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Hepatitis E virus (HEV) is a public health concern due to its zoonotic transmission to human, being pigs a highly recognized reservoir. We previously demonstrated HEV genotype 3 infections in pig herds from the highest commercial active region from Argentina. Here, we present a case of acute symptomatic hepatitis E in an elderly man with occupational exposure to pigs who referred regular consumption of pork and sausages. HEV infection in this patient was demonstrated by serological methods, as well as by HEV RNA detection in serum and stool samples using the HEV/MS2 duplex RT-qPCR, formerly optimized in our laboratory. We further detected HEV RNA in pig faeces from the patient´s farm. To confirm the potential role of swine in the transmission, we performed a phylogenetic analysis of all HEV RNA derived from both, the patient and the pig samples. A 303 nt region within the HEV 5 'ORF2 was amplified by nested RT-PCR and subsequently sequenced. Phylogenetic analysis showed that the strains isolated from the farmer and from his pigs presented a nucleotide identity of 100%. These results support the zoonotic transmission of circulating HEV strains and confirm this epidemiological association for the first time in Argentina.

The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline. Fil: Piñero, Federico. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Tanno, Mario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Hospital Nacional del Centenario; Argentina Fil: Aballay Soteras, Gabriel. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Tisi Baña, Matías. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Dirchwolf, Melisa. Hospital Privado de Rosario; Argentina Fil: Fassio, Eduardo. Hospital Nacional Profesor Alejandro Posadas.; Argentina Fil: Ruf, Andrés. Hospital Privado de Rosario; Argentina Fil: Mengarelli, Silvia Estela. Gobierno de la Provincia de Entre Rios. Hospital San Roque.; Argentina Fil: Borzi, Silvia. Hospital Privado de Cordoba; Argentina Fil: Fernández, Nora. Hospital Británico de Buenos Aires; Argentina 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; Argentina Fil: Descalzi, Valeria. Fundación Favaloro; Argentina Fil: Anders, Margarita. Hospital Alemán; Argentina Fil: Mazzolini, Guillermo. Universidad Austral; Argentina Fil: Reggiardo, Virginia. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina Fil: Marciano, Sebastian. Hospital Italiano. Departamento de Medicina.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Perazzo, Florencia. Hospital Británico de Buenos Aires; Argentina Fil: Spina, Juan Carlos. Hospital Italiano; Argentina Fil: McCormack, Lucas. Hospital Alemán; Argentina Fil: Maraschio, Martín Alejandro. Hospital Privado de Cordoba; Argentina Fil: Lagues, Cecilia. Universidad Austral; Argentina Fil: Gadano, Adrián Carlos. Hospital Italiano. Departamento de Medicina.; Argentina Fil: Villamil, Federico. Hospital Italiano. Departamento de Medicina.; Argentina. Hospital Británico de Buenos Aires; Argentina Fil: Silva, Marcelo. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Cairo, Fernando. Hospital Británico de Buenos Aires; Argentina Fil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina

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

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.

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 American 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 twofold 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 7 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.

INTRODUCTION Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P

We report the first real-world prospective multicenter cohort study that evaluated the effectiveness and safety of original or generic sofosbuvir-based regimens in patients with chronic hepatitis C in Latin America. The main endpoints were assessment of sustained virological response and serious adverse events rates. A total of 321 patients with chronic hepatitis C treated with the following regimens were included: sofosbuvir plus daclatasvir for 12 (n = 34) or 24 (n = 135) weeks, sofosbuvir plus daclatasvir plus ribavirin for 12 (n = 84) or 24 (n = 56) weeks, or sofosbuvir plus ribavirin for 12 (n = 8) or 24 (n = 2) weeks. Patients received either original sofosbuvir (Sovaldi® , Gilead Sciences, n = 135) or generic sofosbuvir (Probirase® , Laboratorios RICHMOND, n = 184) which were randomly assigned by the National Ministry of Health. Overall, 292 (91%) patients had cirrhosis, 136 (42%) were treatment experienced, and 240 (75%) genotype 1. The overall sustained virological response was 90% (95% CI 86-93%); 91% (95% CI 84-95%) in patients who received Sovaldi® , and 89% (95% CI 84-93%) in patients who received Probirase® . Anemia was the most common adverse event and was reported in 52 (17%) patients. Bacterial infection, gastrointestinal bleeding, worsening of ascites or encephalopathy occurred in less than 5% of the patients. During the study, seven (2%) patients died, four of whom died of cirrhosis-related complications. In summary, we observed similar sustained virological response rates than prior studies, both in patients who received Sovaldi® or Probirase® . Serious adverse events were infrequent, in line with prior studies that included patients with cirrhosis treated with protease-inhibitor-free regimes.

Background & Aims Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. Methods We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. Results During a median follow-up period of 26.2 months (interquartile range, 15.3–37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%–5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%–4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2–9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2–3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3–7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1–0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%–0.8%; P = .02) in the overall cohort. Conclusions Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798 .

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. 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. 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. 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)]. 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.

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.; Argentina Fil: 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.; Argentina Fil: 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.; Argentina Fil: 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.; Argentina Fil: 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.; Argentina Fil: 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.; Argentina Fil: 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.; Argentina Fil: 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.; Argentina Fil: 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.

Background & Aims: Cyproterone acetate (CPA), an anti-androgenic drug for prostate cancer, has been associated with drug-induced liver injury (DILI). We aim to expand the knowledge on the spectrum of phenotypes and outcomes of CPA-induced DILI. Methods: Twenty-two males (70±8 years; range 54-83) developing liver damage as a result of CPA therapy (dose: 150±50mg/day; range 50-200) were included. Severity index and causality by RUCAM were assessed. Results: From 1993 to 2013, 22 patients were retrieved. Latency was 163±97days. Most patients were symptomatic, showing hepatocellular injury (91%) and jaundice. Liver tests at onset were: ALT 18±13×ULN, ALP 0.7±0.7×ULN and total serum bilirubin 14±10mg/dl. International normalized ratio values higher than 1.5 were observed in 14 (66%) patients. Severity was mild in 1 case (4%), moderate in 7 (32%), severe in 11 (50%) and fatal in 3 (14%). Five patients developed ascitis, and four encephalopathy. One patient had a liver injury that resembled autoimmune hepatitis. Eleven (50%) were hospitalized. Nineteen patients recovered after CPA withdrawal, although three required steroid therapy (two of them had high ANA titres). Liver biopsy was performed in seven patients (two hepatocellular collapse, one submassive necrosis, two cholestatic hepatitis, one cirrhosis with iron overload and one autoimmune hepatitis). RUCAM category was 'highly probable' in 19 (86%), 'probable' in 1 (4%), and 'possible' in 2 (9%). Conclusions: CPA-induced liver injury is severe and can be fatal, and may occasionally resemble autoimmune DILI. The benefit/risk ratio of this drug should be thoroughly assessed in each patient. Fil: Bessone, Fernando. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Lucena, M. L.. Universidad de Málaga; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España Fil: Roma, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina Fil: Stephens, Camilla. Universidad de Málaga; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España Fil: Medina Cáliz, Inmaculada. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España. Universidad de Málaga; España Fil: Frider, Bernardo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Tsariktsian, Guillermo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Hernández, Nelia. Universidad de la República; Uruguay Fil: Bruguera, Miquel. Liver Unit; España Fil: Gualano, Gisela. Hospital Alejandro Posadas; Argentina Fil: Fassio, Eduardo. Hospital Alejandro Posadas; Argentina Fil: Montero, Joaquin. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Reggiardo, María V.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Ferretti, Sebastian Eduardo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Colombato, Luis. Hospital Británico de Buenos Aires; Argentina Fil: Tanno, Federico. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Ferrer, Jaime. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Zeno, Lelio. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Tanno, Hugo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Andrade, Raúl J.. Universidad de Málaga; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas ; España

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; Argentina Fil: Pages, Josefina. Hospital Universitario Austral; Argentina Fil: Marciano, Sebastián. Hospital Italiano; Argentina Fil: Fernández, Nora. Hospital Británico de Buenos Aires; Argentina Fil: Silva, Jorge. Provincia de San Juan. Hospital Rawson; Argentina Fil: Anders, Margarita. Hospital Alemán; Argentina Fil: Zerega, Alina. Sanatorio Allende; Argentina Fil: 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; Argentina Fil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: D'amico, Claudia. Centro Especialidades Médicas Ambulatorias Mar del Plata; Argentina Fil: Gaite, Luis. Clínica de Nefrología de Santa Fe; Argentina Fil: Bermúdez, Carla. Hospital Italiano; Argentina Fil: Cobos, Manuel. Hospital Alemán; Argentina Fil: Rosales, Carlos. Provincia de San Juan. Hospital Rawson; Argentina Fil: Romero, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: McCormack, Lucas. Hospital Alemán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Reggiardo, Virginia. Gobierno de Santa Fe. Hospital Provincial del Centenario; Argentina Fil: Colombato, Luis. Hospital Británico de Buenos Aires; Argentina Fil: Gadano, Adrián Carlos. Hospital Italiano; Argentina Fil: Silva, Marcelo. Hospital Universitario Austral; Argentina

Background and aims. Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established. Material and methods. We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naive HBV patients treated with ETV for more than 6 months, and predictors of response. Results. A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log 10 IU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported. Conclusion. Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice.

Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real-clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real-world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child-Pugh B at baseline and one patient died due to multi-organ failure. Follow up HCV-RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child-Pugh A cirrhosis in non-European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child-Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region. Fil: Mendizabal, Manuel. Hospital Universitario Austral; Argentina Fil: Haddad, Leila. Hospital Italiano; Argentina Fil: Gallardo, Patricia E.. Fundación Sayani; Argentina Fil: Ferrada, Alejandro. Hospital Clinico San Borja Arriaran; Chile Fil: Soza, Alejandro A.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile Fil: Adrover, Raul. Centro de Hepatología; Argentina Fil: Aravena, Edmundo. Hospital Clinico San Borja Arriaran; Chile Fil: Roblero, Juan P.. Hospital Clinico San Borja Arriaran; Chile Fil: Prieto, Jhon. Clínica Universitaria Colombia y Centro de Enfermedades Hepáticas y Digestivas; Colombia Fil: Vujacich, Claudia. Fundacion Centro de Estudios Infectologicos; Argentina Fil: Romero, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología ; Argentina Fil: Muñoz, Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología ; Argentina Fil: Anders, Margarita. Hospital Alemán; Argentina Fil: Hernández, Nelia. Hospital de Clinicas Dr. Manuel Quintela; Uruguay Fil: Coccozella, Daniel. Centro de Hepatología; Argentina Fil: Gruz, Fernando. Fundación Favaloro; Argentina Fil: Reggiardo, Maria V.. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; Argentina Fil: Ruf, Andres E.. FUNDIEH; Argentina Fil: Varón, Adriana. Instituto de Cardiologia; Colombia Fil: Cartier, Mariano. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología ; Argentina Fil: Pérez Ravier, Roberto. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentina Fil: Ridruejo, Ezequiel. Hospital Universitario Austral; Argentina. Centro de Educación Medica E Invest.clinicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; Argentina Fil: Poncino, Daniel. Sanatorio Municipal Dr. Julio Méndez; Argentina Fil: Vorobioff, Julio. Universidad Nacional de Rosario; Argentina Fil: Aballay Soteras, Gabriel. Sanatorio Mitre; Argentina Fil: Silva, Marcelo O.. Hospital Universitario Austral; Argentina

Background & 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.

Nimesulide is the unique molecule of the sulphonanilides class of non-steroidal antiinflammatory drugs [NSAIDs]: Nimesulide has analgesic, anti-pyretic, potent anti-inflammatory activities and very good gastro-intestinal [GI] tolerability. Therapeutic action is multifactorial, including cyclooxigenase-2 (COX-2) inhibition, scavenging of free radicals and inhibition of various pathways of inflammation. Nimesulide is oxidatively metabolised via liver cytochromes P450. Several unproven hepatotoxicy-predisposing-factors thought to be present in rheumatologic patients have been linked to a higher incidence of hepatic reactions in this sub-population. However, the molecular mechanism underlying hepatotoxicy remains to be elucidated. Nimesulide has been associated over two decades with reports of severe liver damage. The clinical presentation of nimesulide-related-hepatoxicity includes, malaise, pruritus, a wide range of ALT/AST elevation, and an average 4 fold elevation of alkaline phosphatase and GGT. Liver biopsy shows a predominance of hepatocellular involvement, less frequently cholestatic and mixed patterns. Both, the hepatitis pattern and the mixed-type combining cholestatic jaundice, might evolve into fulminant hepatic failure. However, the incidence of nimesulide-inducedhepatotoxicity is not homogeneous across the medical literature. Indeed, most of the countries find it to be comparable to that of other NSAIDs, while a significant higher hepatotoxicity is suggested by reports from Finland, Ireland and Argentina. Our series in Argentina comprising 43 cases is worrisome particularly because it evidences a significant proportion of severe forms. In the present work we analyze the epidemilogical characteristics of nimesulide-induced-hepatotoxicity and we describe the clinical and histologic spectrum of nimesulide-associated-liver damage based on the comparison of our series of 43 cases and worldwide published observations in the pertinent medical literature.

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

Molecular diagnostics based on reverse transcription (RT)-PCR are routinely complicated by the lack of stable internal controls, leading to falsely negative results. We describe a strategy to produce a stable competitive internal control (CIC) based on a Qβ phage derivative (recombinant Qβ [rQβ]) bearing primers KY78 and KY80, which are widely used in the detection of hepatitis C virus (HCV). rQβ was RNase resistant and stable at 4°C for 452 days in SM medium (0.1 M NaCl, 8 mM MgSO 4 ·7H 2 O, 50 mM Tris HCl [pH 7.5], 2% gelatin) and for 125 days after lyophilization and reconstitution. rQβ performance as a CIC was evaluated. rQβ was added to HCV-positive samples, followed by RNA extraction and a CIC-HCV RT-PCR assay. This method combines RT-PCR, liquid hybridization with nonradioactive probes, and enzyme immunoanalysis. No influence of the CIC on qualitative HCV detection was observed independently of viral load, and results had high concordance with those of commercial kits. In conclusion, we describe a versatile, low-cost alternative strategy to armored RNA technology that can be adapted for detection or real-time applications of any RNA target. Moreover, the CIC reported here is an essential reagent for HCV screening in blood banks in resource-limited settings.

Background: There are numerous studies concerning the natural history and prognostic factors in cirrhosis, the results of which are useful in selecting liver transplant candidates. However, little attention has been paid to the prognostic significance of hepatic encephalopathy despite the high frequency of this complication. Methods: We reviewed the charts of 111 cirrhotic patients who developed a first episode of acute hepatic encephalopathy to determine their survival probability and to identify prognostic factors. Results: During follow-up (12±17 months), 82 (74%) patients died. The survival probability was 42% at 1 year of follow-up and 23% at 3 years. With univariate analyses followed by a multivariate analysis, 7 out of 30 clinical and standard laboratory variables were significantly associated with poor prognosis: male sex, increased serum bilirubin, alkaline phosphatase, potassium and blood urea nitrogen, and decreased serum albumin and prothrombin activity. Patients were classified into two groups according to a prognostic index calculated from these 7 variables. Survival probability at 1 and 3 years was 73% and 38%, respectively, in patients with a low prognostic index, and 10% and 3% in patients with a high prognostic index. Conclusion: Hepatic encephalopathy is associated with short survival in cirrhotic patients. Although these patients can be classified into several groups with a different prognosis, the survival probability in every group is lower than that currently expected after liver transplantation. Therefore, cirrhotic patients developing a first episode of acute hepatic encephalopathy should be considered as potential candidates for this therapeutic procedure.

Summary Registration studies show entecavir (ETV) to be effective and safe in NUC-naive patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naive HBeAg-positive and HBeAg-negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty-nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log10 IU/mL. Ninety-two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti-HBe positive; 14% became HBsAg negative and 13% anti-HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off-treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off-treatment, 3 of them showed HBeAg reversion and 4 lost anti-HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.

In vitro, octreotide potentiates vasoconstriction in isolated, preconstricted, mesenteric arterial vessels. In cirrhotic patients, portal pressure (HVPG) reduction induced by propranolol is partly due to splanchnic vasoconstriction.To evaluate HVPG effects of octreotide administration in cirrhotic patients receiving long-term propranolol.A randomized, controlled trial. First study: a total of 28 patients were studied at baseline and 30 and 60 minutes after octreotide (200 mug) (N = 14) or placebo (N = 14) and then treated with propranolol for approximately 30 days (106 +/- 5 mg/day). Second study: after baseline evaluation patients received octreotide or placebo as they were assigned to in the first study and measurements repeated 30 and 60 minutes later.In the first study baseline HVPG was 18.7 +/- 0.9 mmHg and decreased to 17.1 +/- 1.1 mmHg and 17.1 +/- 1.0 mmHg (both P0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Eight patients decreased their HVPG after octreotide. In the second study baseline HVPG was 15.6 +/- 1.3 mmHg (P0.01 vs baseline HVPG in first study) and decreased to 14.1 +/- 1.2 mmHg and 14.1 +/- 1.3 mmHg (25.7 +/- 5% lower than baseline HVPG in the first study, P0.01) (both P0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Nine patients (2 responders/7 nonresponders to propranolol) decreased their HVPG after octreotide. Octreotide effects may be mediated by potentiation and additive mechanisms.Octreotide enhances HVPG reduction induced by propranolol in cirrhotic patients.