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Alveolar echinococcosis is a rare parasitic disease, most frequently affecting the liver, as a slow-growing tumor-like lesion. If inoperable, long-term benzimidazole therapy is required, which is associated with high healthcare costs and occasionally with increased morbidity. The aim of our study was to determine the role 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in staging of patients with alveolar echinococcosis and to identify quantitative imaging parameters related to patient outcome and/or duration benzimidazole therapy. In this single-center retrospective cohort study, 47 PET/CT performed for staging in patients with confirmed alveolar echinococcosis were analysed. In 43 patients (91%) benzimidazole therapy was initiated and was successfully stopped after a median of 870 days (766-2517) in 14/43 patients (33%). In inoperable patients, tests for trend of survivor functions displayed clear trends for longer benzimidazole therapy duration (p=0.05; n=25), and for longer time intervals to reach non-detectable serum concentration of Em-18 antibodies (p= 0.01, n=15) across tertiles of SUVratio (maximum standardized uptake value in the echinococcus manifestation compared to normal liver tissue). Hence, in inoperable patients with alveolar echinococcosis, PET/CT performed for staging may predict the duration of benzimidazole therapy.

Objective The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation. Patients and methods We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B). Results Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers. Conclusion We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria.

International audience; Introduction - Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. Methods - We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. Results - The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10) and higher premorbid body mass index (26.37 ± 0.16 kg/m) than controls (24.44 ± 0.18 kg/m, P = 5.77 × 10). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. Discussion - If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

International audience; Background and aims - Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. Approach and results - We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Conclusions - Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation.We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B).Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers.We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria.

As a result of epidemic levels of obesity and diabetes mellitus, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) will contribute to increases in the liver-related disease burden in Switzerland. A Markov model was built to quantify fibrosis progression among the NAFLD and NASH populations, and predict disease burden up to 2030. Long-term trending of NAFLD prevalence was based on changes in the prevalence of adult obesity. Published estimates and surveillance data were applied to build and validate the model projections. The prevalence of NAFLD increased up to 2030 in tandem with projected increases in adult obesity. By 2030, there were an estimated 2,234,000 (1,918,000–2,553,000) NAFLD cases, or 24.3% (20.9–27.8%) of the total Swiss population (all ages). Increases in NASH cases were relatively greater than NAFLD cases. Incident cases of advanced liver disease are projected to increase by approximately 40% by 2030, and incident NAFLD liver deaths to increase from 580 deaths in 2018 to 820 deaths in 2030. Continued growth in obesity, in combination with an aging population, will result in increasing number of cases of advanced liver disease and mortality related to NAFLD and NASH. Slowing the growth in obesity and metabolic syndrome, along with future potential therapies, are required to reduce liver disease burden. &nbsp.

The aim of the study was to determine the role ofA total of 22 patients undergoing PET/CT at the end of benzimidazole therapy were retrospectively registered. Maximum standardized uptake values (SUVAll patients had no detectable levels of Em-18 antibodies and all echinococcus manifestations were negative on PET/CT, i.e. without focally increased FDG uptake or uptake higher than normal/non-infected liver tissue. All manifestations displayed significantly less FDG-uptake than normal liver tissue, i.e. SUVmax 1.8 (interquartile range (IQR) 1.5-3.5) vs. 3.0 (IQR 2.6-5.7), (p 0.001). Patients were clinically followed for a median of 9.5 years (IQR 6.5-32.0 years) after their initial diagnosis and for 4.5 years (IQR 3.0-14.0 years) after discontinuation of benzimidazole therapy. No patient showed signs of recurrent infection at the last clinical visit. The 10-year and 20-year freedom from all-cause mortality was 95.0% (95% confidence interval 69.5% - 99.3%), for both. Two events occurred in 292 patient years of follow-up; i.e. two patients (9%) died, one because of pancreatic cancer, the other one because of unknown reasons with no detectable antibody levels.Negative FDG-PET/CT results combined with no detectable levels of Em-18 antibodies may allow for the safe discontinuation of benzimidazole therapy in patients with alveolar echinococcosis.

Donation after circulatory death (DCD) liver transplantation is known for potentially worse outcomes because of higher rates of graft non-function or irreversible cholangiopathy. The impact of machine liver perfusion techniques on these complications remains elusive. We aimed to provide data on 5-year outcomes in patients receiving DCD liver transplants, after donor organs had been treated by hypothermic oxygenated perfusion (HOPE).Fifty HOPE-treated DCD liver transplants performed in Zurich between 2012 and 3/2017 were matched with 50 primary donation after brain death (DBD) liver transplants, and with 50 untreated DCD liver transplants in Birmingham. Match factors focussed on short cold ischaemia, comparable recipient age and low recipient laboratory model for end-stage liver disease scores. Primary endpoints were post-transplant complications, and non-tumour-related patient death or graft loss.Despite extended donor warm ischaemia, HOPE-treated DCD liver transplants achieved similar overall graft survival, compared to standard DBD liver transplants. Particularly, graft loss due to any non-tumour-related causes occurred in 8% (4/50) of cases. In contrast, untreated DCD livers resulted in non-tumour-related graft failure in one-third (16/50) of cases (p = 0.005), despite significantly (p 0.001) shorter functional donor warm ischaemia. Five-year graft survival, censored for tumour death, was 94% for HOPE-treated DCD liver transplants vs. 78% in untreated DCD liver transplants (p = 0.024).The 5-year outcomes of HOPE-treated DCD liver transplants were similar to those of DBD primary transplants and superior to those of untreated DCD liver transplants, despite much higher risk. These results suggest that a simple end-ischaemic perfusion approach is very effective and may open the field for safe utilisation of extended DCD liver grafts.Machine perfusion techniques are currently being introduced into the clinic, with the aim of optimising injured grafts prior to implantation. While short-term effects of machine liver perfusion have been frequently reported in terms of hepatocellular enzyme release and early graft function, the long-term benefit on irreversible graft loss has been unclear. Herein, we report on 5-year graft survival in donation after cardiac death livers, treated either by conventional cold storage, or by 1-2 h of hypothermic oxygenated perfusion (HOPE) after cold storage. Graft loss was significantly less in HOPE-treated livers, despite longer donor warm ischaemia times. Therefore, HOPE after cold storage appears to be a simple and effective method to treat high-risk livers before implantation.

© 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 There is a need for hepatitis C virus (HCV) therapies with excellent efficacy across genotypes and in diverse populations. Part A of the C-CREST-1 and C-CREST-2 trials led to the selection of a three-drug regimen of grazoprevir (MK-5172; an HCV NS3/4A protease inhibitor; 100 mg/day) plus ruzasvir (MK-8408; an NS5A inhibitor; 60 mg/day) plus uprifosbuvir (MK-3682; an HCV NS5B polymerase inhibitor; 450 mg/day). Part B of the studies tested this combination as a single formulation in different treatment durations in a broader population. Methods Part B of these randomised, phase 2, open-label clinical trials enrolled individuals from 15 countries who were chronically infected with HCV genotypes 1–6 (HCV RNA ≥10 000 IU/mL) with or without compensated cirrhosis. Those with genotype 1, genotype 2, genotype 4, or genotype 6 were treatment-naive; those with genotype 3 could be treatment-naive or treatment-experienced with pegylated interferon and ribavirin. Randomisation occurred centrally using an interactive voice response system and integrated web response system. Participants were randomly assigned to receive treatment for 8, 12, or 16 weeks with a fixed-dose combination of grazoprevir, ruzasvir, and uprifosbuvir with or without ribavirin. The primary endpoint was the proportion of participants achieving sustained virological response 12 weeks after the end of all study therapy (SVR12), defined as HCV RNA less than the lower limit of quantification (either target detected unquantifiable or target not detected [

In acute attacks of acute intermittent porphyria, the mainstay of treatment is glucose and heme arginate administration. We present the case of a 58-year-old patient with acute liver failure requiring urgent liver transplantation after erroneous 6-fold overdose of heme arginate during an acute attack. As recommended in the product information, albumin and charcoal were administered and hemodiafiltration was started, which could not prevent acute liver failure, requiring super-urgent liver transplantation after 6 days. The explanted liver showed no preexisting liver cirrhosis, but signs of subacute liver injury and starting regeneration. The patient recovered within a short time. A literature review revealed four poorly documented cases of potential hepatic and/or renal toxicity of hematin or heme arginate. This is the first published case report of acute liver failure requiring super-urgent liver transplantation after accidental heme arginate overdose. The literature and recommendations in case of heme arginate overdose are summarized. Knowledge of a potentially fatal course is important for the management of future cases. If acute liver failure in case of heme arginate overdose is progressive, super-urgent liver transplantation has to be evaluated.

BACKGROUND 38; AIMS Steatosis is a prominent feature of hepatitis C especially in patients infected with genotype 3. The analysis of genetic polymorphisms influencing steatosis in chronic hepatitis C has been limited by the studies' small sample size and important single nucleotide polymorphisms (SNPs) such as those in the patatin like phospholipase family 3 protein (PNPLA3) were never evaluated. METHODS We analyzed the role of SNPs from 19 systematically selected candidate genes on steatosis in 626 Caucasian hepatitis C virus (HCV) infected patients. SNPs were extracted from a genome wide association generated dataset. Associations of alleles with the presence and/or different severity of steatosis were evaluated by univariate and multivariate logistic regression accounting for all relevant covariates. RESULTS The risk of steatosis was increased by carriage of I148M in PNPLA3 but only in patients with HCV genotypes non 3 (odds ratio [OR]=1.9 95 confidence interval [CI]=1.6 2.3 p

Fragestellung: In der vorliegenden Arbeit wird untersucht, (a) ob die deutsche Version des Transplant Effects Questionnaire (TxEQ-D), welcher die psychische Verarbeitung einer Organtransplantation erfasst und Hinweise zur Indikation psychosozialer Interventionen liefert, die gleiche faktorielle Struktur wie die englische Originalversion aufweist und (b) ob die Skalenkennwerte sowie die Korrelationen mit den Skalen des SF-36 (Fragebogen zum physischen und psychischen Gesundheitszustand) vergleichbar sind. Methode: Der ins Deutsche ubersetzte Fragebogen TxEQ wurde von einer Stichprobe von 370 herz-, lungen-, leber- und nierentransplantierten Patienten ausgefullt und einer Faktoren- sowie Itemanalyse unterzogen. Zudem wurde zur Prufung der Validitat der Lebensqualitats-Fragebogen SF-36 eingesetzt. Ergebnisse: Der TxEQ-D hat die gleiche faktorielle Struktur wie die englische Originalversion und vergleichbare psychometrische Eigenschaften. Die hochsten Korrelationen mit den 10 Skalen des SF-36 weist der Faktor »Sorge um das Transplantat« auf, die niedrigsten der Faktor »Adherence«. Schlussfolgerungen: Der TxEQ-D ist ein fur die psychosomatische Forschung und psychotherapeutische Praxis geeignetes Screeningintrument zur Erkennung von Patienten mit einer problematischen psychischen Verarbeitung einer Organtransplantation, die zusatzlich zur somatischen Nachbehandlung professionelle psychosoziale Unterstutzung erhalten sollten. = Objectives: The present study investigates a) whether the German version of the Transplant Effects Questionnaire (TxEQ-D), which measures the emotional response to an organ transplantation, has the same factorial structure as the English original version and b) whether the psychometric properties as well as the correlations with the scales of the SF-36 are comparable. Methods: The questionnaire TxEQ was translated into German and filled out by 370 heart, lung, liver and kidney transplant patients. Subsequently, factor and item analyses were conducted. The SF-36 was used to test validity. Results: The TxEQ-D has the same factorial structure as the English version as well as comparable psychometric properties. The TxEQ-D factor “worry about transplant” shows the highest correlations with the 10 scales of the SF-36, the lowest correlations with the 10 scales of the SF-36 scales are found for the factor “adherence”. Conclusions: The TxEQ-D is a useful screening instrument in psychosomatic research and in the psychotherapy practice to detect patients with problematic emotional responses to an organ transplantation.

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

Zusammenfassung Fragestellung: Transplantations-Patienten sind einer Vielzahl psychischer und sozialer Belastungen ausgesetzt. Die vorliegende Studie untersucht den Bedarf an psychosozialer Beratung. Methode: 76 Patienten wurden vor sowie sechs und zwolf Monate nach einer Lungen-, Leber- oder Knochenmarkstransplantation zum Beratungsbedarf befragt. Folgende Messinstrumente wurden eingesetzt: SF-36 (Lebensqualitat), FLZ (Lebenszufriedenheit), HADS-D (Angst/Depression) und F-SozU K-14 (Soziale Unterstutzung). Ergebnisse: In allen Organgruppen ist der Bedarf an psychosozialer Beratung vor der Transplantation am hochsten, er liegt bei 42;9 % (Lunge), 50;0 % (Leber) und 26;7% (Knochenmark). Sechs Monate nach der Transplantation hat der Beratungsbedarf in allen Organgruppen deutlich abgenommen. Bei lebertransplantierten Patienten steigt er allerdings zwischen dem sechsten und zwolften Monat erneut an. Er korreliert zu allen drei Messzeitpunkten signifikant positiv mit Angst, nach zwolf Monaten zudem signifikant...

Background & Aims: The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. Methods: A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. Results: Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. Conclusions: In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.

Objectives Medication non-adherence is a common problem in organ transplantation patients with severe consequences for the patients' health. This study aimed at examining the determinants of intention formation and adherence behavior based on the Theory of Planned Behavior (TPB). Moreover, to account for the role of patients' partners, provided social support by partners was included. Here, support provided by female partners was hypothesized to be more effective than support provided by male partners. Method This cross-sectional study comprised 121 heart, liver, lung, and kidney transplant recipients (n = 81 men; mean age = 54.32, SD = 13.32) and their partners (mean age = 51.99, SD = 13.67). Patients completed a questionnaire with TPB variables and a validated measure of self-reported adherence. Partners reported their provided social support with regard to medication adherence of the patients. Results For the prediction of intention to adhere to medication, the non-significant main effect of provided social support was qualified by partners' gender: Support provided by women was positively related to patients' intention to adhere, whereas support provided by men was slightly negatively related to the intention to adhere in their female spouses. Intentions in turn emerged together with relationship quality as the most important predictor of adherence behavior. Conclusion The beneficial effects of support provided by women could be replicated within the framework of the TPB in the context of organ transplantation. Interventions should focus on increasing the effectiveness of support provision of male partners and on promoting relationship quality.

Objective: While a number of studies have dealt with the psychosocial consequences of transplantation for patients, we know comparatively little about the strains faced by their spouses. The present study investigates the psychosocial health of transplant patients and their spouses, as well as the link between these groups’ physical and psychosocial status, on the one hand, and their degree of burnout and level of life satisfaction on the other. Design: In a cross-sectional study, 121 patients and their spouses are surveyed by questionnaire following heart, lung, liver, or kidney transplant. Methods: The psychosocial parameters investigated in both patients and spouses are sense of coherence, quality of life, quality of the relationship, life satisfaction, and burnout. Results: Patients rate the quality of the relationship higher than their partners do, and they are more satisfied with the relationship than their spouses are (p < .001). Regression analyses show that patients’ life satisfaction is associated with quality of the relationship. Evidence of a full burnout syndrome can be found in three of the patients and two of the spouses. Burnout in the case of both patients and their partners is associated with limitations in one’s own sense of coherence and in one’s mental and physical health (multiple R2 = 0.79 for patients and 0.76 for spouses). Conclusion: Because of the importance of the couple’s relationship, psychosocial counseling should pay more attention to relationship satisfaction. Psychotherapeutic techniques should be used to improve the sense of coherence in both patient and spouse.

Summary QUESTIONS UNDER STUDY: A transplant represents a decisive event for patients and their caregivers. This article deals with the attitudes patients and their spouses have towards the transplantation. METHODS: In a cross-sectional study, 121 patients and their spouses were surveyed by questionnaire after a heart, lung, liver or kidney transplant. Attitudes were assessed by means of semantic differentials. Based on the results, an ‘Attitudes towards Transplantation’ Scale was developed. Sense of coherence (SOC-13), quality of life (Sf-36), quality of the relationship (RAS), burnout (BM) and the patient’s emotional response to the transplant (TxEQ-D) were additional psychosocial variables measured in order to assess the association between the attitudes and psychosocial characteristics of transplant patients and their spouses. RESULTS: The majority of patients and their spouses reported positive attitudes towards the transplant, including the attitudes towards medication, their perceived self and fate of being a transplant patient or spouse. Patients and spouses, however, had a negative attitude towards the transplantation in terms of stress and anxiety. Patients reported greater emotional stress from the transplant and rated their post-transplant perceived fate more negatively than their spouses. Attitudes towards the transplant were significantly associated with the sense of coherence and the quality of relationship. CONCLUSION: The attitudes of patients and spouses to different aspects of the transplant itself and to being a transplant patient or spouse should be deliberately reconsidered and facilitated in the psychosocial counselling with regard to the comprehensibility, manageability and meaningfulness of the transplant experience as well as to potential conflicts in the partnership.

The communication with patients who have undergoned transplantation is greatly influenced by their subjective experience. This paper deals with this subjective transplant-specific experience six months after surgery.Following their heart, lung, liver, or kidney transplantation, 120 patients were questioned concerning their experiences regarding the transplantation, the organ itself, and changes in their personal life. Their statements were investigated by qualitative content analysis.Generally, the statements concerning the transplantation were positive. Interpersonal contact with the medical staff and or family members was perceived as very helpful. Two-thirds of the patients spoke openly about their organ. For the most part, their statements about changes in their personal life were positive, expressed in the sense of personal growth. Fears and insecurities occurred as negative changes.On the whole, the majority of the patients expressed positive experiences regarding their transplantation. Interpersonal and supportive relationships played a significant role.

Objectives: The communication with patients who have undergoned transplantation is greatly influenced by their subjective experience. This paper deals with this subjective transplant-specific experience six months after surgery. Methods: Following their heart, lung, liver, or kidney transplantation, 120 patients were questioned concerning their experiences regarding the transplantation, the organ itself, and changes in their personal life. Their statements were investigated by qualitative content analysis. Results: Generally, the statements concerning the transplantation were positive. Interpersonal contact with the medical staff and or family members was perceived as very helpful.Two-thirds of the patients spoke openly about their organ. For the most part, their statements about changes in their personal life were positive, expressed in the sense of personal growth. Fears and insecurities occurred as negative changes. Conclusions: On the whole, the majority of the patients expressed positive experiences regarding their transplantation. Interpersonal and supportive relationships played a significant role.

BACKGROUND: Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine. METHODS: We performed a nested case-control study including 15 patients with NCPH and 75 matched control subjects of the Swiss HIV Cohort Study to investigate risk factors for the development of NCPH. Matching criteria were similar duration of HIV infection, absence of viral hepatitis, and follow-up to at least the date of NCPH diagnosis in the respective case. RESULTS: All 15 case patients had endoscopically documented esophageal varices and absence of liver cirrhosis on biopsies; 4 died because of hepatic complications. At NCPH diagnosis, case patients and control subjects were similar concerning sex; race; Centers for Disease Control and Prevention stage; HIV-RNA level; CD4 cell count nadir; and lipids and lipodystrophy. Differences were found in age (conditional logistic regression odds ratio [OR] for 10 years older, 2.9; 95% confidence interval [CI], 1.4-6.1); homosexuality (OR, 4.5; 95% CI, 1.2-17); current CD4 cell count

Various non-specific questionnaires were used to measure quality of life and psychological wellbeing of patients after organ transplantation. At present cross-organ studies dealing specifically with the psychological response to a transplanted organ are non-existent in German-speaking countries.The Transplant Effects Questionnaire TxEQ-D and the SF-36 Quality of Life Questionnaire were used to examine the psychological response and quality of life of 370 patients after heart, lung, liver or kidney transplantation. The organ groups were compared with regard to psychosocial parameters.72% of patients develop a feeling of responsibility for the received organ and its function. This feeling is even stronger towards the patient's key relationships i.e. family, friends, the treatment team and the donor. 11.6% worry about the transplanted organ. Heart and lung patients report significantly fewer concerns than liver and kidney patients. Overall, only a minority of patients report feelings of guilt towards the donor (2.7%), problems in disclosing their transplant to others (2.4%), or difficulties in complying with medical orders (3.5%). Lung transplant patients show significantly better adherence.A feeling of responsibility towards those one is close to and towards the donor is a common psychological phenomenon after transplantation of an organ. Conscious feelings of guilt and shame are harboured by only a minority of patients. The fact that heart and lung patients worry less about their transplant might have primarily to do with the greater medical and psychosocial support in this group.

The present study investigates a) whether the German version of the Transplant Effects Questionnaire (TxEQ-D), which measures the emotional response to an organ transplantation, has the same factorial structure as the English original version and b) whether the psychometric properties as well as the correlations with the scales of the SF-36 are comparable.The questionnaire TxEQ was translated into German and filled out by 370 heart, lunge, liver and kidney transplant patients. Subsequently, factor and item analyses were conducted. The SF-36 was used to test validity.The TxEQ-D has the same factorial structure as the English version as well as comparable psychometric properties. The TxEQ-D factor "worry about transplant" shows the highest correlations with the 10 scales of the SF-36, the lowest correlations with the 10 scales of the SF-36 scales are found for the factor "adherence".The TxEQ-D is a useful screening instrument in psychosomatic research and in the psychotherapy practice to detect patients with problematic emotional responses to an organ transplantation.

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

Only few comparative prospective studies have been published on psychosocial issues of organ transplant. This study investigated patient groups with various organ transplants with respect to their quality of life and psychosocial situation before and after surgery.76 patients receiving an organ transplant (lung n = 22, liver n = 26, allogeneic bone marrow n = 28) were investigated with regard to quality of life (SF-36), life satisfaction (FLZ), social support (F-SozU), and psychological symptoms (HADS-D) before (T0) as well as six (T1) and twelve (T2) months after transplant.In the pre-transplant period the values of the psychosocial variables were partly lower than those of the community normal sample. After transplant lung and bone marrow patients reported less anxiety and depression and a higher life satisfaction, and liver patients reported less depression, compared to the norms. Quality of life, life satisfaction and psychological symptoms of all patients improved significantly post-transplant, whereas the perceived social support decreased. Contrary to the other groups, the psychological well-being of liver transplant recipients was deteriorating between T1 and T2.An organ transplant improved the patients' quality of life and psychosocial situation to a great extent. This effect was better in lung and bone marrow than in liver transplant patients.

An increase in fox population has led to an increase in incidence of human alveolar echinococcosis., We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case-finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12– 0.15 during 1956–1992 and a mean of 0.10 during 1993–2000 to a mean of 0.26 during 2001–2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10–15 years later.

Transplant patients are exposed to many different types of mental and social stress. The study investigates these patients' need for psychosocial counselling.At 6 months and again at 12 months following either a lung, liver or bone-marrow transplantation, 76 patients were questioned about their need for psychosocial counselling. The measuring instruments employed were: SF-36 (quality of life), FLZ (life satisfaction), HADS-D (anxiety/depression), and F-SoZu K-14 (social support).The need for psychosocial counselling in all three patient groups was at its greatest before transplantation. It amounted to 42.9 % (lung transplantation patients), 50.0 % (liver transplantation patients) and 26.7 % (bone marrow transplantation patients). Six months after transplantation, the need for counselling in all patient groups had quite clearly decreased. Among liver transplant patients, however, it increased again between the sixth and twelfth months. The need for counselling in all patient groups correlated significantly with anxiety. Moreover, at one-year follow-up, significantly negative correlations with mental health, life satisfaction and social support were observed.Especially during the evaluation phase prior to organ transplantation, transplantation patients demonstrate a considerable need for counselling. Psychosocial counselling should be an obligatory part of therapy before and after organ transplantation.

Long-term benzimidazole therapy benefits patients with non-resectable alveolar echinococcosis (AE). Methods to assess early therapeutic efficacy are lacking. Recently, AE liver lesions were reported to exhibit increased F-18-fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET). To assess the value of FDG-PET for diagnosis and follow-up of AE patients. Twenty-six consecutive patients with newly diagnosed AE were enrolled. Baseline evaluation included CT and FDG-PET. Thirteen patients (11 women; median age 50 years, range 40-76) were resected, the remaining 13 (8 women; median age 60 years, range 39–72) had non-resectable disease, were started on benzimidazoles, and CT and FDG-PET were repeated at 6, 12 and 24 months of therapy. Twelve consecutive patients with newly diagnosed cystic echinococcosis (CE) of the liver were also subjected to baseline FDG-PET. In 21/26 AE patients, baseline PET scans showed multifocally increased FDG uptake in the hepatic lesions' periphery, while liver lesions were FDG negative in 11/12 CE patients. Thus, sensitivity and specificity of FDG-PET for AE vs. CE were 81% and 92%, respectively. In 5 of 10 non-resectable patients with increased baseline FDG uptake, the intensity of uptake decreased (or disappeared) during benzimidazole therapy, in 3 by ≥2 grades within the initial 6 months. FDG-PET is a sensitive and specific adjunct in the diagnosis of suspected AE and can help in differentiating AE from CE. The rapid improvement of positive PET scans with benzimidazole therapy in some patients indicates that absent FDG uptake does not necessarily reflect parasite viability.

Only few comparative prospective studies have been published on psychosocial issues of organ transplant. This study investigated patient groups with various organ transplants with respect to their quality of life and psychosocial situation before and after surgery.76 patients receiving an organ transplant (lung n = 22, liver n = 26, allogeneic bone marrow n = 28) were investigated with regard to quality of life (SF-36), life satisfaction (FLZ), social support (F-SozU), and psychological symptoms (HADS-D) before (T0) as well as six (T1) and twelve (T2) months after transplant.In the pre-transplant period the values of the psychosocial variables were partly lower than those of the community normal sample. After transplant lung and bone marrow patients reported less anxiety and depression and a higher life satisfaction, and liver patients reported less depression, compared to the norms. Quality of life, life satisfaction and psychological symptoms of all patients improved significantly post-transplant, whereas the perceived social support decreased. Contrary to the other groups, the psychological well-being of liver transplant recipients was deteriorating between T1 and T2.An organ transplant improved the patients' quality of life and psychosocial situation to a great extent. This effect was better in lung and bone marrow than in liver transplant patients.

Objective The pretransplant medical evaluation of transplantation candidates includes an assessment of psychosocial data. This study investigates psychosocial vulnerability as a predictor of posttransplant outcome. Methods Seventy-six patients were assessed prior to lung, liver, or bone-marrow transplant. Pretransplant vulnerability markers were cognitive beliefs (sense of coherence and optimism), affect (anxiety and depression), and external resources (social support). In addition, psychosocial functioning was assessed by professionals. Quality of life, general life satisfaction, need for counseling, and survival rate were assessed 12 months after transplant. Results Pretransplant variables explain 21–40% of the variance in posttransplant psychosocial outcome variables. Cognitive beliefs predict mental quality of life; affect (depression) and social support predict life satisfaction; and expert-rated psychosocial functioning predicts life satisfaction and need for counseling. Conclusion The multidimensional vulnerability model is suitable for predicting posttransplant psychosocial outcome. Patients with high pretransplant vulnerability should receive ongoing psychosocial counseling.

In vitro protein synthesis on exogenous messenger ribonucleic acids can be performed in various systems including cytoplasmic extract from eukaryotic cells, rabbit reticulocyte lysate and wheat germ extract. For optimal translation, an energy regeneration system based on creatine phosphate and creatine kinase is commonly employed for the regeneration of the endogenous adenosine triphosphate pools. Creatine kinase purchased from various commercial suppliers can be partially oxidised. Oxidised creatine kinase is not biologically active and might not allow the efficient initiation of translation of exogenous mRNAs in eukaryotic cell extracts in vitro.We successfully used dithiothreitol to reduce and therefore reactivate commercially available creatine kinase. When employed in cytoplasmic extracts obtained from eukaryotic cells grown in monolayers, the reactivated creatine kinase restored translation of the exogenous mRNAs.Lyophilised creatine kinase obtained from commercial suppliers can be purchased as an oxidised monomer. The reactivation of creatine kinase using a reducing agent such as dithiothreitol restores the biological activity of this enzyme. This procedure might therefore be extended to various other in vitro conditions and biological systems in which the maintenance of an efficient ATP-regenerating system is critical.

Hepatitis C virus (HCV) infects hepatocytes and leads to permanent, severe liver damage. Since the genomic sequence of HCV was determined, progress has been made towards understanding the functions of the HCV-encoded proteins and identifying the cellular receptor(s) responsible for adsorption and penetration of the virus particle into the target cells. Several cellular receptors for HCV have been proposed, all of which are associated with lipid and lipoprotein metabolism. This article reviews the cellular receptors for HCV and suggests a general model for HCV entry into cells, in which lipoproteins play a crucial role.

OBJECTIVE: Several studies have reported an increased frequency of cystic fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis has not been analyzed. The aim of our study was to determine the frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis with long-term follow-up and to see whether patients with mutations have a clinically different natural course compared to those without mutations. METHODS: Eighty two patients with chronic pancreatitis and 11 patients with recurrent acute pancreatitis of our well defined pancreatitis cohort were screened for the 31 most common cystic fibrosis gene mutations. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis was assessed. RESULTS: A cystic fibrosis gene mutation was detected in five of 49 patients with alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8 times the expected frequency). No mutations were found in the remaining patients with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent acute pancreatitis. The frequency of pancreatic calcifications was significantly higher in patients with alcoholic chronic pancreatitis without mutations. This result was not confirmed in patients with idiopathic-juvenile chronic pancreatitis. The duration of pain and the frequency of exocrine and endocrine insufficiency was comparable in both subgroups irrespective of the mutation status. CONCLUSION: Our data indicate a significantly increased frequency of cystic fibrosis gene mutations both in patients with alcoholic and idiopathic-juvenile chronic pancreatitis. The natural course was similar in patients with mutations compared to those without mutations.

Three-point mutations (R117H, N211, A16V) within the cationic trypsinogen gene have been identified in patients with hereditary pancreatitis (HP). A genetic background has also been discussed for idiopathic juvenile chronic pancreatitis (IJCP), which closely mimicks the clinical pattern of HP, and alcoholic chronic pancreatitis because only a small number of heavy drinkers develop pancreatitis. This prompted us to screen 104 patients in our well-defined pancreatitis cohort for the currently known cationic trypsinogen gene mutations. The R117H mutation was detected in seven patients (six patients of two clinically classified HP families, one patient with clinically classified IJCP) and the A16V mutation in one IJCP patient. No cationic trypsinogen gene mutations were found in the remaining 96 patients with chronic and recurrent acute pancreatitis of various etiologies. Our results demonstrate the need for genetic testing to exclude HP, particularly in the presence of an atypical or unknown family history. In addition, cationic trypsinogen gene mutations are no predisposing factor in patients with chronic and recurrent acute pancreatitis of different etiologies.