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BACKGROUND: Livers from controlled donation after circulatory death (cDCD) with very prolonged warm ischemic time (WIT) are regularly transplanted after abdominal normothermic regional perfusion (aNRP) plus ex-situ machine perfusion (MP). Considering aNRP as in-situ MP, we investigated whether the results of a pilot experience of extended criteria cDCD liver transplantation (LT) with prolonged WIT, with aNRP alone, were comparable to the best possible outcomes in low-risk cDCD LT. METHODS: Prospectively collected data on 24 cDCD LT, with aNRP alone, were analyzed. RESULTS: The median total and asystolic WIT were 51 and 25 min. Measures within benchmark cut-offs were: median duration of surgery (5.9 h); median intraoperative transfusions (3 units of red blood cells); need for renal replacement therapy (2/24 patients); median intensive care stay (3 days); key complications; overall morbidity, graft loss, and retransplantation up to 12 months; 12-month mortality (2/21 patients). The median hospital stay (33 days, due to logistics) and mortality up to 6 months (2/24 patients, due to graft-unrelated causes) exceeded benchmark thresholds. CONCLUSIONS: This pilot experience suggests that livers from cDCD with very prolonged WIT that appear viable during adequate quality aNRP may be safely transplanted, with no need for ex-situ MP, with considerable resource savings.
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Doadores de Tecidos , Isquemia Quente , Humanos , Isquemia Quente/efeitos adversos , Preservação de Órgãos/métodos , Perfusão/efeitos adversos , Perfusão/métodos , Fígado/cirurgia , Sobrevivência de EnxertoRESUMO
BACKGROUND AND AIM: The World Health Organization (WHO) goal of hepatitis C virus (HCV) elimination by 2030 relies on the scaling-up of both identification and linkage to care of the infected population, worldwide. In Italy, the estimated burden of HCV carriers who are unaware of their infection amounts to 200 000 persons, a projection that reinforces the need for broadening population access to effective screening programmes. METHODS: A pivotal screening programme targeting subjects born between 1969 and 1989 has been conducted in Lombardy, Northern Italy, where point-of-care (POC) testing was offered for free concomitantly to COVID-19 vaccination. RESULTS: Amongst 7219 subjects born between 1969 and 1989 who underwent HCV screening through POC, 7 (0.10%) subjects tested anti-HCV positive: 5 (0.07%) had confirmed anti-HCV positivity (Table 1) and 4 of them (0.05%) were HCV-RNA positive by standard confirmation tests. CONCLUSIONS: This pivotal study demonstrated the feasibility of a POC-based anti-HCV screening programme in young adults undergoing COVID-19 vaccination. The prevalence of HCV infection in subjects born in the 1969-1989 cohort in Italy seems to be lower than previously estimated. Whether the extension of this programme to subjects born before 1969 could lead to improved screening effectiveness should be a matter of debate.
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COVID-19 , Hepatite C , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Anticorpos Anti-Hepatite C , Humanos , Programas de Rastreamento , VacinaçãoRESUMO
OBJECTIVE: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course. DESIGN: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed. RESULTS: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170). CONCLUSIONS: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).
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COVID-19/mortalidade , Transplante de Fígado , Pneumonia Viral/mortalidade , Transplantados , Causas de Morte , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/virologia , Sistema de Registros , Fatores de Risco , SARS-CoV-2 , Listas de EsperaRESUMO
In routine clinical practice, hepatitis C virus-infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE-Lombardia Network database from January 2015, who discontinued DAAs before the predefined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5 years, and 53 (14.5%) patients were HIV-co-infected. Liver cirrhosis was observed in 251 (68.8%) subjects, and the most represented genotypes were 1b (n = 168, 46%) and 3 (n = 59, 16.2%). DAA was discontinued a median of 1 (IQR 1-4) weeks before the predefined EOT, with 164 (44.9%) patients stopping DAAs at least 2 weeks before the planned schedule. In patients with F0-F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for <4 weeks: 50% (n = 2/4) vs. 99.1% (n = 109/110) for ≥4 weeks, p = 0.003. In patients with liver cirrhosis, lower rates of SVR12 were observed in patients treated <8 weeks: 83.3% (n = 25/30) vs. 94.6% (n = 209/221) for ≥8 weeks, p = 0.038. Despite premature discontinuation of DAA, high SVR12 rates were observed in a real-life setting for treatment lasting at least 4 weeks in patients with liver fibrosis F0-F3 and 8 weeks in those with liver cirrhosis. On this basis, feasibility of reducing DAA treatment duration should be explored in randomized clinical trials.
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Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
OBJECTIVE: Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. DESIGN: We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. RESULTS: 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. CONCLUSION: In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.
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Betacoronavirus , Infecções por Coronavirus/epidemiologia , Hepatopatias/cirurgia , Hepatopatias/virologia , Transplante de Fígado , Pneumonia Viral/epidemiologia , Idoso , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Europa (Continente) , Feminino , Hospitalização , Humanos , Hepatopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Estudos Prospectivos , SARS-CoV-2 , Taxa de SobrevidaRESUMO
BACKGROUND & AIMS: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. METHODS: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression. RESULTS: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10 HCV-RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12. CONCLUSIONS: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <
Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. METHODS: All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13â¯kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. RESULTS: A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12â¯weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (pâ¯=â¯0.005) and hepatocellular carcinoma (pâ¯=â¯0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). CONCLUSIONS: SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. LAY SUMMARY: This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.
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Carbamatos , Carcinoma Hepatocelular , Hepacivirus , Hepatite C Crônica , Compostos Heterocíclicos de 4 ou mais Anéis , Cirrose Hepática , Neoplasias Hepáticas , Compostos Macrocíclicos , Sofosbuvir , Sulfonamidas , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Combinação de Medicamentos , Farmacorresistência Viral , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Itália/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Compostos Macrocíclicos/administração & dosagem , Compostos Macrocíclicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , RNA Viral/isolamento & purificação , Retratamento/métodos , Fatores de Risco , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento , Proteínas não Estruturais ViraisRESUMO
BACKGROUND AND AIMS: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting. METHODS: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16â¯weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12â¯weeks after the end of treatment. RESULTS: A total of 723 patients (50% males) were treated with G/P, 89% for 8â¯weeks. The median age of our cohort was 58â¯years, with a median body mass index of 23.9â¯kg/m2, and median liver stiffness measurement of 6.1â¯kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600â¯IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2â¯ml/min, platelet count 209x103/mm3 and albumin 4.3â¯g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8â¯weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes. CONCLUSIONS: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16â¯weeks. LAY SUMMARY: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.
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Benzimidazóis , Hepatite C Crônica , Fígado/patologia , Quinoxalinas , Sulfonamidas , Ácidos Aminoisobutíricos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Biópsia/métodos , Estudos de Coortes , Ciclopropanos , Combinação de Medicamentos , Técnicas de Imagem por Elasticidade/métodos , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Itália/epidemiologia , Lactamas Macrocíclicas , Leucina/análogos & derivados , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas/administração & dosagem , Quinoxalinas/efeitos adversos , RNA Viral/análise , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Resultado do TratamentoAssuntos
Infecções por Coronavirus , Coronavirus , Hepatopatias , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Nível de Saúde , Humanos , Itália , SARS-CoV-2Assuntos
Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Transplante de Rim/efeitos adversos , Sofosbuvir/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada , Transplantados , Resultado do TratamentoRESUMO
The development of steatotic liver disease after liver transplant (LT) is widely described, and epidemiological data have revealed an increased incidence in recent times. Its evolution runs from simple steatosis to steatohepatitis and, in a small proportion of patients, to significant fibrosis and cirrhosis. Apparently, post-LT steatotic disease has no impact on the recipient's overall survival; however, a higher cardiovascular and malignancy burden has been reported. Many donors' and recipients' risk factors have been associated with this occurrence, although the recipient-related ones seem of greater impact. Particularly, pre- and post-LT metabolic alterations are strictly associated with steatotic graft disease, sharing common pathophysiologic mechanisms that converge on insulin resistance. Other relevant risk factors include genetic variants, sex, age, baseline liver diseases, and immunosuppressive drugs. Diagnostic evaluation relies on liver biopsy, although non-invasive methods are being increasingly used to detect and monitor both steatosis and fibrosis stages. Management requires a multifaceted approach focusing on lifestyle modifications, the optimization of immunosuppressive therapy, and the management of metabolic complications. This review aims to synthesize the current knowledge of post-LT steatotic liver disease, focusing on the recent definition of metabolic-dysfunction-associated steatotic liver disease (MASLD) and its metabolic and multisystemic concerns.
RESUMO
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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Colangite Esclerosante , Transplante de Fígado , Listas de Espera , Humanos , Colangite Esclerosante/cirurgia , Colangite Esclerosante/complicações , Colangite Esclerosante/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Itália/epidemiologia , Adulto , Listas de Espera/mortalidade , Recidiva , Idoso , Colangiocarcinoma/cirurgiaRESUMO
The aim of this study was to evaluate the factors affecting the response to treatment and how it could affect survival in a large series of genotype-1 HCV-transplanted patients. Three-hundred and twenty six genotype-1 HCV patients were enrolled. One hundred and ninety-six patients (60.1%) were nonresponders and 130 (39.9%) showed negative HCV-RNA at the end of treatment. Eighty-four of them (25.8%) achieved sustained virological response, while 46 (14.1%) showed viral relapse. Five-year cumulative survival was significantly worse in nonresponders (76.4%) compared with sustained viral response (93.2) or relapsers (94.9%). Sustained responders and relapsers were therefore considered as a single 'response group' in further analysis. Pretreatment variables significantly associated with virological response at multivariate regression analysis were the absence of ineffective pretransplant antiviral therapy, the recurrence of HCV-hepatitis more than 1 year after transplant, an histological grading ≥4 at pretreatment liver biopsy, a pretreatment HCV-RNA level <1.2 × 10(6 ) IU/ml, and the absence of diabetes. As expected, also on-treatment variables (rapid and early virological response) were significantly associated to the response to antiviral treatment. In conclusion, this study shows that postliver transplant antiviral treatment results in beneficial effect on survival not only in sustained responders but also in relapsers.
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Antivirais/administração & dosagem , Genótipo , Hepatite C Crônica/genética , Hepatite C Crônica/cirurgia , Transplante de Fígado/mortalidade , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Hepatite C Crônica/mortalidade , Hepatite C Crônica/patologia , Humanos , Interferon-alfa/administração & dosagem , Itália , Estimativa de Kaplan-Meier , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polietilenoglicóis/administração & dosagem , Valor Preditivo dos Testes , Proteínas Recombinantes/administração & dosagem , Recidiva , Análise de Regressão , Retratamento , Estudos Retrospectivos , Ribavirina/administração & dosagem , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy. Sustained virological response (SVR), adherence-to-therapy, and side effects were evaluated. A multivariate logistic regression model was used after adjusting for possible confounders. The data regarding 342 treated patients were analyzed. SVR was reported in 38.8% of patients. At baseline, male and female did not differ in HCV viral load, histology, or rate of diabetes. SVR was lower in females than in males (29.5% vs. 42.1%; P=0.03). Adherence-to-therapy was also lower in females than in males 43.4% vs. 23.8%; P=0.001); anemia was the main reason for lower adherence. In a multivariate analysis in patients Genotype1, female gender (P<0.04), early virological response (P<0.0001), and adherence to therapy (P<0.0001) were independent predictors for SVR. In conclusion, female gender represents an independent negative prognostic factor for the outcome of HCV antiviral therapy after LT.
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Antivirais/uso terapêutico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Transplante de Fígado , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Feminino , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , RNA Viral/sangue , Recidiva , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento , Carga ViralRESUMO
INTRODUCTION: Hepatitis C virus genotype 4 is predominant in the Middle East and Northern Africa, even if it has recently spread to Southern Europe. Data about the treatment of post-liver transplantation (LT) genotype 4 hepatitis C recurrence are scarce. We report a retrospective analysis of post-LT genotype 4 hepatitis C treatment in 9 Italian transplant centres, focusing on the overall survival rates and treatment outcome. RESULTS: Among 452 recipients, we identified 17 HCV genotype 4 patients (16 males, 1 female) transplanted between 1998 and 2007. All patients received combined antiviral treatment with conventional doses of interferon (recombinant or pegylated) and ribavirin after histological diagnosis of hepatitis C recurrence. The observed overall survival after LT was 100% at 1 year and 83.3% at 5 years. More than 1/3 (35.3%) of patients achieved a sustained virological response (SVR) and 40% (data available in 15 subjects) an early virological response (EVR), which was significantly associated with the achievement of SVR (overall accuracy: 85.7%; predictive values of EVR absence/presence 80/88.8%; chi-square p < 0.05). CONCLUSION: In conclusion, in post-LT genotype 4 hepatitis C treatment, SVR rates are similar to genotype 1. Patients who don't show an EVR are not likely to achieve a SVR.
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Antivirais/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/terapia , Transplante de Fígado , Adulto , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Interferon-alfa/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Recidiva , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sarcopenia , Carcinoma Hepatocelular/complicações , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Qualidade de Vida , Estudos Retrospectivos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/etiologiaRESUMO
The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2 , 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20-3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16-6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11-0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi-disciplinary management approach may improve cardiovascular and possibly liver-related outcomes.
Assuntos
Carcinoma Hepatocelular , Doenças Cardiovasculares , Diabetes Mellitus , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Doenças Cardiovasculares/complicações , Estudos de Coortes , Diabetes Mellitus/tratamento farmacológico , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/epidemiologia , Resposta Viral SustentadaRESUMO
BACKGROUND: Women who have undergone liver transplantation (LT) enjoy better health, and possibility of childbearing. However, maternal and graft risks, optimal immunosuppression, and fetal outcome is still to clarify. AIM: Aim of the study was to assess outcomes of pregnancy after LT at national level. METHODS: In 2019, under the auspices of the Permanent Transplant Committee of the Italian Association for the Study of the Liver, a multicenter survey including 14 Italian LT-centers was conducted aiming at evaluating the outcomes of recipients and newborns, and graft injury/function parameters during pregnancy in LT-recipients. RESULTS: Sixty-two pregnancies occurred in 60 LT-recipients between 1990 and 2018. Median age at the time of pregnancy was 31-years and median time from transplantation to conception was 8-years. During pregnancy, 4 recipients experienced maternal complications with hospital admission. Live-birth-rate was 100%. Prematurity occurred in 25/62 newborns, and 8/62 newborns had low-birth-weight. Cyclosporine was used in 16 and Tacrolimus in 37 pregnancies, with no different maternal or newborn outcomes. Low-birth-weight was correlated to high values of AST, ALT and GGT. CONCLUSION: Pregnancy after LT has good outcome; however, maternal complications and prematurity may occur. Compliance with the immunosuppression is fundamental to ensure the stability of graft function and prevent graft-deterioration.
Assuntos
Doenças do Recém-Nascido , Transplante de Fígado , Complicações na Gravidez , Ciclosporina , Feminino , Humanos , Imunossupressores/uso terapêutico , Recém-Nascido , Transplante de Fígado/efeitos adversos , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , Tacrolimo/uso terapêuticoRESUMO
Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.
Assuntos
Hepatopatias/complicações , Insuficiência Renal Crônica/complicações , Gastroenterologia , Humanos , Itália , Nefrologia , Sociedades MédicasRESUMO
BACKGROUND: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020. RESULTS: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO