Emanuele La Spada

Cyclooxygenase-2 Expression in Chronic Liver Diseases and Hepatocellular Carcinoma : An Immunohistochemical Study

Hepatocarcinogenesis is a multistep process characterized by hepatocyte inflammation, regeneration, and proliferation. These changes are believed to depend on the aberrant expression of various tumor suppressor genes, oncogenes and growth factors. Several studies have shown the involvement of cyclooxygenase‐2 (COX‐2), the inducible isoform of the enzymes that catalyze prostaglandin synthesis in various aspects of carcinogenesis. COX‐2 has been described as being overexpressed in hepatocellular carcinoma (HCC) patients. Using immunohistochemistry, we studied COX‐2 expression in different chronic liver diseases (CLD) including nonalcoholic steatohepatitis (NASH), chronic hepatitis (CH), liver cirrhosis (LC), and HCC in a population referred to a tertiary center in western Sicily, an area moderately endemic for CLD. Sixteen NASH, 35 CH, 15 LC, and 21 HCC samples were analyzed. Positive signs of COX‐2 were observed in the cytoplasm of hepatocytes and median values were 6 (3–9) for NASH, 7 (3–9) for CH, 6 (4–9) for LC, and 4 (0–7) for HCC. COX‐2 expression was significantly lower in HCC than in NASH (P < 0.001), CH (P < 0.0001), and LC (P < 0.0001). In HCC we found a wide range of COX‐2 expression: from no expression in poorly differentiated areas to a high expression in well‐differentiated ones, with an inverse correlation between COX‐2 and tumor grading, according to Edmonson (ρ=−0.67, P < 0.0001). In conclusion: (a) COX‐2 expression was significantly lower in HCC than in the other CLD; (b) COX‐2 expression inversely correlated with tumor differentiation status. These results suggest that COX‐2 expression could be related to the inflammatory phenomena present in the early phases of CLD and eventually to the induction of hepatocarcinogenesis.

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.

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.

Progressive visceral leishmaniasis misdiagnosed as cirrhosis of the liver: a case report.

IntroductionVisceral leishmaniasis is a potentially life-threatening infectious disease which is caused by parasites of the genus Leishmania and characterized in most cases by the presence of fever as well as signs and symptoms similar to those found in liver cirrhosis.Case presentationIn this case report we describe the history of a 50-year-old Caucasian man incorrectly diagnosed as having hepatitis C virus-associated liver cirrhosis, with a massive weight loss of around 100 kg during the previous 2 years. However, suspecting a lymphoproliferative disorder, we were able to make a correct diagnosis of visceral leishmaniasis by bone marrow examination. After a course of therapy with Liposomal Amphotericin-B the patient recovered and now, 20 months post-treatment, he is well and has regained a good part of the lost weight.ConclusionsThis case taught us that patients with massive splenomegaly, even with a diagnosis of liver cirrhosis, should be investigated for infectious or lymphoproliferative diseases.

Response to antiviral therapy and hepatic expression of cyclooxygenases in chronic hepatitis C.

Objectives The aims of this study were to investigate the expression of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) in chronic hepatitis C (CHC) by immunohistochemistry, based on the hypothesis that COXs expression could vary according to genotype, viral load, liver steatosis, BMI and response to therapy and to determine whether the addition of selective COX inhibitors could have a rationale in increasing the efficacy of antiviral therapy. Methods We used 35 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsy from patients with CHC (17F/18M) with one of two types of genotype (1b and 3a). The presence of COX-1 and COX-2 in the cytoplasm of hepatocytes was scored on the basis of: (i) maximum intensity; (ii) dominant intensity; and (iii) extent. Results No significant differences were found in COX-1 and COX-2 expression in CHC patients divided according to genotype or according to the type of response to combination therapy with pegylated-interferon and ribavirin. The only significant correlations were observed between the dominant intensity of COX-2 and the presence of histological steatosis (P<0.01) and an inverse correlation between COX-2 extent and the viral load (P<0.02). Conclusions The lack of correlation between COXs tissue expression and response to antiviral treatment suggests that there is no rationale to adding selective COX inhibitors to increase the efficacy of antiviral therapy, although further studies on larger patient populations are needed. On the contrary, there is a potential application for their use in the prevention and treatment of liver steatosis.

Compliance with the clinical practice guidelines for the management of hepatitis B and C virus-related chronic liver disease: a survey based on hospitalized cirrhotic patients

In recent years, significant progress has been made in furthering our knowledge of chronic liver disease (CLD) and evaluating the therapeutic approaches. These have been updated in the form of recommendations by international scientific societies. Through a retrospective analysis, this study aimed to verify whether these recommendations have been applied in real practice. The study design included data gathered from all patients consecutively hospitalized for decompensated liver cirrhosis during one year. A pre-made master form was used to record data on the patients’ past knowledge of the etiology and management of their liver disease. As expected, hepatitis C virus (HCV) was the most frequent cause of CLD, while 41 cases were cryptogenic. In 69 of 263 patients with HCV infection, viral genotyping had been performed, although only 39 of these cases had been treated. Only 3 of 44 patients suffering from hepatitis B virus (HBV)-related liver cirrhosis had been treated in the past, while 11 patients were still being treated. Among the remaining patients, 15 were not aware that they had CLD and 15 had never been considered for antiviral treatment. In 81 cases, the disease had progressed to hepatocellular carcinoma, but only 19 patients had discovered the tumor following regular ultrasound screening. Thirty-seven patients were receiving specific treatment consistent with the stage of their disease. The management of HBV- and HCV-related CLD in Sicily is far from optimal, and although the natural history and management practices of these diseases are well known, this knowledge is a long way from being applied in our daily practice.