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To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.

BACKGROUND: While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated. AIM: To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy. PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologically METHODS: proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis. RESULTS: Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0% vs 58.7%, P = 0.03), had lower transaminase levels (3.3 ± 2.0 vs 3.8 ± 2.5 u.l.n., P = 0.004), and had higher rate of alcohol intake (38.3% vs 22.5%, P < 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34-2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41-2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69-1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76-1.95). CONCLUSIONS: In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.

© 2015 Macmillan Publishers Limited. All rights reserved.Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined

Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P

Background Only a small proportion of subjects referring to hospitals for hepatitis C virus (HCV) positivity receives antiviral therapy. Aim To evaluate the rate of antiviral treatment and the causes for no treatment in HCV-RNA positive subjects seen in hospital settings. Patients and methods A prospective study enrolling over a 6-month period (February–July 2009) all consecutive anti-HCV positive subjects initially referred (naive patients) to 12 liver units in Southern Italy for HCV treatment. Results Out of 608 subjects evaluated, 74 (12.2%) had no detectable HCV-RNA in the serum and thus were excluded. Of the remaining 534 HCV-RNA positive subjects, 357 (66.9%) were not treated for the following reasons: 49.9% were older than 65 years of age (75% of them >70 years), 14.3% had normal liver enzymes, 13.2% had compensated/decompensated cirrhosis, 10.4% refused treatment, 9.8% had ongoing substance or alcohol abuse. Multivariate analysis showed that females (O.R. 2.27; C.I. 95% 1.05–4.90) and subjects with low educational level (O.R. 4.38; C.I. 95% 1.27–15.11) were more likely to decline therapy. Conclusions The majority of patients with HCV infection does not receive antiviral treatment. The effectiveness of the current standard therapy for HCV infection is low despite its good efficacy.

There is a lack of information on the characteristics of patients with chronic hepatitis C virus infection (HCV) who fail to respond to antiviral treatment. We studied HCV-positive subjects with chronic liver diseases treated with pegylated-interferon (PEG-IFN) and ribavirin (RBV) who failed to clear HCV in routine clinical practice. A total of 2150 consecutive adult patients treated with PEG-IFN plus RBV therapy in 46 Italian centres between 1 July 2004, and 30 June 2005, were studied. Of the 2150 patients, 923 (42.9%) (M/F 585/335, mean age 54.8 years) failed to achieve a serum HCV-RNA clearance. Of these 923 patients, 429 (46.5%) were nonresponders, 298 (32.3%) relapsers, 168 (18.2%) drop-outs for noncompliance or adverse events and 28 (3.0%) were lost during follow-up. Overall, 642 (70.6%) patients received adequate therapy (defined as more than 80% of the drug doses for >80% of the time). Genotypes 1-4 were observed in 76.9% of cases; genotypes 2-3 in 21.2% and mixed in 1.9%, respectively. Multiple logistic regression analysis identified genotypes 1 and 4 as the sole independent predictors of the likelihood of nonresponse to therapy compared with relapse (OR: 4.38; 95% CI = 2.28-8.4). Age older than 65 years was the sole independent factor associated with no adherence to therapy (OR: 2.22; 95% CI = 1.36-3.62). Patients who fail to respond to treatment are a nonhomogeneous population with different features, and the sole factor that discriminates nonresponse from relapse is the distribution of genotypes 1-4. Co-morbidities are unable to determine the type of treatment failure and inadequate adherence to therapy mostly affects patients older than 65 years of age. © 2009 Blackwell Publishing Ltd.

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.Genes and Immunity advance online publication, 10 May 2012; doi:10.1038/gene.2012.17.

Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as “probable” cases. The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of new laboratory tools for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative at IIF. We will also provide a discussion of the history and current status of AMA detection methods. We included IIF AMA-negative PBC sera (n = 100) and sera from patients with other chronic liver diseases (n = 104) that had been independently tested for IIF AMA and ANA; sera were blindly tested with an ELISA PBC screening test including two ANA (gp210, sp100) and a triple (pMIT3) AMA recombinant antigens. Among IIF AMA-negative sera, 43/100 (43%) manifested reactivity using the PBC screening test. The same test was positive for 6/104 (5.8%) control sera. IIF AMA-negative/PBC screen-positive sera reacted against pMIT3 (11/43), gp210 (8/43), Sp100 (17/43), both pMIT3 and gp210 (1/43), or both pMIT3 and Sp100 (6/43). Concordance rates between the ANA pattern on HEp-2 cells and specific Sp100 and gp210 ELISA results in AMA-negative subjects were 92% for nuclear dots and Sp100 and 99% for nuclear rim and gp210. Our data confirm the hypothesis that a substantial part of IIF AMA-negative (formerly coined “probable”) PBC cases manifest disease-specific autoantibodies when tested using newly available tools and thus overcome the previously suggested diagnostic classification. As suggested by the recent literature, we are convinced that the proportion of AMA-negative PBC cases will be significantly minimized by the use of new laboratory methods and recombinant antigens.

OBJECTIVES: The occurrence of decompensation marks a crucial turning point in the course of cirrhosis. The purpose of this study was to assess the risk of mortality according to the clinical characteristics of first decompensation, considering also the impact of acute-on-chronic liver failure (AoCLF). METHODS: We conducted a prospective nationwide inception cohort study in Italy. Decompensation was defined by the presence of ascites, either overt or detected by ultrasonography (UD), gastroesophageal variceal bleeding (GEVB), and hepatic encephalopathy (HE). AoCLF was defined according to the Asian Pacific Association for the Study of the Liver criteria. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or orthotopic liver transplantation (OLT)). RESULTS: A total of 490 consecutive cirrhotic patients (314 males, mean age 60.9±12.6 years) fulfilled the study criteria. AoCLF was identified in 59 patients (12.0%). Among the remaining 431 patients, ascites were found in 330 patients (76.6%): in 257 (77.8%) as overt ascites and in 73 (22.2%) as UD ascites. GEVB was observed in 77 patients (17.9%) and HE in 30 patients (7.0%). After a median follow-up of 33 months, 24 patients underwent OLT and 125 died. The cumulative incidence of failure (death or OLT) after 1, 2, and 3 years was, respectively, 28, 53, and 62% in patients with AoCLF; 10, 18, and 25% in patients with UD ascites; 17, 31, and 41% in patients with overt ascites; and 8, 12, and 24% in patients with GEVB (P

The global spread of hepatitis B virus (HBV) and hepatitis C virus (HCV), their high chronicity rates and their progression to cirrhosis and hepatocellular carcinoma, are major public health problems. Research and intervention programmes for special population groups are needed in order to assess their infection risk and set up suitable prevention and control strategies. Aim of this paper is to give health care professionals information on HBV and HCV infections amongst migrants, drug users and prison inmates. The manuscript is an official Position Paper on behalf of the following Scientific Societies: Italian Association for the Study of the Liver (A.I.S.F.), Italian Society of Infectious and Tropical Diseases (S.I.M.I.T.), Italian Federation Department's Operators and Addiction Services (FederSerD), Italian Prison Medicine and Healthcare Society (S.I.M.S.Pe.). The considered population groups, having a high prevalence HBV and HCV infections, require specific interventions. In this context, the expression “special population” refers to specific vulnerable groups at risk of social exclusion, such as migrants, prison inmates, and intravenous drug users. When dealing with special population groups, social, environmental and clinical factors should be considered when selecting candidates for therapy as indicated by national and international guidelines.

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

Summary. Hepatitis C virus (HCV) infection is associated with a significant reduction of health related quality of life (QOL), the causes and mechanisms of which are still unknown. To explore whether treatment history could affect QOL, we examined patients with detectable HCV viraemia who had a different therapeutic background. Two hundred sixty-four consecutive subjects with chronic HCV infection and detectable viraemia were enrolled. Of these, 163 were untreated patients, 43 were relapsers, 58 were nonresponders (NR) to nonpegylated interferon (IFN) therapy. To assess QOL, three self-report instruments were employed: the Short Form-36 (SF-36), the Chronic Liver Disease Questionnaire (CLDQ-I) and the World Health Organization Quality of Life assessment (WHOQOL-BREF). Clinical and demographic data were collected, and the QOL scores of HCV-positive patients were compared with those of an Italian normative sample and healthy controls. Further antiviral treatment was offered to untreated and relapsed patients but not to NR. All patient groups displayed lower QOL scores compared with the normative sample and controls. NR displayed lower QOL scores in several areas compared with untreated patients and relapsers. In multivariate regression analyses, being NR and having a physical comorbidity were significantly associated with poorer QOL. Conclusions: Treatment history and expectations and physical comorbidity may affect QOL in HCV-positive patients. Untreated and relapsed patients have comparable levels of QOL and higher scores than NR.

Purpose: We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil. in comparable groups of patients with erectile dysfunction (ED). Materials and Methods: This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. Results: Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p

Aim The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008–2013 and 2014–2019. Methods We compared the two eras, era1: 2008–13, era2: 2014–19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. Results In the population hospitalized for DFU in 2008–2013, 59.1% of males and 40.9% of females died, whilst in 2014–2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p < 0.001), just as CKD was severe (14.5% vs. 4%, p < 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07–2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37–2.95, p Conclusions Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality.

Background The last Italian prevalence survey on chronic hepatitis (CH) conducted in 2001 showed that the hepatitis C virus (HCV) was the main agent associated with CH. Aim The aim of this study was to evaluate epidemiological changes in CH occurring after 13 years. Patients and methods Enrollment of 1392 CH consecutive patients referred to 16 Italian liver units in 2014 scattered all over the country (four in the North, four in the Center, four in the South, and four in the Islands) was performed. Results The mean age of the patients was 58.3 years, with a sex ratio (male/female) of 1.5. HCV infection (also with other etiologies) continues to be the most prevalent etiology (58.1%). However, this prevalence was lower (P

Background & Aims: The risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients. Methods: Data from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death. Results: Included were 1000 patients with SVR. Median age was 52.7 (IQR 45.1–59.7) years, 676 (68%) were male and 842 (85%) had cirrhosis. Median follow-up was 5.7 (IQR 2.9–8.0) years. Fifty-one patients developed HCC and 101 had clinical disease progression. The cumulative 8-year HCC incidence was 1.8 (95% CI 0.0–4.3) among patients with bridging fibrosis and 8.7% (95% CI 6.0–11.4) among those with cirrhosis (p = 0.058). Within the cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI 0.0–5.5) among patients 60 years of age at start of therapy (p = 0.006). Multivariable Cox analyses indicated that higher age, lower platelet count and diabetes mellitus were independently associated with development of HCC. After 8 years 4.2% (95% CI 0.1–8.3) of patients with bridging fibrosis and 15.8% (95% CI 12.3–19.3) of patients with cirrhosis experienced clinical disease progression (p = 0.007). Conclusions: Patients with HCV-induced cirrhosis and SVR showed an annual risk of approximately 1% for HCC and 2% for clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before cirrhosis has developed. Lay summary: Patients with cirrhosis who were able to eradicate their chronic HCV infection remain at substantial risk of primary liver cancer. The risk of liver cancer increases with higher age, laboratory makers suggesting more severe liver disease, and presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain included in follow-up for early detection of liver cancer. 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Objective Swallowing and voice impairment are common after thyroidectomy. We evaluated short-term functional changes in esophageal motility in a series of patients who had undergone total thyroidectomy. Several studies have investigated these symptoms by means of interviews or questionnaires. Study Design Prospective study. Setting Academic research. Materials and Methods Thirty-six consenting patients were prospectively recruited. Eligibility criteria were thyroid volume ≤60 mL, benign disease, and age between 18 and 65 years. Exclusion criteria were previous neck surgery, severe thyroiditis, hyperthyroidism, and pre- or postoperative vocal cord palsy. Voice impairment score, swallowing impairment score, lower esophageal sphincter pressure, esophageal motility, upper esophageal pressure, and coordination were evaluated preoperatively and 30 to 45 days after surgery. Results Postoperative swallowing impairment (appearance or worsening of dysphagia) was found in 20% of patients and voice impairment in more than 30%. Both preoperative and postoperative esophageal motility were similar. All patients showed an average decrease of 25% in upper esophageal pressure, although the pressure was within normal range. Swallowing alterations were associated with upper esophageal incoordination (P < .03), and proximal acid reflux was significantly associated with voice impairment (P < .02). Conclusion After uncomplicated thyroidectomy, decreased upper esophageal pressure may explain both pharyngeal (dysphagia) and laryngeal (vocal impairment) exposure to acid. In the future, proton pump inhibitor therapy protocols should be evaluated.

Background Treatment choice for chronic HBV infection is a continuously evolving issue, with a wide range of options. We aimed to evaluate the current practice of HBV therapies in the real world in Southern Italy. Methods A prospective study enrolling over a six month period (February–July 2010) all consecutive HBsAg positive subjects, never previously treated, referred to 16 liver units in two Southern Italy regions (Calabria and Sicily). Results Out of 247 subjects evaluated, 116 (46.9%) had HBV-DNA undetectable or lower than 2000 UI/ml. There were 108 (43.7%) inactive carriers, 103 (41.7%) chronic hepatitis, and 36 (14.6%) liver cirrhosis. Antiviral treatment was planned in 94 (38.0%) patients (26 cases with Interferon or Pegylated Interferon and 68 with nucleos(t)ides analogues). As many as 49.5% of subjects with chronic hepatitis did not receive antiviral treatment. Discussion The majority of chronic HBsAg carrier referring centres for evaluation were not considered suitable for antiviral treatment. Nucleos(t)ides analogues are the preferred first choice for therapy. A long-lasting period of observation may be needed to make appropriate therapeutic decisions in several cases.

OBJECTIVES: The identification of prognostic factors associated with mortality is crucial in any clinical setting. METHODS: We enrolled in a prospective study 352 patients with compensated hepatitis C virus (HCV)-induced cirrhosis, consecutively observed between 1989 and 1992. At entry, patients underwent upper endoscopy to detect esophageal varices, and were then surveilled by serial clinical and ultrasonographic examination. The model for end-stage liver disease (MELD) score was calculated with information collected at enrollment. Baseline predictors and intercurrent events associated with mortality were assessed using the Cox regression model. RESULTS: During a median follow-up of 14.4 years, 194 subjects received a single course of interferon monotherapy, 131 patients developed decompensation (ascites, bleeding, hepatic encephalopathy), 109 patients had hepatocellular carcinoma (HCC), 9 had liver transplant, and 158 died. Esophageal varices were associated with development of decompensation (hazard ratio (HR), 2.09; 95% confidence interval (CI), 1.33-3.30) and liver-related death (HR, 2.27; 95% CI, 1.41-3.66). A MELD score of > 10 predicted overall mortality (HR, 2.15; 95% CI, 1.50-3.09). Overall survival of patients with MELD < or = 10 was 80% at 10 years. HCC occurrence increased the risk of decompensation fivefold (HR, 5.52; 95% CI, 3.77-8.09). Hepatic and overall mortality hazard ratios were 8.62 (95% CI, 5.57-13.3) and 3.80 (95% CI, 2.67-5.42), respectively, for patients who developed HCC, and 16.9 (95% CI, 9.97-28.6) and 7.08 (95% CI, 4.88-10.2) for those who experienced decompensation. CONCLUSIONS: In patients with compensated HCV-induced cirrhosis, the presence of esophageal varices at baseline predicted decompensation and mortality. The development of HCC during follow-up strongly hastens the occurrence of decompensation, which is the main determinant of death. Patients with a MELD score < or = 10 at study entry had a prolonged life expectancy.

Background & Aims: Appearance of auto antibodies have been described during anti-tumor necrosis factor (TNF) alpha therapy; however, their prevalence and clinical relevance are still unclear. We investigated prevalence of autoantibodies in inflammatory bowel diseases (IBD) patients on anti-TNFα treatment and occurrence of clinical symptoms. Methods: Titers of ANA, anti-dsDNA, SMA, AMA, LKM were evaluated from blood samples in patients receiving anti-TNFα inhibitor (adalimumab, infliximab). Results: Among 39 patients treated with anti-TNFα therapy, twenty of them developed ANA, mostly induced by infliximab. 55% ANA positive patients developed peripheral polyarthralgias with no need for intervention. No patients with positive autoantibodies developed a drug-induced lupus. The incidence of dsDNA, SMA and AMA was low and was not associated with autoimmune disease. Conclusions: Immune response induced by anti-TNFα is restricted to ANA, with lower prevalence of dsDNA antibodies, SMA and AMA. Further studies are needed to clarify the role of autoantibodies during anti-TNFα therapy.

It has been shown that sexual hormones have an opposite effect on hepatic fibrosis progression and hepatocellular carcinoma development. Sex differences among 2,762 chronic HBsAg carriers consecutively referring Italian hospitals in 2001 and in 2007 have been evaluated, particularly focusing on the role of gender on severity of liver disease. The overall sex ratio (males/females) was 2.6. Females were more likely born abroad and new diagnosis cases; but less likely HIV coinfected. No sex difference was observed regarding coinfection with other hepatitis viruses. The sex ratio linearly increased with increasing severity of liver disease, being 1.3 in normal ALT, 2.8 in chronic hepatitis, 3.6 in liver cirrhosis, and 6.8 in hepatocellular carcinoma. Adjustment by multiple logistic regression analysis for the confounding effect of age, alcohol intake, HDV infection, HCV infection, and BMI shows that male gender is an independent predictor of the likelihood of more severe liver disease (O.R. 1.7; C.I. 95% = 1.3-2.1). HBV-DNA levels resulted not associated with the outcome of chronic HBV infection. Despite some potential risk factors associated with liver disease, such as HBV genotype or mutations, not having been controlled for due to lack of availability, the observed sex disparity in the outcome of chronic HBV infection may support biological observation that HBV infection could be considered a sex hormone-responsive virus.

I polimorfismi genetici e/o i fattori ambientali, ad esempio l’alcol e/o i farmaci concomitanti, contribuiscono alla suscettibilità individuale nel determinare il danno epatico da farmaci. L’HLA si è dimostrato essere uno dei più importanti predittore di suscettibilità individuale anche per quei farmaci per i quali questa non era stata mai sospettata.

Summary Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.

BACKGROUND AND AIM: Data on maximum resting pressure (MRP) and maximum squeeze pressure (MSP) changes after hemorrhoidectomy are not univocal and follow-up of patients undergoing surgery is mostly short-lived. The aim of this study was to prospectively examine during 1-year follow-up the long-term manometric results of MRP, MSP, and ultra slow wave activity (USWA) within a set of patients undergoing Milligan-Morgan hemorrhoidectomy as compared to healthy controls. MATERIALS AND METHODS: Twenty patients with hemorrhoids of third and fourth degree were enrolled and anorectal manometry was performed preoperatively, on the 5th day, and after 1, 6, and 12 months after surgery. RESULTS: On the 5th and 30th day after hemorrhoidectomy, USWA was slightly increased as compared to preoperative status. Six and 12 months after surgery, patients with USWA were significantly less in comparison to preoperative assessment without differences with healthy subjects. After surgery, MSP values were not significantly different to baseline values. On the 5th postoperative day after hemorrhoidectomy, MRP was significantly greater than baseline preoperative values. Thirty days after surgery, MRP values were similar to those detected preoperatively, but still significantly increased as compared to healthy subjects. After 6 and 12 months, MRP values were significantly lower than those detected during preoperative phase and comparable to healthy subjects. CONCLUSIONS: Our data support that Milligan-Morgan hemorrhoidectomy induces a complete resolution of typical manometric alterations of disease and that the excision of anal cushions is responsible only for mild and transient alteration of anal continence.

Objectives: to evaluate the clinical efficacy and the effects on the quality of life of Iloprost, a prostacyclin analogue, used, according to a new protocol, in patients with Raynaud’s phenomenon secondary to Systemic Sclerosis. Methods: in this randomized study we treated 30 patients with Iloprost given by intravenous infusion, at progressively increasing doses (starting from 0.5 ng/Kg/min up 2 ng/Kg/min) over a period of 6 hours a day for ten days in two consecutive weeks, with repeated cycles at regular intervals of three months for 18 months. The results were compared with those obtained in 30 other patients, who had received the same drug but with different posologic schemes. Results: the total average daily duration of the attacks, the average duration of a single attack and the average daily frequency of the attacks were reduced significantly in all groups of treatment, but the comparison between the groups demonstrated significant differences between patients treated with the new protocol and the others at later times (T12 and T18). The effects on the quality of life, evaluated by SF-36, demonstrate, in the group treated with the new protocol, a marked improvement both regarding the scale relative to the physical aspect of the illness, and especially regarding the scale relative to the mental aspect. Conclusions: in SSc patients, cyclic intravenous Iloprost infusion is efficacious in the treatment of Raynaud’s phenomenon. The protocol that we used, compared with others, is able to determine not only favourable clinical effects but also a marked improvement in the quality of life.