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After the first successful pregnancy in a liver transplant recipient in 1978, much evidence has accumulated on the course, outcomes and management strategies of pregnancy following liver transplantation. Generally, liver transplantation restores sexual function and fertility as early as a few months after transplant. Considering that one third of all liver transplant recipients are women, that approximately one-third of them are of reproductive age (18-49 years), and that 15% of female liver transplant recipients are paediatric patients who have a >70% probability of reaching reproductive age, the issue of pregnancy after liver transplantation is rather relevant, and obstetricians, paediatricians, and transplant hepatologists ever more frequently encounter such patients. Pregnancy outcomes for both the mother and infant in liver transplant recipients are generally good, but there is an increased incidence of preterm delivery, hypertension/preeclampsia, foetal growth restriction, and gestational diabetes, which, by definition, render pregnancy in liver transplant recipients a high-risk one. In contrast, the risk of congenital anomalies and the live birth rate are comparable to those of the general population. Currently there are still no robust guidelines on the management of pregnancies after liver transplantation. The aim of this position paper is to review the available evidence on pregnancy in liver transplant recipients and to provide national Italian recommendations for clinicians caring for these patients. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Recent studies have questioned the role of unidirectional airflow ventilation system in reducing surgical site infection (SSI) in prosthetic implant surgery. The aim of the ISChIA study ("Infezioni del Sito Chirurgico in Interventi di Artroprotesi" which means "Surgical site infections in arthroplasty surgery") was to evaluate, as a contribution to this debate, the association between heating, ventilation and air conditioning systems, microbial air contamination and surgical site infection in hip and knee arthroplasty.The study was performed from March 2010 to February 2012 in 14 hospitals, for a total of 28 operating theatres: 16 were equipped with vertical unidirectional airflow ventilation (U-OTs), 6 with mixed airflow ventilation (M-OTs), 6 with turbulent airflow ventilation (T-OTs). Microbial air contamination in the operating theatre was evaluated by means of passive (Index of Microbial Air contamination, IMA) and active (Colony Forming Units per cubic metre, cfu/m3) sampling. SSI surveillance was carried out according to the Hospitals in Europe Link for Infection Control through Surveillance protocol.A total of 1,285 elective prosthesis procedures (61.1% hip and 38.9% knee) were included in the study. The results showed a wide variability of the air microbial contamination in operating theatres equipped with unidirectional airflow. The recommended values of ≤2 IMA and ≤10 cfu/m3 were exceeded, respectively, by 58.9% and 46.4% of samples from U-OTs and by 87.6% and 100% of samples from M-OTs. No significant difference was observed between SSI cumulative incidence in surgical procedures performed in U-OTs compared with those performed in T-OTs. A lower risk of SSI, even though not statistically significant, was shown in surgical procedures performed in U-OTs with a microbial air contamination within the recommended values (≤2 IMA and ≤10 cfu/m3) compared with those performed in U-OTs where these limits were exceeded, and compared with those performed in T-OTs with microbial air contamination within the recommended values for this type of OTs (≤25 IMA, ≤180 cfu/m3.ISChIA study did not show a protective effect of unidirectional airflow compared with turbulent airflow in arthroplasty surgery. However, the frequent exceeding of recommended air microbial contamination values in OTs equipped with unidirectional airflow, and the lower SSI risk in surgical procedures performed in compliant U-OTs compared with those performed in non-compliant U-OTs and with those performed in compliant T-OTs, suggest the need of further studies, which should consider air microbial contamination and other aspects of SSI prevention that may negate the potential benefits of the ventilation system; differences in intrinsic and extrinsic risk factors, medical treatment and surgical technique are also to be considered. Training interventions aimed at improving the behaviour of operators are essential.

The Perioperative Antibiotic Prophylaxis (PAP) contributes considerably to the total amount of antibiotics used in hospitals and has been shown to be associated with increase in antibiotic resistance and healthcare costs. The level of compliance with the national guidelines of current practices of PAP for elective hip and knee prosthesis procedures in a network of Italian hospitals (the multicentre Surgical Site Infection surveillance project GISIO-ISChIA), has been evaluated.Compliance of the current prophylactic antibiotic practices with the published national guidelines was assessed for each included operative procedure, considering indication, timing of administration, prescribed antimicrobial agent and total duration of prophylaxis.A total of 14 hospitals and 1285 surgical procedures were included. 99.4% of patients received antimicrobial prophylaxis pre-operatively and 73.0% of patients received PAP within the recommended time period (within 60 minutes before incision). The rate of compliance with discontinuation of PAP within 24 hours after initiation of surgery was 70.2%. Taking into account all doses administered, the antibiotic was chosen appropriately in 57.7% of patients. PAP was performed appropriately, in accordance with national guidelines, in 43.6% of surgical operations.Given the increasing number of replacement procedures in Italy and in Europe, the gap between the evidence-based guidelines and practice must be appropriately addressed in order to improve PAP practices.

Carriage of the apolipoprotein E (Apo E) variants, E2, E3 and E4, affects cholesterol metabolism and may be involved in the persistence of hepatitis C virus (HCV) infection. Our aim was to verify whether carriage of specific Apo E variants modulates the course of hepatitis C.We studied a cohort of 116 HCV-positive patients (49 male subjects) with persistently normal transaminases and an Ishak staging score ≤ 2 at an initial biopsy. These untreated patients underwent regular clinical monitoring (median histological follow up: 10 years). Apo E variants were genotyped and results were related to the histological outcome.The mean ± standard deviation staging scores were 0.9 ± 0.7 at entry versus 1.9 ± 1.2 at the end of follow up, P0.0001. Initial and final staging scores in the E3/E3 homozygotes (n = 74) were 1.0 ± 0.7 versus 2.1 ± 1.3, P0.0001, while in the remaining patients (n = 42) they were 0.9 ± 0.6 versus 1.5 ± 1.0, P0.002. A synergistic effect was observed between Apo E polymorphisms and baseline serum cholesterol values: patients not carrying any E3 allele, as well as carriers of a single E3 allele with serum cholesterol concentration190 mg/dL were more likely to have a favorable outcome (final vs initial staging score increased in 7/66, did not change in 10/46, and decreased in 3/4, P0.005).Some of the variability in the natural history of patients with persistently normal transaminases with initially mild hepatitis C can be related to their Apo E genetic background.

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.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. HCC is a major problem worldwide because of its high prevalence and severe natural history and it is the major cause of cancer-related mortality in sub-Saharan Africa and in the Far East (1). HCC is the seventh most prevalent cancer in men and the ninth most common in women, with an estimated total of one million cases occurring each year (2-6). It carries a dismal overall prognosis: 92% of affected individuals will die because of their disease (3). In general, tumor incidence increases with age and occurs most often between the third and fifth decades of life (2). The distribution pattern shows striking and pronounced geographic and racial variations. The biological characteristics of this tumor vary significantly in different geographical areas, from country to country and even from one part of a country to another. Because of the widely divergent rates of HCC worldwide, it is possible to identify high-, intermediate-, and low-incidence areas. In China and south-east and sub-Saharan Africa, as many as 10-30 new cases per 100,000 males in habitants are reported each year, whereas in northern Europe, North America, and Australia, the annual rates of HCC are less than 3 cases a year per 100,000 males.

Aims: The aim of this study was to assess the incidence of fatal, life-threatening side effects and the de novo appearance of non-hepatic morbidity during interferon alfa therapy for chronic viral hepatitis. The relationship of these adverse events to actual total dose and duration of interferon was also evaluated. Methods: We conducted a retrospective study at 73 Italian centers of 11 241 consecutive patients with chronic vital hepatitis who underwent interferon alfa treatment. Results: Five patients died during interferon therapy due to liver failure ( n =4) or complications arising from sepsis. Life-threatening side effects were observed in eight patients: two cases where depression developed and led to a suicide attempt and six patients with bone marrow suppression (granulocytes 3 or platelets 3 ). These symptoms and signs completely disappeared after interferon withdrawal. During interferon treatment, 131 patients developed the following de novo non-hepatic disorders: symptomatic thyroid disease ( n =71), impotence ( n =5), systemic autoimmune disease ( n =5), immune-mediated dermatologic disease ( n =14), diabetes mellitus ( n =10), cardiovascular disease ( n =7), psychosis n =10), seizures ( n =4), peripheral neuropathy ( n =3) and hemolytic anemia ( n =2). Most of these complications are reversible or can be ameliorated. Fatal or life-threatening side effects were not related to actual total dose or duration of interferon alfa, while the majority of patients with de novo non-hepatic morbidity received medium/high doses ( > 200 million units) of interferon alfa or were treated for periods longer than 16 weeks (68% and 80%, respectively). Conclusions: Treatment with interferon alfa may have fatal or life-threatening side effects, their incidence in this study being low (0.04% and 0.07%, respectively) and perhaps no different than in untreated patients with chronic viral hepatitis. Moreover de novo non-hepatic morbidity occurred in 1.2% of patients, and the dose and duration of interferon therapy seem important in determining the frequency of this complication. The development of clinically-overt thyroid disease was most common.