‘Real-life’ experience with direct-acting antiviral agents for HCV after kidney transplant

Introductions and Objectives: The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of hepatitis C is historically challenging. The purpose of the current study was to assess (in a ‘real-life’ setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV. Material and Methods: We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvirbased regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four dropouts obtained SVR. Conclusions: All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a ‘real–life’ clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way

Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.Fil: Piñero, Federico. Hospital Universitario Austral; Argentina. Sanatorio de la Trinidad San Isidro; ArgentinaFil: Pages, Josefina. Hospital Universitario Austral; ArgentinaFil: Marciano, Sebastián. Hospital Italiano; ArgentinaFil: Fernández, Nora. Hospital Británico de Buenos Aires; ArgentinaFil: Silva, Jorge. Provincia de San Juan. Hospital Rawson; ArgentinaFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Zerega, Alina. Sanatorio Allende; ArgentinaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: D'amico, Claudia. Centro Especialidades Médicas Ambulatorias Mar del Plata; ArgentinaFil: Gaite, Luis. Clínica de Nefrología de Santa Fe; ArgentinaFil: Bermúdez, Carla. Hospital Italiano; ArgentinaFil: Cobos, Manuel. Hospital Alemán; ArgentinaFil: Rosales, Carlos. Provincia de San Juan. Hospital Rawson; ArgentinaFil: Romero, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: McCormack, Lucas. Hospital Alemán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reggiardo, Virginia. Gobierno de Santa Fe. Hospital Provincial del Centenario; ArgentinaFil: Colombato, Luis. Hospital Británico de Buenos Aires; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; ArgentinaFil: Silva, Marcelo. Hospital Universitario Austral; Argentin

Serious liver injury induced by Nimesulide: an international collaboration study reporting 57 cases

Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and LATIN DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a 2-fold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤15 days in 12 patients (21%) and one patient developed ALF within seven days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI18-00901; PI 18/01804; PT20/00127) and Agencia Española del Medicamento. Plataforma ISCiii de Investigación Clínica and CIBERehd are funded by ISCIII. MRD holds a Joan Rodes (JR16/00015)/Acción B clinicos investigadores (B-0002-2019) research contract from ISCIII and Consejería de Salud de Andalucía, IAA holds a Sara Borrell research contract from the National Health System, ISCIII (CD 20/00083)

Tratamiento en respondedores con recidiva

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Tratamiento en pacientes con transaminasas normales

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Efficacy, tolerability and safety in the treatment of chronic hepatitis C with combination of PEG-Interferon – Ribavirin in daily practice

Background. Efficacy and safety of Pegylated Interferon alfa (PegIFN)-Ribavirin (RBV) for the treatment of chronic hepatitis C (CHC) in routine clinical practice seems to be comparable with results of randomizedcontrolled trials.Aims. To evaluate the efficacy, tolerability and safety of CHC treatment with PegIFN + RBV in “real world” patients in Argentina and to analyze factors associated with SVR.Methods. Medical records of patients treated according to current guidelines from 2001 to 2008 were reviewed.Results. 235 patients were included and 80.8% completed treatment. Discontinuation occurred in 7.6% due to adverse events (AE), and 1.2% dropped-out treatment. Overall SVR was 60.8%. Multivariate analysis demonstrated that being naive (p 0.031) and low basal viral load (p 0.006) were associated with SVR, whereas F3-F4 (p 0.001) and elevated ALT (p 0.023) were associated with non-response. 80% of planned doses completed was associated with 74% SVR (p <0.001). At least one AE was reported in 93.6% of the patients: neutropenia in 27.6%, thrombocytopenia in 15.3%, anemia in 38.7%, psychiatric symptoms in 63.4%, thyroid dysfunction in 10.2%.Conclusion. Efficacy, tolerability and safety of treatment of CHC in daily practice in Argentina are similar to those reported in randomized controlled trials

Intermediate-advanced hepatocellular carcinoma in Argentina: Treatment and survival analysis

BACKGROUND: Hepatocellular carcinoma (HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC. AIM To describe real-life treatments performed in patients with intermediate-advanced HCC before the approval of new systemic options. METHODS This longitudinal observational cohort study was conducted between 2009 and 2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer (BCLC) HCC stages (BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death. Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios (HR) calculations and 95% confidence intervals (95%CI). RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D. Corresponding median survival were 15 mo (IQR 5-26 mo), 5 mo (IQR 2-13 mo) and 3 mo (IQR 1-13 mo) (P 0.0001), respectively. Among BCLC-B patients (n = 135), 57% received TACE with a median number of 2 sessions (IQR 1-3 sessions). Survival was significantly better in BCLC-B patients treated with TACE HR = 0.29 (CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival [HR = 0.15 (CI: 0.04-0.56, P = 0.005)]. Eighty-two patients were treated with sorafenib, mostly BCLC-B and C (87.8%). However, 12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo (IQR 2.3-11.7 mo); which was lower among BCLC-D patients 3.2 mo (IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients, treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26 (CI: 0.09-0.71); P = 0.013]. CONCLUSION In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.Fil: Piñero, Federico. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Marciano, Sebastián. Hospital Italiano; ArgentinaFil: Fernández, Nora. Hospital Británico de Buenos Aires; ArgentinaFil: Silva, Jorge. Hospital G Rawson; ArgentinaFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Zerega, Alina. No especifíca;Fil: Ridruejo, Ezequiel. Universidad Austral. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Romero, Gustavo. Hospital Udaondo; ArgentinaFil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: D?Amico, Claudia. Provincia de Santa Fe. Municipalidad de Rosario. Secretaría de Salud. Centro de Especialidades Médicas Ambulatorias de Rosario; ArgentinaFil: Gaite, Luis. No especifíca;Fil: Bermúdez, Carla. Hospital Italiano; ArgentinaFil: Reggiardo, Virginia. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Colombato, Luis. Hospital Británico de Buenos Aires; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Silva, Marcelo. Universidad Austral. Hospital Universitario Austral; Argentin

Natural history of hepatitis C virus infection in a cohort of asymptomatic post-transfused subjects

Background &amp; aims. Studies about the natural history of hepatitis C virus (HCV) infection report variable progression to cirrhosis depending on study design. Retrospective cross-sectional liver clinic studies overestimate the rate of fibrosis progression due to inclusion of patients with more severe disease leaving mild and asymptomatic patients underrepresented. We evaluated fibrosis progression in a group of “healthy” asymptomatic subjects, attending to a voluntary campaign for the detection of HCV infection.Material and methods. A detection campaign was launched on subjects transfused before 1993. Of 1699 volunteers, 61(3.6%) had HCV infection. A liver biopsy was performed in 40 (65%). Assessed risk factors for liver fibrosis were: sex, body mass index, alcohol consumption (> 20 g/d♀ - >40g/d♂), genotype, HLA-DRB1 alleles, present age, age at infection and duration of infection.Results. 25 (62.5%) were women with a median age of 52.5 years. The median duration of infection was 21.5 years with a median age at infection of 27 years. As regards fibrosis, 25 (62.5%) had a Low Stage (F0-F1), 8 patients, 20%, had severe fibrosis, one patient (2.5%) had cirrhosis. Alcohol consumption was the only risk factor associated with fibrosis progression.Conclusions. The low progression to cirrhosis may be explained by the clinical characteristics of ourpopulation: asymptomatic middle-aged “healthy” subjects infected at young age. The progression to severe fibrosis was noticeable; hence a longer follow-up might demonstrate changes in this outcome. Significant alcohol consumption clearly worsens the natural history of HCV infection; this is no so evident for occasional or mild alcohol consumers