Background Sarcoidosis is a multisystemic inflammatory granulomatous disease. The prevalence of hepatic involvement is not clear. Aim The aim of this study was to establish the presence and severity of the liver-test abnormalities in sarcoidosis. Methods Retrospectively, patients with confirmed sarcoidosis (n=837) presented with the liver-test abnormalities [alkaline phosphatase, γ-glutamyl transaminase, alanine aminotransferase or aspartate aminotransferase >1.5 times the upper limit of normal (ULN)] who were classified according to severity into mild (zero liver tests ≥3×ULN), moderate (one or two liver tests ≥3×ULN) and severe (three or four liver tests ≥3×ULN) were evaluated. Moreover, the relationship between severity of liver tests and histology was examined. Results Liver-test abnormalities were found in 204 of 837 patients with chronic sarcoidosis (24.4%), among which 127 (15.2%) were suspected of having hepatic sarcoidosis (79 of 127 males, 111 Caucasian, eight African-American). In 22 of 127 patients (17.3%), a liver biopsy was obtained; 21 were compatible with hepatic sarcoidosis. In these 21 patients, severity of liver-test abnormalities was significantly associated with extensiveness of granulomatous inflammation (ρ=0.58, P=0.006) and degree of fibrosis (ρ=0.64, P=0.002). These results remained in the multiple regression analysis when controlled for treatment status, sex, genetics, ethnicity and age. Conclusion Liver-test abnormalities were present in 24% of the studied patients; in 15% highly because of hepatic involvement of sarcoidosis. Moderate and severe liver-test abnormalities seemed to be associated with more advanced histopathological disease. Therefore, in the management of sarcoidosis, for patients with moderate or severe liver-test abnormalities a liver biopsy is recommended.

Background: Calprotectin is present in the cytosol of neutrophil granulocytes and released upon activation. Fecal calprotectin is applied in the clinical management of inflammatory bowel disease whereas serum calprotectin has been discussed as a biomarker in inflammatory disorders. However, its long-term prognostic relevance in critical illness remains unclear. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients. Methods: Serum calprotectin concentrations were analyzed in 165 critically ill patients (108 with sepsis, 57 without sepsis) included in our observational study. Patients were enrolled upon admission to the medical intensive care unit (ICU) of the RWTH Aachen University Hospital. Calprotectin concentrations were compared to 24 healthy controls and correlated with clinical parameters, therapeutic interventions, and survival. Results: Serum calprotectin concentrations were significantly increased in ICU patients as well as in septic patients compared to respective controls (p < 0.001 for ICU patients and p = 0.001 for septic patients). Lower calprotectin concentrations were measured in patients with comorbidities i.e., coronary artery disease. Calprotectin concentrations strongly correlated with the C-reactive protein (p < 0.001) and were closely associated to parameters of mechanical ventilation (i.a. inspiratory oxygen fraction, FiO₂; p < 0.001). The overall survival was significantly impaired in septic patients with high baseline calprotectin concentrations (p = 0.036). However, patients with increasing calprotectin serum concentrations within the first week of ICU admission showed an improved overall survival (p = 0.009). Conclusions: In summary, serum calprotectin concentrations are significantly increased in critically ill patients with sepsis. High calprotectin concentrations at ICU admission predict long-term mortality risk, whereas increasing calprotectin concentrations are associated with a favorable long-term outcome.

Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression.