Drug-induced liver injury (DILI) is a heterogenous entity leading to liver damage. We have analysed the frequency, biochemical and histological patterns and clinical courses of DILI cases due to metamizole at our tertiary care centre in Hamburg, Germany.Methods: Consecutive patients with DILI who presented to our clinic were analysed retrospectively. Causes of acute hepatitis other than DILI were excluded.

Idiosyncratic drug-induced liver injury (DILI) and hepatic injury due to herbal and dietary supplements (HDS) can adapt clinical characteristics of autoimmune hepatitis (AIH), such as the appearance of autoantibodies and infiltration of the liver by immune competent cells. To describe these cases of DILI/HDS, the poorly-defined term “autoimmune(-like)” DILI/HDS came up. It is uncertain if these cases represent a subgroup of DILI/HDS with distinct pathomechanistic and prognostic features different from “classical” DILI/HDS. Besides, due to the overlap of clinical characteristics of “immune-mediated” DILI/HDS and AIH, both entities are not easy to differentiate. However, the demarcation is important, especially with regard to treatment: AIH requires long-term, mostly lifelong immunosuppression, whereas DILI/HDS does not. Only through exact diagnostic evaluation, exclusion of differential diagnoses and prolonged follow-up can the correct diagnosis reliably be made. Molecular mechanisms have not been analysed for the subgroup of “autoimmune(-like)” DILI/HDS yet. However, several pathogenetic checkpoints of DILI/HDS in general and AIH are shared. An analysis of these shared mechanisms might hint at relevant molecular processes of “autoimmune(-like)” DILI/HDS.

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In 2015, more than 13 000 people died due to the consequences of liver cirrhosis in Germany. Frequently, relevant liver fibrosis is diagnosed by non-invasive methods (e. g., ultrasound-based measurement of liver stiffness) already in the compensated stage. Following diagnosis of liver fibrosis, a thorough investigation of the underlying chronic liver disease and effective treatment are important to prevent progression to decompensated cirrhosis. Since morbidity and mortality dramatically increase in the decompensated stage (patients may present with jaundice, ascites, hepatic encephalopathy, gastrointestinal bleeding) with an upsurge in 1-year-mortality from 1 - 3.4 % to 20 - 57 %, prophylactic measures to prevent decompensation are indicated. Based on a risk stratification, these measures include propranolol or carvedilol as non-selective betablockers, as well as endoscopic band ligations as primary prophylaxis to prevent variceal bleeding. Because of the high risk for malignant transformation (2 - 8 % per year depending on the underlying etiology), surveillance by liver ultrasound every six months is essential to detect liver cancer in an early stage and to facilitate curative therapy. Currently under debate is the administration of antibiotics to prevent bacterial infections, which commonly trigger acute decompensation. To this regard, studies are not convincing and the risk to induce drug resistance has to be observed. However, health care providers should check the vaccination status and recommend missing vaccinations. The management of compensated liver cirrhosis also includes counseling and potentially also a drug therapy to prevent osteoporosis and muscle wasting. In this review, we will discuss specific prophylactic measures in the management of compensated liver cirrhosis based on the pathophysiological background and central clinical studies. If a patient decompensates despite these prophylactic measures (approximately 15 % of patients with liver cirrhosis per year), liver transplantation has to be discussed as definitive therapy (especially in patients with MELD > 15).

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An imine synthesis was investigated in a nearly isothermal oscillating segmented flow microreactor at different temperatures using non-invasive Raman spectroscopy. Multivariate curve resolution provided a calibration-free approach for obtaining kinetic parameters. The two different multivariate curve resolution approaches, soft and hard modeling, were applied and contrasted, leading to similar results. Taking heat and mass balance into account, the proposed kinetic model was applied for a model-based scale-up prediction. Finally, the reaction was performed in a 0.5 L semi-batch reactor, followed by in-line Raman spectroscopy and off-line gas chromatography analysis. The successful scale-up was demonstrated with a good agreement between measured and predicted concentration profiles. Highlights • Oscillation segmented flow reactor with inline Raman spectroscopy. • Multivariate Curve Resolution with hard and soft constraints. • High quality kinetic model for scale-up predictions. Graphical abstract

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