Publications by authors named "Teresa Casanovas"

12 Publications

  • Page 1 of 1

Redefining fatty liver disease: an international patient perspective.

Lancet Gastroenterol Hepatol 2021 01 5;6(1):73-79. Epub 2020 Oct 5.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia. Electronic address:

Despite its increased recognition as a major health threat, fatty liver disease associated with metabolic dysfunction remains largely underdiagnosed and undertreated. An international consensus panel has called for the disease to be renamed from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) and has suggested how the disease should be diagnosed. This Viewpoint explores the call from the perspective of patient advocacy groups. Patients are well aware of the negative consequences of the NAFLD acronym. This advocacy group enthusiastically endorses the call to reframe the disease, which we believe will ultimately have a positive effect on patient care and quality of life and, through this effect, will reduce the burden on health-care systems. For patients, policy makers, health planners, donors, and non-hepatologists, the new acronym MAFLD is clear, squarely placing the disease as a manifestation of metabolic dysfunction and improving understanding at a public health and patient level. The authors from representative patient groups are supportive of this change, particularly as the new acronym is meaningful to all citizens as well as governments and policy makers, and, above all, is devoid of any stigma.
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http://dx.doi.org/10.1016/S2468-1253(20)30294-6DOI Listing
January 2021

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure.

Antiviral Res 2020 02 16;174:104694. Epub 2019 Dec 16.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Universitario La Fe, Valencia, Spain.

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of "extra-target" RAS suggests the need for RAS screening in all three DAA target regions.
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http://dx.doi.org/10.1016/j.antiviral.2019.104694DOI Listing
February 2020

Hepatitis B surface antigen loss after discontinuing nucleos(t)ide analogue for treatment of chronic hepatitis B patients is persistent in White patients.

Eur J Gastroenterol Hepatol 2019 02;31(2):267-271

Digestive Diseases Department, Hospital Clínico Lozano Blesa, Zaragoza, Spain.

Objective: The objective of this study was to determine the long-term clinical outcome and persistence of hepatitis B surface antigen (HBsAg) loss after discontinuation of treatment.

Background: The prognosis of patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs) who discontinue treatment after loss of HBsAg remains largely unknown, particularly in White patients.

Patients And Methods: We analysed a cohort of patients with CHB who discontinued NA treatment after loss of HBsAg. A total of 69 patients with hepatitis-B-e antigen-positive or hepatitis-B-e antigen-negative CHB with undetectable HBsAg during NA treatment were included after discontinuation of treatment, and followed up for a median period of 37.8 months (interquartile range: 23.8-54.6 months).

Results: At the end of follow-up, none of the patients showed spontaneous reappearance of HBsAg and only one patient had detectable hepatitis B virus DNA (22 IU/ml). Another patient negative for HBsAg and anti-HBs developed hepatitis B virus reactivation without elevated transaminases after treatment with corticosteroids and vincristine for dendritic cell neoplasm, 38 months after withdrawal of the antiviral treatment. Regarding clinical outcome, a patient with cirrhosis developed hepatocellular carcinoma, 6.6 years after discontinuing treatment. None of the patients had hepatic decompensation or underwent liver transplantation.

Conclusion: HBsAg clearance after discontinuing NAs in patients with CHB is persistent and associated with good prognosis. The risk for developing hepatocellular carcinoma persists among patients with cirrhosis.
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http://dx.doi.org/10.1097/MEG.0000000000001289DOI Listing
February 2019

Successful treatment of hepatitis C virus infection combining daclatasvir and simeprevir in a heart transplant recipient with decompensated cirrhosis.

J Heart Lung Transplant 2016 07 17;35(7):949-51. Epub 2016 May 17.

Microbiology Service, Hospital Universitari de Bellvitge, Barcelona, Spain.

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http://dx.doi.org/10.1016/j.healun.2016.05.005DOI Listing
July 2016

Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

Gastroenterol Hepatol 2014 Jan 17;37(1):1-8. Epub 2013 Dec 17.

Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.

Introduction: Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV).

Objectives: To assess the impact of high doses of RBV on SVR in patients with G3 and HVL.

Methods: Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin β 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin β (B2; n=13).

Results: RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%.

Conclusions: G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin β were safe and well tolerated (Clin Trials Gov NCT00830609).
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http://dx.doi.org/10.1016/j.gastrohep.2013.10.005DOI Listing
January 2014

Assessing outcomes in liver disease patients: reliability and validity of the Spanish version of the Liver Disease Quality of Life Questionnaire (LDQOL 1.0).

Value Health 2010 Jun-Jul;13(4):455-62. Epub 2010 Jan 21.

Liver Transplant Unit, Hospital Universitari, Institut of Investigation of Bellvitge, Barcelona, Spain.

Objective: To assess the reliability and validity of a Spanish version of the LDQOL 1.0 (Liver Disease Quality of Life questionnaire).

Methods: Observational, cross-sectional study in Spanish patients awaiting liver transplantation (LT). Feasibility was assessed by analyzing administration times and missing responses. Ceiling and floor effects were calculated and reliability was tested by examining internal consistency (Cronbach's alpha). Convergent validity was tested by examining correlations between LDQOL disease-specific and Short Form health survey with 36 questions (SF-36) dimensions. Known groups' validity was tested by examining the LDQOL's capacity to discriminate between groups defined by etiology and Child-Turcotte-Pugh (CTP) scores.

Results: A total of 200 patients were included for analysis. Mean age (SD) was 52.6 (9.8) years and 73% of the sample were male. The most common indication for LT was liver cancer (34%). Mean (SD) time to complete the questionnaire was 35.8 minutes (21.2 minutes). Missing responses were highest on the dimensions of sexual functioning and symptoms of liver disease. Ceiling effects were over 20% on 7 of the LDQOL's 12 disease-specific scales. Cronbach's alpha coefficients were over 0.70 on all but 2 dimensions. Correlations between SF-36 and LDQOL disease-specific dimensions generally fulfilled the hypotheses, with 35 of the 40 highest and lowest correlations (87.5%) being in the expected direction. The LDQOL discriminated well between patients in CTP class A and C, and as hypothesized, hepatocarcinoma and alcoholic cirrhosis patients scored better on most dimensions than patients with hepatitis C virus or other etiologies.

Conclusions: The Spanish version of the LDQOL 1.0 has shown satisfactory reliability and validity.
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http://dx.doi.org/10.1111/j.1524-4733.2009.00688.xDOI Listing
September 2010

Treatment of chronic hepatitis C in hemodialysis patients.

Authors:
Teresa Casanovas

Hepatology 2009 Jun;49(6):2126; author reply 2126

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http://dx.doi.org/10.1002/hep.22923DOI Listing
June 2009

[Adefovir dipivoxil compassionate use program in Spain: efficacy and resistance analysis].

Med Clin (Barc) 2007 Oct;129(15):566-70

Servicio de Hepatología, Hospital Universitari Vall d'Hebron, Barcelona, España.

Background And Objective: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine.

Patients And Method: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied.

Results: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected.

Conclusions: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%.
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http://dx.doi.org/10.1157/13111710DOI Listing
October 2007

Cofactors associated with liver disease mortality in an HBsAg-positive Mediterranean cohort: 20 years of follow-up.

Int J Cancer 2006 Aug;119(3):687-94

Epidemiology and Cancer Registration, Institut Català d'Oncologia, and Blod Bank, Hospital Universitari de Bellvitge, Hospitalet del Llobregat, Spain.

The risk of developing liver cancer in hepatitis B virus (HBV) carriers differs across geographical areas, suggesting that exposure to other risk factors may contribute to HBV-linked cancer risk. Our study estimates the mortality due to liver disease and the role of other risk factors in a Spanish HBV cohort. 2,352 hepatitis B surface antigen (HBsAg)-positive and 15,504 HBsAg-negative subjects were identified among blood donors during 1972-1985 and were followed until December 2000 through the Mortality Registry. Clinical examination and an epidemiological questionnaire were performed on 1,000 HBsAg-positive survivors during 1994-1996. In subjects deceased from liver disease, medical records were revised and relatives were interviewed. A nested case-control analysis was conducted comparing both groups. In HBsAg-positive men, an excess mortality from liver cancer [standardized mortality ratio (SMR): 14.1; 7.7-23.6], cirrhosis (SMR: 10.5; 7.0-15.1), haematological neoplasms (SMR: 3.2; 1.2-6.9) and AIDS was detected (SMR: 5.5; 2.2-11.4). In women, an excess was found for cirrhosis (SMR: 7.2; 1.4-21.1). Progression factors to liver disease were alcohol intake [odds ratio (OR): 6.3; 3.1-12.8], diabetes (OR: 3.6; 1.3-9.6), HBV replication (OR: 50.0; 14.9-167.3) and hepatitis C virus (HCV) infection (OR: 27.4; 7.1-107.7). In conclusion, in Spain after 20 years of follow-up, chronic HBV exposure appears as a major risk factor for liver cancer among men and for cirrhosis in both sexes. The risk of death from liver disease among HBV carriers with the presence of HBV replication, HCV, alcohol consumption and diabetes was significantly increased and suggests synergism among these exposures and HBV. Mortality from haematological neoplasms was detected and could be associated to HIV coinfection. These results support screening and adequate follow-up among HBsAg-positive subjects at high risk to develop liver disease, particularly when these risk cofactors are present.
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http://dx.doi.org/10.1002/ijc.21882DOI Listing
August 2006

Applicability of liver transplantation in Catalonia at the end of the millennium. A prospective study of adult patient selection for liver transplantation.

Transpl Int 2003 Apr 21;16(4):270-5. Epub 2003 Feb 21.

Liver Transplant Unit, Hospital Vall d'Hebron, Universidad Autónoma de Barcelona, Paseo Vall d'Hebron 119, 08035, Barcelona, Spain.

We prospectively studied the global applicability of liver transplantation in Catalonia, a region with a high rate of organ donation. We followed 232 adult patients assessed as possible candidates for liver transplantation over 12 months in the three hospitals that perform the procedure in this region. The liver disease leading to patient assessment was cirrhosis in most cases, alone (159 patients) or associated with hepatocellular carcinoma (57 patients). After being assessed, 150 patients (65%) were accepted for transplantation and included on the waiting list, and 82 (32%) were excluded. Death during the period of assessment, advanced tumoral disease, early stage of liver disease, and extrahepatic co-morbidities were the most important reasons for exclusion. The median time of assessment of patients accepted for transplantation was 40 days. Of the 150 patients included on the waiting list, 131 (87%) received transplants, 17 (11%) were removed from the list, and two were still waiting for transplantation at the end of the follow-up period. Death and tumor progression were the most important reasons for patients' removal from the waiting list. The median time on the waiting list was 59 days. In conclusion, among liver-transplant candidates the overall applicability of this therapy in Catalonia was relatively low (131 out of 232 transplant candidates finally underwent transplantation, 56%), and inadequate liver-transplant indications and death or tumor progression during the period of assessment or while the patient was on the waiting list were the most frequent reasons why liver transplantations did not proceed.
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http://dx.doi.org/10.1007/s00147-002-0539-1DOI Listing
April 2003

[Induction therapy with interferon alfa-2a in compensated hepatitis C virus-related cirrhosis. Randomized, multicenter study].

Med Clin (Barc) 2002 May;118(17):641-4

Hospital Universitari Germans Trias i Pujol. Badalona. BArcelona. Spain.

Background: Although standard dose interferon (IFN) is successful in only 5% of patients with compensated hepatitis C virus (HCV)-related cirrhosis, it has been suggested that this therapy might decrease the risk of complications or the incidence of hepatocellular carcinoma. Based on HCV kinetics, daily IFN may improve response rates.

Patients And Method: Forty cirrhotic patients were randomised to receive (Group I: 19) or not (Group II: 21) treatment with IFN (4.5 MU/daily for 24 weeks, followed by 4.5 MU/48 hours for a further 24 weeks period, only if ALT was within normal values).

Results: Dose reduction and discontinuation for adverse events was required in 11 (58%) and 6 (31.5%) cases, respectively. End-of-treatment response was not observed in any of the 21 controls but in 4 of the 19 (21%) treated patients (p = 0.04); a sustained response was achieved in only 2 treated patients (10.5%). The 3-year probability of developing any of the following: ascites, hepatocellular carcinoma, transplantation or death was lower in Group I than in Group II (6% vs 27%; p = 0.05).

Conclusion: Although induction IFN therapy is associated with common side effects and poor sustained response in compensated HCV-related cirrhosis, it might improve the outcome of patients at the medium-term.
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http://dx.doi.org/10.1016/s0025-7753(02)72483-4DOI Listing
May 2002

[Surgical treatment of hepatocellular carcinoma. Long term results].

Med Clin (Barc) 2002 Mar;118(11):410-4

Servicio de Cirugía General, Ciudad Sanitaria y Universitaria de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.

Background: Surgical treatment for hepatocellular carcinoma remains controversial due to a lack of prospective randomized studies.

Material And Method: Between January 1990 and December 2000, 121 liver transplantations (group 1) and 52 hepatectomies (group 2) were performed for hepatocellular carcinoma. Each surgical treatment was carried out depending on patients' and tumor's characteristics.

Results: Patients from group 1 had a more advanced tumoral grade, with higher involvement of two lobes (19 vs 4%; p = 0.015) and higher number of nodules (1.9 DE [2] vs 1.2 [0.6]; p = 0.001); yet the mean tumor size was lower (3 cm [1.5] vs 4.2 [3.2]; p = 0.006). Operative mortality (4% vs 2%; p = 0.66) and 5- and 10-years survival (68% and 42% vs 63% and 45%; p = 0.23) were similar between both groups. Nevertheless, 5- and 10-years recurrence rates (10.6% and 10.6% vs 50% and 65.5%; p < 0.0001) were more favourable in group 1. Prognostic factors of recurrence included microscopic vascular invasion (RR = 12.12; CI, 2.02-75.52) and alpha-fetoprotein levels higher than 300 ng/mL (RR = 7.12; 95% CI, 1.08-47.02) in group 1, and the pT3-4 stage (RR = 3.86; 95% CI, 1.06-14.03) in group 2. Mean time on waiting lists for liver transplantation was 3.06 (2.66) months and it has increased significantly in last years, especially among blood group 0 patients. However, this fact has not been associated with a worsening of survival rates (p = 0.98).

Conclusions: After a good patient selection, either liver transplantation or hepatectomy achieve excellent long term survival rates in patients with hepatocellular carcinoma, though the former allows a better control of the tumoral disease. The increase of mean time on waiting lists for liver transplantation during the last years has not led to a worsening of survival results.
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http://dx.doi.org/10.1016/s0025-7753(02)72404-4DOI Listing
March 2002
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