Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity.

BACKGROUND: Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. METHODS: 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. RESULTS: 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of positive serum anti-nuclear antibodies than CD and IBS patients, and a higher frequency of DQ2/DQ8 haplotypes and duodenal mucosa lymphocytosis than IBS controls. In addition, 50% of NCWS patients showed neuropsychiatric manifestations, while lower percentages were observed in CD (25%) and IBS (28%) controls. Neuropsychiatric symptoms in NCWS were more frequently associated with the male sex, longer duration of symptoms, and IBS-diarrhea-like clinical presentation. CONCLUSIONS: Our data suggest that in patients with IBS-like symptoms and neuropsychiatric manifestations of unknown cause, it could be useful to investigate a correlation of these symptoms with wheat ingestion to identify NCWS patients with this 'atypical' manifestation.

Screening and surveillance for hepatocellular carcinoma: perspective of a new era?

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death with an increasing prevalence worldwide. Early diagnosis of HCC is important since observational studies have reported that, in patients undergoing surveillance, cancer is diagnosed at an earlier stage with increased chances of curative therapies. Anyway, despite the extensive use of screening for HCC, its effectiveness is still a controversial topic since supporting evidence is not unequivocal and some issues need to be explored. Areas covered: The aim of this paper is to review main literature data supporting performance and effectiveness of screening for early detection of hepatocellular carcinoma. Expert commentary: Clinical benefit of screening for HCC is controversial and there are no sufficient data supporting its effectiveness in reducing cancer specific mortality. Since it is unlikely that RCTs will be performed in the future, surveillance should be still reasonably recommended in all at-risk population, until potential data against its effectiveness will be provided. In the future additional and more effective non-invasive tests will be needed, as well as proper surveillance intervals and risk threshold for surveillance enrollment must be assessed and refined by prospective studies.

An update on medical management on Crohn's disease.

INTRODUCTION: The management of Crohn's disease (CD) is continuously evolving. New issues emerging from more recent studies could influence the decision-making process in clinical practice. AREAS COVERED: The aim of this review article is to highlight critical issues on the management of CD, new evidence from clinical trials, long-term prospective studies and real life experience, beyond the current guidelines. EXPERT OPINION: The role of mucosal healing in clinical practice is uncertain, clinical remission remains the primary end point. The timing for the definition of steroid-resistant CD should be considered between 2 and 4 weeks. Early treatment strategy with immunomodulators is effective for inducing remission but no controlled data are available regarding long-term outcome. Combination therapy (anti-TNFs agents and immunosuppressors) is more effective than single therapy but there is a lack of long-term data and an increased risk of malignancy. The effect of mesalazine, metronidazole and azathioprine in reducing postoperative recurrence is not clinically relevant; biologics are effective, but the duration of treatment is unknown. New drugs are under investigation in order to find exit strategy for patients who no longer respond to biologics. Combination therapy set on anti-TNF-α is until now the best option both to achieve fistula healing and avoid recurrence.

Distribution of liver disease in a cohort of immigrants in Sicily: analysis of day-hospital admissions in a migration medicine unit.

The objective of this study was to evaluate the frequency of liver disease and its aetiology in a cohort of immigrants. We retrospectively examined the hospital discharge charts of all the immigrant patients presenting at our day hospital from July 2009 to June 2013, and after evaluating the anamnestic, clinical and laboratory data on these charts we identified subjects with liver disease and its various aetiologies. The total sample population consisted of 1218 patients, of whom 112 (9.2%) had a diagnosis of liver disease. More than two-thirds of the latter (67.8%) came from Africa, while 15.2% were from Asia and 17.0% from Eastern Europe. In most patients the disease was related to HBV (44.6%), followed by alcohol (25%) and then HCV or cryptogenic disease (both 15.2%). Forty-six patients had undergone liver biopsy, which showed eight cases of varying degrees of liver steatosis, 29 cases with a variable severity of chronic liver disease, eight cases with a definite picture of liver cirrhosis and one case of alcoholic hepatitis. These data show that a significant proportion of our immigrant population has liver disease and that the most frequent cause is hepatitis B infection.

The health of irregular and illegal immigrants: analysis of day-hospital admissions in a department of migration medicine.

It is difficult to trace full details of the path which irregular or illegal immigrants follow when seeking assistance in the network of the various hospital departments and health structures. The aim of this work was to analyze the health needs of immigrant people by reviewing the types of treatment given to them in the day-hospital of our Department of Migration Medicine. Our study analyzed day-hospital admissions between 2003 and 2009. The patient charts used for managing day-hospital activity were adopted in 2002 in conformity with the "OSI project". From these it is possible to draw up a scale picture of the distribution of each pathology in the immigrant population. The sample population consisted of 1,758 subjects, representing 7.4% of potential users. More than half came from Africa, followed by Asia, and then Europe. Gastroenterological diseases ranked first, with dyspeptic syndromes most frequently diagnosed. Infections and parasitic diseases ranked second, and the most frequent diagnoses were sexually transmitted diseases. Third were diseases of the genitourinary system. Metabolic disorders ranked fourth, among them, more than half of the cases were of diabetes mellitus, in patients from south-east Asia. Diseases of the circulatory system were sixth, with hypertension the most frequent pathology. Our data confirm a marked persistence of the phenomenon known as the "healthy immigrant effect" in these types of patients, as well as the prominent role played by "social determinants" in conditioning the health of immigrants, particularly in the case of some infectious diseases.

Serological pattern of Hepatitis B, C, and HIV infections among immigrants in Sicily: epidemiological aspects and implication on public health.

The objective of this study was to describe the prevalence of Hepatitis B virus (HBV), Hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in a cohort of immigrants living in Palermo, Sicily. The study was carried out in the period May 2006-June 2010 and recruited a total of 393 patients (59.8% males-median age of 32.6 years). All patients were tested for serological markers of HBV, HCV, and HIV infection. One-hundred thirty-eight (35.1%) individuals did not show any HBV/HCV/HIV serological marker, while 186 (47.3%) were indicative of past or current HBV infection. A total of 42 (10.7%) subjects were HBsAg positive, 59 (15.0%) showed the serological profile "anti-HBc alone", and only 40 (10.1%) were anti-HBs alone. Overall, 22/393 (5.6%) immigrants were anti-HCV positive and 13/327 (4.0%) were infected with HIV. Findings from this study suggest that a suitable screening protocol for the viral blood/sexually transmissible diseases is recommended on entering Italy, and the adoption of health control strategies should also be considered to safeguard the health of the local population.

Hepatocellular carcinoma: comparison of two different periods at the same center.

AIMS: To analyze the main etiological factors and some clinical characteristics of patients with HCC at diagnosis and to compare them with those we described ten years ago. METHODS: 179 patients were included in Group 1, while 132 patients were included in Group 2. For all patients age, sex, serum markers of hepatitis B and C viruses, alcohol consumption, serum alpha feto-protein (AFP) levels and the main liver function parameters at HCC diagnosis were recorded. RESULTS: Mean age was 66.0 years for Group 1 and 69.0 for Group 2 (P=0.005). HCV was responsible for 80.3% of HCC cases in Group 2 versus 72% in Group 1 (P=0.005). HBV alone and co-infection of HCV+HBV decreased, but not significantly. In Group 1 only four patients had an underlying normal liver, while in Group 2 no patients showed an underlying normal liver (P=ns). HCC was more frequently associated with Child class A in Group 2 (P=0.0001), whereas in Group 1 it was more frequently associated with class C (P=0.0001). Staging of HCC correlated inversely when patients of Groups 1 and 2 were compared (P<0.03). AFP serum levels were above normal in 72% of cases in Group 1 and in 41.5% in Group 2 (P=0.0001). CONCLUSION: This study shows that over the last decade a number of characteristics of patients with HCC in our region have changed, particularly age at onset of HCC, staging of underlying liver disease and staging of HCC.

Genomic variants associated with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune hepatobiliary disease characterized by immune-mediated injury of small and medium-sized bile ducts, eventually leading to liver cirrhosis. Several studies have addressed PBC immunopathology, and the data support an immune activation leading to autoantibodies and autoreactive T cells acting against the lipoylated 2-oxoacid dehydrogenase complexes. The causes of the disease remain unknown, but environmental factors and genetic susceptibility both contribute to its onset. Over the past two decades several association studies have addressed the role of genetic polymorphisms in PBC pathogenesis and have reported multiple associations. However, only a few studies had sufficient statistical power, and in most cases results were not independently validated. A genome-wide association study has recently been reported, but this too awaits independent confirmation. The aim of this present work is to critically review the numerous studies dedicated to revealing genetic associations in PBC, and to predict the potential for future studies based on these data.

Immune-mediated bile duct injury: The case of primary biliary cirrhosis.

Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells. Nevertheless, the condition is universally named primary biliary cirrhosis (PBC). The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence. One twin study and numerous epidemiology reports suggest that both a susceptible genetic background and environmental factors determine disease onset while a recent genome-wide association study proposed highly significant associations with several common genetic polymorphisms in subgroups of patients. Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a genetically susceptible host, possibly through molecular mimicry. Importantly, several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria. From a pathogenetic standpoint, new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs. We are convinced that the application of the most recent molecular techniques will soon provide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.