Doppler Ultrasound and Transient Elastography in Liver Transplant Patients for Noninvasive Evaluation of Liver Fibrosis in Comparison with Histology: A Prospective Observational Study.

BACKGROUND AND AIM: Accurate quantification of progressive liver disease is essential for therapeutic decisions and follow-up for patients who underwent liver transplantation. To evaluate the quality of noninvasive assessment of liver fibrosis in these patients, we compared Doppler ultrasound of the hepatic blood vessels as well as transient elastography (TE, FibroScan(®)) with liver biopsy following transplantation. METHODS: We performed Doppler ultrasound of the hepatic veins, hepatic artery, and portal vein as well as a TE in 48 patients who underwent liver transplantation 12 months ago. Hepatic venous flow was evaluated by determination of the resistance index (HVRI) of the right hepatic vein. Doppler and TE results were compared with histopathologic workup of a 12-month protocol liver biopsy after transplantation. RESULTS: HVRI showed a high reliability in predicting liver fibrosis stage FII or higher (AUROC of 0.99 ± 0.001 for FII or higher, the HVRI < 1.05 with a sensitivity and specificity of 100 and 91.43 %) compared to histopathologic workup (Desmet's score) and was comparable to TE analysis. Both HVRI and TE differed significantly in no or minimal fibrosis versus FII or higher (p < 0.001). In contrast, portal vein and hepatic artery did not show significant changes in blood flow in our study population. CONCLUSIONS: Hepatic vein flow resistance index is a valuable tool in noninvasive evaluation of liver fibrosis in liver transplantation follow-up predicting FII or higher and might help reducing the number of protocol biopsies needed.

[Diagnostic value of routine ileum biopsy in patients with chronic diarrhoea--a prospective monocentric study]. / Die diagnostische Bedeutung der Ileumbiopsie bei chronischer Diarrhö--eine prospektive monozentrische Studie.

BACKGROUND AND AIMS: In patients with chronic diarrhoea of unknown origin, colonoscopy with intubation of the terminal ileum and performance of biopsies are standard in the diagnostic work-up. While the importance of random biopsies in the colon even in cases with normal endoscopic appearance has been proven in several studies, the role of biopsies in the terminal ileum under these circumstances is not well defined. PATIENTS AND METHODS: In this prospective observational 24-month study patients with chronic diarrhoea of unknown cause were included. All patients underwent colonoscopy with intubation and biopsy of the terminal ileum. These biopsies have been analysed, their diagnostic value has been compared to the endoscopic appearance and the clinical diagnosis was investigated. RESULTS: In 159 patients, the terminal ileum showed a pathological endoscopic appearance in 27 cases (17 %). In 22 (81.5 %) of these 27 patients diagnostic pathological findings were present, in 4 cases (14.8 %) non-specific histological changes were detected and in one patient (3.7 %), histology was normal. In contrast, only in one of 132 cases with normal endoscopic appearance, did histopathology show a significant pathology (celiac disease). In 30 of the 132 patients (22.7 %) with a normal endoscopic appearance, distinctive histological features were detected (slight eosinophilia or elevated mucosal immune cell count), but not classified as diagnostic. In all cases, these features were also present in simultaneously performed colonic biopsies. CONCLUSIONS: Routine biopsy of the terminal ileum, when normal endoscopic appearance is documented, does not give any additional information and cannot be recommended as a standard procedure in endoscopic work-up of chronic diarrhoea.

[Gastrointestinal bleeding in liver cirrhosis at the ICU]. / Gastrointestinale Blutungen als Komplikation von Patienten mit Leberzirrhose auf der Intensivstation.

Due to portal hypertension and bleeding disorders, patients with liver cirrhosis are at increased risk for severe gastrointestinal bleedings (GIB), commonly requiring therapy at the intensive care unit (ICU). In order to identify epidemiological and prognostic factors for GIB in cirrhotic patients, we retrospectively analysed patients from our medical ICU from 1999 to 2010. Among 7376 critically ill patients, 650 (8.8 %) were diagnosed with liver cirrhosis. Hepatic cirrhosis was frequently found in ICU patients admitted due to severe GIB (23.2 % of 711 patients had cirrhosis). Moreover, patients with cirrhosis were at increased risk to develop severe GIB during intensive care treatment (40.9 % of 44 patients with GIB during ICU stay had cirrhosis). Besides the high rate of variceal bleedings (64.4 %) in cirrhotic patients, non-variceal haemorrhages were also common (28.5 %). We identified the MELD score and necessity of mechanical ventilation as independent risk factors for mortality in cirrhotic patients with severe GIB. Patients with liver cirrhosis and severe GIB had significantly impaired prognosis (case-related fatality rate of 26.1 % with cirrhosis vs. 6.8 % without cirrhosis), especially in cases of newly developed GIB during ICU therapy. Advanced therapeutic approaches and novel strategies are warranted to improve the critical prognosis of these high-risk patients.

Endoscopic ultrasound as an early diagnostic tool for primary sclerosing cholangitis: a prospective pilot study.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease, which typically affects middle-aged men and is frequently associated with inflammatory bowel disease. Early recognition and accurate diagnosis remains a clinical challenge. Invasive diagnostic procedures, such as endoscopic retrograde cholangiography or liver biopsy are needed when magnetic resonance cholangiopancreatography remains inconclusive. As these procedures are associated with significant risks, the current study sought to determine whether endoscopic ultrasound (EUS) of the biliary tract is a useful diagnostic tool in cases of suspected PSC. PATIENTS AND METHODS: In a prospective pilot study, 138 patients presenting with chronic cholestatic hepatopathy were screened and 32 patients with possible PSC were evaluated further. In addition to all routine measures, EUS was included in the diagnostic work-up.  The following parameters were evaluated and compared with the definitive diagnosis: wall thickening ( ≥ 1.5  mm), irregular wall structure, significant changes of caliber of the common bile duct, and perihilar lymphadenopathy. RESULTS: In the 138 patients screened, a PSC prevalence of 13 % was found. Of the 32 patients included in the study, 17 had large-duct PSC diagnosed. When two of the aforementioned four parameters showed PSC-like features, sensitivity and specificity of predicting PSC were 76.4 % and 100 %, with positive and negative predictive values of 100 % and 79 %, respectively. In four patients presenting with strictly intrahepatic disease, EUS was not diagnostic. CONCLUSIONS: EUS proved to be a valuable tool in suspected PSC and accurately predicted extrahepatic disease. EUS should be evaluated further as an early procedure in routine diagnostic measurements. This approach promises a significant improvement in disease detection as well as a reduction in high risk invasive procedures.

Doppler ultrasound of hepatic blood flow for noninvasive evaluation of liver fibrosis compared with liver biopsy and transient elastography.

BACKGROUND: Accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. AIMS: To optimize the quality of non-invasive assessment of liver fibrosis in patients with chronic hepatopathy we compared Doppler ultrasound with liver histology and transient elastography (TE). METHODS: In this prospective observational study, we performed Doppler ultrasound of hepatic blood vessels as well as TE in 125 patients who underwent liver biopsy for diagnostic work-up of hepatopathy. Hepatic venous flow was evaluated by determining resistance index (HVRI) of the right hepatic vein. Doppler and TE results were compared with histological staging, grading and degree of steatosis obtained by liver biopsy. RESULTS: HVRI showed a high reliability in predicting fibrosis stage FII or higher (AUROC 93.7 %, HVRI < 1.185; sensitivity 89.66 % and specificity 86.32 %) and was superior to TE. Neither steatosis nor inflammation had significant influence on HVRI-based estimation of fibrosis (1.45 ± 0.2; 1.26 ± 0.05; 1.06 ± 0.06; 0.87 ± 0.08; 0.46 ± 0.11 for F0-FIV, respectively). HVRI differed significantly in different stages of fibrosis. In contrast, portal vein and hepatic artery only showed significant changes in higher stages of fibrosis. Hepatic artery resistance index was elevated (0.67-0.74; p < 0.05); portal vein flow maximum and undulation were significantly reduced in higher fibrosis (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: Hepatic blood flow analysis, especially HVRI, provides useful information during assessment of hepatopathy and is a reliable predictor of liver fibrosis stage FII or higher as part of the non-invasive diagnostic work-up and follow-up in chronic liver disease.

[When only the pathologist may help. Limitation and possibilities of biopsies in Internal Medicine]. / Wenn nur noch der Pathologe hilft. Grenzen und Möglichkeiten der Biopsie in der Inneren Medizin.

Histological evaluation after biopsy remains the gold standard for the diagnosis of numerous diseases in Internal Medicine. The gastrointestinal tract (e. g. esophagus, liver and large intestine), the kidneys or bone marrow are organs, where biopsy-driven diagnosis and evaluation of therapeutic regimens are of major relevance. Improvement in blood analysis, endoscopic techniques and radiology could significantly reduce the number of biopsies. Hence under certain circumstances, the risk of biopsy can be avoided and non-invasive markers can sufficiently substitute the histological evaluation. However, histological evaluation derived from biopsies remains the standard of diagnosis in many cases in Internal Medicine. In the present review the current standards and future developments of pathologic diagnosis through biopsy are illustrated.

[Bleeding origin, patient-related risk factors, and prognostic indicators in patients with acute gastrointestinal hemorrhages requiring intensive care treatment. A retrospective analysis from 1999 to 2010]. / Ursachen, patientenspezifische Risikofaktoren und prognostische Indikatoren bei akuter gastrointestinaler Blutung und intensivmedizinischer Therapieindikation. Eine retrospektive Untersuchung der Jahre 1999-2010.

BACKGROUND: Gastrointestinal bleeding (GIB) is a common problem in elderly patients involving severe comorbidities and concomitant antiplatelet or anticoagulatory therapy. The risk factors and prognostic indicators of patients with severe GIB requiring intensive care medical treatment have not been well evaluated. METHODS: A retrospective analysis of 7,376 patients from the medical intensive care unit (ICU) at the University Hospital Aachen was carried out between 1999 and 2010. RESULTS: Of 614 patients admitted to the ICU because of acute GIB, 463 (75%) presented with upper GIB (UGIB) and 151 (25%) with lower GIB (LGIB). Despite early endoscopic intervention and ICU treatment, UGIB had a mortality rate of 16%, whereas LGIB showed a significantly better prognosis (mortality <5%) in the ICU setting. Risk factors for OGIB-related mortality were hemodynamic instability, organ failure, comorbidities (especially liver cirrhosis), and rebleeding. In total, 218 patients (36%) were treated with antiplatelet or anticoagulatory drugs, which were associated with a favorable prognosis in the UGIB group. Elevated serum lactate levels upon admission were superior in predicting mortality than established indicators of prognosis such as the Rockall or the Glasgow-Blatchford score. CONCLUSIONS: Despite successful endoscopic intervention, severe acute UGIB is associated with a significant mortality rate of 16% in the ICU setting, determined by hemodynamic failure, organ dysfunction, and comorbidities. The serum lactate levels of patients with GIB on the day of admission to the ICU are prognostic.

Deletion of gp130 in myeloid cells modulates IL-6-release and is associated with more severe liver injury of Con A hepatitis.

IL-6/gp130 dependent signaling plays an important role in modulating inflammation in acute and chronic diseases. The course of Concanavalin A- (Con A) induced hepatitis can be modulated by different immune-mediated mechanisms. IL-6/gp130-dependent signaling has been shown to be protective in hepatocytes. However, the role of this pathway in myeloid cells has not yet been studied. In our present study we used macrophage/neutrophil-specific gp130 knockout (gp130(ΔLys), KO) animals and analyzed its relevance in modulating Con A-induced hepatitis. Additionally, we performed in vitro studies with gp130(ΔLys)-macrophages. We demonstrate that gp130(ΔLys) animals are more susceptible to Con A-induced hepatitis. This is reflected by higher transaminases, higher lethality and more severe liver injury as shown by histological staining. Using flow cytometry analysis we further could show that increased liver injury of gp130(ΔLys) animals is associated with a stronger infiltration of CD11b/F4/80 double-positive cells compared to wild-type (gp130(flox/flox), WT) controls. To further characterize our observations we studied thioglycolate-elicited peritoneal macrophages from gp130(ΔLys) animals. Interestingly, the LPS-dependent IL-6 release in gp130(ΔLys) macrophages is significantly reduced (p<0.05) compared to WT macrophages. Additionally, IL-6 blood levels in vivo after Con A injection were significantly lower in gp130(ΔLys) animals compared to WT animals (p<0.05). In summary, our results suggest that gp130-deletion in macrophages and granulocytes leads to diminished IL-6 release from these cells, which is associated with more severe Con A-induced hepatitis.