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Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Lay summary Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis., Graphical abstract, Highlights • Under real-world conditions, OCA was effective in ~43% of patients who were non-responders to UDCA, according to Poise criteria. • Patients with cirrhosis showed lower efficacy (29.5%), mainly attributed to reduced tolerability and higher discontinuation rate. • Patients with overlap AIH-PBC showed a comparable efficacy to pure PBC, with a higher ALT reduction at 6 months. • Most patients with PBC are still in need of additional therapy if aiming to normalise liver biochemistry.

Background: Hepatocellular carcinoma (HCC) is among the world’s most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab). Aim: The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment of HCC and the potential influence of liver failure over those pathways. Methods: The Food and Drug Administration (FDA)’s and European Medicines Agency (EMA)’s datasheets, results from clinical trials and observational studies have been reviewed. Results: This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions, and adverse events of medical treatments for HCC in cirrhotic patients. Conclusions: The new scenario of systemic HCC therapy includes more active drugs with different metabolic pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the safety of these molecules are urgently needed.

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. © 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.

Hepatocellular Carcinoma (HCC) is a major healthcare problem. Almost ninety percent of HCCs develops on cirrhosis due to chronic viral hepatitis, Non-Alcoholic Steatohepatitis (NASH) and alcohol abuse. Alcohol itself is defined a strong human carcinogenic agent. Some genetic polymorphisms in alcohol-metabolizing systems and more recently, some sequence variations within the genes coding for patatin-like phospholipase encoding 3 (PNPLA3) and Transmembrane 6 superfamily 2 (TM6SF2), have been found to promote liver fibrosis in alcohol abuse, until HCC development. The current management of HCC is related to tumor burden and liver function and it does not differ in alcoholics, although in alcoholics the surveillance for HCC could be less effective because socioeconomic context, such as the recall policy, the stage at the diagnosis and the prognosis are not different compared to viral HCCs. On regards of loco-regional treatment options, there have not been significant advances in the last few years, though an increasing role will be probably reserved to radio embolization and irreversible electroporation in the next future. Sorafenib (SOR) is still the only drug approved as systemic therapy in patients with HCC, whereas immunotherapy represents a promising approach for the treatment of HCC.

Introduction: Concerns were raised about a high occurrence of hepatocellular carcinoma (HCC) after successful treatment of chronic hepatitis C (CHC) by direct-acting antivirals (DAAs). Areas covered: The authors summarize the clinical studies reporting the occurrence rate and risk factors of HCC after DAAs in CHC. Expert opinion: The recent introduction of all-oral DAAs has substantially changed the scenario of CHC, achieving a sustained virological response (SVR) in >90% of cases. Earlier concerns raised about an increasing incidence of HCC post-DAAs were flawed by large heterogeneity of patients, the limited number of well-designed prospective studies (only nine, up to date) and the inclusion of a large number of patients with advanced liver disease, previously excluded from interferon-based studies. Current data on DAAs have shown a lower risk of HCC development; however, they were unable to identify patients at greater risk for HCC occurrence after SVR. Surveillance strategy, likely lifelong, is mandatory in these patients according to general expert opinion.

International Liver Cancer Association Congress 2015, Paris, France, 4–6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4–6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.

International Liver Cancer Association Congress 2015, Paris, France, 4–6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4–6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.

Determinants of alanine aminotransferase levels have never been investigated in real-life settings. The relationship between alanine aminotransferase and age remains controversial. We evaluated epidemiological, anthropometric, and metabolic factors associated with alanine aminotransferase, focusing on the relationship between alanine aminotransferase and age.A 5-year retrospective analysis was performed on data recorded by 120 general practitioners from Naples (Italy), caring for 170,000 subjects. Exclusion criteria were age18 years, diagnosis of chronic liver disease, positive markers for viral hepatitis, alcohol abuse, and alanine aminotransferase100UI/L.44,232 subjects were enrolled (42.7% males, mean age 56±18 years). Alanine aminotransferase showed independent direct associations with body mass index, glycaemia, cholesterol, and triglycerides (p0.001), and inverse associations with high-density lipoprotein cholesterol (p0.001) and creatinine (p0.01). The relationship between alanine aminotransferase and age was better expressed by polynomial regression (r=0.18, p0.001), creating an inverted parabola. Mean alanine aminotransferase increased until the third decade in males and the fifth in females, with a subsequent progressive decrease in both genders. The inverse association between alanine aminotransferase and age in older subjects was independent from metabolic factors.This real-life setting study, supports the concept that dysmetabolism is a strong determinant of liver injury. Based on our data, a reduction of the standard upper limit of normal alanine aminotransferase should be considered for older subjects.

Transarterial chemoembolization (TACE) is considered as the standard therapy for patients with intermediate-stage hepatocellular carcinoma. However, given the high heterogeneity of this population, no common strategy or protocol standardization has been defined yet. In the last few years TACE treatment has been combined with sorafenib systemic therapy, reporting overall positive results both in terms of safety and efficacy. This systematic review presents and critically discusses the evidence available on the use of TACE in combination (concomitant or sequential) with sorafenib, focusing also on clinical trials currently ongoing to better define an optimal therapeutic strategy for this group of patients.

EASL HCC Summit, Geneva, Switzerland, 13–16 February 2014 The European Association for the Study of the Liver (EASL) organized the 2014 EASL HCC Summit in Geneva, Switzerland. We discuss here the most interesting and provocative contents from the clinical program of the summit. The objective of this segment was to provide an in-depth review on the different management issues related to early detection, diagnosis and treatment of hepatocellular carcinoma, and, in addition, to highlight the ways of dealing with such an important and rapidly involving field.

Background & Aims Notwithstanding evidences implicating the lipopolysaccharides (LPS)/toll-like receptor-4 (TLR4) axis in the pathogenesis of NAFLD, there are no studies aimed to characterize hepatic TLR4 expression in NAFLD patients. We aimed to analyse hepatic TLR4 expression and to verify its relationship with disease activity/evolution in NAFLD patients. Methods Liver tissue from 74 patients with NAFLD and 12 controls was analysed by immunohistochemistry (IHC) for TLR4, α–smooth muscle actin (α–SMA) and cytokeratin-7. IHC for α–SMA was used to evaluate activation of fibrogenic cells (hepatic stellate cells and portal/septal myofibroblasts), that for cytokeratin-7 to count hepatic progenitor cells and bile ducts/ductules, and that for CD68, in a subgroup of 27 patients, for detecting macrophages. Serum LPS-binding protein (LBP), a sensitive marker of LPS activity, was determined in 36 patients and 32 controls. Results As confirmed by double-labelling experiments, the highest level of TLR4 expression was observed in hepatic progenitor cells, biliary cells and portal/septal macrophages. TLR4-positive hepatic progenitor cells and bile ducts/ductules correlated with portal/interface inflammation, activity of fibrogenic cells and fibrosis (P

Aim: To evaluate the diagnostic value of Virtual Touch Quantification (VTQ®) for characterizing benign vs. malignant focal liver lesions (FLLs).Material and methods: From January 2015 to January 2016 all consecutive FLLs visualized during a conventional abdominal ultrasound (US), underwent VTQ® evaluation, taking five measurements of both the lesion and the surrounding parenchyma.Results: We studied 119 FLLs, consisting of 52 hemangiomas (HEs), 39 hepatocellular carcinomas (HCCs), and 28 liver metastases (METs). HEs showed a significantly lower shear wave velocity (SWV) values compared to malignant FLLs (HEs SWV median value 1.34 m/sec, IQR 0.9; malignant lesions SWV median value 2.69 m/sec, IQR 1.6; p

Background & Aims The spectrum of volatile organic compounds in the exhaled breath (breath-print, BP) has been shown to characterize patients with cirrhosis and with worse hepatic function. However, the association of different BPs with clinically relevant outcomes has not been described yet. Hence, we aimed to evaluate the association between BPs, mortality and hospitalization in cirrhotic patients and to compare it with that of the “classical” prognostic indices (Child-Pugh Classification [CPC] and MELD). Methods Eighty-nine cirrhotic patients (M/F 59/30, mean age 64.8 ± 11.3, CPC A/B/C 37/33/19) were recruited and followed up for a median time of 23 months. Clinical and biochemical data were collected. Breath collection and analysis were obtained through Pneumopipe® and BIONOTE e-nose respectively. Results Four different BP clusters (A, B, C, D) were identified. BP clusters A and D were associated with a significantly increased risk of mortality (HR 2.9, 95% confidence intervals [CI] 1.5–5.6) and hospitalization (HR 2.6, 95% CI 1.4–4.6), even in multiple adjusted models including CPC and MELD score (adjusted [a]HR 2.8, 95% CI 1.1–7.0 for mortality and aHR 2.2, 95% CI 1.1–4.2 for hospitalization). CPC C maintained the strongest association with both mortality (aHR 17.6, 95% CI 1.8–174.0) and hospitalization (aHR 12.4, 95% CI 2.0–75.8). Conclusions This pilot study demonstrates that BP clusters are associated with significant clinical endpoints (mortality and hospitalization) even independently from “classical” prognostic indices. Even though further studies are warranted on this topic, our findings suggest that the e-nose may become an adjunctive aid to stratify the risk of adverse outcomes in cirrhotic patients.

The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented. Since not all NAFLD with fibrosis evolve to cirrhosis, we investigated the specific risk of cirrhosis conferred in NAFLD patients by carrying this SNP.Three groups were studied: patients with NASH-cirrhosis; patients with biopsy-proven non-cirrhotic NAFLD; healthy subjects undergoing medicine check-ups. Epidemiological, anthropometric, and clinical data were collected, and the SNP was analyzed by pyrosequencing.Sixty-one patients with NASH-cirrhosis, 60 with non-cirrhotic NAFLD, and 125 healthy controls were included. Frequency of the PNPLA3 minor (G) allele was increased in patients with NASH-cirrhosis compared with non-cirrhotic NAFLD and controls (allele frequency: 0.598 versus 0.367 versus 0.2, respectively, p 0.001), and different between the latter two groups (p 0.001). Three-quarters (74%) of NASH cirrhotics carried at least one G allele, and almost half of them (46%) were GG homozygous. By multivariate analysis in the NAFLD population, each copy of the G allele was associated with an almost doubling of the risk of cirrhosis [OR 1.8 (1.02-3.2)], while being GG homozygous with a tripled risk compared with being CC homozygous [3.01 (1.03-10.8)].In NAFLD patients, carriage of the PNPLA3G allele, and particularly of the GG genotype, is significantly associated with the risk of cirrhotic evolution. If confirmed in larger series, these results would suggest that most of NASH cases require the contribution of an altered PNPLA3 function to progress until cirrhosis.

Since the liver plays a key metabolic role, volatile organic compounds in the exhaled breath might change with type and severity of chronic liver disease (CLD). In this study we analysed breath-prints (BPs) of 65 patients with liver cirrhosis (LC), 39 with non-cirrhotic CLD (NC-CLD) and 56 healthy controls by the e-nose. Distinctive BPs characterized LC, NC-CLD and healthy controls, and, among LC patients, the different Child-Pugh classes (sensitivity 86.2% and specificity 98.2% for CLD vs healthy controls, and 87.5% and 69.2% for LC vs NC-CLD). Moreover, the area under the BP profile, derived from radar-plot representation of BPs, showed an area under the ROC curve of 0.84 (95% CI 0.76–0.91) for CLD, of 0.76 (95% CI 0.66–0.85) for LC, and of 0.70 (95% CI 0.55–0.81) for decompensated LC. By applying the cut-off values of 862 and 812, LC and decompensated LC could be predicted with high accuracy (PPV 96.6% and 88.5%, respectively). These results are proof-of-concept that the e-nose could be a valid non-invasive instrument for characterizing CLD and monitoring hepatic function over time. The observed classificatory properties might be further improved by refining stage-specific breath-prints and considering the impact of comorbidities in a larger series of patients.

the European Association for the Study of the Liver (EASL) organized the 2014 EASL HCC Summit in Geneva, Switzerland from 13 to 16 February 2014. A number of interesting issues on the management of hepatocellular carci-noma (HCC) have been addressed during this meeting. However, our feeling is that only few answers have been given to those questions, mainly because of the still poor knowledge of the molecular basis and the natural history of HCC.HCC is a complex disease, associated in the wide majority of cases with under -lying cirrhosis. In addition, HCC pre-sents with high heterogeneity

Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP

Here, we present the case of an extremely subtle peripheral graft infection caused by Staphylococcus aureus. The lack of local signs and the negativity of all imaging studies, including (99m)Tc-HMPAO-Labelled-Leukocyte Scan which is reported to have 100% sensitivity, delayed the diagnosis and therapy, which were both provided by surgery.

Lysosomal acid lipase deficiency (LAL-d) is a rare autosomal recessive disease in which LAL activity is almost absent, with consequent massive microvesicular steatosis evolving to cirrhosis and liver failure. We aimed to determine LAL-activity, and to investigate the most common single nucleotide polymorphism (SNP) affecting the LIPA gene and responsible for 50–70% of LAL-d cases (rs116928232 c.894G>A), in patients with cryptogenic cirrhosis. Sixty-three patients with cryptogenic cirrhosis, 88 cirrhotics of known etiology, and 97 healthy subjects were enrolled. LAL-activity was determined in dried-blood-spot (DBS). The c.894G>A mutation was analyzed by pyrosequencing method in SNP mode. LAL-activity was severely reduced in patients with cryptogenic cirrhosis with respect to healthy subjects [0.62 (0.44–0.86) Vs 0.96 (0.75–1.25) nmol/spot/h, pA SNP except for one patient with HCV cirrhosis. By multivariate analysis, LAL-activity was not associated with age, sex, liver enzymes, liver function or lipid parameters, while it was independently associated with white blood cell (β = 0.2; p

The liver is one of the principal organs involved in glucose metabolism together with skeletal muscle and adipose tissue. A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, but to date several questions remain unsolved. Altered glucose tolerance has been well described in alcoholic CLD, non-alcoholic fatty liver disease, chronic hepatitis C and portal hypertension. Moreover, insulin resistance is assuming an ever-growing importance in CLD; chronic hepatitis C has recently been proposed as a metabolic disease and insulin sensitivity as a predictive factor for liver fibrosis.CLD is also complicated by acquired growth hormone (GH) resistance, characterized by low concentrations of insulin-like growth factor-1 (IGF-1) with respect to normal or elevated GH levels. GH resistance in CLD is determined by several factors, including malnutrition, impaired liver function and reduced expression of hepatic GH receptors. We recently described the possible role of tumour necrosis factor-alpha (TNF-alpha) in blunting the hepatic response to GH in patients with chronic hepatitis C. The role of GH in impaired glucose metabolism is well known, and recent evidence suggests a receptor and/or post-receptor modulation of insulin signalling. Moreover, as in other chronic inflammatory conditions, pro-inflammatory cytokines may directly modulate the signal cascade that follows insulin binding to its receptor in the course of CLD. In this review, the proposed links between impaired glucose tolerance and CLD are analysed, special emphasis being focussed on the most recent findings concerning the interplay of chronic inflammation, GH resistance and insulin resistance.

Summary Background : Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance. Aim : To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis. Methods : Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit. Results : Serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P

Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn’t mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the “old” IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues guiding treatment indication in the next future. The sooner we will change our mind with respect to an a priori obstacle for anti-HCV treatment in the elderly, the sooner we will begin to spare many aged HCV patients from avoidable liver-related complications.

We aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG-IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty-eight patients with genotype 1b high viral loads were treated with PEG-IFN/RBV/TVR. Peg-IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level (

Background Some reports have documented the coexistence of Hepatitis B surfage Antigen (HBsAg) and anti-HBsAg antibodies (HBsAb) in patients with chronic hepatitis B (CHB), often in the absence of amino acid substitutions in the HBsAg sequences of the Hepatitis B Virus (HBV) genome able to explain an immunological escape variant. HBV genome has a very compact coding organization, with four partially overlapping open reading frames (ORFs). Because the reverse transcriptase region (rt) of HBV polymerase overlaps the HBsAg ORF, it is possible that some mutations in the HBsAg region correspond to mutations in the rt ORF, conferring resistance to current antiviral therapies. This unique case explores the response to antiviral therapies of a CHB with concurrent HBsAg and HBsAb positivity, and analyse the clinical implications of possible mutations in rt and HBsAg ORFs. Case presentation Here we describe the case of a 59 year-old Italian man suffering from Hepatitis B envelope Antigen (HBeAg) positive CHB with concurrent HBsAb positivity. By ultra-deep pyro-sequencing (UDPS) technique, mutations conferring immunological escape or resistance to antiviral therapies were found neither in HBsAg nor in HBV rt ORFs, respectively. The patient was unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus entecavir combination. Surprisingly, during entecavir plus tenofovir combination, anti-HBe seroconversion and HBsAg loss were observed, while the titer of HBsAb persisted. Conclusions Concurrent HBsAg/HBsAb positivity in active CHB is a clinical and virological dilemma. In this setting, there are not consistent data about the response to conventional therapies and the immunological balance between host and virus remains so far unexplained. This is, to our knowledge, the first case described of a CHB with HBsAg/HBsAb positivity, wild type for clinically relevant mutations in HBsAg and rt ORFs, successfully treated with a combination of nucleot(s)ide analogues (NAs).

Introduction Cardiotrophin-1 (CT-1) is a member of the interleukin-6 superfamily with known hypertrophic and protective actions upon cardiac myocytes. Although its effects on myocardial tissue and its role in hypertensive heart disease are well documented, there are no studies on CT-1 blood levels in patients with coronary artery disease. In this study we aimed to verify the relationships of serum CT-1 with vascular disease and metabolic parameters in a population of patients undergoing coronary angiography due to clinical indications. Material and methods Serum levels of CT-1 were investigated in a cohort of 81 consecutive patients (median age 68 years (95% CI: 64-71), 59 males) undergoing coronary angiography and carotid Doppler ultrasound. Exclusion criteria were: acute coronary syndrome, already-established ischemic cardiopathy, chronic inflammatory diseases and presence or past history of cancer. Results Levels of CT-1 were inversely correlated with body mass index (BMI) and waist circumference (WC) (ρ = -0.261, p = 0.02; ρ = -0.224, p = 0.05, respectively). Moreover, obese patients showed significantly lower CT-1 concentrations than non-obese ones (1.18 (0.64-1.64) ng/ml vs. 1.56 (1.37-2.04) ng/ml, p = 0.013), and serum CT-1 was significantly reduced in patients with elevated compared to those with normal WC (1.43 (0.94-1.60) ng/ml vs. 1.64 (1.39-2.49) ng/ml, p = 0.047). Concentrations of CT-1 did not correlate either with the other parameters of metabolic syndrome or with markers of cardiovascular disease (carotid intima-media thickness, presence of carotid or coronary artery plaques). Conclusions Our results failed to demonstrate any association between CT-1 and carotid or coronary disease. The inverse association with BMI and WC fits with the latest experimental data on the role of CT-1 in dysmetabolic conditions and could help to further clarify the role of CT-1 in obesity and diabetes.

Henoch-Schönlein Purpura (HSP) is a small vessel-vasculitis that usually affects children and adolescents; its onset in adults is uncommon.We describe a case of HSP complicated with nephritis and extensive deep vein thrombosis in an 81-year-old Caucasian woman, successfully treated with oral corticosteroids. Even at the extremes of age, HSP should be considered in the differential diagnosis of leukocytoclastic vasculitis, with a particular attention to renal involvement, because of its potential morbidity and mortality in the elderly; in addition, ruling out an occult thrombotic event in course of HSP is mandatory, especially in the presence of additional thrombotic risk factors.

Interruption or hypoplasia of the inferior vena cava, with associated azygos continuation, is an uncommon congenital vascular malformation (Ellis et al, Comput Radiol 1986;10:15-22). Although this anomaly causes venous stasis, few patients present with history of deep vein thrombosis (DVT). The exact role of coexisting thrombophilic gene mutations, also heterozygotic, is far from being completely understood. However, in these cases, because of a probable additive effect, treatment of complications and careful prophylaxis for recurrent DVT are recommended lifelong. The authors report a case of inferior vena cava interruption with azygos continuation in a 30-year-old woman who presented with a history of recurrent lower limb DVT. In addition, heterozygosis for the H1299R polymorphism of the factor V gene (Factor V HR2), for the C677T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR C677T) and for the 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene (PAI-1 4G/5G) was found in DNA analyses.