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BACKGROUND & AIMS: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC. METHODS: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. RESULTS: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. CONCLUSION: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. IMPACT AND IMPLICATIONS: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.
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OBJECTIVE: In liver transplantation, chronic rejection is still poorly studied. This study aimed to investigate the role of imaging in its recognition. METHODS: This study is a retrospective observational case-control series. Patients with histologic diagnosis of chronic liver transplant rejection were selected; the last imaging examination (computed tomography or magnetic resonance imaging) before the diagnosis was evaluated. At least 3 controls were selected for each case; radiological signs indicative of altered liver function were analyzed. χ 2 Test with Yates correction was used to compare the rates of radiologic signs in the case and control groups, also considering whether patients suffered chronic rejection within or after 12 months. Statistical significance was set at P < 0.050. RESULTS: A total of 118 patients were included in the study (27 in the case group and 91 in the control group). Periportal edema was appreciable in 19 of 27 cases (70%) and in 6 of 91 controls (4%) ( P < 0.001); ascites and hepatomegaly were present in 14 of 27 cases (52%) and 12 of 27 cases (44%), respectively, and in 1 of 91 controls (1%) ( P < 0.001); splenomegaly was present in 13 of 27 cases (48%) and in 8 of 91 controls (10%) ( P < 0.001); and biliary tract dilatation was present in 13 of 27 cases (48%) and in 11 of 91 patients controls (5%) ( P < 0.001). In the controls, periportal edema was significantly less frequent beyond 12 months after transplant (1% vs 11%; P = 0.020); the other signs after 12 months were not significant. CONCLUSIONS: The identification of periportal edema, biliary dilatation, ascites, and hepatosplenomegaly can serve as potential warning signs of ongoing chronic liver rejection. It is especially important to investigate periportal edema if it is present 1 year or more after orthotopic liver transplantation.
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Ascitis , Hepatopatías , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética , EdemaRESUMEN
There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013-2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42-56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p < .001). 2/16 patients resumed alcohol intake, one at 164 days and one at 184 days. Early LT significantly improves survival in sAH non-responding to medical therapy, when a strict selection process is applied. Further studies are needed to properly assess alcohol relapse rates.
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Hepatitis Alcohólica , Trasplante de Hígado , Femenino , Hepatitis Alcohólica/cirugía , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Recurrencia , Listas de EsperaRESUMEN
There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF-3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3, between 2018 and 2019 were included across 20 transplantation centers. A total of 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted patients with ACLF-3 admitted to the ICU and the number listed or transplanted while in ACLF-3 across centers. By contrast, there was a correlation between the number of patients listed and the number transplanted while in ACLF-3. About 21% of patients who were listed while in ACLF-3 died on the waiting list or were delisted. The percentage of LT for patients with ACLF-3 varied from 0% to 29% for those transplanted with decompensated cirrhosis across centers (average = 8%), with an I2 index of 68% (95% confidence interval, 49%-80%), showing substantial heterogeneity among centers. The 1-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more patients with ACLF-3 (>10 patients) than in centers that listed and transplanted fewer: 36% versus 20%, respectively (p = 0.012). Patients with ACLF-3 face inequity of access to LT across Europe. Waitlisting strategies for patients with ACLF-3 influence their access to LT and, ultimately, their survival.
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Insuficiencia Hepática Crónica Agudizada , Trasplante de Hígado , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/cirugía , Humanos , Unidades de Cuidados Intensivos , Cirrosis Hepática , Trasplante de Hígado/efectos adversos , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Listas de EsperaRESUMEN
The majority of patients undergoing Orthotopic Liver Transplantation (OLT) have increased in age, therefore chronological age may have become an unreliable parameter for supporting clinical decisions. The age-related deficit accumulation model measuring frailty proposed by Rockwood et al., may propose an alternative in providing an estimate of an individual's biological age. No Frailty Index (FI) tailored specifically for OLT patients exists to date. Forty-three consecutive OLT patients with ≥ 20 years of survival with a functioning graft were included in our study. The FI was computed taking to account 39 items (FI-39), meeting the standard criteria for internal validation. Endpoints were polypharmacy, and recent Emergency Room admission. The mean age of our population was 69 (sd 9) years. The mean FI-39 was 0.23 (sd 0.1). The FI-39 was associated with polypharmacy [odds ratio (OR) 1.13; Confidence interval (95%CI) 1.03-1.24; p = 0.01], and recent Emergency Room admission [beta coefficient + 1.98; 95%CI + 0.26, + 3.70; p = 0.03], independent for age and sex. This study demonstrates that an FI can be derived from data collected during routine clinical follow-up and allows for improved differentiation related to the OLT clinical complexity in OLT patients, independent of chronological age. This may lead to the adoption of FI-39 to improve personalized OLT patient care.
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Fragilidad , Trasplante de Hígado , Anciano , Anciano Frágil , Fragilidad/diagnóstico , Evaluación Geriátrica , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Optimal involvement of palliative care (PC) services in the management of patients with decompensated cirrhosis and end-stage liver disease (ESLD) is limited. This may result from both ignorance and the failure to recognize the spectrum and unpredictability of the underlying liver condition. Palliative care is a branch of medicine that focuses on quality of life (QoL) by optimizing symptom management and providing psychosocial, spiritual, and practical support for both patients and their caregivers. Historically, palliative care has been underutilized for patients with decompensated liver disease. This review provides an evidence-based analysis of the benefits of the integration of palliative care into the management of patients with ESLD. Liver Transplantation 24 961-968 2018 AASLD.
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Enfermedad Hepática en Estado Terminal/terapia , Cirrosis Hepática/terapia , Cuidados Paliativos/métodos , Calidad de Vida , Prestación Integrada de Atención de Salud/métodos , Prestación Integrada de Atención de Salud/tendencias , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/patología , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/tendencias , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Trasplante de Hígado , Cuidados Paliativos/tendencias , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. METHODS: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. RESULTS: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. CONCLUSIONS: These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Trasplante de Hígado , Sofosbuvir/uso terapéutico , Listas de Espera , Adulto , Anciano , Carcinoma Hepatocelular/tratamiento farmacológico , Ensayos de Uso Compasivo , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Humanos , Italia , Estimación de Kaplan-Meier , Cirrosis Hepática/cirugía , Cirrosis Hepática/virología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ribavirina/uso terapéuticoRESUMEN
BACKGROUNDS & AIMS: Treating patients with decompensated cirrhosis with direct-acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting. METHODS: One hundred and forty-two HCV-positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up. RESULTS: Forty-four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child-Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty-two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%). CONCLUSIONS: Antiviral therapy allows for a long-term improvement of liver function and the delisting of one-third of treated patients with risk of liver-related complications after delisting being very low.
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Antivirales/uso terapéutico , Carcinoma Hepatocelular/cirugía , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/estadística & datos numéricos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Femenino , Hepatitis C Crónica/complicaciones , Humanos , Italia , Cirrosis Hepática/mortalidad , Cirrosis Hepática/virología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Listas de EsperaRESUMEN
BACKGROUND: In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). METHODS: All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). RESULTS: Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ± 7.2 years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79 obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment. CONCLUSION: An extended course of SOF plus DCV for 24 weeks, with or without RBV, is effective and well tolerated for the treatment of post-LT HCV recurrence with severe fibrosis.
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Antivirales/uso terapéutico , Hepatitis C/cirugía , Imidazoles/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Carbamatos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Italia , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Pirrolidinas , Recurrencia , Valina/análogos & derivadosRESUMEN
BACKGROUND & AIMS: Hepatitis C virus (HCV) re-infection following liver transplant (LT) is associated with reduced graft and patient survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre- to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 weeks of HCV-RNA undetectability at the time of transplant. METHODS: From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One hundred patients were transplanted and 31 patients (31%) treated with SOF/R bridging therapy were studied. RESULTS: Liver transplant indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV-genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV-RNA positive (median HCV-RNA 58 IU/mL). One recipient had a virological breakthrough at week 4 post-transplant; one died, on treatment, 1-month post-transplant for sepsis and 29/31 achieved a 12-week sustained virological response (94%). Acute cellular rejection occurred in three recipients. On September 2016, 30 recipients (97%) were alive with a median follow-up of 18 months (range 13-25). CONCLUSIONS: In patients with suboptimal virological response at LT, a bridging SOF/R regimen helps avoiding post-transplant graft reinfection.
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Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Trasplante de Hígado , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Anciano , Antivirales/efectos adversos , Carcinoma Hepatocelular/terapia , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C/prevención & control , Humanos , Italia , Cirrosis Hepática/terapia , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Periodo Preoperatorio , Recurrencia , Estudios Retrospectivos , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , Respuesta Virológica SostenidaRESUMEN
BACKGROUND & AIMS: Notwithstanding evidences implicating the lipopolysaccharides (LPS)/toll-like receptor-4 (TLR4) axis in the pathogenesis of NAFLD, there are no studies aimed to characterize hepatic TLR4 expression in NAFLD patients. We aimed to analyse hepatic TLR4 expression and to verify its relationship with disease activity/evolution in NAFLD patients. METHODS: Liver tissue from 74 patients with NAFLD and 12 controls was analysed by immunohistochemistry (IHC) for TLR4, α-smooth muscle actin (α-SMA) and cytokeratin-7. IHC for α-SMA was used to evaluate activation of fibrogenic cells (hepatic stellate cells and portal/septal myofibroblasts), that for cytokeratin-7 to count hepatic progenitor cells and bile ducts/ductules, and that for CD68, in a subgroup of 27 patients, for detecting macrophages. Serum LPS-binding protein (LBP), a sensitive marker of LPS activity, was determined in 36 patients and 32 controls. RESULTS: As confirmed by double-labelling experiments, the highest level of TLR4 expression was observed in hepatic progenitor cells, biliary cells and portal/septal macrophages. TLR4-positive hepatic progenitor cells and bile ducts/ductules correlated with portal/interface inflammation, activity of fibrogenic cells and fibrosis (P < 0.001). Also the score of TLR4 positivity of porto-septal inflammatory infiltrate correlated with number of hepatic progenitor cells and bile ducts/ductules, activity of fibrogenic cells and fibrosis (P < 0.01). Serum LBP was increased in patients compared to controls (P < 0.001), and correlated with portal/interface inflammation, activity of portal/septal myofibroblasts and fibrosis (all P < 0.05). CONCLUSIONS: TLR4 expression by regenerating and inflammatory cells at the porto-septal and interface level, favoured by increased LPS activity, is associated with activation of fibrogenic cells and the degree of fibrosis.
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Inflamación/metabolismo , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Sistema Porta/metabolismo , Receptor Toll-Like 4/metabolismo , Actinas/metabolismo , Proteínas de Fase Aguda/metabolismo , Biopsia , Proteínas Portadoras/metabolismo , Técnica del Anticuerpo Fluorescente , Células Estrelladas Hepáticas/metabolismo , Técnicas Histológicas , Humanos , Inmunohistoquímica , Italia , Queratina-7/metabolismo , Cirrosis Hepática/etiología , Glicoproteínas de Membrana/metabolismo , Miofibroblastos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Sistema Porta/fisiopatología , Estadísticas no ParamétricasRESUMEN
Autoantibodies are frequently detected after liver transplantation (LT), but their role is unclear. This study was designed to address three points: autoantibody prevalence pre-LT and over time up to five yr after LT, identification of possible predictors of autoantibody formation, and correlation between autoantibodies and graft dysfunction. To these aims, we retrospectively evaluated 92 consecutive LT recipients for whom prospectively stored frozen sera were available for autoantibodies assessment by immunofluorescence. The overall autoantibody prevalence resulted significantly higher after LT than before LT (64% vs. 27%, p < 0.001 and 35.9% vs. 8.7%, p < 0.001 considering cutoff titer of ≥ 1:80 and ≥ 1:160, respectively). Recipient gender, donor age and gender, and indication for LT and main immunosuppressant (cyclosporine vs. tacrolimus) were not associated with the presence of autoantibodies. Patients with graft dysfunction had a significantly higher autoantibody prevalence irrespective of the etiology of liver injury as compared to those patients with persistently normal liver biochemistry, but only for cutoff titers ≥ 1:160 (p = 0.004). No cases of de novo autoimmune hepatitis were observed. In conclusion, autoantibodies are very frequently detected after LT also at high titers and their association with graft dysfunction likely represents an aspecific indicator of liver injury.
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Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Autoinmunidad , Trasplante de Hígado , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/etiología , Femenino , Estudios de Seguimiento , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Prevalencia , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Hepatopatías , Trombosis de la Vena , Anticoagulantes , Humanos , Cirrosis Hepática , Vena PortaRESUMEN
AIMS: Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening. METHODS: Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption. RESULTS: The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]. CONCLUSIONS: In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.
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Carcinoma Hepatocelular/fisiopatología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Fallo Hepático/epidemiología , Fallo Hepático/fisiopatología , Neoplasias Hepáticas/fisiopatología , Reacción a la Transfusión/complicaciones , Adulto , Factores de Edad , Carcinoma Hepatocelular/etiología , Femenino , Hepatitis C Crónica/etiología , Humanos , Incidencia , Fallo Hepático/etiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Reacción a la Transfusión/epidemiologíaRESUMEN
BACKGROUND: Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. AIM: We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. METHODS: In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. RESULTS: From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). CONCLUSIONS: Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.
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Colangitis Esclerosante , Trasplante de Hígado , Listas de Espera , Humanos , Colangitis Esclerosante/cirugía , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Italia/epidemiología , Adulto , Listas de Espera/mortalidad , Recurrencia , Anciano , Colangiocarcinoma/cirugíaRESUMEN
Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/µL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000-44,000/µL) to 58,000 (49,000-82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04-1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/µL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/µL are unlikely to respond to the drug.
RESUMEN
BACKGROUND: Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. AIMS: To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. METHODS: Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. RESULTS: Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). CONCLUSIONS: Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.
Asunto(s)
Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Infecciones por VIH , Hepatitis C , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Antivirales/uso terapéutico , Recurrencia Local de Neoplasia/patología , Hepatitis C/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
INTRODUCTION: Lenvatinib is approved for the treatment of patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, clinical outcomes of lenvatinib therapy in patients with post-liver transplantation (LT) HCC recurrence remain unclear. We investigated the efficacy and safety of lenvatinib in patients with post-LT HCC recurrence. METHODS: This multinational, multicenter, retrospective study included 45 patients with recurrent HCC after LT who received lenvatinib at six institutions in three countries (Korea, Italy, and Hong Kong) from June 2017 to October 2021. RESULTS: At the time of lenvatinib initiation, 95.6% (n = 43) of patients had Child-Pugh A status, and 35 (77.8%) and 10 (22.2%) participants were classified as having albumin-bilirubin (ALBI) grades 1 and 2, respectively. The objective response rate was 20.0%. With a median follow-up duration of 12.9 months (95% confidence interval [CI]: 11.2-14.7), the median progression-free survival and overall survival (OS) were 7.6 (95% CI: 5.3-9.8) months, and 14.5 (95% CI: 0.8-28.2) months, respectively. Patients with ALBI grade 1 showed significantly better OS (52.3 months, [95% CI: not assessable]) than patients with ALBI grade 2 (11.1 months [95% CI: 0.0-30.4 months], p = 0.003). The most common adverse events were hypertension (n = 25, 55.6%), fatigue (n = 17, 37.8%), and anorexia (n = 14, 31.1%). CONCLUSION: Lenvatinib showed consistent efficacy and toxicity profiles in patients with post-LT HCC recurrence that were comparable to those reported from previous studies among non-LT HCC patients. The baseline ALBI grade correlated with better OS in post-LT lenvatinib-treated patients.