High prevalence of advanced fibrosis in association with the metabolic syndrome in a Belgian prospective cohort of NAFLD patients with elevated ALT. Results of the Belgian NAFLD registry.

INTRODUCTION: Non-alcoholic Fatty Liver Disease (NAFLD) is increasingly recognised as a source of liver related morbidity and mortality. Hard data on epidemiology and natural history are scarce. AIM: To study demographic and metabolic characteristics of the NAFLD patients seen by Belgian hepatologists. METHODS: Belgian hepatologists filled in a questionnaire for every newly diagnosed NAFLD patient between January 1st and December 31st 2004. Liver biopsy was advised if ALT > 1.5 x ULN and if 3/5 of the criteria for the metabolic syndrome (MS) (ATPI-II) were present, but was not mandatory. Biopsy was scored using the Brunt classification. RESULTS: 230 patients were prospectively included in 9 centres; 54% were males; mean age was 49.4 +/- 13.9 y; mean BMI was 30.6 +/- 4.6 kg/m2. The MS was present in 53%. In 16% formerly undiagnosed diabetes was discovered. 51% had a liver biopsy: 25% met the criteria, 26% did not. Grading did not differ between patients with or without MS. Staging was significantly more severe in patients with MS (2.43 +/- 1.25 vs. 1.73 +/- 1.18, p < 0.001). A subgroup of patients with GGT > 5 x ULN were significantly older (55.9 vs. 47.64 y, p = 0.02), more frequently diabetic (53% vs. 23%, p = 0.01) and had more advanced fibrosis (3.42 vs. 1.08, p = 0.008). ALT levels were variable. CONCLUSIONS: The MS is highly prevalent in Belgian NAFLD patients and is associated with more severe disease. Mild to moderate fibrosis is frequent, and the proposed criteria for liver biopsy are not accurate in selecting these patients. Patients with elevated GGT constitute a subgroup with more advanced disease.

Upper gastrointestinal bleeding: what has changed during the last 20 years?

AIM OF THE STUDY: The purpose of this study was to assess the clinical, epidemiological, therapeutic and prognostic changes observed in patients with upper gastrointestinal bleeding (UGIB) during the last two decades. METHODS: Two cohorts of 200 patients with UGIB consecutively recruited during the period 1984-1987 (cohort A) then during the period 2004-2006 (cohort B) were compared. RESULTS: Median age was 61.5 years in the cohort A and 67 years in the cohort B. The main etiologies remained variceal bleeding and peptic ulcer, but esophagitis and Mallory-Weiss syndrome were more frequently observed recently. The intake of gastrotoxic drugs did not decreased despite the widely acknowledged harmful effects of these drugs. Regarding management practices, a therapeutic intervention during the first endoscopy was performed in 36% of the cases in the cohort B but only in 2% of the cases 20 years ago. The frequency and the volume of blood transfusion dramatically decreased during the last two decades. Regarding the outcome, the requirement for surgery and the rate of recurrent bleeding decreased by half, but mortality remained unchanged. CONCLUSION: The main changes observed in patients admitted for UGIB 20 years apart concerned epidemiological features, treatment and prognosis.

A pilot observational survey of hepatitis C in Belgium.

AIM OF THE STUDY: There is a lack of epidemiological data on hepatitis C (HCV) infected patients in Belgium. Therefore our purpose was to address this important question and to evaluate the feasibility of a national HCV observatory. PATIENTS AND METHODS: From November 2003 to November 2004, every new patient prospectively seen for HCV antibody positivity in 9 Belgian hospital centres was recorded and a standardised 10-items questionnaire was completed during the consultation, including a Quality of Live (QOL) visual analogue scale. RESULTS: Three hundred and eighteen consecutive patients were recruited. Fifty five percent were male with a median age of 45 y (11-87 y). The main risk factors for infection were IV drug use (27%), blood transfusion (23%), and invasive medical procedure (11%). On the QOL scale, ranging from 0 and 100, mean value was 61 +/- 31. Transaminases were abnormal in 66% with a median elevation 2 times above normal value. HCV RNA was positive in 87% with a viral load above 800 000 IU/ml in 42%. Genotype 1 was predominant (59%), followed by genotypes 3 (19%) and 4 (14%). A liver biopsy was performed in 190 patients, with minimal fibrosis (METAVIR F0-F1) in 43%, moderate fibrosis (F2) in 35% and advanced stages (F3-F4) in 22%. Antiviral treatment was not considered in 53% because of normal ALT (30%), old age (7%), minimal histological stage (6%) or patient refusal (4%). CONCLUSIONS: This study highlights the feasibility of a national HCV survey using a simple questionnaire. This pilot study could be generalised throughout Belgium, and, if repeated, could allow a regular assessment of the changes in epidemiology and management of HCV infection in our country.

Treatment of acute hepatitis C with interferon alpha-2b: early initiation of treatment is the most effective predictive factor of sustained viral response.

AIM: To evaluate the efficacy of early interferon alpha-2b in non-post-transfusion acute hepatitis C virus: a prospective study with historical comparison. PATIENTS: Group A: 28 patients prospectively treated for acute hepatitis C virus with daily regimen of interferon 5 million units for 2 months. Group B: historical series of 16 patients with untreated acute hepatitis C virus. RESULTS: There was no significant difference between the two groups with regard to gender, age, icterus, alanine aminotransferase, or genotypes. In group B, hepatitis spontaneously resolved in three of 16 (19%) patients (follow-up 1-7 years). In group A, 21 of 25 patients became sustained viral responders (75%; P = 0.0003 vs. group B). Factors include not predictive of sustained viral response: age, gender, sources of infection, presence of icterus, alanine aminotransferase peak, bilirubin peak, incubation period, presence of hepatitis C virus antibodies at presentation, or genotypes. The time from presentation to the start of therapy was, however, significantly shorter in sustained viral responders (43 +/- 31 days) than in relapsers or non-responders (88 +/- 52 days) (P = 0.016). CONCLUSIONS: Early treatment of acute hepatitis C virus with interferon prevents chronicity. A short waiting time from presentation to treatment appears as the most relevant predictive factor for sustained response.

Epidemiology of coeliac disease.

In this article we review recent worldwide epidemiological data of coeliac disease (CD). An emphasis is made on adult figures as there is reduction of infants cases that is counterbalanced by the increase of CD in older children or adults. We review data from Europe, USA, South America, Australia, Asia and Africa. Studies in mixed population and in patients undergoing endoscopy are also mentioned. The prevalence of the disease varies between 1/100-500 in different continents. It is possible that the low incidence of CD in some regions is due to the decrease of the prevalence of classic form of the disease.

Impact of hepatitis C virus infection on the aetiology of cirrhosis and hepatocarcinoma in three affiliated hospitals in southern Belgium.

In a consecutive series of 411 patients with cirrhosis attending the outpatient liver clinics of 3 general hospitals located in the southern part of Belgium, hepatitis C virus infection accounted for 20% of the cases, far behind alcohol (63%). However, in a consecutive series of 57 hepatocarcinoma superimposed on cirrhosis, hepatitis C virus infection was the main aetiological factor accounting for 44% of the cases.

[lymphocytic colitis associated with lansoprazole treatment]. / Colite lymphocytaire associée à la prise de lansoprazole.

We report two cases of lymphocytic colitis with severe diarrhea in patients treated by lansoprazole for six weeks. Complete remission occurred rapidly after lansoprazole withdrawal.

Surveillance for hepatocellular carcinoma: compliance and results according to the aetiology of cirrhosis in a cohort of 141 patients.

Surveillance for early detection of hepatocarcinoma (HCC) in patients with cirrhosis is widely accepted. In a cohort of 141 patients with cirrhosis collected during the year 1995, we conducted a surveillance program by performing liver ultrasonography and blood alpha-foetoprotein measurement every 6 months. The median follow-up was 34 months. This study addressed to two questions: the compliance to the surveillance schedule according to the aetiology of cirrhosis and the results in terms of emergence of HCC and outcome. Aetiology of cirrhosis was alcohol-induced in 86 (61%), HCV-related in 30 (21%) and from other origins in 25 (18%). Compliance to the program schedule was good in patients with HCV-related cirrhosis (29/30--97%) and patients with cirrhosis of "other origins" (20/25--80%) but was poor in patients with alcoholic cirrhosis (45/86--52%). The lack of compliance was significantly linked to the failure to achieve alcohol abstinence. During follow-up, 6 HCC lesions were observed in 6 male patients with median age of 68 years. All 6 HCC were single nodule, less than 4 cm and accessible to percutaneous acetic acid injection. Nevertheless, the outcome was disappointing, four patients dying 3-15 months later (median: 8 months), two of them with extensive HCC. One of the two patients still alive developed extensive HCC, 36 months after percutaneous acetic acid injection.

Prediction of cyclosporine clearance in liver transplant recipients by the use of midazolam as a cytochrome P450 3A probe.

BACKGROUND: Interindividual differences in the kinetics of cyclosporine (INN, ciclosporin) result in part from variations in the activity of cytochrome P450 3A (CYP3A). The biotransformation of midazolam to 1'-hydroxymidazolam is also catalyzed by CYP3A. The objective of this study was to examine the usefulness of midazolam as a CYP3A probe to predict cyclosporine clearance. METHODS: Twenty-six stable liver transplant recipients receiving immunosuppressive therapy with oral cyclosporine (Neoral) were studied. Midazolam (0.015 mg/kg) was administered intravenously and a blood sample was obtained 1 hour later. The plasma concentration of midazolam and 1'-hydroxymidazolam was measured by gas chromatography-mass spectrometry. Blood concentration of cyclosporine was measured by a fluorescence polarization assay. Cyclosporine clearance was calculated as daily dose divided by trough level. RESULTS: There were large interindividual variations in cyclosporine clearance and in midazolam metabolism. Cyclosporine blood levels correlated poorly with dose (r = -0.016). However, there was a significant correlation between cyclosporine clearance and the plasma concentration of 1'-hydroxymidazolam (r = 0.559; P < .001) or the midazolam/1'-hydroxymidazolam plasma concentration ratio (r = 0.668; P < .001). CONCLUSION: Heterogeneity in CYP3A activity contributes to interpatient differences in cyclosporine dosage requirements after liver transplantation. Midazolam metabolism correlated with cyclosporine clearance, but it accounted for only about 40% of the variability in the apparent oral clearance of cyclosporine and this relationship is not tight enough to be useful in the prediction of cyclosporine dosage requirements in the clinical setting.

Thromboembolism in inflammatory bowel disease.

Thromboembolism represents a severe complication of inflammatory bowel disease occurring in young patient, with active disease. Deep venous thrombosis and pulmonary embolism are the most frequent thromboembolism manifestations. Arterial complications and unusual sites for thromboembolism are more rare. Overall, inflammatory bowel disease is a real prothrombotic state as almost all parameters of coagulation are enhanced. Anticoagulation during the episode of thromboembolism is mandatory, and sometimes may ameliorate the course of inflammatory bowel disease.

Hypoxic hepatitis: a difficult diagnosis when the cardiomyopathy remains unrecognized and the course of liver enzymes follows an atypical pattern. A report of two cases.

In a clinical setting of cardiac or circulatory failure, the diagnosis of hypoxic (ischaemic) hepatitis is easy and can be elicited on mere clinical and biochemical features. We report two cases of hypoxic hepatitis where cardiomyopathy remained unrecognized at admission due to the lack of conventional signs of congestive heart failure and where the increase in liver enzymes activities followed an atypical pattern, characterized by only moderate elevation of serum aminotransferases activities, low ASAT/ALAT ratio and elevated ALAT/LDH ratio. This atypical pattern not suggestive of hypoxic hepatitis, could be explained by a delay between the onset of hypoxic injury of the liver and admission to hospital. Moreover one case was complicated by frank jaundice, an unusual feature in hypoxic hepatitis. Consequently, diagnosis and appropriate inotropic treatment were delayed resulting in progressive deterioration and eventually death of both patients. The report of these two cases and the review of other similar cases previously published, enlighten some atypical features of hypoxic hepatitis.

Brain tumor imaging with PET and 2-[carbon-11]thymidine.

METHODS: To assess the potential of thymidine for imaging brain tumors, 20 patients with untreated (n = 14) and recurrent (n = 6) supratentorial intracranial tumors were studied with PET by using 2-[11C]thymidine (Tdr), and the results were compared with [18F]fluorodeoxyglucose (FDG) PET data. RESULTS: Blood analysis consistently revealed a rapid clearance of the intact Tdr together with the appearance of CO2/HCO3- that, with time, accounted for approximately 70% of the total blood activity. As soon as 10 min after tracer injection, brain images showed a low and homogeneous Tdr distribution over the normal brain structures (cortex-to-blood ratio approximately 1). Visual and quantitative analysis revealed increased Tdr uptake (tumor-to-cortex ratio > or = 1.2) in 11 of 14 untreated tumors and in 5 of 6 recurrent tumors. No correlation was found between Tdr uptake and tumor grade. In 12 of the 14 untreated tumors, FDG uptake was low (tumor-to-cortex ratio: 0.83 +/- 0.79), but a FDG hot spot was visualized in 8 of 10 high-grade and in none of the 4 low-grade tumors. FDG uptake was consistently low in recurrent tumors (tumor-to-cortex ratio: 0.49 +/- 0.19), and PET-FDG was negative in 3 of the 6 cases. CONCLUSION: These data indicate the feasibility of brain tumor imaging with Tdr and suggest the potential clinical usefulness of the method in the detection of tumor recurrences. The specificity of the method remains, however, to be investigated.

Prospective evaluation of thoracic-duct drainage in the treatment of respiratory failure complicating severe acute pancreatitis.

Thoracic duct drainage (TDD) may be of value for removing toxic substances released by the inflamed pancreas and which are responsible for lung damage. We have prospectively assessed the efficacy of TDD in improving pulmonary gas exchange in 12 patients with severe acute pancreatitis (SAP) complicated by persistent respiratory failure despite standard conservative treatment including peritoneal dialysis in 8 patients. In group A were 6 patients (mean Ranson score = 7.3) with adult respiratory distress syndrome (ARDS) and in group B were 6 hypoxemic patients (mean Ranson score = 6.6) judged to be at risk of developing ARDS. The duration of TDD ranged from 3 to 10 days and the total amount of drained lymph (L) varied from 770 to 15,600 ml. Immunoreactive trypsin levels were significantly higher in L when compared to blood in both groups. Leukocyte myeloperoxidases in L (normal value less than than 332 +/- 82 ng/ml in plasma) were increased in 5 of 5 group A patients (830 +/- 317 ng/ml) and in 3 of 6 patients in group B (671 +/- 467 ng/ml). After TDD pulmonary gas exchange as measured by median PaO2/FiO2 (mmHg) improved from 148 +/- 60 to 285 +/- 42 in group A and from 192 +/- 37 to 330 +/- 42 in group B (p less than 0.05). All patients were weaned after ventilation for a mean of 8 days in group A and 4 days in group B. All patients survived apart from 1 group B patient who died of sepsis on day 34.(ABSTRACT TRUNCATED AT 250 WORDS)