13C-methacetin-breath test compared to also noninvasive biochemical blood tests in predicting hepatic fibrosis and cirrhosis in chronic hepatitis C.

BACKGROUND: The (13)C-methacetin-breath test and also several noninvasive blood tests comprising routine laboratory parameters have been proposed to predict fibrosis and cirrhosis in chronic hepatitis C. The aim of the study was to compare the diagnostic accuracy between these tests referring to hepatic histology as gold standard. METHODS: 96 patients with chronic hepatitis C virus infection underwent percutaneous liver biopsy and the (13)C-methacetin-breath test. The Fibroindex, the aspartate aminotransferase to platelet ratio index , and the aspartate aminotransferase to alanine aminotransferase ratio were used as parameters for the staging of fibrosis. The main endpoint was the area under the characteristic curves for the diagnosis of advanced fibrosis (F3-F4) and cirrhosis (F4) according to the Batts Ludwig criteria. RESULTS: ROC analysis revealed a cut-off <14.6 per thousand best with 92.6% sensitivity and 84.1% specificity for the (13)C-methacetin-breath test, for the Fibroindex >1.82 70.4% sensitivity and 91.3% specificity, for the aspartate aminotransferase to platelet ratio >1.0 a 66.7% sensitivity and 75.4% specificity, and for the aspartate aminotransferase to alanine aminotransferase ratio >1.0 63.0% sensitivity and 59.4% specificity in predicting liver cirrhosis. The areas under the curve for the breath test, the Fibroindex, aspartate aminotransferase to platelet ratio and the aspartate aminotransferase to alanine aminotransferase ratio were 0.958, 0.845, 0.799, and 0.688, respectively, when predicting cirrhosis. For identifying patients with advanced fibrosis, the areas under the curve were 0.827, 0.804, 0.779, and 0.561, respectively. Discordances between Fibroindex (21%), aspartate aminotransferase to platelet ratio (29%) or aspartate aminotransferase to alanine aminotransferase ratio (37.6%) and liver biopsy were significantly more frequent than between (13)C-breath test (11.6%) and liver biopsy (P<0.05). CONCLUSION: The (13)C-methacetin-breath test is more reliable in predicting advanced fibrosis and cirrhosis than simple biochemical parameters (aspartate aminotransferase to platelet ratio; aspartate aminotransferase to alanine aminotransferase ratio).

The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study.

OBJECTIVE: Hyperhomocysteinemia is a described risk factor of cardiovascular diseases. The aim of this study was the treatment of hyperhomocysteinemia in liver transplant recipients with L-5-methyltetrahydrofolate (L-5-MTHF; 1 mg) vs folic acid (1 mg) vs placebo in a double-blind placebo-controlled study and to compare the relative responsiveness of these patients to L-5-MTHF and folic acid. SUBJECTS/METHODS: Patients were recruited from Hepatology-Transplantation-Unit at Johann Wolfgang Goethe-University, Frankfurt. Sixty patients were included in this study and 12 patients dropped out for different reasons. The patients were treated over 8 weeks with supplemental L-5-MTHF or folic acid or placebo. Serum homocysteine (HCY) was analyzed with high-performance liquid chromatography (HPLC) beside routine lab tests. RESULTS: We observed only a significant decrease of total serum HCY in the L-5-MTHF group during the study period (at week 0: 15+/-7.7 microM; after 8 weeks treatment: 9.41+/-2.6 microM, P<0.001). There was no significant decrease of total serum HCY neither in the folic acid group nor in the placebo group. CONCLUSION: The effects of L-5-MTHF are significantly more potent than folic acid itself. Therefore, lowering serum HCY in liver transplant recipients is effective with L-5-MTHF.

Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation.

OBJECTIVE: The aim of this study was to evaluate the role of the C677T-MTHFR (methylenetetrahydrofolate reductase)-polymorphism (CC, CT and TT) for vascular complications in liver transplant recipients. DESIGN: Retrospective study. SETTING: Hepatology-Transplantation-Unit, Johann Wolfgang Goethe-University, Frankfurt am Main. SUBJECTS: 48 liver transplant recipients were included, no dropouts. METHODS: MTHFR polymorphism was detected by PCR amplification and digestion with Hinfl restriction enzyme. Vascular complications after liver transplantation were detected from the patients' records. The total serum homocysteine (HCY) was analyzed with high-pressure liquid chromatography. RESULTS: In the wild-type group (CC), the HCY levels were slightly high (14.0+/-1 micro M). Among the patients with the CT polymorphism, the HCY values were elevated (22.5+/-3 micro M). In the homozygous TT group, there was a significant increase (31.2+/-6 micro M, P<0.01) of the HCY values. The percentage of vascular complications was higher in the heterozygous CT (47%) and homozygous TT (62.5%) group compared with wild-type CC (21%). Patients with a homozygous TT genotype of the MTHFR polymorphism with a vascular complication had a highly significant elevated HCY level compared to the other genotype groups, both with and without any vascular complications (P<0.001). Recipients with an elevated HCY and the TT polymorphism have a higher probability of developing a vascular complication after transplantation (odds ratio: 4.3 and 11.0; 95% confidence interval: 1.15, 12.25 and 1.41, 85.24). CONCLUSIONS: The C677T polymorphism in the MTHFR gene and subsequent elevation of the total serum HCY is significantly associated with an increased incidence of vascular complications in liver transplant recipients.

13C-breath tests: current state of the art and future directions.

13C-breath tests provide a non-invasive diagnostic method with high patient acceptance. In vivo, human and also bacterial enzyme activities, organ functions and transport processes can be assessed semiquantitatively using breath tests. As the samples can directly be analysed using non-dispersive isotope selective infrared spectrometers or sent to analytical centres by normal mail breath tests can be easily performed also in primary care settings. The 13C-urea breath test which detects a Helicobacter pylori infection of the stomach is the most prominent application of stable isotopes. Determination of gastric emptying using test meals labelled with 13C-octanoic or 13C-acetic acid provide reliable results compared to scintigraphy. The clinical use of 13C-breath tests for the diagnosis of exocrine pancreatic insufficiency is still limited due to expensive substrates and long test periods with many samples. However, the quantification of liver function using hepatically metabolised 13C-substrates is clinically helpful in special indications. The stable isotope technique presents an elegant, non-invasive diagnostic tool promising further options of clinical applications. This review is aimed at providing an overview on the relevant clinical applications of 13C-breath tests.

Predictors of reduced health-related quality of life in adults with coeliac disease.

BACKGROUND: Data available on predictors of reduced health-related quality of life in coeliac disease are not consistent. AIM: To test predictors of reduced health-related quality of life, described in the literature, by a multivariate approach. METHODS: 1000 adult coeliacs of the German Coeliac Society completed a medical and a sociodemographic questionnaire, the Short-Form Health Survey (SF-36), the Coeliac Disease Questionnaire and the Hospital Anxiety and Depression Scale within a postal survey. Predictors of reduced health-related quality of life were tested for by logistic regression analysis. RESULTS: Physical comorbidities (beta = -0.41; OR = 0.66, P < 0.001) and mental disorder (beta = 0.88; OR = 2.4, P = 0.03) were associated with a reduced physical summary score of the SF-36. Mental disorder (beta = 2.5; OR = 11.9, P < 0.001), physical comorbidities (beta = -0.26; OR = 0.77, P = 0.004) and younger age at diagnosis (beta = -0.10; OR = 0.91, P = 0.05) predicted a reduced mental summary score of the SF-36. Mental disorder (beta = 0.90; OR = 2.5, P = 0.03), non-compliance with gluten-free diet (beta = 0.44; OR = 1.6, P = 0.009), active medical comorbidities (beta = -0.28; OR = 0.76, P = 0.007) and dissatisfaction with doctor-patient communication (beta = 0.55; OR = 1.7, P = 0.03) were associated with reduced Coeliac Disease Questionnaire scores. CONCLUSIONS: Reduced health-related quality of life in coeliac disease is associated not only with physical and mental comorbidities, but also with non-compliance with gluten-free diet and dissatisfaction with doctor-patient communication.

Comparative evaluation of a new bedside faecal occult blood test in a prospective multicentre study.

BACKGROUND: Faecal occult blood testing is an established method of colorectal neoplasia screening. Guaiac-based tests are limited by poor patient compliance, low sensitivity, specificity and positive predictive value. Newer immunochemical-based tests, accurate but tedious, require a well-established laboratory set up. There is need for simpler immunochemical tests that can be performed at the out-patient clinic. AIM: To compare the performance characteristics of a new bedside immunological test strip device with a sensitive Guaiac-based and established immunochemical test for detection of faecal occult blood in patients undergoing colonoscopy. METHODS: A total of 389 consecutive patients from four centres who were referred for colonoscopy also provided the stool samples for detection of occult blood without dietary restrictions. Stool tests performed were (i) Guaiac-based, (ii) immunochemical enzyme-linked immunosorbent assay and (iii) bedside immunochemical strip test. RESULTS: At the optimal threshold level, the sensitivity and specificity of the beside immunochemical strip test for detection of significant colorectal neoplasia (adenomas >1.0 cm and carcinomas) were 60% and 95%, respectively. CONCLUSIONS: This bedside immunochemical strip test proved to be a simple, convenient, non-cumbersome and accurate tool with similar performance characteristics for detection of any bleeding lesion including colorectal neoplasia when compared with an established immunochemical faecal occult blood test.

Noninvasive assessment of liver steatosis, fibrosis and inflammation in chronic hepatitis C virus infection.

BACKGROUND: Duplex-Doppler ultrasound is a noninvasive method for the assessment of hepatic hemodynamics beyond conventional gray-scale imaging. The clinical value of the method for the grading and staging of chronic hepatitis C virus (HCV) infection and the prediction of hepatic steatosis still has to be determined. This study aimed to compare Duplex-Doppler and ultrasound with the histologic staging and the estimation of hepatic steatosis in chronic HCV infection. PATIENTS AND METHODS: One hundred and nineteen consecutive patients with chronic HCV infection underwent both liver biopsy and ultrasound with Duplex-Doppler. Maximum portal venous blood flow velocity, portal venous flow undulation, hepatic venous flow pattern and spleen size were assessed and compared with histologic findings. Histologic grading and staging was performed according to the modified HAI and hepatic steatosis was estimated. RESULTS: Doppler ultrasound was unable to discriminate between different degrees of fibrosis. Sensitivity/specificity of portal venous flow and undulations for the diagnosis of hepatic cirrhosis was 74.5%/53% and 76.5%/100%. The PPV and NPV of reduced undulations was 100% and 96.2%. Mono- or biphasic hepatic venous flow indicated advanced hepatic steatosis (sensitivity 88.2%, specificity 74.5%, PPV 36.6%, NPV 97.5%). Spleen size was significantly enlarged both in patients with cirrhosis and steatosis. CONCLUSIONS: Although Duplex-Doppler of the portal and hepatic veins is not a substitute for histologic grading and staging, portal vein undulations can predict liver cirrhosis with considerable accuracy. Moreover, triphasic patterns of hepatic venous flow virtually exclude significant fatty liver disease. Additional studies should perform intraindividual follow-up investigations to further define the role of Duplex-Doppler ultrasound in chronic HCV infection.

An infected esophageal duplication cyst in a patient with non-Hodgkin's lymphoma mimicking persistent disease.

Differentiation of mediastinal cysts appearing as soft-tissue attenuation masses on computed tomography (CT) scans from malignant mediastinal masses is difficult. We report a patient with non-Hodgkin's lymphoma, who was considered to have persistent disease in the posterior mediastinum based on CT scans. However, endoscopic ultrasound (EUS) demonstrated a paraesophageal, fluid-filled cyst with echodens inclusions and no evidence of any solid component. EUS-guided fine-needle aspiration (FNA) revealed mucous, epithelial and inflammatory cells, and additionally candida albicans was cultured. Based on these findings and constant size during follow-up, the diagnosis of an infected esophageal duplication cyst was made. Thus, this report further demonstrated the impact of EUS and EUS-FNA for management of posterior mediastinal cystic lesions in selected cases.

Does the liver ever age? Results of liver transplantation with donors above 80 years of age.

INTRODUCTION: Facing an increasing shortage of donor organs, donor criteria become more extended and so-called marginal organs are accepted for transplantation. For liver donation donor age above 70 years is accepted as a risk factor concerning primary dysfunction or nonfunction. Therefore, the aim of this study was to compare the early outcome of grafts older versus younger than 80 years of age. PATIENTS AND METHOD: Between August 2002 and February 2004, 40 adult liver transplants were performed using triple immunosuppression with tacrolimus, MMF, and low-dose corticosteroids. Recipients with HCC received low-dose rapamycin after postoperative day 14. The outcome of grafts from donors under 80 years of age (n=35) was compared with those from donors 80 years old or more (n=5). For statistical analysis Mann-Whitney-U-Test and Fisher's Exact Test were used with P < .05 considered statistically significant. RESULTS: The average donor age of our population was 54.4 +/- 17.3 years with five donors older than 80 years (80-83 years). These donors all had additional risk factors. The recipients of the latter grafts suffered from HCC and liver cirrhosis Child A (n=2) or from viral hepatitis (n=3). One recipient had advanced cirrhosis with severe complications. The outcomes of both groups were comparable concerning intraoperative and postoperative courses. All recipients of old liver grafts left the hospital with stable graft function. CONCLUSION: Liver grafts over 80 years can be transplanted with good results, especially if given to recipients with malignancy and otherwise stable liver function.

Characterization of the nuclear import of human MutLalpha.

DNA mismatch repair (MMR) is essential for the maintenance of replication fidelity. Its major task is to recognize mismatches as well as insertion/deletion loops of newly synthesized DNA strands. Although different players of human MMR have been identified, the regulation of essential steps of MMR is poorly understood. Because MMR is initiated in the nucleus, nuclear import might be a mechanism to regulate MMR. Nuclear targeting is accomplished by conserved signal sequences called nuclear localization signals (NLS), which represent clusters of positively charged amino acids (aa). hMLH1 contains two clusters of positively charged amino acids, which are candidate NLS sequences (aa 469-472 and 496-499), while hPMS2 contains one (aa 574-580). To study the effect of these clusters on nuclear import, NLS mutants of hMLH1 and hPMS2 were generated and expressed in 293T cells. The subcellular localization of the mutant constructs was monitored by confocal laser microscopy. We demonstrated that missense mutations of two signal sequences, one in hMLH1 and one in hPMS2, lead to impaired nuclear import, which was especially prominent for mutants of the hMLH1 residues K471 and R472; and hPMS2 residues K577 and R578.

13C-methacetin breath test as liver function test in patients with chronic hepatitis C virus infection.

BACKGROUND: The 13C-methacetin breath test enables the quantitative evaluation of the cytochrome P450-dependent liver function. AIM: To find out whether this breath test is sensitive in noncirrhotic patients also with chronic hepatitis C in early stages of fibrosis. METHODS: Sixty-one healthy controls and 81 patients with chronic hepatitis C underwent a 13C-methacetin breath test. In all patients, a liver biopsy was performed. The liver histology was classified according to the histology activity index-Knodell score. RESULTS: Delta over baseline values of the patients at 15 min significantly differed from controls (19.2 +/- 9.2 per thousand vs. 24.1 +/- 5.7 per thousand; P < 0.003). The cumulative recovery after 30 min in patients was 11.4 +/- 4.8% and in healthy controls 13.8 +/- 2.8% (P < 0.002). However, patients with early fibrosis (histology activity index IVB) did not differ in delta over baseline values of the patients at 15 min (23.2 +/- 7.9 per thousand vs. 22.6 +/- 7.2 per thousand; P = 0.61) or cumulative recovery (13.6 +/- 3.7% vs. 13.2 +/- 3.8%; P = 0.45) from patients with more advanced fibrosis (histology activity index IVC). Patients with clinically nonsymptomatic cirrhosis (histology activity index IVD; Child A) metabolized 13C-methacetin to a significantly lesser extent (delta over baseline values of the patients at 15 min: 8.3 +/- 4.9 per thousand; P < 0.005 and cumulative recovery after 30 min: 5.6 +/- 3.2%; P < 0.003). The 13C-methacetin breath test identified cirrhotic patients with 95.0% sensitivity and 96.7% specificity. CONCLUSION: The non-invasive 13C-methacetin breath test reliably distinguishes between early cirrhotic (Child A) and noncirrhotic patients, but fails to detect early stages of fibrosis in patients with chronic hepatitis C.

The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study.

BACKGROUND: Malignant cells characteristically possess high levels of plasminogen activator, which induce local fibrinolysis. The DR-70 immunoassay is a newly developed test, which quantifies fibrin degradation products in serum by a proprietary antibody. AIM: To evaluate the DR-70 immunoassay as a detection assay for the presence of gastrointestinal cancers. METHODS: We prospectively collected blood sera of 85 patients with histologically proven tumour and 100 healthy blood donors. Ten microlitres of the sera was used for the DR-70 immunoassay. Nineteen patients had a hepatocellular and 10 cholangiocellular carcinoma, 13 cancer of the pancreas, 30 colorectal cancer, 10 stomach cancer and three cancer of the oesophagus. RESULTS: Receiver-operator curve analysis revealed <0.7 microg/mL as the best cut-off value to distinguish between patients with cancer and healthy controls. Using this cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 91% and a specificity of 93%. Patients with advanced tumour spread showed significantly higher DR-70 values than those with early-stage tumours (P < 0.0003). CONCLUSION: The DR-70 immunoassay reliably differs between cancer patients and healthy controls. Therefore, it promises to become a useful test for the detection of cancer in clinical practice.

[Lymphangioleiomyomatosis (LAM): a rare cause of ascites and pleural effusion]. / Lymphangioleiomyomatose (LAM): seltene Ursache von Aszites und Pleuraergüssen.

HISTORY AND CLINICAL FINDINGS: A 45 year old woman presented at our hospital for further evaluation of intermittent abdominal pain. The patient reported that she had suffered a spontaneous pneumothorax 8 years and a pleural effusion 3 years before. DIAGNOSTIC FINDINGS AND THERAPY: Abdominal ultrasound showed abdominal fluid which proved to be chylous ascites by diagnostic paracentesis. Radiologic (lymphangiography) findings were consistent with lymphangioleiomyomatosis (LAM). Remarkably, lymphangiography resulted in an immediate disappearance of the ascitic fluid. CONCLUSION: This report depicts a case of LAM which involved both pulmonary and intestinal symptoms. Previous pulmonary problems gave a hint towards the right diagnosis. Though lymphangiography is rarely performed in these days, the method was both diagnostic and therapeutic in the case presented.

Measuring gastric emptying of semisolids in children using the 13C-acetate breath test: a validation study.

BACKGROUND AND AIM: Radioscintigraphy is the gold standard for evaluation of gastric emptying in children, but requires exposure to ionising radiation. Therefore, the aim of the study was to validate the non-radioactive 13C-acetate breath test in children in comparison to radioscintigraphy as reference method. PATIENTS: Twenty-nine children with dyspeptic or respiratory symptoms were tested for gastric emptying disorders simultaneously performing the 13C-acetate breath test and radioscintigraphy. METHODS: A semisolid oatmeal was doubly labelled with 150 mg 13C-acetate and 50 MBq 99mTechnetium. Breath samples were collected every 5-10 min for 4 h. After mass spectrometrical 13C-analysis, curve fitting of the 13C-cumulative recovery to the modified power exponential function Y = m(1 - e(-kt) calculated the half emptying times of the breath test (t 1/2 (breath)). Scintigraphic image acquisition began immediately after the ingestion of the 99mTechnetium-labelled testmeal at a rate of one frame every 60 s for 1 h. RESULTS: Six children showed delayed gastric emptying in scintigraphy (t 1/2(scinti) > 60 min). All these children had prolonged half emptying times t 1/2 (breath) in the 13C-acetate breath test. Using a cut-off t 1/2(breath) > 90 min, the 13C-acetate breath test had a sensitivity of 100% and a specificity of 85%. Scintigraphic and breath test half emptying times were linearly correlated (Y = 0.80x + 47.68, r = 0.76, P < 0.00001). CONCLUSIONS: The 13C-acetate breath test proves to be a reliable, non-radioactive alternative for measuring gastric emptying in children.

[(13)C-breath tests for the assessment of liver function]. / C-basierte Atemtests in der Leberfunktionsdiagnostik.

Routine work-up of hepatic diseases is performed by regular laboratory tests which indicate changes in the metabolic capacity of various hepatic cellular systems. A (13)C-based breath test may offer further selective characterisation of hepatic enzymes by means of a non-invasive technique. We present an overview on current test systems and their potential relevance in the assessment of hepatic diseases.

[Gastroenterology in the G-DRG-System 2004]. / Gastroenterologie im G-DRG-System 2004.

After a year of preliminary voluntarily introduction of casemix funding in hospitals in 2003 nearly every German hospital will be confronted with lump sump payments on the basis of the G-DRG system for their inpatient care starting from January 2004. To analyse weaknesses referring to gastroenterology services within the G-DRG version 1.0 the German Association for Disorders of the Digestive System and Metabolism (DGVS) and the DRG-Research-Group from the University of Muenster conducted a DRG evaluation project. In the analysis patient data from 16 hospitals were included. As a result of the project recommendations for G-DRG adjustments were generated. Those recommendations were implemented in the advancement to G-DRG version 2004. Also the International Classification of Diseases (ICD-10) was modified to ICD-10 German Modification. The classification of procedures OPS-301 was revised. The main adjustments to the G-DRG system and both classifications will be presented in this paper.

[Acute lower gastrointestinal hemorrhage. Diagnosis and management]. / Akute untere Gastrointestinalblutung. Diagnostik und Management.

In most cases (80%), acute lower gastrointestinal bleeding stops spontaneously, but rebleeding is frequent (25%). The intensity and quality of the bleeding--hematochezia, melena, or occult bleeding--determines the diagnostic and therapeutic strategy (endoscopic evaluation of the upper and lower gastrointestinal tract, mesenteric angiography, scintigraphy, enteroscopy, capsule endoscopy) and its urgency. Acute lower gastrointestinal bleeding can mostly be treated conservatively or by endoscopic interventions (injection therapy, clip application, coagulation and ligation methods). Severe hemorrhage can render colonoscopy and the identification of the bleeding source technically difficult. Emergency operations are only indicated when patients with severe hemorrhage cannot be stabilized by interventional endoscopy or angiography with selective embolization.