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Aim: The aim of this study was to define the natural long-term course of HDV compensated cirrhosis., Methods: 166 consecutive patients with compensated HDV-related cirrhosis diagnosed since 1994 were followed up until the first decompensation and then until death, liver transplantation or 31st of December 2004. The survival during follow-up and the survival according to the type of first decompensation were calculated using the Kaplan Meier method. Survival curves were compared using the log-rank test., Results: 56 females (33.7%) and 110 males (66.3%) with a mean age of 40.7+/-7.9 years were included in the study. The mean Child Pugh and MELD score at the first episode of hepatic decompensation was 8.6+/-2.08 and 15.19+/-5.42, respectively. The median survival was 58.3 months since the diagnosis of compensated cirrhosis and the mean time to first decompensation was 21+/-19 months. The probability of survival after the diagnosis of compensated cirrhosis was 94.3%, 82.5%, and 51.5% at 1, 2, and 5 years, respectively. Ascites was the most frequent first decompensation (80.7%), followed by jaundice (30.1%), portal hypertensive gastrointestinal bleeding (PHGIB) (28.9%), hepatic encephalopathy (HE) (12%), hepatocellular carcinoma (HCC) (12%), portal vein thrombosis (8.4%), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome. 86 patients (51.8%) presented more than one complication at initial decompensation. Survival was worse in patients with jaundice and SBP (p=0.001), followed by patients with HE (p=0.05) and patients who presented more than one initial complication (p=0.03). In the multivariate survival analysis only PHGIB as first decompensation and MELD score>15 were independent predictors of death., Conclusion: HDV-related cirrhosis in Romania is an aggressive disease with a median time to decompensation less than 2 years and a median survival less than 5 years. Jaundice, the main clinical consequences of portal hypertension and HCC are the most frequent causes of decompensation and more than half the patients present two or more concomitant initial complications.

Background and Aim: Protein-calorie malnutrition (PCM) occurs in 20-60% of patients with hepatic cirrhosis and is associated with the development of life-threatening complications. We evaluated the effect of a modified, casein-vegetable-based, high-protein high-calorie (HPHC) diet on the outcome of cirrhotic patients with hepatic encephalopathy (HE)., Methods: One hundred and fifty three consecutive cirrhotic patients with overt HE were included in this study. An HPHC diet based on better-tolerated vegetable and milk-derived proteins was initiated in order to ensure the adequate protein-energy requirements of 30 kcal/kg/day and 1.2g proteins/kg/day. Serial (daily) assessments were done, including mental status, asterixis, a conventional Number Connection Test (NCT), bowel movements and blood ammonia level. The assessment of the mental status was performed using the West Haven scale. Favorable evolution or response to HPHC diet was defined as an improvement in HE stage with 1 or more (Delta > or =1 stage) after 14 days of diet., Results: During the HPHC diet, 122 patients (79.7%) improved in terms of response definition. A significant decrease in blood ammonia level was observed after 14 days (p<0.0001) in all patients, whatever the improvement of the mental status. A significant improvement in the NCT scores was also noted (p<0.0001). More patients with advanced HE (West Haven stage 3) precipitated by various factors showed a Delta = -2 improvement of their mental status during the modified HPHC diet compared with patients in lower initial stages (50% vs 18.9%, p=0.002). More patients in Child-Pugh B class had a Delta = -2 decrease in the grade of HE compared with patients in Child-Pugh C class (61.7% vs. 14%, p=0.001)., Conclusions: Almost 80% of patients in our study improved their mental status during the casein-vegetable-based HPHC diet, showing that dietary protein restriction is not required for the improvement of HE. A higher rate of improvement was noted in patients with severe impairment of mental status related to precipitating factors and in patients with well preserved liver function. The daily eating pattern consisting of 4 snack-meals and a late evening meal may contribute to HE improvement by equal protein distribution during the day.

Background and Aim: Pegylated interferon alpha in combination with ribavirin represents nowadays the gold standard therapy in patients with chronic hepatitis C. The aim of this study was to assess early (EVR) and sustained virological response (SVR), tolerability and baseline predictive factors for SVR in patients with chronic hepatitis C treated with peginterferon alpha-2a and ribavirin combination therapy in day-to-day clinical practice., Methods: The analysis included 174 consecutive patients with chronic hepatitis C (naive, relapsers and non-responders after standard therapy) managed in two expertise gastroenterology centers in Romania, mainly on an outpatient basis. The combination therapy was initiated between 1st of June 2002 - 30th of June 2003., Results: The mean age of the study population was 47 years; 41% were men, mean BMI was 26.5 kg/sq.m. Only 7.5% of them had bridging fibrosis/cirrhosis on liver biopsy. EVR and SVR were noted in 78.7% and 51.1%, respectively. Multivariate analysis showed two independent variables associated with SVR: absence of bridging fibrosis/cirrhosis and absence of hepatic steatosis. The rate and profile of side effects associated with pegylated interferon alpha-2a and ribavirin in our clinical setting were all predictable, based on previous experience in the literature. Side effects resulted in interferon and ribavirin dose reductions in 9.2% and, respectively, 25.3%, but permanent discontinuation of the combination therapy was required in only 5.74% of patients., Conclusion: Combination antiviral therapy can be safely and successfully used outside clinical trials. To achieve high response rates and tolerability, similar or better than those reported in clinical trials, hepatitis C patients have to be managed in expertise centers, by experienced physicians, aiming at minimizing side effects, optimizing dosing, and enhancing compliance.

Preliminary results indicate that living donor liver transplantation (LDLT) recipients infected with HCV develop earlier and more severe recurrence than their cadaveric counterparts. The mechanisms underlying this observation are unknown, but could include hepatic regeneration, differences in LDLT recipient demographics, immune homology between donor and recipient, or other factors not previously considered. The optimum clinical approach is to consider LDLT in HCV-infected recipients only as a life-saving procedure and to attempt to eradicate HCV before LT to prevent recurrent infection.

Background: Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging., Patients and Method: We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or 3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value<0.05) associated with the chi-squared test in contingency tables. Multivariate analysis was performed by logistic regression using SPSS 10., Results: There were 31 males (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97 years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29 patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The classic diagnosis was made in 32 patients (58.18%). In the univariate analysis the non-classic diagnosis was associated with: age>18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors., Conclusion: In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.

Mucosa-associated lymphoid tissue (MALT) lymphomas represent a relatively new described class of rare lymphomas, characterized by an indolent course and favourable outcome with specific therapy. Gastric MALT lymphomas are associated with chronic Helicobacter pylori (HP) infection. We report the case of a 67 year old man admitted for an 8-month history of epigastric pain, anorexia and progressive weight loss. He was diagnosed with low-grade primary gastric MALT lymphoma by endoscopy, histopathological examination of gastric mucosa (light microscopy and immunohistochemistry) and endoscopic ultrasonography (EUS). The patient received a 2-week course of anti-HP therapy and chemotherapy with Chlorambucil 0.1 mg/kg/day was started. During the follow-up, continuous improvement of clinical status, endoscopic and EUS appearance was noted. We conclude that, facing the trend toward nonsurgical treatment modalities for primary gastric lymphoma, EUS appears an important tool for staging the disease and defining cases suitable for anti-HP, radio- and chemotherapy, as well as for the detection of local recurrence.

The risk of hepatocellular carcinoma superimposed in the evolution of autoimmune hepatitis or primary biliary cirrhosis is low, even in patients with long-standing cirrhosis. We report a case of hepatocellular carcinoma occurring in a 46 year old woman with liver cirrhosis following overlap syndrome between autoimmune hepatitis and primary biliary cirrhosis, routinely followed while on the waiting list for liver transplantation. The patient had combined biochemical (elevated aminotransferases, alkaline phosphatase and gamma-glutamyl-transpeptidase in the range of 2-3 times above the upper limit of the normal) and serological (anti-smooth muscle antibody > 1/80 and anti-mitochondrial antibody anti-M2 > 1/40) criteria of autoimmune hepatitis and primary biliary cirrhosis. Hepatocellular carcinoma was diagnosed in the setting of chronic liver disease by the combination of two concordant imaging technics (Doppler ultrasound and magnetic resonance imaging) showing a hepatic nodule with arterial hypervascularization and elevated serum levels of alpha-fetoprotein up to 950 ng/ml. Liver transplantation is the best treatment both for the solitary nodule less than 5 cm and underlying autoimmune cirrhosis. Using the new Model for End-Stage Liver Disease allocation system our patient was placed in a prior position for liver transplantation (MELD 29). Unfortunately, a sudden fulminant liver failure complicated with intravascular disseminated coagulopathy was fatal for our patient while awaiting liver transplantation.

Endoscopic ultrasound (EUS) represents a highly sensitive method for the detection of pancreatic masses. When available, EUS-guided fine needle aspiration (FNA) is the best technique for the diagnosis and staging of pancreatic cancer due to its ability to obtain tissue for diagnosis. The standardized indications for pancreatic EUS-FNA comprise the definite diagnosis of malignancy and histopathological confirmation of adenocarcinoma before surgical resection, chemo/radiotherapy, or celiac plexus neurolysis. The technique of performing EUS-FNA is described in detail, from the vizualization of the target lesion and adequate placement of the transducer to allow optimal needle access, to needle penetration and sampling of the targeted lesion. We report a series of 9 patients who underwent EUS-FNA and shortly review the indications, technique, results and impact of EUS-FNA on the management of these patients.

Background and Aims: Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus., Methods: We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis., Results: From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis., Conclusions: Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

Radiation proctitis is a well-recognized complication following radiotherapy for pelvic malignancy. This study was designed to compare the efficacy and complications of argon plasma coagulation (APC) using the power setting of 50 W vs. 60 W in a group of patients with radiation proctitis. Forty-two patients were randomized to undergo APC using the electrical power setting of 60 W (23 patients, group A) or 50 W (19 patients, group B). Patients were asked to estimate the severity of major symptoms before and after APC using a scoring system graded 0-4. The score of major symptoms before and after APC, mean duration of the procedure, number of sessions, side effects/complications were noted. Statistical analysis was performed using Fisher's Exact Test and the 2-tailed p value less than 0.05 was considered statistically significant. A significant improvement of major symptoms was noted in all patients treated with APC, irrespective of the wattage we used, apart from the presence and severity of tenesmus. The mean number of treatment sessions to achieve control of bleeding was 1.34 for group A and 1.9 for group B and the mean time of treatment sessions was significantly shorter for group A (15 min vs. 17 min for group B). No significant differences in early side effects and long term complications between the two groups were evidenced. We can conclude that there is no statistical significance concerning efficacy and side effects of APC application between the 60W and 50W power setting, but the number of sessions and duration of the procedure tend to differ significantly. Rectal stenoses have been described only in patients treated with higher power settings.

Aim: The aim of the study was to report the efficacy and tolerability of infliximab therapy in the first 24 patients with refractory and fistulizing Crohn's disease (CD) treated at our center between August 2000-May 2002., Patients and Methods: The medical records of 24 patients (13 males, 11 females) treated with infliximab for refractory or fistulizing CD were reviewed. CD was diagnosed using conventional clinical, endoscopical and histological criteria. Infliximab was administered at a dose of 5 mg/kg body mass as a 2-hours i.v. infusion in a single infusion for inflammatory CD, and a triple infusion regimen for fistulizing CD (at 0, 2, and 6 weeks). Efficacy was analysed by means of 1) clinical outcome, 2) mucosal healing, 3) steroid tapering/sparing effect and 4) need for surgery., Results: Sixteen patients were treated for inflammatory CD, 7 patients for fistulizing CD and 1 patient for both inflammatory and fistulizing CD. A total number of 49 infusions were administered during the study interval (median number 2); the median time of follow-up was 26 weeks (12-79 weeks). An overall positive clinical response was seen in 12/16 patients (75 % with inflammatory CD and 5/7 patients (71.4 %) with fistulizing CD. The median time to clinical response was 5.6 days (range 1-11 days) and the median duration of clinical response was 6.53 mo. (4 weeks-21 months). Mucosal healing was noted in 10/17 (58 %). Steroid tapering or cessation was succesfully attempted in 17 patients (80.9 %), complete steroid withdrawal being possible in 15 patients (71.4 %). Three non-responder patients required surgical therapy. Infusion-related adverse reactions were seen in 4 patients (16.6 %). Two patients (8.3 %) developed severe adverse events; one of them, a young female patient with intrapartum onset of a severe CD developed sepsis and deceased from intavascular disseminated coagulopathy. During the follow-up, none of our patients developed serious infections, tuberculosis or malignancy., Conclusion: Our study provides additional evidence that infliximab is beneficial and safe in clinical practice for refractory and fistulizing CD patients. Additionally, our study proved the high mucosal healing rate and the steroid-sparing and surgery-saving properties of infliximab

Gastroduodenal tuberculosis is a rare location of abdominal tuberculosis. It usually occurs secondary to pulmonary tuberculosis. We report a case of a 63-year-old woman admitted to the referral center for symptoms of upper gastrointestinal obstruction caused by ulcerohypertrophic antroduodenal tuberculosis. The lesion was misdiagnosed as malignancy at endoscopy. Even at surgery, the lesion was considered gastric cancer and imposed an oncologic resection. The diagnosis was established in the presence of giant-cell granulomas with caseating necrosis in the surgical resected specimens. In our case, the rare gastroduodenal location of abdominal tuberculosis occurred as primary tuberculosis, in the absence of other identifiable locations.

Carcinoid tumours are enigmatic, slow growing malignancies, which occur most frequently (74%) in the gastrointestinal tract. Symptoms of the carcinoid syndrome (flushing and diarrhoea) are infrequent, occurring in approximately 10% of the patients with small bowel carcinoid. A 45-year-old patient with multiple liver metastases, diagnosed in 1994 with nonHodgkin's lymphoma after undergoing surgery for a distal ileal tumour, was referred to us by the Department of Haematology. At that moment the issue of a differential diagnosis with a carcinoid tumour arose, due to the long evolution and lack of evidence to support the initial diagnosis. The carcinoid syndrome was in fact present (the patient experiencing flush after small amounts of alcohol and emotions) and also we identified elevated values of 5HIAA. Reevaluation of the histologic sections of the ileal tumour as well as an ultrasound guided fine needle aspiration of an intrahepatic lesion confirmed the diagnosis of "carcinoid tumour". This conclusion lead to new therapeutic options for this patient. One of the main therapeutic options used in treating multiple liver metastases from a carcinoid tumour is chemoembolization and this case offered an excellent opportunity to present this therapy.

European experience in endoscopic mucosal resection (EMR) for early gastric cancer is still relatively low, since early stomach cancer is diagnosed at a much lower rate in Europe than in Japan and generally operable patients are referred to surgery for radical resection. Endoscopic mucosal resection or mucosectomy was developed as a promising technology to diagnose and treat mucosal lesions in the esophagus, stomach and colon. In contrast to surgical resection, EMR allows "early cancers" to be removed with a minimal cost, morbidity and mortality. We present the case of a patient with hepatic cirrhosis incidentally diagnosed with an elevated-type IIa early gastric cancer. Echoendoscopy was performed in order to assess the depth of invasion into the gastric wall confirming the only mucosal involvement. We performed an EMR using "cup and suction" method. After the procedure, the patient experienced an acute upper gastrointestinal bleeding from the ulcer bed requiring argon plasma coagulation. The histopathological examination confirmed an early cancer, without involvement of muscularis mucosae. The patient has had an uneventful evolution being well at six months after the procedure