafted by a steering committee, underwent a Delphi survey. A multicenter, observational study was conducted to validate the developed HepaDisk versus other tools (CLDQ-I, SF-36, WPAI:HCV), and to evaluate its correlation with disease severity in Italian patients with HCV. The 10-item questionnaire was validated in 214 patients. HepaDisk showed a high correlation with CLDQ overall score and WPAI:HCV activity impairment (Spearman's rank correlation: 0.651 and 0.595, respectively) and a lower correlation with SF-36. Strong internal consistency (Cronbach coefficient: 0.912), good test–retest reliability (Pearson's correlation coefficient: 0.789; 95% CI, 0.714–0.865), and responsiveness to changes among improved patients were demonstrated. HepaDisk is a reliable and user-friendly tool that can monitor disease impact on patient QoL over time, providing a visual representation easily understandable by both patients and physicians. [ABSTRACT FROM AUTHOR]

• Novel coronavirus (COVID-19) directly or indirectly may affect cerebral nervous system. • We described the first case of cerebral nervous system vasculitis triggered by COVID-19. • Medical treatment with both immunoglobulins and steroids ameliorated both MRI and clinical symptoms. We describe a patient affected by Covid-19 acute respiratory distress syndrome with a cerebral nervous system vasculitis triggered by SARS-Cov-2, managed at the University hospital, in Novara, Italy in the area most impacted by the pandemic and where 749 Covid-19 positive patients were admitted from March 1st until April 25th, 2020. [ABSTRACT FROM AUTHOR]

Background The red cell distribution width is a biomarker of early mortality across various disease states. Aim To verify whether it may refine estimates of survival in hepatocellular carcinoma. Methods The red cell distribution width measured at diagnosis was analyzed in relationship to mortality by any cause both in a retrospective training cohort ( N = 208), and in an independent prospectively collected validation cohort ( N = 106) of patients with hepatocellular carcinoma. Based on Cox proportional hazards modelling, a prognostic index was validated. Results In the training and the validation cohort, median survival time was respectively 1026 and 868 days in patients with red cell distribution width ≤14.6%, vs. 282 and 340 days in patients with red cell distribution width >14.6%; the corresponding hazard ratios were 0.43 (95% CI: 0.31–0.60), p < 0.0001 and 0.28 (95% CI: 0.17–0.47), p < 0.0001. At multivariate analysis, the red cell distribution width remained an independent predictor of survival ( p < 0.001) in a Cox model including other widely accepted prognostic factors. Applying to the validation dataset the prognostic index derived from the training dataset, the ability of the model to discriminate the survival probabilities of patients was confirmed (Harrell's C = 0.769). Conclusions The red cell distribution width is a novel, reproducible, prospectively validated predictor of survival in patients with hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: Background: Increasing evidence shows that Hepatitis B virus infection associates with B-cell but not T-cell malignancies. It remains unclear (a) whether this association is restricted to discrete subtypes of B-cell neoplasms and (b) if occult hepatitis B virus infection can impact on the risk of B-cell malignancy. Methods: We analysed the prevalence of occult hepatitis B virus infection in three age and sex matched groups: patients with multiple myeloma, chronic lymphocytic leukaemia and healthy volunteers (N =80 each group). Hepatitis B virus sequences were detected by PCR in blood mononuclear cells isolated prior to treatment. Results: Fifteen subjects tested positive for occult hepatitis B virus infection and its distribution significantly favoured chronic lymphocytic leukaemia (p <0.02) over the other groups. No difference in age, gender and proportion of anti-HBc seropositivity was noted according to occult hepatitis B virus infection status. Chronic lymphocytic leukaemia had an odds ratio of 4.6 (95% CI 1.5–13.9) for the presence of occult hepatitis B virus infection in comparison to multiple myeloma and controls. Most occult hepatitis B virus infection cases (10/15, 67%) were detected in completely hepatitis B virus seronegative subjects. Conclusions: Our data support a potentially causal relationship for hepatitis B virus in chronic lymphocytic leukaemia but not in multiple myeloma. HBsAg seropositivity alone may bias the study of this association, potentially leading to underestimation. Primary occult hepatitis B virus infection appears the most frequent setting in our patients, extending the clinical relevance of hepatitis B virus vaccination to a preventative measure for B-cell neoplasms. [Copyright &y& Elsevier]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus responsible for a variety of clinical manifestations that, besides the lungs, can involve several other organs, leading to both mild and severe complications.1–3 [ABSTRACT FROM AUTHOR]

Background & Aims Transarterial chemoembolization (TACE) is used to treat hepatocellular carcinoma (HCC), but it is a challenge to predict patient survival. The hepatic arterial embolization prognostic (HAP) score has been shown to predict which patients will have shorter survival times and should not undergo TACE. We aimed to validate this scoring system in a prospective study of patients in Europe and Asia. Methods We evaluated the prognostic accuracy of the HAP score in estimating overall survival (OS) of 126 patients with HCC who received TACE in the United Kingdom or Italy (training set) from 2001 through 2013. We also analyzed data from 723 patients treated in Korea and Japan (validation set), including 79 with newly diagnosed HCC, who underwent TACE in Korea or Japan from 2004 through 2013. Response to TACE was determined based on computed tomography analysis. OS was calculated from the time of the first TACE until death or the last follow-up evaluation. Results OS was associated with hypoalbuminemia, α-fetoprotein level greater than 400 ng/mL, and tumor size greater than 7 cm at diagnosis ( P < .01), but not a bilirubin level greater than 17 umol/L ( P > .05), in both data sets. The lack of association between OS and bilirubin level was confirmed using receiver operating characteristic analysis. We developed a modified version of the HAP score, based on the level of albumin and α-fetoprotein and tumor size, which predicted OS with increased accuracy in the training and validation cohorts. Conclusions In a multicenter validation study, we developed a modified version of the HAP that predicts survival of patients with HCC treated with TACE in Europe and Asia. This system might be used to identify patients with HCC most likely to benefit from TACE in clinical practice. [ABSTRACT FROM AUTHOR]

Hypoxia inducible factors (HIFs) are a hallmark of inflammation and are key regulators of hepatic immunity and metabolism, yet their role in HBV replication is poorly defined. HBV replicates in hepatocytes within the liver, a naturally hypoxic organ, however most studies of viral replication are performed under conditions of atmospheric oxygen, where HIFs are inactive. We therefore investigated the role of HIFs in regulating HBV replication. Using cell culture, animal models, human tissue and pharmacological agents inhibiting the HIF-prolyl hydroxylases, we investigated the impact of hypoxia on the HBV life cycle. Culturing liver cell-based model systems under low oxygen uncovered a new role for HIFs in binding HBV DNA and activating the basal core promoter, leading to increased pre-genomic RNA and de novo HBV particle secretion. The presence of hypoxia responsive elements among all primate members of the hepadnaviridae highlights an evolutionary conserved role for HIFs in regulating this virus family. Identifying a role for this conserved oxygen sensor in regulating HBV transcription suggests that this virus has evolved to exploit the HIF signaling pathway to persist in the low oxygen environment of the liver. Our studies show the importance of considering oxygen availability when studying HBV-host interactions and provide innovative routes to better understand and target chronic HBV infection. Viral replication in host cells is defined by the cellular microenvironment and one key factor is local oxygen tension. Hepatitis B virus (HBV) replicates in the liver, a naturally hypoxic organ. Hypoxia inducible factors (HIFs) are the major sensors of low oxygen; herein, we identify a new role for these factors in regulating HBV replication, revealing new therapeutic targets. [Display omitted] • Primate hepadnaviridae encode conserved hypoxia response elements. • Hypoxia inducible factors bind HBV DNA and activate the basal core promoter. • Pharmacological stabilization of hypoxia inducible factors and low oxygen increases HBV transcription and particle genesis. • Knockdown studies show a role for both HIF-1α and HIF-2α in regulating HBV transcription. [ABSTRACT FROM AUTHOR]

The article talks about treatment failure after the interferon-free treatment of hepatitis C as a clue of undetected hepatocellular carcinoma. the study of researchers showing that in presence of active hepatocellular carcinoma (HCC), chances of successful hepatitis C virus (HCV) therapy with direct-acting antivirals (DAA) is low.

Hepatocellular carcinoma (HCC) is increasing globally. Prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Tumour-derived circulating cell-free DNA (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We evaluate the accuracy of ctDNA as a biomarker in HCC. Plasma cell-free DNA, matched germline DNA and HCC tissue DNA were isolated from patients with HCC (n = 51) and liver cirrhosis (n = 10). Targeted, multiplex polymerase chain reaction ultra-deep sequencing was performed using a liver cancer–specific primer panel for genes ARID1A , ARID2 , AXIN1 , ATM , CTNNB1 , HNF1A and TP53. Concordance of mutations in plasma ctDNA and HCC tissue DNA was determined, and associations with clinical outcomes were analysed. Plasma cell-free DNA was detected in all samples. Lower plasma cell-free DNA levels were seen in Barcelona Clinic Liver Cancer (BCLC A compared with BCLC stage B/C/D (median concentration 122.89 ng/mL versus 168.21 ng/mL, p = 0.041). 29 mutations in the eight genes (21 unique mutations) were detected in 18/51 patients (35%), median 1.5 mutations per patient (interquartile range 1–2). Mutations were most frequently detected in ARID1A (11.7%), followed by CTNNB1 (7.8%) and TP53 (7.8%). In patients with matched tissue DNA, all mutations detected in plasma ctDNA detected were confirmed in HCC DNA; however, 71% of patients had mutations identified in HCC tissue DNA that were not detected in matched ctDNA. ctDNA is quantifiable across all HCC stages and allows detection of mutations in key driver genes of hepatic carcinogenesis. This study demonstrates high specificity but low sensitivity of plasma ctDNA for detecting mutations in matched HCC tissue. • Tumour-derived circulating cell-free DNA (ctDNA) can be detected in patients with hepatocellular cancer. • Levels of ctDNA correlate with disease stage, such that levels increased with worsening tumour stage. • Mutations in key known drivers of carcinogenesis were identified in ctDNA. • All mutations in ctDNA were found in matched tumour tissue. [ABSTRACT FROM AUTHOR]

Recent evidence implicates adaptive immunity as a key player in the mechanisms supporting hepatic inflammation during the progression of nonalcoholic fatty liver disease (NAFLD). In these settings, patients with NAFLD often show an increase in the circulating levels of antibodies against oxidative stress-derived epitopes (OSE). Nonetheless, the actual role of humoral immunity in NAFLD is still unclear. This study investigates the contribution of B-lymphocytes to NAFLD evolution. B-lymphocyte immunostaining of liver biopsies from NAFLD patients showed that B-cells were evident within cell aggregates rich in T-lymphocytes. In these subjects, B/T-lymphocyte infiltration positively correlated with both circulating IgG targeting oxidative stress-derived epitopes (OSE) and interferon-γ (IFN-γ) levels. Furthermore, high prevalence of lymphocyte aggregates identified patients with more severe lobular inflammation and fibrosis. In mouse models of NAFLD, the onset of steatohepatitis was characterized by hepatic B2-lymphocytes maturation to plasma cells and by an elevation in circulating anti-OSE IgG titers. B-cell responses preceded T-cell activation and were accompanied by the up-regulation in the hepatic expression of B-cell Activating Factor (BAFF). Selective B2-cell depletion in mice over-expressing a soluble form of the BAFF/APRIL receptor Transmembrane Activator and Cyclophilin Ligand Interactor (TACI-Ig) prevented plasma cell maturation and Th-1 activation of liver CD4 + T-lymphocytes. Furthermore, TACI-Ig mice showed milder steatohepatitis and a decreased progression to fibrosis. Similarly, mice treatment with the BAFF-neutralizing monoclonal antibody Sandy-2 prevented hepatic B2-cell responses and ameliorated steatohepatitis. From these data we conclude that B2-lymphocyte activation is an early event in NAFLD evolution and contributes to the disease progression through the interaction with T-cells. Furthermore, combined clinical and experimental data suggest that elevated circulating anti-OSE IgG can identify a subset of NAFLD patients in whom adaptive immunity has a relevant role in the disease evolution toward fibrosis. [ABSTRACT FROM AUTHOR]

Background Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. Aim To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. Patients Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. Results The mean age of subjects was 60.3 years, with a male/female ratio of 1.7; 74.9% of cases had Child A cirrhosis and 17.9% superimposed hepatocellular carcinoma. HCV infection, alone or in combination with other aetiologic agents, was responsible of 58.6% of cases, HBV aetiology accounted for the 17.6% and alcohol abuse for the 16.0%. Compared with virus-related cirrhotic patients, those alcohol-related more frequently showed decompensation (p = 0.02). Conclusions Compared to previous surveys performed in 1992 and in 2001, we observe a statistically significant (p < 0.05) decreasing role of both HCV infection and alcohol abuse as aetiologic agents of liver cirrhosis in Italy, explaining, at least in part, the slow, progressive decline of the mortality rate for liver cirrhosis in the last decades in this country (from 34.5 deaths/100,000 inhabitants in1980 to 10.8 in 2012). [ABSTRACT FROM AUTHOR]

Background & Aims Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient’s mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. Methods We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n = 1461) accrued from Europe, the United States and Asia. Results Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection ( p <0.001), transarterial chemoembolization ( p <0.001) and sorafenib ( p <0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study ( p <0.001). Conclusions In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. Lay summary Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC. [ABSTRACT FROM AUTHOR]

Aim Catecholamine excess along with an exaggerated sympathetic stimulation appears to play a major role in the pathophysiological mechanism of tako-tsubo cardiomyopathy (TTC), which mimics acute ST-elevation myocardial infarction (STEMI). The aim of the present study was to investigate differences in the distribution of allelic variants of β1- and β2-adrenoceptors between TTC and anterior STEMI patients compared to normal subjects. Methods and results β1- and/or β2-adrenoceptor polymorphisms in 97 patients with TTC (92 females, 96%; mean age 66.8 ± 11.6 years; range 35 to 87 years) were compared with 81 patients with anterior STEMI (77 females, 95%; mean age 72.5 ± 12.8 years; range 32 to 96 years) and 101 controls (95 females, 94%; mean age 62.3 ± 10.4 years; range 44 to 92 years). Differences in genotype frequencies were assessed using the Pearson χ 2 test. β1-Adrenoceptor (Gly389Arg) and β2-adrenoceptor (Arg16Gly and Gln27Glu) genotype frequencies were significantly different among groups (p < 0.001, p = 0.024, p = 0.008, respectively). However, differences did not achieve statistical significance when TTC and anterior STEMI patients were compared by post-hoc analysis. The cardiovascular risk factor profile was worse in anterior STEMI patients, who more often had a history of systemic arterial hypertension, diabetes and coronary artery disease. Conclusions In a large TTC cohort compared with anterior STEMI patients, β-adrenoceptor polymorphisms were similar. However, the cardiovascular risk factor profile was different between the two groups. β-Adrenoceptor polymorphisms in TTC patients differed from normal subjects. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation, with an abnormal pulmonary and systemic inflammatory response to tobacco smoking. Systemic inflammation promotes atherosclerosis, to treat the complications of which beta-blockers are paramount. In the COPD setting, however, the use of beta-blockers has been limited by fears that they could adversely affect lung function. However, by controlling adrenergic drive and reducing the heart rate, beta-blockers could reduce the risk of arrhythmias and sudden death among COPD patients. Thus, beta-blocker use is strongly supported by evidence in COPD patients with history of myocardial infarction, but warrants consideration in other cardiovascular comorbidities. Studies specifically designed to ascertain the role of beta-blockers in patients with COPD with cardiovascular conditions are still needed, because the majority of the current evidence is based on retrospective observational studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: In hypertension clinics, screening patients for the metabolic syndrome (MetS) is common practice, while performing the cumbersome oral glucose tolerance test (OGTT) is not. How large is the underestimation of diabetes and prediabetes that ensues is unknown. Methods: We recruited N=1397 patients with essential arterial hypertension who underwent a 75-g OGTT and were classified as normally glucotolerant (NGT) or having impaired glucose metabolism (IGM), and as affected or not by MetS (ATPIII criteria). The agreement between the OGTT and the ATPIII criteria in attributing a high cardiovascular risk was estimated by matching the categories of MetS and no-MetS with NGT and IGM. Results: n=677/1397 patients (48%) satisfied criteria for MetS, while n=757/1397 (54%) had an IGM. MetS and IGM were both present in n=512/1397 patients (36.6%), and both absent in n=475/1397 (34%). Further n=410/1397 patients (29%) were discordant for the two conditions: n=165/410 (40%) had the MetS but were NGT, and n=245/410 (60%) had IGM but no MetS. Among IGM patients, n=168/757 (22%; of which 45 had no MetS) received a new diagnosis of diabetes based on OGTT criteria. Among all discordant patients, those with IGM and no MetS were more commonly males (p<0.001), and had older age (p<0.001) and lower body mass index (p<0.05). Conclusions: Among patients with hypertension, the estimate of the prevalence of diabetes and prediabetes, hence of the global cardiovascular risk, can be seriously flawed unless an OGTT is performed. Our results support a wider use of the OGTT in the management of hypertension. [Copyright &y& Elsevier]

Background & Aims: A single nucleotide polymorphism (rs12979860 C/T) 3kb upstream of the interleukin 28B (IL-28B) gene was shown to be associated with hepatitis C clearance. We verified whether this association also translates into a different genotype distribution at the end of the disease trajectory. Methods: A RFLP-PCR technique was used to genotype 412 patients with cirrhosis due to hepatitis C (n =199), hepatitis B (n =75), alcohol (n =110), and other causes (n =28), of whom 256 underwent liver transplantation (OLT). Hepatocellular carcinoma (HCC) was demonstrated in the native liver of 85 OLT patients, 52 with viral cirrhosis, and 33 with non-viral cirrhosis respectively. A group of 292 patients (235 HCV and 57 HBV positive) with mild chronic hepatitis and 344 healthy subjects served as controls. Results: A significant difference (p =0.0005) was observed in IL-28B rs12979860 genotype frequencies between patients with viral cirrhosis (C/C=99, C/T=137, T/T=38) and those with non-viral cirrhosis (C/C=72, C/T=58, T/T=8). Patients with HCV related cirrhosis carried more frequently the T/T genotype in comparison to mild hepatitis C or HBV-related cirrhosis. IL-28B rs12979860 genotype frequencies were C/C=23, C/T=50, T/T=12 among OLT patients with cirrhosis complicated by HCC, and C/C=79, C/T=78, T/T=14 among patients with cirrhosis not complicated by HCC (p <0.005). Conclusions: IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. Among OLT patients, carriage of this allele seems to augment the risk of developing HCC. [ABSTRACT FROM AUTHOR]

Abstract: Genetic polymorphisms of interleukin-6 (IL-6) (-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C) may affect the outcomes of several diseases. This study was aimed to verify the role of these polymorphisms on the disease progression of patients with hepatitis C virus (HCV) infection and persistently normal transaminases (PNALT). A total of 121 PNALT patients did not receive any antiviral treatment but underwent periodic clinical monitoring, including repeat biopsies, for a median of 120 months. IL6-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C polymorphisms were related to histologic fibrosis progression. Among patients whose grading and staging scores increased at the end of the follow-up ≥2 Ishak points (N = 60 and N = 26, respectively), IL-6 -174G>C genotype frequencies were GG 37/66, GC 21/45, CC 2/10 (p = 0.041) and GG 18/66, GC 8/45, CC 0/10 (p = 0.040), respectively. The following frequencies were observed for the 572G>C polymorphism: GG 50/105, GC 10/16, CC 0/0, and GG 19/105, GC 7/16, CC 0/0, respectively. Grading progression was independently associated with carriage of the G allele in -174G>C polymorphism (oddd ratio = 5.07%, 95% confidence interval = 0.959–26.8, p = 0.023). Staging progression was independently associated with carriage of the C allele in -572G>C polymorphism (odd ratio = 4.60%, 95% confidence interval 1.42–14.8, p = 0.012). IL-6 polymorphisms influence histologic progression of HCV in patients with PNALT. [Copyright &y& Elsevier]

Abstract: Objectives : To verify the value of indirect serum markers in the non-invasive assessment of liver fibrosis in patients with persistently normal or near normal alanine aminotransferases levels (NALT). Design and methods : Forty HCV RNA positive, untreated patients with NALT (30 non-drinkers) underwent two liver biopsies, with a median interval of 78.5 months. The AST/ALT ratio, age–platelet index, AST to platelet ratio index (APRI), Forns fibrosis index and Bonacini''s discriminant score were simultaneously determined. Results : In 19 patients, worsening of fibrosis was observed at the second biopsy in comparison to the index biopsy. Among non-drinkers, an APRI >0.4 had a 100% sensitivity in identifying subjects with significant liver fibrosis (Ishak staging score >2) and an APRI ≤0.4 had a 100% negative predictive value in excluding significant liver fibrosis. Conclusions : APRI performs better, in comparison to all other markers, in correctly classifying patients with NALT with no progression to significant liver fibrosis. [Copyright &y& Elsevier]