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Apoptotic caspases are substantially activated in liver and serum caspase activity has been suggested as a marker of early liver injury.To investigate whether serum levels of caspase-generated fragments of cytokeratin-18 are associated with the severity of histologic lesions in chronic hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease (NAFLD).We included 134 patients with chronic HCV infection and 58 patients with NAFLD, who consecutively underwent liver biopsy, and 40 healthy controls. Caspase-generated cytokeratin-18 fragment levels were blindly measured in stored serum samples.Median cytokeratin-18 fragment levels were lower in HCV-positive patients with minimal/mild than patients with moderate/severe histologic lesions (174 U/L vs. 223 U/L, P0.001) offering moderate accuracy for differentiation between the 2 groups (c-statistic: 0.74). Cytokeratin-18 fragments levels were lower in healthy subjects (148 U/L) than patients with simple fatty liver (174 U/L, P=0.013) than patients with nonalcoholic steatohepatitis (355 U/L, P0.001) offering excellent diagnostic accuracy for differentiation between the 2 latter groups (c-statistic: 0.87).Serum apoptotic caspase activity is associated with the severity of liver histologic lesions in both chronic HCV infection and NAFLD, but it has excellent diagnostic accuracy in NAFLD and moderate accuracy in chronic HCV patients.

To evaluate the prevalence and clinical burden of serendipitously discovered abnormalities in hospitalized patients, unrelated to their presenting symptoms and physical signs.A total of 478 patients consecutively admitted in the Department of Medicine were enrolled in the study. In the end of first diagnostic work-up, the previously undetected imaging or endoscopic asymptomatic abnormalities termed as incidental findings (IFs) were recorded and some of them were further investigated.One hundred thirty eight (28.8%) patients had IFs. The most common IFs were located in the kidney and genitourinary system followed by liver and gallbladder. The most common method of detection of IFs was ultrasonography (US) of the abdomen. The patients with IFs compared with those without, were older (P=0.007), had no previous hospitalizations (P0.001) and stayed longer in the hospital (P0.001). The 25 (18.1%) patients with IFs were not evaluated further. One hundred seventy seven IFs discovered in 113 patients were further evaluated by medical specialists and additional tests were performed if warranted. In the end of the diagnostic work-up, in a total of 113 patients with IFs, 78.7% had insignificant and 21.2% potentially significant IFs. The latter group had higher rate of IFs compared with the former group, usually more than 3 (P=0.017).IFs were prevalent in a hospital population. Hospitalized patients with IFs were more than 60 years old and had no previous hospitalization. A large number of IFs were potentially significant deserving further clinical management.

Background Survivin is a new member of the Inhibitor of apoptosis protein family that has a dual function as a mitotic regulator and apoptosis inhibitor. Survivin is prominently expressed in transformed cell lines and in many human cancers, including colorectal carcinoma. The aim of this study is to investigate the expression of survivin in colorectal carcinomas and its possible associations with clinicopathological parameters and patient survival. Materials and Methods Sections of formalin-fixed paraffin-embedded tissues from 77 colorectal carcinomas were immunohistochemistry stained for survivin. Results Survivin was mainly detected in the bottom of the glands of normal mucosa with mainly cytoplasmic localization. No survivin expression was found in infiltrating lymphocytes, fibroblasts, smooth muscle cells or neural tissue. Survivin staining was detected in 68/77 (88.3%) colorectal carcinomas. Survivin expression was found to be significantly associated with tumor differentiation (P = 0.02) but not with gender, age or Dukes stage. Survival did not differ according to survivin expression. Conclusion Survivin was found in the majority of colorectal carcinomas, suggesting that its expression is an early event in colorectal carcinogenesis. Its expression is statistically significantly associated with tumor differentiation but not with patient survival.

The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH.We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n=39) or C (n=51). Thrombophilic factors were evaluated on the day of the liver biopsy.One or more thrombotic RFs were detected in 37% of NAFLD patients, andor= 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; Por= 0.001). Among NAFLD cases, one or more thrombotic RFs were significantly more frequently present in NASH than simple fatty liver (56% vs. 8%; odds ratio [OR]: 13.8, 2.8-67.4, P0.001). In multivariate analysis, NASH was independently associated with moderate to severe steatosis (adjusted OR: 24.3; P=0.001) and the presence of one or more thrombotic RFs (adjusted OR: 38.7; P=0.002). Fibrosis stage was worse in NASH patients with than without thrombotic RFs (2.5+/-1.1 vs. 1.3+/-1.1; P=0.002).Thrombotic RFs are frequently present in patients with NAFLD and are associated with NASH and more advanced fibrosis. Such an association may have significant clinical implications, even though it is not clear yet whether it represents a primary or secondary phenomenon.

Chronic hepatitis C (CHC) induces insulin resistance (IR) and subsequently diabetes.To examine viral, metabolic and histological predictors of IR in 275 CHC patients to test the hypothesis that IR differs among HCV genotypes and that viral replication directly affects IR.We studied 275 nondiabetic treatment-naïve CHC patients. Histological lesions were evaluated according to Ishak. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR).HOMA3.0 was found in 37% of patients, independently associated with higher BMI and GGT. In genotype non-3 patients, HOMA3.0 was associated with higher BMI and GGT values, while no significant association was noted in genotype 3 patients. In non-obese patients with minimal fibrosis, HOMA3.0 was found in 20% of cases without significant differences among genotypes. No association between HOMA3.0 and HCV-RNA levels was found. Severe fibrosis (stage 5-6) related to older age (OR:1.048), HOMA-IR (OR:1.177), necroinflammation (OR: 2.990) and higher ALT (OR: 1.009) and GGT (OR:1.006).IR develops at early stages of CHC without significant differences among genotypes. It is more frequent in obese patients with steatosis and contributes to fibrosis progression. However, IR does not seem to be associated with viraemia and therefore its exact pathogenetic mechanism in CHC remains elusive.

BACKGROUND/AIMS: Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. METHODS: We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. RESULTS: At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. CONCLUSION: In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.

SUMMARY. Despite several studies, the association of glucose intolerance with chronic hepatitis B (CHB) or C (CHC) virus infection remains controversial. We evaluated the prevalence of glucose intolerance by oral glucose tolerance test (OGTT) in patients with CHB or CHC in comparison with matched controls. In total, 189 consecutive outpatients with CHB or CHC and 189 subjects individually matched for age, sex and body mass index (BMI) were included. OGTT was performed in all cases, except in known diabetics, and glucose intolerance was defined as impaired glucose tolerance (IGT), OGTT-diabetes or known diabetes. Most patients with abnormal OGTT had normal fasting glucose (IGT: 69.8%, OGTT-diabetes: 54.5%). Compared with their own controls, CHB patients had a higher prevalence of IGT (13.6% vs 2.5%, P = 0.018) and family history of diabetes (34.6% vs 16.0%, P = 0.011), while CHC patents had higher prevalence of glucose intolerance (37.0% vs 15.7%, R = 0.001), mostly because of more frequent IGT (21.3% vs 6.5%, R = 0.003). After age and BMI adjustment, patients with CHC compared with those with CHB had significantly higher prevalence of glucose intolerance (37.0% vs 29.6%, P = 0.037). In conclusion, increased prevalence of glucose intolerance is documented by OGTT both in CHC and CHB patients compared with age, sex and BMI matched controls. Glucose intolerance is more frequent in CHC than CHB patients, regardless of known risk factors. An OGTT might be necessary at the baseline work-up of CHB or CHC patients, as a normal fasting glucose value does not exclude IGT or OGTT-diabetes.

The results of retrospective studies suggest an association between smoking, insulin resistance, steatosis and fibrosis in patients with chronic hepatitis C (CHC); no data are available for chronic hepatitis B (CHB). The purpose of this study was to evaluate the relationship, if any, of such factors on liver fibrosis in a cohort of patients with CHB and CHC.The study prospectively included 271 consecutive patients with CHB (n=95) or CHC (n=176) who had undergone liver biopsies. Each patient completed a questionnaire on smoking habits; anthropometric measurements and laboratory examinations were carried out and histological lesions were recorded.In CHC patients, severe fibrosis was independently associated with a higher body mass index (BMI) (OR: 1.180, 95% CI: 1.028-1.354; p=0.019), heavy smoking (OR: 3.923, 95% CI: 1.356-11.348; p=0.012), higher alanine aminotransferase (ALAT) levels (OR: 1.010, 95% CI: 1.003-1.017; p=0.005) and alkaline phosphatase (ALP) levels (OR: 1.016, 95% CI: 1.001-1.030; p=0.03) and presence of necroinflammation (OR: 11.165, 95% CI: 1.286-96.970; p=0.029). Moreover, steatosis was independently associated with high gamma-glutamyl transpeptidase (GGT) values, heavy smoking and presence of necroinflammation. In CHB patients, no association between smoking habits and fibrosis or steatosis was noted.Heavy smoking is associated with severe fibrosis in CHC but not CHB. Heavy smoking is also significantly associated with steatosis in CHC and this could be the link between smoking and fibrosis progression.

Background Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. Methods A prospective study was conducted over a 6-month period. All patients consecutively admitted were enrolled in the study. Analysis included: (1) an evaluation of the frequency of ADR-related hospital admissions and their causality, severity, and preventability; (2) a description of the type of drugs involved; (3) a report of the most common clinical manifestations related to these ADRs; and (4) an assessment of the factors that were predictive of ADRs. Results Seventy of the 548 admissions (12.8%) were related to an ADR. Hemorrhage represented the most common ADR (37.3%), followed by metabolic and renal events (10.8% each). The drugs most often involved were non-steroid anti-inflammatory drugs (NSAIDs), followed by diuretics, aspirin, oral anticoagulants, and oral hypoglycemic agents. A comparison between ADR and non-ADR-related admissions showed that mean number of medications and age were significantly higher for patients admitted for an ADR than for those who were not. Gender, chronic disease at admission, days of hospitalization, cognitive impairment, renal insufficiency, physical activity impairment, and use of psychoactive drugs did not differ between the two groups. In the multivariate analysis, number of drugs was the only independent predictor of ADR-related hospital admission (OR = 1.064, 95% CI 1.019–1.109). In 13 of 70 (18.6%) ADR-related hospital admissions, ADRs were coded as severe. Conclusions ADRs are common causes of hospital admissions and may have important consequences. The most important determinant for ADR-related hospital admissions is the number of drugs taken.

The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNAor=2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading scoreor=7 and/or stageor=2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNAor=200,000, 20,000-199,999, 2,000-19,999, and2,000 IU/mL, respectively (P0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation.HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNAor=20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA20,000 and even2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up.

Aim We investigated whether changes of liver and muscle enzymes activity are associated with rigor of several causes and have any prognostic significance. Methods Seventy-five patients with rigor were prospectively evaluated. Serum enzymes were measured at the onset of rigor and during the three following days. Results Causes of rigor were bacteremia ( n = 28), cholangiitis ( n = 12), protozoan infections ( n = 9), viral infections ( n = 10) and platelet transfusions ( n = 16). Increases in enzymes activity were observed with rigors from infectious causes, but not with that following platelet transfusions. Patients with cholangiitis demonstrated the highest ALT elevations, while those with viral infections the highest CPK levels. In bacteremia, CPK values increased significantly only in cases with dehydration and hypokalemia. Conclusions Rigor per se does not cause increases in muscle or liver enzymes activities. Rather these changes are associated with the rigor's causative agent (infectious or not), the patient's general condition and the severity and extent of the underlying disease.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Activating mutations in tyrosine kinase receptors KIT or platelet-derived growth factor receptor alpha (PDGFRA) are the main mechanisms causing the disease. Patients generally present with non-specific symptoms, while a number of tumors are discovered incidentally and may be metastatic at the time of diagnosis. Aggressive GISTs have a defined pattern of metastasis to the liver or throughout the abdomen, or both. Though GISTs rarely present systemic or isolated paraneoplastic reactions, a few cases have been reported in the literature. We present the case of a 54-year-old patient with metastatic GIST at diagnosis and the emergence of paraneoplastic manifestations during follow-up.

Background/aims Hepatic steatosis has not been adequately studied in chronic hepatitis B, while it is considered to be a cardinal feature in chronic hepatitis C and to be mainly metabolically induced in patients infected with genotype 1. We investigated the prevalence of and the parameters associated with steatosis in HBeAg-negative chronic hepatitis B. Methods We studied 213 patients with HBeAg-negative chronic hepatitis B and compared them with 163 patients with genotype-1 chronic hepatitis C. Steatosis was semi-quantitatively graded. Results Steatosis was significantly less frequent in chronic hepatitis B than chronic hepatitis C (60% versus 72%, P = 0.016), but there was no difference in the prevalence of moderate/severe steatosis. In chronic hepatitis B, steatosis was associated only with higher body mass index (P = 0.002), while moderate/severe steatosis was associated only with higher body mass index (P = 0.043) and diabetes (P = 0.031). Steatosis was relatively less frequent in chronic hepatitis B than chronic hepatitis C non-diabetic, normal-weight patients (45.6% versus 62.5%, P = 0.063), but it did not differ in diabetic and/or overweight/obese patients with chronic hepatitis B or chronic hepatitis C. Conclusions Hepatic steatosis in HBeAg-negative chronic hepatitis B (a) is less frequent than in genotype-1 chronic hepatitis C, (b) is mainly associated with presence of host metabolic factors, such as high body mass index and diabetes and (c) does not seem to be associated with the severity of liver histological lesions.

Autoimmune thyroid diseases have been correlated with a variety of autoimmune diseases also affecting the skin. A 56-year-old patient with a history of vitiligo is presented who was admitted for hyperthyroidism (Graves disease) and a blistering eruption. Clinical and histological appearance of the skin disorder, rapid response to corticosteroids, recurrence and remission of the lesions with discontinuation and reintroduction of corticosteroids, respectively, were all suggestive of an autoimmune blistering disease accompanying autoimmune hyperthyroidism and vitiligo.

Cytotoxin-associated gene A (CagA) diversity with regard to EPIYA-A, -B, -C, or -D phosphorylation motifs may play an important role in Helicobacter pylori pathogenesis, and therefore determination of these motifs in H. pylori clinical isolates can become a useful prognostic tool. We propose a strategy for the accurate determination of CagA EPIYA motifs in clinical strains, based upon one-step PCR amplification using primers that flank the EPIYA coding region. We thus analyzed 135 H. pylori isolates derived from 75 adults and 60 children Greek patients. A total of 34 cases were found to be EPIYA PCR negative and were consequently verified as cagA negative by cagA -specific PCR, empty-site cagA PCR, and Western blotting. Sequencing of the remaining 101 PCR-positive amplicons confirmed that an accurate prediction of the number of EPIYA motifs on the basis of size distribution of the PCR products was feasible in all cases. Furthermore, our assay could identify closely related H. pylori subclones within the same patient, harboring different numbers of EPIYA repeats. The prevalence of CagA proteins with three EPIYA motifs (ABC) or four EPIYA motifs (ABCC) was the same within the adult and children groups. However, CagA species with more than four EPIYA motifs were observed exclusively within adults (8.6%), suggesting that CagA-positive strains may acquire additional EPIYA-C motifs throughout adulthood. Our strategy requires no initial cagA screening of the clinical isolates and can accurately predict the number of EPIYA repeats in single or multiple closely related subclones bearing different numbers of EPIYA motifs in their CagA, which may coexist within the same patient.

Hepatic granulomas have been reported in 2-15% of unselected liver biopsies, with a wide clinical profile responsible for their presence. To date, no series concerning the prevalence and the etiology of granulomas from Greece has been reported.To evaluate the prevalence and the etiology of hepatic granulomas and to investigate whether there has been an alteration in distribution of diagnoses in our series compared with those published so far in the literature.The results of liver biopsy specimens performed in a Department of Medicine, between 1999 and 2004, were retrospectively reviewed and the cases revealing hepatic granulomas had their medical notes and the liver biopsies recorded.Over the study period, 1768 liver biopsies were performed. Hepatic granulomas were identified in 66 (3.7%). Of those, 51 were female with a mean age of 57 years (range 34-74 years) and 15 were male with a mean age of 42 years (range 18-78 years). Autoimmune liver diseases including primary biliary cirrhosis, overlap syndrome and autoimmune hepatitis accounted for the majority of cases (68%), followed by sarcoidosis (7.5%), chronic hepatitis B virus and hepatitis C virus infection (7.5%), idiopathic (6%), drugs (3%) and other miscellaneous causes (7.5%).Our series showed that autoimmune liver diseases, mainly primary biliary cirrhosis was the most common cause of granuloma formation, a finding rather similar to that stated in the studies from Western countries. A rather small number of idiopathic cases were recorded. Chronic viral hepatitis and sarcoidosis rates were equal, a finding possibly reflecting a fairly high proportion of viral hepatitis in our sample.

We describe a case of a long-standing, untreated achalasia with a huge sigmoid esophagus in a 58-year-old Caucasian man who declined surgery. All means of classical endoscopic approach for pneumatic dilation, including the use of an overtube, were impossible because any attempt to propel the balloon dilator made the guide wire pull back out of the stomach because of the large loops and the tortuosity of the esophagus. For this reason, we used, for the first time, a combined approach of percutaneous gastrostomy and endoscopy in order to fix the guide wire at two points, achieving a pneumatic dilation in this way. A few months later, a significant improvement in the symptoms and nutritional status of the patient were observed.

We assessed the value of the recently developed aspartate aminotransferase to platelet ratio index (APRI) for predicting significant fibrosis or cirrhosis in patients with chronic hepatitis C or HBeAg-negative chronic hepatitis B.In total, 489 patients (chronic hepatitis C, 284 patients; HBeAg-negative chronic hepatitis B, 205 patients) were included. APRI values of 0.50 or less and greater than 1.50 were evaluated for predicting significant fibrosis, and APRI values of 1.00 or less and greater than 2.00 for predicting cirrhosis. Liver biopsies were evaluated according to the Ishak's classification. Fibrosis was considered to be significant in cases with scores 3-6, and cirrhosis to be present in cases with fibrosis scores of 5 and 6.Significant fibrosis was observed in 56/148 (38%) patients with APRIor = 0.50, 130/227 (57%) patients with 0.50APRIor = 1.50 and 84/114 (74%) patients with APRI1.50 (P10). Cirrhosis was observed in 47/311 (15%) patients with APRIor = 1.00, 29/93 (31%) patients with 1.00APRIor = 2.00 and 37/85 (44%) patients with APRI2.00 (P10). The areas under receiver-operating characteristic curves were 0.65 and 0.70 for prediction of significant fibrosis or cirrhosis, respectively. The combination of APRIor = 0.50 and APRI1.50 classified correctly 36% of patients with or without significant fibrosis, while the combination of APRIor = 1.00 and APRI2.00 classified correctly 62% of patients with or without cirrhosis. There was no significant difference in the predictive values of APRI between patients with chronic hepatitis C and chronic hepatitis B.APRI is significantly associated with the extent of fibrosis, but it does not classify correctly 40-65% of patients with chronic hepatitis C or HBeAg-negative chronic hepatitis B, and thus it cannot replace liver biopsy.

Background/aims Treatment of chronic delta hepatitis is long and difficult and better monitoring is needed. Methods In this study, hepatitis delta virus (HDV) RNA, hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA were retrospectively quantified in 53 patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis delta. Twenty-one had received 28 courses of 3–5 MU interferon-α2b (IFN-α2b) thrice weekly for a median of 12.6 months (interquartile range [IQR]: 7.3–31.6), five had received eight courses of 100 mg lamivudine (LAM) daily for 23.6 months (IQR: 8.4–61.5) and 27 were untreated. The controls were 54 untreated, randomly selected, HBeAg-negative chronic hepatitis B patients without delta infection. Quantification of serum HDV RNA, HBsAg and HBV DNA were performed at baseline, during and at the end of treatment and end of follow up. Results Untreated patients had significantly higher median HBsAg levels than controls (5,872 vs 3,501 IU/ml; P=0.046), but lower median HBV DNA levels (2.933 vs 6.459 log10 copies/ml; P10 copies/ml) was similar in IFN-α2b-treated, LAM-treated and untreated patients. At the end of treatment, IFN-α2b significantly suppressed in paired measurements HDV RNA ( P=0.012) and HBsAg ( P=0.043), but LAM was inefficient. In IFN-α2b-treated patients, HDV RNA became undetectable in five patients within a median of 30 months (IQR: 8–90), followed by a slower decrease in HBsAg. Conclusions In untreated chronic delta hepatitis, suppressed HBV replication is associated with significantly increased HBsAg serum levels. IFN-α2b significantly suppresses both HDV RNA and HBsAg, but LAM has no effect. Long-term IFN-α2b treatment (IQR: 1.5–5.0 years) appears necessary for undetectable serum HDV RNA and further treatment is required for HBsAg loss. Monitoring of HDV RNA and HBsAg serum levels in patients with chronic delta hepatitis provides insight during treatment.

Background and Aim: It has been suggested that propranolol may have a protective effect on the development of spontaneous bacterial peritonitis by increasing the motility of the bowel and lowering the pressure of the portal vein. The aim of this study is to evaluate the association between the use of propranolol and development of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. Methods: We retrospectively evaluated 134 patients with cirrhosis and ascites admitted consecutively for a period of 2 years. Diagnosis of spontaneous bacterial peritonitis was based on an ascitic fluid neutrophilic count of >250/mm3 and/or a positive culture without evidence of secondary peritonitis. Results: Spontaneous bacterial peritonitis was diagnosed in 39 of 134 (29%) patients and 12 of 39 (31%) patients died in hospital compared to only 4% (four of 95) of those without spontaneous bacterial peritonitis (P

Ulcerative jejunoileitis (UJI) is a rare condition which usually develops in patients with established or simultaneously diagnosed coeliac disease (CD) and has been suggested to represent cryptic low-grade enteropathy-associated T-cell lymphoma (EATL). We report a case of a 78-year-old male patient with UJI and CD diagnosed at the same time. He presented with abdominal pain, diarrhoea and weight loss and had serological, endoscopical, radiological and histological findings compatible with the diagnoses of both UJI and CD. The possibility of EATL was carefully excluded. The patient exhibited significant symptomatic improvement with a gluten-free diet, probably indicating an early stage of disease despite his old age. In conclusion, this rather unusual case of an elderly patient presenting with UJI and CD without evidence of EATL supports the great heterogeneity of these diseases not only in their clinical presentation but even in their course and complications.

Polymorphic variability in Helicobacter pylori factors CagA and VacA contributes to bacterial virulence. The presence of one CagA EPIYA-C site is an independent risk factor for gastroduodenal ulceration (odds ratio [OR], 4.647; 95% confidence interval [CI], 2.037 to 10.602), while the presence of the vacA i1 allele is a risk factor for increased activity (OR, 5.310; 95% CI, 2.295 to 12.287) and severity of gastritis (OR, 3.862; 95% CI, 1.728 to 8.632).

Background and Aims: The validity of the rapid urease (CLO) test to diagnose Helicobacter pylori infection in patients with bleeding ulcers has been questioned. The aim of this paper is to evaluate the validity of the CLO test in comparison with histology in diagnosing H. pylori infection in patients with acute upper gastrointestinal bleeding (UGB), irrespective of non-steroidal anti-inflammatory drug (NSAID) use. Methods: Upper gastrointestinal endoscopy was performed within 24 h of admission for all patients with UGB admitted to the Department of Pathophysiology, Medical School, Athens, for a period of 12 months. Patients with variceal bleeding, previous gastric operation, recent treatment with proton pump inhibitors (< 2 months) and those with a history of H. pylori eradication therapy were excluded from the study. At least four biopsies (two from the antrum and two from the body) were obtained for the CLO test and histology (modified Giemsa). Results: Seventy-two consecutive patients (aged 18–90 years, 51 men, 21 women) were included. Forty-six patients (64%) used NSAID. Thirty-two patients (44%) were found to be positive for H. pylori infection by the CLO test, while 44 patients (61%) were found to be positive on histology (P < 0.045, 95% CI, 0.004–0.331). The sensitivity and specificity of the CLO test were 68 and 93% respectively; positive and negative predictive values were 94 and 65%, respectively. The age of the patient and visible blood in the stomach did not inflence results of either the CLO or histology. Conclusions: The CLO test, performed within 24 h of hospital admission in patients with UGB, irrespective of NSAID use, is unreliable for the detection of H. pylori infection. The age of the patient and the presence of blood in the stomach do not seem to influence these results.

Carnitine palmitoyltransferase II (CPT2) deficiency is an inherited disorder associated with rhabdomyolysis. The adult form of CPT2 deficiency is usually "benign", characterized by episodes of rhabdomyolysis without extramuscular manifestations and with a good outcome, while the infantile type characteristically presents with severe metabolic symptoms such as hypoketotic hypoglycemia. We present here a case of severe rhabdomyolysis with acute renal failure and hypoglycemia in an adult patient with CPT2 deficiency.

A patient who survived for 21 years since initial discovery of glucagonoma with concurrent liver metastases is described. Psychiatric symptoms, weight loss, necrolytic migratory erythema, diarrhea, and diabetes mellitus developed gradually after diagnosis of the tumor. No specific treatment was administered. The longevity of this patient may be related to the slow tumor growth expressed histologically by ischemic necrosis of the malignant cells and in imaging by extensive tumor calcifications, a very rare finding in this type of the tumor.

Sixty patients with advanced gastric carcinoma who refused to receive cytotoxic chemotherapy were examined for serum immunoglobulin levels (IgG, IgM, IgA, IgE). Three samples were obtained every two months thereafter. The group of patients who had above-normal values of one or more of the examined immunoglobulins had a longer survival than the other (p

Osteomyelitis of the pubic symphysis or pubic osteomyelitis is a rare entity that is encountered in certain groups of people such as athletes, intravenous drug users, patients with pelvic malignancy, and patients who have undergone surgical manipulations of the genitourinary system. The most frequent causative organism is Staphylococcus aureus. K pneumoniae is a common pathogen in diabetic patients, but pubic osteomyelitis due to K pneumoniae has not previously been described. We present a diabetic patient with pubic osteomyelitis caused by K pneumoniae without known predisposing factors.

The objective of this study was to assess the efficacy of a new regimen in eradicating Helicobacter pylori (Hp) in patients with duodenal ulcer (DU) who were previously treated unsuccessfully with standard triple therapy (tripotassium dicitratobismuthate [TDB] 120 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or proton-pump inhibitor (PPI) dual therapy (omeprazole 20 mg BID and amoxicillin 500 mg QID). The study included 133 consecutive patients aged 17 to 83 years with endoscopically diagnosed DU (diameter ≥5 mm) in whom standard triple therapy or PPI dual therapy had failed to eradicate Hp. A rapid urease (CLO) test was performed on four biopsy specimens at study entry and at least 1 month after the end of treatment to confirm Hp colonization and eradication, respectively. Patients were considered to be Hp positive if any CLO test was positive within 2 hours, and Hp was considered to be eradicated if all CLO tests were still negative after 24 hours. In 31 randomly selected patients, Hp eradication was confirmed histologically as well. Patients were given omeprazole 60 mg/d (20 mg in the morning and 40 mg in the evening) plus amoxicillin 500 mg QID for 10 days and subsequently were given metronidazole 500 mg TID for 10 days plus TDB 120 mg QID for 6 weeks. One hundred and twenty-four patients were followed up; five (4%) withdrew because of side effects (protracted diarrhea, stomatitis, skin rashes). Per-protocol analysis showed Hp eradication in 113 of 119 patients (95%) and ulcer healing in 118 of 119 (99%). Intent-to-treat analysis showed an Hp eradication rate of 85% (113 of 133 patients) and an ulcer healing rate of 89% (118 of 133 patients). In per-therapy analysis, the Hp eradication rate was 91% (113 of 124 patients), and the ulcer healing rate was 95% (118 of 124 patients). Side effects were observed in 39 of 119 patients (33%) and were generally mild. The four-drug regimen used in this study, when given to patients previously treated unsuccessfully with standard triple therapy or PPI dual therapy, was highly effective in eradicating Hp and healing DUs and had no major side effects.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of non-Hodgkin lymphoma with systemic manifestations, including fever, lymphadenopathy, rash, and rarely arthritis. We report the case of a patient who presented with symmetric inflammatory polyarthritis and skin nodules resembling rheumatoid arthritis (RA). The patient responded initially to low-dose prednisolone, but 12 months later, he developed typical features of AITL. The characteristics of AITL-associated arthritis from 16 additional cases from the English literature are also reviewed. AITL-associated arthritis is an uncommon manifestation of angioimmunoblastic lymphoma that can mimic RA, especially when the typical systemic features of lymphoma are absent. This type of arthritis should be included in the differential diagnosis of patients presenting with an inflammatory polyarthritis.

The aim of this study was twofold: first, to investigate the effectiveness of a standard triple therapy (tripotassium dicitrato bismuthate, 125 mg q.i.d., tetracycline hydrochloride 500 mg q.i.d., and metronidazole 500 mg t.i.d.) in eradicating Helicobacter pylori in patients with duodenal ulcer successfully healed with omeprazole or ranitidine; second, to examine the influence of the eradication on duodenal ulcer recurrence rate after 12 months. Two hundred forty-five consecutive H. pylori-positive patients with healed duodenal ulcer either with omeprazole (20 mg/day, 126 patients) or with ranitidine (150 mg b.i.d., 119 patients) given at random, began triple therapy for 15 days. H. pylori eradication was looked for 4-5 weeks later by culture of biopsy material, hematoxylin-eosin stain, and rapid urease test. H. pylori-eradicated patients were followed up for 12 months. Endoscopy was carried out at the end of the follow-up or whenever symptoms appeared. Five patients (2.0%) withdrew because of triple-therapy-related side effects. The eradication rate was 92% (220 of 240 patients); no difference was found between those healed with omeprazole (93%, 114 of 123 patients) or ranitidine (91%, 106 of 117 patients). Of 220 successfully treated patients, 132 completed the 12-month follow-up. The duodenal ulcer recurrence rate was 4% (5 of 132 patients); 3% (2 of 70) in the omeprazole group and 5% (3 of 62) in the ranitidine group healed. All the recurrences were asymptomatic. H. pylori recurrence rate was 11% (14 of 132 patients); no difference was found between patients healed with omeprazole (10%, 7 of 70 patients) or with ranitidine (11%, 7 of 62 patients). All the recurrent duodenal ulcers occurred in H. pylori-positive patients (36%, 5 of 14 patients). Standard triple therapy after duodenal ulcer healing with omeprazole or ranitidine eradicates H. pylori in comparable high rates. Side effects were mild and dropouts were only 2%. Ulcer recurrence rate 12 months after eradication was low and comparable between those healed with omeprazole or ranitidine.

The case of a 37-year-old man with chronic hepatitis C virus (HCV) infection is presented. The patient had received a 6-month course of antiviral therapy with peg interferon alpha-2a and ribavirin, with concomitant clearance of hepatitis C virus ribonucleic acid (HCV-RNA) from serum at the end of treatment. Three months after the treatment course he developed clinical and laboratory features of hypothyroidism along with high titers of thyroid peroxidase antibodies. Later on, while on treatment with levothyroxine, he developed all the clinical features of Graves disease along with increased levels of thyroid stimulating hormone (TSH)-receptor antibodies.This patient exhibited a rare sequence of immune-mediated thyroid disorders as a result of interferon alpha treatment. At the end of treatment, the patient developed Hashimoto thyroiditis, a typically Th1-response-mediated disease, followed sequentially after 6 months by Graves disease, a typically Th2-response-mediated disorder. Although both clinical entities have been described in patients receiving interferon-based regimens, to our knowledge, the changing pattern of immune-mediated thyroid disease in the same individual has not been reported in the literature.

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease both in the general and pediatric population and has been associated with increased cardiovascular risk. Arterial function and early atherosclerotic changes are markers of cardiovascular disease and independent predictors of the corresponding risk. Through a global approach, we investigated the relationships between NAFLD and functional arterial changes and early atherosclerosis. METHODS A total of 23 consecutive patients (mean age 55 ± 14 years, 11 males) with biopsy evidence of NAFLD and 28 control subjects matched for age, gender, body mass index, and other cardiovascular risk factors participated in the study. RESULTS Compared to controls, NAFLD subjects had significantly higher carotid-femoral pulse wave velocity (PWV; 8.2 ± 1.3 m/s vs. 6.9 ± 1.3 m/s, P = 0.001), higher carotid intima-media thickness (IMT; 0.79 ± 0.18 mm vs. 0.67 ± 0.13 mm, P = 0.01), and reduced flow-mediated dilatation (FMD; 1.92 ± 2.11% vs. 4.8 ± 2.43%, P < 0.001). In multivariable analysis, presence of NAFLD was an independent determinant of both PWV and FMD, whereas leptin was an independent determinant of PWV (B = 0.036, P < 0.05), and adiponectin was independently associated with FMD (B = 0.104, P < 0.05). In addition, histological activity of liver disease expressed by the global Brunt Grade was associated independently with FMD (B = -1.054, P < 0.05). CONCLUSIONS NAFLD is associated with arterial stiffness and endothelial dysfunction. Given the important independent prognostic role of these arterial indexes, these findings have important implications for increased cardiovascular risk in patients with NAFLD.

Gastroesophageal reflux disease (GERD) is a chronic condition that usually requires long-term maintenance therapy with proton-pump inhibitors (PPIs). In clinical practice, patients receive PPIs at the lowest dose to control symptoms. However, it is not known whether this approach adequately controls acidic esophageal reflux. We sought to investigate the efficacy of three different dosages of esomeprazole in patients receiving maintenance therapy for GERD, using the Bravo pH system.Patients with a previous history of erosive esophagitis A or B (LA classification) that was healed at the time of enrollment or endoscopy-negative reflux disease (ENRD), documented with an abnormal pH study, were randomized to receive maintenance therapy with esomeprazole 40 mg twice daily (group A), once daily (group B), or every other day (group C). Intraesophageal pH was monitored for two consecutive days using the Bravo wireless system, 30 days after randomization. The parameters subjected to analysis were percent of total time pH4 and the De Meester score.The pH results from 73 patients (group A=24, group B=24, group C=25 patients) were subjected to final analysis. On the first day of the study, the mean (+/-s.d.) percent of total time pH4 and the De Meester score were group A: 0.9(1.2) and 4.1(4.0); group B: 1.5(1.6) and 7.0(6.9); group C: 1.3(1.0) and 6.0(3.3), respectively (P=0.262 and 0.134, respectively). On the second day of the study, the corresponding values were group A: 0.7(1.0) and 3.9(5.9); group B: 1.5(1.8) and 6.4(6.6); group C: 7.0(4.4) and 29.4(19.4), respectively. The difference was statistically significant (P0.0001 and0.0001, respectively). Further analysis showed that patients not receiving PPI had a significantly higher mean percent of total time pH4 and De Meester score as compared with patients on PPI once or twice daily (P0.001 and0.001 respectively).The administration of esomeprazole 40 mg every other day does not control acidic esophageal reflux on the day off PPI. Esomeprazole 40 mg once daily effectively controls reflux of acid in patients with history of mild esophagitis or ENRD, whereas doubling the dose does not seem to confer any further advantage.

To investigate the burden and recent epidemiological changes of the main chronic liver diseases in a Greek referral tertiary centre.We evaluated the main epidemiological characteristics of 1080 consecutive adult patients, seen at our outpatient liver clinic between 2002 and 2007, with chronic hepatitis B (HBV) and/or C (HCV) virus infection, alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD). Our patient population was divided into two groups in relation to the time of the first visit (period A: 2002-2004, period B: 2005-2007).Among our patient population, 86.1% had chronic HBV and/or HCV infection (chronic HCV alone: 44.9%), 9.2% NAFLD and 4.8% ALD. From period A to B, there was a decrease in chronic HBV cases (44.0 vs. 37.8%, P = 0.045) with immigrants being responsible for 35.5% of them and being more frequent in period B than A (39.7 vs. 30.5%, P = 0.046). In chronic hepatitis B, hepatitis B e antigen-positive patients, who were more frequent immigrants compared with hepatitis B e antigen-negative patients (65.5 vs. 29.5%, P = 0.001), increased from period A to B (8.0 vs. 17.6%, P = 0.045). Intravenous drug use was reported by 41.2% of HCV patients with its proportion increasing from period A to B (32.5 vs. 47.4%, P = 0.002). Decompensated cirrhosis was present in 67, 10, 11 and 3% of patients with ALD, HBV, HCV and NAFLD, respectively.At Greek tertiary centres, chronic viral hepatitis remains responsible for most chronic liver disease cases, but its epidemiology is changing owing to immigrants and intravenous drug users.

Dose reductions of Peg-IFNa because of severe neutropenia may affect the virologic response in patients with hepatitis C infection (HCV). Granulocyte colony-stimulating factor (G-CSF) has been used occasionally but studies addressing its safety and efficacy in the current treatment of HCV infection are missing. The database of 232 naive patients with HCV genotype-1 who received PEG-IFNalpha2b 1.5 mcg/kg/week plus Ribavirin 800-1,400 mg/day and completed the treatment was examined. Nineteen patients who exhibited significant neutropenia and received 150-300 microg G-CSF (Group A) with 19 matched control patients who had dose reductions of Peg-IFNalpha according to the standard recommendations (Group B) were examined. None of the patients had treatment modifications due to thrombocytopenia or anemia. The mean decline of the neutrophils was similar in groups A and B (1,760 +/- 1,030/mm(3) at 11 +/- 8.6 weeks and 1,630 +/- 890 at 12.3 +/- 6.1, respectively). Nadir neutrophil values were also not statistically different. Patients who received G-CSF two before IFNalpha, maintained neutrophils between 1,400/mm(3) and 2,700/mm(3) and remained on G-CSF for 29 weeks (2-40). Virologic response at the end of treatment was observed in 12/19 (63%) patients and at 6 months follow-up in 6/19 (32%) in group A as compared to 9/19 (47%) and 4/19 (21%) in group B, respectively. No side effects related to G-CSF were encountered. Administration of G-CSF 2 days before Peg-IFNalpha is safe, maintains sustained neutrophil count, improves adherence to treatment and seems to increase the virologic response in patients infected with HCV genotype 1 who develop Peg-IFN-alpha2b related severe neutropenia.

In patients with diabetes and microalbuminuria, small changes of GFR could have been missed, due to the lack of sensitive methodology for GFR determination in clinical practice (creatinine based calculations). Therefore we explored the relation of the degree of albumin excretion with Cystatin C, which has been recently proved to be a better marker of GFR, compared to serum creatinine.We studied 179 patients with type 2 diabetes, in whom renal function and microalbuminuria were evaluated.In patients with normal renal function, GFR/MDRDor=60 ml/min/1.73 m(2), (n=79), urinary albumin concentration (UAC) was significantly correlated with Cystatin C, both in patients with normoalbuminuria (r=0.547, p0.023) or microalbuminuria (r=0.305, p0.035), while it was not correlated either with serum creatinine or calculated creatinine clearance. In patients with GFR/MDRD60 ml/min/1.73 m(2), (n=100), UAC was significantly correlated with Cystatin C, also both in patients with normoalbuminuria (r=0.536, p0.032) or microalbuminuria (r=0.340, p0.016), while it was significantly correlated with serum creatinine and calculated creatinine clearance only in those with microalbuminuria.Subtle changes in renal function, as judged by Cystatin C concentration, may parallel the degree of albuminuria, even in the normoalbuminuric stage. This finding needs further confirmation by more appropriate methodology in prospective follow up studies.

Acute exacerbations in HBeAg negative patients with chronic hepatitis B virus (HBV) infection are invariably associated with concurrent increases in the index of IgM class antibodies against the core protein (anti-HBc) of the virus. This study aimed to investigate whether this was related to the clearance of variants from the quasispecies pool and the appearance of new ones, with aminoacid substitutions in well recognized B-cell epitopes. In this study, 5 HBeAg negative patients (A to E) with 13 sequential serum samples (A1-A2, B1-B2-B3, C1-C2, D1-D2-D3, E1-E2-E3) were investigated after amplification of the entire core encoding region followed by cloning/sequencing studies. The sequences at different time points were compared with those from a single HBeAg positive patient with no apparent acute exacerbations. The results from sequence comparison showed that virus variants emerged in all (A2, B3, C2, D3, E2, and E3) but two (B2 and D2) subsequent sera with amino-acid substitutions affecting B-cell epitopes. It is concluded that the rise in the values of IgM anti-HBc may be attributed to the alteration of the antigenic epitopes leading to new antibody production in the majority of the cases. However, it appears that increases in IgM anti-HBc indexes in a few cases may relate to other possible mechanisms which are discussed.

AIM: To evaluate survival rate and clinical outcome of cholangiocarcinoma. METHODS: The medical records of 34 patients with cholangiocarcinoma, seen at a single hospital between the years 1999-2006, were retrospectively reviewed. RESULTS: Thirty-four patients with a median age of 75 years were included. Seventeen (50%) had painless jaundice at presentation. Sixteen (47.1%) were perihilar, 15 (44.1%) extrahepatic and three (8.8%) intrahepatic. Endoscopic retrograde cholangiography (ERCP) and/or magnetic resonance cholangiography (MRCP) were used for the diagnosis. Pathologic confirmation was obtained in seven and positive cytological examination in three. Thirteen patients had co-morbidities (38.2%). Four cases were managed with complete surgical resection. All the rest of the cases (30) were characterized as non-resectable due to advanced stage of the disease. Palliative biliary drainage was performed in 26/30 (86.6%). The mean follow-up was 32 mo (95% CI, 20-43 mo). Overall median survival was 8.7 mo (95% CI, 2-16 mo). The probability of 1-year, 2-year and 3-year survival was 46%, 20% and 7%, respectively. The survival was slightly longer in patients who underwent resection compared to those who did not, but this difference failed to reach statistical significance. Patients who underwent biliary drainage had an advantage in survival compared to those who did not (probability of survival 53% vs 0% at 1 year, respectively, P = 0.038). CONCLUSION: Patients with cholangiocarcinoma were usually elderly with co-morbidities and/or advanced disease at presentation. Even though a slight amelioration in survival with palliative biliary drainage was observed, patients had dismal outcome without resection of the tumor.

Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C (CHC), but little is known about the role of resistin in chronic liver diseases. The objective of this study was to investigate serum levels of the above three adipokines in relation to the etiology of liver disease and to determine their associations with histological severity.We prospectively evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70, NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological, anthropometric and laboratory data were recorded. Histological lesions were evaluated blindly according to the Ishak and the Brunt classifications for CHB/CHC and NASH, respectively.Serum adipokine levels were similar between CHB and CHC patients, while CHB/CHC patients had significantly lower leptin levels compared with NASH patients (8.3+/-7.3 versus 17.6+/-16.6 ng/ml, p=0.012) and higher adiponectin (10.2+/-5.1 versus 7.5+/-4 microg/ml, p=0.018) and resistin levels (7.1+/-2.5 versus 5.7+/-2.8 ng/ml, p=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and levels of adipokines, while the presence of moderate/severe fibrosis (stages 4-6) was associated with higher leptin and adiponectin levels in male but not in female patients and with lower resistin levels irrespective of gender or other factors (adjusted odds ratio=0.788, p=0.035).Serum adipokine levels depend on the etiology of liver disease differing between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, whereas in the association of leptin and adiponectin levels with fibrosis, it seems to be a gender effect.

Treatment with tumor necrosis factor (TNF) antagonists in patients with rheumatic diseases has been associated with increased rates of tuberculosis due to reactivation of latent Mycobacterium tuberculosis (MTb) infection (LTBI). Diagnosis of LTBI is based mainly on the tuberculin skin test (TST), which has certain limitations.We compared the TST with an enzyme-linked immunospot interferon-gamma (IFN-gamma) release assay (Elispot; T SPOT TB) for the diagnosis of LTBI in 70 patients with various rheumatic diseases starting treatment with anti-TNF agents. All patients underwent a standard initial evaluation for LTBI including clinical examination, chest radiograph, and standard TST. Freshly isolated peripheral blood mononuclear cells were stimulated ex vivo with MTb-specific antigens (ESAT-6 and CFP10), and IFN-gamma-producing cells were counted (Elispot assay).Twenty-seven patients (38.6%) were TST+ and 16 were Elispot+ (22.8%). The overall level of agreement between the 2 tests was 72.8%, being much higher in patients who were TST- (39/43, 90.6%) than in those who were TST+ (12/27, 44.4%). Discordant results were observed in 19 patients (27.1%). Among TST- patients (n = 43), 4 were Elispot+ (9.3%); we also identified 15 Elispot- patients among 27 TST+ patients (55.6%). Multivariate analysis showed that a history of bacillus Calmette-Guérin (BCG) vaccination was associated with TST+/Elispot- discordant results (p = 0.01), whereas steroid use was linked to TST-/Elispot+ discordant results (p = 0.04).Elispot assay is a useful test for diagnosis of LTBI in rheumatic patients scheduled for anti-TNF therapy and identification of patients with false-positive TST results due to previous BCG vaccination.

Several types of human immunodeficiency virus (HIV)-associated vasculitides, including polyarteritis nodosa-like syndromes have been reported in patients with HIV infection. The pathogenic mechanism is thought to be related to either circulating immune complexes or direct endothelial involvement by HIV per se. In HIV-related necrotizing systemic vasculitis, affected arteries are smaller than those seen in classic polyarteritis nodosa, and it rarely becomes a multisystem and life-threatening disease with the exception of cases with heart, kidney, central nervous system, or gut involvement. We describe a case of systemic necrotizing vasculitis in an HIV-infected individual presented with fever, purpuric rash, and polyarthritis who eventually had development of mesentery artery thrombosis and nephrotic syndrome. The patient, solely under triple antiretroviral therapy, remains symptom free, with no evidence of his multisystem disease and no progression of his HIV infection after 10 years of follow-up. All patients with a vasculitis of unidentified etiology should be evaluated for HIV infection.

AIM: To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver biopsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholangitis/cholangiolitis in 20% of patients. Mixed hepatitic/cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was observed in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was associated with increased hospitalization in the ICU prior death (P = 0.026). CONCLUSION: Features of hepatitis and steatosis are the main histological findings in the liver in the majority of patients dying from sepsis.

In chronic hepatitis C and non-alcoholic fatty liver disease, apoptotic caspases are activated in liver, and serum caspase activity has been suggested as a sensitive marker of early liver injury. An investigation was carried out into whether the serum levels of caspase-generated fragments of cytokeratin-18 (CK-18) are associated with the severity of liver lesions in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Patients/CK-18 fragment serum levels were determined in 115 treatment-naive, consecutive HBV patients and 30 healthy controls. Hepatic-expression of CK-18 fragments was evaluated by immunocytochemistry in chronic hepatitis B patients.CK-18 fragment levels (U/l) were significantly lower in healthy controls (mean (SD), 154 (31)) than in 53 inactive carriers (172 (24), p = 0.003) and in 62 chronic hepatitis B patients (474 (488), p0.001). The receiver operating characteristic curve showed excellent diagnostic accuracy (c-statistic: 0.87) for differentiating inactive carriers from chronic hepatitis B patients. A CK-18 fragment cut-off level of 240 U/l gave a sensitivity of 60%, and a specificity and positive predictive value of 100% for chronic hepatitis B diagnosis. CK-18 fragment levels were also lower in inactive carriers than in 16 chronic hepatitis B patients with transiently normal alanine aminotransferase (ALT; 327 (256), p = 0.001), offering good accuracy for such a differentiation (c-statistic: 0.78). In chronic hepatitis B patients, serum CK-18 fragments correlated positively with ALT/aspartate aminotransferase (AST), viraemia, grading score and their immunohistochemical hepatic expression, and negatively with platelet counts, but not with fibrosis or steatosis severity.Serum apoptotic caspase activity is strongly associated with the presence of liver injury in patients with HBeAg-negative chronic HBV infection. CK-18 fragment levels seem to be a very useful marker for differentiation between the inactive HBV carrier state and HBeAg-negative chronic hepatitis B, but not for estimation of the severity of liver histological lesions among HBeAg-negative chronic hepatitis B patients.

BACKGROUND/AIM: Hepatic steatosis is considered to be mostly associated with viral factors in genotype 3 and metabolic factors in genotype 1 chronic hepatitis C, while there are rather few data for genotype 4. We determined the parameters associated with steatosis in 350 chronic hepatitis C patients, focusing on genotype 4. METHODS: Histological lesions were evaluated according to Ishak's classification and steatosis was semiquantitatively graded. Several patient characteristics on the biopsy day were also evaluated. RESULTS: Steatosis was present in 73% of patients without significant differences among genotypes. Moderate/severe steatosis was more frequent in genotype 3 than 4 (44% vs 26%, P= 0.025) and similar between genotype 4 and 1 patients. Moderate/severe steatosis was associated with body mass index (BMI) in genotype 4 (P= 0.023) and gamma-glutamyl-transpeptidase in genotype 3 patients (P= 0.044). In 150 nondiabetic patients with BMI < or =25 kg/m(2), moderate/severe steatosis was present in 15, 40, and 11% of genotype 1, 3, and 4 patients, respectively, (P= 0.005) and was independently associated only with genotype 3. In multivariate analysis, steatosis grade or moderate/severe steatosis was independently associated with higher BMI, genotype 3, and lower cholesterol. CONCLUSIONS: Moderate or severe steatosis is significantly less frequent in genotype 4 than 3 chronic hepatitis C patients and similar between genotype 4 and 1. In nondiabetic, nonoverweight patients, moderate or severe steatosis is present in only 10-15% of genotype 4 or 1 compared with 40% of genotype 3 patients. Thus, hepatic steatosis in genotype 4 is mostly associated with metabolic factors, similar to those in genotype 1.

AIM To investigate the mode of transmission and the natural history of chronic hepatitis B virus (HBV) infection in children of different ethnicities in Greece. This study was part of the Interreg I-II EC project. PATIENTS AND METHODS One hundred seventy-three hepatitis B surface antigen (HBsAg)(+) carriers, median age 6.9 (5-12) y, were prospectively followed-up for a mean period of 5.3 (1-12) y for serological markers of HBV infection, serum alanine aminotransferase (ALT), HBV-DNA, alpha-fetoprotein levels and ultrasonography. RESULTS Vertical transmission predominates (61.8%) in Moslem children and horizontal (44%) in those born in Russia. At entry, 73 of 173 (42%) HBsAg(+) genotype D children were hepatitis B e antigen (HBeAg)(+), ranging from 27% to 67% among ethnic groups; 55 of 173 (32%) had ALT > 2 x upper normal limit (UNL), ranging from 21% to 39%. Of 100 anti-HBe(+) children, 85 (85%) were inactive carriers. During the follow-up period, seroconversion to anti-HBe was observed in 40 of 73 (55%) children with an annual rate of 11%; 35 of 40 (87.5%) had biochemical remission, and 28 of 35 (80%) lost HBV-DNA. In the anti-HBe(+) group, 27 of 100 (27%) lost HBV-DNA and 9 of 100 (9%) lost HBsAg. The annual seroconversion rate for HBeAg was significantly lower: in children with vertical transmission compared with horizontal (7.7% vs 14.8%, respectively, P < 0.001) and in Muslim children compared with both Christian children and those born in Russia (8.6% vs 12%, respectively, P < 0.001). No differences were found among the ethnic groups after adjusting for the mode of infection. Two of 173 children had progression of liver disease. CONCLUSIONS The differences in HBeAg(+) status and seroconversion rate among the ethnic groups are related to the time/mode of HBV infection. The majority of children who developed anti-HBe immunity had biochemical remission, and a substantial number of the inactive carriers lost viremia during the observation period of up to 12 y.

Sub-acute focal neurological manifestations are reported rarely in systemic rickettsial diseases and are considered to be secondary to immune-mediated mechanisms. We present two cases of transient sensorineural hearing loss complicating the course of severe rickettsial diseases caused by Rickettsia typhi and Rickettsia conorii, respectively. The diagnosis was based on the presence of high IgM antibodies and the prompt response to doxycycline treatment. In both cases, hearing loss presented during convalescence and resolved automatically without administration of specific treatment.

Hepatitis B virus (HBV) strains carrying the precore stop-codon mutation (A1896) have been considered among the predisposing factors for reactivation during chemotherapy for malignancies. The role of the T1762/A1764 basic core promoter (BCP) mutations has not been fully evaluated. We aimed to record any changes in HBV serological markers after reactivation, detect the presence of A1896 and BCP mutations and evaluate the type of cytotoxic drugs involved. We retrospectively screened eight patients presenting with HBV reactivation following chemotherapy for malignancies. The chemotherapy regimens used included corticosteroids (CSs), fludarabine and cyclophosphamide/adriamycine. The INNO-LiPA HBV PreCore kit was used for the detection of the A1896 and BCP mutations. Six patients who were hepatitis B surface antigen (HBsAg)-(+)/hepatitis B e antigen (HBeAg)-(-) before chemotherapy, had disease reactivation following a mean of four cycles of chemotherapy. Four survived and two died of hepatic failure. At the time of reactivation, all six patients carried the A1896 and five of them the BCP mutations. The remaining two patients were HBsAg-(-)/anti-HBs-(+)/anti-hepatitis B core (HBc)-(+)/HBeAg-(-) before chemotherapy. One of them reverted to HBeAg-(+) status but remained HBsAg-(-), while the other became HBsAg-(+)/HBeAg-(+), following three and eight cycles of fludarabine treatment, respectively. The former carried the A1896 and the latter the wild-type virus. Both died from causes associated with their haematological disease. All but one of our patients with HBV reactivation during chemotherapy carried the precore stop-codon and BCP mutations. Whether this occurs more frequently in such patients than those carrying the wild-type virus needs further investigation. Fludarabine should be added to the list of drugs inducing HBV reactivation. HBV reactivation following fludarabine treatment occurred in HBsAg-(-) patients who had been anti-HBs-(+).

To determine: (a) whether the components of metabolic syndrome (MetS) cluster more frequently than predicted by chance alone and (b) whether increased risk for MetS is associated also with values of each component below, but close to the cutoff points defining MetS.Anthropometrical and biochemical measurements were performed and a dietary questionnaire was filled-in in 1833 randomly selected non-diabetic subjects, 916 men and 917 women, 20-74 years old, in nine centres in five Mediterranean countries. The prevalence of MetS and of possible combinations of its individual components was measured. The expected frequencies of the above combinations were calculated according to the mathematical formula of probabilities.The overall prevalence of MetS was 27.2%, but varied greatly among countries, from 5.8% in Algeria to 37.3% in Greece. The observed prevalence of each combination diagnostic of MetS was higher than the expected by chance. Thus, the observed overall prevalence of MetS was also higher than the expected, 27.2 vs 24.0%, P=0.03. Furthermore, for each individual component (except high-density lipoprotein), as values in the normal range, approached the cutoff point, the risk of having MetS (i.e. clustering of the other components) increased significantly (odds ratio 2.2-4.6, P0.001).The MetS is not related to the Mediterranean type of diet and its prevalence varies greatly among five Mediterranean countries. The clustering of the components defining the MetS is not due to chance and moreover even 'high normal' levels of each component confer increased risk for the syndrome.

Liver transplantation remains an underdeveloped technique in Greece; currently there is no information on outcomes in Greek patients. In this study, data were provided on the outcomes of liver transplantation in 71 patients with a mean follow-up of 6 (0.1 to 16) years in our center. Mean age at transplantation was 46 +/- 13 years, while the main cause for transplantation was hepatitis B (16 patients, 23%) or C (six patients, 8%) virus. In the first posttransplantation year, three patients died, while 18 (25%) required at least one hospitalization with a median stay of 30 days. At the end of follow-up, 56 patients (79%) are alive. The leading cause of death was de novo malignancies (40%), appearing at a mean of 5.2 +/- 3.3 years. Late adverse effects of immunosuppressive therapy included hypertension (42%), hyperlipidemia (24%), chronic renal failure (21%), and diabetes mellitus (24%). With the exception of diabetes, all the above abnormalities were significantly associated with cyclosporine-based but not with tacrolimus-based immunosuppressive regimens. Relapse of primary disease in liver transplants occurred in 21 (29.6%) patients at a mean time of 1.5 +/- 1.4 years, of whom 67% were related to viral hepatitis. The quality of life (Karnofsky scale 1 to 6) was excellent in 64% of surviving patients, affordable in 21%, and poor in 15%. In conclusion, after 6 mean years, the majority of Greek liver transplant recipients conduct a normal life, although metabolic abnormalities are often observed. A national registry is needed to provide more solid evidence of outcomes.

We investigated in detail the difference between serum and plasma potassium levels in patients with several conditions associated with pseudohyperkalemia. In total, 435 patients with either thrombocytoses, erythrocytoses, leucocytoses, or a mixed-type disorder and 30 healthy controls were included. In each case, the index Dk [serum potassium minus plasma potassium] and the index Dk100 (Dk x 100,000/platelets), which indicates the Dk value that corresponds to platelets of 100,000/mm(3), were estimated. Median Dk was significantly higher in the groups with platelet, erythrocyte, or mixed-type disorders than in the controls (P=0.001). Among these groups, Dk values were significantly higher in patients with thrombocytosis or mixed-type disorders compared with those with erythrocytosis (P0.001, for both). Furthermore, no significant difference was observed in Dk values between controls and patients with white blood cell disorders (P=0.74). Dk values did not exceed 2.61 mmol/L, whereas Dk100 values were inversely related to platelet counts (r=-0.351, P0.01). In conclusion, pseudohyperkalemia is mainly present in patients with thrombocytosis or mixed-type disorders, probably as a result of the degranulation of platelets, which offers a potassium load to the surrounding plasma at the time of clot formation in vitro. However, the degree of pseudohyperkalemia does not increase proportionally with the increase of platelet counts, which may be associated with transfer of part of potassium load from the plasma back into red and white blood cells.