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

Hepatitis E virus infection in a patient with alcohol related chronic liver disease: a case report of acute-on-chronic liver failure

Background: The hepatitis E virus (HEV) infection has been described as a causing factor for acute-on-chronic-liverfailure (ACLF) in patients with underlying chronic liver disease (CLD), such as chronic hepatitis or cirrhosis, which could end in the failure of one or more organs and high short-term mortality. There are scarce data about the association of HEV in patients with chronic liver disorders in South America. Case presentation: A 56-year-old hypertensive male with a history of type 2 diabetes was diagnosed with alcoholrelated-liver cirrhosis in February 2019. A year later, the patient was admitted to hospital due to fatigue, jaundice and acholia. No evidence of hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, herpes zoster virus and cytomegalovirus infections were found. Nevertheless, in February and March, 2020 the patient was positive for HEVIgM and HEV-IgG, and HEV genotype 3 RNA was detected in sera. Afterwards, he presented grade I hepatic encephalopathy and, therefore, was diagnosed with acute hepatitis E-on-chronic liver disease. The patient reported a recent travel to the Argentine coast, where he consumed seafood. Besides, he reveled to have consumed pork meat and had no history of blood transfusion. Conclusion: This report describes a unique case of hepatitis E virus infection in a patient with alcohol-related cirrhosis. This is the frst report of a patient with HEV-related ACLF in Argentina and it invokes the importance of HEV surveillance and treatment among patients with CLD, such as alcohol-related cirrhosis.Fil: Fantilli, Anabella Clara. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: López Villa, Sarah Daniela. Instituto Modelo de Cardiología; ArgentinaFil: Zerega, Alina. Sanatorio Allende; ArgentinaFil: Di Cola Bucciarelli, Guadalupe. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: López, Luis. Instituto Modelo de Cardiología; ArgentinaFil: Wassaf Martínez, Maribel. LACE Laboratorios; ArgentinaFil: Pisano, María Belén. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Ré, Viviana Elizabeth. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

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

A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America

© 2018 Elsevier Masson SASBackground and aim: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America. Methods: From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005–2006, 2007–2008, 2009–2010 and 2011–2012 were considered. Etiology of liver disease was confirmed in the explant. Results: Participating LT centers per country included 2 from Brazil (n = 191), 5 transplant programs from Argentina (n = 98), 2 from Colombia (n = 65), 4 from Chile (n = 49), 2 from Mexico (n = 12), and 1 from Peru (n = 11) and Uruguay (n = 9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis a

Surveillance for Hepatocellular Carcinoma: Does the Place Where Ultrasound Is Performed Impact Its Effectiveness?

Background: Biannual ultrasound (US) is recommended as the clinical screening tool for hepatocellular carcinoma (HCC). The effectiveness of surveillance according to the place where US is performed has not been previously reported. Aims: To compare the effectiveness of US performed in the center responsible for follow-up as opposed to US proceeding from centers other than that of follow-up. Methods: This is a multicenter cohort study from Argentina. The last US was categorized as done in the same center or done in a different center from the institution of the patient’s follow-up. Surveillance failure was defined as HCC diagnosis not meeting Barcelona Clinic Liver Cancer (BCLC) stages 0-A or when no nodules were observed at HCC diagnosis. Results: From 533 patients with HCC, 62.4% were under routine surveillance with a surveillance failure of 38.8%. After adjusting for a propensity score matching, BCLC stage and lead-time survival bias, surveillance was associated with a significant survival benefit [HR of 0.51 (CI 0.38; 0.69)]. Among patients under routine surveillance (n = 345), last US was performed in the same center in 51.6% and in a different center in 48.4%. Similar rates of surveillance failure were observed between US done in the same or in a different center (32% vs. 26.3%; P = 0.25). Survival was not significantly different between both surveillance modalities [HR 0.79 (CI 0.53; 1.20)]. Conclusions: Routine surveillance for HCC in the daily practice improved survival either when performed in the same center or in a different center from that of patient’s follow-up.Fil: Piñero, Federico. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Rubinstein, Fernando Adrian. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Marciano, Sebastián. Hospital Italiano; ArgentinaFil: Fernández, Nora. Hospital Británico de Buenos Aires; ArgentinaFil: Silva, Jorge. Hospital G Rawson; ArgentinaFil: Zambelo, Yanina. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Anders, Margarita. Hospital Aleman; ArgentinaFil: Zerega, Alina. Hospital Privado de Córdoba; ArgentinaFil: 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: Miguez, Carlos. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. 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. Clínica de Nefrología; ArgentinaFil: Bermúdez, Carla. Hospital Italiano; ArgentinaFil: Rosales, Carlos. Hospital G Rawson; ArgentinaFil: Romero, Gustavo. Hospital Udaondo; ArgentinaFil: Mc Cormack, Lucas. Hospital Alemán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reggiardo, Virginia. Provincia de Santa Fe. Municipalidad de Rosario. Secretaría de Salud. Centro de Especialidades Médicas Ambulatorias de Rosario; 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

Adherence to Barcelona Clinic Liver Cancer therapeutic algorithm for hepatocellular carcinoma in the daily practice: A multicenter cohort study from Argentina

Background and aim Adherence to the Barcelona Clinic Liver Cancer (BCLC) staging algorithm for the treatment of hepatocellular carcinoma is challenging in the daily practice. We aimed to analyze adherence to BCLC along with its effect on patient survival. Patients and methods A cohort study was conducted in 14 hospitals from Argentina including patients with newly diagnosed hepatocellular carcinoma (2009-2016). Adherence was considered when the first treatment was the one recommended by the BCLC. Results Overall, 708 patients were included. At diagnosis, BCLC stages were as follows: stage 0 4%, A 43%, B 22%, C 9% and D 22%. Overall, 53% of the patients were treated according to BCLC, 24% were undertreated, and 23% overtreated. Adherence to BCLC increased to 63% in subsequent treatments. Independent factors associated with adherence to BCLC were the presence of portal hypertension [odds ratio: 1.63; 95% confidence interval (CI): 1.11-2.39] and BCLC stage C (odds ratio: 0.32; 95% CI: 0.12-0.72). In a multivariable model adjusting for portal hypertension and BCLC stages, adherence to BCLC showed improved survival (hazard ratio: 0.67; 95% CI: 0.52-0.87). Conclusion Adherence to BCLC represents a challenge in the daily practice, with almost half of the patients being treated accordingly, showing that the decision-making process should be tailored to each individual patient.Fil: Piñero, Federico. 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: Marciano, Sebastian. 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: Fernández, Nora. 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: Silva, Jorge. 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: Zambelo, Yanina. 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: Cobos, Manuel. 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: Zerega, Alina. 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: 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: Miguez, Carlos.Fil: Ameigeiras, Beatriz.Fil: D'amico, Claudia Alejandra.Fil: Gaite, Luis.Fil: Coronel, Matías.Fil: Bermúdez, Carla.Fil: Rosales, Carlos.Fil: Romero, Gustavo.Fil: Mc Cormack, Lucas.Fil: Reggiardo, Virginia.Fil: Colombato, Luis.Fil: Gadano, Adrián Carlos.Fil: Rubinstein, Fernando Adrian.Fil: Silva, Marcelo

Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries.

Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96-760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57-141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis