Multidrug-resistant bacterial infections after liver transplantation: Prevalence, impact, and risk factors.

BACKGROUND & AIMS: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). METHODS: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. RESULTS: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. CONCLUSION: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. IMPACT AND IMPLICATIONS: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C / Modelos predictivos para el desarrollo de carcinoma hepatocelular tras la respuesta viral sostenida en pacientes con hepatitis C avanzada

Background & aims: Life-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods: 491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical–biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. Results: During a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01–1.05), age (HR, 1.04; 95% CI, 1.01–1.08) and albumin levels (HR, 0.90; 95% CI, 0.84–0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08–1.37) and albumin (HR, 0.90; 95% CI, 0.84–0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. (AU)

Antecedentes y objetivos: En pacientes con hepatitis C avanzada se recomienda la vigilancia del carcinoma hepatocelular (CHC) de por vida tras la respuesta viral sostenida (RVS). La identificación de pacientes que podrían interrumpir de manera segura el screening es esencial, por ello nuestro objetivo fue identificar subgrupos de pacientes con bajo riesgo de desarrollo de CHC. Métodos: Se realizó un seguimiento prospectivo de 491 pacientes con fibrosis avanzada y compensada (≥F3) tras la RVS obtenida con terapias libres de interferón. Se registraron parámetros clínico-biológicos y se midió la rigidez hepática mediante elastografía de transición (ET) antes del inicio del tratamiento y en la respuesta viral sostenida y se realizó screening para el desarrollo de CHC. Resultados: Durante una mediana de seguimiento de 49,8 meses, 29 (5,9%) pacientes desarrollaron CHC. (Tasa de incidencia: 1,6/100 pacientes-año [PA]). Se propusieron dos modelos predictivos basados en la puntuación de ET (Modelo-A) o FIB-4 (Modelo-B). Se incluyeron los parámetros en RVS en los modelos porque mostraron una mayor precisión para predecir CHC que las mediciones basales. Las variables asociadas de forma independientes con CHC fueron: ET (HR 1,03 IC; IC 95%, 1,01-1,05), edad (HR 1,04; IC 95%, 1,01-1,08) y niveles de albúmina (HR 0,90; IC 95%, 0,84-0,97) en el Modelo-A, y FIB-4 (HR 1,22; IC 95%, 1,08-1,37) y albúmina (HR 0,90; IC 95%, 0,84-0,97) en el Modelo-B. Ambos modelos permiten la estratificación del riesgo de CHC, identificando grupos de bajo riesgo con una tasa de incidencia de CHC de 0,16/100 y 0,25/100 PA, respectivamente. Se observó un aumento general del riesgo de desarrollar CHC con el tiempo. (AU)

Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predniso(lo)ne administration.

BACKGROUND AND AIMS: In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options. APPROACH AND RESULTS: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047). CONCLUSIONS: In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C.

BACKGROUND & AIMS: Life-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. METHODS: 491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical-biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. RESULTS: During a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01-1.05), age (HR, 1.04; 95% CI, 1.01-1.08) and albumin levels (HR, 0.90; 95% CI, 0.84-0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08-1.37) and albumin (HR, 0.90; 95% CI, 0.84-0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. CONCLUSION: Simple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.

Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Long-term Outcome.

BACKGROUND: Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. METHODS: Retrospective multicentre study of 79 patients who received LT for PSVD. RESULTS: Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. CONCLUSIONS: LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.

Noninvasive Prediction of Outcomes in Autoimmune Hepatitis-Related Cirrhosis.

The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy.

Low applicability of the ‘‘six-and-twelve score” in hepatocellular carcinomatreated with drug-eluting bead transarterial chemoembolization

Objective: the effectiveness of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) dependson the selection of suitable patients. The ‘‘six-and-twelve score” distinguishes three groups of ideal patients with different overall survival, based on the sum of the number and size of tumors. This may impact on clinical practice and trial design. The aim of this study was to assess the reproducibility and prognostic value of the model in western patients treated with drug-eluting beads (DEB)-TACE.Methods: an observational, retrospective, unicentric study with consecutive compensated patients treated with DEBTACE from October 2008 to October 2017. Exclusion criteria were Child-Pugh ≥ 8 and DEB-TACE used as a bridge to liver transplantation.Results: a total of 225 consecutive HCC patients were included; BCLC-0/A, n = 131 (single nodules > 5, n = 29) andBCLC-B, n = 94. Median overall survival (OS) was 27 months (95 % CI, 23.8-30.2). OS was different between BCLC-0/A and BCLC-B: 30 vs. 24 months (p = 0.03), Child-Pugh A5 vs. A6-B7: 30 vs. 27 months (p = 0.003). ‘‘Six-and-twelve score” groups discriminated OS: group 1, n = 123, 32 months (95 % CI, 27.5-63.5); group 2, n = 101, 24 months (95% CI, 19.6-28.4); and group 3, n = 1, 27 months (p = 0.024). When comparing the three scores, the ‘‘six-and-twelve score” showed the best discrimination power: C-index, 0.603; Akaike’s informationcriterion (AIC), 1.642; likelihood ratio test (LRT), 16.21.Conclusion: The ‘‘six-and-twelve score” is a prognostic tool for patients with HCC treated with DEB-TACE. However, few patients were included in the third group (score > 12) and no differences were observed with BCLC, therefore applicability is limited. (AU)

Low applicability of the ''Six-and-twelve score" in hepatocellular carcinoma treated with Drug-Eluting Beads Transarterial Chemoembolization.

OBJECTIVE: The effectiveness of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) depends on the selection of suitable patients. The ''Six-and-twelve score" distinguishes three groups of ideal patients with different overall survival, based on the sum of the number and size of tumors. This may impact on clinical practice and trial design. The aim of this study was to assess the reproducibility and prognostic value of the model in western patients treated with Drug-Eluting Beads (DEB)-TACE. METHODS: Observational, retrospective, unicentric study with consecutive compensated patients treated with DEB-TACE from October 2008 to October 2017. Exclusion criteria were Child-Pugh ≥ 8 and DEB-TACE used as a bridge to liver transplantation. RESULTS: 225 HCC consecutive patients were included; BCLC-0/A n=131 (single nodules > 5, n=29) and BCLC-B n=94. The median overall survival (OS) was 27 months (95% CI 23.8-30.2). OS was different between BCLC-0/A vs BCLC-B: 30 vs 24 months (p= 0.03), Child-Pugh A5 vs A6-B7: 30 vs 27 months (p= 0.003). ''Six-and-twelve score" groups discriminated OS: group 1, n=123, 32 months (95% CI 27.5-63.5), group 2, n=101, 24 months (95% CI 19.6-28.4) and group 3, n=1, 27 months (p=0.024). When comparing the three scores, the ''Six-and-twelve score" showed the best discrimination power: C-index 0.603, Akaike's information criterion (AIC) 1.642, likelihood ratio test (LRT) 16.21. CONCLUSION: The ''Six-and-twelve score" is a prognostic tool for patients with HCC treated with DEB-TACE. However, few patients were included in the third group (score >12) and no differences were observed with BCLC, therefore its applicability is limited. .

Impact of Alcohol Abstinence on the Risk of Hepatocellular Carcinoma in Patients With Alcohol-Related Liver Cirrhosis.

INTRODUCTION: Although alcohol cessation is the only effective treatment for alcohol-related liver disease, few data exist concerning its influence on the risk of hepatocellular carcinoma (HCC). We aimed to evaluate the effect of alcohol abstinence on the incidence of HCC in patients with alcohol-related cirrhosis. METHODS: We studied 727 patients with alcohol-related cirrhosis (247 with compensated disease and 480 with previous decompensation) who were included in a surveillance program for the early detection of HCC and prospectively followed. Baseline clinical and biological parameters and alcohol consumption during follow-up were recorded. Abstinence was defined as the absence of any alcohol use. RESULTS: During follow-up (median 54 months), 354 patients (48.7%) remained abstinent and 104 developed HCC (2.3 per 100 person-years). Factors independently associated with the risk of HCC among patients with previous decompensation were age, male gender, and aspartate aminotransferase, whereas abstinence was not linked to a reduced risk (hazard ratio 0.95; 95% confidence interval 0.59-1.52). However, among patients without previous decompensation, prothrombin activity and abstinence were independently associated with the risk of HCC. Abstinent patients had a significant decrease in the risk of developing tumor (hazard ratio 0.35; 95% confidence interval 0.13-0.94). These results did not change after applying a competing risk analysis where death and liver transplantation were considered as competing events. DISCUSSION: Alcohol abstinence reduced the risk of HCC in patients with alcohol-related cirrhosis, but only in those without a history of decompensated disease. This finding emphasizes the need for an early diagnosis of alcohol-related liver disease and for implementing strategies leading to an increase in the rate of achieving and maintaining abstinence among this population.

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study.

INTRODUCTION: Obeticholic acid (OCA) and fibrates therapy results in biochemical improvement in placebo-controlled trials in patients with primary biliary cholangitis and insufficient response to ursodeoxycholic acid. There is scarce information outside of clinical trials. Therefore, we have assessed the effectiveness and adverse events of these treatments. METHODS: Data from patients included in the ColHai registry treated with OCA, fibrates, or both were recorded during a year, as well as adverse events and treatment discontinuation. RESULTS: Eighty-six patients were treated with OCA, 250 with fibrates (81% bezafibrate; 19% fenofibrate), and 15 with OCA plus fibrates. OCA group had baseline significantly higher alkaline phosphatase (ALP) (P = 0.01) and lower platelets (P = 0.03) than fibrates. Both treatments significantly decreased ALP, gamma-glutamyl transferase (GGT), and transaminases and improved Globe score. Albumin and immunoglobulin type M improved in the fibrates group. ALP decrease was higher under fibrates, whereas alanine aminotransferase decline was higher under OCA. Although baseline transaminases and GGT were higher in patients with OCA plus fibrates, significant ALP, GGT, alanine aminotransferase, and Globe score improvement were observed during triple therapy. Adverse events were reported in 14.7% of patients (21.3% OCA; 17.6% fenofibrate; 10.7% bezafibrate), mainly pruritus (10.1% with OCA). Discontinuation was more frequent in fenofibrate treatment mainly because of intolerance or adverse events. DISCUSSION: Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.

Evaluation of cardiovascular events in patients with hepatocellular carcinoma treated with sorafenib in the clinical practice. The CARDIO-SOR study.

BACKGROUND AND AIMS: The effectiveness of systemic treatment in advanced hepatocellular carcinoma (HCC) depends on the selection of patients, management of cirrhosis complications and expertise to treat adverse events. The aims of the study are to assess the frequency and management of cardiovascular events in HCC patients treated with sorafenib (SOR) and to create a scale to predict the onset of major adverse cardiovascular events (MACE). METHOD: Observational retrospective study with consecutive HCC patients treated with SOR between 2007 and 2019 in a western centre. In order to classify cardiovascular risk pre-SOR, we designed the CARDIOSOR scale with age, hypertension, diabetes, dyslipidaemia and peripheral vascular disease. Other adverse events, dosing and outcome data were collected during a homogeneous protocolled follow-up. RESULTS: Two hundred ninety-nine patients were included (219 BCLC-C). The median overall survival was 11.1 months (IQR 5.6-20.5), and duration of treatment was 7.4 months (IQR 3.3-14.7). Seventeen patients (6%) stopped SOR due to cardiovascular event. Thirty-three patients suffered MACE (7 heart failure, 11 acute coronary syndrome, 12 cerebrovascular accident and 8 peripheral vascular ischemia); 99 had a minor cardiovascular event, mainly hypertension (n = 81). Age was the only independent factor associated to MACE (HR 1.07; 95% CI 1.03-1.12; P = .002). The CARDIOSOR scale allows to identify the group of patients with higher risk of MACE (sHR 3.4; 95% CI 1.4-6.7; P = .04). CONCLUSION: The incidence of cardiovascular events in HCC patients treated with SOR is higher than expected. Multidisciplinary approach and clinical tools like CARDIOSOR scale could be helpful to manage these patients.

Diabetes is not associated with an increased risk of hepatocellular carcinoma in patients with alcoholic or hepatitis C virus cirrhosis.

BACKGROUND AND AIMS: diabetes has been reported as a risk factor for hepatocellular carcinoma (HCC) in population-based studies but there are controversial data in patients with cirrhosis. Metformin could have a protective role in HCC development. The aim of this study was to determine the influence of diabetes on the risk of developing HCC in patients with alcohol- and hepatitis C virus (HCV)-related cirrhosis. METHODS: a cohort of 982 Caucasian patients were analyzed with alcoholic or HCV cirrhosis, included from 1992 to 2014 in a HCC surveillance program and prospectively followed. The influence of diabetes on the development of HCC was analyzed by Kaplan Meier analysis and adjusted with a Cox regression for relevant co-factors. RESULTS: after a median follow-up of 49.5 (24.0-96.0) months, 156 patients (15.8 %) developed HCC. There were no differences in the cumulative incidences of HCC after 20 years between diabetic and non-diabetic patients in the global (53.5 % vs 45.4 %; p = 0.26), alcoholic (50.4 % vs 45.4 %; p = 0.21) or HCV (60 % vs 43.1 %; p = 0.57) cirrhosis series. Diabetes did not constitute a risk factor after adjusting for other potential co-factors, neither in the whole series (hazard ratio [HR]: 1.12, 95 % CI: 0.78-1.51; p = 0.26), alcoholic (HR: 1.160, 95 % CI: 0.74-1.82; p = 0.50) or HCV cirrhosis cohort (HR: 1.17, 95 % CI: 0.63-2.19; p = 0.60). These figures did not change after excluding patients treated with metformin. CONCLUSIONS: in Caucasian patients with alcoholic or HCV cirrhosis, diabetes is not a risk factor for developing HCC. This lack of an association does not seem to be a consequence of the protective effect of metformin.

Genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients with HCV infection.

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses, trimming peptides and loading onto HLA class I molecules. Coding single nucleotide polymorphisms within ERAP1 are associated with autoimmune diseases, viral infections, and cancer development. Our purpose was to analyze the influence of ERAP1 variants on fibrogenesis in hepatitis C virus (HCV)-infected patients. A range of ERAP1 polymorphisms were genotyped in 722 unrelated Caucasian patients diagnosed with chronic HCV from two Spanish cohorts. Patients were classified according to their fibrosis stage. Paraffin-embedded tissue microarrays were constructed to assess ERAP1 expression (HCV = 38; alcoholic = 20) by immunohistochemistry. A statistical algorithm was applied to derive a fibrogenesis prediction model. The ERAP1 variants rs30187/T (K528, pc < 0.001) and rs27044/G (Q730, pc < 0.001) were related with severe fibrosis. These results were validated in the two independent cohorts. Furthermore, patients with the rs30187/T allele had stronger ERAP1 protein expression than those with the rs30187/C (p < 0.05). The statistical model showed that patients with rs30187 C/T and T/T genotypes took 15.58 years (median) to develop advanced fibrosis, but this value was 32.08 years in patients carrying C/C genotype (p < 0.005). ERAP1 variants may influence the clinical course of fibrogenesis in HCV-infected patients. These polymorphisms could be exploited as constitutive new markers of fibrosis evolution. The results highlight the possibility of using modulators of ERAP1 to generate a protective immune response against chronic HCV infection. KEY MESSAGES: What is known Several ERAP1 polymorphisms are associated with autoimmune diseases and cancer. ERAP1 trims peptides to HLA class I presentation. What is new here ERAP1 polymorphisms are associated with fibrogenesis. The ERAP1 polymorphisms genotype could help us in clinical management of patients. Potential translational impact The use of modulators of ERAP1 could generate a protective response depending on SNPs.

Modificaciones en las características de los ingresos hospitalarios por cirrosis descompensada en la era de los antivirales de acción directa frente al virus de la hepatitis C / No disponible

INTRODUCCIÓN: el desarrollo de los regímenes libres de interferón, basados en antivirales de acción directa (AADs), ha supuesto una revolución en el tratamiento de la infección por el virus de la hepatitis C (VHC). OBJETIVO: conocer si han existido cambios en las características de los ingresos hospitalarios por cirrosis descompensada desde la introducción de los AADs. MÉTODOS: se recogieron de forma prospectiva todos los ingresos hospitalarios por cirrosis descompensada en dos periodos: octubre/12-octubre/14 (P-I) y julio/16-julio/18 (P-II). Se registraron variables demográficas y clínicas y se utilizaron los métodos estadísticos habituales para su análisis. RESULTADOS: se registraron 746 ingresos (347 en P-I y 399 en P-II). Los pacientes del P-I fueron más jóvenes (59 vs. 63 años; p = 0,034), mientras que la proporción de ingresos por cirrosis-VHC fue inferior en el P-II (15,8 % vs. 21,6 %; p = 0,041). No hubo diferencias significativas en la proporción de ingresos por otras etiologías de la cirrosis entre ambos periodos. Analizando los ingresos por cirrosis-VHC, los pacientes del P-II tuvieron menos frecuentemente infección viral activa (57,1 vs. 97,3 %; p = 0,001) y en ellos coexistía con mayor frecuencia un consumo excesivo de alcohol (55,5 % vs. 30,7 %; p = 0,003), mientras que la coinfección con VIH fue menos frecuente (1,6 % vs. 10,7 %; p = 0,039). CONCLUSIONES: la proporción de ingresos por cirrosis descompensada ocasionada por el VHC ha descendido en torno a un 30 % desde la introducción de los AADs. Además, las características de los pacientes que ingresan por complicaciones de la cirrosis relacionada con el VHC han cambiado desde la aplicación de los regímenes libres de interferón

No disponible

The development of early ascites is associated with shorter overall survival in patients with hepatocellular carcinoma treated with drug-eluting embolic chemoembolization.

BACKGROUND: A single-centre cohort study was performed to identify the independent factors associated with the overall survival (OS) of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization with drug-eluting beads (DEB-TACE). METHODS: A total of 216 HCC patients who underwent DEB-TACE from October 2008 to October 2015 at a tertiary hospital were consecutively recruited. The analysis of prognostic factors associated with overall survival after DEB-TACE, stressing the role of post-TACE events, was performed. RESULTS: The objective response (OR) rate (Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria) to the first DEB-TACE (DEB-TACE-1) was 70.3%; the median OS from DEB-TACE-1 was 27 months (95% confidence interval (CI), 24-30). In the multivariate analysis, tumor size, AFP < 100 ng/mL and serum alkaline phosphatase were independent factors for survival following DEB-TACE-1. The most important clinical event associated with poor survival was the development of early ascites after DEB-TACE-1 (median OS, 17 months), which was closely related to the history of ascites, albumin and hemoglobin but not to tumour load or to response to therapy. CONCLUSIONS: Early ascites post-DEB-TACE is associated with the survival of patients despite adequate liver function and the use of a supra-selective technical approach. History of ascites, albumin and hemoglobin are major determinants of the development of early ascites post-DEB-TACE.

Changes in the characteristics of hospital admissions due to decompensated cirrhosis in the era of direct-acting antivirals against hepatitis C virus.

BACKGROUND: the development of interferon-free regimens, based on direct acting antivirals (DAAs) has revolutionized the treatment of hepatitis C virus (HCV) infection. AIMS: to determine if there have been changes in the characteristics of hospital admissions due to decompensated cirrhosis in a general hospital since the introduction of DAAs. PATIENTS AND METHODS: this was a prospective study of all hospital admissions due to decompensated cirrhosis during two periods: October 2012-October 2014 (P-I) and July 2016-July 2018 (P-II). Clinical and demographic variables were collected and standard statistical methods were used for the analysis. RESULTS: there were 746 hospital admissions; 347 in P-I and 399 in P-II. P-I patients were younger (59 vs 63 years; p = 0.034), while the proportion of admissions due to HCV-cirrhosis was lower in P-II (15.8 % vs 21.6 %; p = 0.041). There were no significant differences in the proportion of admissions due to other etiologies of cirrhosis between both periods. Patients in the P-II group presented an active viral infection (57.1 vs 97.3 %; p = 0.001) less frequently and had a higher rate of excessive alcohol consumption (55.5 vs 30.7 %; p = 0.003) when admitted, while HIV co-infection was less frequent (1.6 % vs 10.7 %; p = 0.039). CONCLUSION: the proportion of admissions due to decompensated HCV-related cirrhosis has decreased by almost 30 % since the introduction of the DAA. In addition, the characteristics of patients admitted have changed since the application of interferon-free regimens.

Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): An International Observational Study.

Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.