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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 (22IU/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.

[Abstract] 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. Ministerio de Economía y Empresa; IDI-20151125 Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-R

Objective To evaluate the differences in perceived state of health (PSH) according to patient age younger or older than 60 years. Patients and Methods One hundred sixty-two patients were entered on the waiting list for renal transplantation from July 2003 at 4 hospitals in California and were observed prospectively for 2 years. Data were obtained at baseline and at 3 and 12 months after transplantation. All patients answered a generic Perceived State of Health (PSH) questionnaire, the 36-item Short-Form Health Survey (SF-36), and the EuroQol (EQ-5D) questionnaire. Data were analyzed using the t test for independent variables and the χ 2 test for contingency tables. Results Patients aged 60 years or older had higher PSH scores compared with those younger than 60 years on all dimensions of the SF-36 and on the 2 summary scores. Scores for the physical domains were significantly improved at all follow-up visits. After transplantation, scores for the EQ-5D were higher for older patients vs younger patients (mean [SD], 80 [16] vs 67 [14]; P = .01). The PSH score for the older patients was similar to that for the general population (>45 points). The PSH scores for the physical and mental health domains were worse for the younger patients compared with the general population; no differences were noted for clinical variables. Conclusion Patients older than 60 years have higher PSH scores compared with patients younger than 60 years. However, scores for the younger patients were significantly improved at 1 year after transplantation.

Fundamento y objetivo El tratamiento prolongado con lamivudina de los pacientes con hepatitis B cronica se asocia a la emergencia de resistencias. Los pacientes con resistencia a la lamivudina presentan una perdida de la respuesta tanto bioquimica como virologica y una mayor progression de la enfermedad hepatica. El adefovir dipivoxil, un analogo de los nucleotidos, es eficaz en el tratamiento de los pacientes con resistencia a la lamivudina. El objetivo de este estudio ha sido evaluar la eficacia, la seguridad y las resistencias del adefovir dipivoxil en pacientes con hepatitis B cronica refractarios al tratamiento con lamivudina. Pacientes y metodo Se ha incluido a 120 pacientes afectados de hepatitis B cronica y refractarios al tratamiento con lamivudina que recibieron tratamiento con adefovir dipivoxil. En 74 de ellos se realizo seguimiento durante 2 anos. En todos los casos se determino el ADN del virus de la hepatitis B por reaccion en cadena de la polimerasa, y en los casos sin respuesta al tratamiento se estudio la presencia de resistencias a adefovir dipivoxil y lamivudina. Resultados A los 2 anos de tratamiento se observo respuesta virologica en el 54,1% de los pacientes, respuesta bioquimica en el 62,2% y eliminacion del antigeno e de la hepatitis B en el 21%. Se detectaron resistencias a adefovir dipivoxil en el 20% de los casos, y las mutaciones detectadas con mayor frecuencia fueron A181V, A181T y N236T. La seguridad del farmaco fue excelente, pues se detecto solo un efecto adverso relacionado con el tratamiento. Conclusiones El tratamiento durante 2 anos con adefovir dipivoxil en monoterapia en pacientes previamente refractarios a lamivudina se asocia a una alta tasa de respuesta bioquimica y virologica, con una seguridad excelente. La tasa de resistencias al adefovir dipivoxil a los 2 anos fue del 20%.

Objective To validate a Spanish version of the Liver Disease Quality of Life Questionnaire (LDQOL 1.0) among patients awaiting hepatic transplantation. Methods This observational, cross-sectional study was performed between May 2002 and June 2006. We included ambulatory or hospitalized patients aged 18 or over with chronic liver disease awaiting transplantation. Patients completed the LDQOL 1.0. The feasibility of the LDQOL for clinical use was tested by examining the administration time and values for the questionnaire’s 12 disease-specific scales. Reliability was tested by examining the internal consistency of the scales (Cronbach’s alpha). Known group validity was tested by examining the questionnaire’s ability to discriminate between patients with hepatocellular (HCC), liver cirrhosis (CH), hepatitis C virus infection, and alcohol-induced CH. Results A total of 200 patients were included in the analysis. Their mean age (SD) was 52.6 (9.8) years; 73% of the sample were men. The most common indication for liver transplant was HCC (34%). The mean (SD) time to complete the LDQOL 1.0 was 35 minutes (21 minutes). Over 20% of patients scored at the ceiling (maximum possible score) on seven of the 12 disease-specific scales. Floor effects were less marked. All dimensions had Cronbach alpha coefficients over 0.60. The lowest value (0.64) was found in the sexual problems (women) dimension. Patients with HCC had significantly higher scores on several scales, including symptoms of liver disease (P = .000), effects of liver disease (P = .000), concentration (P = .002), memory (P = .015), quality of social interaction (P = .030), sleep (P = .000), loneliness (P = .043), and stigma (P = .028). Statistically significant differences were found between HCC patients and alcohol-induced CH patients in only two dimensions. Conclusions Among pretransplant patients, the Spanish version of the LDQOL 1.0 showed substantial ceiling effects and the length of administration makes its application in clinical practice difficult. This preliminary analysis showed good internal consistency for the disease-specific scales and acceptable known group validity.

SUMMARY Background Sustained virological response rates of up to 52% have been obtained with peginterferon α2a (40 kDa) plus ribavirin in patients suffering from chronic hepatitis C genotype 1 in randomized-controlled trials. Aim To assess early virological response and its clinical utility in predicting an sustained virological response in patients suffering from chronic hepatitis C genotype 1 in routine clinical practice in Spain. Methods Treatment-naive patients received pegylated interferon α2a (40 kDa) 180 µg/week plus ribavirin 1000/1200 mg/day for 48 weeks, and were followed for a further 24 weeks. Overall, 475 patients received at least one dose of medication and were included in the efficacy population. Results The overall sustained virological response rate was 48%. Of those with week 12 virological data, 83% had an early virological response. The negative predictive value of an early virological response was 93%. Conclusion If sustained virological response is the goal, a treatment-decision based on a 12-week evaluation during routine clinical practice is feasible.

The specific questionnaire Liver Disease Quality of Life (LDQOL) is a valid tool for measuring quality of life (QOL) and has been used to show that liver transplantation (LT), which is an effective treatment for end-stage liver disease, may improve QOL.This study aims to identify aspects of QOL that improve after LT and those that do not.Patients accepted for LT were invited to answer the LDQOL at baseline and after transplantation at 6 and 12 months. LDQOL contains the 36-item Short Form Health Survey (SF-36) and 12 specific dimensions. Responsiveness was assessed using the paired Student t test.The study included a cohort of 156 patients, 73% males, of an average age of 53 (26-67) years, with the following common indications: tumor (35%), hepatitis C (23%), and alcohol-related (21%) liver disease. Mean scores showed a statistically significant (P.05) improvement after 1 year in 6 of 8 SF-36 dimensions, in the physical component summary score, and in 7 of 12 disease-specific dimensions. The two dimensions that showed no improvement in the SF-36 dimensions were "social functioning" and "vitality," whereas the specific dimensions to not improve were "sleep problems," "social interaction," "activities of daily living," and "concerns about the future."Findings suggest that perceived QOL after LT improves but could be further enhanced with the use of specific programs for amending sleep disorders and physical aspects.

Instruments of health-related quality of life (HRQOL) help us to interpret the results of treatments and health interventions. In Spain there is no HRQOL instrument specifically designed for use in patients with liver disease or to measure the effect of interventions such as liver transplantation. The Liver Disease Quality of Life (LDQOL 1.0) questionnaire is an American instrument developed for use in these patients. The aim of this study was to produce an appropriate version of this questionnaire for use in Spain. Cultural adaptation was performed in 3 phases: a) modification for use in Spain of a Hispanic version of this questionnaire supplied by the original authors; b) back-translation to English of a new version of the questionnaire and comparison with the original version in English, and c) a pilot test in a small sample of patients. In the first phase consisting of revision of the Hispanic version, the changes were mainly linguistic due to cultural and idiomatic differences. The validated Spanish version of the SF-36 was directly incorporated and items that could be of interest to local investigators were added. Few changes were made in the second phase of the process: changes involved an item on the appearance of feces and another item on taking naps. In the final phase, various changes suggested by the patients were introduced. Before applying the new version of the LDQOL 1.0 in clinical studies in Spain, its psychometric properties (its reliability, validity and sensitivity to change) must be verified in a subsequent validation study.

Fundamento El tratamiento quirurgico del hepatocarcinoma (HCC) sigue siendo un tema controvertidopor falta de estudios prospectivos aleatorizados. Pacientes y metodo Entre enero de 1990 y diciembre de 2000 se realizaron en nuestro centro121 trasplantes hepaticos (grupo I) y 52 hepatectomias (grupo II) por HCC. La indicacion deuna u otra tecnica dependio de las caracteristicas del paciente y del tumor. Resultados Los pacientes del grupo I presentaron un estadio tumoral mas avanzado, con mayorincidencia de bilobularidad (19 frente a un 4%; p = 0,015) y un mayor numero de nodulos(1,9 DE [2] frente a 1,2 [0,6]; p = 0,001), pero el tamano tumoral medio fue inferior (3 cm[1,5] frente a 4,2 cm [3,2]; p = 0,006). La mortalidad operatoria (4 frente a un 2%; p =0,66), y la supervivencia a los 5 y 10 anos (68 y 42% frente a 63 y 45%; p = 0,23) fueron similarespara los dos grupos. Sin embargo, la incidencia de recidiva a los 5 y 10 anos (10,6 y10,6% frente a 50 y 65,5%; p Conclusiones Con una buena seleccion de los pacientes, tanto el trasplante hepatico como lahepatectomia obtienen excelentes supervivencias a largo plazo en los pacientes con HCC, aunqueel primero permite un mejor control de la enfermedad tumoral. Las causas de mortalidadson diferentes para cada uno de los tratamientos. La prolongacion del tiempo en lista de esperade trasplante que se ha producido en los ultimos anos no ha originado un empeoramiento delos resultados de supervivencia.

Introduccion El trasplante hepatico domino consiste en la utilizacion para el trasplante del organo extirpado en el momento de realizar un trasplante hepatico en pacientes con polineuropatia amiloidotica familiar (PAF). Pacientes y metodo Entre febrero de 1999 y marzo de 2001 hemos realizado en nuestra unidad 131 trasplantes hepaticos con 121 donantes cadaver. En 10 ocasiones se realizo un trasplante hepatico domino. Resultados Los pacientes afectados de PAF eran mas jovenes (37 anos) que los receptores del segundo trasplante hepatico (64 anos). La evolucion de los pacientes trasplantados por PAF ha sido excelente y en la actualidad todos los pacientes se encuentran vivos y sin complicaciones. Entre los receptores del segundo trasplante hepatico un paciente fallecio en el postoperatorio. Otros 2 pacientes murieron por recidiva tumoral a los 18 meses y por recidiva del virus de la hepatitis C a los 9 meses. El resto de enfermos no ha presentado sintomas de aparicion de PAF durante el seguimiento. Conclusion Los resultados del trabajo permiten concluir que el trasplante hepatico domino es tecnicamente factible y permite incrementar el numero de injertos sin riesgo aparente para ninguno de los dos receptores, el afectado de PAF y el trasplantado con el higado del anterior.

Introduction Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. Objective The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. Patients and Methods This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. Results The median age of the patients was 55 years. The median time since transplantation was 4.1 ± 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. Conclusions The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

Background. Recurrence of autoimmune hepatitis after liver transplantation is not rare, but there is little information about its time of onset, risk factors, response to treatment and prognosis. The aim of this study was to evaluate the rate of recurrence and outcome of autoimmune hepatitis after transplantation. Methods. The records of patients transplanted in eight centers in our country between 1984 and 1996 were retrospectively analyzed. Results. Forty-three of the 2331 (1.8%) recipients fulfilled diagnostic criteria of autoimmune hepatitis at the time of transplantation. Sixteen patients were excluded from evaluation. Nine (33%) of the 27 patients evaluated fulfilled criteria for recurrence of autoimmune hepatitis, with a mean time of recurrence after orthotopic liver transplantation of 2.6±1.5 years. Patients with recurrence had a longer follow-up time after transplantation (5.1 vs. 2.5 years, P=0.0012) and were receiving less immunosuppressive treatment. The estimated risk of recurrence of autoimmune hepatitis in the graft increased over time: 8% over the first year and 68% 5 years after transplantation. None of the seven patients with liver-kidney microsomal-positive antibodies recurred (P=0.059). Fifty percent of the patients failed to respond or responded only partially to therapy, although none of the patients have deteriorated clinically after 2.4±1.06 years of follow-up after recurrence. Conclusions. Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced. Although response to treatment is poor, patient and graft survival do not appear to be decreased.

Objective Our aim was to evaluate the efficacy and safety of adding adefovir to lamivudine therapy for hepatitis B virus (HBV)-infected patients resistant to Ramivudine. Patients and methods Among 17 studied patients, 7 had chronic active HBV infection and 10 were posttransplant with HBV infection (9 with de novo HBV). They received lamivudine plus adefovir therapy for 2 years. We assessed reductions in serum HBV-DNA and alanine aminotransferase (ALT) levels, loss of HBeAg (in HBeAg+ cases), and HBsAg clearance. Results A virological response, as defined by HBV-DNA below the cut off by hybridization, was observed in 12 (70.6%) patients and loss of HBeAg in 4 (44.4%) of the 9 initially HBeAg-positive cases. A biochemical response, defined as a decreased serum ALT to the normal range, occurred in 4 (26.7%) patients. Median serum creatinine increased in 3 of 15 (20%) patients, excluding those on hemodialysis. There were two noteworthy cases of sustained HBsAg seroconversion with adefovir (11.8%): one patient with de novo HBV infection posttransplantation and positive hepatitis C virus–RNA serology, and one patient with decompensated HBV cirrhosis in whom viral replication ceased, making him eligible for transplantation. Conclusions Currently, adefovir is an effective rescue therapy that broadens the existing range of options for patients with lamivudine-resistant chronic hepatitis B infection, particularly those with decompensated cirrhosis awaiting a liver graft, and those with recurrent posttransplantation HBV. The relatively small biochemical response seen in these patients may be attributable to the high prevalence of concomitant hepatitis C virus infection (41%).

We present the experience of the liver transplantation program at the Hospital of Bellvitge with 500 transplantations performed during 15 years, to describe changes in liver transplantation observed throughout the time and to analyze the long term results.Five groups each one including 100 consecutive transplantations are studied.The main indications were hepatocellular carcinoma (23%), alcoholic cirrhosis (22.8%), and post-hepatitis C cirrhosis (18.8%). Sixty-five retransplantations were performed in 59 patients (13%), being the more frequent indications arterial thrombosis (13 patients) and primary nonfunction of graft (10 patients). In 10 patients a hepatorenal transplantation was performed. In group I, the most frequent donor cause of death was cranial traumatism (80%), while in group V it was the vascular pathology (52%). There were other significative differences between these groups of patients (I vs V): patients with stage 2 or 3 from UNOS status (45 vs 19%), blood use (29.6 [26] vs 4.6 [5.3] PRBC), ICU stay (13 [13] vs 7.4 [11] days), hospital stay (40 [52] vs 23.7 [17] days), rejection rate (46 vs 20%) and primary graft nonfunction (9 vs 3%). However, the infection rates (48 vs 54.5%) and biliary tract complications (26 vs 20%) have not shown statistically significant differences. Actuarial one and 5-year survival are 83 and 70% respectively.An important and progressive improvement of liver transplantation results has been observed. However, de novo tumours, hepatitis C virus recurrence and chronic rejection can limit long term results.

Our aim was to validate Spanish and Catalan versions of the Liver Disease Quality of Life questionnaire (LDQOL) for use in liver transplant patients.The LDQOL consists of the SF-36 generic measure of health-related quality of life (HRQOL) and 12 disease-specific dimensions for liver disease patients. The Spanish and Catalan versions of the questionnaire were administered to 138 patients with a liver transplant. Cronbach's alpha coefficients (CAC) were used to test the internal consistency of disease-specific scales. Test-retest reliability was calculated using the Intraclass Correlation Coefficient (ICC) in a sub-group of 41 patients who completed the questionnaire on two occasions 1 to 2 weeks apart. Validity was analysed by determining the instrument's capacity to discriminate between patient groups classified according to years since transplant, disease etiology, and symptom severity. Ceiling and floor effects were also calculated.Internal consistency in the disease-specific dimensions was acceptable or good (CACs 0.60-0.97), as was test-retest reliability in all dimensions (statistically significant CCIs of 0.62-0.89), except the symptoms dimension (CCI=0.46, P.05). Few differences were found in disease-specific dimension scores between patients classified according to number of years since transplant or etiology, but differences were found in some dimensions according to symptom severity. Moderate to severe ceiling effects were found in several disease-specific dimensions.The Spanish and Catalan versions of the LDQOL may be useful for measuring HRQOL in this population, though it will be important to investigate further the instrument's sensitivity to change.

This chapter will deal with the present role of Liver Biopsy in determining liver disease prognosis in hepatitis B and C patients on haemodialysis and its role in establishing treatment strategies and in the decision-making process prior to kidney transplant. In recent years, progress has been made in determining the natural history of this disease in renal patients (Espinosa et al., 2004; Jadoul et al., 2004). Chronic hepatitis due to HCV is frequent in renal transplant recipients and in dialysis patients and has a significant impact on their survival (Hanafusa et al., 1998; Orloff et al., 1995; Pouteil-Noble et al., 1995). Mathurin et al., (1999) demonstrated in a case-control study that anti-HCV and HBsAg positive were independently associated with patient and graft survival. This was the first time that a 10 year follow-up was carried out; previous publications are based on shorter follow-ups and fewer patients. It is known that the prevalence of chronic infection with the hepatitis C virus (HCV) in patients with chronic kidney disease is higher than in the general population (Lavanchy, 2009). The estimated prevalence of chronic infection in haemodialysis patients is 13%, ranging from 10 to 65 %, depending on the geographical zone (Hmaied et al., 2006; Huraib et al., 1995; Santos & Souto, 2007; Shamshiraz et al., 2004). When considering patients candidates to kidney transplantation we have to take into account that immunosuppressive therapy after renal transplantation predisposes a reactivation of chronic viral hepatitis B or C, which is usually a mild disease for patients remaining under haemodialysis. It should be noted that HBV and HCV may induce de novo glomerulonephritis and chronic allograft nephropathy which can lead to graft failure (Aouifi & Garcia, 2001). In such cases, patients have to undergo dialysis again and therefore it is beneficial to eradicate HCV RNA before transplantation and to control and maintain HBV DNA negative (Huskey & Wiseman, 2011). A routine liver histological analysis could improve a patient’s chance of being selected for renal transplantation. Liver biopsy has been considered the “gold standard” for many years, because it provides us with information that was otherwise unobtainable (Ghany et al., 2010). Nowadays however, due to progress in non-invasive methods, liver biopsy is only

Treatment of recurrent hepatitis C after liver transplantation is indicated in selected cases. During the combined treatment with pegylated interferon and ribavirin, some patients develop immune-mediated liver dysfunction similar to the previously described “de novo” autoimmune hepatitis. Herein we have presented three liver transplant patients who during or after combined antiviral treatment were diagnosed as autoimmune hepatitis related to interferon based on their clinical, biochemical, and liver histology features. There were two women and one man, of ages 49, 52, and 49 years who were transplanted due to cirrhosis related to hepatitis C virus genotype 1. In two patients, elevated liver enzymes occurred during antiviral therapy and in the third, after the therapy. The diagnosis of autoimmune hepatitis was reached after excluding other possible causes. One patient had a sustained viral response; and two cases were nonresponders. Antinuclear antibodies were present in two subjects and antinuclear antibodies and anti-smooth muscle antibodies in the other case. First-line treatment of autoimmune hepatitis with prednisone and azathioprine stabilized clinical and biochemical parameters'. In order to avoid the long-term use of prednisone, everolimus was introduced in the three patients. Interestingly, hepatitis C did not progress and clinical, biochemical, as well as histological parameters stabilized. In one patient, the liver fibrosis stage as assessed by histology showed improvement. However, one subject experienced repeated cerebral hemorrhage and died. Although this is heterogeneous population with partially known characteristics, with a difficult differential diagnosis, the objectives of preserving liver function and avoiding recurrent progressive hepatitis C seemed to be achieved by adding everolimus. In addition, we totally stopped prednisone therapy. In conclusion, treatment with everolimus in combination with cyclosporine achieved a partial remission in two liver transplan cases of autoimmune hepatitis related to interferon therapy.

Background & Aims : Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV The prognosis and risk factors for morbidity and mortality in this condition were determined. Methods A retrospective study of 652 consecutiveanti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. Results Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3–2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1–1.8; P = 0.01). Conclusions The results of transplantation for HCV related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 16, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Introduction and Aims It has been described that patients who receive a transplant display a better Health Related Quality of Life (HRQoL). Our objective was to describe the HRQoL before and after a solid organ transplantation, comparing results among various transplantations. Methods This HRQoL study using the SF-36 was implemented before as well as at 3 and 12 months posttransplantation. Posttransplantation were compared with pretransplantation scores as well as with the general population. Results One hundred sixty-two renal, 159 liver, and 58 lung candidates were included before transplantation, among whom there were 126 renal, 108 liver, and 22 lung recipients. The median age of all transplant recipients was 53 years with 68% men. The various transplant types began with different HRQoL: lung showed the worst, followed by the liver, and then renal. The scores of the SF-36 before and 3 months posttransplantation showed significant improvements, except for “Pair.” At 12 versus 3 months, mental health was somewhat better for renal, and almost all dimensions showed significant improvement for liver and lung patients. All subjects showed clear improvements after transplantation. Conclusion All patients showed clear improvements after transplantation when mental health was compared with the general population, particularly lung transplant recipients who expressed the greatest improvement. However, they still showed deficits in physical health.

Our aim was to study the changes in the Health Related Quality of Life (HRQoL) during the first year following liver transplantation.Among 159 patients awaiting orthotopic liver transplantation (OLT) who were prospectively studied at 4 hospitals in Catalonia, 108 actually obtained an organ. HRQoL over time, namely, before, as well as at 3 and 12 months after transplantation, was recorded using the Short Form-36 (SF-36) and the Liver Disease Quality of Life (LDQOL 1.0). After we searched medical, clinical, and sociodemographic records to examine the studied variables on the HRQoL at each moment, the significance was explored using t tests and one-way analysis of variance (ANOVA).Comparison of the SF-36 dimensions before and at 3 months after transplantation revealed almost all domains to show significant improvements (P.01), except bodily pain, role-physical, social functioning, and PCS. Comparisons between 3 and 12 months after transplantation showed only significant improvements in role-physical, physical functioning, and PCS (P.05). The other dimensions showed similar or slightly better scores, but the differences were not significant. For LDQOL 1.0 before and 3 months after transplantation, the dimensions with significant differences (P.01) were: effects of liver disease on activities of daily living; concentration; health distress; sleep problems; stigmata of liver disease; and sexual function. Comparing 3 and 12 months posttransplantation, no dimension showed a significant improvement. A negative correlation existed between hypertensive patients and PCS on the SF-36 (P.001). The clinical diagnosis of alcoholic liver disease showed better scores in some dimensions of the LDQOL than the other diagnoses. Female subjects showed significantly worse HRQoL than men (P.001). Child-Pugh and Model for End-Stage Liver Disease (MELD) classifications were not associated with the HRQoL either before or after transplantation.The most important finding in this study was that all domains showed significant improvements in HRQoL at 3 months after transplantation with only slight improvements at 12 months.

Introduction At present, there is little published information on the outcome of treatment with pegylated interferon (Peg-IF alpha 2a) in hepatitis C virus (HCV)-infected hemodialysis patients awaiting renal transplantation. The objective of this study was to assess the efficacy and tolerance of Peg-IF alpha 2a in this population. Patients and methods Twelve noncirrhotic HCV-infected patients (10 men, 50 ± 8 years of age, genotype 1b 84%), were prescribed Peg-IF alpha 2a, at 135 μg/wk for 48 weeks. Liver biopsy was performed in 11 of 12 cases. Results Six patients completed 48 weeks of treatment, with one end of treatment response (ETR), two sustained viral responses (SVRs), and three HCV relapses. Treatment was shorter in the six remaining patients: two cases 24 weeks (one due to medical reasons with relapse, one due to nonresponse), one patient chose to discontinue at 14 weeks (with relapse), one patient died of stroke at 10 weeks, and in two additional patients interferon was withdrawn at 18 weeks because of severe anemia (SVR) and at 26 weeks due to prolonged fever (relapse). Other secondary treatment-related events included anemia (requiring transfusion in two patients and major erythropoietin administration in six), and fever in four patients. Conclusions Peg-IF had limited efficacy in this group, with ETR in 83%, SVR in only 25%, and recurrence in 50%. Tolerance was moderate, with 4/12 (33%) discontinuing treatment due to adverse events, personal decision, or death. Large randomized controlled studies are needed to determine the role of Peg-IF treatment in this population.

Sustained virological response rates of up to 52% have been obtained with peginterferon alpha2a (40 kDa) plus ribavirin in patients suffering from chronic hepatitis C genotype 1 in randomized-controlled trials.To assess early virological response and its clinical utility in predicting an sustained virological response in patients suffering from chronic hepatitis C genotype 1 in routine clinical practice in Spain.Treatment-naïve patients received pegylated interferon alpha2a (40 kDa) 180 microg/week plus ribavirin 1000/1200 mg/day for 48 weeks, and were followed for a further 24 weeks. Overall, 475 patients received at least one dose of medication and were included in the efficacy population.The overall sustained virological response rate was 48%. Of those with week 12 virological data, 83% had an early virological response. The negative predictive value of an early virological response was 93%.If sustained virological response is the goal, a treatment-decision based on a 12-week evaluation during routine clinical practice is feasible.

Instruments of health-related quality of life (HRQOL) help us to interpret the results of treatments and health interventions. In Spain there is no HRQOL instrument specifically designed for use in patients with liver disease or to measure the effect of interventions such as liver transplantation. The Liver Disease Quality of Life (LDQOL 1.0) questionnaire is an American instrument developed for use in these patients. The aim of this study was to produce an appropriate version of this questionnaire for use in Spain. Cultural adaptation was performed in 3 phases: a) modification for use in Spain of a Hispanic version of this questionnaire supplied by the original authors; b) back-translation to English of a new version of the questionnaire and comparison with the original version in English, and c) a pilot test in a small sample of patients. In the first phase consisting of revision of the Hispanic version, the changes were mainly linguistic due to cultural and idiomatic differences. The validated Spanish version of the SF-36 was directly incorporated and items that could be of interest to local investigators were added. Few changes were made in the second phase of the process: changes involved an item on the appearance of feces and another item on taking naps. In the final phase, various changes suggested by the patients were introduced. Before applying the new version of the LDQOL 1.0 in clinical studies in Spain, its psychometric properties (its reliability, validity and sensitivity to change) must be verified in a subsequent validation study.

In domino liver transplantation (LT), the explanted liver of a patient with familial amyloidotic polyneuropathy (FAP) is donated to another patient.Between February 1999 and March 2001 we performed 131 LT with 121 cadaveric donors in our unit. Ten domino LTs were performed.Patients with FAP were younger (37 years) than recipients of the second LT (64 years). The evolution of patients undergoing transplantation for FAP was excellent and all are currently alive and without complications. Among recipients of the second LT, one patient died in the postoperative period. A further two patients died from tumoral recurrence and hepatitis C virus recurrence 18 months and 9 months after transplantation, respectively. The remaining patients have shown no symptoms of FAP during the follow-up.The results of this study show that domino LT is technically feasible. The technique increases the number of grafts without apparent risk either to the recipient with FAP or to the recipient of the latter's explanted liver.

Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined.A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen.Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01).The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Recurrence of autoimmune hepatitis after liver transplantation is not rare, but there is little information about its time of onset, risk factors, response to treatment and prognosis. The aim of this study was to evaluate the rate of recurrence and outcome of autoimmune hepatitis after transplantation.The records of patients transplanted in eight centers in our country between 1984 and 1996 were retrospectively analyzed.Forty-three of the 2331 (1.8%) recipients fulfilled diagnostic criteria of autoimmune hepatitis at the time of transplantation. Sixteen patients were excluded from evaluation. Nine (33%) of the 27 patients evaluated fulfilled criteria for recurrence of autoimmune hepatitis, with a mean time of recurrence after orthotopic liver transplantation of 2.6+/-1.5 years. Patients with recurrence had a longer follow-up time after transplantation (5.1 vs. 2.5 years, P=0.0012) and were receiving less immunosuppressive treatment. The estimated risk of recurrence of autoimmune hepatitis in the graft increased over time: 8% over the first year and 68% 5 years after transplantation. None of the seven patients with liver-kidney microsomal-positive antibodies recurred (P=0.059). Fifty percent of the patients failed to respond or responded only partially to therapy, although none of the patients have deteriorated clinically after 2.4+/-1.06 years of follow-up after recurrence.Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced. Although response to treatment is poor, patient and graft survival do not appear to be decreased.

A retrospective analysis of our experience in the treatment of hiliary cholangiocarcinoma or Klatskin tumor was performed with the aim of evaluating the morbi-mortality and prognosis of its treatment to thereby determine the usefulness of the different therapeutic options. From 1989 to 1997, 51 patients diagnosed with hiliary cholangiocarcinoma were treated in our hospital. Surgery was indicated in 16 with curative aims (group I) while palliative treatment with percutaneous biliary drainage was indicated in 35 (group II). Biliary resection was carried out in 8 patients being associated with hepatic resection in 4 (group IA) and in 8 patients undergoing liver transplantation (group IB). Clinico-epidemiologic data and hospital stay were similar in all the groups. The frequency of complications was similar in groups I and II although the frequency of cholangitis (49%) in group II was noticeable. The percentage of readmissions was also greater in group II (12 vs 46%, respectively; p = 0.03) with prosthesis obstruction being the most frequent cause. Accumulated survival at 1, 2, and 3 years in group I was 84, 64 and 48% with a median survival of 33 months, while in group II the median survival was of 6 months with no patient surviving more than 2 years (p = 0.0001). When groups IA and IB were compared, greater frequency of complications in groups IA (100 vs 37%; p = 0.002), similar frequency of readmissions (87 vs 75%; p = NS), median survival greater in group IB (12.5 months vs 48 months) and significantly higher actuarial survival in group IB (48% in 2 years vs 83% to 2 years; p = 0.02) was observed. In conclusion, surgery is the treatment of choice in hiliary cholangiocarcinoma whenever possible, given the greater survival without a significant increase in morbimortality. Likewise, we consider that liver transplantation is a useful option in the treatment of patients with cholangiocarcinoma type IV of Bismuth.

Patients who have received a L.T. have a higher risk of developing «de novo» neoplasia than the general population.

IFN is the most accepted treatment for HCV chronic infection in immunocompetent patients. But IFN is not without risk in transplanted patients, because possible deleterious effects on the graft.

The initial enthusiasm for orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) soon vanished as early recurrences appeared. OLT in HCC remains a controversial issue. We evaluated the efficacy of preoperative studies to select No-Mo patients and determined whether pT stage and histopathological grade (G) have a prognostic significance. A group of 25 patients, all previously thoroughly studied to rule out extrahepatic disease, underwent OLT for HCC. All patients were pNo after pathological study and none of the six patients who died in the postoperative period showed extrahepatic dissemination at necropsy (pMo). The recurrence rate was 43%. The 2 and 5 years actuarial survival was 62% and 43% respectively. The pT and G were not prognostic factors for long-term survival. We think that HCC is still a good indication for OLT because almost 50% of patients have good survival prospects.

The initial enthusiasm for orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) soon vanished as early recurrences appeared [3, 5, 6]. OLT in HCC remains a controversial issue. We evaluated the efficacy of preoperative studies to select No-Mo patients and determined whether pT stage and histopathological grade (G) have a prognostic significance. A group of 25 patients, all previously thoroughly studied to rule out extrahepatic disease, underwent OLT for HCC. All patients were pNo after pathological study and none of the six patients who died in the postoperative period showed extrahepatic dissemination at necropsy (pMo). The recurrence rate was 43%. The 2 and 5 years actuarial survival was 62% and 43% respectively. The pT and G were not prognostic factors for long-term survival. We think that HCC is still a good indication for OLT because almost 50% of patients have good survival prospects.