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Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000–2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women’s risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

Introduction. Until now, there has been limited evidence, primarily from US cohorts, focusing on frailty as a patient-oriented outcome after liver transplantation (LT). Our study aimed to explore the relationship between pre- and post-LT frailty in a multicenter European cohort of outpatients with cirrhosis undergoing LT. Methods. We conducted a prospective analysis of data from 180 LT recipients recruited between 2018 and 2020 from 5 Spanish centers. Participants underwent objective and subjective frailty assessments using the Liver Frailty Index (LFI) and the Subjective Clinician Assessment (SCA) pretransplant and at 3- and/or 6-mo posttransplant. Results. The median pretransplant LFI was 3.9, showing minimal change at 3 mo (3.8; P = 0.331) and improvement at 6-mo post-LT (3.6; P = 0.001). Conversely, the SCA significantly improved early post-LT: at 3 mo, poor SCA decreased from 11% to 1%, and good SCA increased from 54% to 89% (P

BackgroundDespite the WHO's report of 24 available SARS-CoV-2 vaccines, limited data exist regarding vaccination policies for liver transplant (LT) patients. To address this, we conducted a global multi-society survey (EASL-ESOT-ELITA-ILTS) in LT centers.MethodsA digital questionnaire assessing vaccine policies, safety, efficacy, and center data was administered online to LT centers.ResultsOut of 168 responding centers, 46.4%, 28%, 13.1%, 10.7%, and 1.8% were from European, American, Western Pacific, Southeast Asian, and Eastern Mediterranean Regions. Most LT centers prioritized COVID-19 vaccine access for LT patients (76%) and healthcare workers (86%), while other categories had lower priority (30%). One-third of responders recommended mRNA vaccine exclusively, while booster doses were widely recommended (81%). One-third conducted post-vaccine liver function tests post COVID-19 vaccine. Only 16% of centers modified immunosuppression, and mycophenolate discontinuation or modification was the main approach. Side effects were seen in 1 in 1,000 vaccinated patients, with thromboembolism, acute rejection, and allergic reaction being the most severe. mRNA showed fewer side effects (−3.1, p = 0.002).ConclusionCOVID-19 vaccines and booster doses were widely used among LT recipients and healthcare workers, without a specific vaccine preference. Preventative immunosuppression adjustment post-vaccination was uncommon. mRNA vaccines demonstrated a favorable safety profile in this population.

Background & Aims: Frailty is prevalent in liver transplant (LT) candidates. It is considered an independent predictor of adverse outcomes pre- and post-transplant according to data obtained in the United States. We aimed to externally validate the liver frailty index (LFI) in a multicenter cohort of LT candidates. Methods: Outpatients with cirrhosis were prospectively recruited from five Spanish centers (2018-2020). Patients were defined as “frail” by an optimal cut-off of LFI ≥4.5. Patients were followed for at least 6 months to study associations of pre-LT frailty with pre- and post-transplant mortality, length of hospital and intensive care unit (ICU) stays, risk of early (

Abstract Background Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. Method Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. Results Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77–2.67). The median follow‐up period was 5.1 95% CI [4.7–5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51–10.59], P

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into ‘low’ or ‘high’ responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted ‘low’ humoral response, whereas viral hepatitis and antiviral therapy predicted ‘high’ humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a ‘lower’ humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a ‘higher’ humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.

In patients with cirrhosis, sarcopenia is a critical reduction in skeletal muscle mass and frailty represents a status of global physical dysfunction caused by under nutrition, muscle wasting, and functional impairment. Both are prevalent conditions in liver transplant candidates and have shown to be independent predictors of adverse outcome. Evidence supports their incorporation into clinical practice both as a prognostic factor guiding clinical decision making and as a tool to identify candidates for physical and nutritional interventions. The wide heterogeneity of instruments used for sarcopenia and frailty measurement, the absence of a single suitable instrument for sarcopenia and frailty assessment in the outpatient versus inpatient acute‐on‐chronic clinical scenario, and the lack of strong evidence showing a beneficial effect of sarcopenia and frailty improvement on outcomes before and after transplantation are some of the questions that remain unanswered.

Introduction and Objectives: Outcomes of liver transplantation (LT) with donors after circulatory death (DCD) have been considered suboptimal due to higher rates of ischemic cholangiopathy, especially when the super-rapid recovery (SRR) technique is used. This study aimed to compare the incidence of complications between recipients receiving DCD vs those receiving donors after brain death (DBD) in a large-volume liver transplant centre. Methods: We performed a retrospective cohort study (LT from January 2015 to December 2018) comparing recipients who underwent a LT with DCD vs. a control group of LT with DBD, matched 1:1 without replacement by propensity score matching that included the following variables: LT indication, recipient sex and age, donor age and MELD score. Results: 51 recipients with DCD-LT (29 SRR, 22 normothermic regional perfusion [NRP]) were matched with 51 DBD-LT recipients. Biliary complications were more frequent in DCD, 10% (n=5), all with SRR technique, vs 2% (n=1) in the DBD group, p=0.2. Two patients (4%) suffered primary graft non-function in the DCD group (1 SRR and 1 NRP) versus zero in the DBD group (p=0.49). Postoperative bleeding and reinterventions were also higher in the DCD group: 7 (13.7%) vs 1 (1.95%) and 8 (15.7%) vs 2 (3.9%) respectively (p=0.06 and 0.09). On the 1st postoperative day AST/ALT peak was higher in DCD (p≤0001). The incidence of rejection, vascular complications, renal injury, hospital stay, and readmissions were similar in both groups. Cumulative 1-, 2-, 3- and 4-year graft and patient survival were also similar. Conclusions: DCD donors are an adequate option to increase the donor pool in LT, achieving similar graft and patient survival rates to those achieved with DBD donors, especially when the NRP technique is used.

Abstract Background Previous studies have described sex-based differences in the epidemiological and clinical patterns of non-alcoholic fatty liver disease (NAFLD); however, we understand relatively little regarding the underlying molecular mechanisms. Herein, we present the first systematic review and meta-analysis of NAFLD transcriptomic studies to identify sex-based differences in the molecular mechanisms involved during the steatosis (NAFL) and steatohepatitis (NASH) stages of the disease. Methods Transcriptomic studies in the Gene Expression Omnibus database were systematically reviewed following the PRISMA statement guidelines. For each study, NAFL and NASH in premenopausal women and men were compared using a dual strategy: gene-set analysis and pathway activity analysis. Finally, the functional results of all studies were integrated into a meta-analysis. Results We reviewed a total of 114 abstracts and analyzed seven studies that included 323 eligible patients. The meta-analyses identified significantly altered molecular mechanisms between premenopausal women and men, including the overrepresentation of genes associated with DNA regulation, vinculin binding, interleukin-2 responses, negative regulation of neuronal death, and the transport of ions and cations in premenopausal women. In men, we discovered the overrepresentation of genes associated with the negative regulation of interleukin-6 and the establishment of planar polarity involved in neural tube closure. Conclusions Our meta-analysis of transcriptomic data provides a powerful approach to identify sex-based differences in NAFLD. We detected differences in relevant biological functions and molecular terms between premenopausal women and men. Differences in immune responsiveness between men and premenopausal women with NAFLD suggest that women possess a more immune tolerant milieu, while men display an impaired liver regenerative response. Graphical abstract

Wilson disease (WD) is a rare, inherited metabolic disorder manifested with varying clinical presentations including hepatic, neurological, psychiatric, and ophthalmological features, often in combination. Causative mutations in the ATP7B gene result in copper accumulation in hepatocytes and/or neurons, but clinical diagnosis remains challenging. Diagnosis is complicated by mild, non-specific presentations, mutations exerting no clear effect on protein function, and inconclusive laboratory tests, particularly regarding serum ceruloplasmin levels. As early diagnosis and effective treatment are crucial to prevent progressive damage, we report here on the establishment of a global collaboration of researchers, clinicians, and patient advocacy groups to identify and address the outstanding challenges posed by WD.

Introduction and objectives: Non-alcoholic steatohepatitis (NASH) indication of liver transplant (LT) has increased recently, whereas alcoholic cirrhosis remains a major indication for LT. To characterize NASH-related cases and to compare the post-transplant outcome of these two conditions represents our major objective. Material and methods: Patients undergoing LT for NASH between 1997 and 2016 were retrieved. Those transplanted between 1997 and 2006 were compared to an “age and LT date” matched group of patients transplanted for alcoholic cirrhosis (ratio 1:2). Baseline features and medium-term outcome measures were compared. Results: Of 1986 LT performed between 1997 and 2016, 40 (2%) were labeled as NASH-related indications. NASH-related cases increased initially (from 0.8% in 1997–2001 to 2.7% in 2002–2006) but remained stable in subsequent years (2.3%). Hepatocellular carcinoma (HCC) prevalence was greater in NASH-vs alcohol-related cirrhosis (40% vs 3%, p = 0.001). The incidence of overweight, obesity, arterial hypertension, dyslipidemia, diabetes, hyperuricemia, renal insufficiency and cardiovascular (CV) disease was similar in both groups at 5 years post-LT. Five-year survival was higher in NASH but without reaching statistical significance (83% vs 72%, p = 0.21). The main cause of mortality in NASH-LT patients was HCC recurrence. Conclusion: Most previously considered cryptogenic cases are actually NASH-cirrhosis. While the incidence of this indication is increasing in many countries, it has remained relatively stable in our Unit, the largest LT center in Spain. HCC is common in these patients and represents a main cause of post-transplant mortality. Metabolic complications, CV-related disease and 5-yr survival do not differ in patients transplanted for NASH vs alcohol.

The ratio between slower and faster frequencies of brain activity may change after stroke. However, few studies have used quantitative electroencephalography (qEEG) index of ratios between slower and faster frequencies such as the delta/alpha ratio (DAR) and the power ratio index (PRI; delta+theta/alpha+beta) for investigating the difference between the affected and unaffected hemisphere poststroke. Here, we proposed a new perspective for analyzing DAR and PRI within each hemisphere and investigated the motor impairment-related interhemispheric frequency oscillations. Forty-seven poststroke subjects and twelve healthy controls were included in the study. Severity of upper limb motor impairment was classified according to the Fugl–Meyer assessment in mild/moderate (n=25) and severe (n=22). The qEEG indexes (PRI and DAR) were computed for each hemisphere (intrahemispheric index) and for both hemispheres (cerebral index). Considering the cerebral index (DAR and PRI), our results showed a slowing in brain activity in poststroke patients when compared to healthy controls. Only the intrahemispheric PRI index was able to find significant interhemispheric differences of frequency oscillations. Despite being unable to detect interhemispheric differences, the DAR index seems to be more sensitive to detect motor impairment-related frequency oscillations. The intrahemispheric PRI index may provide insights into therapeutic approaches for interhemispheric asymmetry after stroke.

BACKGROUND:Data on the true prevalence of hepatitis C virus (HCV) infection in the general population is essential. We evaluated a program implementing free universal HCV screening using a non-invasive point-of-care test (POCT) (OraQuick-HCV rapid test) in oral fluid in an urban area in Valencia, South-Eastern Spain. METHODS:A cross-sectional study was performed during 2015-2017. Free HCV screening was offered by regular mail to 11,500 individuals aged 18 and over, randomly selected from all census residents in the Health Department. All responding participants filled in a questionnaire about HCV infection risk factors and were tested in their tertiary Hospital. In those with a positive POCT, results were confirmed by enzyme-immunoassay and HCV-RNA. RESULTS:1,206 persons agreed to participate (response rate: 11.16%). HCV antibodies were detected in 19 (1.60%) cases (age-sex standardized rate: 1.31%; 95%CI: 0.82-2.07), but only 8 showed positive HCV-RNA (age-sex standardized rate: 0.56%; 95%CI: 0.28-1.14). The majority (89%) of the cases were born before 1965 and 74% had at least one known risk factor for HCV infection. All anti-HCV positive individuals were already aware of their infection, and no undiagnosed cases were detected. The performance of the POCT was excellent for detecting active infection. CONCLUSIONS:These preliminary data suggest that HCV population screening with a POCT is feasible but, in our setting, mailing recruiting is not effective (11% response rate). The low prevalence of HCV antibodies and active infection in the participant population (with no new diagnoses made) suggests that, in our setting, underdiagnosis may be uncommon.

RESUMEN Introducción: la colangitis biliar primaria (CBP) es una enfermedad rara, de la que existe información limitada en España sobre su epidemiología y manejo en la práctica clínica habitual. Objetivos: conocer la epidemiología, flujo del paciente, diagnóstico, seguimiento y tratamiento de la CBP en España. Métodos: revisión de la literatura y estudio siguiendo la metodología Delphi con participación de 28 especialistas en dos rondas de consulta y un taller de validación de resultados presencial. Resultados: existen, aproximadamente, 9.400 pacientes con CBP en España, con una incidencia anual de entre 0,51 y 3,86 casos/100.000 habitantes, aunque el margen de error se presupone alto dada la escasez de estudios. El intervalo entre sospecha y confirmación diagnóstica puede ser de varios meses, realizándola mayoritariamente un gastroenterólogo o hepatólogo. El papel de la biopsia hepática en el diagnóstico y seguimiento es heterogéneo. El 95% de los pacientes son tratados con ácido ursodesoxicólico (AUDC) y la respuesta se monitoriza mayoritariamente utilizando el criterio de Barcelona. El seguimiento es semestral, con un uso heterogéneo de las diferentes técnicas disponibles. No existen recomendaciones ni fármacos comercializados en segunda línea en caso de no respuesta, respuesta insuficiente o intolerancia al tratamiento con AUDC. Conclusiones: aunque es posible estimar la epidemiología a partir de la opinión de expertos, se necesitan registros nacionales que aporten información precisa y actualizada sobre la epidemiología, el estadio y la respuesta al tratamiento de los pacientes con CBP, así como tratamientos nuevos para ciertos grupos de pacientes.

Wilson disease (WD) is a rare disorder caused by mutations in ATP7B, which leads to the defective biliary excretion of copper. The subsequent gradual accumulation of copper in different organs produces an extremely variable clinical picture, which comprises hepatic, neurological psychiatric, ophthalmological, and other disturbances. WD has a specific treatment, so that early diagnosis is crucial to avoid disease progression and its devastating consequences. The clinical diagnosis is based on the Leipzig score, which considers clinical, histological, biochemical, and genetic data. However, even patients with an initial WD diagnosis based on a high Leipzig score may harbor other conditions that mimic the WD’s phenotype (Wilson-like). Many patients are diagnosed using current available methods, but others remain in an uncertain area because of bordering ceruloplasmin levels, inconclusive genetic findings and unclear phenotypes. Currently, the available biomarkers for WD are ceruloplasmin and copper in the liver or in 24 h urine, but they are not solid enough. Therefore, the characterization of biomarkers that allow us to anticipate the evolution of the disease and the monitoring of new drugs is essential to improve its diagnosis and prognosis.

Background. Milan criteria are widely used for liver transplantation selection in hepatocellular carcinoma but have been recognized to be too restrictive. Milan-out criteria are increasingly being adopted. Our aim was to analyze if liver transplantation waitlisted Milan-out hepatocellular carcinoma patients have different outcome than Milan patients. Methods. Retrospective study including all consecutive patients with hepatocellular carcinoma admitted in the waiting list for liver transplantation between January 2012 and January 2015. We included 177 patients, 146 of which eventually transplanted. Downstaging was achieved in the Milan-out cases (n = 29) before waitlisting. Results. From diagnosis to last follow-up, 29% patients died. Survival at 1 and 5 years from diagnosis was 93% and 75%, respectively in the within Milan group compared with 91% and 61% in the Milan-out group (P = 0.03). Treatment failure occurred in 20% of cases due to tumor progression in the waiting list (44%), death on the waiting list (20%), and hepatocellular carcinoma recurrence postliver transplantation (9%). Milan-out criteria was the only variable predictive of treatment failure remaining in the multivariate analysis with a hazard ratio (HR) of 1.7 (HR, 1.7; 95% confidence interval, 1.34-4.55; P = 0.010) and HR of 1.43 (1.23-6.5) in the hepatocellular carcinoma recurrence. Conclusions. Milan-out criteria are associated with a higher intention-to-treat liver transplantation failure from time of inclusion in the waiting list. However, survival rates are still >50% at 5 years of follow-up.

Background and rationale. The REPLACE study (NCT01571583) investigated telaprevir-based triple therapy in patients who have recurrent genotype 1 hepatitis C virus (HCV) infection following liver transplantation and are on a stable immunosuppressant regimen of tacrolimus or cyclosporin A. Patients received telaprevir 750 mg 8-hourly with pegylated interferon 180 μg weekly and ribavirin 600 mg daily, followed by a further 36 weeks of pegylated interferon and ribavirin alone and 24 weeks of follow-up. Efficacy (sustained virological response [SVR] 12 weeks after last planned study dose), safety and tolerability of telaprevir throughout the study were assessed. Pharmacokinetics of telaprevir, tacrolimus and cyclosporin A were also examined.Results. In total, 74 patients were recruited. Overall, 72% (53/74; 95% CI: 59.9 to 81.5) of patients achieved SVR at 12 weeks following completion of treatment. Anticipated increases in plasma concentrations of tacrolimus and cyclosporin A occurred during telaprevir treatment and were successfully managed through immunosuppressant dose reduction and, for tacrolimus, reduced dosing frequency. Safety and tolerability of telaprevir-based triple therapy were generally comparable with previous data in non-transplant patients, although rates of reported anemia (55% [41/74]) were higher. Elevated plasma creatinine (46% [34/74]) was observed during REPLACE - consistent with the post-liver transplant population and the co-administered immunosuppressants.Conclusion. Telaprevir-based triple therapy in patients with recurrent genotype 1 HCV infection following liver transplantation produced high rates of SVR. Therapeutic concentrations of immunosuppressants were maintained successfully through dose modification during telaprevir treatment.

Background and rational. Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220).Results. The mean patient age was 55 years, 67% male. Type of prior response was 22% naïve, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%), respectively. Sixty-five percent were non-CC IL28B genotype. Week-12 sustained virologic response (SVR12) was significantly higher among F2-naïve patients (78%) compared with F3/F4-naïve patients (60%; p = 0.039) and among F2 non-responders (67%) compared with F3/F4 non-responders (42%; p = 0.014). SVR12 among relapsers was remarkably high in both groups (F2:89% vs. F3/F4:78%). Severe anemia and thrombocytopenia were more frequent among patients with F3/F4 than those with F2 (p < 0.01). Overall, 132 patients (22%) discontinued treatment: 58 due to adverse effects, 42 due to the stopping-rule, and 32 due to breakthrough. Premature discontinuation was more frequent among patients with F3/F4 (p = 0.028), especially due to breakthrough (p < 0.001). Conclusions. This multicenter study demonstrates high efficacy and an acceptable safety profile with regard to TBT in F2-patients in clinical practice.

Abstract Aims the aim of this study was to verify the effects of different intensities of locomotor exercise on corticospinal excitability. Methods 18 healthy subjects (27.6 ± 6.5 years,) participated in a design study of three different exercise protocols on a cycle ergometer: (i) 10 min at 75% Wmax (high intensity); (ii) 15min at 60% Wmax (moderate intensity) or (iii) 30 min at 45% Wmax (low intensity). The protocols of lower body cycling were assigned in random order in separate sessions. A control session was done with subjects at rest. Corticospinal excitability was assessed before (baseline) and every 5 min for 15min after the end of exercise/rest (time: 0, 5, 10 and 15) by measurement of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation in the relaxed first-dorsal interosseus muscle. Results Compared to the resting session, a significant decrease (64%) in the motor evoked potential amplitudes was found only in the session of exercise of high intensity. This result seems depend on the level of physical activity of subject. No change was found after rest, low and moderate exercises. Conclusions These findings suggest that changes in the corticospinal excitability depend on exercise intensity and level of physical activity of subjects.

Haemophagocytic syndrome (HS) is a rare disease that is often fatal despite treatment. HS is characterized by fevers, lymphadenopathy, hepatosplenomegaly, cytopenias and hyperferritinaemia due to deregulated activation and proliferation of macrophages, leading to uncontrolled phagocytosis of platelets, erythrocytes, lymphocytes, and their hematopoietic precursors throughout the reticuloendothelial system. Mycobacterium tuberculosis-associated HS is a rare and underdiagnosed association with only 39 cases reported. We describe a case of HS associated with disseminated Mycobacterium tuberculosis in the setting of post-liver transplantation anti-hepatitis C therapy with pegylated interferon (pegIFN), ribavirin (RBV) and telaprevir (TVR). Despite the delay in the etiologic diagnosis, the patient was treated properly with corticosteroids, cyclosporine and tuberculostatic agents. It is unknown whether telaprevir, a drug that only recently has been started off-label in liver transplant recipients, may have contributed to the development of the HS. Unfortunately, as in many reported cases of HS, the outcome was unfavourable resulting in the death of the patient.

Introduction. Combined liver-kidney transplantation (LKT) is the best therapeutic option for patients with end-stage liver and kidney disease. Objectives. To analyze baseline characteristics and clinical outcome of LKT compared to isolated liver transplantation (LT).Material and methods. The study included 16 LKT performed between 1998 and 2006 and 32 LT matched by age, sex, date and indication for transplantation. Demographic, pretransplant, post-transplant and survival variables were analyzed.Results. As planned by the study design, mean age, distribution by sex and indication for LT were similar between groups. The most common indication for LT was HCV- and/or alcohol-induced cirrhosis. The most common indication for KT was renal failure, in most cases secondary to glomerulonephritis. Twelve patients (69%) were on dialysis before LKT. Hepatocellular carcinoma and diabetes mellitus pre-transplantation were similar between groups. However pretransplant arterial hypertension (AHT) was higher in LKT than LT (50% vs. 19%; p = 0.02). In the post-transplant: reoperation due to bleeding, bacterial infections, liver rejection, AHT and median creatinine levels at 1st and 3rd years were similar in LKT and LT. In contrast, early post-transplant dialysis was higher in LKT than LT (31% vs. 3%; p = 0.01). Survival rates at 1st, 3rd, 5th and 7th years were similar in both groups (87.5%, 74%, 74% and 66% vs. 81%, 75%, 75% and 75% in LT and LKT, respectively).Conclusions. LKT is an effective therapeutic option in patients with end-stage liver and kidney disease. Most early and late complications and long-term survival are similar to those observed with LT.