Overlap of concurrent extrahepatic autoimmune diseases is associated with milder disease severity of newly diagnosed autoimmune hepatitis.

BACKGROUND: Concurrent extrahepatic autoimmune disorders (CEHAID) are frequently observed in autoimmune hepatitis (AIH). It is not clear whether there is any prognostic significance of CEHAID on AIH. The aim of this study was to examine the prognostic impact of CEHAID and the correlation with the disease severity of AIH. METHODS: This study included 65 hospitalized subjects who fulfilled the accepted criteria for AIH during an 8-year period (2009-2016). All records were manually screened for presence of associated autoimmune diseases. Disease severity of AIH was assessed by liver laboratory tests including the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and liver histology. RESULTS: Among the enrolled patients, 52 (80%) were female (median age 61 years, IQR 45-75). Fifty-six (86.2%) were classified as type-1 AIH. In 26 (40%) patients at least one additional extrahepatic autoimmune disease was diagnosed. Thirty-four subjects were referred to our hospital because of acute presentation of AIH (supposed by an acute elevation of hepatic enzymes) for subsequent liver biopsy resulting in initial diagnosis of AIH. This group was stratified into 3 subgroups: (A) AIH alone (n = 14); (B) overlap with primary biliary cirrhosis (PBC) / primary sclerosing cholangitis (PSC) (n = 11); and (C) with CEHAID (n = 9). AST/ALT ratio was the lowest in subgroup C (median 0.64, IQR 0.51-0.94; P = 0.023), compared to subgroup A (median 0.91, IQR 0.66-1.10) and subgroup B (median 1.10, IQR 0.89-1.36). Patients with AIH alone showed a trend to the highest grade of fibrosis (mean 2.3; 95% CI: 1.5-3.0) with no statistical significance compared to subjects with CEHAID (lowest grade of fibrosis; mean 1.5; 95% CI: 0.2-2.8; P = 0.380) whereas the ongoing inflammation was comparable. CONCLUSIONS: AST/ALT ratio and extent of fibrosis were lower in subjects with AIH and CEHAID, compared to subjects with only AIH. Therefore, the occurrence of CEHAID might be a predictor for lower disease severity of newly diagnosed acute onset AIH, possibly caused by an earlier diagnosis or different modes of damage.

Olfactory Function is Affected in Patients with Cirrhosis Depending on the Severity of Hepatic Encephalopathy.

INTRODUCTION AND AIM: Olfactory functions are altered to a variable degree by chronic liver disease. Few studies including only small populations of patients emphasized the possibility of hepatic encephalopathy (HE) influencing olfactory nervous tasks. So far, no study has explicitly focused on olfactory function depending on the severity of HE as assessed by objective diagnostic procedures. Thus we performed a study using the "Sniffin' Sticks" test system, critical flicker-fusion frequency (CFF) and clinical West Haven criteria. MATERIAL AND METHODS: 54 cirrhotic patients with liver cirrhosis were included. Furthermore, 43 adult volunteers participating as a non-cirrhotic control group. Olfactory testing was performed using the "Sniffin' Stick" test battery (Burghart Medizintechnik, Wedel, Germany) which renders a widely-used tool both in clinical and research settings for the assessment of olfactory threshold, odor identification and discrimination. Several complications of cirrhosis were diagnosed by reference methods. Statistical analysis of cirrhosis-associated complications and their relation to olfactory function was performed. Assessment of HE and classification of different stages were performed according to clinical criteria (West- Haven criteria) and according to CFF, which was determined using a portable analyzer. RESULTS: Olfactory function was significantly reduced in cirrhotic patients (in 61.1%) compared to controls (p < 0.001). Among cirrhotics patients, the prevalence of olfactory deficits (hyposmia, anosmia) increased with the severity of HE as assessed by CFF and clinical criteria (p = 0.008 and p = 0.097, respectively). No correlation was observed between olfactory deficits and severity of liver disease as assessed by Child-Pugh-Score, etiology of cirrhosis and complications of cirrhosis such as ascites and portal venous hypertension. CONCLUSIONS: Olfactory testing serves as a screening tool for HE and may facilitate grading of HE-severity.

[Liver disease in systemic Lupus erythematodes - results of an explorative observational study]. / Hepatopathie bei systemischem Lupus erythematodes ­ Ergebnisse einer explorativen Beobachtungsstudie.

INTRODUCTION: Systemic lupus erythematodes (SLE) represents an autoimmune disease with a highly variable clinical course affecting numerous organs. Hepatic manifestation seems to be rare. It is not clear whether hepatic disease in SLE is of any prognostic importance or whether it correlates with disease activity. METHODS: Our patient cohort included 172 patients with proven SLE, all treated at Bogenhausen Hospital between 01.2009 and 12.2015. Retrospectively, all admissions as inpatients and outpatients were analyzed (n = 671; mean 3.9 per patient). Liver damage was diagnosed by evaluation of laboratory parameters on the basis of pathological liver enzymes and by imaging methods. Disease activity of SLE was calculated by using European Consensus Lupus Activity Measurement-(ECLAM-)Score. Additionally, parameters of SLE including disease duration, organ damage and immune suppressive medication and their possible association with hepatopathy were analyzed. RESULTS: Elevated liver parameters (ASAT, ALAT, GGT, AP) indicating liver damage were detectable in 109 patients (63.4 % of total population) demonstrating significant association with disease activity (on the basis of ECLAM-score, p < 0.001), duration of treatment, frequency of admissions (p < 0.01, respectively), number of used immunosuppressive agents (p < 0.018), increased blood sedimentation rate (p < 0.001) and reduction of serum complement (p < 0.03). Abnormal ultrasound findings of the liver (e. g., non-alcoholic fatty liver disease) were diagnosed in 19.8 %. DISCUSSION: Elevated liver parameters occur frequently in patients with SLE, especially in context with increased disease activity (on the basis of ECLAM-Score or intensified immunosuppressive therapy) and prolonged course of the disease. Liver enzymes should be obtained regularly in patients with SLE and, if necessary, further diagnostic steps should be initiated. Further prospective studies might clarify whether abnormal liver parameters must be included in activity indices to judge disease activity in SLE.

Traveler's Diarrhea, vision abnormalities and unsteady gait in a young woman.

We report on the course of disease in a young woman, originally admitted with suspected refractory infectious tropical traveler's diarrhea. However, symptoms did not resolve upon either symptomatic or subsequent antibiotic therapy. When neurologic deterioration was observed, imaging studies revealed a dramatic series of thromboembolic events, including intracranial hemorrhage caused by extensive sinus vein thrombosis as well as thrombi of the right cardiac ventricle. Colonic mucosal biopsy samples finally led to the histologic diagnosis of ulcerative colitis. Having excluded thrombophilia or any other disease potentially related to a prothrombotic state, we interpreted the thromboembolic events as secondary to the primary manifestation of the underlying inflammatory bowel disease.The increased risk of thromboembolic complications-especially deep vein thrombosis and pulmonary embolism-in inflammatory bowel disease is well documented in the literature. However, sinus vein thrombosis and cardiac thrombi represent a remarkable dimension of this risk and a rare course of coagulopathy secondary to an acute flare of ulcerative colitis. Still, there is a lack of awareness of this risk, resulting in poor implementation of preventive measures modifying risk factors and allowing for pharmacological prophylaxis. We therefore emphasize that-in line with the 2014 German S3 Guideline-thromboprophylaxis in the setting of an acute flare of inflammatory bowel disease is mandatory and should not be restricted because of safety concerns.

Selective mitochondrial Ca2+ uptake deficit in disease endstage vulnerable motoneurons of the SOD1G93A mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that targets some somatic motoneuron populations, while others, e.g. those of the oculomotor system, are spared. The pathophysiological basis of this pattern of differential vulnerability, which is preserved in a transgenic mouse model of amyotrophic lateral sclerosis (SOD1(G93A)), and the mechanism of neurodegeneration in general are unknown. Hyperexcitability and calcium dysregulation have been proposed by others on the basis of data from juvenile mice that are, however, asymptomatic. No studies have been done with symptomatic mice following disease progression to the disease endstage. Here, we developed a new brainstem slice preparation for whole-cell patch-clamp recordings and single cell fura-2 calcium imaging to study motoneurons in adult wild-type and SOD1(G93A) mice up to disease endstage. We analysed disease-stage-dependent electrophysiological properties and intracellular Ca(2+) handling of vulnerable hypoglossal motoneurons in comparison to resistant oculomotor neurons. Thereby, we identified a transient hyperexcitability in presymptomatic but not in endstage vulnerable motoneurons. Additionally, we revealed a remodelling of intracellular Ca(2+) clearance within vulnerable but not resistant motoneurons at disease endstage characterised by a reduction of uniporter-dependent mitochondrial Ca(2+) uptake and enhanced Ca(2+) extrusion across the plasma membrane. Our study challenged the notion that hyperexcitability is a direct cause of neurodegeneration in SOD1(G93A) mice, but molecularly identified a Ca(2+) clearance deficit in motoneurons and an adaptive Ca(2+) handling strategy that might be targeted by future therapeutic strategies.

[Deficits in Health-Literacy of Inpatients - a Cross-Sectional Study]. / Defizite in der Gesundheitskompetenz stationär behandelter Patienten ­ eine Querschnittstudie.

INTRODUCTION: Systematic investigations of health literacy in German patients are rare and mostly based on subjective self-assessment. METHODS: In a cross-sectional survey, 196 patients (female 38 %, male 62 %) in medical and surgical units were asked to complete a questionnaire that we had developed for this purpose. This questionnaire contained 43 questions about common medical terms. We investigated whether patients were familiar with these terms and could name the meaning according to correct definition. Furthermore, the association with the patients' socio-economic and demographic parameters (e. g. education, insurance status, utilization of media) was analyzed. RESULTS: Among all questions of the questionnaire, more patients claimed to know their meaning than this was the case by objective testing. Association of medical knowledge with demographic and socio-economic data revealed that correct answers were more frequent among women compared to men (51.1 % vs. 47.2 %; p = 0.12). Patients' age was negatively correlated with medical knowledge (p < 0.001). Higher educational level was associated with a higher percentage of correct answers (p < 0.001). Private insurance status had significant influence on medical knowledge (p = 0.002). Male patients working intellectually (compared to working physically) had a higher percentage of correct answers (p = 0.001). Other factors like reading newspapers, watching TV and number of consultations per year did not influence the percentage of correct answers. SUMMARY: Physicians should make sure by active inquiries whether the patient understands them correctly. Furthermore, there is a considerable gap between subjective and objective medical knowledge that future evaluations of health literacy should be aware of.

Elevated mRNA-levels of distinct mitochondrial and plasma membrane Ca(2+) transporters in individual hypoglossal motor neurons of endstage SOD1 transgenic mice.

Disturbances in Ca(2+) homeostasis and mitochondrial dysfunction have emerged as major pathogenic features in familial and sporadic forms of Amyotrophic Lateral Sclerosis (ALS), a fatal degenerative motor neuron disease. However, the distinct molecular ALS-pathology remains unclear. Recently, an activity-dependent Ca(2+) homeostasis deficit, selectively in highly vulnerable cholinergic motor neurons in the hypoglossal nucleus (hMNs) from a common ALS mouse model, the endstage superoxide dismutase SOD1(G93A) transgenic mouse, was described. This functional deficit was defined by a reduced hMN mitochondrial Ca(2+) uptake capacity and elevated Ca(2+) extrusion across the plasma membrane. To address the underlying molecular mechanisms, here we quantified mRNA-levels of respective potential mitochondrial and plasma membrane Ca(2+) transporters in individual, choline-acetyltransferase (ChAT) positive hMNs from wildtype (WT) and endstage SOD1(G93A) mice, by combining UV laser microdissection with RT-qPCR techniques, and specific data normalization. As ChAT cDNA levels as well as cDNA and genomic DNA levels of the mitochondrially encoded NADH dehydrogenase ND1 were not different between hMNs from WT and endstage SOD1(G93A) mice, these genes were used to normalize hMN-specific mRNA-levels of plasma membrane and mitochondrial Ca(2+) transporters, respectively. We detected about 2-fold higher levels of the mitochondrial Ca(2+) transporters MCU/MICU1, Letm1, and UCP2 in remaining hMNs from endstage SOD1(G93A) mice. These higher expression-levels of mitochondrial Ca(2+) transporters in individual hMNs were not associated with a respective increase in number of mitochondrial genomes, as evident from hMN specific ND1 DNA quantification. Normalized mRNA-levels for the plasma membrane Na(+)/Ca(2+) exchanger NCX1 were also about 2-fold higher in hMNs from SOD1(G93A) mice. Thus, pharmacological stimulation of Ca(2+) transporters in highly vulnerable hMNs might offer a neuroprotective strategy for ALS.