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Liver cirrhosis is characterized by remodeling leading to nodules that are difficult to discern from hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) serum levels are used for the screening for HCC, with limited success. We evaluated angiopoietin-2 as a serum marker in patients with cirrhosis and with HCC.In a retrospective study, we measured angiopoietin-2 serum levels in 131 patients with HCC, 180 patients with cirrhosis, and 40 healthy controls. We also determined AFP serum levels in patients with HCC and compared the test characteristics of both serum markers. The expression patterns of angiopoietin-2 were determined by in situ hybridization in healthy and cirrhotic livers as well as in HCC.Angiopoietin-2 serum levels were elevated in patients with liver cirrhosis (P0.0001) compared with healthy controls. Levels were further elevated in patients with HCC compared with healthy controls (P0.0001) and cirrhotic patients (P0.0001). The combination with AFP measurements led to improved discrimination between HCC and cirrhosis. Angiopoietin-2 message was present in tumor cells of HCCs but was absent from hepatocytes of cirrhotic and healthy livers. In cirrhosis, message was detected within the strands of fibrous tissue.Serum angiopoietin-2 levels are elevated in patients with cirrhosis, implicating a possible role of the angiopoietin-Tie-2 system for neoangiogenesis in cirrhosis. Serum levels are further elevated in patients with HCC, suggesting the potential use of angiopoietin-2 as a marker for the detection of cirrhosis and HCC.

Background CTLA4 is an inhibitory receptor expressed on a subset of T lymphocytes. Single nucleotide polymorphisms of the CTLA4 gene have been implicated in autoimmune diseases, including autoimmune hepatitis and primary biliary cirrhosis. In reverse form, CTLA4 variations are associated with chronic infections such as chronic hepatitis B. Methods CTLA4 variations - 318C > T and + 49A>G were analyzed in 2366 patients with chronic liver disease of various etiologies, including 323 patients with chronic hepatitis B virus (HBV) infection, 1181 patients with chronic hepatitis C virus infection, 180 patients with primary biliary cirrhosis, and 127 patients with autoimmune hepatitis, as well as 202 healthy control individuals. Genotyping was performed by melting curve analysis. Results The - 318C>T variation was underrepresented in patients with chronic HBV infection compared with healthy controls (14.6 vs. 25.7%, P= 0.002) and with patients with chronic liver disease of other origin (14.6 vs. 20.7%, P=0.011). Patients with cryptogenic cirrhosis also showed a lower frequency of the - 318T allele than healthy controls (12.0 vs. 25.7%, P=0.014). No association of the + 49G >A variation was found with any diagnosis, including autoimmune hepatitis and primary biliary cirrhosis. Conclusion We describe the association of the CTLA4 -318C>T variation with chronic HBV infection and cryptogenic cirrhosis but find no association of the +49G>A variation with autoimmune liver disease.

Background: Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (AMA). Autoantibodies specific for the mitochondrial M4 antigen can be detected by a complement fixation test (CFT) but not by immunoblotting. The aim of this study was to elucidate the identity of the M4 antigen. Patients and methods: M4 proteins were purified by affinity chromatography using IgG fractions of PBC marker sera being CFT positive (n=5) or negative (n=5) and identified by Western blotting, silver staining and sequence analysis. Further, a cohort of 57 PBC patients was tested for the reactivity to M4 and pyruvate dehydrogenase complex (PDC). Results: Two AMA patterns of the marker sera were visualized: CFT-positive sera were defined as PDC-E2+/E1+ and the CFT-negative sera as PDC-E2+/E1−. The major proteins in the M4 fraction could be related to the PDC-E1 subunits. A clear-cut association between anti-M4 reactivity in the CFT and the reactivity to both PDC subunits could also be documented in the cohort of 57 PBC patients showing anti-PDC-E1α and E1β antibodies at a frequency of 74% and 67%. Conclusions: CFT reactivity against M4 antigens could be preferentially identified as a reaction against PDC-E1. As PDC-E1 subunits as compared with PDC-E2 lack lipoyl-binding sites, they probably have to be considered as an independent and important target.

Background: Ileocolonoscopy represents the diagnostic standard in the work-up of patients with inflammatory bowel diseases (IBD). Patients are often reluctant to be colonoscoped because of the invasiveness and pain sensation during colonoscopy. Aims: To compare the usefulness of transabdominal ultrasound (US) and magnetic resonance imaging (MRI) in assessing disease extension and activity in patients with IBD restricted to the terminal ileum and large bowel. Patients and Methods: 61 patients with IBD [37 Crohn's disease (CD) and 24 ulcerative colitis (UC)] were prospectively studied. All patients underwent clinical and laboratory assessment, ileocolonoscopy, transabdominal sonography, and MRI within 5 days. Involved bowel segments were defined as those with bowel wall thickness >3 mm and increased Doppler signal on US or contrast enhancement of the bowel wall on MRI. To compare disease activity endoscopic, MRI and US findings were graded with newly developed scores. Results: The segment-by-segment analysis revealed an overall accuracy of 89% for US and 73% for MRI in identifying active IBD. The accuracy was better in patients with UC than in patients with CD for both US and MRI. The endoscopic activity index (EAI) correlated stronger with the US activity index (r = 0.884) than with the MRI activity index (r = 0.344). The correlation of US and MRI activity indices with EAI was better in patients with UC compared with patients with CD. All three imaging methods showed a significant correlation with clinical disease activity in patients with UC but not in patients with CD. Conclusion: This study provides strong evidence that US should be considered as a first-choice method for follow-up of patients with IBD of the terminal ileum and large bowel.

Background/Aims : Efficacy and safety of interferon-α (IFN-α)/ribavirin retreatment with or without amantadine sulphate were evaluated in non-responders with chronic hepatitis C. Methods : Two hundred twenty five consecutive non-responders to previous antiviral treatment(s) with IFN-α alone or in combination with ribavirin or amantadine were treated with IFN-α 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000–1200 mg/d. One hundred fifteen of 225 patients were randomized to receive amantadine sulphate 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24. Results : An overall sustained virologic response with undectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 ( P P =0.011) and only one previous antiviral treatment ( P =0.032) were more likely to respond to antiviral retreatment. There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-α/ribavirin alone (25 versus 18%, P =0.172). Conclusions : The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-α/ribavirin alone, in particular in patients with low baseline viremia.

Obesity is a rather documented risk factor for the formation of gallstones (GS) in women. The magnitude of the increased risk and the rates of GS occurrence, however, have not been well quantified, except for two studies on the risk of symptomatic stones in obese women. We analyzed the incidence of GS in 157 moderately obese women (body mass index, 31.4 +/- 3.6 kg/ m2) followed up prospectively by ultrasound for 2-6 yr (mean 3.95 yr). Women with morbid obesity (body mass index40 kg/m2) were excluded from the study, as well as patients having diseases with lithogenic risk. All the enrolled women had normal cholecystosonogram results at the beginning of the study. Age, family history of GS or obesity, parity, age of obesity onset, hyperlipoproteinemia type, plasma cholesterol (total, HDL, LDL), and triglycerides were assessed. The Student's t, the Mann-Whitney rank sum and the Fisher's exact tests were used, as well as the multiple logistic regression for the multivariate analysis. During the survey, 16 of 157 women (10.2%) developed GS. GS were asymptomatic in 11 persons (68.8%). The cumulative incidence of both asymptomatic and symptomatic GS was 2.6 cases/100 obese women.year. During the follow-up, most of the detected GS were asymptomatic, and this explains the higher GS incidence rate found compared with that previously calculated for symptomatic GS. The following risk factors were associated with GS formation: age (p = 0.002), family history of GS (p = 0.011), early obesity onset (p = 0.003), and hyperlipoproteinemia type IV (p = 0.011). A high risk class might be thus identified among obese women, offering a more realistic approach for the primary prophylaxis of GS.

The present study retrospectively analyses all the necropsies (5, 112) performed in the two departments of pathology of a large Romanian town (Cluj-Napoca) during a ten-year interval (1983-1992) in order to estimate the prevalence of hepatocellular carcinoma (HCC). To evaluate the time trends of the association of HCC with liver cirrhosis, all cirrhotic subjects necropsied during two consecutive ten years intervals in one of the departments of pathology (Third Medical Clinic) were analysed. The prevalence of HCC was 8/100,000, with a derived incidence of 1.6/100,000 population/year. HCC was more frequent in males, and it occurred more frequently in cirrhotics (13.8%) than in noncirrhotics (0.6%) (p0.0001). The trends in the incidence of HCC in liver cirrhosis were evaluated for the 258 cirrhotic subjects necropsied during two ten year periods (1973-1982 and 1983-1992) in the Third Medical Clinic. HCC was found in cirrhotics older than 40 years, in proportions between 14 and 25% for the different age groups. There was an increasing tendency of HCC incidence in cirrhotic subjects over the last 20 years, significant for the 70-79 years age group. These data indicate a low incidence of HCC in our geographic area and suggest an increasing trend of the HCC association to liver cirrhosis over the last 20 years, more obvious in the advanced ages.

Ultrasound of the abdomen was performed in 30 artificially respirated patients under intensive care conditions for 7 days per patient over a time period of 6 months to elucidate the therapeutic value of different ultrasonographic findings with respect to the diagnosis "reactive acute cholecystitis". Our results show, that neither the detection of concrements or sludge within the gallbladder, nor the transient dilatation of the bile duct, nor a transient wall-thickening or the occurrence of a three-layered wall of the gallbladder can be interpreted as reliable sonographic criteria for the occurrence of an acute reactive cholecystitis. From this we conclude, that reactive acute cholecystitis leading to the indication for cholecystectomy can only be diagnosed from the combination of clinical and sonographic findings. However, reactive acute cholecystitis can almost certainly be excluded, even in obscure upper abdominal symptoms, when the sonogram of the gallbladder is normal.

Revealing a sensitivity of 97.5% and a specificity of 95.12% this study emphasizes the excellent diagnostic value of sonography in the elucidation of patients with clinical signs of "acute appendicitis". Evaluation of morphology on the one hand and maximal diameter of the organ and the organ wall on the other, in conjunction with the clinical presentation, allows a restrictive management of the surgical treatment and thus decreases the rate of negative laparotomy.

We conducted a longitudinal follow-up of 72 patients with liver cirrhosis (LC) in order to assess gallstone (GS) incidence. The period of survey was 24.5 +/- 12.2 months. Patients were divided into two groups: group I--26 patients with ascites at the start or appearing during follow-up, and Group II--46 patients with compensated LC (no ascites) throughout the survey. During follow-up, 12 of 72 (16.6%) patients developed GS. The global cumulative incidence of GS was 5.5 cases/100 people/year. Age and sex had no influence on the incidence of GS in LC; neither had etiology or cirrhosis. On the contrary, the study revealed a significant increase in the incidence of GS in decompensated cirrhosis. In group I patients, GS appeared more frequently (34.6%) than in group II patients (6.5%) (chi 2 9.479; p less than 0.002). The cumulative incidence of GS was five times higher in decompensated versus compensated LC.

A 74 year old woman with symptomatic common bile duct dilatation and gastric outlet obstruction because of Waldenstroem’s macroglobulinaemia (WM) with nodal and duodenal involvement, underwent endoscopic retrograde cholangiography (ERC) …