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Whipple's disease (WD) is a rare and infectious condition leading to multi-organ impairment caused by Tropheryma whipplei (TW), a ubiquitously occurring bacterium. TW can be detected in tissues by histological detection of PAS ("periodic acid-ship reaction")-positive macrophages and by polymerase-chain-reaction (PCR). Clinically, WD is often characterized by diarrhea, abdominal pain, and weight loss. These symptoms are also typical for a flare in Crohn's disease (CD) and, therefore, can lead to fatal misdiagnosis and wrong treatment by using biologics (e.g., anti-TNF-α).We here report a young male patient with pre-existing CD. The patient's symptoms were misinterpreted as a flare of CD and illustrate the multifaceted nature of WD. After intensifying immunosuppressive therapy, the patient developed therapy-refractory diarrhea with several opportunistic infections with a final, fatal outcome.Patients with inflammatory bowel disease (IBD) are not only at risk from infectious complications known with clostridium difficile or cytomegalovirus (CMV); infection with WD should also be ruled out by endoscopy and biopsy before the escalation of the immunosuppressive regime.Der Morbus Whipple (WD) ist eine seltene und infektiöse Erkrankung, die zu Multi-Organbefall führen kann, ausgelöst durch Tropheryma whipplei (TW), ein allgegenwärtig vorkommendes Bakterium. TW kann im Gewebe durch histologischen Nachweis von PAS (“Periodic Acid-Ship Reaction”)-positiven Makrophagen und durch Polymerasekettenreaktion (PCR) nachgewiesen werden. Klinisch ist WD häufig durch Durchfall, Bauchschmerzen und Gewichtsverlust gekennzeichnet. Diese Symptome sind aber auch typisch für einen Schub bei Morbus Crohn und können daher zur Fehldiagnose und falscher Behandlung unter Verwendung von Biologika (z.B. anti-TNF-α) führen.Unser Fallbericht beschreibt einen jungen männlichen Patienten mit bereits bestehendem Morbus Crohn (CD). Die Symptome des Patienten wurden als Schub des M. Crohn falsch interpretiert und veranschaulichen die vielfältige Natur der WD-Infektion. Der Patient entwickelte nach Intensivierung der immunsuppressiven Therapie einen Therapie-refraktären Durchfall sowie zahlreiche opportunistische Infektionen mit tödlichem Ausgang.Patienten mit chronisch-entzündlicher Darmerkrankung (CED) sind nicht nur durch bekannte Infektionen mit Clostridium difficile oder Cytomegalovirus (CMV) gefährdet; eine Infektion mit T. whipplei sollte auch vor Eskalation der immunsuppressiven Therapie mittels Endoskopie und Biopsie ausgeschlossen werden.

Introduction The aim of this study was to investigate patients' preferences regarding the evolving treatment landscape in Crohn's disease (CD) and ulcerative colitis (UC) based on a discrete choice experiment. Methods Eligible patients (aged 18 years or older) had a confirmed diagnosis of CD or UC and were willing and able to participate in telephone interviews. The survey design is based on a prior literature review, a pilot study, and clinical expert discussions. Preferences related to clinical and practical features of advanced therapies, like tumor necrosis factor alpha inhibitors, anti-integrins, anti-interleukins, and Janus kinase inhibitors, were assessed. Patients were asked to choose between two different hypothetical treatment alternatives visualized in up to 11 choice scenarios. Based on these choices, the relative importance of treatment characteristics was derived from regression coefficients estimated by a conditional logit model. Results Of the 291 patients included, 219 (75%) were eligible for this analysis. Among the evaluated attributes in CD, 1-year remission rate was ranked highest, with 42.3% relevance for the overall decision. The second most important attribute was the frequency of serious adverse events (AE) (25.1%), followed by sustained remission over 2 years (17.8%). Lower importance was assigned to the administration mode (14.6%) and none to the frequency of non-serious AE (0.1%). In UC, preferences were driven by efficacy (25.3% for mucosal healing; 23.4% for corticosteroid-free remission) and the frequency of serious AE (18.3%), followed by the administration mode (18.1%). Also, non-serious AE were classified as relevant factors for decision-making (10.7%), while maintaining remission for at least 2 years showed no significant impact (4.4%). Conclusion For both indications, efficacy outcomes were rated most important, followed by the frequency of serious AE. Variations were mainly found in the evaluation of non-serious AE and sustained remission. Considering patient preferences may improve the effectiveness of available therapies for moderate to severe CD and UC.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have emerged as leading causes of chronic liver diseases worldwide. ALD and NAFLD share several pathophysiological patterns as well as histological features, while clinically, they are distinguished by the amount of alcohol consumed daily. However, NAFLD coexists with moderate alcohol consumption in a growing proportion of the population. Here, we investigated the effects of moderate alcohol consumption on liver injury, lipid metabolism, and gut microbiota in 30 NAFLD-patients. We anonymously assessed drinking habits, applying the AUDIT- and CAGE-questionnaires and compared subgroups of abstainers vs. low to harmful alcohol consumers (AUDIT) and Cage 0–1 vs. Cage 2–4. Patients who did not drink any alcohol had lower levels of γGT, ALT, triglycerides, and total cholesterol. While the abundance of Bacteroidaceae, Bifidobacteriaceae, Streptococcaceae, and Ruminococcaceae was higher in the low to harmful alcohol drinking cohort, the abundance of Rikenellaceae was higher in the abstainers. Our study suggests that even moderate alcohol consumption has an impact on the liver and lipid metabolism, as well as on the composition of gut microbiota.

Transjugular intrahepatic portosystemic shunt (TIPS) is one of the main treatment options in patients with decompensated liver cirrhosis but is still associated with partly severe complications. For adequate patient selection, prognostic parameters are of crucial importance. The liver maximum capacity (LiMAx) breath test measures enzymatic liver function and could potentially represent an efficient prognostic marker. We therefore aimed to assess the role of LiMAx in predicting survival of TIPS patients in a prospective analysis. LiMAx was performed for patients who underwent TIPS implantation between October 2016 and February 2018. Associations with transplant-free survival after 24 weeks were assessed by logistic regression. A total number of 30 patients were included, of whom seven received liver transplantation (N = 2) or died (N = 5) during follow-up. LiMAx values after (P = 0.01, OR = 1.24, 95% CI = 1.04–1.47) and before (P = 0.03, OR 1.21, 95% CI = 1.02–1.43) TIPS implantation and MELD score (P = 0.03, OR = 0.79, 95% CI = 0.63–0.98) were significantly associated with transplant-free survival according to univariate logistic regression. In AUROC analysis, LiMAx at day one after TIPS (sensitivity 85.7%, specificity 78.3%, AUROC 0.85, cut-off ≤ 165 µg/kg/h), LiMAx value at the day before TIPS (sensitivity 100%, specificity 73.9%, AUROC 0.82, cut-off ≤ 205 µg/kg/h) and MELD score (sensitivity 71.4%, specificity 73.9%, AUROC 0.82, cut-off ≥ 15) had the highest prognostic accuracy. LiMAx values prior and after TIPS procedure seem to be good prognostic parameters regarding prediction of transplant-free survival of patients undergoing TIPS implantation.

Background and Aims An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNF alpha agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analysed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis. Methods This cross-sectional study evaluated patients with established CD, with and without anti-TNF alpha treatment, analysing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP) and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analysed gut microbiota composition and mediators of bile acid (BA) signalling via stool and serum analysis. Results Patients on anti-TNF alpha treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNF alpha therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNF alpha treatment. Low abundance of Firmicutes was associated with higher triglyceride levels. Conclusions Anti-TNF alpha treatment is associated with reduced steatosis, lower triglyceride levels, alterations in FXR-signalling (eg FGF19) and microbiota composition in CD. PM is supported by the German Research Foundation/Deutsche Foschungsgemeinschaft-(MA-6864/1-1) and the European Association for the Study of the Liver (EASL). SS received funding from the EASL and the German Liver Foundation (Deutsche Leberstiftung). AL is supported by the funds of the European Commission through the 'European funds for regional development' (EFRE) as well as by the regional Ministry of Economy, Science, and Digitalization as part of the Autonomie im Alter research group. FJC received funding from MINECO Retos (SAF2016-78711), EXOHEP-CM (S2017/BMD-3727), NanoLiver (CM Y2018/NMT-4949), ERAB (Ref. EA 18/14), AMMF (2018/117), UCM (25-2019), COST Action (CA17112), RYC (2014-15242) and Gilead Liver Research 2018. AC is supported by the Wilhelm-Laupitz-Foundation. LPB is supported by the German Research Foundation/Deutsche Foschungsgemeinschaft (BE-3967/3-1) and the Dr Werner Jackstaedt-Foundation.

Co-infection of Hepatitis B (HBV) and Delta viruses (HDV) represent the most severe form of viral hepatitis. While treatment with pegylated Interferon alpha (PEG-IFNα) is well established, therapy with nucleoside or nucleotide analogues (NA) has been a matter of debate. We aimed to investigate the role of NA treatment in a well-defined single centre cohort.In a retrospective approach, we observed 53 HDV RNA positive and/or anti-HDV-positive patients recruited at a German referral centre between 2000 and 2019. Patients were followed for at least 3 months (mean time of follow up: 4.6 years; range: 0.2-14.1 years). Patients who had liver transplantation or hepatocellular carcinoma at the time of presentation were excluded. 43% (n = 23) were treated with NA, 43% (n = 23) received IFNα-based therapies and 13% (n = 7) were untreated.Liver cirrhosis was already present in 53% (28/53) of patients at first presentation. During follow-up, liver-related endpoints developed in 44% of all patients (n = 23). NA-treatment was associated with a significantly worse clinical outcome (P = .01; odds ratio [OR] = 4.92; CI = 1.51-16.01) compared to both, untreated (P = .38; OR = 0.46; CI = 0.80-2.61) and IFNα-based-treated patients (P = .04; OR = 0.29; CI = 0.89-0.94) in univariate logistic regression analysis. HBsAg levels declined by more than 50% during NA-based therapy in only 7 cases (7/23; mean time: 3.6 years; range: 0.8-8.5 years) and during IFNα-based therapy in 14 cases (14/23; mean time: 2.8 years, range 0.7-8.5 years). HDV RNA became undetectable during follow up in 30% of patients receiving NA alone (7/23; mean time: 5.0 years; range: 0.6-13.5 years), in 35% of patients receiving IFNα-based therapy (8/23; mean time: 2.9 years, range: 0.3-7.6 years).The effect of NA in patients with HBV/HDV co-infection is limited. Treatment with NA was associated with a higher likelihood of clinical disease progression. Interferon alpha therapy was beneficial in reducing liver complications and improves long-term outcome. CA extern

Background Transjugular intrahepatic portosystemic shunt (TIPS) is indicated in patients with decompensated portal hypertension (PH). Hepatic venous pressure gradient (HVPG) is considered gold standard for assessment of PH. Because HVPG measurement is invasive, non-invasive methods for evaluating severity of PH are warranted. Patients and methods We retrospectively correlated spleen stiffness as measured by FibroScan with HVPG in patients who underwent TIPS. Twenty-four patients with spleen stiffness measurement (SSM) one day before (D-1), one day after (D + 1) and 28 days after TIPS (D + 28) were included. Results SSM was positively correlated with pre-TIPS HVPG (HVPG 24 mmHg, median SSM: 75.0 ± 6.2 kPa; p 2 = 0.72; p Conclusions Our study highlights the utility of SSM as non-invasive tool in patients with chronic liver disease in evaluating degree of PH potentially offering a confirmable additional parameter in surveillance of patients undergoing TIPS procedure.

Background and Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice in decompensated portal hypertension. TIPS revision due to thrombosis or stenosis increases morbidity and mortality. Our aim was to investigate patient- and procedure-associated risk factors for TIPS-revision. Patients and Methods: We retrospectively evaluated 189 patients who underwent the TIPS procedure. Only patients who required TIPS revision within 1 year (Group I, 34 patients) and patients who did not require re-intervention within the first year (Group II [control group], 54 patients) were included. Results: Out of 88 patients, the majority were male (69.3%) and mean age was 56 ± 11 years. Indications for TIPS were refractory ascites (68%), bleeding (24%), and Budd-Chiari syndrome (8%). The most frequent liver disease was alcohol-induced cirrhosis (60%). Forty-three patients (49%) received bare and 45 patients (51%) covered stents, thus resulting in reduction of hepatic venous pressure gradient (HVPG) from 19.0 to 9.0 mm Hg. When comparing patient- and procedure-related factors, the type of stent (p < 0.01) and interventionalist’s experience (number of performed TIPS implantations per year; p < 0.05) were the only factors affecting the risk of re-intervention due to stent dysfunction, while age, gender, indication, Child-Pugh, and model of end-stage liver disease score, platelet count, pre- and post-HVPG, additional variceal embolization, stent diameter, and number of stents did not significantly differ. Conclusion: Patients undergoing TIPS procedure should be surveilled closely for shunt dysfunction while covered stents and high-level experience are associated with increased ­patency.

Here we report a case of a 68-year-old woman who presented to our centre for further evaluation of elevated liver function tests (LFTs). She reported a 20-year history of elevated liver enzymes. She had known dyslipidaemia (low-density lipoproteincholesterol of 232 mg/dL) and was treated with atorvastatin and ezetimibe. Diabetes and cardiovascular events were not reported. Family history was suspected as a factor as her father died due to heart attack and also had a history of elevated LFTs; her brother died due to cryptic cirrhosis. The patient underwent multiple liver biopsies in several liver centres (1996, 1999, 2003 and 2008). Histology results similarly demonstrated microvesicular fatty liver with minimal fibrosis. In line with the patient’s metabolic profile, her case was treated as non-alcoholic steatohepatitis (NASH)-related although histological …

In their Letter to the Editor, Wei et al . address on the role of spleen stiffness measurement (SSM) for predicting the late recurrence (>24 months post-surgery) of hepatocellular carcinoma (HCC) after resection (1). They comment on a recently published manuscript by Marasco and colleagues, who could show that spleen stiffness measured by transient elastography was the only predictor of late HCC recurrence after surgery (2).

BACKGROUND: Guidelines regarding treatment for autoimmune hepatitis (AIH) favour two strategies for azathioprine (AZA) introduction: concurrent with steroids at induction or delayed by 2-4 weeks. The safety and efficacy of both strategies have been unexplored. METHODS: We established a cohort of 900 AIH patients from 12 centres in 7 European countries. There were 631 patients who used AZA as part of the therapeutic regimen. We distinguished two groups: patients with early AZA (

Cholangitis in patients with ulcerative colitis (UC) can lead to misdiagnosis of primary sclerosing cholangitis (PSC). Furthermore, it can mimic cholangiocellular carcinoma, which also can lead to inappropriate and potentially harmful treatment of the patient. An 18-year-old male patient with known UC presented with pain in his right upper abdomen and elevation of the cholestatic liver enzymes (alkaline phosphatase: 197 U/L, γ-glutamyltransferase: 229 U/L) and increased inflammatory parameters (leukocytosis and CrP of 13.6 mg/L). Magnetic resonance cholangiopancreatography revealed unclear stenosis in the bifurcation of the main hepatic bile duct as well as in the prepapillary bile duct. Ultrasound (US) examination and endoscopic retrograde cholangiopancreatography showed dilatation of the intra -and extrahepatic bile ducts, which raised the suspicion of PSC. US image with dilated intra- and extrahepatic dilatation of the bile duct was also suggestive for autoimmune cholangitis. However, serum analysis revealed an elevated soluble interleukin-II receptor (1,305 U/mL), while immunoglobulin G4 was within normal ranges. Liver biopsy demonstrated hepatic inflammation and presence of granulomatous cells within the portal fields – convenient to sarcoidosis. After starting treatment with steroids, we observed a rapid clinical response with improvement of the dilated bile ducts and decrease of the initially elevated cholestatic liver enzymes. Sarcoidosis within the bile duct is a rare condition. Steroids are the treatment of choice and – along with the histology – are furthermore helpful to differentiate between several potential differential diagnoses like IgG4 cholangitis, primary biliary cholangitis, or PSC.

Aim: To assess the diagnostic accuracy of liver maximum capacity (LiMAx®) test compared to transient elastography (TE) and serum biomarkers for the noninvasive detection of different stages of liver fibrosis and cirrhosis. Patients and Methods: We retrospectively correlated LiMAx®, TE, aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) score with histological specimens in 102 patients with chronic liver disease (CLD) who underwent liver biopsy (either percutaneously or via mini-laparoscopy) at the University Clinic of Essen between 10/2016 and 12/2017. Results: Median LiMAx® values showed a tendency to decrease in accordance with increasing histological degree of fibrosis based on the Desmet scoring system (F0: 446.5 [381.0–592.5] µg/h/kg, F1: 405.0 [343.0–547.0] µg/h/kg, F2: 337.0 [250.0–394.0] µg/h/kg, F3: 281.0 [262.0–364.0] µg/h/kg, and F4: 181.5 [130.0–256.5] µg/h/kg. Furthermore, ­LiMAx® was superior to TE, FIB-4, AAR, and APRI in detecting different stages of fibrosis, while Spearman’s rank correlation test showed a statistically significant association of –0.68, 0.62, 0.61, 0.46, and 0.42, respectively. However, the combination of TE and LiMAx® had the highest diagnostic accuracy in detecting liver cirrhosis (sensitivity 88.9%, specificity 84.6%, Youden index 0.735). Conclusion: Enzymatic liver function measured by LiMAx® showed strong correlation with histology in patients with CLD irrespective of its underlying etiology and was superior to TE and serum biomarkers, possibly making it useful as a novel and noninvasive tool for the determination of hepatic disease severity.

© 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.

Background/Aims: Portal hypertension (PH) is a common complication of chronic liver disease and results in esophageal and gastric variceal bleeding, which is associated with a high mortality rate. Measurement of the hepatic venous pressure gradient (HVPG) is considered the gold standard for diagnosing PH and estimating the risk of varices and bleeding. In contrast, upper gastrointestinal (GI) endoscopy (UGE) can reliably demonstrate the presence of varices and bleeding. Both measures are invasive, and HVPG is mainly restricted to tertiary centers. Therefore, the development of noninvasive methods of assessing the severity of PH and the risk of variceal bleeding is warranted. Methods: We retrospectively examined the correlation of spleen stiffness (SSM) and liver stiffness measurements (LSM) with the incidence of variceal bleeding among 143 patients who underwent combined liver and spleen elastography between 2013 and 2015. Results: For 19 of 103 patients (16.8%), upper GI variceal bleeding was diagnosed and treated endoscopically. The median SSM of all patients was 35.3 kilopascals (kPa); the median LSM, 11.7 kPa. Patients with previous bleeding episodes had significantly higher SSM (75.0 kPa) and LSM (37.3 kPa) than those without a history of bleeding (SSM, 30.6 kPa; LSM, 8.2 kPa; p < 0.0001). Seventy-five patients (66.4%) underwent UGE in addition to SSM and LSM: 25 with no esophageal varices (EVs; SSM, 29.5 kPa; LSM, 11.4 kPa), 16 with EV grade 1 (SSM, 35.9 kPa; LSM, 33.4 kPa), 21 with EV grade 2 (SSM, 67.8 kPa; LSM, 27.0 kPa) and 13 with EV grade 3 (SSM, 75.0 kPa; LSM, 26.3 kPa). No statistically significant differences were found between respective grades of EV but were found between the presence and absence of varices. At a calculated cutoff level of 42.6 kPa (with application of 95% CI), SSM had sensitivity of 89% and specificity of 64% in determining the risk of bleeding, with a negative predictive value (NPV) of 0.97 (LSM sensitivity, 84%; LSM specificity, 80%; LSM NPV, 0.96 at LSM cutoff level of 20.8 kPa). When LSM (cutoff level, 20.8 kPa) and SSM (cutoff level, 42.6 kPa) were combined, the NPV was 1 (sensitivity, 100%; specificity, 55%). Conclusion: SSM and LSM as determined by FibroScan (a noninvasive method of detecting PH) is positively correlated with upper GI variceal bleeding (optimal SSM cutoff level, 42.6 kPa; optimal LSM cutoff level, 20.8 kPa). No patients with both SSM and LSM below cutoff levels had a history of bleeding complications.

Background/Aims: Autoimmune hepatitis (AIH) is a relatively rare cause of liver dysfunction and may lead in some cases to acute liver failure (ALF). The aim of our study was to evaluate the clinical course and outcome of patients with AIH-induced ALF. Methods: We retrospectively enrolled 32 patients with AIH-induced ALF and 93 age- and sex-matched patients with chronic AIH (cAIH) who were enrolled at the University Clinic Essen from 1988 to 2014. All ALF patients were treated with corticosteroids after diagnosis. Results: Overweight, higher γ-globulin levels, the absence of anti-smooth muscle antibodies and human leukocyte antigen (HLA) B8 and the presence of anti-mitochondrial antibodies and HLA DR7 were risk factors for an ALF vs chronic hepatitis manifestation of AIH. Liver histology was significantly more often typical for AIH in an ALF setting than in cAIH. The spontaneous survival rate was 91% and 97% in ALF and cAIH patients, respectively, at 6 months after diagnosis and only 1 patient in the ALF group developed sepsis under therapy. Conclusion: Liver biopsy in an AIH-mediated ALF setting was both safe and effective in diagnosing AIH. Corticosteroid therapy was not associated with high mortality or sepsis. Our findings suggest that corticosteroid treatment of AIH-mediated ALF may improve the outcome.

Aim To investigate potential triggering factors leading to acute liver failure (ALF) as the initial presentation of autoimmune hepatitis (AIH). METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients (9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver (AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data (liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and fnally, outcome of our patients. RESULTS The majority of patients with ALF were female (84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody (LKM). We could identify potential triggering factors in 26/52 (50.0%) of previously healthy patients presenting ALF as their frst manifestation of AIH. These were drug-induced ALF (57.7%), virus-induced ALF (30.8%), and preceding surgery in general anesthesia (11.5%), respectively. Unfortunately, 6 out of 52 patients (11.5%) did not survive ALF and 3 patients (5.7%) underwent liver transplantation (LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore (P < 0.001), age (P < 0.05), creatinine (P < 0.01), and finally, ALT-values (P < 0.05) reached statistical signifcance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome. OA gold - CA Kahraman

Patients chronically infected with hepatitis C virus (HCV) frequently develop mixed cryoglobulinemia (MC), a monoclonal expansion of immunoglobulin M (IgM)+ autoreactive B cells, and also have an increased B-cell lymphoma risk. Whether HCV infection also impacts the B-cell compartment and the B-cell receptor repertoire in patients not affected by MC or lymphomas is poorly understood. Flow cytometric analysis of peripheral blood B cells of 30 MC-negative HCV-infected patients and 15 healthy controls revealed that frequencies of class-switched memory B cells were increased in the patients, whereas frequencies of transitional and naive B cells were decreased. For 22 HCV+ patients and 7 healthy controls, we performed high-throughput sequencing of immunoglobulin heavy chain VDJ rearrangements of naive, mature CD5+, IgM+ memory, and class-switched memory B cells. An increased usage of several IGHV genes, including IGHV1-69 and IGHV4-59, which are closely linked to MC and HCV-associated lymphomas, was specifically seen among IgM+ memory B cells of the patients. Moreover, many, and partly very large, expanded clones were seen predominantly among IgM+ memory B cells of all HCV-infected patients analyzed. Thus, chronic HCV infection massively disturbs the B-cell compartment even in patients without clinically detectable B-cell lymphoproliferation and generates many large B-cell clones, especially among non-class-switched memory B cells. Because B-cell clones in MC and lymphomas derive from this B-cell subset, this establishes IgM+ memory B cells as a general target of lymphoproliferation in HCV+ patients, affecting apparently all patients.