ABSTRACT
Herpes simplex virus (HSV)-2 is a rare cause of hepatitis that can lead to acute liver failure (ALF) and often death. The earlier the initiation of acyclovir treatment the better the survival. With regard to ALF, controlled randomized data support the use of therapeutic plasma exchange (TPE) both as bridge to recovery or transplantation-possibly by modulating the systemic inflammatory response and by replacing coagulation factors. Seraph 100 Microbind Affinity Blood Filter (Seraph; Ex Thera Medical, Martinez, CA), a novel extracorporeal adsorption device, removes living pathogens by binding to a heparin-coated surface was shown to efficiently clear HSV-2 particles in vitro. Here, we tested the combination of Seraph with TPE to reduce a massive HSV-2 viral load to reach a situation in that liver transplantation would be feasible. DESIGN: Explorative study. SETTING: Academic tertiary care transplant center. PATIENT: Single patient with HSV-2-induced ALF. INTERVENTIONS: TPE + Seraph 100 Microbind Affinity Blood Filter. MEASUREMENTS AND MAIN RESULTS: We report Seraph clearance data of HSV-2 and of Epstein-Barr virus (EBV) in vivo as well as total viral elimination by TPE. Genome copies/mL of HSV-2 and EBV in EDTA plasma were measured by polymerase chain reaction every 60 minutes over 6 hours after starting Seraph both systemically and post adsorber. Also, HSV-2 and EBV were quantified before and after TPE and in the removed apheresis plasma. We found a total elimination of 1.81 × e11 HSV-2 copies and 2.11 × e6 EBV copies with a single TPE (exchange volume of 5L; 1.5× calculated plasma volume). Whole blood clearance of HSV-2 in the first 6 hours of treatment was 6.64 mL/min (4.98-12.92 mL/min). Despite much lower baseline viremia, clearance of EBV was higher 36.62 mL/min (22.67-53.48 mL/min). CONCLUSIONS: TPE was able to remove circulating HSV-2 copies by 25% and EBV copies by 40% from the blood. On the other hand, clearance of HSV-2 by Seraph was clinically irrelevant, but Seraph seemed to be far more effective of removing EBV, implicating a possible use in EBV-associated pathologies, but this requires further study.
ABSTRACT
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 of 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.
Subject(s)
Duration of Therapy , Positron Emission Tomography Computed Tomography , Benzimidazoles/therapeutic use , Echinococcosis , Humans , Retrospective StudiesABSTRACT
PURPOSE: To investigate the potential role of follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in therapy control of inoperable patients with alveolar echinococcosis. MATERIALS AND METHODS: In this single-center retrospective cohort study, 48 PET/CT of 16 patients with confirmed alveolar echinococcosis were analysed. FDG-uptake of the most active echinococcosis manifestation was measured (i.e., maximum standardized uptake value (SUVmax) and in relation to background activity in normal liver tissue (SUVratio)) and compared to immunodiagnostic testing. For clinical patient follow-up, patient demographics, laboratory data, including E. granulosus hydatid fluid (EgHF) antibody units (AU) as well as clinical and treatment information were assessed for all patients at the time of PET/CT, and at the last recorded clinical visit. RESULTS: Metabolic activity of PET/CT measured in the echinococcosis manifestation was significantly correlated with EgHF AU (p < 0.001). The differences in metabolic activity of echinococcosis manifestations between two consecutive PET/CT examinations of the same patient and differences in EgHF AU in the respective time intervals displayed a significant positive correlation (p = 0.01). A trend for a more rapid decline in SUVratio liver over time was found in patients who stopped benzimidazole therapy versus patients who did not stop therapy (p = 0.059). CONCLUSION: In inoperable patients with alveolar echinococcosis, the course of metabolic activity in follow-up PET/CT is associated to the course EgHF antibody levels. Both parameters may potentially be used to evaluate the course of the disease and potentially predict the duration of benzimidazole therapy.
Subject(s)
Echinococcosis , Positron Emission Tomography Computed Tomography , Benzimidazoles , Echinococcosis/diagnostic imaging , Fluorodeoxyglucose F18 , Follow-Up Studies , Humans , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography/methods , Radiopharmaceuticals , Retrospective StudiesABSTRACT
Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure.
Subject(s)
Liver Transplantation , Quality of Life , Humans , Liver Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Liver/surgeryABSTRACT
PURPOSE: The aim of the study was to determine the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) at the end of benzimidazole therapy in alveolar echinococcosis. METHODS: A total of 22 patients undergoing PET/CT at the end of benzimidazole therapy were retrospectively registered. Maximum standardized uptake values (SUVmax) were measured in remaining echinococcus manifestations and compared to normal liver tissue. Long-term clinical follow-up was performed, and recorded data included laboratory parameters, clinical information and imaging. RESULTS: All 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. CONCLUSIONS: 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.
Subject(s)
Duration of Therapy , Echinococcosis/therapy , Positron Emission Tomography Computed Tomography/statistics & numerical data , Adult , Aged , Female , Humans , Male , Middle Aged , SwitzerlandABSTRACT
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 × 10-17 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10-10 ) 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 × 10-8 ) 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.
Subject(s)
Genetic Predisposition to Disease/genetics , Liver Cirrhosis, Alcoholic/genetics , Databases, Genetic , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , Risk FactorsABSTRACT
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 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). 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.
Subject(s)
Alcohol Drinking/epidemiology , Coffee , Diabetes Mellitus/epidemiology , Liver Cirrhosis, Alcoholic/epidemiology , Marijuana Use/epidemiology , Obesity/epidemiology , Smoking/epidemiology , Tea , Alcoholic Beverages , Australia/epidemiology , Case-Control Studies , Female , France/epidemiology , Germany/epidemiology , Humans , Logistic Models , Male , Medical History Taking , Middle Aged , Risk Factors , Switzerland , United Kingdom/epidemiology , United States/epidemiology , WineABSTRACT
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.
Subject(s)
Carcinoma, Hepatocellular/prevention & control , Cold Ischemia , Liver Neoplasms/prevention & control , Liver Transplantation , Neoplasm Recurrence, Local/prevention & control , Organ Preservation/methods , Graft Survival , Humans , Oxygen , Perfusion/methodsABSTRACT
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.  .
Subject(s)
Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Obesity/complications , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Female , Humans , Male , Markov Chains , Middle Aged , Obesity/enzymology , Switzerland/epidemiology , Young AdultABSTRACT
BACKGROUND & AIMS: 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). METHODS: 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. RESULTS: 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 (pâ¯=â¯0.005), despite significantly (pâ¯<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 (pâ¯=â¯0.024). CONCLUSIONS: 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. LAY SUMMARY: 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 1-2â¯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.
Subject(s)
Graft Rejection/prevention & control , Hypothermia, Induced/methods , Liver Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Tissue and Organ Procurement , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Graft Survival , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Time FactorsABSTRACT
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 ≥10â000 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 [<15 IU/mL]). The trials are registered at ClinicalTrials.gov, numbers NCT02332707 and NCT02332720. FINDINGS: 676 participants were randomly assigned between Feb 18, 2015, and Aug 16, 2016. In all 675 participants who received at least one dose of study drug (full analysis set), SVR12 for the 8-week regimen of grazoprevir, ruzasvir, and uprifosbuvir with and without ribavirin was achieved in 39 (93% [95% CI 81-99]) of 42 participants with genotype 1a, 45 (98% [88-100]) of 46 with genotype 1b, 54 (86% [75-93]) of 63 with genotype 2, 98 (95% [89-98]) of 103 with genotype 3, and seven (100% [59-100]) of seven participants with genotype 4. SVR12 for the 12-week regimen with and without ribavirin was achieved in 87 (99% [95% CI 94-100]) of 88 participants with genotype 1, 61 (98% [91-100]) of 62 with genotype 2, and four (100% [40-100]) of four with genotype 6. Among participants with cirrhosis who were infected with genotype 3, SVR12 for the 12-week regimen with and without ribavirin was achieved in 28 (97% [95% CI 82-100]) of 29 of those who were treatment-naive and 29 (100% [88-100]) of 29 who were treatment-experienced. SVR12 for the 16-week regimen with and without ribavirin was achieved in 26 (100% [95% CI 87-100]) of 26 participants with genotype 2 infection and 72 (96% [89-99]) of 75 participants with genotype 3 infection. The most common adverse events were headache (143 [22%] of 664), fatigue (129 [19%] of 664), and nausea (83 [13%] of 664). 16 (2%) of 664 participants had serious adverse events. INTERPRETATION: The combined regimen of grazoprevir (100 mg/day), ruzasvir (60 mg/day), and uprifosbuvir (450 mg/day) has the potential to provide a simplified treatment for HCV that is effective and well tolerated in most individuals infected with HCV, as well as a shorter duration of treatment in many individuals. FUNDING: Merck & Co, Inc.
Subject(s)
Antiviral Agents/administration & dosage , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/complications , Uridine/analogs & derivatives , Adult , Amides , Antiviral Agents/adverse effects , Carbamates , Cyclopropanes , Drug Administration Schedule , Female , Genotype , Hepatitis C, Chronic/genetics , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Heterocyclic Compounds, 4 or More Rings/adverse effects , Humans , Liver Cirrhosis/drug therapy , Male , Middle Aged , Pyrrolidines/administration & dosage , Pyrrolidines/adverse effects , Quinoxalines/administration & dosage , Quinoxalines/adverse effects , Ribavirin/administration & dosage , Ribavirin/adverse effects , Sulfonamides , Sustained Virologic Response , Thiazoles/administration & dosage , Thiazoles/adverse effects , Uridine/administration & dosage , Uridine/adverse effectsABSTRACT
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.
ABSTRACT
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.
Subject(s)
Attitude to Health , Organ Transplantation/psychology , Spouses/psychology , Adaptation, Psychological , Adult , Aged , Analysis of Variance , Anxiety , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Quality of Life , Sense of Coherence , Surveys and Questionnaires , Transplantation/psychologyABSTRACT
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.
Subject(s)
Intention , Medication Adherence/psychology , Organ Transplantation/psychology , Postoperative Care/psychology , Social Support , Adult , Aged , Cross-Sectional Studies , Female , Femininity , Humans , Interpersonal Relations , Male , Medication Therapy Management , Middle Aged , Predictive Value of Tests , Psychological Tests , Psychological Theory , Sex Factors , Spouses/psychology , Surveys and QuestionnairesABSTRACT
BACKGROUND & 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<0.001) and similar, albeit weaker associations were found for SNPs in peroxisome proliferator-activated receptor-γ (PPARG) and interleukin-28B (IL28B). Carriage of a SNP in the microsomal triglyceride transfer protein (MTTP) increased the risk of steatosis, but only in patients with HCV genotype 3 (rs1800803, OR=3.4, 95% CI=2.4-4.9, p=0.001). CONCLUSIONS: The rs738409 SNP in PNPLA3 is associated with an increased risk of steatosis in patients infected with HCV genotypes non-3. Host genes affect steatosis depending on the infecting HCV genotype, suggesting their interaction with viral factors.
Subject(s)
Fatty Liver/genetics , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Polymorphism, Single Nucleotide , Adult , Carrier Proteins/genetics , Fatty Liver/complications , Fatty Liver/virology , Female , Genotype , Humans , Interferons , Interleukins/genetics , Lipase/genetics , Logistic Models , Male , Membrane Proteins/genetics , Middle Aged , PPAR gamma/genetics , Severity of Illness IndexABSTRACT
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.
Subject(s)
Adaptation, Psychological , Heart Transplantation/psychology , Kidney Transplantation/psychology , Liver Transplantation/psychology , Lung Transplantation/psychology , Patient Satisfaction , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Physician-Patient Relations , Postoperative Complications/psychology , Social Adjustment , Social Support , Young AdultABSTRACT
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 <200 cells/microL (OR, 34.3; 95% CI, 4.3-277); diabetes mellitus (OR, 8.8; 95% CI, 1.6-49); alanine aminotransferase level higher than normal (OR, 13.0; 95% CI, 2.7-63); alkaline phosphatase higher than normal (OR, 18.3; 95% CI, 4.0-85); and platelets lower than normal (OR, 20.5; 95% CI, 2.4-178). Cumulative exposure to antiretroviral therapy (OR per year, 1.3; 95% CI, 1.0-1.6), nucleoside reverse-transcriptase inhibitor (OR, 1.3; 95% CI, 1.1-1.7), didanosine (OR, 3.4; 95% CI, 1.5-8.1), ritonavir (OR, 1.4; 95% CI, 1.0-1.9), and nelfinavir (OR, 1.4; 95% CI, 1.0-1.9) were longer in case patients. Exposure to nonnucleoside reverse-transcriptase inhibitor and other protease inhibitors were not different between groups. In bivariable models, only the association of NCPH with didanosine exposure was robust; other covariables were not independent risk factors. CONCLUSIONS: We found a strong association between prolonged exposure to didanosine and the development of NCPH.
Subject(s)
Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Didanosine/adverse effects , HIV Infections/complications , HIV Infections/drug therapy , Hypertension, Portal/chemically induced , Hypertension, Portal/epidemiology , Anti-HIV Agents/therapeutic use , Case-Control Studies , Didanosine/therapeutic use , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVES: Quality of life and psychosocial well-being usually improve after an organ transplant and remain stable for a minimum of several years. These findings, however, mainly apply to the "average" trend for transplant patients. This study aims to investigate whether transplant patients fall into different groups in good or poor psychosocial outcome after organ transplantation. METHODS: One hundred thirty-one patients were assessed before and 6, 12, and 24 months after a heart, lung, liver, kidney, or bone-marrow transplant. Cluster analysis was applied to identify typical outcome profiles of the patients' mental health (SF-36); differences between the clusters were investigated with regard to further psychosocial parameters (sense of coherence, optimism, psychosocial functioning, anxiety, depression, life/health satisfaction, medication experience). RESULTS: The analysis revealed two clusters of transplant patients. Cluster A (n=78, 59.5%) showed a fairly good psychosocial outcome, improving over the posttransplant period of 2 years. Cluster B (n=53, 40.5%) included patients who reported a limited or poor outcome, deteriorating after the transplant. Furthermore, there are significant differences between clusters A and B in psychosocial parameters and physical functioning. CONCLUSIONS: These findings indicate that the experience of the transplant process may vary greatly from patient to patient, and that a considerable number of transplant recipients require psychosocial support, despite the majority of patients showing an unquestionable posttransplant improvement in psychosocial well-being.
Subject(s)
Bone Marrow Transplantation/psychology , Health Status , Heart Transplantation/psychology , Kidney Transplantation/psychology , Liver Transplantation/psychology , Lung Transplantation/psychology , Quality of Life , Attitude , Cognition , Follow-Up Studies , Humans , Mental Health , Patient Selection , Social Adjustment , Surveys and Questionnaires , Time Factors , Transplantation, Homologous/psychologyABSTRACT
PRINCIPLES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.