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1.
Clin Res Hepatol Gastroenterol ; 45(4): 101514, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33714907

RESUMO

BACKGROUND: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis. METHODS: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used. RESULTS: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact. CONCLUSION: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.

2.
J Hepatol ; 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33503489

RESUMO

BACKGROUND & AIMS: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. METHODS: This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 µmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0. RESULTS: A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%. CONCLUSION: In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. LAY SUMMARY: The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.

4.
Am J Transplant ; 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33382179

RESUMO

Hepatocellular carcinoma recurrence after liver transplantation is a well-known complication but the development of de novo hepatocellular carcinoma in non-cirrhotic allograft with no previous history of hepatic malignancy either in the donor or the recipient is extremely rare. A 33-year-old man underwent deceased donor liver transplantation due to HBV-HDV cirrhosis in 1991. The donor was healthy, with negative viral serology. Pretransplant assessment and explant liver pathology revealed no tumor. He developed an 8 cm mediastinal thymus cancer in 2014, a chronic myeloid leukemia in 2015 and a 16 mm renal cell carcinoma in 2017. After 27 years, in 2018, his routine follow-up sonography showed incidentally a 37 mm hepatic nodule in segment VII which revealed after percutaneous liver guided biopsy a hepatocellular carcinoma. As no extra hepatic metastasis was noted, segmentectomy was done. The pathological report confirmed a moderately differentiated hepatocellular carcinoma nodule of 50 mm diameter with absence of microvascular invasion and the non-tumoral liver showed histological features of NASH (SAF score: S1A2F3, NAS score: A3F3 and LAFSc:5) with absence of HBsAg and HBcAg. This case emphasizes the importance of long-term close surveillance by imaging of the graft even in the absence of viral recurrence and graft cirrhosis.

5.
J Hepatol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212089

RESUMO

BACKGROUND & AIMS: Despite improvements of medical and surgical techniques, post-hepatectomy liver failure (PHLF) remains the leading cause of death in that context. High postoperative portal vein pressure (PPV) and portocaval gradient (PCG) are the most important determinants of PHLF, and are not predictable using current tools. Our aim was therefore to evaluate a digital twin to predict the risk of postoperative portal hypertension (PHT). METHODS: We prospectively included 47 patients resected for major hepatectomy. A mathematical (0D) model of the entire blood circulation was assessed and automatically calibrated from patient characteristics. Hepatic flows were obtained from preoperative flow MRI (n=9), intraoperative flowmetry (n=16), or estimated from cardiac output (n=47). Resection was then simulated in these three groups and the PPV and PCG computed were compared to intraoperative data. RESULTS: Simulated post-hepatectomy pressures did not differ between the three groups, comparing well with collected data (no significant differences). In the entire cohort, the correlation between measured and simulated PPV values was good (r=0.66, no adjustment to intraoperative events) or excellent (r=0.75) after adjustment, as well as for PCG (respectively r=0.59 and r=0.80). The difference between simulated and measured post-hepatectomy PCG was ≤3mmHg in 96% of cases. Four patients suffered from lethal PHLF for whom the model satisfactorily predicted their postoperative pressures. CONCLUSIONS: We demonstrated that a 0D model could correctly anticipate postoperative PHT, even using estimated hepatic flow rates as input data. If this major conceptual step is confirmed, this algorithm could change our practice toward more tailor-made procedures, while ensuring satisfactory outcomes.

6.
Dig Liver Dis ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33139195

RESUMO

INTRODUCTION: Liver transplantation (LT) is the therapeutic option for end-stage liver disease associated with alpha1 antitrypsin (A1AT) deficiency. The aim of the present retrospective study was to report on long-term outcomes following LT for A1AT deficiency. METHODS: The medical records of 90 pediatric and adult patients transplanted between 1982 and 2017 in France and Geneva (Switzerland) were reviewed. RESULTS: The study population consisted of 32 adults and 58 children; median age at transplant was 13.0 years (range: 0.2-65.1), and 65 were male (72.2%). Eighty-two patients (94.8% of children and 84.4% of adults) had the PI*ZZ genotype/phenotype and eight patients (8.9%) had the Pi*SZ genotype/phenotype. Eighty-four patients (93.3%) were transplanted for end-stage liver disease and six (all Pi*ZZ adults) for HCC. Median follow-up after LT was 13.6 years (0.1-31.7). The overall cumulative patient survival rates post-transplant were 97.8% at 1 year, and 95.5%, 95.5%, 92.0%, 89.1% at 5, 10, 15, 20 years respectively. The overall cumulative graft survival rates were 92.2% at 1 year, and 89.9%, 89.9%, 84.4%, 81.5% at 5, 10, 15 and 20 years, respectively. CONCLUSIONS: In a representative cohort of patients having presented with end-stage-liver disease or HCC secondary to A1AT, liver transplantation offered very good patient and graft survival rates.

7.
JHEP Rep ; 2(6): 100170, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33205034

RESUMO

Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

10.
Transplantation ; 104(10): 2078-2086, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969987

RESUMO

BACKGROUND: We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection. METHODS: LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined. RESULTS: Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m (aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss. CONCLUSIONS: Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.

11.
Transplantation ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32890134

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in USA. HCC recurrence is the main complication affecting short- and medium-term outcome after LT. METHODS: A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age: 57.8 ± 8.5 years; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and since 2014, AFP score to be listed. Patients with HCC recurrence were classified into early (≤ 2years) and late recurrence (> 2years) and were retrospectively reviewed. RESULTS: Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and UCSF criteria, high AFP score and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5 and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence respectively 64.0% and 27.1% (p<0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months respectively in the two groups (p<0.001). Multivariable cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (HR=3.074; p=0.007), bi-lobar tumor at time of LT (HR=2.001; p=0.037), and a tumor size (>50mm) in the explant (HR=1.277; p=0.045) as independent predictors of early recurrence. CONCLUSION: Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence improve long-term survival.

12.
Liver Transpl ; 26(11): 1465-1476, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32869469

RESUMO

Longterm use of a calcineurin inhibitor (CNI)-based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry (EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate [eGFR]), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60 months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6 ± 5.1 years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR <60 mL/minute/1.73 m2 and was maintained in those with baseline eGFR ≥60 mL/minute/1.73 m2 . Among patients with chronic kidney disease (CKD; baseline eGFR <60 mL/minute/1.73 m2 ), 55% converted to EVR within 3 months (early conversion) and 39.4% converted between 4 and 12 months after transplantation (mid-conversion) experienced improvement in eGFR (≥60 mL/minute/1.73 m2 ) at month 36. Only 20.9% and 17.4% among those converted beyond 12 months (late conversion) experienced improvement respectively at month 36 and 60. A logistic regression analysis in patients with CKD stage ≥3 demonstrated that late conversion, age, and female sex were associated with nonimprovement of eGFR (≥60 mL/minute/1.73 m2 ). Data from this real-life use of EVR indicate that renal function was maintained from the preconversion period until month 36 even in patients with advanced CKD. However, early rather than late conversion appears to be a safe approach to preserve longterm renal function in LTRs.

13.
Ann Surg ; 272(5): 820-826, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833755

RESUMO

BACKGROUND AND AIMS: LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. STUDY DESIGN: Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. RESULTS: A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P < 0.001). CONCLUSIONS: Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/patologia , Idoso , Feminino , Hepatectomia , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Fatores de Risco , Terapia de Salvação , Taxa de Sobrevida
14.
Dig Dis Sci ; 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32607807

RESUMO

BACKGROUND: In patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial. AIM: To identify the predictive factors of histological remission and to assess the relapse rate after treatment withdrawal in AIH patients with prolonged biochemical response. METHODS: Patients with AIH and sustained biochemical remission on first-line treatment were retrospectively included. Histological response was defined as complete regression of interface hepatitis and lobular necrosis and no or minimal portal inflammation and relapse as any elevation of serum aminotransferase or gammaglobulin/IgG levels. RESULTS: Sixty-two patients were included. Forty-seven had a biopsy after a median biochemical response of 49.7 months. Twenty-five of them were histological responders. Independent predictors of histological remission were older age (OR = 1.1; CI 95%: 1.0; 1.2), mild-to-moderate fibrosis at diagnosis (OR = 8; CI: 1.4; 47.6) and aspartate aminotransferases < 0.6 × ULN (OR = 7.1; CI: 1.3; 36.7). Thirty-nine patients stopped therapy after a median biochemical response of 48.6 months. Twenty-four of them had a biopsy before treatment withdrawal: 21 were histological responders. The cumulative rate of relapse was 25% at 64 months. CONCLUSIONS: This study indicates that older age, mild-to-moderate fibrosis at diagnosis and serum aspartate aminotransferases in the lower range of normal are independent predictors of histological response in AIH with prolonged biochemical response. The relapse rate after treatment withdrawal may be limited to 25% at 64 months when patients are selected on the basis of prolonged biochemical remission and, when available, histological response.

15.
Kidney Int ; 98(1): 195-208, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571483

RESUMO

Apolipoprotein A1 amyloidosis (ApoAI) results from specific mutations in the APOA1 gene causing abnormal accumulation of amyloid fibrils in diverse tissues. The kidney is a prominent target tissue in ApoAI amyloidosis with a remarkable selectivity for the renal medulla. Here, we investigated six French families with ApoAI Glu34Lys, p.His179Profs∗47, and a novel p.Thr185Alafs∗41 variant revealing unprecedented clinical association of a glomerular with a retinal disease. Comprehensive clinicopathological, molecular and proteomics studies of numerous affected tissues ensured the correlation between clinical manifestations, including novel unrecognized phenotypes, and apoA-I amyloid deposition. These ophthalmic manifestations stemmed from apoA-I amyloid deposition, highlighting that the retina is a previously unrecognized tissue affected by ApoAI amyloidosis. Our study provides the first molecular evidence that a significant fraction of ApoAI amyloidosis cases with no family history result from spontaneous neomutations rather than variable disease penetrance. Finally, successful hepatorenal transplantation resulted in a life- and vision-saving measure for a 32-year-old man with a hitherto unreported severe ApoAI amyloidosis caused by the very rare Glu34Lys variant. Our findings reveal new modes of occurrence and expand the clinical spectrum of ApoAI amyloidosis. The awareness of glomerular and ocular manifestations in ApoAI amyloidosis should enable earlier diagnosis and avoid misdiagnosis with other forms of renal amyloidosis. Thus, documented apoA-I amyloid deposition in the retina offers new biological information about this disease and may change organ transplantation practice to reduce retinal damage in patients with ApoAI amyloidosis.

16.
Gut ; 69(10): 1832-1840, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32571972

RESUMO

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.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Hepatopatias/cirurgia , Hepatopatias/virologia , Transplante de Fígado , Pneumonia Viral/epidemiologia , Idoso , 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 , Taxa de Sobrevida
17.
Artigo em Inglês | MEDLINE | ID: mdl-32595103

RESUMO

BACKGROUND: Although it has now been excluded that direct-acting antivirals (DAA) are associated with a significant risk of hepatocellular carcinoma (HCC) in HCV-infected patients, a possible effect of DAA on tumor growth is still a subject of debate. We performed a blind comparison of the kinetics of HCC recurrence in patients after HCV treatment with or without DAA to evaluate the potential aggressiveness of HCC after DAA treatment. BASIC PROCEDURES: Thirty-nine HCV-infected patients from the AFEF/ANRS CO22 Hepather cohort who experienced HCC recurrence after so-called curative treatment were evaluated. Contrast-enhanced CT and/or MR images were read blindly 6 months before HCC recurrence and during the follow-up period. Seventeen patients who received DAA (DAA+) before HCC recurrence were compared to the 22 who did not receive (DAA-), according to the LiRads and mRECIST criteria. MAIN FINDINGS: There were 28 men and 11 women, median age 62 years old, 37 (95%) with cirrhosis. DAA+ patients had a lower median MELD score (8±2 vs. 10±4, P=0.0286) than DAA- patients. The median time to HCC recurrence (time from the date of curative treatment to the diagnosis of recurrence) was not different (20 vs. 18 months) (P=0.73) between the two groups. There was no difference between the 2 groups in the overall survival and/or transplantation-free survival (P=0.71) and for the mRECIST time to progression (P=0.25). CONCLUSION: This blinded analysis of HCC recurrence after HCC treatment does not support any negative impact of DAA therapy on the severity or progression of recurrent HCC.

18.
Neurology ; 94(21): e2189-e2202, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32398357

RESUMO

OBJECTIVE: To evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation. METHODS: French patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed. RESULTS: Eighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p < 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p = 0.0007). Severe sepsis (p = 0.011) and intensive care unit admission (p = 0.001) before LT were significantly associated with death. CONCLUSIONS: LT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.


Assuntos
Degeneração Hepatolenticular/cirurgia , Transplante de Fígado/estatística & dados numéricos , Adolescente , Avaliação da Deficiência , Resistência a Medicamentos , Feminino , Humanos , Testes de Função Hepática , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Adulto Jovem
19.
Liver Int ; 40(8): 1853-1859, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383275

RESUMO

BACKGROUND: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis. METHODS: HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan® <9.5 kPa and Fibrotest®  < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12). FINDINGS: Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan® , 100 had F0-1 fibrosis score. FIB-4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance-associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24. INTERPRETATION: Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks.

20.
J Viral Hepat ; 27(10): 964-973, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32436335

RESUMO

Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real-world data available for this regimen. To evaluate the real-life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1-1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real-life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV.

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