[Assessment of validity of the German version of the Manchester Triage System]. / Validierungsstudie des deutschsprachigen Manchester Triage Systems.

BACKGROUND: The Manchester Triage System (MTS) was first introduced in 1996. Since then, the original English MTS version has undergone multiple evaluations of its validity and reliability. Due to translation and differing algorithms, only contradictory data regarding accuracy are available for the German MTS version. The aim of this study was to assess the validity of the current German version of the MTS in a retrospective observational setting. MATERIALS AND METHODS: All surgical and medical patients presenting at the emergency department of an Austrian regional hospital between 1 and 30 July 2020 were included in this study. Data of vital parameters at the time of triage, overall hospitalisation rate, length of hospitalisation, mortality rate as well as referral and discharge modalities were collected. RESULTS: A total of 773 patients were included in the study after primary triage. There was a significant correlation between risk level and both hospitalisation rate (p < 0.001) and the length of hospitalisation (p = 0.001). Interestingly, this correlation was lower in patients over 70 years (r2 = 0.101 vs. 0.045). Vital signs and mortality rate did not correlate significantly with the initial risk level. The average time for one triage process was 2.1 ± 3.9 min. CONCLUSION: The German version of the MTS shows good correlation with central risk surrogates, but this correlation is weaker in the subgroup of elderly patients. As the original English version, it does not predict long-term mortality. In clinical practice, the German version of the MTS is as good as the original version in enabling the urgency of treatment to be rapidly assessed so that resource allocation can be optimised.

Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

[Intensive care treatment before and after liver transplantation]. / Intensivmedizinisches Management vor und nach Lebertransplantation.

BACKGROUND: Liver transplantation (LT) has become an established therapeutic option for patients with acute and chronic liver failure. Overall survival has dramatically increased over the last decades, mainly due to improved surgical techniques, the introduction of new immunosuppressive and anti-infective drugs but also due to continuous progress in the pre- and post-operative intensive care management of these patients. AIM: This article aims to give a short overview of the main aspects regarding pre- and post-LT critical care issues. RESULTS: Intensive care treatment plays a major role in the management of patients with acute and acute-on-chronic liver failure in order to enable a life-saving LT for these patients. Severe infections/sepsis mostly accompanied by multi-organ failure represent the major challenges for intensive care specialists. The immediate postoperative care takes place in the intensive care unit (ICU) in almost all patients. The expected ICU stay has been significantly shortened over the years to an average of about 1-2 days. Infections as well as acute kidney injury are the main complications in the first post-operative weeks being responsible for prolonged ICU stays. Immunologic and surgical complications are additional important issues in the post-LT intensive care setting. CONCLUSION: The intensive care management pre and post LT is an important, multidisciplinary challenge in the successful treatment of patients with acute and chronic liver failure.

Serum prolactin in advanced chronic liver disease.

Hyperprolactinemia is a frequent endocrine disorder with well known harmful effects on the reproductive system and bone metabolism. Besides prolactinomas several drugs and disorders such as renal failure and hypothyroidism have been shown to cause hyperprolactinemia. Based on former studies, liver cirrhosis has also been suggested to cause hyperprolactinemia, while mechanisms have not been identified yet. In this study, we set out to investigate the prevalence and predictors of hyperprolactinemia in 178 patients with liver cirrhosis of different etio-logies. Eighteen out of 178 patients - 7 females and 11 males - displayed elevated serum pro-lactin levels. When patients were excluded who suffered from co-morbidities or took medication that are discussed to potentially interfere with prolactin metabolism, only 3 males displayed increased serum prolactin levels. Prolactin levels were similar in patients with liver cirrhosis of different etiologies. Our data suggest that hyperprolactinemia is not commonly found in patients with liver cirrhosis, but is mostly associated with intake of drugs or presence of comorbidites which are known to potentially cause hyperprolactinemia. We thus hypothesize that in contrast to former studies liver cirrhosis is not a common cause of hyperprolactinemia and that in the absence of co-morbidities or drugs that are known to potentially increase prolactin levels, marked hyperprolactinemia needs further investigation in patients with liver cirrhosis.

The liver graft as Trojan horse-multilineage donor-derived hematopoiesis after liver transplantation: case report.

Hematopoietic macrochimerism, which is rarely seen after orthotopic liver transplantation (OLT), has been linked to the development of graft versus host disease (GvHD). We report on a patient with GvHD after OLT in whom full engraftment of donor-derived, multilineage hematopoiesis occurred, indicating that the liver contains pluripotent hematopoietic progenitor cells (HPC) capable to restore hematopoiesis in recipients. Although preventing graft rejection, standard immunosuppressive therapy may be under certain immunological conditions not sufficient to prevent GvHD. Age-, disease-, and treatment-related variables might be critical determinants for the development of an effective alloreactive T-cell response leading to the establishment of full hematopoietic chimerism.

[Monitoring of organ functions. Dysfunction of kidneys, liver, gastrointestinal tract, and coagulation]. / Monitoring von Organfunktionen. Dysfunktion von Niere, Leber, Gastrointestinaltrakt und Gerinnung.

Monitoring of organ function is one of the core tasks of intensive care medicine. Although various monitoring devices and parameters have already been established for some organs, there are no or only few conditionally useful parameters or scores available for the kidneys, liver, gastrointestinal tract, and blood coagulation. Therefore, specific biomarkers and scores as well as combinations of both are currently investigated for better monitoring of these organs. This article gives a critical overview of currently used as well as investigational biomarkers, tests and scores in general, and shows some examples of the implications for common diseases, clinical situations and constellations in the intensive care unit.

Hepatitis C and autoimmunity: a therapeutic challenge.

Hepatitis C virus (HCV) infection causes not only acute and chronic liver disease, but also extrahepatic symptoms. To our knowledge, this is the first case report of a patient who developed simultaneously subacute cutaneous lupus erythematosus and a small CD20+ B-cell clone because of chronic HCV infection and relapse after standard of care therapy (pegylated interferon plus ribavirin). Treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, was successful.

Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Sorafenib is the new reference standard for patients with advanced hepatocellular carcinoma (HCC). AIM: To identify prognostic factors in sorafenib-treated HCC patients and to evaluate outcomes with respect to liver function. METHODS: In this retrospective study, 148 HCC patients received sorafenib 400 mg b.d. across 11 Austrian institutions. Seventy-eight HCC patients who received best supportive care (BSC) in the pre-sorafenib era served as a control. RESULTS: In sorafenib-treated patients, low baseline α-fetoprotein, low Child-Pugh (CP) score, compensated cirrhosis, and low baseline aspartate aminotransferase (AST) were associated with significantly longer overall survival (OS) on univariate analysis. CP score and baseline AST remained independent prognostic factors on multivariate analysis. In patients with Barcelona Clinic liver Cancer (BCLC) stage B or C HCC (sorafenib: n = 139; BSC: n = 39), CP-A patients had a median OS of 11.3 (sorafenib [n = 76]) vs. 6.4 (BSC [n = 17]) months (P = 0.010), and CP-B patients had a median OS of 5.5 (sorafenib [n = 55]) vs. 1.9 (BSC [n = 22]) months (P = 0.021). In the sorafenib group, median OS according to baseline AST was 11.8 (<100 U/L [n = 58]) vs. 3.9 (≥100 U/L [n = 15]) months for CP-A patients (P = 0.127), and 6.5 (<100 U/L [n = 33]) vs. 2.1 (≥100 U/L [n = 21]) months for CP-B patients (P = 0.011). There was no survival difference between sorafenib and BSC in patients with BCLC stage D HCC (1.5 vs. 1.4 months; P = 0.116). CONCLUSIONS: Sorafenib was associated with improved survival in both CP-A and CP-B patients. In CP-B patients, baseline AST may be helpful in determining which patients are most likely to benefit from sorafenib.

The role of apolipoprotein A5 in non-alcoholic fatty liver disease.

BACKGROUND: Apolipoprotein A5 (apoA5) is a recently described liver-specific protein that has been shown to influence triglyceride (TG) metabolism. ApoA5 transgenic mice display dramatically reduced TG levels, while in contrast apoA5 deficiency in humans was reported to result in marked hypertriglyceridemia. ApoA5 exerts its extracellular effects by increasing lipolysis of TG-rich lipoproteins, while in vitro data suggest additional intrahepatic effects. METHODS: In this study the authors set out to investigate a possible role of apoA5 in non-alcoholic fatty liver disease (NAFLD). We thus determined hepatic apoA5 expression in 15 obese subjects with histologically proven NAFLD undergoing bariatric surgery. In addition, the authors established a hepatic cell culture model of apoA5 knockdown by transfecting human hepatoma cells (HepG2) with apoA5 small interfering (si) RNA, and determined intracellular TG content and expression levels of key enzymes and transcription factors of intrahepatic lipid metabolism in these cells. RESULTS: Pronounced weight loss and associated histologically verified improvement of hepatic steatosis were accompanied by significant reductions of hepatic apoA5 mRNA expression levels. Significant apoA5 knockdown in HepG2 cells resulted in a marked decrease of intracellular TG content. When HepG2 cells were co-transfected with apoA5 and peroxisome proliferator-activated receptor gamma (PPARγ), reductions in hepatic TG accumulation were significantly less pronounced when compared to apoA5 siRNA transfected HepG2 cells. CONCLUSIONS: In obese subjects, hepatic apoA5 mRNA expression decreases after weight loss and improvements in hepatic steatosis. The authors' in vitro data demonstrate that apoA5 influences intrahepatic TG metabolism and that these intracellular effects of apoA5 are accompanied by changes in PPARγ mRNA expression. In summary, the data suggest that as well as several other factors, apoA5 might be involved in the pathogenesis of hepatic steatosis.

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

Kaposi sarcoma in solid organ transplant recipients: a single center report.

BACKGROUND: Human herpes virus (HHV8) is associated with Castleman's disease, primary effusion lymphoma, and the Kaposi's sarcoma (KS). PATIENTS AND METHODS: Among 3815 solid organ transplants performed at our center between 1977 and 2003, five patients (0.1%) were identified with KS. RESULTS: There were one cardiac, one liver, and three renal allograft recipients of median age of 52 (range 38 to 60) years, three of whom were females. Three patients were of Italian and one of Turkish descent; only one patient was a native Austrian. The onset of the disease was 2.0, 7.5, 7.8, 9.4 months, and 22 years posttransplant. Diagnosis of KS was based in all cases on histology. The heart recipient developed a tumor on the planta pedis; one renal recipient, on both legs. The liver and the two remaining renal recipients presented with disseminated disease. Treatment in all cases consisted of reduction in immunosuppression, together with surgery (n = 1), chemotherapy (n = 1), or irradiation (n = 2). Furthermore, immunosuppression was switched in two cases from Tacrolimus to Sirolimus. In the liver recipient a complete response was achieved; he died, however, due to noncompliance followed by graft failure. One renal recipient died without evidence of recurrent disease from myocardial infarction. The cardiac and two renal recipients are alive between 4 months and 17 years with well-functioning grafts and no evidence of recurrent disease. DISCUSSION: HHV8-associated lesions seem to be extremely rare in the Central European transplant population. Nevertheless, awareness of KS is important for early diagnosis and optimal treatment.

Infectious complications limit the outcome of liver transplantation in medical urgency code 2 patients.

The Organ shortage has caused an accumulation of acutely decompensated patients listed as medical urgency code 2 (MUC 2) (United network for Organ Sharing 2) while awaiting liver transplantation. Between June 1997 and June 2003, 22 of 360 liver transplantation patients (6%) were listed as MUC 2. Prophylactic immunosuppression consisted of calcineurin inhibitor-based drug therapy, using antithymocyte globulin or interleukin-2 receptor antagonist induction in 64%. The overall perioperative infection rate was 50%, and the rejection rate was 23%. We observed 7 episodes of oral or genital herpes simplex virus lesions; 2 patients (both with cytomegalovirus-mismatched transplants) developed cytomegalovirus disease, and another 5 patients received ganciclovir for preemptive therapy or prophylaxis. Two patients developed pneumonia: 5, sepsis that originated in 4 cases from a contaminated central venous line; and 1 methicillin-resistant endocarditis, which resulted in Staphylococcus aureus lethal outcome. After a median follow up of 3 years, 1 patient underwent a repeat transplantation procedure and 6 patients had died, 4 of them from infectious complications. Liver transplantation of MUC 2-listed patients may result in acceptable results similar to those of MUC 3 and MUC 4 categories.

Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis.

Atorvastatin and other members of the statin family are widely used for the treatment of hypercholesterolaemia in order to reduce the risk of atherosclerosis and cardiovascular disease. Atorvastatin-induced adverse events are mostly mild and only a few cases of lupus-like syndrome or severe acute hepatitis have been documented. In this case report we describe a patient who developed an atorvastatin-induced severe autoimmune hepatitis. In addition, this patient presented with a concomitant systemic lupus-like syndrome which has been already described for statins but not in association with severe liver disease. Although the drug was immediately withdrawn the disease persisted and even deteriorated to a fulminant disease with evidence of acute hepatic failure. The patient failed to respond to conventional immunosuppression with corticosteroids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery of the patient. Interestingly, the patient was HLA DR3- and HLA DR4-positive, which are well-known genetic factors associated with autoimmune diseases. This case is the first report of a drug-induced lupus-likesyndrome concomitant with a severe autoimmune hepatitis in a genetically predisposed patient.

Massive progression of diffuse hepatic lymphangiomatosis after liver resection and rapid deterioration after liver transplantation.

Hepatic involvement is an exceptional presentation of lymphangiomatosis. In this case report we describe a patient who underwent liver transplantation secondary to progressive hepatic involvement, which occurred 2 yr after partial hepatectomy. Within 1 yr after liver transplantation the disease condition deteriorated, with rapid progression of pre-existing skeletal lesions and development of pulmonary disease. We conclude that liver transplantation may be a treatment option for hepatic lymphangiomatosis. In the presence of pre-existing extrahepatic lesions, however, liver transplantation seems to be contraindicated.

Muscle cramps: a 'complication' of cirrhosis.

Muscle cramps are a common complaint in clinical practice. They are associated with various metabolic, endocrine, neurological and electrolyte abnormalities. A variety of hypotheses have been generated to explain the cause of muscle cramping, yet none has been able to support a consistent pathophysiological mechanism. Muscle cramps are painful, involuntary contractions of skeletal muscle. They occur frequently in individuals with cirrhosis, regardless of the etiology, and are thought to be a symptom of cirrhotic-stage liver disease. The pathophysiology of these cramps remains elusive; hence, a specific therapy has not been identified. Many therapeutic approaches have been offered, yet their efficacy, safety and mechanism of action remain poorly defined. This review defines muscle cramps and illuminates its prevalence in the cirrhotic individual. Current theories relating to the pathogenesis of muscle cramps are reviewed, and an overview of the various pharmacological agents that have had therapeutic success for this distressing and frustrating symptom is provided.

Successful use of continuous intravenous prostacyclin in a patient with severe portopulmonary hypertension.

INTRODUCTION: Portopulmonary hypertension, defined by a mean pulmonary artery pressure > 25 mm Hg in the presence of normal pulmonary capillary wedge pressure and portal hypertension, is a known complication of end-stage liver disease that has been associated with high morbidity and mortality at the time of liver transplantation. DESIGN: Descriptive case report. PATIENT: A 32 year old male patient suffering from end-stage hepatitis C liver cirrhosis presented with severe portopulmonary hypertension. At presentation the following pulmonary hemodynamics were measured: systolic pulmonary artery pressure (PAP) 76 mm Hg, mean PAP 42 mm Hg, pulmonary vascular resistance index (PVRI) 931, pulmonary capillary wedge pressure (PCWP) 9 mm Hg, and cardiac output (CO) 4.03 l/min. INTERVENTION: After acute hemodynamic testing the patient received 8 ng/kg/min epoprostenol (prostacyclin) by continuous intravenous infusion with an infusion pump. Hemodynamic evaluation was performed monthly by transthoracic echocardiography and right heart catheterisation after 5 months. RESULTS: After 5 months of continuous therapy right heart catheterisation revealed the following hemodynamics: systolic pulmonary artery pressure (PAP) 59 mm Hg, mean PAP 32 mm Hg, pulmonary vascular resistance index (PVRI) 561, pulmonary capillary wedge pressure (PCWP) 7 mm Hg, and cardiac output (CO) 6.95 l/min. This presents a decrease in systolic pulmonary artery pressure of approximately 22%, a decrease in mean pulmonary artery pressure of approximately 30%, a decrease in pulmonary vascular resistance of approximately 40% and an increase in cardiac output of approximately 73%. Echocardiography demonstrated a decrease in estimated systolic pulmonary artery pressure of about 37% after 8 months of therapy. No complications were observed during epoprostenol therapy. CONCLUSION: In this adult patient suffering from end-stage liver disease and portopulmonary hypertension, administration of continuous intravenous epoprostenol resulted in significant reduction of pulmonary hypertension and therefore in acceptance for orthotopic liver transplantation. Utilisation of this new therapeutic strategy might be a helpful pharmacological tool for patients with portopulmonary hypertension to make them acceptable for orthotopic liver transplantation.