Search

Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

Background The aim of this cross-sectional study was to establish an online inflammatory bowel disease (IBD) registry for a first picture of the situation of IBD outpatients' treatment in Germany. Methods Between March 2006 and July 2007 IBD outpatients from 24 gastroenterological specialist practices and two hospitals in Germany were enrolled in an Internet-based registry to evaluate the outpatients' clinical status, psychological impairments, provided health care, as well as medical treatment and medication costs. Results 1032 IBD patients (ulcerative colitis/UC: 519; Crohn's disease/CD: 511; indeterminate colitis: 2) were enrolled in the study (age: 43 ± 14 years/M ± SD). Disease duration of all patients averaged 10 ± 8.5 years. In 519 UC-patients (49% male; 33% pancolitis), 66% were in remission as were 55% of CD patients (37 % male; 41 % active smokers). Associated with higher rates of disease activity (CDAI ≥ 150; CAI > 4) were corticosteroids (CD, UC), topical medication (UC), relevant reported depressive symptoms (15%; 6-31%) and impairments in sexuality (21%; 9-42%). Relevant medication groups prescribed were oral aminosalicylates (UC: 70%; CD: 47%); immunosuppressive therapy - mostly azathioprine/6 MP (CD: 47%; UC: 26%), and Infliximab (CD: 8%; UC: 3%). Strongly associated with their clinical disease activity in UC as well as CD patients, 15% (6–31%) reported relevant depressive symptoms and 21% (9–42%) relevant impairments in sexuality. Conclusions The registry constitutes a large complemental database for the patient population in Germany. About one third of the IBD patients were not in clinical remission (CDAI ≥ 150/CAI > 4) (CD: 45%; UC: 27%), although high rates of immunosuppressive drugs (CD: 47%; UC 26%) were administered. This study shows a large burden of active disease associated with an unexpectedly high (co)morbidity and high psychosocial impairments, indicating a reduced health state in IBD patients.

Hintergrund und Fragestellung: Die chronische Hepatitis-B-Virusinfektion ist in Deutschland ein groses Gesundheitsproblem. Die vorliegende Arbeit hatte zwei Hauptziele: (I) Kenntnisse zur Behandlung der betroffenen Patienten in Deutschland unter Berucksichtigung epidemiologischer und soziookonomischer Charakteristika zu gewinnen, (II) das Wissen uber Hepatitis B bei Angehorigen infizierter Patienten zu untersuchen. Patienten und Methodik: Als Kooperationsprojekt der Modellregion Nord des Kompetenznetz Hepatitis wurden 1000 Patienten mit chronischer Hepatitis B kontaktiert. Zusatzlich wurden im Rahmen dieser Patientenbefragung auch Angehorigenfragebogen mit der Bitte um Weiterleitung an Familienangehorige versandt. Ergebnisse: Patientenfragebogen gingen von 312 Patienten ein (Rucklaufquote 31 %). Ein Grosteil (73 %) der Patienten hatte einen Migrationshintergrund. Das Wissen uber die eigene Erkrankung war in der Kohorte sehr heterogen. Wahrend die Patienten relativ gut uber ihre Leberwerte informiert waren, gab es grose Defizite im Wissen um die Viruslast. Es zeigte sich auserdem, dass Patienten mit niedrigem sozialem Status haufiger einen Arzt aufsuchten, jedoch nicht zwangslaufig haufiger medizinische Untersuchungen erhielten. Das Wissen der Angehorigen ( 384 Angehorige aus Familien von 216 Patienten) uber die Ubertragungsmoglichkeiten und Schutzmoglichkeiten war ebenfalls heterogen. Nur 84 % der Lebenspartner und Kinder waren gegen HBV geimpft, und lediglich 75 % der Befragten war bekannt, dass Kondome vor einer HBV-Ubertragung schutzen. Folgerung: Nicht nur an Hepatitis B Erkrankte, sondern auch deren Angehorige mussen uber die Konsequenzen von Lebererkrankungen und HBV-Infektion informiert werden. Der schlechte Impfstatus vor allem der Sexualpartner von HBV-Infizierten sollte beachtet werden und zu einer besseren Aufklarung fuhren.

Background: Adequate bowel preparation is essential for accurate colonoscopy. Both oral sodium phosphate (NaP) and polyethylene glycol-based lavage (PEG-ELS) are used predominantly as bowel cleansing modalities. NaP has gained popularity due to low drinking volume and lower costs. The purpose of this randomized multicenter observer blinded study was to compare three groups of cleansing (NaP, NaP + sennosides, PEG-ELS + sennosides) in reference to tolerability, acceptance, and cleanliness. Patient and Methods: 355 outpatients between 18 and 75 years were randomized into three groups (A, B, C) receiving NaP = A, NaP, and sennosides = B or PEG-ELS and sennosides = C. Gastroenterologists performing colonoscopies were blinded to the type of preparation. All patients documented tolerance and adverse events. Vital signs, premedication, completeness, discomfort, and complications were recorded. A quality score (0–4) of cleanliness was generated. Results: The three groups were similar with regard to age, sex, BMI, indication for colonoscopy, and comorbidity. Drinking volumes (L) (A = 4.33 + 1.2, B = 4.56 + 1.18, C = 4.93 + 1.71) were in favor of NaP (P = .005). Discomfort from ingested fluid was recorded in A = 39.8% (versus C: P = .015), B = 46.6% (versus C: P = .147), and C = 54.6%. Differences in tolerability and acceptance between the three groups were statistically not significant. No differences in adverse events and the cleanliness effects occurred in the three groups (P = .113). The cleanliness quality scores 0–2 were calculated in A: 77.7%, B: 86.7%, and C: 85.2%. Conclusions: These data fail to demonstrate significant differences in tolerability, acceptance, and preparation quality between the three types of bowel preparation for colonoscopy. Cleansing with NaP was not superior to PEG-ELS.

The acute effect of metoclopramide on oesophageal motility was investigated prospectively in 33 consecutive patients (20 men and 13 women; mean age 60.5 +/- 12.6 years) with type I (n = 8) or type II (n = 25) diabetes. 15 patients had a peripheral sensory-motor polyneuropathy only and three just an autonomic cardial neuropathy. Both lesions were present in ten, none in five. No patient had oesophago-gastroduodenal lesions. Sphincter pressure, relaxation time, contraction amplitude and propulsion velocity of bolus-induced oesophageal peristalsis were measured manometrically after intravenous administration of 10 mg metoclopramide. Resting pressure in the lower oesophageal sphincter rose significantly by 26.7%, contraction amplitude in the tubular portion of the oesophagus by more than 30%, and propulsion velocity by more than 20% (P for each < 0.05). At the same time the amount of segmental and aperistaltic oesophageal contractions regressed significantly. The effect of metoclopramide was demonstrated regardless of the type of diabetes, duration of diabetes and any manifestation of autonomic cardial or peripheral sensory-motor neuropathy.

In 124 patients with Crohn's disease (69 women, 55 men; mean age 33.7 [11-66] years) and 53 with ulcerative colitis (30 women, 23 men; mean age 36.2 [19-74] years) the incidence of lactose intolerance, as measured by the H2 breath test and blood sugar concentration, was determined prospectively. To exclude abnormal bacterial colonization of the small intestine or rapid small-intestine transit after partial resection of the small intestine as a cause of lactose intolerance, the oro-caecal transit time for lactulose (H2 breath test) was measured. While 21 of 124 patients with Crohn's disease (16.9%) had the expected incidence of lactose intolerance, this was present in only 2 of 53 patients with ulcerative colitis (3.8%; P < 0.05). The lactose intolerance was independent of the site of any inflammatory changes, disease activity and extent of small-intestine resection. Oro-caecal transit time for lactose was similar for all patients. There was no lactose intolerance in two patients with abnormal small-intestinal bacterial colonization.--Because of their considerable diagnostic and prognostic significance, tests for lactose intolerance should be performed routinely in all cases of Crohn's disease or ulcerative colitis.

History and clinical findings A 18-year-old girl suffered from chronic active ulcerative colitis for ten years with growth retardation, primary amenorrhoea and osteopenia, so that total colectomy had been discussed as a possible treatment option. However, clinical remission was reached using a medication with budesonide (9 mg), mesalazine (3 g) and azathioprine (100 mg) when a painful ulcer occurred at the right lower leg. Investigations The clinical examination revealed an ulcer of 7 cm diameter with a red-bluish margin at the right lower leg. The typical clinical features led to the diagnosis of pyoderma gangrenosum. Treatment and course High doses of orally administered prednisolone induced the healing of the pyoderma gangrenosum within 2 months. After another 2 months systemic steroids were discontinued. Further laboratory tests confirmed secondary adrenal and ovarian failure (negative CRH-GnRH-test). Change of drug therapy to hydrocortisone (25 mg) in combination with mesalazine (3 g) and azathioprine (100 mg) improved the clinical course. Hydrocortisone was gradually reduced until CRH-GnRH-response returned to normal. Conclusion Drug therapy with azathioprine can be regarded as a treatment option in pediatric patients with chronic active inflammatory bowel disease. It can be concluded from this case report that faced with controversial therapeutic options in adolescent patients the decision mainly depends on the clinical experience of the physician than on the results of controlled clinical trials.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies. Patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 34 German IBD experts have elaborated concrete proposals for the utility of clinical symptom assessment, endoscopy and the use of laboratory parameters including foecal markers of inflammation. Furthermore, we discuss the significance of conventional X-rays, computed tomography, ultrasound and magnetic resonance tomography. These recommendations are illustrated by case studies from everyday practice in the participating centres.

Knowledge about the epidemiology, demography and social status of patients with replicative chronic hepatitis B (CHB) in Germany is still scarce. This cross-sectional study evaluated in patients with chronic hepatitis B infection, with a serum HBV-DNA concentration of at least 10,000 copies/mL ( 2000 IU/mL) at documentation visit, the epidemiology, socio-demographics, time of diagnosis, history of disease, prior therapies as well the therapeutic decision.74 German centres with predominately hepatologic focus, recorded in an online-survey the pseudonymised data of patients with chronic HBV-infection with a serum HBV-DNA-concentration of at least 10,000 copies/mL (n = 35).65 % of the patients were male. The mean age was 40 ± 14 years. 63 % were immigrants (i. e., country of birth not being Germany). 37 % were HBeAg-positive. Mean ALT value 114 ± 183 IU/mL in males and 77 ± 176 IU/mL in females. ALT was above the upper limit of normal (ULN) in 59 % and 9 % of the patients were cirrhotic. The large immigrant groups, Turks (22 %), people from the former USSR (11 %) or from Southeast Asia (10 %) differed in terms of age, sex, HBeAg-status and clinical parameters clearly from each other as well as from German patients. 55 % of the patients from SE-Asia were female and overall considerably younger than German patients. 69 % of the patients with HBV-DNA 10,000 copies/mL combined with ALT-levels above ULN, and 87 % with advanced fibrosis recieved antiviral treatment.This database currently contains the largest collection of epidemiological data of CHB patients in Germany. It therefore allows a representative overview on the disease in Germany. In Germany CHB epidemiology is triggered by migration from countries with higher CHB prevalence. However, the high proportion of patients coming from states of the former USSR is likely to be a historical peculiarity of Germany. The sometimes weak German language skills as well as the cultural specifics in the different immigrant groups are still a challenge for health-care providers. The high proportion of viraemic patients, already being treated, could indicate a suboptimal efficacy of the available therapeutic options at the time documentation.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies against TNF-α and patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 38 German IBD experts have elaborated concrete proposals for dealing with corticosteroids, immunosuppressants and TNF-α antibodies on the basis of the published literature and their own personal experience in order to close the gap between these guidelines and daily clinical practice. Statements were developed on the choice of correct timing of initiation, dose and duration of the individual substances and on how to proceed with patients exhibiting treatment failure. Moreover, recommendations are also made on drug combination strategies, safety monitoring and the risks regarding the development of infectious complications and malignancies. These recommendations are illustrated by case studies from everyday practice in participating centres.

Little is known about the epidemiology of chronic hepatitis C (CHC) in Germany and especially about the importance of transmission, duration of infection, genotypes, symptoms and quality of life of the patients. The current study prospectively evaluates epidemiological and clinical data of patients infected with the hepatitis C virus (HCV). Using online data entry, various characteristics of 10,326 untreated patients with CHC were documented from March 2003 until May 2006 in 352 centres all over Germany. Mean age of patients was 43.4 years. Patients infected by i.v. drug abuse were considerably younger (36.5 years) than the remaining patients (49.2 years). As indicated by their native language, 64.4% of the patients came from Germany and 19.2% from Russia. 61.7% were infected with genotype 1 and 34.9% with genotype 2 or 3. 45.5% of the patients had been infected by i.v. drug abuse. In at least 5.4% of the patients liver cirrhosis had been proved by biopsy. 63.5% of the patients felt an impairment of quality of life caused by CHC. In many patients infected with hepatitis C socio-economic issues are existent. This is reflected, i.e., in very high rates of unemployment in special subpopulations. Coinfections with hepatitis B and HIV occurred in 1.5% and 4.7%, respectively. Nearly 80% of patients were managed near their homes. The data of the 10 326 patients represent about 2% of all German patients with CHC. This database is up to now the largest of its kind and gives a representative insight into the epidemiological situation of CHC in Germany.

The differential diagnostic assignment of patients with hereditary non-polyposis colorectal cancer among patients with non-familial colorectal carcinoma is difficult but essential to provide early sufficient cancer screening. In order to analyze the actual situation of outpatients, 36 gastroenterologists in private practice have been interviewed with respect to their experience concerning outpatients. The interview data revealed that care for patients with colorectal cancer is a fundamental component of their work. A third of the gastroenterologists deal with patients suffering from colorectal cancer before 45 years of age. Yet these gastroenterologists did not report a single HNPCC patient. Especially gastroenterologists with long lasting experience in private practice did not mention HNPCC patients at all. These results may indicate that identifying the cases at risk for HNPCC is difficult in daily routine work. The possibility of genetic diagnostics (and counselling) should be taken into consideration in individual cases. In consequence comprehensive screening programs can be initiated for patients and their families.

In Germany screening colonoscopy was introduced into the national program on colorectal cancer prevention in October 2002 for asymptomatic subjects older than 55 years. It is the aim of this program to reduce the rate of mortality of colorectal cancer (CRC) during the next decade. Up to now no data are available concerning the outcome and patient tolerance of screening colonoscopy.Patients were enrolled in the prospective study between October 2002 and June 2003. The diagnoses from colonoscopy and complications were recorded. A short interview provided information on individual family risks of CRC. During June 2003 all subjects were handed a questionnaire to evaluate their satisfaction and tolerance concerning screening colonoscopy. All subjects were offered sedation (Disoprivan: Propofol).A total of 1117 subjects (776 [69.5 %] female, 341 [30.5 %] male) underwent screening colonoscopy; age: 64.3 +/- 6.9 years. 1104 (98.8 %) requested sedation. In 1090 cases (97.6 %) colonoscopy was completed to the cecum (photographic documentation of cecal landmarks). A total of 11 patients had invasive cancer (1 %), 4 of these had adenomas containing invasive carcinoma. The stage was T1/N0 or T2/N0. A total of 138 (12.4 %) patients had 168 polypoid lesions, which were treated by complete polypectomy. 402 small polypoid lesions (0.5 cm) were only detected by biopsy. In this group 233 adenomas (20.9 %) were found. Complications were: 1 perforation and 4 haemorrhages after polypectomy. Patient tolerance was very high. 99.4 % of all subjects agreed to a control colonoscopy or recommended screening colonoscopy to their relatives and friends.Screening colonoscopy is an effective and well-accepted method in our unit for gastroenterology. The high prevalence of adenoma and invasive carcinoma suggests that screening colonoscopy should be provided for all persons at the age of 55, especially for men.

scores, duration, site and concomitant medications were recorded. Pregnancy outcomes including mode of delivery, miscarriage, ante/postnatal complications, age at conception and need for escalation of IBD treatment during pregnancy were also assessed. Neonatal outcomes including low birth weight, pre-term delivery, NICU stays or perinatal infection and timing of vaccines were also recorded. Data were analysed using t testing, contingency and logistic regression analyses. Results: From an IBD population of over 2,500 patients, 31 individual females who underwent anti-TNF treatment during pregnancy from 2008 2013 were identified with a total of 36 pregnancies. Median disease duration at time of pregnancy was 12 years (IQR 3 17). 85% had Crohn’s Disease, 15% Ulcerative Colitis. Median Harvey Bradshaw Index pre-pregnancy was 4.5 (IQR 2 13). Median Mayo score was 1 (IQR 0 3). 57.3% received infliximab, 38% adalimumab, 4.7% certolizimab. 53.8% were on concomitant immunemodulators. The majority of patients stopped biologic treatment at the start of the third trimester. 67% had treatment reinstated in the postpartum period. Median age at conception was 30.5 (IQR 25 35). 19% had previous miscarriages. 92% had successful term pregnancies. 22% required escalation of treatment during pregnancy. 19.3% had a pregnancy complication including emergency section. 16% neonates had a low birth weight with 2 preterm deliveries and one case of NICU stay for meconium ileus. No perinatal infections were reported. 20% mothers breastfed. The majority of mothers delayed live vaccination of their children. Interestingly, there was a significant independent association between disease activity at time of conception and low birthweight (p < 0.01). There was no association between adverse outcomes or neonatal infections and anti-TNF use noted in this cohort. Conclusions: Disease control at time of conception and through pregnancy should be the main goal of treatment in this patient cohort and the use of TNF alpha antagonists to achieve this appears to warranted to improve pregnancy outcomes though definitive safety has yet to be proven.

An example of acute pancreatitis developing five weeks after initial treatment with 5-aminosalicylic acid (5-ASA) and methylprednisolone for severe Crohn's disease is reported in a 37 year old female patient. She had undergone cholecystectomy for gall stones some years earlier. There was no evidence of acute or chronic pancreatitis. No morphological changes of the upper gastrointestinal tract were found except for some irregularity of the main pancreatic duct and the secondary ducts on endoscopic retrograde pancreatography. Rechallenge with 5-ASA did not induce recurrent pancreatitis or changes in pancreatic enzymes. This case report supports the concept of an association between acute pancreatitis and Crohn's disease.

In patients with liver cirrhosis and upper gastrointestinal bleeding development of hepatic encephalopathy is a major problem. The aim of the present study was to evaluate the efficacy of the mannite lavage in a controlled randomized trial with respect to the Child-Pugh classification.After initial gastroscopy (+/- sclerotherapy) 39 patients with cirrhosis (18 F, 21 M; age: 57.5 +/- 11.9 yr; Child A: 6, Child B: 16, Child C: 17) and upper gastrointestinal-bleeding were classified according to the Child-Pugh-criteria (A,B,C) and randomized in 2 groups (A,B) for each Child-Pugh level. Patients in group A (n = 18) were initially treated with 2000 mL mannite solution (10%) during the first 2 hours using a naso-gastric tube. Treatment was continued using 2000 mL mannite solution (10%) per day until no rectal blood could be observed. Patients in group B (n = 21) were treated with paromomycine ter in die (1 g tid) and lactulose (10 mL tid). There were no statistical differences between both groups concerning age, sex, Child-Pugh-scores, severity or source of bleeding, initial hemoglobin-levels, number of given blood-transfusions or number of patients with sclerotherapy.Patients in group A were treated with a total of 3325 +/- 1897 mL mannite solution. The application was well tolerated. In addition, kinetics of serum creatinine, potassium and sodium levels did not show any significant changes. No significant differences between both groups could be shown with respect to clinical criteria of encephalopathy according to O'Grady and the length of intensive care unit treatment. Moreover, kinetic of ammonia-levels showed a pronounced decrease (P = 0.05) on day 2 versus day 1 in group A (110.0 +/- 24.2 vs. 156.4 +/- 98 mg/dL) as compared to group B (210.0 +/- 52.7 vs. 162.0 +/- 45 mg/dL). In group A, 6 patients (33.3%) died during the study as compared to 3 patients (14.3%) in group B (P0.05). The lethality rate was strongly associated with the larger proportion of Child-C-patients in group A.The data indicate that whole gut irrigation with mannite is equally efficacious as compared to standard treatment for prophylaxis of hepatic encephalopathy after upper gastrointestinal bleeding in liver cirrhosis. In contrast to previously published controlled studies, no impact of the lavage on the mortality rate or duration of intensive care unit treatment could be shown. With respect to the lower costs for the mannite solution as compared to paromomycine and lactulose (ROTE LISTE, Germany), the mannite lavage should be recommended for the prophylaxis of hepatic encephalopathy after upper gastrointestinal bleeding in patients with liver cirrhosis.

The efficacy of a therapy with interferon-α-2b and ribavirin in patients with hepatitis C not responding to the initial treatment remains controversial. Objective of the present study was to determine the efficacy of a combination therapy with 3 MU interferon-α thrice weekly and 1,000-1,200 mg ribavirin daily for six months in an open label trial. Methods: 44 consecutive patients (genotype 1: 79.5%) who had been previously treated with a minimum dose of 3 MU interferon-α thrice weekly for at least three months were monitored. Sustained response was defined as virological response with clearance of HCV-RNA after a follow-up period of six months after the end of therapy. Results: A significant decrease of the mean levels of AST (34.3 ± 27.6 vs. 16.4 ± 13.5 U/L) and ALT (59.6 ± 48.8 vs. 23.2 ± 20.7 U/L) was observed. In 15/44 patients (34.1%) a virological end-of-treatment response was evident. 8/44 patients (18.2%) achieved a sustained response. In 33.3% of the previous non-responders biochemical response with normal aminotransferases, but no virological response was evident. A significant decrease of the mean hemoglobin level was observed during therapy (12.0 ± 1.7 vs, 14.6 ± 1.0 g/dl; p

A 18-year-old girl suffered from chronic active ulcerative colitis for ten years with growth retardation, primary amenorrhoea and osteopenia, so that total colectomy had been discussed as a possible treatment option. However, clinical remission was reached using a medication with budesonide (9 mg), mesalazine (3 g) and azathioprine (100 mg) when a painful ulcer occurred at the right lower leg.The clinical examination revealed an ulcer of 7 cm diameter with a red-bluish margin at the right lower leg. The typical clinical features led to the diagnosis of pyoderma gangrenosum.High doses of orally administered prednisolone induced the healing of the pyoderma gangrenosum within 2 months. After another 2 months systemic steroids were discontinued. Further laboratory tests confirmed secondary adrenal and ovarian failure (negative CRH-GnRH-test). Change of drug therapy to hydrocortisone (25 mg) in combination with mesalazine (3 g) and azathioprine (100 mg) improved the clinical course. Hydrocortisone was gradually reduced until CRH-GnRH-response returned to normal.Drug therapy with azathioprine can be regarded as a treatment option in pediatric patients with chronic active inflammatory bowel disease. It can be concluded from this case report that faced with controversial therapeutic options in adolescent patients the decision mainly depends on the clinical experience of the physician than on the results of controlled clinical trials.

Topics of this review are the bronchopulmonary manifestations of gastroesophageal reflux disease, cirrhosis of the liver and chronic inflammatory bowel diseases. About 20% of patients with chronic obstructive airway disease show evidence of gastroesophageal reflux disease. Reflux bronchoconstriction seems to be of greater importance than microaspiration. First studies show the positive effects of acid inhibition by proton pump inhibitors on pulmonary symptoms. Hepatorenal syndrome is characterized by arterial hypoxemia with PaO2-values70 mm Hg. Different mediators (endotoxins, amines, polypeptides or allergens) are discussed. Furthermore, elevated levels of prostacycline, atrial natriuretic factor and platelet activating factor have been described. Recently published studies focused on the role of nitric oxide (NO). Patients with cirrhosis of the liver show a higher rate of a pathologically elevated airway resistance which might be induced by a reduced histamine clearance. Ascites leads to reversible restrictive airway disease. Bronchopulmonary manifestations in chronic inflammatory bowel diseases include obstructive and restrictive airway diseases, vascular or serosal changes and show low clinical evidence. In contrast, pathological changes of the common function tests were found in 30 to 50%. These findings may be induced by circulating immune complexes, vasculitis, increased permeability or a combined immune reaction of both, the bronchial and intestinal mucosa. Undesired effects of salicylates should be taken into account. This review shows that bronchopulmonary manifestations in diseases of the Gl-tract or the liver are more common than usually known and should be taken into clinical consideration.

53 unselected patients with Crohn's disease (CD) (35 female, 18 men; mean age: 32.3 +/- 12.5 y.; mean duration of CD: 78.6 +/- 65.7 months) and 23 patients with ulcerative colitis (UC) (8 female, 15 men; mean age: 43.7 +/- 17.9 y.; mean duration of UC: 100.7 +/- 86.0 months) were examined by quantitative computertomography (lumbar spine 1-3). Incipient (manifest) osteopenia (OP) was defined as a reduced axial bone mineral density from -1 standard deviations (SD) to -2 (SD) (-2SD) as compared to a control Group. Reduced bone mineral density was found in 30.2% (16/53) of patients with CD and 9% (2/23) with UC (p0.05). In particular 12/53 pts. (22.6%) with CD and 1/23 pts. (4.35%) with UC showed incipient OP, whereas 4/53 pts. (7.5%) with CD and 1/23 pts. (4.35%) with UC showed manifest OP. With respect to the location of CD the mean relative bone density (SD) was found to be significantly lower in patients with ileal involvement of CD (-0.88 +/- 0.8 SD; n = 39) as compared to patients with colonic involvement (-0.09 +/- 0.86 SD; n = 14) and UC (-0.09 +/- 0.55 SD; n = 23) (p0.05). No significant correlation to the duration of the disease was found. Previous therapy with steroids led to lower mineral bone density as compared to untreated patients. As a trend duration of steroid treatment and bone density were shown to be correlated inversely.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute effect of metoclopramide on oesophageal motility was investigated prospectively in 33 consecutive patients (20 men and 13 women; mean age 60.5 +/- 12.6 years) with type I (n = 8) or type II (n = 25) diabetes. 15 patients had a peripheral sensory-motor polyneuropathy only and three just an autonomic cardial neuropathy. Both lesions were present in ten, none in five. No patient had oesophago-gastroduodenal lesions. Sphincter pressure, relaxation time, contraction amplitude and propulsion velocity of bolus-induced oesophageal peristalsis were measured manometrically after intravenous administration of 10 mg metoclopramide. Resting pressure in the lower oesophageal sphincter rose significantly by 26.7%, contraction amplitude in the tubular portion of the oesophagus by more than 30%, and propulsion velocity by more than 20% (P for each0.05). At the same time the amount of segmental and aperistaltic oesophageal contractions regressed significantly. The effect of metoclopramide was demonstrated regardless of the type of diabetes, duration of diabetes and any manifestation of autonomic cardial or peripheral sensory-motor neuropathy.

The aim of the study was to examine the effects of maintenance molsidomine therapy on portal and cardiac haemodynamics in patients with confirmed alcoholic or nonalcoholic liver cirrhosis and portal hypertension. Molsidomine is a selective reducer of preload without development of tolerance. 16 patients with portally decompensated cirrhosis of the liver following an initial or recurrent episode of bleeding form oesophageal/fundal varices were on long-term treatment (4-24 months) with 2 or 3 x 8 mg molsidomine/day (Corvaton retard). They were followed up after 3-6 months. 6 of the 16 had been treated previously with propranolol for haemorrhage prophylaxis over 11 +/- 15 months. In a total of 70 treatment months with propranolol, 10 recurrent bleeds had occurred. During 166 treatment months with propranolol, 10 recurrent bleeds had occurrences of bleeding. This long-term treatment showed reductions in hepatic venous pressure gradient of 24.8% (n = 8) (p0.05), variceal pressure of 28.7% (n = 7) (p0.05) and size of varices of 17% (n = 8). This occurred without any clinically relevant impairment of systemic cardiovascular regulation. Therefore long-term therapy with molsidomine may be suitable for prophylaxis of haemorrhage of oesophageal varices.

In 124 patients with Crohn's disease (69 women, 55 men; mean age 33.7 [11-66] years) and 53 with ulcerative colitis (30 women, 23 men; mean age 36.2 [19-74] years) the incidence of lactose intolerance, as measured by the H2 breath test and blood sugar concentration, was determined prospectively. To exclude abnormal bacterial colonization of the small intestine or rapid small-intestine transit after partial resection of the small intestine as a cause of lactose intolerance, the oro-caecal transit time for lactulose (H2 breath test) was measured. While 21 of 124 patients with Crohn's disease (16.9%) had the expected incidence of lactose intolerance, this was present in only 2 of 53 patients with ulcerative colitis (3.8%; P0.05). The lactose intolerance was independent of the site of any inflammatory changes, disease activity and extent of small-intestine resection. Oro-caecal transit time for lactose was similar for all patients. There was no lactose intolerance in two patients with abnormal small-intestinal bacterial colonization.--Because of their considerable diagnostic and prognostic significance, tests for lactose intolerance should be performed routinely in all cases of Crohn's disease or ulcerative colitis.

In a prospective study we compared the usefulness of various laboratory tests (albumin, alpha-1-proteinase inhibitor (A1PI), cholinesterase (CHE), C-reactive protein, erythrocyte sedimentation rate, hematocrit) and activity indices (CDAI, VHAI) in relation to the disease activity by endoscopic criteria. Except for hematocrit highly significant differences (p less than 0.0005) of the mean values of all test results were found for patients without or with slight mucosal lesions compared with patients with severe inflammation of the mucosa. Further analysis of the data indicates the highest test efficiency (84%), sensitivity (80%), and specificity (88.6%) for CHE. CHE showed good correlations to all other tests; the highest correlation was found between CHE and VHAI (r = -0.78). We suggest that a suppression of CHE synthesis mediated by endotoxins and cytokines rather than an increased intestinal loss explains the decreased CHE in severe Crohn's disease. It is concluded from the data that CHE is a useful test to assess the inflammatory activity of Crohn's disease.

In a prospective study, we evaluated 33 diabetic patients [type I (n = 8) and type II (n = 25)]. Esophageal motor functions were examined by registering clinical symptoms and by performing esophageal manometry. We also investigated peripheral and autonomic neuropathy. In diabetics, the lower and upper esophageal sphincter pressure and amplitudes of peristaltic waves were reduced. Compared with controls (n = 30), in diabetics the esophageal peristaltic velocity was reduced significantly, and the duration of contractions were decreased as well. Multipeaked waves were uncommon in diabetics, while non-propulsive contractions were seen more often. No correlation was found between esophageal dysfunction and peripheral or autonomic neuropathy. Some 60% of diabetics reported esophageal symptoms; however, no relationship between these symptoms and the extent of dysfunction in esophageal motility was found.

Significantly decreased levels of serumcholinesterase (CHE) were found in acute Crohn's disease (= CD) (3.2 +/- 1.0 KU/L) and acute ulcerative colitis (= UC) (3.54 +/- 1.6 KU/L) as compared to patients with mild or quiescient disease (CD: 5.5 +/- 1.1 KU/L; UC: 5.59 +/- 0.94 KU/L) and healthy controls (5.69 +/- 1.3 KU/L). Suppression of CHE was most evident in Crohn's colitis (2.98 +/- 1.0 KU/L) and extensive UC (2.96 +/- 1.28 KU/L). Intraindividual comparison showed an increase of CHE-levels during treatment with steroids and salicylates. There was no significant correlation to the reduced bodyweight-levels in severe IBD. Best correlations were seen between CHE/albumin (CD: r = +0.61; UC: r = +0.73) and CHE/hematocrit (CD: r = +0.50; UC: r = +0.61) in severe inflammatory bowel disease. The results of a discriminant analysis showed that CHE-levels can predict the degree of activity correctly in the majority of patients with CD and UC. It is suggested that the decrease of serumcholinesterase reflects an inhibition of liver synthesis as an acute phase response-induced by endotoxins and cytokines.

Although fecal incontinence is one of the more frequent clinical symptoms of the gastrointestinal tract, its assessment is often neglected in clinical practice. The psychosocial aspects of the symptoms are also often overlooked: The number of undetected cases in comparison to those registered illustrates that not only patients but also physicians avoid this topic during clinical routine. Consequences of fecal incontinence for the quality of life of patients have rarely been investigated, but we could show that there are specific impacts of incontinence on family life, specifically with respect to sexuality, and on the job situation of those affected. Finally, it has been shown that in most cases continence can be achieved by management strategies deriving from psychological learning theory such as biofeedback training.