The significance of resection margins on R0 results in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma with an increasing incidence worldwide. Surgical resection is still the only potential cure, and survival rates are dismal due to disease relapse after resection and/or metastatic disease. Positive resection margins are associated with recurrence, with conflicting studies regarding the benefits of wide resection margins to reduce recurrence rates. METHODS: 126 patients with an R0 resection treated with hepatic surgery for intrahepatic cholangiocarcinoma at the Surgical Department at the Medical University Centre Essen, Germany were identified in a database and retrospectively analysed. Patients were grouped into three groups according to margin width, <1 mm (very narrow margin width) 1-5 mm (narrow margin width) and >5 mm (wide margin width). Epidemiological as well as perioperative data was analysed, and a univariate analysis as well as Kaplan-Meier plots carried out to investigate recurrence-free and overall survival. RESULTS: Wider resection margins did not lead to better recurrence-free survival. A wider resection margin >5 mm was not significantly associated with improved overall survival. Positive lymph nodes (HR 2.50, 95% CI 1.11-5.61, p=0.027) and non-anatomic resections (HR 2.06, 95% CI 1.13-3.75, p=0.019) are significantly associated with poorer overall survival. Regarding recurrence-free survival, V2 vascular invasion was the only risk factor statistically significantly associated with poorer recurrence-free survival (HR 8.83, 95% CI 0.85-2.83, p=0.005). CONCLUSION: Resection margins did not have a significant impact on disease free survival or overall survival following hepatic resection for intrahepatic cholangiocarcinoma. Non-anatomical resections, lymph node and vascular invasion all significantly impacted oncological outcomes.

Idiosyncratic Drug-Induced Liver Injury in a Healthy Patient following PCSK9-Inhibitor Injection.

Background: Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion: This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge.

Prognostic factors of poor postoperative outcomes in gastrectomies.

Background: Gastric cancer is one of the most common cancers worldwide and is the third most common cause of cancer related death. Improving postoperative results by understanding risk factors which impact outcomes is important. The current study aimed to compare immediate perioperative outcomes following gastrectomy. Methods: 302 patients following gastric resections over a 10-year period (January 2009-January 2020) were identified in a database and retrospectively analysed. Epidemiological as well as perioperative data was analysed, and a univariate and multivariate analysis performed to identify risk factors for in-hospital mortality. Results: In general, gastrectomies were mainly performed electively (total vs. subtotal 95% vs. 85%, p = 0.004). Patients having subtotal gastrectomy needed significantly more PRBC transfusions compared to total gastrectomy (p = 0.039). Most emergency surgeries were performed for benign diseases, such as ulcer perforations or bleeding and gastric ischaemia. Only emergency surgery was significantly associated with poorer overall survival (HR 2.68, 95% CI 1.32-5.05, p = 0.003). Conclusion: In-hospital mortality was comparable between total and subtotal gastrectomies. Only emergency interventions increased postoperative fatality risk.

One-year Allograft and Patient Survival in Renal Transplant Recipients Receiving Antiplatelet Therapy at the Time of Transplantation.

BACKGROUND: Antiplatelet therapy is common in patients on the waiting list for kidney transplantation. OBJECTIVE: To evaluate the incidence of post-operative bleeding in patients with antiplatelet therapy undergoing kidney transplantation and analyze the impact on the outcome. METHODS: We studied all patients with concomitant antiplatelet therapy undergoing kidney transplantation in our center from January 2007 to June 2012. Data were collected by chart review. Univariate and multivariate logistic regression and Cox proportional hazard model were used to identify risk factors for the long-term outcome. RESULTS: Of 744 kidney transplant recipients during the study period, 161 received oral antiplatelet therapy and were included in the study. One-third of the patients demonstrated signs of bleeding, half of which requiring surgical treatment. Coronary artery disease, deceased donor kidney transplantation, and dual antiplatelet medication were independent risk factors for post-operative bleeding. One-year allograft survival was significantly better in the non-bleeding group (91.4% vs 75.9%, p=0.023). Multivariable analysis found that post-operative bleeding, recipient age, and biopsy-proven rejection were independent risk factors for graft survival. Recipient age and biopsy-proven rejection were also identified as independent risk factors for patient survival. CONCLUSION: This analysis indicated a high risk for post-operative bleeding in renal transplant patients under antiplatelet therapy. The associated negative effect on allograft survival underscored the need to reduce any risk factors for post-operative bleeding.

Assessment of standard laboratory tests and rotational thromboelastometry for the prediction of postoperative bleeding in liver transplantation.

BACKGROUND: Perioperative bleeding remains a major challenge in liver transplantation. We aimed to compare standard laboratory tests with thromboelastometry (ROTEM ® ) with regard to their ability to predict postoperative non-surgical bleeding. METHODS: Data from 243 adult liver transplant recipients from January 2012 to May 2014 were evaluated retrospectively. Upon admission to the intensive care unit, coagulation status was assessed using standard laboratory tests [prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and platelet count] and ROTEM ® whole blood coagulation assays. Bleeding was defined as transfusion of ≥ 3 units of red blood cells or reoperation for non-surgical bleeding within 48 h after transplantation. Coagulation test results were analysed using receiver operating characteristics (ROC) in order to identify variables predictive of postoperative bleeding. Coagulation management was based on ROTEM ® -guided factor concentrate treatment. RESULTS: The overall incidence of bleeding was 12.3% ( n =30). Twenty-three (9.5%) patients underwent reoperation and seven (2.9%) received ≥3 units of red blood cells and non-operative management. Standard laboratory tests predictive of postoperative bleeding were aPTT and PT [area under the ROC curve (AUC) 0.688 and 0.623, respectively]. Tests predictive of bleeding with ROTEM ® were CT EXTEM , CFT INTEM , A10 FIBTEM , and MCF FIBTEM , with AUCs of 0.682, 0.615, 0.615, and 0.611, respectively. Fibrinogen concentration, platelet count, and other ROTEM ® variables failed to demonstrate predictive value for postoperative bleeding (AUC <0.6). Dialysis-dependent kidney failure, 30 day mortality, and median model for endstage liver disease score were all significantly higher in bleeding patients. CONCLUSIONS: Although both postoperative standard laboratory tests and ROTEM ® assays could identify patients at risk for postoperative bleeding, ROTEM ® assays demonstrated a greater predictive value for impaired fibrinogen polymerization-related coagulopathy.

[Coagulation management in patients with liver disease]. / Gerinnungsdiagnostik und -therapie bei Leberinsuffizienz.

BACKGROUND: End-stage liver disease is associated with complex alterations in hemostasis. Whereas prognosis is essentially affected by life-threatening bleeding complications in some patients, others, especially those with cholestatic liver diseases, suffer from thromboembolic complications. Standard laboratory values (SLVS; prothrombin time, activated partial thrombin time, platelet count) cannot sufficiently reflect the altered balance of pro- and anticoagulatory factors. Moreover, a couple of studies indicated that SLVS are not able to predict bleeding complications in patients with acute liver failure or decompensated liver cirrhosis. DIAGNOSIS AND THERAPY: Use of bed-side coagulation diagnostics such as thrombelastometry/-graphy, detection of thrombocyte function by multiple electrode aggregometry and selective measurement of single factors allows a targeted and causal therapy of hepatic coagulopathies especially in the context of bleeding complications or surgical interventions. In recent years, coagulation management guided by these new devices has contributed to a reduction in transfusion of allogenic blood products, which may be associated with undesirable side effects. DISCUSSION: The current review summarizes the complex pathophysiological alterations of hemostasis associated with advanced liver insufficiency and discusses recent upcoming diagnostics and coagulation management in this patient cohort.

[Drug-induced liver injury as predominant cause of acute liver failure in a monocenter study]. / Medikamentös-toxische Schädigung als wichtigste Ätiologie des akuten Leberversagens.

BACKGROUND AND AIM: Clinical course and mortality of acute liver failure (ALF) are determined by its causes. Traditionally, fulminant hepatitis B infection (HBV) was thought to be the predominant etiology of ALF in Germany. However, recent studies, conducted in American and European cohorts pointed to drug-induced liver injury (DILI) as the major cause. Aim of this study was to identify currently predominant etiologies of ALF in a monocenter study at a leading transplant center in Germany. PATIENTS AND METHODS: The data of 161 patients admitted with ALF from 1/2002 to 12/2012 were analyzed retrospectively. All patients fulfilled the criteria of the "Acute Liver Failure Study Group Germany" (international normalized ratio (INR) ≥ 1.5, hepatic encephalopathy ≥ stage 1). RESULTS: DILI was the leading cause of ALF in this cohort. About 20 % of ALF patients with DILI died or received liver transplantats. Mortality rate was highest in ALF patients with unknown etiology and those without specific therapy available. CONCLUSIONS: In Europe ALF etiologies exhibit a North-South divide. In Germany the most common cause for ALF is idiosyncratic pharmacological intoxication followed by acute hepatitis B.

[Liver parameters in intensive care medicine]. / Leberparameter in der Intensivmedizin.

Elevated liver function tests in ICU-bound patients are associated with a greater risk of mor-tality. Chronic liver diseases as well as acute events and complications of therapy are among the causes. The disorder could further be investigated by assessment of liver cell integrity markers (AST, ALT and GLDH), cholestasis parameters -(bilirubin, GGT, ALP) and liver synthethic function (albumin, coagulation profile). Ultrasound and elastography are cheap and mobile options to evaluate chronic liver disease, cholestasis or perfusion of the liver. The interpretation of the results should include the medical history on the ICU. Liver injury could be due to septic or isch-aemic complications as well as toxic side effects or parenteral nutrition. The main therapeutic option is to identify the cause of the liver dysfuntion and to eliminate it as far as possible.

Limits and pitfalls of haemodynamic monitoring systems in liver transplantation surgery.

Cardiac output (CO) and other hemodynamic variables measured during liver transplantation are often obtained by pulmonary artery catheter (PAC) and in many centers by the transthoracic thermodilution method and/or intraoperative transesophageal echocardiography (TEE). Newer non-invasive technology, such as the PiCCO(®) system, the LiDCO(®) Plus monitor, and the FloTrac/Vigileo(®), have been proposed as more reflective of ongoing hemodynamic response to intraoperative manoeuvres. In contrast to the standard "semicontinuous" thermodilution method, which gives information over a set period of time, the new monitoring systems use a different time period or measure over a running several beat average. It has been stated that algorithms based on arterial pulse contour analysis can potentially facilitate rapid diagnosis and prompt therapeutic interventions. However, as the use of these technologies has spread, so has the understanding of their limitations. This has led to an increased scepticism among the previously enthusiastic "pioneering" practitioners. Given the poor agreement reported in various studies on liver transplant surgery between PAC and the new "calibrated" and "uncalibrated"-derived measurements, multicenter trials aiming at evaluating the performance of the non-invasive methods in different hemodynamic conditions and dedicated monitoring-driven treatment protocols are necessary.

Acute management of refractory variceal bleeding in liver cirrhosis by self-expanding metal stents.

BACKGROUND AND AIMS: Current treatment strategies of variceal bleeding (VB) include banding and sclerotherapy. However, up to 10% of bleeding events remain refractory to standard therapy with high mortality. With this study, we aimed to evaluate the implantation of self-expanding metal stents (SEMS) for the management of therapy-refractory variceal bleeding. PATIENTS AND METHODS: Eight cirrhotic patients who presented to our unit with a total of 9 refractory bleeding events were treated by SEMS placement. RESULTS: Stenting resulted in immediate hemostasis in all cases without recurrent bleeding with SEMS in situ. After stabilization, 1 patient was treated by transjugular intrahepatic portosystemic shunt (TIPS) and after the second bleeding episode by TIPS dilation. One patient underwent orthotopic liver transplantation (OLT). The remaining patients were treated with standard drug regimens to reduce portal pressure. The SEMS were removed after a median of 11 days. No acute hemorrhage was noted on stent retrieval. While no early rebleeding occurred in the patients after TIPS implant, TIPS dilation or OLT, 3 out of 5 patients on conservative treatment experienced recurrence of VB within 9 days after SEMS removal. CONCLUSIONS: SEMS placement sufficiently stops hemorrhage in refractory VB. Due to the high rebleeding rate after conservative treatment alone following SEMS removal, this procedure may be utilized as a mere bridging method. Additional interventional and/or surgical methods to effectively reduce portal pressure (i.e. TIPS, OLT) should be considered. Further studies to evaluate the optimum treatment algorithm of refractory esophageal VB are warranted.

Outbreak due to a Klebsiella pneumoniae strain harbouring KPC-2 and VIM-1 in a German university hospital, July 2010 to January 2011.

We describe the epidemiology and characteristics of the pathogen and patients (n=7) associated with an outbreak of a carbapenem-resistant Klebsiella pneumoniae (CRKP) strain in a German university hospital from July 2010 to January 2011. Species identification and detection of carbapenem resistance were carried out using standard microbiological procedures. Carbapenemases were detected by phenotypic methods and specific polymerase chain reactions (PCRs). DNA fingerprinting profiles were performed with repetitive sequence-based PCR. Medical records of colonised or infected patients were retrospectively reviewed. Antibiotic resistance profiles, PCR-specific amplification products and genotyping demonstrated that the outbreak occurred because of the spread of a single CRKP clone harbouring both KPC-2 and VIM-1. Five of the seven patients had invasive infections with the CRKP strain; the deaths of four of them were directly related to the infection. Early implementation of infection control interventions brought about efficient containment of further cross-transmission. Rapid dissemination of carbapenemase-producing Enterobacteriaceae is a serious concern in patient care and is a problem that has emerged in western Europe.

Efficacy and safety of linezolid in liver transplant patients.

Bacterial infections are the main cause of death within the first year after liver transplantation, and the increased incidence of multidrug-resistant gram-positive pathogens has created a major challenge in the treatment of these patients. Linezolid, the first US Food & Drug Administration-approved oxazolidinone, offers a valuable novel treatment option for serious gram-positive infections. Linezolid is relatively non-toxic but prolonged treatment with linezolid was associated with thrombocytopenia. Here we report on the experience of linezolid treatment in adult liver transplant patients, who are at an increased risk for thrombocytopenia because of hypersplenism. From November 2003 until December 2009, we evaluated the clinical course of 46 liver transplant patients (27 male/19 female) in our surgical intensive care unit. For proven or probable gram-positive infection, all patients received linezolid 600 mg intravenously every 12 h. On clinical improvement, treatment was changed to oral linezolid 600 mg twice daily. Treatment duration was 11 ± 7 days. Treatment indications were pneumonia (n = 8), blood stream infection (n = 30), and surgical site/abdominal infection (n = 3). Clinical cure was achieved in 43 out of 46 patients. During the course of treatment, no cases of severe thrombocytopenia occurred and a statistically significant platelet count increase was seen from day 1 (110 ± 73/nL) to day 7 (165 ± 116/nL) and day 14 (180 ± 140/nL). We did not observe any further adverse events, especially no severe neurological complications (e.g., serotonin syndrome) or signs of lactate acidosis. Two patients died from uncontrolled vancomycin-resistant Enterococcus faecium sepsis with septic shock and one due to uncontrolled methicillin-resistant Staphylococcus aureus pneumonia. These deaths were considered to be unrelated to linezolid treatment, and linezolid was regarded as the optimal treatment choice in these patients. A subgroup analysis of patients treated for >14 days revealed no statistically significant differences when compared with patients on shorter treatment. In particular, no cases of thrombocytopenia occurred during longer treatment. In conclusion, linezolid is a safe and effective treatment for adult liver transplant patients with gram-positive infections.

Glutathione-S-transferase subtypes α and π as a tool to predict and monitor graft failure or regeneration in a pilot study of living donor liver transplantation.

OBJECTIVE: Glutathione-S-transferase (GST) subtype α and π are differentially expressed in adult liver tissue. Objective of the study was if GST α and π may serve as predictive markers for liver surgery, especially transplantations. METHODS: 13 patients receiving living donor liver transplantation (LDLT) and their corresponding donors were analyzed for standard serum parameters (ALT, AST, γGT, bilirubin) as well as GST-α and -π before LDLT and daily for 10 days after LDLT. Patients (R) and donors (D) were grouped according to graft loss (R1/D1) or positive outcome (R2/D2) and above named serum parameters were compared between the groups. RESULTS: R1 showed significantly increased GST-α and significantly lower GST-π levels than R2 patients or the donors. There was a positive correlation between GST-α and ALT, AST as well as bilirubin and a negative correlation to γGT. However, γGT correlated positively with GST-π. Graft failure was associated with combined low GST-π levels in donors and their recipients before living donor liver transplantation. CONCLUSION: Our data suggest that high GST-α serum levels reflect ongoing liver damage while GST-π indicates the capacity and process of liver regeneration. Additionally, GST-π may be useful as marker for optimizing donor and recipient pairs in living donor liver transplantation.

Infectious complications in the early postoperative period in liver transplant patients.

Liver transplantation (LTx) is a technically well established procedure in acute and in end-stage liver diseases. However, opportunistic infections remain one of the important complications in short and long-term outcome of LTx patients. Bloodstream and pulmonary infections are the major cause of death in the first year following liver transplantation. Due to extended use of chinolons and third generation cephalosporines there is a shift towards multidrug-resistant bacteria including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and extended b-lactamase-producing gram negative rods. Fungal infections are mainly due to Candida spp. Viral infections, such as with cytomegalovirus, human herpesvirus 6, herpes simplex virus, and Epstein-Barr virus infections are another major cause of morbidity in patients receiving solid organ transplants, including liver transplant patients. Studies of infection following LTx are necessary to improve management and to provide a better outcome after LTx. This review focuses on the most important bacterial, fungal and viral infections in LTx patients.

A Rare Case of Propofol-Induced Acute Liver Failure and Literature Review.

The incidence of drug-induced acute liver failure is increasing. A number of drugs can inhibit mitochondrial functions, alter ß-oxidation and cause accumulation of free fatty acids within the hepatocytes. This may result in hepatic steatosis, cell death and liver injury. In our case, propofol, an anesthetic drug commonly used in adults and children, is suspected to have induced disturbance of the mitochondrial respiratory chain, which in consequence led to insufficient energy supply and finally liver failure. We report the case of a 35-year-old Caucasian woman with acute liver failure after anesthesia for stripping of varicose veins. Liver histology, imaging and laboratory data indicate drug-induced acute liver failure, presumably due to propofol. Hepatocyte death and microvesicular fatty degeneration of 90% of the liver parenchyma were observed before treatment with steroids. Six months later, a second biopsy was performed, which revealed only minimal steatosis and minimal periportal hepatitis. We suggest that propofol led to impaired fatty acid oxidation possibly due to a genetic susceptibility. This caused free fatty acid accumulation within hepatocytes, which presented as hepatocellular fatty degeneration and cell death. Large scale hepatocyte death was followed by impaired liver function and, consecutively, progressed to acute liver failure.

Attitude of health care professionals to organ donation: two surveys among the staff of a German university hospital.

The persistent shortage of organs for transplantation could be minimized by increasing the number of potential donors. The opinion of the staff of a university hospital toward organ donation is of special interest because they are directly involved in solid organ transplantation. In 2007, we conducted a first voluntary survey concerning organ donation among the staff of the university hospital of Essen. A short information campaign and further opinion poll among staff as well as visitors was performed in 2009 to compare professional and public attitudes toward organ donation. The first poll comprised 242 questionnaires showing 55% of the hospital staff carrying organ donor cards, particularly more women (60%) than men (46%). After this survey, an additional 19% of the hospital staff imagined they might carrying an organ donor card in the future. In the second survey, we analyzed 151 questionnaires, showing 66% of staff members carrying an organ donor card, an incidence significantly greater than among visitors (48%). The need for information regarding organ donation was greater among visitors (35%). However, 21% of the hospital staff still also need education concerning organ donation. More education and increased transparency of transplantation practice are necessary for hospital staff to act successfully as initiators. Hospital staff with positive attitudes toward organ donation may have a positive impact on the attitudes of the general public toward organ donation.

Donor/recipient algorithm for management of the middle hepatic vein in right graft live donor liver transplantation.

BACKGROUND: The aim of this study was to delineate an algorithm for donor and recipient criteria and middle hepatic vein (MHV) management in right-graft live-donor liver transplantation (LDLT) on the basis of computerized 3-dimensional computed tomographic image analysis. METHODS: Data on 94 consecutive right-graft LDLTs were prospectively collected. Graft and remnant data for the first 23 cases were retrospectively evaluated by means of 3-dimensional computed tomographic reconstructions, and on the basis of that preliminary series, a graft selection algorithm using 3 parameters-hepatic vein dominance classification, graft and remnant graft volume/body weight ratios, and congestion volumes-was created. It was subsequently applied to the next 71 right-graft LDLTs. RESULTS: Fifty-nine right grafts contained the MHV. Four of the 12 grafts with no MHVs required MHV reconstructions. In 18 cases, small liver grafts were used. The postoperative function of liver grafts and remnants with versus without MHVs was not statistically different. CONCLUSIONS: The proposed algorithm favored the inclusion of the MHV with the right grafts. It also allowed for the procurement of grafts that were potentially small for size without compromising donor or recipient safety.

Combined mycophenolate mofetil and minimal dose calcineurin inhibitor therapy in liver transplant patients: clinical results of a prospective randomized study.

BACKGROUND: Long-term complications of calcineurin inhibitor (CNI)-based immunosuppression after liver transplantation (LT) have a marked impact on patient morbidity and mortality. METHODS: In this prospective study, LT patients with renal dysfunction were randomized (2:1) to either receive mycophenolate mofetil (MMF) followed by stepwise reduction of CNI with defined minimal CNI trough levels (MMF group) or to continue their maintenance CNI dose (control group). RESULTS: In the MMF group (n = 60), renal function assessed by serum creatinine improved >10% in 67% of patients, was stable in 32%, and deteriorated >10% in 2% after 12 months compared with baseline values. Mean serum creatinine levels (+/-SD) significantly decreased from 1.86 +/- 0.43 to 1.55 +/- 0.38 mg/dL and the corresponding calculated glomerular filtration rate (cGFR) significantly increased from 39.9 +/- 10.1 to 49.2 +/- 11.9 mL/min over a 12-month follow-up period. Blood pressure and levels of liver enzymes significantly decreased, and no allograft rejection occurred. In the control group (n = 30), there were no significant changes in mean serum creatinine and cGFR (1.78 +/- 0.59 mg/dL at baseline vs 1.93 +/- 0.86 mg/dL at month 12, and 41.3 +/- 13.2 mL/min vs 38.7 +/- 11.2 mL/min, respectively), liver enzymes and blood pressure throughout the study. CONCLUSIONS: Combined MMF and minimal dose CNI therapy after LT is safe, and improves kidney function and the cardiovascular risk profile.

Acute liver failure in a metropolitan area in Germany: a retrospective study (2002 - 2008).

OBJECTIVES: To determine current etiologies of acute liver failure (ALF) and clinical and laboratory parameters associated with the outcome upon ALF, so as to identify the frequency of present causes of ALF in Germany as well as potential new prognostic parameters. PATIENTS: 134 adult patients (63 % females / 37 % males) aged 41 +/- 16 years (median: 38 years) with established ALF criteria. DESIGN AND SETTING: A retrospective study (1 / 2002 - 4 / 2008) on ALF patients from the Ruhr Area, the largest urban region located in northwestern Germany. Clinical and laboratory data were collected for a period of four weeks after study admission. RESULTS: Etiologies of ALF were identified as drug toxicity (39.6 % of the cases); combined viral hepatitides (23.1 %); or miscellaneous (16.4 %). In 20.9 % of the cases, the etiology remained indeterminate. Overall patient survival at four weeks was 81.3 %. While 89 patients (66.4 %) recovered under best supportive therapy, 26 patients (19.4 %) had to undergo liver transplantation. Increased body mass indices were significantly (p < 0.003) associated with a poor outcome. Intriguingly, high levels of cholestatic enzymes significantly (p < 0.01) correlated with a positive outcome. CONCLUSIONS: In providing first data on current ALF etiologies Germany, this study reveals that drug toxicity - in particular due to acetaminophen - has replaced viral hepatitis as the most single frequent cause of ALF in a densely populated urban area; this correlates with similar findings in the USA, the UK and Scandinavia. Lower body mass indices and elevated cholestatic enzyme levels had statistically significant prognostic power.