Chronic hepatitis C in Austria, 1992-2006: genotype distribution and demographic factors.

Chronic hepatitis C is a leading cause of end-stage liver disease and, with a worldwide prevalence of up to 3%, is a pandemic infectious disease. Austria, like most western European countries can be considered as a low prevalence country. This analysis aimed to assess the distribution of hepatitis C virus (HCV) genotypes in patients with chronic HCV infection in Upper Austria. Between September 1992 and December 2006, we identified 1,318 consecutive patients who tested positive for HCV RNA. Genotyping was routinely performed in 1,239 of the 1,318 patients, and in a subgroup of 617 patients data on the source of transmission were collected. Additionally we obtained data on liver histology and body mass index in a subsample of 273 of the 617 patients. Hepatitis C genotypes 1, 2, 3, 4, 6 and co-infections were found in 80.4%, 4.5%, 12.3%, 2.7%, 0.1% and 0.2% of the patients, respectively. There was a highly significant age difference in relation to gender at the time of diagnosis of chronic hepatitis C, with women being older than men (men: 45.0 years; women: 49.3 years; p<0.0001). The number of new cases of chronic hepatitis C decreased substantially over the last decade, but although risk factors for obtaining HCV are well established, we did not find a decrease in the age of first diagnosis. Besides consistent screening in defined risk groups it is important to raise awareness for risk factors for HCV acquisition and liver disease progression.

Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

Therapeutic step-up strategy for management of hereditary pancreatitis in children.

BACKGROUND/PURPOSE: Various different regimes exist for the treatment of hereditary pancreatitis in childhood. Here, we propose a therapeutic pathway with emphasis on endoscopic and surgical procedures. METHODS: From 2006 to 2013, 12 patients with a diagnosis of hereditary pancreatitis were prospectively included in a therapeutic step-up schema. The treatment outcome was evaluated and correlated to aetiological factors and pathoanatomic findings. RESULTS: After diagnostic work-up (laboratory data, ultrasound examination, magnetic resonance cholangiopancreatography and genetic testing), all 12 patients underwent early endoscopic retrograde cholangiopancreatography (ERCP), which was successfully performed in ten children. Obstructive pancreatitis was found in eight children, and required sphincterotomy, dilation and stenting for 12 months. In two children with unsuccessful ERCP, open surgical drainage procedures were performed. After a mean follow-up of 32 months all children are free of recurrence of pancreatitis without any impairment of everyday activities. CONCLUSIONS: For children with hereditary pancreatitis, a therapeutic step plan with early ERCP and open surgical drainage procedures in case of impossible or insufficient endoscopic treatment prevents recurring pancreatitis and offers a normal quality of life without any major complications.

Bile duct adenocarcinoma mimicking veno-occlusive disease after autologous bone marrow transplantation for acute leukaemia.

A 52-year-old female underwent autologous BMT because of acute myeloid leukaemia FAB M4 in second remission. Since the patient had no HLA-identical sibling she received a purged autologous BM transplant. On day +5 she developed signs of a sepsis syndrome with fluid retention and was treated with broad-spectrum antibiotic therapy. However, her body weight remained high, ascites and an increase of total serum bilirubin and alkaline phosphatase developed. The icterus worsened to a total bilirubin level of 25 mg/100 ml. Sonographic and endoscopic imaging showed a dilated gall bladder but disclosed a post-hepatic cause for the icterus. A transjugular liver biopsy on day +71 revealed severe cholestasis and siderosis. The patient remained aplastic with constantly increased bilirubin levels. On day +73 septic shock syndrome occurred and the patient died of multiorgan failure 3 days later. At autopsy, a highly differentiated bile duct adenocarcinoma at the porta hepatis, so-called Klatskin tumour, was found, explaining the fatal course with intractable cholestasis.

The relationship between juxtapapillary duodenal diverticula and biliary stone disease.

OBJECTIVE: To assess the relationship between juxtapapillary duodenal diverticula (JDD) and common bile duct stones and biliary stone disease in general. DESIGN: A retrospective study. METHODS: We analysed 1115 patients who underwent consecutive endoscopic retrograde cholangiopancreatography examinations. The patients were subdivided into three groups: the first group (group I; n = 482) had no biliary stone disease, the second one (group II; n = 329) had common bile duct stones, and the third group (group III; n = 304) had biliary stone disease of the gallbladder but without evidence of common bile duct stones. Additionally, the patients were subdivided into age groups of < 50, 50-59, 60-69, 70-79, and > or = 80 years of age. Logistic regression was applied for statistical analysis. RESULTS: Juxtapapillary duodenal diverticula were diagnosed in 111 (10.0%) patients. The incidence of JDD was 6.9% in group I, 14.3% in group II and 10.2% in group III. Age was the most dominant influence factor for JDD, common bile duct stones, and biliary stone disease (P < 0.0001). Sex was also a factor, female patients having a higher risk for common bile duct stones (P = 0.01) and biliary stone disease (P < 0.0001). After adjustment for age and sex, JDD was found to have a noticeable, but not statistically significant (P = 0.073), influence on common bile duct stones and no influence on biliary stone disease (P = 0.15). CONCLUSION: Our data support only moderately the existence of a relationship, which had been conjectured in a part of the literature, between JDD and common bile duct stones. No noticeable influence on biliary stone disease was found.

[Pancreatic carcinoma--diagnosis and screening--endoscopic therapy]. / Pankreaskarzinom--Diagnose und Screening--endoskopische Therapie.

Diagnosis of pancreatic carcinoma is nowadays established by means of transabdominal sonography and computed tomography. In cases remaining unclear or accompanied by obstructive jaundice ERCP is also required. Small tumours can only be detected by ERCP or endosonography with sufficient accuracy. Biopsy (percutaneous or ductal during ERCP) should be restricted to cases in which the histologic or cytologic results influence therapeutic concepts substantially. Magnetic resonance imaging and endoscopy of the pancreatic duct are currently being evaluated. Tumor markers such as CA 19-9 are mostly useful in confirming suspicious morphology; their specificity and the sensitivity in small tumours are unsatisfactory. Precise pretherapeutic staging with computed tomography, endosonography, and laparoscopy can avoid superfluous surgical procedures. Early diagnosis of pancreatic cancer appears possible at present only by means of ERCP or endosonography, but patients at risk still have to be defined since blind screening would be ineffective due to insufficient specificity, expensive and dangerous due to the complications of the applied methods. In the patient with obstructive jaundice unfit for surgery, or with metastatic spread of the disease, endoscopic stent insertion is the palliative treatment of choice. Because of longer patency metal stents are superior to plastic endoprotheses.

[Effect of a lactose-free diet on irritable bowel syndrome]. / Einfluss einer laktosefreien Ernährung auf das Reizdarmsyndrom.

Pathological lactose-H2-breath test is a frequent finding in patients with suspected irritable bowel syndrome. We found it in 33 of 55 patients (60%) with chronic non-specific abdominal symptoms. Follow-up examinations after 15 months (mean) exhibited that lactose-free diet relieved symptoms in 57% of these patients completely or nearly completely. In contrast, only 12% of the patients without lactose malabsorption showed equal amelioration on the various unspecific diets and medications. The lactose-free diet succeeded particularly in young patients and patients with a short history of complaints. Therefore, we recommend lactose-H2-breath test in all patients with suspected irritable bowel syndrome for optimizing therapy.

25-hydroxyvitamin D absorption in patients with Crohn's disease and with pancreatic insufficiency.

Vitamin D malabsorption could be one possible reason for the high prevalence of vitamin D deficiency and osteopenia in patients with Crohn's disease (CD) and pancreatic insufficiency (PI). Hence, we performed a modified 25-hydroxyvitamin D (25-OHD) absorption test Stamp in 15 healthy controls, 31 patients with CD and 10 patients with PI. Serum 25-OHD levels were measured before, and 2, 4, 8, and 24 hours after oral administration of 5 micrograms 25-OHD/kg body weight. Basal 25-OHD levels were below the normal range of 12-36 ng/ml in 68% of patients with CD (median: 10; interquartile range: 4-12 ng/ml) and 70% of patients with PI (median: 3; interquartile range: 2-14 ng/ml). Peak levels were reached at 4 or 8 hours after ingestion of 25-OHD. Three patients with CD (10%) and 5 patients with PI (50%) showed decreased 25-OHD absorption. 25-OHD levels normalized in all but two patients with PI after 24 hours. Pattern of involvement or previous resections did not show a significant influence on 25-OHD absorption. Vitamin D malabsorption may be one reason for vitamin D deficiency in many patients with PI, but there is little evidence of vitamin D malabsorption in patients with CD. Oral 25-OHD administration seems to be a useful therapeutic alternative to native vitamin D in patients with possible malabsorption and vitamin D deficiency.

Von Willebrand Factor as a new marker for non-invasive assessment of liver fibrosis and cirrhosis in patients with chronic hepatitis C.

BACKGROUND: Staging of liver fibrosis in patients with chronic hepatitis C (CHC) is recommended prior to anti-viral therapy. As vWF-Ag was shown as a predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis, we performed this study to investigate if vWF-Ag is able to predict different fibrosis stages and if it is comparable to other fibrosis scores. AIM: To investigate if vWF-Ag is able to predict different fibrosis stages and if it is comparable to other fibrosis scores. METHODS: We analysed 294 patients with chronic hepatitis C who underwent biopsy. We assessed stage of liver fibrosis according to Metavir, measured vWF-Ag and calculated different fibrosis scores (APRI, FCI, FORNS, FI, Fib-4) and compared them by AUCs. We also calculated a new score: vWF-Ag/thrombocytes (VITRO score) for prediction of fibrosis. RESULTS: vWF-Ag levels were increasing with stage of fibrosis: F0: vWF-Ag was median 136.5%, FI 140.6%, FII 157.5%, FIII 171.0%, FIV 252.0%; P < 0.001. vWF-Ag and VITRO score produced AUCs of 0.7 and 0.72 for ≥F2, comparable to the AUCs of APRI, Fib-4, FORNS with 0.75, 0.65 and 0.64 (P > 0.05). For ≥F3 AUCs were 0.79 and 0.86 for vWF-Ag and VITRO score, comparable with AUCs of 0.79, 0.86 and 0.87 for APRI, Fib-4 and FORNS. Cirrhosis shows AUCs of 0.84 and 0.89 for vWF-Ag and VITRO score, APRI, Fib-4 and FORNS showed similar results with AUCs of 0.82, 0.88 and 0.87. CONCLUSIONS: vWF-Ag and VITRO score offer an easy possibility to evaluate the stage of fibrosis to diagnose subclinical cirrhosis in patients with chronic hepatitis C. Both vWF-Ag and VITRO score show equal performance in comparison to other fibrosis scores assessed in our study.

[Gastro-highlights 2012]. / Gastro-Highlights 2012.

The annual Gastro Highlights training event, held at the university Hospital Zurich last autumn, also celebrated the 60th birthday of prof.Dr.med. Michael Fried, who initiated this widely recognized event 17 years ago. Featured at the symposium was a round up of the most important new discoveries in the field of gastroenterology and hepatology to be published during the course of the previous year or represented at the Digestive Disease Week (DDW). To mark the birthday of Prf. Dr. med. Michael Fried, two international experts made a special report on the key developments in the gastroenterology to emerge over the past decades.

[Use of infliximab in ulcerative colitis]. / Infliximab in der Therapie der Colitis ulcerosa.

Infliximab, a chimeric monoclonal anti-tumour necrosis factor alpha (TNF) antibody has dramatically changed the management of various chronic inflammatory disorders such as Crohn's disease (CD), rheumatoid arthritis, ankylosing spondylitis or psoriasis. This drug is well established for the treatment of CD in case of steroid-refractoriness, failure to respond to an immunosuppressant agent or fistulizing disease. The immunological concept that ulcerative colitis (UC) reflects primarily a T-helper cell type-2 mediated disease prevented the earlier use of anti-TNF agents in this disease. Promising initial pilot studies in steroid-refractory UC patients led to two large placebo-controlled trials in patients with moderate to severe UC. These studies clearly showed a benefit for infliximab treatment in UC with mucosal healing and improved life quality. Infliximab therefore can be used in patients not responding adequately to steroids and/or immunosuppressants. Furthermore, one study showed evidence that infliximab might also be effective in severe, intravenous steroid-refractory UC. Therefore, infliximab might be used alternatively to cyclosporine A or tacrolimus in this patient group. Infliximab has now been established as an additional treatment option in patients with chronic-active UC not responding to an immunosuppressive agent and/or in case of severe acute UC. Experienced gastroenterologists should be involved in the decision making for such a therapy to balance thoroughly the benefit/risk ratio for our patients.

Safety and efficacy of endoscopic balloon dilation for treatment of Crohn's disease strictures.

BACKGROUND AND STUDY AIMS: Strictures are a substantial cause of morbidity in patients with Crohn's disease. Endoscopic balloon dilation is a therapeutic option in limited strictures to avoid intestinal surgery, although there have been few reports regarding the long-term outcome. PATIENTS AND METHODS: Balloon dilation was scheduled for 46 patients (26 women, 20 men; median age 34) with Crohn's-associated symptomatic and radiographically confirmed intestinal stenosis. The study plan envisaged up to four consecutive treatments within the first 2 months until relief of symptoms, and thereafter dilations depending on clinical requirements. RESULTS: Dilation was not possible in seven of the 46 patients (15 %), due to technical problems (n = 2), internal fistulas (n = 3), or absence of a stenosis (n = 2). Thirty-nine patients received at least one treatment. The site of obstruction was the ileocolonic anastomosis in 23 of the 39 patients (59 %) and surgically untreated areas in 16 patients (41 %). After the initial dilation series (median 1, interquartile range 1-2), strictures were traversed in 37 of the 39 patients (95 %). During a median follow-up period of 21 months (range 3-98 months), 24 of the 39 patients (62 %) underwent a repeat intervention, including 12 (31 %) with repeat dilation, 11 (28 %) with surgical resection, and one patient who received an intestinal stent. The cumulative percentages of patients without a repeat intervention or surgery at 6, 12, 24, and 36 months were 68 %, 48 %, 36 %, and 31 %, and 97 %, 91 %, 84 % and 75 %, respectively. Two perforations and one case of severe bleeding were seen in the 73 dilation procedures (4 %) performed. CONCLUSIONS: Endoscopic balloon dilation is a safe and effective method that allows surgery to be avoided in approximately 75 % of patients with Crohn's-associated short intestinal strictures. However, recurrent symptoms frequently make it necessary to repeat the procedure.

Diagnostic endoscopic retrograde cholangiopancreatography.

Although diagnostic endoscopic retrograde cholangiopancreatography (ERCP) has been replaced in many fields by magnetic resonance cholangiopancreatography (MRCP), considerable amounts of research are still ongoing. Major fields of interest include ways of reducing the incidence of post-ERCP pancreatitis, new ways of improving the yield of tissue sampling, and the diagnosis of sphincter of Oddi dysfunction. In addition, there are new data comparing the diagnostic accuracy of ERCP with that of MRCP and endoscopic ultrasonography.

Diagnostic endoscopic retrograde cholangiopancreatography.

Since the introduction of magnetic resonance cholangiopancreatography (MRCP), the focus in endoscopic retrograde cholangiopancreatography (ERCP) has shifted from diagnosis to treatment - a change that has organizational implications in relation to teaching and providing access to ERCP. Most of last year's papers on ERCP described refinements of the technique and indication, tissue sampling, and efforts to reduce complications. Many studies compared MRCP with various other imaging methods and with histopathological findings. Bile duct stones and strictures are still the main target, but new entities for evaluation with MRCP have been found: primary sclerosing cholangitis, choledochal cysts, chronic pancreatitis, pancreatic injury, and postoperative abnormalities. Helical computed-tomographic cholangiography is still attracting some interest. This review closes with a comparison of ERCP with MRCP with regard to availability, legal aspects, operator-dependency, and cost-effectiveness.