Search

BACKGROUND AND AIMS 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.

La sarcoidosis es una afectación granulomatosa sistémica de etiología incierta. Se diagnostica ante el hallazgo de granulomas no necrotizantes en ausencia de otros procesos autoinmunes, infecciosos o agentes externos. La incidencia de la afectación gastrointestinal se estima en un 0,1-1,6% mientras que la afectación hepática ocurre en el 50-65% de los casos, pudiendo ser subclínica o descubierta en el estudio de una alteración de las enzimas hepáticas. Presentamos el caso de un varón de 51 años con un cuadro de saciedad posprandial, dolor epigástrico y ascitis refractaria en contexto de una sarcoidosis con afectación gastrointestinal y hepática. Se inició tratamiento con prednisona y azatioprina con estabilización clínica posterior.

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.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. Methods: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan–Meier and Cox regression methods were used for data analysis. Results: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4–67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2–0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8–0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0–75.8]; specificity 95.2% [95% CI: 89.9–97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3–2.1). Conclusion: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided, This study was supported in part by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, number PI20/01302, awarded to Agustín Albillos and number PI 21/01310, awarded to Luis Téllez. CIBEREHD is funded by the Instituto de Salud Carlos III using grants cofinanced by the European Development Regional Fund “A way to achieve Europe” (EDRF). María Carlota Londoño received support from the Plan Nacional de I+D+I co- funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER-"Una manera de Hacer Europa") (PI17/00955)

Background Chronic hepatitis delta is a severe liver disease with rapid progression to cirrhosis. The impact of hepatitis delta virus (HDV)-RNA on disease progression and interferon treatment in a real-world cohort has been barely explored. Aim To assess the development of clinical events in a cohort of chronic hepatitis delta patients according to the presence or absence of HDV-RNA METHODS: Multicentre study at four academic hospitals in Spain included anti-HDV-positive patients with compensated liver disease with a follow-up ≥12 months. Results Among 2888 HBsAg-positive subjects, 151 (5.2%) tested positive for anti-HDV, and 118 were included (58% men; median age, 49 years; 73% detectable HDV-RNA and 30% cirrhosis, most often in subjects with HDV-RNA). After a median follow-up of 8 years, subjects with initially detectable HDV-RNA were more prone to developing cirrhosis (31% vs 0%, P = .002) and/or liver decompensation (28% vs 3%, P = .019). Mortality rate was 0.44 per 1000 person-months. The probability of a clinical event was 6%, 25%, and 80% according to initial baseline-event-anticipation score. HDV-RNA became undetectable in 21 (24%) subjects either due to interferon or spontaneously (48% vs 52%, P = .29). Liver decompensation was reduced in interferon-treated patients (13% vs 38%, P = .026). Conclusions Subjects with persistently positive HDV-RNA had a worse prognosis in terms of clinical events. Baseline-event-anticipation score is useful in predicting the risk of developing liver decompensation and hepatocellular carcinoma. Interferon was beneficial in reducing liver decompensation, even in the absence of virological response.

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 number and size of tumors. This may impact clinical practice and trials design. The aim of the study is to assess the reproducibility and the prognostic value of the model in western patients treated with Drug-Eluting Beads (DEB)-TACE. Methods observational, retrospective, unicentric study developed in 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), 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 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.

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.

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.

Preemptive TIPS Individual Data Metanalysis, International Variceal Bleeding Study and Baveno Cooperation Study groups., [Background & Aims] Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS., [Method] We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients., [Results] Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323–0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307–0.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253–0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy., [Conclusions] In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy., Juan Carlos García-Pagán received support in part through grants from the Spanish Ministry of Education and Science (SAF-2016–75767-R and PIE 15/00027) and from the “Commissioner for Universities and Research of the Generalitat de Catalunya” (AGAUR SGR 2017). CIBERehd is funded by the Instituto de Salud Carlos III. Edilmar Alvarado-Tapias and Anna Baiges are recipients of a "Río Hortega" fellowship grant from the Instituto de Salud Carlos III. The study was partially supported by a GORE grant for statistical support.

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.

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.

Introduccion: el desarrollo de los regimenes libres de interferon, basados en antivirales de accion directa (AADs), ha supuesto una revolucion en el tratamiento de la infeccion por el virus de la hepatitis C (VHC). Objetivo: conocer si han existido cambios en las caracteristicas de los ingresos hospitalarios por cirrosis descompensada desde la introduccion de los AADs. Metodos: 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 demograficas y clinicas y se utilizaron los metodos estadisticos habituales para su analisis. Resultados: se registraron 746 ingresos (347 en P-I y 399 en P-II). Los pacientes del P-I fueron mas jovenes (59 vs. 63 anos; p = 0,034), mientras que la proporcion 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 proporcion de ingresos por otras etiologias de la cirrosis entre ambos periodos. Analizando los ingresos por cirrosis-VHC, los pacientes del P-II tuvieron menos frecuentemente infeccion viral activa (57,1 vs. 97,3 %; p = 0,001) y en ellos coexistia con mayor frecuencia un consumo excesivo de alcohol (55,5 % vs. 30,7 %; p = 0,003), mientras que la coinfeccion con VIH fue menos frecuente (1,6 % vs. 10,7 %; p = 0,039). Conclusiones: la proporcion de ingresos por cirrosis descompensada ocasionada por el VHC ha descendido en torno a un 30 % desde la introduccion de los AADs. Ademas, las caracteristicas de los pacientes que ingresan por complicaciones de la cirrosis relacionada con el VHC han cambiado desde la aplicacion de los regimenes libres de interferon.

BACKGROUND AND AIM Surveillance for hepatocellular carcinoma (HCC) intends to detect tumors at an early stage to improve survival. The study aims were to assess the frequency and risk factors associated with HCC surveillance failure. METHODS The study analyzed data from 188 consecutive patients diagnosed with HCC within a surveillance program conducted among 1,242 cirrhotic patients and based on ultrasonography and alpha-fetoprotein (AFP) testing every 3 or 6 months. Program failure was defined as the detection of HCC exceeding the Milan criteria. Variables recorded at entry into the program, during follow-up and at HCC diagnosis, were analyzed. RESULTS At diagnosis, 50 (26.6%) HCC tumors were beyond the Milan criteria. In univariate analysis, Child-Pugh B at entry (P = 0.03), development of complications of portal hypertension before tumor diagnosis (P = 0.03), and failure to complete the prior screening round (P = 0.02), Child-Pugh B/C (P = 0.001) and AFP ≥ 100 ng/mL (P = 0.03) at diagnosis, were associated with failure. In multivariate analysis, only Child-Pugh B/C (hazard ratio, 3.18; 95% confidence interval, 1.66-6.10, P

Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.

Patient adherence to screening for hepatocellular carcinoma (HCC) is not well known. Our aims were to analyze the adherence to a surveillance program in a prospective cohort of cirrhotic patients and to examine its association with HCC stage at diagnosis. A total of 770 patients with cirrhosis were examined semiannually by ultrasound and alpha-fetoprotein at a tertiary center. We collected data on 17 variables at baseline. Suboptimal adherence was defined as failure to complete 2 consecutive screening rounds. Over a median follow-up period of 42.0 months (interquartile range: 60.0), 125 patients (16.2%) had suboptimal adherence. Active or previous intravenous drug use [hazard ratio (HR), 5.33; 95% confidence interval (CI), 3.07-9.23], active alcohol consumption (HR, 3.03; 95% CI, 2.03-4.51), absence of liver decompensation before the inclusion in the program (HR, 1.65; 95% CI, 1.07-2.55) and aspartate transaminase/alanine transaminase ratio ≥1.6 (HR, 1.82; 95% CI, 1.23-2.70) were independent predictors of suboptimal adherence. Compared with those with optimal adherence, patients with suboptimal adherence had a more advanced HCC stage at diagnosis (P=0.015), they were less frequently treated with curative intention (P=0.078) and survived less (median: 14.2 mo; IQR: 36.0 vs. 22.7 mo; IQR: 47.4; P=0.160), although these differences were not significant. The adherence to the process of HCC surveillance can be considered as adequate among cirrhotic patients. Active alcohol consumption and a history of intravenous drug use are the strongest predictors of suboptimal adherence. These patients have a more advanced HCC stage at diagnosis and tend to be less frequently treated with curative intention.

Background & Aims: Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/rito navir plus dasabuvir (OMV/PTV/r + DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice. Methods: Data from HCV genotype 1 patients treated with either OMV/PTV/r + DSV +/- ribavirin (RBV) (n = 1567) or LDV/SOF +/- RBV (n = 1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded. Results: The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV +/- RBV and 95.8% with LDV/SOF +/- RBV. No significant differences were observed in SVR according to HCV subgenotype (p = 0.321 [OMV/PTV/r + DSV +/- RBV] and p = 0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV +/- RBV] and p = 0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p < 0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r + DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%. Conclusions: In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r + DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles. Lay summary: In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex. (c) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Background and aims Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r +/- DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. Material and methods Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. Results Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan (R), 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient ' s decision. Conclusions These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials., MCL has served as consultant for AbbVie, MSD, Janssen, BMS and Gilead; MRB has received grant research from Gilead Science, and speaker fees from AbbVie, Gilead and MSD; MR has received speaker fees from AbbVie; MD has received grant support and consultancy fees from AbbVie, Bayer, Bristol-Myers Squibb, Gilead and Merck, Sharp & Dhome; FGR has served as speaker for AbbVie, Gilead and BMS; MLM has served as a speaker for AbbVie, BMS, Gilead, Janssen, MSD and ViiV; as a consultant for AbbVie, BMS and Janssen and has received research funding from FIPSE 36465/03, FIPSE 36680/07.-NEAT IG5 (NEAT is a project funded by the European Union under the 6th Framework programme) contract number LSHP-CT-2006-037570; MAC has served as a consultant for Gilead and and ViiV healthcare, and has received speaker fees from Janssens, Gilead, ViiV Healthcare; MMA reports personal fees from ViiV Healthcare, Gilead Sciences, Merck, Janssen, AbbVie and ABBOTT Laboratories, outside the submitted work; AR has received consultancy and speaker fees from AbbVie, Gilead Sciences and Merck Sharp & Dohme; JM has received honoraria, speaker fees, consultant fees or funds for research from AbbVie, BMS, Boehringer-Ingelheim, Gilead, Janssen, MSD, Roche and ViiV; EGP has received speaker fees from AbbVie and Gilead; LGB has served as consultant for AbbVie and Intercept and has received speaker fees from Gilead and MSD; AA, RMG, CB, TAE, MLG, BPL, IC, SB, LB, JGS, MJP, IMG, LM, IdlS, ML and JEL don't have a financial interest or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this paper; CdA and AM are paid employees of AbbVie and may hold stock or options. The specific roles of these authors are articulated in the 'author contributions' section. The design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the manuscript.

Surveillance for hepatocellular carcinoma (HCC) intends to detect tumors at an early stage to improve survival. The study aims were to assess the frequency and risk factors associated with HCC surveillance failure.The study analyzed data from 188 consecutive patients diagnosed with HCC within a surveillance program conducted among 1,242 cirrhotic patients and based on ultrasonography and alpha-fetoprotein (AFP) testing every 3 or 6 months. Program failure was defined as the detection of HCC exceeding the Milan criteria. Variables recorded at entry into the program, during follow-up and at HCC diagnosis, were analyzed.At diagnosis, 50 (26.6%) HCC tumors were beyond the Milan criteria. In univariate analysis, Child-Pugh B at entry (P = 0.03), development of complications of portal hypertension before tumor diagnosis (P = 0.03), and failure to complete the prior screening round (P = 0.02), Child-Pugh B/C (P = 0.001) and AFP ≥ 100 ng/mL (P = 0.03) at diagnosis, were associated with failure. In multivariate analysis, only Child-Pugh B/C (hazard ratio, 3.18; 95% confidence interval, 1.66-6.10, P 0.001) and AFP ≥ 100 ng/mL, both at diagnosis (hazard ratio, 2.80; 95% confidence interval, 1.37-5.71, P = 0.005), were independently associated with failure. Survival was higher among patients with tumors within the Milan criteria than those with program failure (33.9 vs 7.6 months, P 0.001).Approximately 25% of HCC cases diagnosed among patients included in a surveillance program were beyond the Milan criteria. Child-Pugh B/C and AFP ≥ 100 ng/mL at diagnosis were associated with program failure. However, Child-Pugh B at entry and development of liver-related complications during follow-up can be early predictors of failure.

Background: The standard therapy in advanced hepatocellular carcinoma (HCC) is sorafenib (SOR), which has the inconvenience of toxicity and discontinuation. Patient selection and the use of early markers are critical for optimizing the potential benefit of SOR. Alpha-fetoprotein (AFP) has an established role in HCC prognosis. The objective was to evaluate whether AFP variation during SOR treatment reflects the lack of progression to SOR and can be used as a prognostic factor. Methods: AFP levels were prospectively analyzed in 114 patients to determine whether the time to progression of AFP (TPA) at 3 months had a prognostic value for survival. Results: Between July 2007 and October 2012, 114 patients were included (mean age 64 years, 97 male, 96 with cirrhosis). Etiology was alcohol 47 (41%) and hepatitis C virus (HCV) 31 (27%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system: A (one case), B (24 cases) and C (89 cases). The Child-Pugh was Class A in 89 cases. The general condition of the patient according to ECOG-PS was 0 in 73 cases. The median duration of treatment was 5 months (3.47 - 6.53, 95% CI). The median overall survival (OS) was 9.23 months. The standard dose was maintained in 26 patients (22.8%). Sixty-seven percent of patients experienced at least one adverse event grade 3-4. The time to progression of AFP lower or higher than 3 months was an independent prognostic factor of OS (univariate and multivariate analysis): 8.10 vs. 18.85 months, P 3 months had longer OS, and TPA was an independent prognostic factor.

BACKGROUND The incidence of hepatitis delta virus (HDV) infection has decreased during the last decades. However, an increasing trend has been reported recently. PATIENTS AND METHODS We carried out a case-control study to analyze changes in its prevalence in 1215 chronic hepatitis B virus (HBV) patients, diagnosed consecutively in a tertiary center, between 1983 and 2012. According to the year of diagnosis, patients were distributed into two groups: A [1983-1997 (n=786)] and B [1998-2012 (n=429)]. RESULTS The prevalence of anti-HDV was 8.2% (9.4% in group A and 6.1% in group B) (P=0.04). Multivariate regression revealed that intravenous drug use [odds ratio (OR) 261.0; 95% confidence interval (CI), 28.7-2368.5; P